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Full text of "Marihuana and health. Third Annual Report"

AlAKIHIIANA ANI» HEALTH 



Third Annual Report to the U.S. Congress 

From the Secretary of 
Health, Education, and Welfare 




NATIONAL INSTITUTE ON Oltlir. ABUSE 



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MARIHUANA AND HEALTH 
THIRD ANNUAL REPORT TO CONGRESS 
FROM 
THE SECRETARY OF HEALTH, EDUCATION, AND WELFARE 



National Institute on Prug Abuse 
5600 Fishers Lane 
Rockville, Maryland 20852 



DHEW Publication No. (ADM) 74-50 
Printed 1974 



For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402 - Price $1.85 



11 



ACKNOWLEDGEMENTS 



The preparation of a report of this type would be impossible without 
the willing cooperation of the many members of the scientific community 
who have generously made available reports of their current marihuana 
research. Their comments and assistance are gratefully acknowledged. 

Scientists of the National Institute of Mental Health who have had the 
primary responsibility for preparing each of the sections of this report 
are — 

Dr. Monique Braude — Sections on toxicity and neurophysio- 
logical and endocrinological research in animals. 

Miss Eleanor Carroll -- Section on marihuana use in other 
countries. 

Dr. Norman Krasnegor — Section on behavioral effects in 
animals . 

Dr. Jo Ann Nuite — Section on pharmacological research in 
animals. 

Dr. Alan Ramsey — Section on the effects in man, viz: acute 
physical toxicity, chronic physical effects, genetic and 
birth defects and psychiatric illness. 

Dr. Louise Richards — Section on extent, patterns and social 
context of use in the United States. 

Dr. Stephen Szara — Section on the effects in man, viz: the 
active ingredient, route of administration, metabolism, 
subjective, physiological and biochemical aspects, intel- 
lectual and psychomotor effects. 

Dr. Robert Willette — Section on chemistry and metabolism. 

Dr. Robert Petersen edited and coordinated the preparation of 
the report in addition to preparing the introduction, 
summary and section on future research directions. 



iii 



CONTENTS 



Acknowledgements iii 

Introduction 1 

Summary 3 

Extent, Patterns, and Social Context of Use 

in the United States 21 

Marihuana Use in Other Countries 43 

Preclinical Research 85 

Effects in Man 129 

Future Research Directions 161 



INTRODUCTION 



It is now two years since the first annual report on Marihuana and Health 
was transmitted to the Congress. During those two years there have been 
significant advances in our understanding of the implications of marihuana 
use. Some of these were summarized in last year's report. In addition, a 
Presidential Commission has carefully considered the marihuana issue and com- 
pleted its comprehensive examination of many aspects of the problem. 

In accordance with the requirements of the "Marihuana and Health Reporting 
Act" (Title V of P.L. 91-296), the Secretary of Health, Education, and 
Welfare has the continuing responsibility of submitting annual reports on the 
health consequences of cannabis use. As in previous years, "health conse- 
quences" are defined as the effects of the drug on the individual's mental 
and physical health, as well as effects of use on the society to the extent 
that scientific investigation is relevant to that question. Unlike the 
report of the National Commission on Marihuana and Drug Abuse, however, we 
have continued to restrict our observations to areas in which a scientific 
judgment is possible. There are equally important issues of values, law and 
social custom that have been considered by the Commission and that will un- 
doubtedly be a part of a continuing dialogue within the larger society. By 
supplying a relatively dispassionate summary of the accumulating scientific 
data concerned with marihuana and its use, however, it is hoped that this 
report will be maximally useful to all who are concerned with the present 
state of our knowledge concerning this socially controversial drug. 

A continuing major purpose of these annual reports is to serve as a widely 
available, up-to-date compendium of scientific information bearing on the 
issue of marihuana and health. In order to make the report as helpful as 
possible to the widest possible audience, we have attempted to report find- 
ings both technically and, to the extent possible, in more everyday language. 

To a greater degree than in previous years, we have placed primary stress on 
recently accumulated evidence, rather than attempting a more comprehensive 
overview. More recent research is, of course, evaluated in the context of 
the total body of our knowledge. 

Because it is unwise to overinterpret the uncorroborated findings of any 
single study, we have again emphasized converging lines of evidence to sup- 
port many of our observations. Despite more recent evidence, there are still 
important unresolved questions. One of these concerns the implications of 
long-term use; another the possible interactive effects of cannabis with 
other drugs in widespread use. There is significant new evidence regarding 
the implications of long-term cannabis use. However, much of it is based on 
overseas populations quite different from an American user population both 
in their patterns of drug use and in the demands their society makes upon 
them. Moreover, ours is a society that makes simultaneous use of many drugs. 
They are used recreationally, as self medication and by prescription. The 
multiple forms this polydrug use takes makes it especially difficult to be 
certain how marihuana use may interact with use of these other substances. 

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Finally, although evidence concerning marihuana use in other cultures remains 
spotty, the interest in it (and the lack of ready availability of recent 
information elsewhere) seem to warrant its continued inclusion in the report. 
Such information has been included only when it updates last year's report. 



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SUMMARY 



In the past year our understanding of the problem of marihuana use and its 
possible implications has continued to expand at a rapid rate. While some of 
the advances may appear to the layman to be primarily "technical", all con- 
tribute to our greatly enlarged knowledge regarding the health consequences 
of marihuana use both now and in the future. Much, if not most of the re- 
search, is relatively undramatic and its implications frequently are not 
obvious . 

In this summary we will again attempt to translate the findings from many 
disparate sources into as adequate and complete an answer as can currently be 
framed to the basic question: What are the health implications of marihuana 
use for the American people? In attempting to answer this apparently simple, 
but in reality difficult and complex question, we are well aware that any 
answers rest on multiple assumptions, many of which are open to question. 
Present social patterns of typical use may change markedly as may the quality 
and quantity of the material used. To the extent that marihuana use has some 
aspects of a fad, we can easily over or underestimate longer term consequences 
of use. In the past it was frequently suggested that marihuana use might for 
many supplant alcohol use and thus reduce the severity of the alcohol problem. 
In reality, it now appears that alcohol use is a typical concomitant of canna- 
bis use. And, of course, with the general increase in marihuana users has 
also come an increase in those who use it heavily either alone or in combina- 
tion with other drugs. 

As will be discussed in greater detail later, even relatively heavy use in 
cultures where it is socially sanctioned may have quite different implica- 
tions from use in a society in which more extensive or even moderate use is 
viewed as social deviant. Not only are the populations attracted to such use 
different but so may be the ways in which the user's self concept and ongoing 
behavior are altered by use. Moreover, in many societies in which use has 
been largely restricted to the lowest social classes, it is often difficult 
to know to what extent ascribed characteristics of users represent altera- 
tions related to drug use or the institutionalized prejudices of those of 
higher social status. 

We have emphasized in previous reports that any sophisticated understanding 
of cannabis must take into account many aspects of use patterns. These include 
such obvious aspects as potency, dosage, and frequency of drug use, but must 
also include the psychological set and the setting of use, especially the cul- 
tural context. When human performance is considered, task complexity, per- 
sonal values and level of motivation are also important variables. 



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EXTENT AND NATURE OF MARIHUANA USE IN THE UNITED STATES 



Presently available information on the extent and nature of marihuana use is 
considerably more detailed than it has been in the past. We now have national 
data concerning use in the general population and relatively detailed studies 
on youthful use especially among those enrolled in high schools and colleges. 
There is an accumulating, body of data on the social and personal correlates 
of use and there has been research delineating family and peer relationships 
of various kinds of users. Information on marihuana and hashish dealers has 
been included in this report for the first time. The dealer data have been 
included because dealing and using are frequently carried out by the same 
individuals, especially if they are regular users. 

Generally, the use of cannabis in the United States has not increased dramat- 
ically. The rate of increase in some segments of the population may have 
diminished. Recent estimates indicate that about 24 million persons have ever 
used cannabis. It should be emphasized that over half of those who have ever 
used have only experimented with the drug. Probably not more than one in 
twenty uses on a daily basis. The most common frequency reported by regular 
users is one to four times per month. 

Use is highly age-related and to a lesser extent related to educational status. 
The highest rates of "ever used" are consistently found among college students 
(54 percent - an overall increase of twelve percentage points from 1971 figures) 
Although the National Commission's survey of 1971 found 15 percent of adults 
over 18 years of age had tried marihuana at some point, other surveys have 
found lower rates in this group. Since the ways in which data are collected 
and reported are not consistent across surveys, comparisons are sometimes dif- 
ficult or can be misleading. 

A consistent finding for several years has been that cannabis use is more com- 
mon in the Northeast and West than in Central or Southern States. It is also 
more common among urban than among rural residents. 

Even though one study found that use by members of military services stationed 
in the United States (those overseas were not included) was higher than civil- 
ians of the same age, additional data are needed to clarify the causes and 
implications of this finding. 

Overall, it has been found that males are twice as likely as females to have 
tried marihuana. Males are not only more likely to have tried the drug, but 
are also more likely to be using it with greater frequency. There are, how- 
ever, many indications that the number of, and rate of use by girls and women 
is increasing. In college populations, the ratio of male to female use is 
about 3:2 and recent data on high school use suggest that marihuana use by 
the two sexes is approaching parity. In several studies the differences in 
use rates by the two sexes are no longer statistically significant. 

Interestingly enough, rates of use are considerably higher in single sex col- 
leges and universities than they are in coeducational institutions. For both 

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males and females the percentage using tends to be about a third higher in 
those schools segregated by sex. Social opportunities present in coeduca- 
tional colleges may serve to reduce overall interest in drug use. 

Certain patterns of related drug use have been found. Most characteristic 
is the use of alcohol and tobacco prior to and concurrently with marihuana 
use. Among college populations the drugs used, from the most to least fre- 
quently, are: beer, wine, hard liquor, lower potency marihuana, higher 
potency marihuana and hashish followed in diminishing frequency by LSD and 
other drugs. Heroin use in this group is extremely uncommon. 

It has been found that user perceptions of both safety and of availability 
are significant determinants of choice of drugs although availability is the 
more important of the two. 

A nationwide study of college students' life styles at fifty- four colleges 
and universities has now done a second year survey of their drug use. During 
the most current academic year that has been analyzed the percentage of 
students who have used marihuana during the academic year has risen from 23 
to 37. It was found that twice as many students were beginning use as com- 
pared to those discontinuing such drug use. The researchers conducting this 
survey estimate that drug use in the nation's college populations will proba- 
bly stabilize at about the point where two-thirds make some use of marihuana. 

Overall, present trends, especially of frequent or heavy use among high school 
and college populations, do not appear as alarming as they have in the past. 
Given some of the fad-like aspects of marihuana use, it can be expected that 
rates in individual schools will vary widely from the national averages. 
Judging by trend data in some areas of high use, more frequent marihuana use 
may be stabilizing and the rate of increase decreasing. 

Studies of non-student groups are of particular interest since less is known 
about them. Health professionals are of special interest because of their 
sophistication in health matters, their role as models and the possible risk 
for them associated with drug use. One study of a physician sample in New 
York City, San Francisco, upstate New York and Nebraska found that over a 
third of those who responded (about 50 percent of those queried) reported 
having tried marihuana. Only seven percent reported current use and, as ex- 
pected, younger physicians and those living in New York City and San Francisco 
were more frequent users than those in the other areas. Among nurses and 
nursing students rates of use were appreciably lower. Only three percent of 
graduate nurses reported ever having used and only a third of these were doing 
so currently (one percent of total). 

Because of the publicity given drug use in Vietnam, military use patterns of 
marihuana are also of special interest. A worldwide study of enlisted men 
done in 1971 indicated that somewhat less than a third used marihuana in the 
preceding year. Not unlike the civilian population, about half would have 
been more appropriately classified as "experimenters" rather than as users. 
However, a much higher percentage of users (40 percent) reported using 
several times per week or more. Use rates, although somewhat higher than for 
those of comparable age in civilian life, were not strikingly so. 

-6- 



During the past year we have learned more concerning the ways in which people 
learn about marihuana and the role of family and peer influences in its use. 
The sources of information most commonly mentioned by children from ages 11 
to 17 are television, parents, friends and other students. In the fifth 
grade reliance seems to be placed on TV and parents. By contrast eleventh 
graders rate peer influences (friends and other students) as the most impor- 
tant sources . 

Several studies have investigated the role of parents and peers in adolescent 
drug use. The teenagers' use is closely correlated with use by his friends. 
When none of a teenager's friends reported use of drugs, only one out of fif- 
teen youngsters themselves reported use. When all of their friends reported 
use, nine out of ten had also used the drug. When brothers or sisters have 
used, three-quarters of those reporting have also used. Conversely, when 
their siblings are non-users, half as many giving self reports are themselves 
users. The more peer-oriented as opposed to parent-oriented the youngster is, 
the more likely he is to be a user (by peer-oriented is meant the amount of 
time spent with friends, greater reliance on advice of friends than on that of 
parents, etc.). 

Not too surprisingly, drug use by children is related to drug use by parents. 
When both parents use drugs such as alcohol, tobacco and other psychoactive 
drugs, there is a greater likelihood that their children will use marihuana. 
This relationship has less to do with parents' actual drug use than it does 
with the adolescent's perception of such use. The probability of drug use is 
also associated with such factors as lack of family cohesiveness, use of other 
medications and less parental emphasis on self control. 



Marihuana Dealing 

The typical marihuana dealer is not a street dealer of such drugs as heroin 
or cocaine. He is typically himself a user, middle class, not otherwise 
involved in criminal activity and his selling is closely correlated with his 
level of use. A user is far more likely to sell if he uses on a daily basis 
than if he uses only monthly or less often. If he is more heavily involved 
in the drug culture in that he and his friends are regular users of marihuana 
and other drugs, he is more likely to deal. 



MARIHUANA USE IN OTHER COUNTRIES 



There is considerable evidence that cannabis use is increasing among young 
people throughout the world. Even in those countries in which use has been 
endemic but previously restricted to the lowest classes an interest in mari- 
huana has developed among middle and upper class youth. This pattern of dif- 
fusion seems to have resulted not from emulation of traditional local use, but 
from adopting the youth norms of Europe and the United States. 



-7- 



Although we have included a brief description of cannabis use abroad in this 
year's report as we have in the past, we are including additional information 
only on those countries for which there are new developments to report. It 
is again worth emphasizing that the uses of cannabis are highly varied. In 
countries where use is traditional marihuana is more often used as a folk 
medicine or to make arduous work less so, than it is for recreation. It 
should be emphasized that the quality of information available on use in 
other countries ranges from limited, anecdotal accounts to carefully conducted 
anthropological and sociological research. Unfortunately, the more limited 
accounts predominate* making comparisons more difficult. 

English Speaking Countries 

In England, Australia and New Zealand there are indications of an increasing 
use of cannabis although hard data on the level and patterns of use in those 
countries are generally lacking. There has been sufficient concern in all 
three to justify creation of special commissions to look into the problem. 
The recommendations that have been made by these groups have been generally 
similar to those made here in the United States - i.e., they have urged a 
less punitive approach to the user, a more thoughtful examination of the 
problem, and are supporting much needed research. 

In Canada during this past year the Commission of Inquiry into the Non-Medical 
Use of Drugs published its report on cannabis. The Canadian Commission has 
functioned very like our own National Commission. It has held extensive 
public hearings and commissioned a number of studies concerned with Canadian 
use. Although the data involved have not yet been completely analyzed, Canada 
has clearly experienced a rapid increase in cannabis use very like our own. 
From an estimated 79,000 in 1966, the number of those who have used cannabis 
one or more times has risen to one and a half million. Use appears to be 
concentrated among young people. The bulk of those who have used are infre- 
quent users and the statistical breakdown and patterns of use appear to be 
generally similar to those in the United States. 

The Canadian Commission's recommendations went beyond those of our National 
Commission in advocating Federal quality standards for cannabis and permitting 
sale and distribution subject to restrictions similar to those for alcohol. 



Mexico 

Although marihuana use has had a long history in Mexico and there has been a 
recent marked increase in interest in drug problems, there is little in the 
way of objective surveys to report. While there have been reports of in- 
creasing use by middle and upper class youth, there is little evidence to 
suggest that the increase has been as large as that of our Canadian neighbors, 



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Other Latin American Countries 

Many of the Latin American countries have shown official concern about drug 
abuse. However, the exact dimensions of the problems are in doubt. In 
Venezuela, for example, a Special Commission in its report to the Chamber of 
Deputies indicated that drug use was reaching epidemic proportions. They 
indicated that some 85 percent of youth in the Caracas area (the capitol) had 
used drugs at least once. In Ecuador it has been claimed that as many as ten 
percent of the population are abusing drugs. Although there is some increase 
in drug use reported in Chile, the very limited amount of data on marihuana 
use among high school students suggest very few are using (about' 7 percent). 
Generally, these countries are now stressing a multifaceted approach to the 
problem of abuse including preventive, educational and rehabilitative aspects. 

Europe 

We have little new information on cannabis use in European countries except 
for a major survey of student drug use in the Netherlands. Since this study 
involves three phases, a survey in 1969, one in 1971, and another to take 
place in 1973, it provides some indication of trends in a country whose drug 
policy with respect to cannabis has been frequently described as "liberal." 
In the first survey it was found that 11 percent of the students queried had 
used an illicit drug one or more times - in almost nine out of ten cases the 
drug was marihuana or hashish. By 1971 the number had nearly doubled although 
the percentage of frequent users remained relatively low. The authors of this 
study are optimistic pointing out that while overall there has been an increase, 
in schools that earlier had the problem there has not been the expected dou- 
bling of rates. Most of the increase can be accounted for by diffusion to 
new schools rather than a dramatic increase in those already using. 



The Middle East 

The major source of new data with respect to cannabis use in this area is an 
extensive study of users in the United Arab Republic. Although there are no 
exact figures on the number of hashish users, the major researcher concerned 
with the problem, estimated that in 1967 they comprised about 17 percent of 
the male population between the ages of 20 and 40. Beginning as early as 1957 
an extensive series of studies has been conducted. Data from the most recent 
study became available this year. Some highlights of this extensive socio- 
logical and psychological research include the following: Urban users were 
found to smoke hashish about fifty percent more frequently than rural users 
(12 vs. 8 times per month). The ten percent of most frequent users did so 50 
or more times per month. Most (62-70 percent) began use before the age of 
twenty with few doing so after 28. Self described motives for use in order of 
importance were: group conformity, desire for euphoria, curiosity and the 
desire to appear like "real men." A small group setting was favored for use 
of the drug. 



-9- 



The most recent data concerns a prison sample of users matched with nonusers. 
Among users it was found that heavier users tended to begin earlier and that 
substantial percentages also used opium and alcohol. By contrast with non- 
users, cannabis users were generally found to have fewer criminal offenses 
and are described as slower learners. Performance on a wide array of psycho- 
logical testing was generally poorer among users. However, the use of other 
drugs, the rather heavy hashish use and other cultural factors make the rele- 
vance of this data to American use patterns uncertain. 



The Far East 

New information is primarily available from India and the Philippines. At a 
recent drug seminar in New Delhi in July 1972, the participants, representing 
many health and social welfare agencies, agreed that drug abuse is a growing 
problem among upper class students. Firm statistics to support the extent of 
the problem are lacking. The delegates emphasized the desirability of launch- 
ing research studies to determine the extent and causes of youthful drug abuse 
and the need to encourage more effective prevention efforts by both government 
agencies and the mass media. A subsequent meeting of the Delhi Medical Asso- 
ciation and other health agencies emphasized more effective control over the 
problem of drug abuse. Efforts to tighten restrictions on the distribution 
and sale of psychotropic and narcotic drugs are being considered. 

Although statistics on the extent of marihuana abuse in the Philippines are 
also limited, it has been estimated that 60,000 youths are engaged in drug 
experimentation, mostly with cannabis. As a result of an increasing concern 
with many aspects of drug abuse over the past several years, a number of new 
organizations and facilities have been created and new legislation has been 
passed. The new law creates a Board with broad responsibilities for develop- 
ing educational programs, special training of police and rehabilitation per- 
sonnel and conducting drug research. 



Jamaica 

A major study of thirty lower class users matched with an equal number of 
nonusers was completed during the period covered by this Report. In addition 
to the biomedical research commented on elsewhere, a systematic effort was 
made to understand the context of use on the island. Users are predominantly 
from the lower class and marihuana, called "Ganja" in Jamaica is used for 
many purposes. It is smoked, chewed, taken in tea, cooked and added to food. 
It is widely used as a folk medicine as well as to ward off fatigue or to help 
endure discomfort. It is estimated that two out of five adult males are regu- 
lar users who typically smoke the drug as a work adjunct. Although it is 
widely believed to facilitate work performance and increase energy output, 
careful research conducted by anthropologists using videotape recordings did 
not support this belief. 

Cultural expectations with respect to marihuana bear little resemblance to 
American and European views of the drug which emphasize the recreational, 

-10- 



"mind expanding" aspects. Rather it is seen as an aid to more alert work 
functioning. Although the age of introduction appears to be declining, use 
is typically begun in the early teens and represents in part a rite of pas- 
sage into manhood. 

Most recently, as in other parts of the world, there has been increasing con- 
cern expressed regarding the diffusion of use to include middle and upper 
class youth. This use, like that of the lower class, is illegal, but unlike 
the use by the working class, is not generally sanctioned by members of the 
group. 



PRECLINICAL RESEARCH IN ANIMALS 



Animal research continues to be an important source of increased knowledge 
about the implications of cannabis use by humans. The genetic history of 
animals can be controlled as can their learning history, their drug use and 
the environmental conditions surrounding them. This makes it possible to 
study problems which, for ethical, scientific or practical reasons, cannot be 
studied nearly as well in humans. At the same time it must be kept in mind 
that animal -human differences in physiology, the greater complexity of the 
human situation, differences in dosage levels and the possible role of multi- 
ple drugs in real life human drug use, all make difficult the direct transla- 
tion of animal results into human terms. 

Perhaps the most important finding deriving from animal research in the past 
year is that both synthetic Delta-9 -Tetrahydrocannabinol* and natural mari- 
huana, even when given in relatively high doses over extended periods, appar- 
ently have no deleterious effects on pregnancy, fetal development or the 
newborn. Testing was done in accordance with the guidelines of the Food and 
Drug Administration for assessing possible adverse effects of drugs on preg- 
nancy and fetal development. Although this finding is reassuring, it illus- 
trates some of the problems alluded to above. There is no way of being 
certain that cannabis when used in combination with other drugs might not 
produce adverse effects that may not occur when used alone. Although there 
is, at present, no evidence of this, even the remote possibility makes it 
desirable that unnecessary drugs including cannabis not be used during preg- 
nancy. 

Although our knowledge has expanded of the ways in which marihuana and Delta- 
9 -Tetrahydrocannabinol are rapidly changed into their metabolites, the specific 
role of each is still not certain. Several of these metabolites appear to be 
psychologically active. 

One of the more interesting effects of Del ta-9 -Tetrahydrocannabinol in animals 
is that it increases the depressant effects of barbiturates and yet it also 



* In order to simplify the text, when THC is used without qualification it 
refers to Delta-9 -Tetrahydrocannabinol - the presumed principal psychoactive 
material in natural material. 

-11- 



enhances the stimulating effects of amphetamines. The clinical implications 
of this finding in the human use situation are not yet clear although it may 
be a factor in multiple drug use. 

The issue of tolerance was discussed in some detail in last year's report. 
According to recent studies it appears certain that tolerance develops, at 
least at high doses in animals, for some of the effects of cannabis. This 
marked tolerance, however, has not been adequately reproduced in man. The 
ways in which tolerance may be complicated by drug interactions is illustrated 
by animal research which suggests that rats which have developed tolerance to 
Delta-9 -Tetrahydrocannabinol are in turn less susceptible to the acute effects 
of alcohol. Conversely, rats tolerant to the effects of alcohol appear to be 
less affected by Delta-9-Tetrahydrocannabinol. While this question has not 
been systematically investigated in man, it suggests that heavy users of alco- 
hol may have greater resistance to the effects of marihuana and vice versa. 
The basis for this apparent cross tolerance is not known at the present time. 

Although an abstinence syndrome following prolonged administration of Delta- 
9 -Tetrahydrocannabinol has been found to occur in Rhesus monkeys, this result 
must be interpreted with caution. The syndrome, consisting of hyperirrita- 
bility, increased aggressiveness, muscle tremors and yawning, has thus far 
only been found in a small number of animals under heavy dosage conditions. 

An early Russian report of a specific antagonist (phenitrone) to the action of 
marihuana, i.e., a drug which blocks its actions, has not been substantiated 
by other investigators. However, evidence that cannabidiol, a natural ingre- 
dient in marihuana, may prevent the depressant effect of Delta-9-Tetrahydro- 
cannabinol in mice, is resulting in an increased interest in the possibility. 
It also suggests that the action of the natural material is complex in that 
additional ingredients other than Delta-9-Tetrahydrocannabinol may modify the 
effects . 

At present, the relationship of marihuana use to various aspects of brain 
chemistry is still under study. However, early results have shown that mari- 
huana has specific effects on neurohormonal distribution, i.e., on the com- 
pounds which are involved in the mechanism of action of most psychoactive 
drugs. 

A variety of attempts to examine the possible effects of cannabis and Delta- 
9 -Tetrahydrocannabinol on lung function are currently underway. In one study 
of isolated lung tissue, smoke from marihuana cigarettes was found to cause 
changes in cells similar to changes caused by smoke from ordinary tobacco 
cigarettes. This suggests the possibility that marihuana may be a lung irri- 
tant like tobacco. The implications of this for an American population are 
uncertain since despite deep inhalation the frequency of typical American use 
of marihuana is so much lower than that of tobacco. 

Studies of animal behavior while under the influence of marihuana and Delta-9- 
Tetrahydrocannabinol are of particular interest because of the high degree of 
control that can be exerted over learning history and other variables affect- 
ing behavior. Two areas that are of special interest are the effects on time 

-12- 



perception and on aggression. There is objective confirmation from the 
animal laboratory that time perception is altered in animals in ways similar 
to those reported by human users. There is also evidence that marihuana and 
Delta-9 -Tetrahydrocannabinol generally reduce aggression in animals. However 
under chronic administration, the opposite effect occurs in animals, i.e., canna- 

binoids produce hyperirritability and increased aggressiveness. Further ex- 
ploration of conditions under which this is true may help to better understand 
marihuana's effects on aggressive behavior in humans. There have been some 
anecdotal accounts of marihuana -related aggression in humans although the pre- 
dominant view is that it tends to induce greater passivity. Animal research 
may help to explain the somewhat contradictory reports stemming from different 
levels of intoxication, extent of use and possible abstinence effects. 



EFFECTS IN MAN 



Although many of the immediate effects of marihuana were described in last 
year's Report, the past year has provided additional verification of some of 
these observations and clarification of still others. 

While it is now rather firmly established that Delta-9 -THC is the principal 
psychoactive ingredient, other chemically identified ingredients of the 
natural material play a role in producing some of cannabis' effects. Delta-8- 
THC, a related compound to Delta-9-THC which occurs in relatively small quanti- 
ties in the natural product, has been found to be psychoactive, although some- 
what weaker than Delta-9 -THC. Cannabadiol, another natural ingredient, has 
been found to produce slight changes in subjective feelings and an increased 
pulse rate. Since, in at least one animal study, this ingredient has been 
found to block certain effects of THC, it is possible that its presence in 
natural material modifies the response to THC in man as well. However, there 
is no indication at present that Delta-9-THC is not capable of reproducing 
the total subjective and objective effects of the plant material. 

Marihuana and THC are physiologically transformed in the body into metabolites 
such as ll-Hydroxy-Delta-9-THC. A number of these metabolites have now been 
positively identified and are being carefully studied. A simple method of 
detecting cannabis smokers by having them breathe on chemically treated paper 
has been suggested. Although the method is sensitive for two hours after use, 
the smoking of tobacco interferes with results and the test is not yet practical 

The role of user expectations in perceived marihuana effects has been under- 
scored by research in which inactive material (placebo) was subjectively seen 
as having generally similar effects to those of marihuana. These effects were, 
however, described as only a third as intense as those with the active drug. 
Particularly at lower doses, the role of expectations and the setting of use 
help to explain the wide variations of subjective response that would not be 
readily predictable from the drug's pharmacologic profile. 

Immediate physiological effects such as increased pulse rate, reddening of the 
eyes and a decrease in intraocular pressure reported last year have been 

-13- 



systematically investigated, There is some concern that a persistently high 
pulse rate produced at the time of marihuana intoxication might be dangerously 
increased by the use of certain other drugs in treatment following say, an 
auto accident. There have, however, been no reports of serious consequences 
ensuing. 

A careful study using thirty young male volunteers indicates there is little 
question that marihuana reduces intraocular pressure in a dose-related way 
(i.e., the higher the dose the greater the pressure reduction within the eye). 
THC appears to be the ingredient in cannabis primarily responsible for this 
effect. The obvious potential of this effect for the treatment of glaucoma, 
an eye disease in which increasing intraocular pressure can impair vision, 
has been investigated on a very limited basis. However, before cannabis or 
THC can be used routinely for this purpose, considerable further study and 
testing are required. Its superiority over drugs presently available for this 
purpose remains to be demonstrated. 

A number of studies concerned with more subtle physiological effects of can- 
nabis have been conducted. The effects of marihuana on breathing are being 
studied as are its effects on electrical activity in the brain and on sleep. 
The results of most of this research are primarily of technical interest at 
this time. One interesting aspect of the sleep research is that marihuana, 
which was expected to enhance dreaming, did not do so. 

In studies done on the vestibular system (a system in the inner ear essential 
to maintaining proper balance) the effect of marihuana in social dose levels 
has been found to be negligible in one study and in another to interfere with 
balance only with closed eyes at higher dose levels. 

With respect to psychomotor and intellectual functioning, a consistent finding 
has been that the more complex the task demands, the more consistently they 
are affected by marihuana intoxication. As has been pointed out in the past, 
more experienced users seem to be, in general, better able to compensate for 
the drug effects than are the inexperienced. 



Driver Performance 

In previous years the limited data on driver performance cast doubt on whether 
marihuana use at the usual social levels seriously impaired driver performance. 
At the present time there seems to be little question that marihuana use im- 
pairs performance. In one study poorer automobile handling performance was 
found with both alcohol and marihuana although driving speed under marihuana 
was consistently slower. In another study it was found that marihuana resulted 
in longer reaction times and a greater frequency of wrong and inadequate driver 
responses to a simulated driving task. In a simulated automobile passing task 
both alcohol and marihuana affected decision-reaction times although alcohol 
did so to a greater extent. 

In a set of experiments designed to study the effects of alcohol and marihuana 
on driving-related visual functions, it was found that marihuana interfered 

-14- 



with peripheral vision as well as central vision to a greater extent than 
alcohol under a wider variety of task demands. This deficit was interpreted 
as the result of momentary lapses of attention under marihuana intoxication. 
Apparent movement of a fixed light source which might also be important under 
some driving conditions was only insignificantly changed by alcohol but more 
markedly affected by doses of cannabis within the usual social range. Con- 
trary to a preliminary report included last year, there was no evidence of an 
impairment in glare recovery time (the time required to readapt following 
exposure to such glare as oncoming headlights) associated with marihuana use. 

In another study marihuana was found to interfere more than alcohol with per- 
formance when subjects had to time their response accurately in order to 
respond correctly. Even when subjects received an immediate indication as to 
whether their responses were correct, early or late, those under the influence 
of marihuana in contrast with alcohol, made a greater number cf errors. 

Although additional research on cannabis, driving and driving-related tasks 
will be helpful in better understanding the mechanisms by which driver per- 
formance is impaired, there is sufficient evidence at this time to justify 
the warning that even social doses of marihuana may impair performance suffi- 
ciently to lead to motor vehicle accidents. Systematic research on the effects 
of marihuana in combination with alcohol and other drugs on driving has not yet 
been undertaken. It is, however, reasonable to expect that combinations will 
often be more hazardous than marihuana used alone. 



Chronic Physical Effects 

While there is little evidence to suggest that there are deleterious physical 
effects arising from a single episode of use or from infrequent use of mari- 
huana, the issue of long-term, chronic use and its effects remains unresolved, 
It is generally conceded that there is no such thing as an entirely "safe" 
drug and cannabis is not likely to be an exception. As has been pointed out 
in previous Reports, most of the earlier accounts of chronic effects are by 
current scientific standards seriously deficient. Current clinical case 
reports dealing with one or more cases may provide clues for more systematic 
study but rarely in themselves prove a causal connection between drug use and 
its presumed consequences. While there have been more systematic studies of 
users matched with nonusers these too can be faulted on a variety of grounds. 
If the adverse consequence of chronic use is rare or very subtle it may go 
undetected especially when small numbers of users are studied. Again, as has 
been suggested in earlier reports, when several sources of data - the labora- 
tory, clinical observation, animal and human research - converge toward a 
common conclusion, we can be more confident of its validity. In this Report 
as in the previous versions we have attempted to report even on single case 
studies of interest. This is done to suggest where more systematic observa- 
tion is needed as well as to give some indication of the present state of our 
knowledge. 

Among the case reports that have appeared in the past year is one indicating 
breast enlargement in three young adult males with a history of several years 

-15- 



of relatively heavy marihuana use. In the absence of other causes (e.g., 
liver or glandular abnormality) the authors speculate that the similarity of 
the THC in marihuana to a hormone having a feminizing effect may be the cause. 
Although there have been some reports of liver abnormalities associated with 
cannabis use, more systematic studies of larger samples have not confirmed 
this. It is noteworthy that in a study of chronic users in Jamaica carefully 
matched with nonusers and conducted under NIMH aegis, no evidence of liver 
damage was found nor was such evidence found in a Canadian study of 200 regu- 
lar cannabis users. 

Since the Jamaican study represents a significant attempt to study all aspects 
of possible effects in chronic users under carefully controlled circumstances, 
it is described in some detail in the body of the Report. In all, sixty care- 
fully matched male users and nonusers from a lower class Jamaican population 
were studied. These men averaged thirty-four years of age and had typically 
been smoking relatively strong marihuana for over seventeen years at the rate 
of seven cigarettes per day. They were subjected to very thorough physical 
and psychiatric examinations including measures of psychological and neuro- 
logical functioning. Results of this study have integrated into the appro- 
priate sections of the Report. 

A relatively consistent observation even from the earlier scientific and 
medical literature has been that chronic users experience respiratory problems. 
In the past year additional reports have appeared that support this observa- 
tion. A report based on 200 cases of heavy hashish smokers stationed with the 
U.S. Army in Europe emphasized a variety of upper and lower respiratory com- 
plaints. While most of these were relatively minor, ten percent of the group 
had bronchitis and showed diminished lung capacity (vital capacity) . Micro- 
scopic examination of bronchial tissue in this subsample showed abnormal 
changes described as similar to those found in older, heavy cigarette smokers. 
A study of seventeen additional heavy hashish users from the same source fur- 
ther confirmed this observation. 

While there were no important statistically significant differences between 
users and nonusers in the Jamaican study, there was a tendency for various 
lung functions to be diminished with increasing years and total quantity of 
use. It should be emphasized that this relationship appeared to be more 
closely related to any type of cigarette smoking (tobacco or marihuana) than 
to marihuana use as such. 

As has been noted earlier, there is also some evidence that isolated lung tis- 
sue exposed to marihuana smoke shows greater cell changes than that exposed to 
cigarette smoke. A number of additional studies are being conducted to further 
explore this important question. 

The issue of possible brain damage was highlighted early in the year by a 
report on thirteen young adults referred for psychiatric treatment. The 
authors' clinical impression was that the symptoms shown (apathy, mental slug- 
gishness, loss of interest in personal appearance, recent memory problems, 
mental confusion, etc.) were related to the level of marihuana use and its 
toxic effects on the brain. Some of the symptoms described are like those of 

-16- 



acute marihuana intoxication and in view of the inherent sampling bias (the 
patients were referred for their difficulties rather than randomly chosen from 
a population of users; they had also used other drugs), it is difficult to be 
certain of the role that cannabis played. Since there is no simple test of 
cannabis intoxication, it is possible that some of the patients were actually 
using the drug shortly before examination. In the Jamaican study there was no 
evidence of brain damage in the sample studied. 

Twenty-three heavy hashish users referred as part of a much larger group of 
American soldiers having psychiatric complications related to hashish use con- 
tinued to show confusion, memory loss and inability to concentrate after they 
discontinued hashish use. The authors view these symptoms as consistent with 
brain damage, but since there was no objective way of confirming that cannabis 
was no longer being used or the extent of other drug use, interpretation is 
difficult. 

Details of an extensive study of 850 hashish users in the United Arab Republic 
became available this year. These users and a population of nonusers, both 
drawn from prison populations were given a variety of tests of psychomotor and 
intellectual performance. While users had lower scores than did nonusers, 
interpretation is complicated by the fact that users had also frequently been 
users of opium as well. Despite the relatively large number studied, the lack 
of additional detail (e.g., on nutrition and other aspects of life style) 
limits any conclusions that can be drawn. 

Systematic study of brain electrical activity (EEG records) in matched user- 
nonuser populations in both Jamaica and Greece have not disclosed abnormali- 
ties associated with cannabis use. 

Based on present evidence it is not possible to offer definitive conclusions 
regarding a possible association between heavy cannabis use and organic brain 
damage. The obvious seriousness of such a consequence, particularly if it is 
irreversible, continues to make research on this question a high priority issue, 



Genetic and Birth Defects 

The possibility that cannabis preparations might cause genetic or birth 
defects has been a source of concern although there has been little evidence 
to support it. The bulk of present evidence, particularly that of well con- 
trolled studies, suggests that the likelihood of genetic or neonatal abnormali- 
ties arising from cannabis use at present social levels of use is low. There 
is no convincing evidence that chromosomal abnormalities arise from marihuana 
use. The Jamaican study of chronic users as well as other studies of the 
effects of THC on chromosomes in human lymphocytes (a type of white blood cell) 
indicate no changes related to cannabis use. Although there have been isolated 
case reports of abnormal offspring born to mothers who have used marihuana and 
other illicit drugs during pregnancy, more systematic controlled investigation 
has not borne this out. As has been indicated, animal research at substantially 
higher dosage levels than those likely to be employed by users showed no evi- 
dence of hazard to fetal development. 

-17- 



Despite this lack of evidence of hazard it should again be emphasized that 
there is no way of being certain that cannabis, possible in combination with 
other drugs, might not have adverse reproductive consequences under some cir- 
cumstances. The potential seriousness of such effects makes the use of mari- 
huana during pregnancy particularly unwise. 

Cannabis and Psychopathology 

The relationship between cannabis use and possible psychiatric disorders 
arising from its use has been of interest for many years. Unfortunately, 
virtually all of the earlier studies dealing with this issue have suffered 
from multiple deficiencies. Since previous reports have described their 
defects in some detail, we will only reiterate that they have suffered from 
such shortcomings as: Biased sampling, poor diagnosis, failure to distinguish 
preexisting psychopathology from that related to use, other confounding vari- 
ables, etc. 

During the past year a number of reports have appeared relating to psychiatric 
problems associated with cannabis use. In one military population (U.S. Army 
personnel stationed in West Germany) two percent were referred for medical 
reasons related to hashish use. Sixty percent of these were infrequent users 
with minor respiratory problems related to use. A small percentage of the 
group referred (less than three percent) had acute panic reactions or toxic 
psychoses related to a single high dose of hashish. The remainder showed 
symptoms ranging from acute psychosis (related to hashish and other drug use 
in combination), to chronic cannabis intoxication of a degree that interfered 
with functioning. While infrequent lighter use had few psychiatric complica- 
tions, heavy use and use in association with other drugs had a variety of 
adverse effects. A Scandinavian study of acute and chronic psychoses asso- 
ciated with cannabis use (mostly of hashish) found that most of those with a 
chronic psychosis had had a previous history of serious mental illness. By 
contrast, less than ten percent of those who had had acute cannabis -related 
psychoses lasting from one to five weeks had such a history. Typically there 
had been a marked increase in cannabis use just prior to the episode. 

Several American studies have suggested that frequent users are more likely to 
admit to psychological distress than are nonusers or to have verified psychi- 
atric problems. Evidence cited in previous Reports suggests that this is 
especially true of heavy users . 

Whether or not cannabis is a causal factor in an "amotivational syndrome" is 
still an open question. While a loss of conventional values with their stress 
on competitive career achievement has been commented on by numerous observers, 
it is often difficult to separate a possible drug-use related loss of motiva- 
tion from that produced by the prevailing values of a youthful counterculture. 
Thus, it is difficult to know whether the value shift resulted in greater 
emphasis on drug use. or vice-versa. While a decline in conventional motivation 
has been attributed to cannabis use in other cultures, evidence from the 
Jamaican study does not suggest that chronic users are less motivated than 
nonusers. Present studies of longer term users and of drug user careers in 

-18- 



the United States may be helpful in clarifying this issue. 

Overall then, present evidence suggests that marihuana use can result in psy- 
chiatric complications under some circumstances. Such complications, including 
acute panic and psychotic reactions, appear to be more common in those with a 
previous history of psychological difficulties or in those taking larger doses 
to which they are not accustomed. Nevertheless, serious complications of canna- 
bis use appear to be relatively infrequent. Chronic cannabis intoxication can 
be a problem in much the same way that chronic alcoholism is although there is 
little basis for knowing the comparative risk each of the drugs might pose 
under conditions of equal social acceptability. Loss of motivatiorir resulting 
from cannabis use remains an unverified possibility although there is little to 
suggest that it is an inevitable consequence of chronic use. 



FUTURE RESEARCH DIRECTIONS 



Our knowledge of the health implications of marihuana use has rapidly expanded 
over the past several years. However, there continue to be important areas in 
which additional research is needed. One of the most important is an expansion 
of research both here and overseas on the implications of chronic use. In addi- 
tion to making us aware of the health implications of widespread use such re- 
search can provide insight into the cultural context of use that may be helpful 
in limiting possible adverse effects. 

Other important areas for expanded research include: Study of marihuana use 
patterns among various segments of the population including minority groups, 
longitudinal studies of users over extended periods to determine the relation- 
ship of drug use to other aspects of life style, studies of the role of peer, 
family and institutional influences on patterns of drug diffusion, development 
of uniform data collection procedures, development of more sophisticated epi- 
demiological methods and cross cultural studies of cannabis use. Research in 
these areas will better enable us to estimate the degree of public health 
problem that marihuana use is likely to assume in future years and may provide 
valuable clues to methods of minimizing the public health hazard. 

There is a continuing need to probe the implications of marihuana use in indus- 
try and the possible hazard to industrial safety which such use may entail. 

Study of the biomedical aspects of marihuana use remains an essential ingre- 
dient of a continued program. The study of larger samples of chronic users 
abroad so as to detect less frequent hazards of long-term use is an essential 
aspect of this activity. Further knowledge of the mechanisms of action of 
marihuana and of the way in which it is physiologically transformed in the 
body are important areas. Such research can enhance our understanding of mari- 
huana itself, and may help us to anticipate possible adverse consequences of 
the interaction of marihuana with other commonly used drugs. 

Attempts are currently underway to develop uniform analytical methods in order 
to insure that analyses of cannabis here and abroad are comparable. Another 

-19- 



important technical goal is that of developing a simple, easily applied test 
of the level of marihuana intoxication. Such a test will be invaluable for 
both clinical and research purposes. 

The study of the interaction of marihuana with a limited number of other drugs, 
including alcohol, is already underway. This work needs to be systematically 
expanded in order to better assess health hazards that may be posed by multiple 
drug use. 

Possible adverse effects on specific organ systems such as the heart, lungs 
and central nervous system must be systematically studied both in animals and 
man. 

There have been a variety of clinical reports of various symptoms which may be 
related to marihuana use. These and other clinical case reports must be care- 
fully followed up by well designed animal and human research to determine the 
role of marihuana and other possible causative factors. It might be possible, 
for example, to develop an animal model for the frequently reported "amotiva- 
tional syndrome" to examine cannabis effects which would be difficult to study 
in human populations. 



20- 



EXTENT, PATTERNS, AND SOCIAL CONTEXT OF USE IN THE UNITED STATES 



This section contains a summary of present use patterns and trends in the 1972 
report. Brief summaries of the conclusions of that report are given, followed 
by new data available since its preparation in late 1971. There are two parts 
of this section that treat new topics in more depth than in former reports, 
however. These are concerned with sex differences in use, and drug selling. 
Research results that were omitted from previous reports and that seem particu- 
larly relevant today are also included. 

There is an increasingly solid mass of data on which to base descriptions of 
marihuana use in late 1972, compared with that which was available for the 
Marihuana and Health Reports of 1971 and 1972. The full report of the National 
Commission on Marihuana and Drug was released shortly after the 1972 report and 
included results of a detailed nationwide survey of marihuana use. (27) New 
figures are also available from the National Commission representing overall 
rates for 1972. (35b) Several surveys included in the past two Marihuana and 
Health Reports have new data to report comparing past with present rates. 
(5,32,37) An updated cumulative list of studies, surveys, and polls of il- 
legal drug use of all types has also recently been published. (4) Significant 
studies of special subjects such as family and peer influences, personality, 
and drug dealing have been reported during the past year. (7,8,20,18,34) Thus 
a more adequate picture of the epidemiology and etiology of marihuana use is 
now possible. 

Despite these advances, there are certain questions still unanswered. Among 
these are questions about the nature of the spread of use, the nature and con- 
ditions of cessation, the role of the law, and attitudes and communication 
influencing use. In addition, patterns of marihuana use in older age groups 
are less known; the same is true of use patterns among ethnic minorities at 
all ages. 

The issues of confidentiality and validity of data are still a concern in 
research on marihuana use. Most researchers make a special effort to protect 
the anonymity of subjects. This is both to protect the subjects from inad- 
vertent disclosure of their illegal behavior and to improve the chances that 
their self-reports will be accurate. There is evidence that falsification of 
high school students' self-reports is low, probably under five percent of a 
given group. (10) Several years have passed since many surveys and polls were 
initiated, and the continuing lack of evidence of large discrepancies gives us 
some measure of confidence in these data. 

Unfortunately, the methods of measurement of marihuana use, as well as that 
of other illicit drug use, are not consistent across studies. This makes it 
somewhat difficult to compare results. Consistent treatment of frequency, 
regularity, and recency of use, as well as the differentiation of marihuana 
and hashish, are not found as often as would be desirable. 



-21- 



ESTIMATES OF RATES OF NATIONWIDE CANNABIS USE AND CHANGES IN 1972 



The 1972 Marihuana and Health Report described two major sources of estimates 
of marihuana use in the general population. McGlothlin provided an estimate 
that by mid-1971 nine percent of the total population age 11 and older had 
used marihuana at some time. (26) Within the group of users, he estimated 
that almost half (46 percent) had stopped using or had used less than ten 
times. Only three percent were using daily, and the rest were using less than 
daily but at least once a month. Data collected in a nationwide survey by the 
National Commission on Marihuana and Drug Abuse released in January 1972 indi- 
cated higher rates: 14 percent of 12-17 year olds and 15 percent of adults 18 
years and older, for an estimated total of 24 million persons. (27) Three 
types of users were portrayed. The range of percentages of each was: experi- 
menters 50-60 percent; intermittent users 2-19 percent; moderate users 5-6 per- 
cent; and heavy users 2-4 percent.* At the time of the 1972 report, the dis- 
crepancy between the two nationwide estimates could not be explained except 
possibly as the result of different methods used in the surveying or estimating 
procedures . 

One year later, in mid-1972, McGlothlin again estimated total nationwide use 
for persons 11 years and older using all available survey data. (23) The 
overall percentage who had ever used was estimated as 14.2 percent, a total 
of slightly over 22 million persons. The distribution by age or grade and 
sex was : 



Percent Who Ever Used Marihuana, Mid-1972 







Mid-1972 






Total 


Male 


Female 


Grades 6-8 


7 


8 


6 


Grades 9-12 


28 


32 


25 


College 


54 


62 


41 


Age 18-24 (nonstudent) 


30 


39 


20 


Age 25-34 (nonstudent) 


15 


19 


10 


Age 35+ (nonstudent) 


6 


9 


3 


Total, age 11 and over 


14.2 


18.9 


9.5 


a McGlothlin, 1972 

















The National Commission on Marihuana and Drug Abuse estimates of the rates 
for the total population for mid-1972 are close. The estimate for the 12-17 
year group is 14 percent and for the 18-and-older group, 16 percent. (35b) 
McGlothlin' s estimates are well within the tolerance of sampling error of the 
Commission's study. Thus, the proportion of the population of 11 years and 
older who have ever used marihuana lies between 14 and 16 percent. 



* These percents did not total 100 percent because a small proportion of 
respondents did not answer the question. 

-22- 



According to McGlothlin's estimates for 1971 and 1972, total marihuana use 
increased about 5 percentage points during the year (from 9 percent to 14 per- 
cent). The Commission's two studies, however, indicate a much smaller in- 
crease - 1 percentage point at most. There is no satisfactory resolution of 
these differences, since inexactness exists in either set of estimates. Evi- 
dence from repeated surveys of segments of the population indicate, however, 
that stabilization of rates probably is occurring among adolescents. 

McGlothlin estimated that hashish use was about 20 percent of total marihuana 
use in mid -1972 and that it had increased. (23) 

There is some tentative evidence that rates of exposure to marihuana may be 
stabilizing for the teenage group. Results of a nationwide household inter- 
view survey of youngsters 12 to 17 years old conducted in May 1972 have now 
become available. (37) They show that the 15 percent rate found in an earlier 
1971 survey did not change; the same proportion was found in 1972. A West 
Coast junior and senior high school survey that has been repeated consecutively 
for four years also reports virtually no overall increase in marihuana use. (5) 
Details of these findings are described in the section on Marihuana Use by 
Students below. 

In McGlothlin's mid-1972 estimates of frequency of use, about the same propor- 
tion as in 1971 had stopped using or used less than 10 times (48 percent) ; a 
few more were using daily (5 percent) ; the rest were using at intermediate 
frequencies (20 percent at 1-4 times a month, 17 percent at 1-2 times a week, 
10 percent at 3-6 times a week) . The differences between these figures and 
those from 1971 are so slight as to be virtually non-significant. The National 
Commission's detailed findings of this type will be available in their 1973 
report . 

A consistent finding has been that states in the Northeast and West have con- 
siderably higher rates of use than those in the North Central area or in the 
South. Residents of metropolitan areas used marihuana more often than rural 
residents. Use has been found to be slightly higher among persons with above- 
average incomes and distinctly higher among those with higher education. Rates 
did not differ significantly among racial groups and only slightly by religious 
affiliations. (26) There is no new data suggesting that these patterns have 
changed . 

Youth continues to be a strong correlate of marihuana use, though the over-25 
groups have experienced an increase in use, according to McGlothlin's esti- 
mates. College students nationwide have used marihuana at a considerably 
higher rate than their non-college counterparts. (23) A nationwide study of 
high school graduates one year after graduation highlights aspects of this 
transition point with regard to drug use. (1) In 1970, non-student youth 
during their first year out of school used at the same rate as college fresh- 
men. (This rate rose from 21 percent of the high school seniors in 1969 to 
34 percent of the same 1 group in 1970.) In 1969, the college bound seniors had 
had a somewhat lower rate than the non-college bound in the first year of the 
study, but in 1970 were "catching up" in the freshmen year. Based on estimates 

-23- 



of college student use shown above, use rates of college students continue to 
increase at a rapid rate in subsequent years. 

There is comparatively little data regarding the kinds of persons most apt to 
adopt marihuana use when they are no longer students. The study mentioned 
above offers an interesting finding, however. (1) It found that males with 
the highest rate of "conversion" to drugs (including marihuana) one year after 
high school were those in (domestic) military service. (Those in overseas 
military service were not included in the study.) The group with the lowest 
rate were employed in civilian jobs. There are several implications in this 
finding, but more data need to be collected on a longitudinal basis for firm 
conclusions to be made. 

Findings are fairly consistent across studies regarding one related behavior 
of people who have ever used marihuana. They are more apt than nonusers to 
make use of such legal drugs as alcohol and tobacco. This finding has appeared 
repeatedly in studies of students and also was found in the Commission's survey 
results on adults. (27) Differences in frequency and regularity of use must 
be taken into account in identifying "types" of users. As use spreads to 
broader segments of the population it is to be expected that users will more 
and more resemble the "average person." 



Sex Differences 

McGlothlin, summarizing marihuana use rates in student populations for 1972, 
states, "For college students, the male-female ratio is about 3:2, and is 
somewhat closer at the high school level." (23) His data also indicated that 
in the general population, males were about twice as likely to have tried mari- 
huana as were females. Not only have more males than females tried marihuana, 
males are also more likely to use the drug with greater frequency. The propor- 
tion of females who have used marihuana three or more times per week is about 
half that for males. Recent data indicate, however, that there is a trend 
toward increasing use of marihuana among females. 

One study based on an area of relatively high use reports that the number of 
females who have used marihuana has increased since 1971. (5) In the category 
of "any use during the year," male and female rates for grades 7 through 12 
were strikingly similar. Males tend to average a few percentage points higher 
than girls, but the overall differences are slight. The percentage of mari- 
huana use was found to be from 17 to 61 percent for males and from 13 to 53 
percent for females, depending on school grade. Both male and female rates 
increased slightly after 1971, but the difference in use between the sexes is 
not great. The details of those differences are seen below: 



-24- 



Marihuana Use in San Mateo Schools, by Sex and 
Frequency of Use, 1971 and 1972 a 





Any use 


i in the 




past 


year 


MALES 






GRADE 


1971 


1972 


7 


17.6 


17.2 


8 


29.1 


33.3 


9 


44.4 


43.9 


10 


49.7 


51.9 


11 


57.9 


58.0 


12 


59.1 


60.8 


FEMALES 






7 


12.6 


13.2 


8 


25.8 


29.2 


9 


40.5 


39.0 


10 


48.1 


49.3 


11 


49.6 


52.4 


12 


48.3 


53.0 



10 times or more 



50 times or more 



1971 



5, 
14, 
26. 
33. 
42.3 
43.7 



4.1 
12.4 
23.3 
31.1 
32.6 
30.6 



1972 

5.8 
17.2 
26.8 
36.8 
41.2 
45.0 



4.6 
14.1 
23.0 
32.2 
35.7 
35.5 



1971 



17.2 
23.2 
30.2 
32.3 



b 
b 

11.6 
17.0 
19.3 
18.5 



1972 



15.9 
25.5 
28.2 
31.7 



b 

b 
12.5 
19.1 
20.7 
20.4 



a Blackford, 1972 

b Information not available 



-25- 



The San Mateo figures are consistent for "use ten times or more" and "use 
fifty times or more." Again, males tend to average only about five points 
higher than the females for each category. The range for "10 times or more" 
was from 6 to 45 percent for males, and from 5 to 36 percent for females. 
For the "50 times or more" category, rates ranged from 16 to 32 percent for 
males and 13 to 21 percent for females. (5) 

In another recent study conducted in Montgomery County, Maryland (a Washington, 
D.C. suburb), also on junior and senior high school students, both males and 
females showed significant increases in marihuana use over 1969. However, the 
differences between males and females' use were not pronounced. The reported 
rates for those who had used marihuana, but had ceased, were from 2 to 20 per- 
cent for males and from 2 to 15 percent for females. However, rates of daily 
use for males appear to be almost twice as high as those for females. An 
exception was found in the tenth grade where the rate for females was slightly 
higher than that for males (males: 4.2 percent; females: 4.8 percent). By 
the senior year, the daily usage rate for males was more than twice that of 
females (males: 7 percent; females: 4 percent). (11) 

In the Montgomery County study, the monthly and weekly rates varied with age 
(or grade level). In some instances, the males' rates were higher, in others 
it was the females'. The data indicate that at either extreme (7th or 12th 
grade), the males' usage rate exceeds the females', although there may be 
variability in the middle grades, with the females' rates often exceeding the 
males'. (11) 

Similar results were also obtained from a study of current users of non- 
medical drugs at one university. Data from a four-year period show that the 
rates for male usage of marihuana and hashish was 95 percent, and for females, 
91 percent. (9) 

In many instances male-female differences do occur as expected. A study con- 
ducted in North Carolina on forty- four junior and senior high schools, for 
example, showed that 29 percent of the males and 20 percent of the females 
reported trying marihuana at least once. (24) It might be expected to follow 
this traditional pattern in the South and other areas where marihuana use has 
not been as heavy as in coastal and urban areas. 

In one interesting analysis of institutional differences in marihuana use, 
coeducational institutions were compared with all-male and all-female schools. 
(14) The rates of marihuana use were generally lower at the coeducational 
institutions. The findings .from this study indicated that drug usage for both 
males and females at co-ed schools is not as great for either sex as it is at 
single sex institutions. It appeared as though the presence of members of the 
opposite sex on campuses lowered the amount of marihuana use for both males 
and females. The reported rate for males at all-male institutions was 
decidedly greater (58 percent) than their rate at coeducational institutions 
(41 percent). This difference was also reported for the female colleges (31 
percent) versus 25 percent in co-ed schools. The overall rate for both males 
and females was 34 percent at coeducational schools, less than the combined 
rates for males and females at single sex colleges and universities. The 

-26- 



study concludes, "...heterosexual relations may well play an important role., 
in reducing drug participation." (14) 

These studies shed more light on the question of male-female differences in 
drug use. Generally, the studies indicate that there is not as great a dif- 
ference between male and female use of marihuana as has existed in previous 
years. However, with larger amounts of marihuana and increased frequency of 
use, the males' usage rate still remains somewhat greater than the females'. 



MARIHUANA AND INDIVIDUAL DRUG HISTORIES 



There is very little new data to report on individual marihuana use patterns 
over time. As noted above, on a nationwide basis, about half of all those who 
ever used marihuana are current users. Half are virtual nonusers, having used 
it less than ten times. (23) In the nationwide study of teenagers in 1971, 
however, it was noted that the size of the group who continued use beyond 
initial experimentation was larger for marihuana use than for any other drug. 
(10) 

It is important to keep these aspects of use clearly in mind when assessing 
the extent of marihuana use. Different conclusions can be drawn depending on 
the type of question asked, as was pointed out by researchers studying stu- 
dents' drug use in New Haven over a two-year period. (3) Increases in those 
who "ever used" were highly evident, but when "currently use" was recorded 
separately, the increases were much less evident for most drugs. In the case 
of marihuana, current use did increase slightly from 1971 to 1972, but it was 
not as pronounced as the increase in "ever used." The latter group, of course, 
include many teenagers who have experimented only once or twice. 

Studies of the duration of use, in contrast to frequency or regularity of use 
are few. Some longitudinal studies are attempting to trace individual use 
patterns over time, but none has been in operation long enough to make con- 
clusive statements about typical use histories. Since many users are in 
younger age groups, it will be a number of years before adequate long-term 
drug histories from these groups are available. One study of hippies followed 
up after their initial visit to the Haight-Ashbury Clinic (beginning in 1967) 
suggests a pattern that might be expected of multiple drug users from that 
unique subculture. (36) Based on data from those who could be located and 
interviewed several years after contact with the clinic, it appears that the 
use of a wide variety of drugs has declined but that a majority of this group 
continues to use marihuana and the milder psychedelics. 

Associations between marihuana use and the use of other drugs are similar to 
those previously reported. The pattern of association between alcohol or 
tobacco use and that of marihuana has been mentioned. If other drugs are 
used, marihuana is typically the first illegal one in the sequence. Users 
who associate with "hard" drug users and are involved with selling are more 
likely to later use opiates and cocaine. (16, 17) 



-27- 



Several interesting conclusions were drawn by investigators testing the inci- 
dence and frequency of use of a number of illegal drugs for underlying con- 
sistency. The investigators were interested in whether the adoption of various 
drug use follows a predictable pattern of mild to strong, and in learning any 
other basis^ for decisions to use or not to use a particular drug frequently. (33) 

They found that among college students a predictable pattern does occur. The 
various drugs tried can be predicted reliably from knowledge of the last one 
tried. The substances could be ordered as follows from greatest to least extent 
of use: "Beer, Wine, hard liquor, midwestern pot, non-midwestern pot, hash, LSD, 
mescaline, speed, barbiturates, opium, psilocybin, THC, MDA, thorazine, cocaine, 
DMT, and heroin." (This pattern held true for another sample of drug users, 
but not for an ex-addict sample; they hardly ever used psychedelics, but used 
heroin and cocaine more often.) (33) 

The investigators who looked at the patterns of various drug used were also 
interested in the factors that might be responsible for this predictable order. 
Based on judgments of perceived safety (i.e., hazard to health) and availability, 
it was determined that both these attributes played a role in determining the 
rank order of use. Availability was more influential than safety, however; it 
was about five times as powerful a factor. (33) As an example of this process, 
marihuana headed the list for safety but alcohol was more widely used because 
it was seen as more available. Based on this tendency, one might expect use 
of a new drug to become more widespread if the substance is easily available, 
with a lesser effect on spread of use related to the perceived hazard of such 
use. The more sophisticated type of analysis illustrated here considerably 
enhances our knowledge of the basic processes underlying surface events and 
makes better prediction possible. 

MARIHUANA USE BY STUDENTS 



Student use increased in the country as a whole in 1972, but high school drug 
use may not be increasing at as high a rate as before. There continues to be 
wide variation in rates from school to school. (4, 31) Among all school studies 
reported, both high school and college, the proportions who ever used marihuana 
range from 6 to over 60 percent . 

High Schools 

In the first section of this chapter, the findings from a nationwide teenage 
survey and a West Coast community (San Mateo, California) were mentioned. 
Analysis of the nationwide survey is not yet complete, but details of the San 
Mateo data can be presented here. 

The San Mateo series is now five years old. It shows a steady increase in 
annual use (any use in the preceding year) of marihuana at all grade levels. 
Overall, however, marihuana use appears to have stabilized at about 50 percent 
of the students in grades 10-12. Though use was slightly higher in 1972 than 

-28- 



in 1971, the rate of increase was distinctly lower in 1972. Stabilization 
also seemed to occur in the higher frequency of use categories. (See table 
below) 



San Mateo County, California, Schools Grades 10-12 a , Percent 
Reporting Marihuana Use in the Past Year 



Marihuana Use 1968 1969 1970 1971 1972 

Any use during past 31.9 39.5 42.0 49.7 51.0 
year 

10+ times during 17.5 24.4 26.3 32.9 34.5 
past year 

50+ times b b 15.9 21.2 21.8 

a - Blackford, 1972 
b - Not collected 



The levelling trend in the senior high school was also true in the junior high 
grades. A word of caution: There is some danger in considering those trends 
permanent ones. A levelling trend also appeared in the San Mateo figures 
between 1969 and 1970, but did not continue. Rates went up sharply the fol- 
lowing year. (5) 

Several other school systems have started annual series and now have second- 
wave results to report. A longitudinal study of personality, cigarette smok- 
ing, and drug use from 4th through 12th grade in Boston suburban schools has 
second -wave results. Those figures show a slight tendency for higher rates 
in 1972, but the two years' rates were not dissimilar. (34) Montgomery County, 
Maryland, an affluent suburb of Washington, D.C., has reported a doubling of 
rates, starting with the 9th grade, since 1969, a span of 3 years. The cur- 
rent figure is 40 percent reporting having ever used marihuana and 15 percent 
who report using it "regularly." (11) 

Two high school studies are especially interesting because of the composition 
of the samples. One study examined drug use rates for three years in five 
Houston, Texas, schools with different ethnic composition. (6) The other 
study of interest was of high-achieving juniors or seniors listed in "Who's 
Who Among American High School Students" who responded to a mail question- 
naire in 1971 (with 46 percent replying). (28,29) 

The Houston study indicated that the two predominantly black schools were 
consistently lower than the other three schools in marihuana use in the three- 
year period. The two predominantly Anglo schools were highest, and the hetero- 
geneous school with a large number of Chicanos was intermediate in use. Use 

-29- 



of marihuana was fairly stable over the three years, except for the two Anglo 
schools where there were significant increases. Rates were consistent by socio- 
economic status, also, the higher rates more typical of higher status. (6) 

The high-achieving "Who's Who" students were surveyed in 1970 and 1971. (28) 
Although return rates were not as high as desirable in the two surveys, the 
results indicate that marihuana was in evidence as part of the behavior reper- 
toire of many prominent high school students in both years. In 1970, 10 per- 
cent of those replying said they used marihuana then. In 1971, 13 percent 
reported using it more than twice. (21 percent had used it at least once.) (28) 

The trends in marihuana use at the high school level are not as striking as 
in past years. The proportion who have ever used the substance nationwide 
has increased only slightly if at all. Undoubtedly in some schools it will 
continue to rise as the fad-like quality of the behavior dominates. In other 
schools, the rate seems to have stabilized. The situation should be watched 
closely in the coming year to see if this trend is a reliable one. 

Colleges 

As noted above in McGlothlin's estimates, college students' extent of use of 
marihuana was greater than that of any other group by mid -1972. The increase 
in percentage points from 1971 to 1972 also was greater for the college 
student group than for any other. 

A major nationwide study of college students' life styles, including drug use, 
has reported changes in student rates between the 1969-70 and 1970-71 academic 
years. (Other factors investigated include concomitants of drug usage, insti- 
tutional characteristics, and consequences of usage.) (32) Among a cohort of 
students in fifty four-year colleges across the country, large increases 
occurred in both marihuana and hashish use during that one-year period. In 
both years, the cannabis products were used by more students than used any of 
the other illegal drugs. The figures were as follows: 



Percent of College Students Using Cannabis * 



1969-70 



1970-71 



Used During 
Ever Used Academic Year 



Used During 
Ever Used Academic Year 



Marihuana 


27.6 


23.6 


41.6 


37.3 


Hashish 


18.4 


16.2 


27.6 


23.2 


a - Rossi, 


1972 









-30- 



Most other drugs besides cannabis also increased in use during the same year. 
It is not known how much overlap there might be among users of the various 
drugs. It should be noted that almost all those who had ever used either 
substance had used it during that academic year. 

In an analysis of those who did or did not use cannabis in 1969-70 compared 
with those who did or did not use in 1970-71, it was found that more students 
were taking up use (21 percent of former nonusers) than were dropping use 
(11 percent of former users). The investigators estimated that a final "equi- 
librium" incidence of extent of exposure will be about 66 percent, based on 
analysis of current trends. 

Another recent study of nationwide drug use rates, analyzed by type of college, 
reported that higher rates were associated with the following institutional 
traits: more selective (as to admission), larger, public, male, or non- 
sectarian. (14) Individual student characteristics associated more often with 
drug experience were: higher education or economic achievement of parents; 
liberal political affiliation; male; lack of active religious affiliation; 
certain academic majors (social sciences, humanities, or the arts); higher 
aspiration for an advanced degree; higher grade point average; and negative 
attitudes toward the war and government. Of the set of factors associated 
with drug experience, the authors found that anti-war activism, religion (lack 
of, or affiliation as Jewish), sex, and characteristics of the institution, 
were the strongest predictors of drug use. The characteristics listed above 
are not substantially different from those found in other studies of high 
school and college students. (26) The authors pointed out, however, that a 
wider "net" of predictors needs to be tested in such studies. (14) 

By far the largest number of surveys of drug use available have been conducted 
with school or college populations. Some are sophisticated in design and 
analysis and add much to our understanding of drug use. Implications of some 
of these studies are found in the sections below on social aspects of use and 
personality characteristics of users. Some other school and college studies 
have been done with less thought and can at best only provide statistics of 
interest in the local area. Regardless of their limited applicability, these 
scattered studies do provide a "feel" for conditions. The rates vary quite 
widely, suggesting that in many areas students may be potential (not actual) 
drug users merely because of local conditions of drug supply, school ethos, 
contact with college populations, or other unknown forces. The results of all 
school surveys are consistent in showing increases by grade and in the order 
of "popularity" of illegal drugs. Marihuana is consistently the most popular 
and heroin the least. 



MARIHUANA. USE IN OTHER GROUPS 



In the 1971 and 1972 Marihuana and Health Reports, research was reported from 
scattered studies of military populations, psychiatric patients, school drop- 
outs, a group of occupations, hippies, Negro men in St. Louis, employed youth 
and ghetto youth. The highest rates of marihuana use found in that disparate 
set of studies were among hippies and school dropouts. 

-31- 



There are still relatively few studies of marihuana use per se among non- 
student groups. Military groups are an exception; several studies of service 
personnel, both in the U.S. and abroad, were published in 1972. Other than 
the military, the only new studies of special groups available are those on 
physicians, nurses, and nursing students. 

In three surveys of health professionals, Lipp and his associates have found 
some surprisingly high rates of marihuana use. They are surprising, consider- 
ing the values held by such groups and the risk to their careers of engaging 
in illegal behavior. The most surprising rate was the one reported for physi- 
cians -- four samples of A.M. A. members in New York City, San Francisco, 
upstate New York, and Nebraska. It should be mentioned that the return rate 
for the survey was rather low (only about half the sample), so these results 
must be interpreted cautiously. (21) 

The proportion of physicians who had been "exposed to use" of marihuana was 
37 percent; within this group, 25 percent had used it at least once; and 7 per- 
cent were using it currently. There were significant differences in use by age, 
younger physicians having used at a higher rate than older ones. There were 
also significant differences by geographic area: the New York City and San 
Francisco rates were higher than those in the other two areas. (21) 

In two surveys of nurses and nursing students conducted at their national con- 
ventions, rates were lower than among the physician groups described above. 
Not surprisingly, nursing students had higher rates than nurses. Among students, 
13 percent had used marihuana and 4 percent reported doing so currently. Among 
graduate nurses, 3 percent had used it, and only 1 percent were doing so cur- 
rently. (22) 

r 

Military Use 

Reports are now available on several well-conducted surveys of military popula- 
tions made in 1971. Rates of use are reported here along with some description 
of individual characteristics related to drug use. 

A large sample survey of all the Armed Services (enlisted) worldwide in 1971, 
produced an overall figure of 30 percent who had used marihuana in the preceding 
year. Among all who had used it, about half had used it less than ten times. 
About 40 percent of those using reported doing so several times a week or more. 
When asked whether they had used marihuana while on duty, from 3 to 16 percent 
reported having done so in the preceding year. Up to 45 percent in one branch 
said they had seen marihuana used on duty. (12) 

More Army personnel used marihuana than did those in other branches of the 
Armed Services; Marine Corps personnel were next, then Navy and last, Air Force 
personnel. (These differences may reflect varying socio-demographic character- 
istics of those branches rather than conditions inherent in the institutions.) 
Rates of use were higher among younger enlisted men, at lower pay grades. Use 
was somewhat higher in Vietnam than at other service locations. Use by indi- 
viduals in the service was highly related to former use in civilian life. (12) 

-32- 



Another large study of enlisted military personnel was done at Fort Lee, 
Virginia, in 1970. The group included military students (about 70 percent), 
support personnel, and instructors. Overall marihuana use reported totalled 
44 percent; this figure represented all previous use of the substance and was 
not limited to use in the preceding year (as was the figure for enlisted men in 
the above study). All marihuana users were tabulated in three different groups, 
an analytic distinction that proved interesting in examining the correlates of 
the three types. One group (19 percent) consisted of persons who had used mari- 
huana only and no other illegal drugs; a second group (also 19 percent), called 
Multiple drug users, had used marihuana and other substances except heroin; the 
third group (6 percent) had used heroin, marihuana and may have used other sub- 
stances. Among the "marihuana only" users, over half (52 percent) had used it 
only once or twice. (15) 

All three of the drug-using groups differed in some respects from nonusers, in 
that they were more likely to be younger, single, educated, and of lower rank. 
They also had somewhat more convictions for various legal offenses (excluding 
traffic offenses). However, all three marihuana -using groups differed from one 
another too. The "marihuana only" group was somewhat older than the other two 
drug-using groups, better educated, and had fewer offenses. Heroin users, 
compared with the other two user groups, were the youngest, more likely to be 
non-white, had the least education, and more often had convictions for offenses. 
(15) 

Several other studies of the military, in Vietnam and in Korea, were published 
in 1972. They reported marihuana use rates ranging from 20 to 40 percent of 
the groups surveyed. (35, 2) The majority of smokers who started in Vietnam 
did so in the first three months of their tour of duty. 

One additional isolated finding is available to illuminate a different facet 
of the military's experience with marihuana. (30) It is a report on American 
soldiers in West Germany and their use of hashish in 1970 and 1971. According 
to that report, 46 percent of the soldiers had smoked hashish at least once; 
16 percent had smoked it regularly three times a week or more often. (30) This 
rate is much higher than that estimated for the general population of the U.S. 
(20 percent of all marihuana use). 

Taken altogether, the findings on military use of marihuana indicate that their 
rate of use is somewhat higher than the overall non-military rate. If age is 
taken into account, however, the differences would not be striking. Many of 
the characteristics of military users compared with nonusers are the same as 
those found in studies of the civilian population. 



SOCIAL AND PERSONAL ASPECTS OF MARIHUANA USE 



Earlier reports in 1971 and 1972 described other social aspects of marihuana 
use, such as peer or group support, that continue to be closely associated 
with use. Also mentioned earlier was the probability that potential users pass 
through several different stages in the process of becoming an actual user. A 

-33- 



fair number of new topics of interest have been explored and reported in detail 
during the past year: a study of information sources for decisions about mari- 
huana; the roles of family and peers in drug use by young people; and drug deal- 
ing. Also, a longitudinal study of personality and drug use has reported some 
unique findings. 

One study has focused on the sources of information used by elementary and 
secondary students in various stages of acquaintance with marihuana. (20) The 
sources of information about marihuana mentioned most frequently by all students 
in the study were parents, television, and friends. But there were distinct 
differences in the types of sources accepted by students at various 'grade levels 
For 5th graders, television and parents were most significant; for 7th graders, 
friends and television; and for 11th graders, friends and other students played 
the largest role. In general, younger children use more socially approved 
sources compared with older students (who tend to rely on "non-authority u 
sources). The authors commented that many students appear unaware of the in- 
fluence process surrounding their decisions about marihuana use. (20) 



Parents and Peers 

Three studies have investigated the relationship between adolescent use of 
marihuana and use of marihuana and other drugs by parents and peers. Two of 
the studies were conducted on adolescents between 12 and 17 years of age, in an 
interval of several years. One study confirms the crucial role of peers in ado- 
lescent drug use. (18) Adolescents' use of marihuana is directly related to the 
best friend's self-reported drug use. An adolescent's marihuana use is also 
related to the proportion of friends reported to have used marihuana. When 
none of the adolescent's friends used marihuana or other drugs, only 7 percent 
of such youngsters were found to use it themselves. By contrast, when all their 
friends reported use of marihuana, 92 percent had also used it. Similarly, 
adolescents are more likely to be users (76 percent) if their brothers and 
sisters are users, and to be nonusers (38 percent) if their siblings have never 
'tried marihuana. 

Results from another study also underscore the strong influence of peers on an 
adolescent's drug use. (10) Data from the Columbia study of teenage drug use 
indicate that drug users in all grades were much more likely than nonusers to 
report having at least a few close friends who use one of the following drugs: 
marihuana, amphetamines, LSD, barbiturates, or heroin. Eighty-seven percent 
of the drug users reported that their friends also used marihuana, while only 
4 percent of the nonusers had such friends. 

Adolescent use of marihuana is related not only to the best friend's use, but 
also to the frequency with which the friend has used marihuana. Drug use is 
also directly related to the frequency of mere contact with peers and to being 
peer-oriented rather than parent-oriented. (18) Marihuana users are more 
likely to be found among students who visit with their friends on a daily 
basis, among those who would continue to see their friends over their parents' 
objections, or among those who respect their friends' opinion over their 
parents', when confronted with a problem. Similarly, these users are found 

-34- 



to rely on peers and contemporaries as sources of Information about drugs, 
while nonusers are reported to have learned (or obtained most of their knowl- 
edge) from their parents, mass media or the school. 

Both parents' and best friends' drug use have an independent effect on the 
adolescents' marihuana use. The effect of peers, as illustrated, is larger 
than that of parents. Lowest rates of marihuana use are found to occur when 
neither the parent nor the best school friend have used psychotropic drugs, and 
the highest rate (71 percent) is found when both have used them. (18) 

In addition to the influence of peer drug use on an adolescent's marihuana use, 
perceived, as well as self -reported, parental use of psychotropic drugs has been, 
shown to have a profound effect on an individual's drug use. These data report 
that there is a minimum of 50 percent increase in the rate of marihuana use 
among those individuals who report that their parents are users of psychoactive 
drugs, as compared with those who do not report parental drug use. Associations 
based on the adolescent's perceptions of behavior are more than twice as high 
as the associations based on parental self-reports, or parental actual drug use. 

Data also indicate that parents tend to deny the extent of their children's 
drug use and that they are ineffective in enforcing parental rules concerning 
drug use. 

Results from a study of family factors indicate that drug use is part of a 
constellation of beliefs and practices related to the child-rearing goals and 
personal beliefs of the parents. A study of white, black and Mexican-American 
families indicates that there are certain factors that increase the probability 
of drug use in children. These characteristics include: lack of cohesion in 
the family, use of alcohol and medications by parents, and less emphasis on 
self-control. Families which tend not to encourage drug use are characterized 
as cohesive, support authority in the home, and are generally more content. (8) 

Drug Dealing 

The subject of dealing or selling marihuana illegally has received little con- 
sideration in previous reports on marihuana use. Dealing is ordinarily viewed 
as a separate phenomenon from using. Recently, however, research on the West 
Coast has shown that marihuana dealers are marihuana users, and that dealing 
is encouraged in a social context, with friends and peers. (7) The typical 
marihuana dealer is not a street dealer of hard drugs such as heroin or cocaine. 
He is reported to be middle class, in his twenties, not involved with criminals 
and rarely delinquent in other ways. The dealer is generally a user and selling 
is largely a function of the amount he uses. 

The extent of use significantly affects the amount a dealer sells. Sales are 
most frequently made between friends or acquaintances. Among those using 
every day, 96 percent had sold, while among those using less than once monthly, 
only 29 percent had sold. Selling marihuana is also associated with the extent 
of multiple drug use, as well as involvement with a drug centered subculture, 
tooile 13 percent of those who had used only marihuana had also sold it, 64 per- 
cent of those who had used three or more other illicit drugs had done so. 

-35- 



Selling marihuana is also linked to the number of close friends who are regu- 
lar smokers. Among those who claimed 60 percent or more of their friends were 
users, over two-thirds sold marihuana. Of those claiming between 29 percent or 
less of their friends used marihuana regularly, only 21 percent sold the drug. 

The dealer is usually a distributor and provides marihuana to his friends 
through informal transactions. Dealing is common and reportedly widespread, and 
the transition from experimenter to user to dealer is often rapid. The process 
is more likely to occur if the user enjoys drugs and risk taking. The proba- 
bility is further increased if his friends are regular users. Other factors 
which contribute to regular marihuana dealing include an interest in money, 
desire for peer approval and prestige, and a willingness to violate the law. 
Additional findings also indicate that selling is associated with an avoidance 
of traditional work and experimental life styles. 

Most regular marihuana users are reported to have been involved in dealing at 
one time in their lives. Cannabis was also found to be the preferred drug by 
dealers. Most reported experiences with both marihuana and hashish. Daily use 
remained constant for approximately 44 percent of all users after age 19. 

Investigation of high school marihuana sellers shows that marihuana was the 
first illicit drug used by 68 percent of these individuals. Dealers stated 
that they had sold off-campus as well as on, although they did not necessarily 
always sell to fellow students. On-campus sales were reported more frequent, 
and most customers were friends or acquaintances of the seller. 

Marihuana users or dealers were not found to be common among junior high school 
students. Drug use by young teenagers is primarily social and usually occurs 
at home. Only 10 percent of junior high students using marihuana indicated 
that they obtained their supply from a "professional dealer," Supplying drugs 
to other students was reported by about one-fourth of the junior high school 
students . 

An interesting finding in this study was that many dealers believed that there 
should be regulation or criminal statutes for opiates, amphetamines, barbitu- 
rates, hallucinogens, tranquilizers, alcohol and tobacco, but not for marihuana. 
The rationale given for control of these other substances was that all the other 
drugs (except cannabis) are known to be potentially harmful. Another reason 
some dealers supported the need for regulation of harder drugs was to assure 
purity of the preparation. 

Personality Predictors 

The social and demographic correlates of marihuana users compared with nonusers 
have been reported frequently, and they tend to be fairly consistent (see above). 
No study so far has been able to show whether there are other personal character- 
istics existing prior to initial drug use that would give clues to susceptibility 
to use of marihuana. One study now has preliminary data to report on one group 
of junior and senior high students' and their characteristics before they ex- 
perimented with drugs . (34) 

-36- 



According to the study of students in six selected school systems near Boston, 
in 1969, a small number of characteristics were quite in evidence among students 
who later, in 1972, would use marihuana. (Data were available on students as 
early as the 4th grade.) Among these characteristics were: rebelliousness, low 
grade point average, cigarette smoking, and favorable attitude toward cigarette 
smoking.* Among these, rebelliousness toward authorities and rules was the 
strongest predictor. All of these characteristics were more true of marihuana 
users than nonusers, and more true of heavier users than of lighter users. (34) 
As this study progresses, more findings will be available to describe later 
experimenters and those who discontinue use. 



* Attitudes toward drugs were not measured in 1969 



-37- 



Bibliography 

1. Anon. Drug Use Among Nation's Youth Explored in Study; Many 

Drugs Rejected, Marihuana Attitudes Divided, In Institute 
for Social Research Newsletter , Ann Arbor, Michigan, Spring 
1972, 'pp. 4-5. 

2. Baker, S e L., Jr., Drug Abuse in the United States Army. Bulletin 

of the New York Academy of Medicine , Vol. 47,541-549, June 1971. 

3. Berberian, Rosalie M. , "Drug Use among Adolescents." Paper pre- 

sented at the annual meeting of the American Public Health 
Association, Nov. 14, 1972. 

4. Berg, Dorothy, & Broecker, Line 11, Illicit Use of Dangerous Drugs 

in the United States , June 1972, Bureau of Narcotics & Dangerous 
Drugs, Washington, D.C. 

5. Blackford, Lillian, "Preliminary Report, 1972, San Mateo County, 

California, Surveillance of Student Drug Use," San Mateo, 
California, May 24, 1972, (NIMH Grant DA 00094). 

6. Bloom, Robert, J. Ray Hays, and G. Michael Winburn. Marijuana 

Use in Urban Secondary Schools :a Three Year Comparison. 1972. 
Texas Research Institute of Mental Sciences, Houston, Texas, 
submitted for publication. 

7. Blum, Richard, The Dream Sellers , 1972, San Francisco; Jossey-Bass 

Inc., 1972. 

8. Blum, Richard H. , & Associates, Horatio Alger's Children , San 

Francisco; Jossey-Bass, Inc., 1972. 

9. Dvorak, Edward J., A Longitudinal Study of Non-Medical Drug Use 

Among University Students: A Brief Summary, Journal of the 
American College Health Association , Feb. 1972, Vol. 20, No. 3, 
212-215. 

10. Elinson, Jack, A Study of Teen-Age Drug Behavior, Columbia Univer- 

sity School of Public Health, New York, N.Y., NIMH Grant DA-00043, 
Progress Reports, 1971-72. 

11. Elseroad, Homer, and Goodman, Samuel, "Teenager's Attitudes Toward 

the Use of Drugs, Alcohol and Cigarettes: Findings of a Survey 
Conducted in January 1972, Among Students in Grades 7 through 
12 of the Montgomery County, Maryland, Public Schools," August 
31, 1972. 



-38- 



12. Fisher, Allan H. Jr., "Preliminary Findings from the 1971 DoD 

Survey of Drug Use," March 1972, Human Resources Research 
Organization, Alexandria, Virginia. Technical Report No. 72-8. 

13. Fisher, Allan H. , K. Eric Nelson, & Jacob Panzarella, "Patterns 

of Drug Usage among Vietnam Veterans," May 1972, Human Resources 
Research Organization, Alexandria, Virginia, Professional Paper, 
No. 12-72. 

14. Gergen, Mary, Kenneth Gergen & Stanley Morse, Correlates of 

Marihuana Use Among College Students. Journal of Applied Social 
Psychology , 1972, Vol. 2, No. 1, 1-16. 

15. Greden, John F., & Donald W. Morgan, Patterns of Drug Use and 

Attitudes Toward Treatment in a Military Population, Archives 
of General Psychiatry , Feb. 1972, Vol. 26,113-117. 

16. Goode, Erich, Cigarette Smoking and Drug Use on a College Campus, 

The International Journal of the Addictions , Vol. 7, No. 1, 
133-140, 1972. 

17. Grupp, Stanely, E., Marihuana Use and Emergent Drug-Use Patterns. 

NIMH grant MH-14157, MH-17196. 

18. Kandel, Denise. "Adolescent Marihuana Use and Interpersonal 

Influences." Paper presented at the annual meeting of the 
American Sociological Association, August 1972. 

19. Kandel, Denise. Family Processes in Adolescent Drug Use, NIMH 

grant DA 00064. Progress report, 1972. 

20. Kowitz, Albert & Richard Clark, Ways Youth Receive Information 

about Marihuana, NIMH DA 00144, Final Report Summary, July 31, 
1972. 

21. Lipp, Martin & Samuel Benson, Physician Use of Marihuana, Alcohol, 

and Tobacco, American Journal of Psychiatry , Vol. 12 9, No. 5, 
Nov. 1972, 612-616. 

22. Lipp, M. R., S. G. Benson, & P. S„ Allen, Marihuana Use by Nurses 

and Nursing Students, American Journal of Nursing , 2339-2341, 
December 1971. 

23. McGlothlin, William H. , Marihuana: An Analysis of Use, Distribution 

and Control, Contemporary Drug Problems , Vol. 1, No. 3, Summer 
1972, 467-500. 



-39- 



24. McLeod, Jonnie, and Gloria Grizzle. "Alcohol & Other Drug Usage 

Among Junior and Senior High School Students in Charlotte-Meck- 
lenberg," Prepared for Community Drug Action Committee, 
Charlotte-Mecklenberg, North Carolina, June 19, 1972. 

25. Marihuana and Health , A Report to Congress from the Secretary 

UoS„ Department of Health, Education, and Welfare. Subcommittee 
on Alcoholism and Narcotics of the Committee on Labor and 
Public Welfare, United States Senate, Washington; D.C.; U.S„ 
Government Printing Office, 1971. 

26. Marihuana and Health . Second annual report to Congress from the 

Secretary of Health, Education, and Welfare. Subcommittee 
on Alcoholism and Narcotics of the Committee on Labor and Public 
Welfare, United States Senate, Washington; U.S. Government 
Printing Office, May 1972. 

27. Marihuana : A Signal of Misunderstanding, First report of the 

National Commission on Marihuana and Drug Abuse . Washington, 
D C. ; U.S. Government Printing Office, March 1972. 

28. Merit Publishing Company. "Second Annual National Opinion Survey." 

1971. Northfield, Illinois. 

29. Merit Publishing Company. "Survey of High School Achievers." 

1970. Northfield, Illinois. 

30. Rensberger, Boyce, Moderate Hashish Use Found to Cause Few Ills, 

New York Times . Friday, July 7, 1972. 

31. Research Triangle Institute. NIMH Contract HSM-42-72-169. Survey 

of Current Studies. 

32. Rossi, Peter. Study of Life Styles and Campus Communities. 

Department of Social Relations, Johns Hopkins University, 
Baltimore, Maryland, NIMH grant DA 00156. Progress Report, 
1972. 

33. Sinnett, E.R., K„S. Wampler, & WoM,, Harvey, Consistency of Patterns 

of Drug Use, Psychological Reports , 1972, Vol. 13:143-152. 

34. Smith, Gene, Drugs and Personality, NIMH grant DA 00065. Progress 

Report, 1972. 

35. Stanton, M, D„, Drug Use in Vietnam: A Survey Among Army Personnel 

in the Two Northern Corps , Archives of General Psychiatry , 
Vol. 26:279-286, March 1972. 



•40- 



35b. Sussman, Ralph, personal communication, National Commission on 
Marihuana and Drug Abuse. 

36. Wallach, Amira. Varying Fates of Young Drug Users, Pre-publication 

draft of paper presented at Meetings of the California State 
Psychological Association Annual Convention, Coronado, Jan. 1971. 

37. Zanes, Anne. Personal communication concerning NIMH grant DA 000^3, 

A Study of Teen-age Drug Behavior, School of Public Health, 
Columbia University, New York, N.Y. 



-41- 



MARIHUANA USE IN OTHER COUNTRIES 



Introduction 



The herb that Linnaeus named Cannabis sativa over two centuries ago originated 
somewhere in the desert regions to the south and east of the Caspian Sea. (6) 
Today it grows in almost all countries of the world, in a wide variety of 
climates and physical environments, ranging from the equator north to 60 
degrees latitude. This adaptability is due, almost certainly, to human inter- 
vention over a long period of time. Human exploitation of cannabis is thought 
to reach back as far as 6,000 years, with actual cultivation beginning only 
slightly more recently. 

Although the common name hemp has come to be associated with this genus and 
species, there are actually more than twenty plant families that produce 
products known as hemp. It is this fact, in addition to the botanical name 
changes it has undergone over time, that make it so difficult to trace a true 
ethnobotanical history of cannabis - not only that which is grown for fiber 
and other industrial uses, but also that which is cultivated for its known 
pharmaceutical properties. 

In the fifteenth century B.C. (6), the Chinese book known as the Rh-Ya was 
compiled and in it there is mention of the herb Ma, the Cannabis sativa plant. 
Not only were the fibers and the potent resins employed at the time, but the 
Rh-Ya describes the first ritual of shamanistic use of the plant. The most 
detailed early account of the uses of cannabis in early China is to be found 
in the Shu-King, written in 500 B.C. It was the practice of the early Chinese 
to carve the main stem of the plant into the likeness of a serpent coiled 
around a rod (something like the symbol of the caduceus). This image was used 
in curing rituals; a relative of the patient beat on the sickbed with the 
snake rod in order to dispel evil spirits. In the second century of the 
Christian era, at least one celebrated Chinese physician performed surgery 
using cannabis resins mixed with wine as an anesthetic. 

The ancient Mediterranean peoples were well acquainted with the use of various 
narcotic plants, such as the opium poppy, mandrake, henbane, deadly night- 
shade, as well as cannabis. There is a classic Greek term cannabeizen (6), 
which means to smoke cannabis. This smoking frequently took the form of 
inhaling vapors from an incense burner in which these resins were mixed with 
other resins such as myrrh, balsalm, frankincense, and perfumes. 

The Greek historian Democritus (ca., 460 B.C.) knew cannabis as potomaugis, 
and said that it was drunk with wine and myrrh to produce visionary states. 
The first Greek- botanist , Theophrastus (310-287 B.C.), wrote of cannabis 
under the name dendromache, and gave one of the first accurate accounts of 
the plant. 

Lucilius was the first Roman writer to give an account of the plant, ca. , 
100 B.C. The fiber of the plant was highly esteemed as cordage in most of 
the early vessels. According to Emboden (6), the fiber also had a prominent 

-43- 



place in mythology: it was said to be the stuff that Penelope wove and tore 
apart to discourage her suitors during the absence of Ulysses. 

The famous physician Galen (A.D. 130-200) spoke of cannabis as a medicinal, 
but he also recorded non-medicinal, non-ritualistic use of cannabis mixed with 
wine to be used as a final course at a banquet. Strangely enough, the ancient 
Egyptians seem to have known nothing of the plant and any of its various uses. 

There is historically documented use of cannabis in the funeral customs of 
the ancient Scythians, a nomadic people who ranged eastward as far as what is 
now central Siberia. (6) The Soviet archaeologist, S. I. Rudenko, discovered 
archaeological evidence of the use of Cannabis sativa to induce trances in 
Scythian funeral rites during his excavations of the great burial mounds 
(kurgans) at Pazaryk in the Altai, between 1947-51. Rudenko found metal sup- 
port rods and bronze censing vessels containing not only stones which had been 
heated to produce hemp-seed vapors but even the seeds themselves, some of them 
burnt . 

The Scythians seem to have become acquainted with the ritual use of cannabis 
when they were defeated in battle by the Thracian Getae early in the sixth 
century B.C. The shamans of the Getae used hemp smoke to induce visions and 
oracular trances. In the Scythian funeral rites the mourners rolled heated 
rocks from the funeral fires and placed them in censers. Hemp seeds were then 
thrown on the rocks and the resulting vapors were inhaled. Some other accounts 
dating from about the same time say that the smoldering herbs were covered with 
large skin blankets, which were lifted at intervals so all could inhale the 
vapors , 

In a study done in 1936, a Polish linguistic scholar (Bentowa, now resident in 
the United States) compiled a list of more than 100 synonyms for the cannabis 
plant. (6) She began by studying all the words meaning hemp in Indo-European, 
Finnish, Turkish and Tartar languages, and Semitic language groups, and then, 
having eliminated the obviously borrowed words (whether they were Finnish, 
Turkish, Celtic or Roman), she was left with four groups of languages to 
investigate - all of which had remarkably similar words for the plant cannabis. 
They are Sanskrit, cana; Slav, konopla; Semitic, for example, in Assyro- 
Babylonian, kannab; Greek, cannabis. In all these languages the words mean- 
ing hemp have a common root, kan. This root with the double meaning of "hemp" 
and "cane" is common to almost all the languages of antiquity. 

The ending "bis" can be found through study of several Semitic texts from 
Oriental antiquity. In the original text of the Old Testament and its Aramaic 
translation (the Targum Onculos) the word "kane" or "kene" sometimes appears 
alone, and sometimes linked with the adjective "bosm" in Hebrew or "busma" in 
Aramaic, which means aromatic, to smell good. Both the Biblical kane bosm, 
and the Aramaic kene busma mean hemp. The linguistic evolution of the term in 
question leads to the formation of the unique term kanabos or kanbos. The 
Mischna, the collection of traditional Hebrew law which contains many Aramaic 
elements, contains the term kanabos. The astonishing resemblance between the 
Semitic kanbos and the Scythian cannabis may be proof of the fact that the 
Scythian word was of Semitic origin. Historical evidence would seem to give 

-44- 



credence to the hypothesis drawn etymologically. The Iranian Scythians were 
probably related to the Medes who were neighbors of the Semites and could 
easily have assimilated the word for hemp. 

By the tenth century A.D. cannabis was well-known throughout the Mediterranean 
and Arab worlds. (2) The use of the drug was not prohibited by Mohammed 
(570-532) although alcohol was. Even so, some African Moslems have banned its 
use on religious grounds, while most of the rest of the Moslem world has not. 
Legal restraints have been comparatively recent, dating from the nineteenth 
and twentieth centuries. 

According to modern Arabic historians (9), cannabis came to be planted and used 
in Egypt around the mid-twelfth century A.D. In that country, as in India, the 
plant seems to have aroused controversy from the very beginning; at least three 
different groups of writers took part in the arguments: 1. those who were for 
hashish and against alcohol; 2. those who defended alcohol against hashish; 
and 3. those who condemned both. 

Poems from the tenth to thirteenth centuries describe the behavioral changes 
attributable to hashish; those considered most desirable have a strangely modern 
ring to them. They include euphoria, sociability, feeling of being important, 
feeling of being carefree, meditativeness, activation of intelligence By way 
of comparison with alcohol the writers pointed out that it was cheap, not pro- 
hibited by the Islamic religious authorities, required a comparatively small 
quantity to achieve the desired effect, had a smell which was not easily de- 
tectable, and was never pressed by the feet (as the grapes were) to be made 
ready for consumption. The opponents of hashish presented a series of arguments 
which could easily be transposed to the current scene. Hashish use causes sub- 
missiveness, debility, insanity, some sorts of organic brain damage. 

In the seventeenth century A.D., a comprehensive Arabic pharmacopoeia was pub- 
lished by Daoud Al Entaqui in which the author mentioned cannabis under the 
Persian name Shahdang. The author prescribes the drug for the treatment of 
various somatic conditions, but he also mentions the psychotropic effects - 
euphoria, lethargy, sensory debilitation, and temporary sexual potency tailing 
off eventually into impotence. Such writings are still consulted by certain 
segments of Egyptian society. 

It is probable that the most likely route of migration for cannabis into India 
is by way of Iran, since modern botanists believe that the plant is not indige- 
nous to the country, (6) It may be that prior acquaintance and use of plants 
with tranquilizing properties such as Rauwolfia serpentina , and sedative 
properties such as Withania somnifera facilitated the easy acceptance of 
cannabis. 

The earliest Indian uses seem to have been religious, and there are many 
legends indicating that it was a holy plant to some Hindus, just as peyote is 
today to many North American and Mexican Indians. The first medical uses of 
the plant seem to have dated from about the twelfth century A.D. 

There is little ^irm documentation concerning the routes by which cannabis 
entered the African continent as a whole, but presumably it could have come by 
way of India or Saudi Arabia. In addition, there was differential diffusion, 

-45- 



depending on the particular part of the continent and its openness to con- 
quest, and/or trade by other countries. To cite but two examples, reports 
from Ghana state that the use of cannabis "wee" is not indigenous, that it is 
not known to native herbalists as a therapeutic, and is not used in any native 
religious ceremonies. All reports indicate that its introduction was compara- 
tively recent, probably around the end of World War II. On the other hand, 
there are reports from South Africa, dating from the end of the seventeenth 
century, that the first Dutch jovernor found cannabis (called "dagga") already 
in use by the Hottentots and Bushmen. European visitors to the Congo in the 
late nineteenth century noted vestiges of cannabis usage among the Baluba, a 
Bantu speaking tribe of the Belgian Congo. The Balubas subjugated many other 
tribes (6) and extended the use of cannabis to them. This extension of use 
was a matter of policy on the part of the conquering Balubas, since cannabis 
religious usage was intended to replace the other religious practices and 
tribal gods in the conquered territory. 

Knowledge of the use of cannabis by various indigenous groups located in dif- 
ferent sections of Africa is of interest not only in regard to that continent 
itself, but also in regard to the supposed diffusion to the New World of this 
practice by Negro slaves. A great deal is known about the parts of Africa 
from which slaves were recruited for service either in North or South America 
or the Caribbean Islands, but to our knowledge no one has attempted a system- 
atic study to attempt to determine the linkage between the parts of Africa 
from which these slaves came, and the particular parts of the New World to 
which they were sent and their supposed introduction of cannabis. 

For example, most observers agree that there was no knowledge of the psycho- 
tropic, or even the possible medical uses of hemp in American plantations 
which employed many Negro slaves. However, the American colonies, particularly 
before the time of independence, were major growers of hemp (to be used for 
ship cordage) for the mother country. In Brazil, on the other hand, with no 
growing of hemp, but rather concentration on such crops as sugar, many writers 
feel that cannabis was introduced by way of slaves. 

The route of introduction of cannabis into Europe is very obscure. Although 
usage was certainly noted in Arab countries as early as the time of the 
Crusades (in fact this is the date of the legendary Hasan, from whose name 
both the terms hashish and assassin are said to have been derived), there 
seems to be no record that the Crusaders either used this drug themselves 
while far from their homelands, or that they carried knowledge of its psycho- 
tropic or therapeutic properties back with them to Europe. Similarly, to our 
knowledge, there has been to date no published accounts of the extent to which 
Arabic medicine, introduced into Spain certainly at the time of the Moorish 
conquest and undoubtedly much earlier, introduced at the same time a knowledge 
of the therapeutic uses of cannabis. 

The drug was mentioned by Prosper Alpino in his book De Medicina Aegyptorum 
as early as the sixteenth century (9), by Rumph of Hanau in Herbier d'Amboyne 
towards the end of the seventeenth century and, of course, by Linnaeus 
slightly after the mid-eighteenth century. The surgeons and physicians 
attached to Napoleon's army during the invasion of Egypt in the early 1800' s 

-46- 



became acquainted with the use of cannabis as part of the Arabic medical 
armamentarium. However, the first book which attempted to explore the thera- 
peutic uses of cannabis dates back to 1845 with a publication of a book by 
Dr. Jacques Moreau of the Hopital de Bicetre. 

Moreau was one of the first modern psychiatrists to experiment with psycho- 
tropic drugs in the treatment of mental illness, since he had used datura for 
his patients and later substituted cannabis. Moreau was also one of the first 
persons to describe the variety of drug effects which might be obtained from 
hashish, emphasizing that the differences in effect could be due to person- 
ality, physical condition, motivation, self-control, dosage, setting, mixture 
with other drugs (he described, for example, the Arabian practice of mixing 
hashish with opium and datura), expectations of effect. 

Moreau seems to have been unsuccessful in inducing his medical colleagues to 
experiment with the drug, but he did succeed in introducing a group of artists 
and writers to its use, and this led to the formation of the famous Club des 
Haschischins. 

Members of this Club (particularly Baudelaire and Gautier) wrote extensively 
of the mood-altering effects of the drug (which, interestingly enough, they 
did not smoke, but used in the form of a sweetmeat Dawamese, just as it had 
been used by Arabs for hundreds of years). Further, the accounts of the 
meetings of the Club suggest a strongly ritualistic character. Meetings were 
held monthly (almost like regularly scheduled religious services) with flicker- 
ing lights, ceilings painted with mythological scenes, appropriate music. It 
is interesting that Baudelaire had been to India but apparently had not learned 
of its religious or medical use there, but became acquainted with it in France 
through the introduction of a medical man (Moreau) as well as his fellow 
artists and writers. 

It should be remembered that the European world, at least certain sections 
of the avant-garde, had had an extraordinary interest in the Orient and the 
Middle East from the end of the eighteenth through the middle nineteenth 
centuries. A whole movement, known by literary historians as Orientalism, 
took place about this time, and many classics of the literature of India, 
Persia, and the Middle East were translated and adapted into various European 
languages. (It was during this period that the first translation of the 
Arabian Nights appeared.) 

It is perhaps understandable then that the Parisian writers and authors, 
introduced to the knowledge of cannabis through a psychiatrist, should have 
seized upon and exploited the mystical (oriental), consciousness altering 
qualities of the drug, and to have been comparatively unconcerned about its 
medical and therapeutic uses. 

In England, however, even more exposed to the influence of the Orientalists 
(since the Institution of the Asiatic Society of Bengal came about in 1784 
and the Royal Asiatic Society of Great Britain in 1824) knowledge of cannabis 
came with emphasis on its therapeutic, rather than mind -expanding uses. The 
interest in the possible medical uses of cannabis was initiated by the wori' 

-47- 



(in 1838) of Dr. W. B. 0' Shaughnessy, a professor of chemistry in the Medical 
College of Calcutta. He used it in the treatment of patients suffering from 
such diverse ailments as rabies, rheumatism, epilepsy and tincture of hemp. 
He also found that tincture of hemp was an effective analgesic, and to have 
anti-convulsant and muscle relaxant properties. 

0' Shaughnessy' s work kindled widespread interest in England, the United States, 
as well as many non-English speaking countries, and physicians experimented 
with the use of cannabis (in various forms but not as smoking material) for a 
wide variety of ailments. Interestingly enough, there were few reports of the 
so-called mind-altering or euphoriant effects of the drug although there were 
many articles on the therapeutic efficacy of cannabis published during the 
last forty years of the nineteenth century. However, we were well along in 
the current upsurge of psychological research dealing with the psychotropic 
drugs before the full importance of expectation as a critical variable was 
recognized. It should be remembered that the nineteenth century physicians 
were not unaware of the possibilities of the mind-altering effects of drugs; 
after all, they were familiar with the uses of morphine, and not only as a 
potent painkiller. 

It is tempting to speculate on what the results might have been if cannabis 
had been smoked instead of being used in other forms since smoking, in most 
of the developed Western world, had long since become associated with the pro- 
duction of a sense of well-being. In fact, many authors attribute the phe- 
nomenal spread of the use of cannabis not only to the inherent properties of 
the drug itself, but to the fact that smoking of tobacco introduced many 
persons to the notion that it was possible to attain a sense of well-being 
in some other way than through the use of beverages. In addition, in many 
parts of the world where use of cannabis is well entrenched, cannabis and 
tobacco are mixed together. 

Tobacco itself has a history which is almost as curiously mixed (used in a 
variety of settings, for a variety of purposes) as cannabis. It was a sacred 
plant to North American Indians, and at the time of the early English set- 
tlers was not used in a secular context. Either as a beverage or as smoking 
material, nicotine is still used by some primitive South American Indian 
groups for ritual purposes, divination, and healing. Some writers claim 
that ingestion of huge amounts of nicotine (particularly some of the strong 
varieties found in some parts of South America) can lead to hallucinatory 
experiences, although this is still a matter of dispute. 

Cannabis and nicotine also share a long history of strongly held divergent 
views about their value; when tobacco was introduced into Europe, it was 
hailed by some as a universal nostrum, and by others as a spawn of the devil. 
Moreover, early accounts of the introduction of tobacco into Europe show 
that the first persons to take up the habit were regarded as avant-garde 
members of their society, and a certain amount of ritual (including special 
classes to teach young gentlemen how to blow smoke rings) came into being. 
As the habit spread, however, and diffused to members of all social classes, 
the ritual character disappeared, the types of persons using (except perhaps 
for females) became indistinguishable from the nonusers . Much the same thing 

-48- 



seems to be happening with respect to cannabis users in industrialized Western 
countries . 

Even in countries where cannabis use has long been a settled habit among mem- 
bers of the lower classes, a good case can be made that present day use by 
youngsters from the middle and upper classes is not a matter of emulating 
lower class citizens at home, but rather their counterparts in more highly 
industrialized countries. It is no accident that in some countries (Chile, 
for example) where the use of cannabis is not indigenous, the spread of the 
habit is being fought not only on moral but also on patriotic grounds. 

Cannabis is not indigenous to the New World, and there is no firm documenta- 
tion on exactly how the plants, prized for their psychotropic qualities, first 
entered this continent. Accounts are clear, however, concerning the dates for 
the introduction of hemp plant cultivation into both Canada and the United 
States, and in both countries this introduction came very early in the colonial 
period. Most observers agree, however, that cannabis as an intoxicating drug 
was introduced into the United States by way of Mexico. 

There is no mention of cannabis in all the accounts of North American Indian 
medicine assembled by early travelers (some of them physicians) to this 
continent. There is also no evidence that the early settlers, who borrowed 
many folk remedies from the Indians, had ever heard of the possible medicinal 
properties of this herb. There is ample evidence, of course, that they en- 
thusiastically (for the most part) adapted the cultivation and use of tobacco, 
which was considered sacred by the Indians because of its wonderful qualities. 

In the extensive collection of materials on Aztec Material Medics assembled 
in Mexico by Sahagun shortly after the Conquest, one finds no mention of the 
herb. Similarly, no accounts of cannabis appear in the documentation regard- 
ing the Inca territory although there is extensive discussion of coca (which 
incidentally, has served and continues to serve almost as wide a variety of 
uses as has cannabis itself). 

The plants may have been introduced by the Spaniards to Mexico, Central and 
South America, either at the time of the Conquest or shortly thereafter. It 
should be remembered that not only had Spain been occupied by the Moors, but 
that Arabic medicine was held in high repute throughout the world. On the 
other hand, there seems to be no published documentation of its employment 
by any of the Spanish surgeons and physicians who accompanied the early Con- 
quistadores. There is every evidence, on the other hand, that the Spaniards 
continued to employ the chief intoxicating drug of their homeland, alcohol, 
in the New World and some of their earliest efforts were directed to vini- 
culture. 

Negro slaves were early employed in Spain and Portugal (even before the 
Conquest) and it may be that some of them knew of the use of the plant. In 
Brazil, the words for cannabis (which include maconha, liamba, diamba) are 
closely linked to same words for the plant used in various sections of Africa. 
But accounts of early employment of the plant as a medicinal are strangely 
lacking, even though there has been extensive documentation of the contribution 

-49- 



of the slaves to the knowledge of the utilization of various plants both as 
healing herbs and as standard elements of the distinctive Brazilian cuisine. 

Negro slaves were recruited for service in the New World from various parts 
of Africa, and some sections of that vast continent knew of the uses of 
cannabis before the tremendous expansion of the slave trade. To date, how- 
ever, even with the burgeoning literature on African survivals in the New 
World (which was inspired by Herskowitz in great part), there has been no 
published documentation on the route of diffusion of cannabis to the New 
World. 

It should be borne in mind also that, with the exception of the Rastafarians 
in Jamaica (who learned of cannabis use through its introduction by East 
Indians), there seems to be comparatively little use of cannabis by religious 
groups which show the strongest evidence of African Negro ancestry. This is 
true of cults which stress possession such as Candomble in Brazil, Shango in 
Trinidad, Vodun in Haiti. 

The method of use of cannabis has a great deal to do with whether it is used 
in a social-secular context (as a recreational drug, or as work adjunct) 
almost exclusively, or whether it still retains part of its religious charac- 
ter because of its use in a ritual setting. 

The use of the plant for medical and religious purposes, to aid in the per- 
formance of work (either to stimulate or to allay feelings of fatigue), 
probably preceded its use as an intoxicant. Even today, for many, if not most 
of the users in various parts of the world, the value of the drug lies pri- 
marily in its use in medical practice, including self-medication, in religious 
rites (many of them concerned with petitions for aid in curing illness, or 
pleas for help to maintain health) rather than as an intoxicant. 

In many countries cannabis has been, and continues to be used, for religious 
purposes, for example, India, among certain cult groups in Central and South 
Africa, Brazil, Mexico and Jamaica. In India, according to the Indian Hemp 
Commission report, it was bhang, the weakest variety of the plant, which 
tended to be used in religious ceremonies. In other countries (some parts 
of the Near East, at least one section of Mexico, among the Rastafarians in 
Jamaica) a stronger variety - ganja or hashish - may be employed. 

It is not possible to give a fully documented current history of the thera- 
peutic uses of the plant, since ethnohistorical, anthropological, and socio- 
logical and economic research concerning the using populations and the uses 
to which the drug is put has lagged far behind the pharmacological and bio- 
chemical. In India, the uses of cannabis both in traditional folk medicine, 
and in the more classic theories of medicine have been fairly extensively 
documented . 

Both opium and cannabis have been employed as therapeutic agents by the 
Ayurveda and Unani Tibbi systems of medicine in India for over ten centuries. (2) 
Apparently both agents were known and employed as folk medicine even earlier - 
as early as the fourth to third century B.C. During the last two centuries, 

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traditional folk medicine and the classical Indian medicine have become almost 
synonymous . 

Both the Ayurvedic and Unani Tibbi systems apparently introduced both cannabis 
and opium into their medical armamentarium as a result of borrowing from 
Arabic medicine, brought to India about the ninth century A.D. by the Muslims. 
Today the medical needs of well over one-half the. population of India (espe- 
cially rural India) are attended to, almost exclusively, by practitioners 
trained in these two traditions. It has been estimated that there are about 
500,000 Ayurvedic physicians in the country. To bar the use of opium and 
cannabis to these physicians would mean that there would be a vacuum created 
in medical service, because it will be a long time before modern doctors can 
be persuaded (in any great numbers) to practice in rural areas. (2) 

Cannabis has been used, and continues to be used, in many parts of the world 
as a stimulus, to prevent fatigue, in a sense as a work adjunct. This is 
true in India, South Africa, Jamaica, parts of Mexico, and undoubtedly in 
other places where full documentation is still to be forthcoming. The 
earliest users in the United States seem to have been the stevedores, and 
Mexican immigrant farm laborers. Whether, in fact, cannabis does serve as a 
stimulant and actually aids in the performance of physically demanding labor, 
in the manner of the true stimulants, is a matter which has not been fully 
settled. In a later section of this report dealing with the study of chronic 
cannabis users in Jamaica, we comment more fully on this phenomenon. The 
Canadian government report suggests that it is advisable to directly test the 
theory by initiating a series of performance tests for athletes. 

It is illuminating to note that a good deal of the research having to do with 
cannabis and its effect on work performance and work habits has been carried 
on in highly industrialized Western societies, where the amount of sheer 
physical labor required by the working force is being successively reduced 
through the introduction of labor-saving devices. 

It should be borne in mind that the drug has been and continues to be used 
in many countries, not only for the treatment of purely somatic complaints, 
but also those which seem to be more emotionally based. For example, in India 
cannabis is used to treat insomnia, nervous irritability, and to stimulate 
appetite, as well as for dysentery, neuritis, and upper respiratory complaints, 

The foregoing brief summary of the history of cannabis use and diffusion 
points up not only the comparatively sparse amount of knowledge concerning 
the social and cultural concomitants of cannabis use, but also the necessity 
to involve more social scientists (historians, anthropologists, sociologists, 
economists, psychologists) in its study. 

From the published reports, even though they are admittedly insufficient, 
the picture seems to be this. Until the present time (when the use of canna- 
bis has spread to the middle and upper class adolescent in the traditional 
cannabis using countries as well as the more industrially advanced Western 
nations) the typical cannabis user tended to be a young male, usually from a 
lower socioeconomic background. The user could be found in urban or rural 
(note studies from Egypt and South Africa) areas. 

-51- 



In a series of articles emanating from Nigeria in the fifties and sixties, 
Lambo has pointed out the possibilities for cannabis diffusion with the rise 
of industrialization because many workers are transients, moving from one big 
construction project to another, either within the borders of their own 
country or outside it. 

World War II as well as all the wars since then have also tended to spread 
the knowledge of cannabis use, especially to the age cohort which has always 
been most attracted. The use of cannabis by United States Forces in Vietnam 
has been well documented. Israel reports that some of her citizens have 
become acquainted with the use of hashish as a result of their exposure to 
use during the Six Day War in 1967. 

Migration from traditional cannabis using countries to countries where canna- 
bis use has not been entrenched has been cited as a factor in its spread. 
Israel reports that this is true for many of the migrants coming from Middle 
Eastern and North African cultures, England cites this for its Asian and 
African migrants, and it is probably also true of France, with many people 
returning to the mother country from the Middle East or from her former 
African colonies. 

In some countries (parts of South Africa), the Caribbean, cannabis use is 
the direct result of the introduction of the plant by East Indian migrants. 

What all of the above methods of diffusion of the plant have in common is the 
fact that the methods of social control common in the countries of origin 
(with centuries of use) are no longer operative. In addition, one has to 
consider in countries with a strong Moslem tradition, the relative availa- 
bility of an alternative intoxicant, alcohol, as well as its comparative cost, 

There is little information available on the methods of introduction to the 
use of the plant (by peers or by an older user, by family members or" out- 
siders, or the number of persons who either abandon the effort to find usage 
attractive after the first few attempts, those who persist as occasional 
users, those who incorporate cannabis use as a major feature of their life 
style). Present reports from Western countries indicate that the occasional 
user is typical in America and Europe, while in Near Eastern countries heavy 
users predominate. 

What we know of alcohol use in our own country would seem to indicate a wide 
pattern of diversity of use. (It is instructive to remember that nationwide 
studies in this area are very recent - only within the last ten years.) 
Studies of the use of psychotropic drugs in the general population (drugs 
employed for many of the same reasons that cannabis is used) are even more 
recent. 

There is a great need for good cross-cultural studies to look into many of 
the phenomena mentioned above, but they are exceedingly difficult to mount. 
In many of the countries where cannabis use is a centuries old phenomena, 
there is a shortage of trained epidemiologists and social scientists in 
general - yet any adequate account of cannabis use must take into account the 
cultural matrix in which it is embedded. Unfortunately, in many of the 

-52- 



industrialized Western countries where cannabis use has been seen as a growing 
problem, some scientists (usually physical) have sought to translate their own 
interest in one aspect of cannabis use, and their own research techniques, to 
another setting in another country, with little or no effort to investigate 
anything but the most obvious (employment and criminal records) socio-cultural 
concomitants of use. 



English Speaking Countries 

Within the past four years, notable reports on cannabis have been published 
in Great Britain, Canada, Australia, and New Zealand. Each of these reports 
drew on a variety of professional disciplines during the compilation, and 
each of the Commissions charged with the duty of writing the report sought 
testimony from citizens (non-professional) to determine something of the 
public temper regarding the drug. 

England 

There are at present no published surveys similar to the national household 
survey in Canada, or the national survey in the United States published by 
the Marihuana Commission. There is, in addition, no large scale survey data 
available on use by secondary or university students. A number of small 
scale studies indicates, however, that the introductory drug for many high 
school students seems to be some variety of stimulant. These drugs, since 
they can apparently be gotten from the parental medicine chests, are cheaper 
than hashish or marihuana, to which young people graduate about the time they 
are either earning their own money or have achieved a higher allowance when 
they enter the universities. England, however, has never had a widespread 
outbreak of stimulant abuse, such as that suffered by Sweden. There is indi- 
cation in literature (novels, short stories, etc.) that the course of cannabis 
use in England has been closely parallel to that in the United States and 
Canada - initial use by an avant-garde intellectual or artistic elite with 
ritual and/or mystic overtones, and then with diffusion to other social classes, 
a differential use pattern. The picture in England, however, must differ to 
some extent from that of the United States and Canada, because of the tre- 
mendous migration in the last few years of British nationals from traditional 
cannabis using countries to the mother country. 



Australia and New Zealand 

As we indicated in last year's report, Australia and New Zealand is an area 
where the use of narcotics, marihuana, and stimulants is relatively uncommon. 
There was little if any use of intoxicating substances by the pre-European 
indigenous people; there has been comparatively little migration to either of 
these countries by people from countries where the use of cannabis was well 
entrenched. Alcohol use, on the other hand, in both countries, continues to 
be a major problem. 



-53- 



In the 1971 report we summarised the findings (1970) of a special committee, 
set up under the Board of Health, to report on Drug Dependency and Drug Abuse 
in New Zealand The committee indicated, at that time, that they were not 
prepared to give a complete picture of cannabis use in New Zealand, but be- 
lieved that several groups could be identified - multiple drug users (combina- 
tion of cannabis and other drug use), and the cannabis only users, who could be 
split intb experimental and occasional or spree users. Reports available to 
the Commission at the time of the publication of the report indicate that in 
New Zealand, as in England, the drug of initiation is not usually cannabis. 

To our knowledge there have been no nationwide studies of the use of cannabis 
or other drugs in New Zealand, or even specialized studies of the use of can- 
nabis by university or secondary school students. There is always a publica- 
tion lag, however, in addition to the explosion of articles having to do with 
cannabis. The Canadian report suggests that some sort of an International 
Documentation Center be set up to insure not only that researchers in various 
countries be kept abreast of studies being carried on, but also to insure that 
there not be duplication of effort. 



Australia 

In 1969 a special Select Committee of the Senate, consisting of eight members, 
was appointed to look into the problem of drug abuse in Australia, with wide 
terms of reference. This committee did not contain as many medical members 
as similar committees have in England, or Canada, so there is not so much 
emphasis on pharmacology as there is on the problem of people (5) as the Senate 
members themselves report. 

The report to the Senate was made in 1971. Commission members found that the 
drugs most widely used and abused in Australia, in order of frequency, are 
alcohol and tobacco, barbiturates, bromides and other sedatives, minor anal- 
gesics, cannabis, amphetamines, opiates, LSD. Although there are no fully 
reliable statistics, the evidence points to the fact that cannabis, mainly in 
the form of marihuana, is the illicit drug most widely used. 

Cannabis use has spread through all sections of society from young experi- 
menters to professional groups, but there is as yet little evidence that there 
is extensive use among older age groups. The committee found that, according 
to present evidence marihuana is not so dangerous a drug as might have been 
previously believed; however, they state that scientific evidence is not yet 
sufficiently conclusive to warrant the removal of existing restrictions on 
the use of any of the cannabis derivatives. 

They recommended that the Australian government initiate action for the trans- 
fer of cannabis and its derivatives from Schedule I of the 1961 Single Con- 
vention on Narcotic Drugs to an appropriate schedule in the Convention on 
Psychotropic Substances. They also recommended that cannabis research should 
be encouraged, but specified the following conditions: 

1. Unless specifically original research, these efforts should be channelled 
into complementing overseas research instead of duplicating it. 

-54- 



2. Priority should be given to research complementary to investigations 
being undertaken in the United States and that projects be arranged under 
the existing Australian-American Scientific and Technical Cooperation 
Agreement . 

3. Sociological research should be encouraged as a matter of urgency in 
Australia by Australian organizations. 

4. Legislation should provide adequate protection in law for those taking 
part in approved cannabis projects. 

5. The allocation of funds for medical research should be the function of 
the National Health and Medical Research Council. 

The Committee further recommended that urgent action (5) be taken by the 
Commonwealth Department of Health with the cooperation of State Departments 
of Health to organize, survey and assemble statistics on all forms of drug 
abuse on a uniform basis throughout Australia and that such information be 
made available freely to research and other interested organizations. 

Funds, separate from those already allocated to the National Health and 
Medical Research Council for general medical research, should be provided 
by the Commonwealth Government for the stimulation and conduct of research 
into drug abuse in Australia. Consideration should be given to the appoint- 
ment of a Director of Social Medicine either as part of the Commonwealth 
Department of Health or as the leader of a separate institute whose role 
would be to serve as focal point for the coordination of all activities 
into medical, education, and statistical research related to drug abuse in 
Australia. 

The Committee found that existing education programs aimed at correcting 
drug abuse are inadequate. (5) They recommended that no program directed 
against drug abuse in isolation be undertaken since they felt that, almost 
by definition, it would be ineffective. Instead, commission members sug- 
gested that education programs in schools be designed as "education for 
living" as the best long-term preventive measures. 

They recommended that one national group, a National Education Council 
representative of the Commonwealth and all the States, with membership 
drawn from a variety of disciplines (including education, medicine, social 
health, the legal profession, social workers and youth leaders) be set up 
to supervise all education programs. This Council would be charged with 
the duty of 1) developing specially planned programs designed to meet the 
needs of differing age groups; 2) undertaking curriculum research to estab- 
lish guidelines for new school programs in all States and Territories of the 
Commonwealth; 3) develop programs for the training of teachers and counselors; 
4) support programs, including seminars directed specifically to the adult 
population; 5) serve as a National Resource Center for the collection and 
dissemination of factual information. 



-55- 



The Senate Committee, in the course of hearings conducted throughout the 
Commonwealth, found that there was strong evidence of the need for psychi- 
atric and counseling services among children, and recommended progressive 
development of these resources with the central government contributing 
financial support. They further suggested that in any proposals for the 
extension of child care centers it should be ensured that full advantage be 
taken of all available research knowledge. 

One of the most important recommendations of the Senate Committee, and one 
fully in accord with their emphasis on the human rather than the pharma- 
cological aspects of drug use, was one concerned with the living environ- 
ment. (5) "The priority being placed on the growth, development and material 
wealth should be critically examined so that greater resources may be devoted 
to improving the living environment of the community." 



Canada 

In 1972, the Commission of Inquiry into the Non-Medical Use of Drugs pub- 
lished their report on Cannabis. An Interim Report had been published, and 
at least one more summary volume, dealing with multiple drug use, will be 
forthcoming. The Cannabis report deals with the nature and effects of 
cannabis, its distribution, patterns and extent of use. The Commission also 
examines the existing laws concerning cannabis, and makes recommendations to 
the Federal Government concerning legislative policy. In other words, the 
Canadian report encompasses, in one study, the types of material from the 
United States which must be searched for in two studies - the annual Mari- 
huana and Health Report from the Department of Health, Education, and Wel- 
fare, and Marihuana, A Signal of Misunderstanding, emanating from the Mari- 
huana Commission (a specially appointed body). 

To place this report in proper perspective it is necessary to recall the 
Commission's terms of reference, set forth in the Order -in- Council 
(P.C. 1969 - 1112) which established the Commission on May 29, 1969. 

(a) to marshal from available sources, both in Canada and abroad, 
data and information comprising the present fund of knowledge 
concerning the non-medical use of sedative, stimulant, tran- 
quilizing, hallucinogenic and other psychotropic drugs or 
substances ; 

(b) to report on the current state of medical knowledge respecting 
the effect of the drugs and substances referred to in (a); 

(c) to inquire into and report on the motivation underlying the 
non-medical use referred to in (a); 

(d) to inquire into and report on the social, economic, educa- 
tional and philosophical factors relating to the use for 
non-medical purposes of the drugs and substances referred 
to in (a) and in particular, on the extent of the phenome- 
non, the social factors that have led to it, the age groups 
involved, and problems of communication; and 

-56- 



(e) to inquire into and recommend with respect to the ways or means by 

which the Federal Government can act, alone or in its relations with 
Government at other levels, in the reduction of the dimensions of 
the problems involved in such use. (4) 

To carry out its work the Commission held a series of public hearings, under- 
took a series of special research studies, sought advice and consultation 
from experts drawn from a variety of disciplines, both inside and outside 
the country. 

The Commission points out that they relied to a significant degree on re- 
search in the social sciences to amplify their knowledge and understanding 
of cannabis use. (4) 

The Commission held public hearings for 46 days, visiting 27 cities and 23 
university campuses in all provinces of the country. Members estimate that 
approximately 12,000 persons attended these hearings, and they feel that they 
provided the means by which the Commissioners could get a feeling of the 
response of the public to non-medical drug use. 

The Commission initiated several national surveys to determine the extent and 
patterns of use of cannabis and other drugs, studied the use of cannabis and 
other drugs by young people using participant observer techniques. It con- 
ducted a formal survey of psychiatric hospitals, a study of physicians 
practicing in the Ottawa area and an investigation of innovative service 
and street clinics, as well as some formal treatment facilities in various 
parts of the country. The Commission also conducted a study (one of the 
very few in existence) of the social and personal characteristics of Canadians 
over 27 who were conventionally employed and also users of cannabis. 

To determine the legal and economic implications of cannabis use, the Com- 
mission initiated a study to determine the sources and distribution networks 
involved, as well as detailed empirical assessment of the existing law and 
law enforcement methods. 

The Commission conducted three systematic national surveys in 1970 of high 
school students, university students, and the rest of the population. 
These were the first such national surveys which had been conducted. The 
samples of these populations are as follows: 

(1) High school students from the ages of 12 to 19 years, enrolled 
in grades 7 to 12 or 13. These students were interviewed in 
homes selected for the National Household Survey, described in 
(3) below. More than 1,200 students were interviewed in this 
survey. 

(2) A total of 1,213 students attending colleges and universities 
in Canada at either the undergraduate or graduate level. Each 
student selected for this survey was provided with a letter 
explaining the study, a copy of the questionnaire and material 
for return mailing. The students selected were from 8 large 
and 12 smaller institutions representing all regions of the 
country. 

-57- 



(3) Some 2,800 households, in which an individual in each house- 
hold was interviewed under a method of selection that ensured 
an equal opportunity to be interviewed for each member of the 
household 12 years of age or older who was not attending a 
primary or secondary school. (4) 

The Commission of course also had the results of previous partial surveys 
which had been made of high school and university students. Although final 
analysis of the data collected in these various surveys has not yet been com- 
pleted, enough analysis has been done to show that there has been a very 
rapid and sharp increase in cannabis use in Canada within the past five 
years. On the East Coast hashish is the drug most in use apparently because 
of its greater availability, but on the West Coast, because of proximity to 
Mexico, marihuana is still the drug of choice. 

According to their surveys an estimated 79,000 persons had begun to use 
cannabis by 1966. By 1970 an estimated 850,000 persons had used it at 
least once. By mid-1971 it is estimated that as many as 1,500,000 had done 
so. The surveys indicate that a significantly large number of persons who 
have used cannabis have used it only on an experimental basis (two or three 
times). Continuing analysis of the survey data will allow estimation of the 
number of experimenters who have graduated to occasional or frequent use. 

During the mid-sixties cannabis use was concentrated on college campuses, 
and university students continue to have a higher incidence of use than any 
other segment of the population. Apparently, the proportion of university 
students who are users is still rising. In Canada, as in the United States 
and other countries, the extreme differences between users and nonusers, 
such as the "hang-loose ethic" found by Suchman in 1967 no longer apply. 
The users and nonusers can still be distinguished along some societal 
variables, but it is likely that even these distinctions will eventually be 
eliminated if the present trend towards greater use and acceptance continues. 

An ever increasing number of high school students are being introduced to 
the drug while in their early teens, and the distinctions between users and 
nonusers is becoming more blurred in that group as well. There are no sur- 
veys of drug use among grammar school students in Canada. 

The general population national survey indicated that by April 1970 approxi- 
mately 3.4 percent of the population had used cannabis (about half a million 
persons) . The accumulated evidence to date indicates that it is primarily 
a middle and upper class phenomenon found among those in their twenties and 
thirties . 

The Commission used anthropological (primarily participant observer) tech- 
niques to study those persons whose highly mobile life styles generally 
insure that they are missed in more conventional surveys. Because of the 
lack of any surveys and the constantly changing dimensions of the population, 
it is difficult to give any reliable estimate of the number of so-called 
"street people," but there is no doubt that the number in Canada, as in the 
United States, has been increasing in the last five years. In addition, in 

-58- 



Canada as in this country there is an increasing number of persons living in 
communes of various sorts. 

In Canada the "street people" range in age from thirteen or fourteen (during 
the summer months) to the mid-thirties or even older (4), but most are between 
eighteen and twenty- four with the average age for males being about twenty- 
one and perhaps slightly lower for females. Males tend to be overrepresented. 
In the early days of this phenomenon (1967) it was primarily middle and upper 
class youngsters who were attracted to the street scene, but now there is in- 
creasing evidence that more and more poorly educated young people drawn from 
the working class have become street people. The influx of working class 
youth, as well as an attenuation in the attraction of the Flower Children 
myth has led to a decline in the number of middle and upper class youths who 
are found in these favored enclaves, but the overall number continues to rise 
as the number of facilities (free clinics, hostels, drop-in centers) developed 
to serve the special needs of this population increase. 

Each Canadian city, as each American city, has at least one and perhaps more, 
favored areas - in Vancouver, "Chemical Row" in Kitsilano and Gas town; in 
Toronto, Yorkville; in Ottawa, the very center of the city along a public 
shopping mall and the grounds of the National Arts Center. 

In Montreal street people are linguistically, culturally, and ecologically 
divided. French-speaking persons tend to congregate near the Carre St. Louis 
and old Montreal, and English-speaking young persons favor an area (known as 
the Ghetto) just east of McGill University, and another section quite close 
to Sir George Williams University. 

The daily smoking of cannabis or hashish is more the rule than the exception 
among street people, and there are no mystic qualities associated with the 
drug or the purposes for which it is used. Just as in the United States, 
many of the hard drug users are recruited from the ranks of the street people. 

However, most cannabis users do not end up in the street populations. The 
Commission, in an attempt to tighten up the ill-defined boundaries concerned 
with levels of cannabis use, came up with three categories. The first level 
of continued consumption (beyond initial experimentation) was called occa- 
sional use (defined as once a month use or less). (4) More cannabis users 
studied by the Commission fell into this category than any other. 

Occasional use characterized 29 percent of secondary school users, 39 per- 
cent of university users, and 46 percent of those interviewed in the national 
survey. It is, of course, impossible at this juncture to predict how many 
will give up cannabis altogether, and how many will advance to more extensive 
use. For the occasional user, cannabis is a pleasant diversion and is not 
viewed as occupying a prominent place in his life, is not pursued to the 
extent that he feels it necessary to be in touch with a regular dealer. 

The moderate -regular users, for the purposes of the Commission, were defined 
as those who use cannabis more than once a month but not more than once a 
week. Nearly 29 percent of secondary school students, and 22 percent of 

-59- 



university students fall into this category. It is, of course, necessary for 
these users to have a regular supply of the drug. In general, however, their 
drug taking is confined to occasions when it will not interfere with other 
activities. Use usually takes place in a recreational context. 

The third pattern of consumption of cannabis is heavy-regular use - for the 
purposes of the Canadian survey defined as all those who regularly smoke 
cannabis from more than twice a week to several times each day. Only 6 per- 
cent of the cannabis using university and secondary school students used the 
drug as frequently as several times a week, and an additional 1 percent of 
the high school students and 3 percent of the university students claimed 
that they smoked every day. This is the pattern of consumption that is found 
in many non-Western communities, but it is relatively rare in a North American 
sample to find this heavy consumption pattern, and even rarer to find a canna- 
bis only consumption pattern. 

The Commission points out that they did not collect data on a systematic 
national basis on the relative potency of cannabis used in Canada. (4) Al- 
though the existing data shows that cannabis is not usually adulterated with 
other active drugs, it is sometimes cut with inactive materials. The report 
suggests that continuing qualitative and quantitative analysis of randomly 
selected samples from police seizures, as well as samples procured from other 
sources, would be a suitable method of monitoring the purity and potency of 
cannabis used in Canada. This kind of data, of course, should be supplemented 
with material from other countries. Unless and until there is a sizable body 
of such information available, cross-country comparisons will be exceedingly 
difficult to make. 

They point out that in the past almost all research has been conducted on 
healthy young adult males. (4) The time has come to investigate other popula- 
tions, adolescents, females, and older persons of both sexes. It is note- 
worthy that the Commission itself moved to remedy this deficit by using 
females in one of their experiments (the third phase of their continuing 
study of chronic cannabis use). 

The Commission members also suggest that further attention be directed to the 
possible effect of cannabis on muscle strength and work performance by 
measuring, under both laboratory and natural conditions, the effects of acute 
and chronic cannabis use. (4) The existing literature in the field is far 
from conclusive although some deficit is suggested. Since cannabis is used 
as a work adjunct or as a stimulus in so many countries of the world, this 
kind of research would be very valuable. 

The Commission recommended (4) : 

The Federal Government should remove cannabis from the Narcotic 
Control Act , as the Commission recommended in its Interim Report . 

The Federal Government should immediately initiate discussion with 
the provincial governments to have the sale and use of cannabis 
placed under controls similar to those governing the sale and use 

-60- 



of alcohol, including legal prohibition of unauthorized distribu- 
tion and analogous age restrictions. Furthermore, this government - 
distributed cannabis should be marketed at a quality and price that 
would make the 'black market' sale of the drug an impractical enter- 
prise. 

The Federal Government should initiate a program to develop efficient 
practical methods for cannabis production and marketing in Canada. A 
standard form of natural marihuana would seem to be most feasible at 
this stage, but hashish and synthetic preparations should also be 
explored. 

The Federal Government should initiate prospective multi-disciplinary 
epidemiological research to monitor and evaluate changes in the 
extent and patterns of the use of cannabis and other drugs, and to 
explore possible consequences to health, and personal and social 
behaviour, resulting from the controlled legal distribution of 
cannabis. 

All stages of the production and marketing of cannabis should be 
conducted by the Federal and/or provincial governments. 

One commissioner, Ian L. Campbell dissented, "I must dissent from the recom- 
mendation of the majority of my colleagues and recommend that the prohibition 
on the possession of cannabis be maintained, for the time being at least. 
Possession of cannabis should be punishable, upon summary conviction, by a 
fine of $25.00 for the first offence and by a fine of $100.00 for any subse- 
quent offence." 

"With respect to the cultivation of cannabis other than for purposes of 
trafficking, I recommend that it continue to be an offence with penalties 
identical to thos*=> which I recommend for simple possession." (4) 



Europe 

The bulk of the cannabis use in Europe is in the form of hashish, a more 
potent form than the marihuana of the United States. Some Western European 
countries became concerned about drug use among juveniles much earlier (1967) 
than did the Eastern European nations, if national surveys about drug use 
provide a valid indication of concern. Moreover, there is a difference 
between countries in the .type of drug which first triggered their concern, 
and the country's concern with, and knowledge of the use of a legal drug, 
alcohol. 

For example, Sweden has been aware of the problems of alcoholism for at 
least a century and a half, and was one of the first countries of the Western 
world to deal with the problem of what amounted to almost an epidemic of 
stimulant drug abuse. The first studies which involved monitoring a number 
of pharmacies to determine the amount of amphetamines dispensed, were pub- 
lished in 1944. As early as 1966 a committee, The Narcotics Drug Committee, 

-61- 



comprised of five subcommittees dealing with such aspects as social medical 
aspects, methods of prevention, and treatment and legislation, was set up. 
Sweden has since conducted a series of model epidemiological surveys, not 
only dealing with drug use among juveniles of all social classes but also 
keeps a national register of drug abuse cases coming to the attention of 
hospital authorities (both mental and general hospitals). As early as 1967 
Swedish authorities conducted a study of 130,000 pupils in secondary schools, 
and found that about 3.6 percent of the pupils took, or had taken, "narcotic" 
drugs. Sweden classifies cannabis among the narcotic drugs. At the time of 
that early survey about 1,260 pupils had used cannabis. Sweden is still far 
more concerned about the abuse of amphetamines than it is about the use of 
cannabis . 

It is interesting to note that a neighboring country, Denmark, has not had 
to contend with the problem of amphetamine abuse to any great extent. Hashish 
still seems to be the illicit drug of choice. Scientists have conducted a 
series of surveys in the last four years to determine the drug using habits 
of adolescents both in and out of the schools. These studies indicate that 
between 12 to 28 percent of the samples had tried hashish. Only between one 
and four percent of any sample smoked the drug as often as once a week or 
more. Findings as to the type of youngsters who experimented with hashish 
use were similar to those in the United States and Canada, that is, the 
higher the educational attainments of the father and the mother, the greater 
the incidence of experimentation. In addition, as the number of experimenters 
increased the Danish investigators found that it was not possible to distin- 
guish regular users from their nonusing confreres in terms of such demographic 
variables as sex, age, status, background, or degree of urbanization. For 
these, and similar reasons, the researchers have concluded that it is not 
theoretically productive to consider drug use from the point of view of 
deviancy, but rather from the point of view of social change. Needless to 
say, the influence of this type of view on the lawmakers and law enforcers 
could have far-reaching implications. 

The Scandinavian countries, and the Netherlands must deal not only with the 
problems of drug abuse by their own nationals, but also that of the armies 
of young people (from various countries including the United States) who 
arrive in the summer months . 

Some European countries (for example: Germany, Belgium, France) within the 
last ten years have witnessed an unprecedented influx of workers or migrants 
from countries where hashish and/or opium use has long been a culturally 
accepted fact of life. Germany, in particular, has ranged far afield to 
find workers for her expanding economy. While many of these have been re- 
cruited from within neighboring European countries, many of them have also 
come from the Middle East. Belgium also employs many Middle Eastern 
nationals. France, at the close of the Algerian war, accepted thousands of 
settlers (French citizens) who came from North Africa. Although there is 
little documented information to indicate the extent to which some of these 
immigrants have been involved in the increasing social acceptance of hashish, 
there is a considerable amount to show that a few of them have had a definite 
role to play in getting the preferred drug to the market. 

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It is extremely difficult (some would say almost impossible) to get a clear 
assessment of the social climate of any country, the massive attempts (not 
yet very successful) to develop social indicators in the United States, are a 
clear indication of that. However, it is increasingly clear that in the 
developed, industrialized nations, as well as the so-called underdeveloped 
nations (where the cannabis habit has had the longest history) any really 
thoroughgoing study of drug use (of which cannabis is only a part) will have 
to take into account the diversity of population groups represented, the 
amount of drug use, legal and illegal, prescription and over the counter 
drug use. Moreover, the general mind set of the country will also have to be 
considered. 

It is no accident, for example, that the Netherlands, with a fairly liberal 
policy to deal with drug use, is also the country which is in the forefront 
of liberal Catholicism. The general attitudes towards health and illness 
(including physical and mental) and the favored methods to either maintain 
health (avoid illness, attain a state of emotional well-being) or to regain 
health, all play a part in the use of drugs. 

It would seem, finally, that the time is long overdue to initiate a compara- 
tive study not only on drug use per se , but on the methods of dealing with it. 
No one pretends that there is sufficient data available in any one country to 
undertake a thoroughgoing systems analysis, and of course the problem is mag- 
nified a hundred times if one attempts a cross national survey. Still a start 
could be made (there could be a central depository) which could contain data 
on the volume of psychotropic drug prescriptions, as well as the prescribing 
practices of medical doctors and psychiatrists in several countries. This 
could be coupled with general data on health (morbidity, mortality). The 
school systems could be asked to furnish data on health education classes 
(if any) carried on. The number of examples could of course be multiplied 
many times over. At present, the kinds of data we are speaking of may be 
available, but the potential researcher must search for it in too many places 
and must consult too many government bureaus to make it worthwhile. Still, 
it would seem reasonable to muster a major amount of research effort to at- 
tempt to get an overall picture which is as comprehensive as possible. 



The Netherlands 

In 1968, in order to supply some hard data about the extent of drug-taking in 
the Netherlands, a series of studies was undertaken by Buikhuisen and 
Timmerman of the Criminological Institute of Groningen University. These 
studies included: 1. an investigation of drug-taking and drug policy at 
youth centers; 2. a survey of the extent of drug- taking among secondary 
school children, of the sociological and psychological characteristics of 
those children who" take drugs, and a field study in depth of drug-taking in 
a small provincial town. The investigators have carried out two studies, 
one in 1969 and one in 1971, of the drug-taking habits of secondary school 
children, and they plan a third survey in 1973. 



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In the first survey in 1969, 11,659 students in 156 schools, scattered 
throughout the Netherlands, answered the questionnaires. Data collected in- 
cluded standard demographic material such as sex, age, father's occupation, 
type of course being taken and certain particulars on the use of drugs. Of 
the children queried, 1,300, or a little over 11 percent, said they had taken 
one or another drug at least once. Hashish and marihuana were by far the most 
popular drugs and 88.3 percent of the users had taken them. The proportion of 
students who had taken the cannabis drugs in addition to others such as am- 
phetamines, LSD and the opiates was comparatively small; amphetamines were 
taken by 13.7 percent and LSD by 12.3 percent of the users, while the opiates 
were taken by only 7.2 percent of the students , 

There was a difference in magnitude of drug use according to the type of 
school. It was highest at schools of the arts - almost 30 percent, little 
over 15 percent at secondary schools, and almost 9 percent at technical schools 
Moreover, there is no difference by age groups in the drug and non-drug users 
at the arts schools, but at the other two types of schools, the drug- takers 
tended to be older. In all types of schools, the proportion of drug- takers is 
higher 'among boys than among girls. Relatively more of the drug- takers belong 
to the upper social class than to the middle class. (It should be borne in 
mind that class differences are not nearly so marked in the Netherlands as 
they are in larger countries.) 

The investigators repeated this survey in 1971, and a total of 17,708 children 
in 32 towns were studied. By this time the percentage of school children who 
have taken drugs at some time or another had advanced to slightly over 20 per- 
cent and those who had taken drugs more than 20 times had gone from a little 
over 2 percent to 6 percent. The type of drug favored was still marihuana 
or hashish. The differences found in 1969 in regard to social class and age 
had disappeared by 1971. Only the sex variable was still a factor. 

The researchers believe, on the close examination of their data, that drug- 
taking is already reaching a saturation point in the Netherlands. The 
expected near doubling in the number of drug-taking children in all schools 
has not occurred. In those schools in which the rate was high in 1969, the 
increase in 1971 was small - most of the increase represented diffusion to 
new schools. The overall frequency remained comparatively low, although 
there was an increase in the number of girls using drugs. 



The Near and Middle East 

In previous reports we have commented on the extensive literature available 
on cannabis use in countries in this section of the world where cannabis 
(primarily in the form of hashish) has long been employed, and have stressed 
the extreme caution with which these reports must be viewed. It is in good 
part from these countries that Europeans acquired their knowledge of the 
"good" and "evil" qualities of the drug. In this report, we summarize the 
results of an extensive study of hashish use in a Near Eastern population - 
that of Soueif in Egypt . 



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E£V£t 

Egypt was one of the first countries (1879) to ban the use of hashish, even 
though at that time there was very little cannabis under cultivation. Illegal 
hashish immediately began to pour into the country from Greece, Lebanon, and 
Syria. Today the latter two countries are still seen as the major suppliers 
of the market. 

Since 1879 (10) successive laws have shown a persistent tendency to enforce 
more and more severe penalties on traffickers and users, which presumably 
shows that the problem of use has been growing. There is also some indication 
that the absolute amount of hashish used has been increasing in the country 
in the years since the close of World War II. However, the enforcement offi- 
cials seem to have been able to keep the supply of narcotic drugs including 
opium, heroin, and cocaine at about the same levels during this period. 

Although there are no exact figures on the number of hashish users in Egypt, 
Soueif (the leading researcher in the field) estimated in 1967 that there 
were approximately 180,000 users, the majority of them young men between the 
ages of 20 and 40. The estimated number of young men in that group out of 
the entire population of Egypt was about 3,000,000. 

In 1957 Dr. M. Soueif of Cairo University undertook a series of far-reaching 
studies of hashish users which give by far the most complete data available 
for all of the Middle East. The investigators began by constructing a schedule 
of questions which were derived not only from suggestions made by psychiatrists, 
psychologists, and workers in related fields, but also through voluntary inter- 
views (obtained through contact men) with hashish users themselves. 

Demographic data was collected on age, education, monthly income, marital 
status and other related items, but the interview schedule was also designed 
to elicit information on the following topics: 

1. Personal estimation of the distribution of hashish use in 
different sectors of the society. 

2. The effects of hashish use as experienced by the interviewee. 

3. The sexual behavior of the interviewee. 

4. Hashish effect on appetite for food, drink, and general energy 
output. 

5. Perception and thought, emotional set, self-image. 

6. Interviewee's opinion regarding the increasing severity of the 
successive legislation regarding hashish consumption and 
trafficking. 

7. Any evidence of cumulative effects of the habit. 

8. Work and recreation. 

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9. Description of group use "hashish party". 

10. Extensive data both on family of origin and of procreation, 

with particular attention paid to history, if any, of pattern 
of hashish use within the family. 

The interview schedule for the controls was identical; only those items con- 
cerning first-hand experience with the drug were eliminated. After a series 
of trials it was decided to word the questions in colloquial Arabic which 
proved comprehensible both to literate and illiterate subjects. 

Interviewers were required to have at least a bachelor's degree in psychology 
and in addition were screened to be sure that they were adaptable, interested 
in the work at hand, and above average in intelligence. Each interviewer was 
trained for three months before starting the job; not only were they tho- 
roughly grounded in the methodology involved in the construction and adminis- 
tration of the schedule and the method to be followed in recording different 
types of answers to different types of questions, they also observed the 
interviewing process of senior interviewers. In addition, they conducted a 
series of interviews under the direction of experienced staff members. 

In 1967 Soueif reported on the first group of studies done with two groups 
of users, one recruited from Cairo, the other from semi -urban and rural parts 
of upper Egypt. Hashish use was defined as at least once a month in the year 
preceding the time of the interview. Two studies were done with control 
groups - a control was defined as one who had never had the experience of 
taking hashish. All interviewees were volunteers, and all were paid. In 
this first series of studies no prisoners or mental hospital patients were 
included. The investigators do not state that the groups represent a truly 
random sample since users were located through the use of a key informant 
and then so-called snow-balling technique, a method it should be recalled 
which has been extensively used in United States studies. 

The hashish users from Cairo constituted a group of 204, ranging in age 
between 20 and 52 with a modal age of about twenty-two and a half years. 
Thirty subjects were illiterate, 43 semi-literate, 110 had had from 4 to 9 
years of formal schooling and 20 were university graduates. There was a 
roughly even distribution between the married and the unmarried. Most of 
the subjects were Moslem. 

The group of rural users comprised 49 subjects ranging in age from 20 to 47 
years with a modal age of about 20. Fourteen of these subjects were illit- 
erate, 15 semi-literate, 13 had completed 4 to 9 years of formal schooling 
and only one was a university graduate. The majority of the subjects were 
married. All subjects were Moslem. 

The favorite method of consumption for both groups (urban and rural) was 
smoking with a "josah." This is somewhat similar to the pipe nargileh 
used in Lebanon. The second most favored method of consumption is through 
smoking of hashish cigarettes. There is no information given in the pub- 
lished material as to the amount of tobacco, if any, mixed with the hashish. 
Most hashish was consumed in a group setting. 

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The modal frequency of hashish use for the urban group was about 12 times a 
month, with the upper 10 percent of the sample exceeding 50 times per month. 
The modal frequency for the rural group was about 8 times per month. About 
70 percent of the subjects in the urban group had begun to take hashish before 
the age of 20, and the corresponding proportion for the rural group was 62 per- 
cent. Very few of the subjects began use after the age of 28. 

The main motives for starting to take the drug in both urban and rural groups 
are (in descending order of frequency): Conformity to group norms, desire for 
euphoria, curiosity, and the desire to appear like "real men." It is a little 
difficult, from the published material, to determine what is included in the 
concept "real men." It was a separate category, distinguished from "sexual 
behavior." Incidentally, enhancement of sexual performance or enjoyment came 
rather far down on the list of desirable attributes associated with the taking 
of the drug. 

One of the most interesting findings of this study, and one which differs 
fairly sharply from findings in the Western World, was that concerning the 
makeup of the group in the group setting favored by an overwhelming majority 
of the users for consumption. All members of these groups seemed to feel a 
sense of social nearness, although more often than not, they belonged to 
various occupational categories and sometimes came from different socio- 
economic strata. Much of the cohesiveness of the groups in both the rural 
and urban settings seems to depend on the characteristics of the leader. The 
leader should be a man who is modest, an organizer and a fluent conversationa- 
list, according to those interviewed. 

The two control groups (about 115 in the urban sample and 40 in the rural 
sample) were matched on all relevant variables. They were defined, it will 
be recalled, as persons who had never taken hashish. Unfortunately, the 
published data does not tell us why they had never used hashish since pre- 
sumably they would have been exposed to the drug with about the same fre- 
quency as the users. Also, the definition of a control excludes persons 
who might have tried the drug once or twice and then abandoned it either 
because they found the drug physically or mentally upsetting, or because of 
fear of arrest. 

Late in 1971, Dr. Soueif reported on a large study undertaken with prisoners 
(both users and nonusers of hashish) . The experimental group (850) included 
the entire male population convicted exclusively for use of hashish and 
detained in Egyptian prisons from June 1967 through March 1968. Ages ranged 
from 15 to slightly over 50, with an average age of 39. Subjects were drawn 
both from urban (460) and rural prisons (390). The majority (50 percent) 
of subjects were illiterate, about 25 percent of the group were skilled 
laborers and the rest had held a variety of unskilled jobs. 

Controls (defined as those who never took hashish or any other narcotic sub- 
stance, as defined by Egyptian law) were selected from among a group of con- 
victs in the same prisons where the experimental users were confined. To 
reach controls the investigators depended on key men and preliminary screen- 
ing interviews. The control group is fairly well matched to the experimental 

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group regarding age, urban or rural background, and percentage of skilled 
laborers. There were fewer illiterates (roughly 55 percent among the controls) 
and the control group also included 44 subjects with high school certificates 
and 9 university graduates. 

In addition to the interviewing items which had been included in the earlier 
surveys, the investigators also included a series of twelve psychological 
tests, in order to examine a series of hypotheses developed during the earlier 
surveys. It is noteworthy that the researchers decided that the tests to be 
used should meet certain criteria (to be widely known among Egyptian psy- 
chologists and those in other countries and to be as culture free as possible) 
so that they could serve to make possible future comparisons across researchers 
and across cultures. 

Both interviewing and psychological testing was designed to be accomplished 
in one session, and tests were administered (in random order) at the end of 
the session. Interview and testing were carried out in a private testing room. 

The psychological tests included Tool matching, H marking, Speed testing, 
Mark making, all taken from the General Aptitude Test Battery. There was 
also one test (Trail Marking - Part A) taken from the Reitan Battery, the 
Bender Gestalt, Digits Forward and Backward from the Weschler Adult Intelli- 
gence Scale, and an initial reaction time test which utilized four Rorschach 
cards, and timed the verbal response of the subjects in seconds from the time 
of the presentation of the cards. 

The prison study found that smoking continued to be the preferred method of 
administration (almost 90 percent) . Smoking as a preferred method of admin- 
istration was slightly related to the number of times per month the subject 
used the drug - 87 percent of heavy users (defined as those who take the 
drug more than 30 times a month) preferred smoking as opposed to 93 percent 
of the moderates (those who take the drug 30 times or less). More heavy 
than moderate smokers tended to take the drug at definite hours of the day. 
Almost all drug users prefer (94.2 percent) to take the drug in the evening, 
and in groups of four to six members (82.5 percent). Only about 17 percent 
of users take hashish on their own and heavy users do not differ from moderate 
users in this respect. However, city dwellers have a significantly higher 
proportion of lone users than do rural inhabitants. 

The frequency of hashish use was significantly related to the time of the 
beginning of the habit; for example, 76 percent of those who started drug use 
before 22 were heavy users, as opposed to only 56 percent of those who started 
after 22. 

Some of the hashish users also took other drugs known to act on the central 
nervous system. Almost one third of the group admitted that they also used 
opium, and almost 23 percent also used alcohol. Unfortunately, there is no 
indication in the printed work of exactly how much opium or alcohol the 
subjects used. 



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Motivation for use in the prison population did not differ much from the non- 
institutionalized samples studied in the first group. (In rank order these 
reasons for use include conformity to group expectations, seeking euphoria, 
acting like real men, and so on.) It should be borne in mind that the prison 
group differed markedly from the subjects in the first study, where the modal 
amount of urban use was about 12 times a month. In the prison study about 70 
percent of the users take hashish more than 30 times a month. 

In regard to cannabis use, the investigators found that attempts to interrupt 
the habit as well as the frequency of drug use were related to age at onset; 
the earlier the age of onset, the fewer the attempts at interruption and the 
higher the frequency of drug taking. In addition, the Investigators estab- 
lished a positive relationship between duration of hashish use and opium 
taking. (Unfortunately, the results published so far do not indicate whether 
opium and hashish were mixed or whether opium was used alone.) 

By comparison with controls, cannabis users have had fewer criminal offences 
(other than those directly connected with using or selling narcotics). Canna- 
bis users are, in general, slower learners than the controls. In addition, 
the differences between users and controls were accentuated when considered 
in light of their educational attainments; the higher the educational attain- 
ments, the larger the discrepancies between users and controls on the objective 
tests. 

The final results of the prison study still have not been published. It is to 
be hoped that future work will take into account the possible confounding 
effect of opium and alcohol use as it relates to the test performance of the 
hashish users. 



Latin America 

Cannabis is not indigenous to the New World. The cultivation of hemp was 
apparently introduced into North America by Champlain's apothecary in 1606, 
in the territory of Nova Scotia. Shortly thereafter, the Pilgrims planted 
hemp in New England. Both France and England encouraged the cultivation of 
hemp in their colonies both for domestic requirements such as clothing and 
cordage, and to provide sails and rigging for their ships. Later, this en- 
couragement was supplanted by regulations requiring the growing of hemp (for 
example, in Virginia), and fines were imposed on those who refused to comply, 
There were suggestions made in New Spain (Mexico) as early as the first 
century after the Conquest, that hemp be introduced as a major crop. 

The varieties of cannabis which might be utilized for medical, religious, 
work adjunct, or recreational purposes were also unknown in the New World. 
There is no mention of the plant in North American Indian medicine, or in 
early studies made of native hallucinogenic or medicinal plants in countries 
conquered by the Spaniards, including Mexico, the Central and South American 
countries (except Brazil) and many of the Caribbean islands. The cannabis 
plant is not represented in any pre-Conquest sculpture or painting (although 
many other hallucinogenic plants are) . 

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What was in existence, however, particularly in that part of North America 
now belonging to the United States, as well as in Mexico, Central America, 
and all of South America, was not only a tremendous store of other narcotic 
and hallucinogenic plants, but also a culture which would encourage their use. 
Schultes, for example, points out that the New World cultures have employed 
many more species of plants hallucinogenically than have the Old World cul- 
tures. The reason cannot be botanical, for there is no evidence to suggest 
that the flora of the Eastern hemisphere are poorer (or richer) in plants 
possessing hallucinogenic compounds than those of the Western hemisphere. 
Weston La Barre has suggested that one reason for this curious disparity may 
be that the American Indians (both North and South) basically preserved as 
their religion the shamanistic ideology of ancient hunting peoples, with a 
necessity for a direct psychic experience of the forces of nature, in order 
to divine their purpose, to try to enlist their aid, or at least avoid their 
enmity. La Barre believes that substantial portions of this shamanism sur- 
vived even in societies that turned to sedentary agriculture. In the Old 
World, however, these plants became less and less important as the old shaman- 
istic religions were supplanted and suppressed by new religions adapted to the 
demands of agricultural and feudal society. Medieval concerns with devils and 
witches show some carryover in the belief of sacred and/or magic plants. There 
are other survival traces in fairy tales and folklore of the magical effect of 
certain plants. 

It should be borne in mind that use of a plant in religious ritual, particu- 
larly in underdeveloped regions of the world, by primitive peasants, cannot 
easily be separated from use of the plant as a direct medicinal tool. Many 
of the religious rituals are concerned either with divination of a particular 
illness, mental or physical, or curing of an illness. Since life for many 
Indians in Latin American countries is indeed nasty, poor, brutish, and 
short, it should not be surprising that they would also cherish any plant 
which would help in their work, relieve them of fatigue, or serve to allay 
the pangs of hunger. 

In view of the above considerations, it should be borne in mind that any 
studies of the use of cannabis in Latin America must first of all differentiate 
the various patterns of use by varying populations. Studies in the countries 
with a heavy Indian population (for example, Mexico, Ecuador, Colombia, 
Bolivia, Peru) would be expected to have a different pattern of use than say 
a country like Chile, or Argentina, where there is a comparatively small 
Indian population. 

In Mexico, we cite two examples of the ritual adaptation of cannabis in sec- 
tions of the country well acquainted with other hallucinogenic plants. Un- 
doubtedly, with the growing interest on the part of anthropologists in this 
field, other instances of the same type will turn up. On the other hand, we 
should bear in mind that a plant once used ritually (especially by oral con- 
sumption) may turn to have more secular-social uses when consumed in another 
manner, for example, by smoking. That was certainly the fate of cannabis in 
many Near Eastern countries. 



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A third caution to be borne in mind is the tremendous urban explosion in 
many Latin American countries, with hundreds of thousands of peasants stream- 
ing into the poor barrios and favelas of all large cities. This type of heavy 
urban migration has always contributed to the growth of drug use, and moreover 
drug use which is removed from the social control and sanctions of the rural 
areas. In last year's report, we listed the countries where there was evi- 
dence of increased governmental interest and concern, usually expressed in 
tightening up of the laws concerning traffic and possession. These countries 
(preliminar}^ report) included Venezuela, Argentina, Brazil, and Paraguay. 
The number of countries has increased this year but there is also heartening 
evidence that equal weight is being given to prevention, education, and 
treatment. 

In Venezuela, the report of the Special Commission Appointed to Study the 
Drug Problem was submitted to the Chamber of Deputies in June 1972. Al- 
though the Commission stated that they believed that the use of drugs was 
reaching epidemic proportions, they admitted that there was a dearth of 
reliable statistics. For example, they believe that 85 percent of all young 
people between the ages of 15 and 25 in the Caracas metropolitan area have 
used drugs at least once, and that youths of all social classes are involved. 
Marihuana is stated to be by far the most widely used drug, and most of it 
is said to come from Colombia. The use of hallucinogens is believed to be 
limited, but increasing, as is the case with heroin and cocaine. The report 
did not supply any traffic pattern for these two hard drugs. There is vir- 
tually uncontrolled sale and an indication of a growing use of stimulants 
and depressants. 

The Commission recommends that the government and private groups must work 
simultaneously on three aspects of an anti-drug campaign -- prevention, 
repression and rehabilitation. They believe that it is necessary to launch 
a massive educational campaign which will involve training of parents and 
teachers as well as school children. Rehabilitation facilities are com- 
pletely inadequate, but there has been a start. This year, for the first 
time, the government is providing funds for drug rehabilitation. 

The recommendations for other funds for drug rehabilitation seem puzzling, 
especially in view of the fact that the drug most used seems to be cannabis. 
The Commission comes out strongly against the legalization of cannabis, or 
any reduction in penalties for use. They do maintain, however, that there 
should be a distinction in the law between addicts and traffickers, for 
cannabis and all other drugs. 

The Commission recommended that the government (1) take steps to ban the 
sale of medicine in any place other than a drugstore, and also to require 
that amphetamines and barbiturates be sold only by prescription; (2) desig- 
nate a special commission of jurists to study modifications in the penal 
code and the narcotics law; (3) attempt to establish a community center to 
deal with adolescent problems; (4) provide drug treatment service in psy- 
chiatric hospitals, jails, and prisons. 

The Venezuelan report is quite general in nature, acknowledges that much 
more investigation and study is necessary but the widespread publicity it 

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has received in leading Maracaibo and Caracas newspapers is an indication of 
the public interest in the field. 

In Ecuador, public concern about drug usage has apparently been aroused 
through a series of articles in the newspaper "El Comercio of Quito." Based 
on interviews with Interpol and the Criminal and Security Police, as well as 
certain educators and other authorities not identified, the newspaper claimed 
in June that about 600,000 people in Ecuador, about 10 percent of the popula- 
tion, use drugs of one kind or another. Half of the users are said to be in 
Guayaquil, about one sixth in Quito, with the remaining one third concen- 
trated in other areas of the country, particularly in Esmeraldas, El Oro, 
and Los Rios . 

According to El Comercio, 90 percent of the drug users are males and 80 per- 
cent of these are youths between the ages of 15 and 25. Thirty percent of 
the users are said to be high school or college students, 10 percent uni- 
versity faculty members, and about 55 percent are said to be vagrants or 
delinquents. About 60 percent of users are said to be lower class with the 
rest evenly divided between middle and upper class. 

There are no reports so far appearing in the literature on indigenous use of 
cannabis in Ecuador, although there is indigenous use of other hallucinogenic 
plants. 

In July of 1972, the Ecuadorean customs police was reorganized along military 
lines to help intercept a growing amount of drug shipment across Ecuadorean 
borders. Enforcement was also stepped up within the cities, and in one 
evening three cocaine processing laboratories were raided in and near 
Guayaquil . 

The government has announced its intention to ban all "hippies" from Ecuador, 
although no one is exactly sure what constitutes a "hippy" - a point which 
has been extensively satirized in the press. It was also announced that 
airlines flying hippies to Ecuador will be fined, and will be required to 
remove the offending passengers. 

The National Court for Minors has begun a campaign against drug usage by 
minors. Cooperating agencies include the Ministry of Health, the Ministry 
of Social Welfare and Labor, and the Ministry of Public Education. One of 
the initial ideas of this group is to separate minors from other criminals 
in prisons, which means additional space and hence more money. The National 
Department of Narcotic Control and Enforcement is planning to give a series 
of lectures in all middle level schools on the dangers of drug abuse. 

There are heartening signs that many of the governments of Latin America are 
now trying to enlist the aid of specialists in the health and behavioral 
sciences, as well as from the enforcement ranks, and that, in addition, they 
are asking U.S. aid in this attempt. 



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Mexico 

Although Mexico is widely known as one of the world's leading producers of 
marihuana, and the word itself is of Mexican origin, there is comparatively 
little historical or contemporary socio-cultural material bearing on cannabis 
use in that country. The lack of historical material is perhaps understandable 
in view of the fact that marihuana is not indigenous to any New World country. 
The lack of current material can be explained by the fact that marihuana use 
was not a widespread phenomenon in Mexico until the last few years. 

In contradistinction to marihuana (6), there is extensive documentation, begin- 
ning immediately after the Conquest, concerning many of the psychotropic drugs 
which were used by various indigenous populations in pre-Colombian times and 
continue to be used. Sahagun (1575-77), for example, described the appearance, 
place of origin, method of use, and reasons for use of such plants as peyote, 
ololiuqui (Rivea corymbosa) and teonanacatl ("flesh of the gods") , the hallu- 
cinogenic mushrooms. All of these plants were used formally in a sacred con- 
text by trained priests or shamans, according to a precise prescribed ritual. 
Most of the time the drugs were used to communicate with the gods to discover 
a favored course of action for a community, or to prescribe for members who 
were ill, or for other divinatory purposes. Even when the drugs were used by 
those other than shamans, for example, when peyote was used to cure people 
suffering from fevers, the sacred character of the plants was never lost sight 
of, and the social control mechanisms militated against their use for simple 
hedonistic purposes. 

Although Sahagun was interested in the entire indigenous herbal medicine 
armamentarium, he paid particular attention to the drugs which were involved 
in religious ceremonies because of his desire to substitute Catholicism for 
the indigenous cults and cult ceremonies. By the beginning of the seventeenth 
century, writers were beginning to comment on the incorporation of the uses of 
some of these drugs into Catholic ceremonies. There is no mention of the use 
of these drugs in the latter part of the seventeenth nor in the eighteenth or 
nineteenth centuries, but the practice never died out since modern anthro- 
pological research has uncovered many sections of the country, and many 
indigenous groups who continue to use these drugs in much the same way as 
they were used in pre-Colombian times. 

The kind of drug used depends now (as it did before the coming of the Spaniards) 
on the particular sections of the country and the climatic conditions there. 
Peyote was used in desert regions, ololiuqui in temperate areas and mushrooms 
in the humid mountains and woodlands. Use of various types of fermented 
beverages is common throughout most of the country and causes major problems. 
This was apparently true even at the time of the Conquest, since the Aztecs 
provided severe penalties (even including death) for some cases of drunkenness. 

In none of the early writings is there any mention of marihuana, in fact, 
none of the drugs so far described Were inhaled. There was, however, exten- 
sive use of tobacco in some parts of Mexico especially along the Gulf of 
Mexico. During the colonial period there is a similar lack of reference to 
marihuana, and some of the monks recommended during this time that the 

-73- 



cultivation of hemp be introduced into New Spain. In view of the early oppo- 
sition of the missionaries to the use of mind-altering drugs in non-Christian 
religious services, it seems certain that the intoxicating properties of canna- 
bis were unknown to them. 

No mention of marihuana is found in the proceedings of the Holy Office during 
the Inquisition, although all of the other narcotic and hallucinogenic drugs 
are specifically singled out for condemnation. In the exhaustive study of 
Mexican flora and fauna carried out by Alexander Von Humboldt in the latter 
part of the nineteenth century, there is no mention of marihuana. 

There is no firm historical evidence to support the varying views of when 
and by whom marihuana was introduced into Mexico. Some persons claim that 
it was introduced by Negro slaves, and others that it was brought in by sailors 
from the Philippines to the Port of Acapulco very early in the colonial period. 

According to one author, use of marihuana in Mexico came during the regime of 
Porf irio Diaz and involved primarily prisoners and soldiers. (1) Prisons and 
barracks were essentially the same because of the Army recruitment system 
enforced at the time. When a man was found guilty of a minor crime such as 
robbery or a drunken brawl, he was offered the alternative of going to jail 
or joining the Army. The country was at peace during this time, so service 
in the Army involved watching over isolated peasant and tribal groups, as 
well as service in an auxiliary police force. In fact some authorities think 
that the word marihuana itself may be derived from the terms Maria and Juan, 
the latter a derisive term applied to soldiers in general to indicate a lack 
of individuality (something like GI Joe) and the former Maria to designate 
their female companions. 

Distribution and consumption of the plant spurted upwards about the begin- 
ning of the Mexican Revolution in 1910 since the regular Army already included 
many marihuana users and the revolutionaries adopted it readily. It should be 
remembered that the Revolution lasted for 18 years and affected almost all 
regions of the country and all classes of society. The soldiers were trans- 
ported by train to various assignments and one of the revolutionary songs of 
the time attests to the popularity not only of marihuana, but also the method 
of transportation. The song is La Cucaracha. Although it has innumerable 
verses, each speaking of one aspect or another of the Revolution, it is the 
recurrent theme which has become the most popular - the cockroach/ the cock- 
roach cannot walk, because he's lacking, because he has no marihuana to smoke. 

It is probable also that production of marihuana was extended to various 
parts of the country at that time since the conditions under which it thrives, 
small secluded valleys with sandy soil, low humidity and a rather cold cli- 
mate, are characteristic of about 70 percent of the country. 

When peace returned, according to most observers, use tended to be once more 
concentrated among soldiers and criminals, but there is no documentation of 
this finding. Certainly there is agreement as to the fact that Mexican 
agricultural laborers, coming into the United States as early as the 1920 's, 
brought their "mota" along with them. 

-74- 



The first cases involving the use of marihuana began to come to the attention 
of Mexican psychiatrists in the 1930' s and in 1937, Dr. Segura Millan pub- 
lished the first and to date the only historical account of cannabis use in 
Mexico. Such an account, with due heed paid to the interaction of cannabis 
use patterns with the use of other drugs, both alcohol, native narcotic and 
hallucinogenic drugs, urgently needs to be written. 

Most authorities agree that the early use of cannabis was largely confined to 
lower socio-economic groups. In addition to the soldiers mentioned earlier, 
Millan also speaks of miners, lumberjacks, cane cutters, stevedores, and other 
laborers who perform difficult unpleasant work. By the 1930 's use had spread 
to the urban ghettos of many cities, and the activities of the young unemployed 
users brought summary attention from the authorities, so that penalties for 
use and possession were increased. Most of these laws, however, seem to have 
been enforced primarily in the urban areas, and use in rural areas by specific 
labor groups seems to have continued undisturbed. 

Most observers agree that there are several different patterns of cannabis 
consumption current at the present time; these include students, the upper 
classes (of varying ages) in resort areas, Army personnel and prisoners, 
laborers of various types, indigenous Indian groups who may use cannabis 
ritually, urban ghetto residents. 

There is no doubt of the fact that Mexico is experiencing the first wave of 
the drug using phenomenon which has long since affected her two neighbors to 
the North. 

Accounts of ritual use of cannabis in Mexico are comparatively scarce, but it 
may be that further studies will appear in the literature now that anthro- 
pological interest in drug use is increasing. Roberto Williams Garcia 
describes a communal curing ceremony among the Tepehua (6), who live in 
scattered communities in the mountains of Veracruz, Hidalgo and Pueblo, and 
belong linguistically and culturally to the Totonac of Veracruz, northern- 
most branch of the Mayan language family. 

The curing ceremony is centered around a plant called santa rosa, "The Herb 
Which Makes One Speak," and Garcia identifies this plant botanically as 
Cannabis sativa. According to this investigator santa rosa is considered 
both as an herb and as a special intercessor with the Virgin. It is wor- 
shipped as an earth deity and is thought to be alive and comparable to a 
piece of the heart of God. It is also dangerous - were it not for prayers 
and rituals, it could affect people adversely. It could assume the form of 
a man's shadow (soul) and make him sick, put him in a rage, or even lead to 
his death. 

Although the ceremony is conducted by a shaman, the central portion of the 
ritual involves the consumption of the herb by all the participants. The 
female participants dance in a circle and speak in a high voice. The atmos- 
phere during this part of the ceremony is not at all solemn, but later on the 
atmosphere changes to one of fervent music, dancing, ringing of bells, im- 
passioned oratory, and prayer. The shaman prays, and then dances with a 

-75- 



handkerchief, an act signifying that all children in the village suffering 
with grippe are cured. The ceremony lasts a good part of the night. 

A North American ethnobotanist who has spent several years in Oaxaca provides 
another illustration of the acceptance of a comparatively new hallucinogenic 
plant in an area which has had extensive experience with the magic mushrooms. 
The experienced farmers in this area have discovered that the finest cannabis 
is derived from plants that have been "tortured" by an extreme environment 
and unusual pruning practices. When the plants are just beyond the seedling 
stage, they are pinched to remove the apical meri stem which terminates the 
shoot tip. This part of the plant is responsible for the production of auxins, 
plant hormones, and the absence of this site of synthesis causes side shoots 
to become active. This results in the production of a small bush, instead of 
the usual tall cane. This pinching continues every week, so that it never 
rises more than a few feet from the ground. The plant assumes an urn shape 
in the course of such pruning. Shoots which would normally fill the interior 
are removed, so that as resins are formed they volatilize within the confines 
of this urn-like shrub. 

At maturity the "urn" is so coated with resins that the surface of the plant 
has a crystalline appearance. The normal flowering of the female plants is 
interfered with because of the frequent pinching, and the auxin changes some- 
times lead also to a change in pigmentation. Cyanins, which give a red appear- 
ance to plants, may accumulate, giving the plant a peculiar color as well as 
form. The mode of harvesting as well as cultivation departs from the normal. 
As the blood-like color begins to appear the plants are "crucified" by insert- 
ing wooden splinters through the stem at right angles to one another just 
above the ground. The resultant material, which acts rather like hashish, is 
used exclusively in the area in which it grows for ritual purposes akin to 
those involving the use of indigenous hallucinogens. 



Central America - Guatemala 

The First National Conference for the Study and Evaluation of Drug Problems 
(June 1972) was inaugurated by the President against a background of increasing 
official concern (but little actual knowledge) of the drug problem as reflected 
in the recent upsurge of arrests. The conference received extensive press 
coverage for several days prior to its opening, throughout the conference, 
and has been followed by numerous drug related articles and editorials. One 
of the more significant press contributions to the conference was the report 
of a survey by one of the local newspapers which stated that six percent of 
the secondary students use, or have used drugs, and listed those places (by 
category) where those drugs are most easily obtained. The accuracy of the 
information can be called into question given the nature of the sampling and 
collection techniques used - still it is the only available information on 
drug use in the country. 



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South America 



Chile 



Two studies have been published within the past year concerning student mari- 
huana use in Chile. There is no record of indigenous group use in that country, 
and national interest and concern apparently began about 1968. One study was 
conducted at a coeducational high school, with an equal number of boys and 
girls, and an age range of from 13 to 18. (8) The authors do not give any 
socioeconomic data other than the educational levels of the parents, of whom 
63 percent had finished high school, and 44 percent had college degrees. The 
investigators used a 61 item questionnaire, divided into three categories. 
The first section consisted of essentially demographic information, although 
it also included questions on religion and church attendance. The second sec- 
tion contained questions on use of alcohol and tobacco, and the third section 
was devoted exclusively to marihuana - levels of use, effects, motivations for 
use, or desire to try and so on. 

The level of use among these students is much lower than their counterparts 
in other parts of the Americas. Of 732 students who completed the question- 
naire, only 51 or barely 7 percent had ever smoked and of these, 31 had smoked 
only one or two cigarettes. A little over 17 percent of the students, 118, 
stated that they would like to try marihuana. A comparatively high proportion 
of student smokers reported adverse reactions to the drug which the investi- 
gators feel may be due to lack of knowledge of the drug. 



Argentina 

Argentina has asked for help from the United States in setting up programs 
for educational, rehabilitation and assistance programs. They view this as 
a two-way process, with Argentine psychiatrists and social workers coming to 
the U.S. for short visits to observe methods used here, and U.S. experts 
going to Argentina for more extended periods of time to help in inauguration 
of prevention and education programs. 



The Caribbean - Jamaica 

The material in this section is an adaptation of the findings from an exten- 
sive study of ganja use in Jamaica carried out by the Research Institute for 
the Study of Man, in cooperation with the University of the West Indies from 
August 1970 to December of 1971, under the aegis of the Center for Studies 
of Narcotic and Drug Abuse of the National Institute of Mental Health. Ganja 
is a strong form of marihuana. 

Research topics included a study of the anthropological, medical, psychological, 
and psychiatric effects and parameters of use and nonuse of cannabis. Basic 
background studies of cannabis use in seven ecologically different communities 
were conducted by teams of anthropological field workers from June 1970 through 

-77- 



December 10, 1971. In collaboration with the Faculty of Medicine of the 
University of the West Indies, and under the special sponsorship of Dr. 
Michael Beaubrun, Professor and Chairman of the Department of Psychiatry, 
thirty smokers and thirty controls were admitted to the hospital for a period 
of six days to undergo a series of intensive medical, psychological, and 
psychiatric examinations. The subjects ranged in age from 23 to 53 and were 
drawn from the working class strata of Jamaica: farmers, fishermen, artisans, 
and tradespeople. Smokers and controls were matched for age, socioeconomic 
status, and residence. Comprehensive life histories were recorded for each 
subject. 

The results of the physiological, psychological, and psychiatric tests are 
reported in another section of this report. We shall be concerned here with 
the anthropological findings (a term to be considered in its widest applica- 
tions since the researchers have attempted to examine many facets of the 
entire socio-cultural matrix of ganja use). This study has aroused widespread 
interest in the anthropological community (ethnologists are now exploring or 
have explored the possibilities of doing cannabis research in at least five 
other countries) as well as concerned governmental bodies, particularly those 
in the neighboring islands of the Caribbean. Penalties for ganja use have 
been reduced in Jamaica itself as a direct result of the study. 

Young anthropological graduate students (from the United States and Jamaica) 
worked in the field under direct supervision of senior anthropologists (a 
departure from the usual anthropological practice of unsupervised field work). 
This has created an important pool of young workers who could be profitably 
used to carry on, in other cultures, the much needed basic groundwork for any 
truly valid cross cultural research in cannabis use. 

Documentary evidence points to the fact that cannabis (as well as the multi- 
tude of uses to which it could be put) was introduced by East Indian contract 
laborers who were brought to Jamaica about 1845. The name used is "ganja," 
an East Indian term. There is use of chillum pipes as well as "spliffs" 
(cigarettes) for smoking; and, there is pragmatic as well as ritual use 
(ganja plays a role in folk medicine which is equally as important as the 
role it played and continues to play in Indian folk medicine). 

The whole socio-cultural complex of beliefs about ganja use was probably 
diffused to the Negro population through contact with East Indian laborers 
on the sugar plantations. The lower class native Jamaican seems to have 
embraced the use of the drug because it served significant psychosocial as 
well as economic functions. 

Today the principal users of ganja, usually called herbs (bad herb means 
cannabis of high potency) are still found to be among the lower classes, 
although, in common with most other countries of the world, more and more 
users are being drawn from the middle and upper classes. Users of cannabis 
in these classes speak of marihuana and probably the route of diffusion for 
these users was through the United States, England, and Canada. 



-78- 



Ganja is smoked, occasionally chewed, taken in "bush teas" for a wide range 
of ailments, as well as to build up strength, and cooked as a vegetable or 
added to soups, stews, and sweets. Smoking is usually confined to men, but 
children are introduced to ganja quite early through the medium of bush teas. 
This use may even start at birth, because some midwives in rural areas may 
recommend that an infusion of ganja be rubbed on the fontanell of the new- 
born infant to assure "wisdom," and also insist that the neonate be washed 
down with "ganja" tea to give him "strength" and prevent marasmus. 

The use of ganja in the bush teas is almost universally accepted, and many 
persons who are loud in their denunciations of ganja smokers may regularly 
use the teas. Use of ganja in beverage form is never connected in any way 
with questions of social deportment- -for example, it is never the tea drinkers 
who are accused of crimes or bizarre or psychotic behavior. It is never the 
ganja tea drinkers who are the object of periodic public crackdowns. 

Ganja smoking is extremely widespread among lower class Jamaicans -- 
Dr. Beaubrun estimates that about 40 to 50 percent of the adult males could 
be considered regular users. It should be remembered that there is an ex- 
tremely small middle and upper class on the island. The use of ganja seems 
to be situation specific - it can be used to give extra energy and stave off 
fatigue, or it can be used to induce restful slumber - it can reduce or in- 
crease appetite and so on. By far the most compelling reason given for the 
use of ganja by smokers other than those in their adolescent years has to do 
with its capacity to give energy - "it makes you feel to work." This find- 
ing is particularly important in view of the preoccupation of investigators 
in the United States and other industrialized Western nations with the so- 
called amotivational syndrome. This aspect of ganja use was studied not 
only through interview data, but also through videotaping of actual work 
behavior in a farming community with and without the use of ganja, under 
normal conditions to see whether the perceived increases of energy levels 
actually takes place. The films prove that there is no actual increase in 
energy, and in fact, there may be a decrease in work output. This investi- 
gator prefers the hypothesis (which may be applicable in other parts of the 
world as well) that this use may serve as a subconscious strategy for main- 
taining the community status quo in the face of ecological and population 
pressure on limited resources. 

In general, the cultural expectations and the subjective experiences of 
Jamaican working class smokers bear little, if any, relationship to the so- 
called mind -altering, mind -expanding experiences so often described by 
American users. On the contrary one of the values most frequently ascribed 
to ganja by working class is "keeping conscious" which is seen as cognitive 
advancement and support for rational rather than instinctive behavior. 

The age of initial use of ganja seems to have been steadily moving downward 
in the last ten years so that now the age of introduction for some boys may 
be as early as ten,, although the modal age still hovers around the early 
teens. Smoking for boys is seen as a rite du passage, is generally a group 
activity, and has in it some of the elements of the thrill of illegal and 
disapproved behavior. As the user becomes older however, smoking tends to 
become part of his everyday round of activities. 

-79- 



The Far East 

Two drugs, opium and cannabis, have a centuries old documented history of 
use in the countries of the Far East (India, Pakistan, Burma, Laos, Thailand, 
Ceylon, Korea, Vietnam, Taiwan, the Philippines, for the purpose of this dis- 
cussion). In some countries, even those dominated by Moslem thinking, there 
is use of alcohol, a growing use of synthetic drugs, the amphetamines and 
barbiturates. 

The countries under discussion (most of them underdeveloped) comprise a 
population of well over 972,000,000 embracing a diversity of populations, 
cultures, histories of divergent patterns of drug use. There is not a com- 
pletely adequate census of drug users in any of the countries mentioned; 
indeed, in several of them there is no adequate population census. 

In many of the countries, although use of cannabis and opium is technically 
against the law, it has been tolerated to a greater or lesser degree depend- 
ing, in great part, on the country's awareness and receptivity to plans for 
reduction in drug use emanating from more advanced Western countries. Of 
late, as use has spread from the traditional user, the lower class male, to 
adolescents of the middle and upper classes, the countries have begun to 
respond to internal pressure to develop some mechanisms to deal with the 
growing drug problem. In addition, there are indications, in several of the 
countries, that there has been a shift in choice of drugs (from opium to 
heroin) as well as a shift in the method of use. 

In almost all of these countries there is a significant lack of trained 
personnel in education, training, and treatment, in addition to inadequate 
treatment facilities. In many of them the presenting socioeconomic problems 
are of such magnitude that, until recently, little time or effort could be 
jpent on dealing with the drug problem per se. More funds, proportionately, 
ha^e been spent on enforcement, but there is increasing evidence that this 
approach has not served to stem the tide of rising drug use. 

In previous years we have commented on drug use patterns in India, Pakistan, 
Afghanistan, Nepal, Korea, Vietnam, Thailand, Cambodia, Singapore, Hong 
Kong, and Japan. 

In this year's report we have chosen to highlight only two countries, India 
and the Philippines, since the short dispatches indicate very graphically 
the problems faced by many of the countries in this part of the world as 
they attempt to grapple with the problems of drug abuse problems, in most 
instances, whose dimensions and parameters are unknown, and where the most 
familiar problem-solving devices stem from the police and the law courts 
rather than from the medical profession, the behavioral scientist, and the 
social workers. It should also be borne in mind in many of these countries 
that there is not the tradition of self-help through voluntary charitable 
agencies which exists in Western industrialized nations. Most action will 
have to be taken with government agencies which are, for the most part, 
understaffed and underfinanced. 



-80- 



With the opening of the channels of scientific information and exchange 
between Mainland China and the United States, it is to be hoped that informa- 
tion will soon be forthcoming not only concerning the methods which the 
government has used to reduce the number of opium users s but also any informa- 
tion about the use/nonuse of cannabis in that country. Since China is one of 
the first countries in the world in which there is documented information on 
the use of cannabis for medical purposes, and we know that there has been 
extensive fostering by the government of interest and use of native medicinal 
herbs, it would be of interest to know whether cannabis continues to be em- 
ployed, and in what ways, in either folk medicine or by the establishment. 



India 

A two-day seminar on Drug Abuse and Youth held in New Delhi in July 1972, 
was attended by some 75 delegates and 60 observers representing governmental 
and private agencies concerned with the health, education and welfare of 
children. All observers agreed that the problem of drug use is growing 
among Indian students, primarily those coming from upper class families, but 
no firm statistics are available. 

The seminar made a series of recommendations which they planned to submit to 
the Government for early implementation. These recommendations include the 
following items: 

1. Research studies be launched immediately to identify in the 
Indian context the dimensions and causes of drug abuse among 
young people (students and workers) in both urban and rural 
areas . 

2. Establishment of an interdisciplinary committee of experts, 
administrators, law enforcement officials, and social workers 
to serve as an advisory committee to the Government for 
policy-making in the prevention of drug abuse and addiction. 

3. Development of a concerted preventive program by the Govern- 
ment departments of health, education and social welfare with 
special emphasis on family responsibility of parents towards 
their children. 

4. Legal action should be confined mainly to drug peddlers; 
young persons found to be using drugs should be treated in 
special psychiatric clinics. 

5. Representatives of the mass media should be involved in a 
planned campaign to inform the public of the dangers of drug 
abuse. 

The delegates to this convention, which was open to the general public, were 
generally much concerned about the growing incidence of drug use and abuse 
among Indian young people, but handicapped in trying to establish a firm 

-81- 



policy since there were no reliable statistics available on the nature and 
extent of the problem throughout the country. 

In September the Delhi Medical Association, in cooperation with the Directorate 
of Health Services, Delhi Administration, and the Ministry of Health, held a 
one -day seminar on drug abuse. Mr. P. S. Ramachandru, the Drug Controller of 
India, asked for more effective control by the Government over the cultivation 
of cannabis. 

Presumably in response to these two seminars the Central Government acted 
promptly to begin implementation. The Ministry of Health has appointed a 
special committee to consider measures to tighten up the regulations concern- 
ing the distribution and sale of narcotics and psychotropic drugs. Drug 
manufacturing firms have been directed to discontinue free distribution of 
certain types of tranquilizers and other drugs as physicians' samples. 
Publishers of medical journals have been urged to emphasize that chemists 
and drugstores may supply psychotropic drugs only on presentation of bona 
fide prescriptions from qualified doctors. State Government Drug Controllers 
have been instructed to keep a closer check on the activities of retail drug- 
gists. 

The Philippines 

Prior to World War II widespread drug dependence (7) was unknown in the 
Philippines, but in the last 35 years, particularly in the last ten, the 
abuse of drugs has become a serious national problem. A recent report by 
the Chief of the Narcotics Division estimates that at least 60,000 young 
people are engaged in drug experimentation. The main drug used is marihuana, 
and there are indications that some local dealers are growing their own sup- 
plies. Cannabis plantations have been found in the Manila area as well as 
in Caloocan City, Quezon City, Las Pinas, Rizal and Cavite. There are also 
some plantations on neighboring islands such as Negros, the Bicol Region, 
Mindanao and Central Luzon. 

The National Mental Hospital and related treatment centers in other regions 
of the Philippines have numerous patients, from various social classes, 
admitted for dependence on a variety of drugs including heroin, morphine, 
cocaine, amphetamines, barbiturates and tranquilizers. One treatment center, 
located at Tagaytay City, and run by the National Bureau of Investigation, 
currently houses about 80 addicts (dependent on morphine and heroin) who come 
from Tondo, a slum area of Manila. 

The Addiction Institute of the National Bureau of Investigation provides 
detoxification, psychiatric service, vocational guidance and follow-up 
domiciliary care for any addict who requests it. In addition, a new organi- 
zation, The Narcotic Foundation of the Philippines, has been formed. This 
is a private organization primarily devoted to the raising of funds for the 
treatment and rehabilitation of young addicts as well as to launch various 
drug education and prevention programs. 



-82- 



At the end of March 1972, President Marcos of the Philippines signed into 
law the Dangerous Drugs Act of 1972, thereby providing the country with neces- 
sary new legislation to allow the country to deal with its growing drug abuse 
problem. The passage of the Bill and its signing brought to a close a process 
which had begun early in 1971 when new narcotic legislation was introduced 
into both houses of the legislature. In 1971 the House passed the Bill, but 
the Senate failed to bring it to a final vote. However, early in 1972 the 
first piece of legislation the Senate passed was the Dangerous Drugs Act. 
The Bill enjoyed wide support and its legislative course was remarkably free 
of the partisan politics that frequently affect major legislation in the 
Philippine Congress. 

The legislation creates a national Dangerous Drugs Board to implement the 
provisions of the Act. This nine member Board will be composed of three 
experts appointed by the President and, as ex-officio members, the Secre- 
taries of Justice, National Defense, Health, Education, Finance and Social 
Welfare or their representatives. Among other duties this Board is charged 
with the development of educational drug abuse programs for the general 
public, the provision of special training for police agencies, school authori- 
ties and personnel of rehabilitation centers, the conduct of research on 
dangerous drugs, preparing and coordinating the implementation of a national 
treatment and rehabilitation program. 

In general the Act emphasizes harsh penalties for those who engage in illegal 
production or trafficking in dangerous drugs, and stresses rehabilitation 
for drug users. Within the first six weeks of the passage of the legisla- 
tion, more than ten persons have been convicted on charges of illegal posses- 
sion or use and selling of dangerous drugs with sentences ranging from six 
months to twelve years. This upsurge of harsh sentences, many of them given 
out to middle class persons, has created a flurry of public debate about how 
severely the law should be implemented against users. Several Senators who 
co-sponsored the Senate version of the Bill have already called for amend- 
ments to insure that drug users receive treatment rather than prison sentences. 

The country is woefully short of resources both on the enforcement and 
rehabilitation, education ends of the continuum. According to press reports, 
President Marcos has been unable to find qualified persons to fill the three 
permanent positions on the Dangerous Drugs Board, and until he does, most 
of the educational and rehabilitative programs called for by the Act are 
unlikely to be started. 



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References 



1. Bueno, D.U. , M.D. The Problem of Drug Addiction in Mexico. In 
R.T> Harris, W.M. Mclssac, and C.R. Schuster, Jr. (Eds.) Drug 
Dependen.ce . Austin, Texas: University of Texas Press, 1970. 

2. Blum, R. Society and Drugs . San Francisco: Jossay-Bass, 1969. 

3. Buikhuisen, W. and Timmerman, H. The development of drug-taking 
among secondary school children in the Netherlands. Bulletin on 
Narcotics , 24:3-16, 1972. 

4. Cannabis - A Report of the Commission of Inquiry into the Non- 
Medical Use of Drugs . Ottawa: Information Canada, 1972. 

5. Drug Trafficking and Drug Abuse Report from the Senate Select 
Committee . Canaberra: Australian Government Publishing Service, 
1971. 

6. Emboden, W.A. , Jr. Ritual Use of Cannabis Sativa L: A Historical 
Ethnographic Survey. In: P. Furst (ed.) Flesh of the Gods . 

New York: Praeger, 1972. 

7. Goduco-Auglar, C. A note on drug abuse in the Philippines. 
Bulletin on Narcotics , 24(2), 43-44, 1972. 

8. Gomberoff, M. A study of the conscious motivations and the effects 
of marihuana smoking on a group of adolescents in Chile. Bulletin 
on Narcotics , 24(3), 27-33, 1972. 

9. Soueif, M.I. The social psychology of cannabis consumption: myth, 
mystery and fact. Bulletin on Narcotics , 24(2), 1-10, 1972. 

10. Soueif, M.I. Hashish consumption in Egypt, with special reference 
to psychosocial aspects. Bulletin on Narcotics, 19(2), 1-12, 1967. 



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PRECLINICAL RESEARCH 



This section summarizes a wide range of investigations, chemical, biochemical, 
pharmacological and behavioral. Studies reported this year have included 
evaluation of the effects of repeated as well as single administrations of 
cannabinoids and give us a better picture of what can be expected in long-term 
use in man. Tolerance to many of the effects of cannabinoids has been reported 
in long-term studies, but there is still disagreement regarding the mechanisms 
involved in the production of tolerance. 

One of the most important findings this year has been to confirm in animal 
studies that synthetic or natural marihuana appears to have no serious dele- 
terious effects on pregnancy, the fetus or the newborn. While such evidence 
cannot categorically rule out such effects in humans, it is nevertheless reas- 
suring. 

Although many of the cannabinoids isolated from marihuana have become avail- 
able through synthesis, there is still considerable interest in the plant 
itself, the factors influencing its variations in potency and the biosynthesis 
of its active components. 

Considerable research also continues in the analytical area towards development 
of new techniques, such as radioimmunoassay, for detection and quantification 
of cannabinoids. 

Studies of cannabinoid metabolism have continued at an accelerated pace. It 
is now certain that cannabinoids are rapidly transformed in the body and there 
are now at least twenty-two known metabolites of marihuana that have been 
identified either in vivo or in vitro . However, there is not yet conclusive 
evidence about which metabolite or metabolites are responsible for the psycho- 
logical effects r-f rarihuana in man. Considerable effort has been made to 
develop large scele syntheses of these metabolites, especially of the 11-OH 
metabolite of delta-9-THC but progress has been slow. Metabolites are still 
being produced on a very limited scale, in milligram amounts. This scarcity 
of materials has so far prevented in depth pharmacology studies of these com- 
pounds. Nevertheless, it has been confirmed this year that the 11 -hydroxy 
metabolite of delta-9-THC is a potent psychoactive agent and its effect at 
least equal to that of the parent compound. 

The abuse potential of delta-9-THC is still under debate with one study report- 
ing some "abstinence signs" in a small number of animals upon discontinuance 
of the drug. In the same study, some of the monkeys were able to initiate 
and maintain self-administration of THC while in another study this did not 
happen. 

It has been confirmed this year that biogenic amines, as well as cholinergic 
compounds, are implicated in the mechanisms underlying the effects of marihuana 
and that marihuana has definite effects on the neuroendocrine system. 

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In the past two years, a wealth of data has been published regarding the 
effects of marihuana on behavior. Reversal of behavior, from sedation to 
aggressiveness and fighting has been confirmed in the rat after long-term 
(more than two weeks) administration of doses of del'ta-9-THC at behavioral dose 
levels. This tendency towards aggressiveness seems to be increased by food 
deprivation. Cannabis seems also to induce an inversion in social hierarchy 
but is partially dependent upon the testing situations and the contingencies 
operating in the environments. The same is true of studies of the effects on 
cannabinoids on avoidance performance and behaviors maintained by aversive 
control which may or may not be affected by marihuana. 



-86- 



CHEMISTRY 



In the First and Second Annual Marihuana and Health Report to Congress, (125, 
126) detailed descriptions of the plant Cannabis sativa, its chemical composi- 
tion and analytical methods used for detecting and assaying Cannabis and can- 
nabinoids were given. In this Report, only the more significant developments 
that have appeared in the past year will be discussed. 



Drug Sources 

Although many of the cannabinoids isolated from marihuana and related materials 
have become available through synthesis, considerable interest and research 
continues with the plant itself, Cannabis sativa . In what might be a model 
study for all states, a detailed survey of a sample county in Kansas has re- 
vealed the extent of Cannabis growing wild (45). Further, various methods of 
controlling the plant were compared, indicating a variety of useful techni- 
ques. Additional studies showed the influence of seasonal and environmental 
effects on cannabinoid content (110) . They confirmed the earlier studies 
showing that most native Cannabis is genetically derived from hemp producing 
varieties, which apparently have not changed significantly in their lack of 
ability to produce much of the active cannabinoid delta-9 -tetrahydrocannabinol 
(delta-9-THC) . This concept of low THC-producing varieties in this country 
may have to be revised in light of findings recently reported by Mishioka's 
group in Japan (152). By a massive screening of Cannabis varieties, they 
were able to find a strain that does not produce delta-9 -THC, stopping at the 
biogenetic precursor cannabidiol (CBD). Cross pollination experiments with 
other strains always gave offspring that produced higher amounts of THC indi- 
cating that high THC-producing strains, e.g., Mexican, are genetically domi- 
nant, whereas the hemp varieties are genetically recessive. This may mean 
that the introduction of Mexican, etc., varieties may allow the common hemp 
varieties to become more "active." It has been observed that the Mississippi 
grown crops have shown higher THC contents in each succeeding crop (192), 
which may partially be a result of improved cultivation methods. 

Yagi, of the Mishioka group, also reported direct evidence for the elucidation 
of the biosynthesis of cannabinoids in Cannabis (152). This was accomplished 
by finding a strain that was able to absorb and assimilate radio labeled pre- 
cursors. Previous studies were hampered by the low levels of incorporation. 
Thus, the pathway as proposed by Mechoulam (138) but until now unsubstantiated, 
was shown to proceed from malonic and mevalonic acids and geraniol to canna- 
begerolic acid (CBGA) to CBD-acid to delta-9 -THC acid. Also, in an alternate 
pathway CBGA is converted to cannabichrominic acid. The acids make up the 
largest amount of cannabinoid content in fresh marihuana and hashish and are 
decarboxylated on aging and smoking to THC, CBD, etc. 

Although long known to be present in Cannabis products, delta-9 - tetrahydro- 
cannabinol^ acid (delta-9 -THCA) has only recently been isolated and character- 
ized (40). In some samples investigated delta-9-THCA was present in a 5:1 
ratio to delta-9-THC. 

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Further confirmations of the presence and properties of side chain homologs in 
hashish has appeared (50, 189). The propyl and methyl analogs of THC, CBD and 
cannabinol (CBN) were reported to have considerably lower activity than the 
parent amyl derivatives (189) . It was recommended to give the propyl series 
the class name cannabivarol instead of the previously suggested name cannabi- 
varin to avoid confusion with alkaloids and glycosides. The methyl derivatives 
were named as cannabiorcols . 

Certain alkaloids of this type are known to have psychotomimetic properties, 
although it seems doubtful that the trace amounts present here would account 
for any of the effects of Cannabis products. Their complete characterization 
is required to settle this question. The roots of Cannabis have been examined 
and shown to contain triterpenes and a cinnamamide derivatives, which had weak 
analgetic properties (177) 

The question of delta-9-THC stability has been extensively studied. Its con- 
version to the more stable delta-8 isomer occurs readily in the presence of 
acids, but apparently does not during smoking (187). The temperature depen- 
dence and mechanism for these conversions under various conditions have been 
studied (166). On porous surfaces exposed to circulating air, delta-9-THC was 
readily oxidized to CBN. Solutions in ethanol were found to be the best means 
of stabilizing delta-9-THC for long periods of time and have been shown to be 
stable up to one year (166). 

A recent study of the effects of the smoking process on cannabinoid content 
showed that the decomposition of THC was not only dependent on the degree of 
dryness, the air current and temperature, but on the presence of other canna- 
binoids, e.g., CBD (30). If alone, as in spiked cigarettes, delta-9-THC was 
found to be affected to a much greater degree Earlier studies by a number of 
investigators give somewhat conflicting results (187). As the results depend 
on the techniques used, considerable caution must be exercised in their com- 
parison. 

Most of the synthetic and naturally derived samples of delta-9-THC, supplied 
to investigators, contain small amounts of delta-8-THC and CBN. Earlier 
samples also contained the exocyclic isomer, delta-9,ll-THC, but this was 
later eliminated as manufacturing technique improved. A microparticulate gel 
chromatography method is recommended as a convenient technique of obtaining 
small quantitie:-' of pure delta-9-THC in the laboratory (167). 

Intensive efforts have continued towards improved and new synthetic methods 
for obtaining biologically significant cannabinoids . This important work is 
providing limited quantities of some of the less readily available natural 
cannabinoids and metabolites for research purposes. It is essential to under- 
stand the biological properties of each to gain a clear picture of the overall 
effects of Cannabis. For example, there have been reported the synthesis of 
delta-9,ll-THC (161) and the active metabolites ll-hydroxy-delta-8-THC (151), 
and ll-hydroxy-delta-9-THC (193). Also new syntheses of radiolabeled THC's 
have appeared (66, 116) 



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Analytical Techniques 

Considerable activity continues in the area of developing new and more refined 
technique for the detection and estimation of cannabinoids and their metabo- 
lites. Such methods are important for forensic and screening purposes and for 
determining biological levels and distribution of the cannabinoids. Gas chro- 
matography continues to be the technique most widely employed. Its character- 
istic sensitivity and separating abilities have been steadily improved upon. 
By using a solid sample injection system the contents in as little as 1 mg. of 
dried plant material may be quantified (165). The use of more easily detected 
derivatives (175) and a survey of suitable conditions (86) have been reported. 

One of the other techniques that continues to be investigated is thin layer 
chromatography using highly flourescent cannabinoid derivatives. Although 
very useful for the analysis of chemical mixtures, the method has still not 
been perfected for use with biological samples, e.g., urine or blood (54). 
Radioimmunoassays (RIA) continue to command intense interest as they would 
provide a highly sensitive and convenient method of detecting cannabinoids in 
biological media. Unfortunately, a number of problems continue to plague the 
development of a suitable method. Progress has been made on fluorescence 
quenching (71) and other immunological techniques (188) and a suitable uni- 
versal method appears imminent. 

The use of an automated process based on a new technique of mass fragmentometry 
has been reported (72) . A simple method of detecting Cannabis smokers by 
breathing onto strips of a test paper impregnated with Fast Blue B dye has been 
suggested (133). It is sensitive up to two hours after smoking although some 
tobaccos interfere. 



Structure-Activity Relationships 

Since last year's Annual Report, little additional information has been re- 
ported on the rather unique structural features associated with cannabinoid- 
like activity. The rather limited number of structural variations possible 
to retain biological activity only serves to dramatize the characteristic 
action of this series of chemicals. Often a detailed study of chemical 
features associated with the biological activity within a group of compounds 
can shed some understanding into their mechanism of action. This has not been 
true so far in the case of the cannabinoids whose stereospecific nature is 
indicative of very specific receptor interactions in the central nervous system 
(CNS) . As yet, these receptors or sites of action remain to be elucidated. 

Of particular structural interest is the growing body of information about the 
activity of cannabinoid isomers and metabolites, which will be discussed in 
further detail later. A comparison between the activity of delta-8- and 
delta-9-THC isomersand metabolites by intravenous and intracerebral adminis- 
tration in mice has been reported (21) . Reportedly, they found that there is 
no difference in potency in their biological assay between delta-8- and 
delta-9-THC and that their principle metabolites, the 11-hydroxylated THC's, 
are nearly fifteen times more active by the cerebral route and twice as potent 

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even by the intravenous route. This agrees with other data that suggests 
that the metabolites are primarily responsible for the major pharmacological 
effects of the THC's. The more highly oxygenated metabolites were considerably 
less active as were CBD and CBN (21). Considerably more research is required 
in this area. In particular, details of brain levels, better controls and 
studies in other species are needed. 

A number of synthetic analogs of the cannabinoids have been prepared and 
tested (166) . These analogs contain an additional heterocyclic atom of nitro- 
gen or sulfur. The nitrogen analogs were designed to have some relationship 
to other classes of compounds known to have CNS activity, e.g., stimulants, 
depressants, psychotomimetics and narcotics. These analogs have exhibited 
various degrees of these activities and do resemble the cannabinoids in a 
number of ways. The sulfur analog was quite similar to delta-9-THC (154). 
Further work with these and other analogs is in progress. 



PHARMACOLOGY 



In the last four years, there has been intense activity in the field of mari- 
huana research. Significant aspects of the preclinical pharmacology of mari- 
huana have been reported in numerous articles, reviews, and symposia (2, 41, 
76), as well as reviewed in the last two Marihuana and Health Reports (125, 
126). Controversy exists concerning several aspects, but progress is being 
made towards a better understanding of marihuana and its pharmacological 
effects. In view of the wealth of literature on marihuana and the two recent 
reports, no attempt will be made to conduct a comprehensive review of the pre- 
clinical pharmacology of marihuana. Rather, the preclinical pharmacological 
profile of delta-9-THC, the commonly agreed upon active component of marihuana, 
will be generally summarized and pertinent aspects emphasized. 



Preclinical Pharmacological Profile 

The effects of delta-9-THC in animals are best described pharmacologically 
as unique and complex. A variety of factors influence the ultimate response. 
Dose, vehicle, time after administration, prior sequence of administration, 
species, sex and environmental surroundings, all affect the response ultimately 
attributed to delta-9-THC. 

The pharmacological syndrome observed is paradoxical in nature. In general, 
central nervous system depression is mixed with CNS stimulation, depending 
upon the dose and time after administration. For example, in rodents low 
doses of delta-9-THC or marihuana extract produce depression of spontaneous 
locomotor activity mixed with periods of hyperactivity. With larger doses, 
the animals are catatonic but paradoxically hyperreactive to sound or tactile 
stimuli (76). Analogous effects have been observed in dogs (95) and pri- 
mates (1). Moreover, delta-9-THC interacts contradictorily with stimulant 
and depressant drugs. Reportedly, delta-9-THC potentiates the depressant 
effects of barbiturates and enhances the stimulation of locomotor activity 
produced by amphetamine (63) . 

-90- 



Further complexity is introduced by the phenomenon of tolerance. Tolerance 
develops to at least certain behavioral effects of delta-9-THC in rats, pigeons, 
dogs, and monkeys; a comprehensive review of this phenomenon (137) was summa- 
rized in the 1972 Marihuana and Health Report (126). Recently, Pirch et al . 
have expanded these observations to studies of the effect of delta-9-THC and 
marihuana extract distillate (MED) on the rat electrocorticogram. Acutely, there 
was an overall decrease in integrated voltage, a decrease in the amplitude of 
low voltage activity, and the appearance of high voltage "spindle-like" activity 
after MED and delta-9-THC. Notably, when MED was administered chronically, 
tolerance appeared to develop to some, but significantly, not all of delta-9- 
THC's effects on the rat electrocorticogram (160). These, and many other 
studies, exemplify the complexity of the phenomenon of tolerance development 
to delta-9-THC or marihuana extract. 

Recently, investigators have pursued the question of whether cross tolerance 
develops between delta-9 and ethyl alcohol in rats. Newman et al . , proceeding 
from earlier reports of an interaction between chronic marihuana and ethanol 's 
acute effects (137, 92), studied both drugs chronically in the rat (150). Re- 
portedly, rats tolerant to delta-9-THC were less susceptible to the acute effects 
of ethanol in a one-way avoidance paradigm. Moreover, rats tolerant to ethanol 
were correspondingly less affected by delta-9. These results are intriguing 
both from a sociological and mechanistic viewpoint. A more definitive state- 
ment on this phenomenon, as well as its potential significance, will require 
further study. 

In addition, this year, in contrast to earlier assumptions, self -administration 
of delta-9-THC was reported in the rhesus monkey (33, 93). After 36 days of 
chronic administration of delta-9 -THC, two of six monkeys initiated and main- 
tained self-administration of THC. Moreover, all six rhesus monkeys chronically 
treated reportedly demonstrated "abstinence signs" upon discontinuance of the 
drug. These signs consisted of hyperirritability, increased aggressiveness, 
muscle tremors and twitches, and yawning. Interpretation of this data is 
hazardous at best in view of the relative small number of animals which self- 
administered delta-9 -THC, the severity of the treatment and the resemblance 
of the "abstinence signs" to chronic effects of delta-9-THC alone. Moreover, 
others have had difficulty inducing monkeys to self -administer delta-9 -THC 
(77). Nevertheless, this observation is highly provocative and will undoubtedly 
stimulate further research along similar lines. 

An early report of a specific antagonist to marihuana has been seriously ques- 
tioned. A Russian account reported that phenitrone, [3- (hexahydro-lH- 
azepin-1-yl) -3' -nitropropiophenone HCll , appeared to block behavioral effects 
in dogs exposed to hashish smoke. However, subsequently, at least three groups 
have been unable to reproduce this effect in dogs, rats, or monkeys using more 
refined preparations of marihuana (119, 181). However, a somewhat related 
report of the blockade of the depressant effect of delta-9-THC in mice by 
cannabinol (194), although preliminary, has spurred interest in the possibility 
of finding antagonists to delta-9-THC, 



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Cardiovascular Effects 

In contrast to the dose-related tachycardia observed in humans after adminis- 
tration of marihuana or the cannabinoids, bradycardia is generally observed in 
animals. In anesthetized dogs and rats, delta-9-THC produced bradycardia and 
long lasting hypotensive effects (39, 141). Spinal section of C2-C4 plus bi- 
lateral vagotomy reportedly prevents these effects (14). In contrast, however, 
atropine, ganglionic blocking agents, nor beta-blockers individually reportedly 
appear to be able to completely block these effects (36, 107). These and re- 
lated data, reviewed in the last two Marihuana and Health Reports (125, 126), 
have prompted a number of investigators to postulate that the effect of delta-9- 
THC on the cardiovascular system is at least in part mediated centrally and 
that the characteristic effects of delta-9 are probably a result of diminished 
sympathetic outflow from the brain. 

In the unanesthetized animal, however, although bradycardia is still observed, 
no significant hypotension is apparent (36, 109). Thus, it appears that at 
least the hypotensive component of delta-9-THC effect in the anesthetized 
animal is most probably a result of interaction between the anesthetic agent 
used and delta-9-THC. 

Recently, Cavero et al . have performed a detailed analysis of the relationship 
between the respiratory and cardiovascular effects of delta-9-trans-tetrahy- 
drocannabinol in the anesthetized dog (15). Using a relatively high dose 
(5 mg/kg) , they showed that delta-9 induced transient hyperpnea and hypoxia 
in spontaneously breathing dogs, but not in artificially ventilated animals. 
Moreover, a marked and reproducible hypotensive effect occurred in the arti- 
ficially ventilated animals not in the spontaneous breathers. In the latter, 
a diminished, more variable effect on blood pressure was evident. Thus, there 
appeared to be a relationship between the hypotensive effects of delta-9 -THC 
and the maintenance of blood gas parameters within physiological values. The 
bradycardia produced by delta-9-THC, however, was similar on both groups of 
animals and therefore did not appear to be affected by these changes in venti- 
lation. These results may explain some of the variability in results pre- 
viously reported regarding delta-9-THC's effect on blood pressure. 



Neurochemical Effects 

In an attempt to delineate the mechanism of action of marihuana in the brain, 
a number of investigations have centered around the effect of marihuana 
extract or of the tetrahydrocannabinols on the brain biogenic amines. Ini- 
tially, these concentrated on effects on whole brain levels of serotonin or 
norepinephrine. Now studies have been expanded to include analysis of turn- 
over rates, localized sites in the brain, uptake and release mechanisms, 
amino acid uptake, and more recently to effects on other postulated neuro- 
transmitters in the brain. A good deal of this work has been recently sum- 
marized in the 1971 Proceedings of the New York Academy of Sciences (186) 
and in last year's Marihuana and Health Report (126), 



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The voluminous literature on the effects of marihuana extract or the tetrahy- 
drocannabinols on brain serotonin is quite contradictory. In 1964, Bose (2) 
reported a fourfold increase in whole rat brain serotonin after a single in- 
jection of marihuana extract. In 1965, Garattini (61) could find no alteration 
in serotonin levels in rat brain following either acute or chronic administra- 
tion of cannabis extract. 

Subsequent studies with pure delta-9-THC are still equivocal. Holtzman et_al. 
(88), expanding these earlier observations, found that doses from 10-50 mg/kg 
i.p. of delta-9-THC produced a small, but significant, elevation of whole 
brain 5-HT levels in the mouse. These same dose levels produced a slight de- 
crease in NE levels. Moreover, these changes in biogenic amine levels appeared 
to parallel the behavioral effects of delta-9-THC. 

Later, two groups of investigators (194, 180), reproduced similar effects with 
respect to 5-HT, yet there was disagreement about the localization of the 
effect in the brain. Ho et al . (84) recently reported analogous results in 
mice after intravenous administration of 5-10 mg/kg of delta-9-THC. However, 
this group found that in the monkey IV doses of 2 mg/kg and higher produced 
decreases of both 5-HT and NE. In addition, delta-8-THC exerted a greater 
effect on both biogenic amines despite the fact that delta-9 appeared more 
potent behaviorally . A somewhat related contradiction was reported by Welch 
et al . In their studies, cannabinol (CBN) exerted an effect similar to delta-9 
on telencephalic serotonin in the mouse (194) . 

Other groups (60, 113) have recently reported that there appears to be a dis- 
sociation between the behavioral effects of delta-9-THC in the rat and altera- 
tions in brain serotonin. An analogous result was found in mice (95). Al- 
though the behavioral effects of delta-9-THC were evident at the doses studied, 
no statistically significant change was observed in 5-HT levels. 

The effects of cannabinoids on catecholamines have also received their share 
of attention. At least three groups (174, 194, 113) have been unable to con- 
firm the previously reported decrease in norepinephrine levels. Studies are 
proceeding on more complex measures of NE effects in the brain. As previously 
summarized (186), the schedule of administration of ^h-NE and THC seems to 
affect the results on norepinephrine. Increased retention of J H-NE appears 
evident if THC is administered first (186); conversely if the tritiated NE 
is equilibrated prior to THC, there seems to be an increase in NE turnover at 
least initially (186, 122). Moreover, other investigators have found increased 
catecholamine levels in specific brain areas using fluorescent histochemistry 
(26, 143, 59). These findings in specific areas of brain may ultimately 
explain some of the differences observed in studies on alterations of whole 
brain biogenic amines. A dopaminergic mechanism has also been recently impli- 
cated in the behavioral effects of delta-9-THC (57). Following acute and 
chronic (8 days) i.p. injections of 5 and 10 mg/kg delta-9-THC in rats, 
endogenous levels of dopamine were reduced in the brain stem, but not in the 
forebrain. Homovanillic acid levels were elevated by acute delta-9 -THC. 

In addition to studies on NE and 5-HT, there has been some investigation of 
effects on other postulated neurotransmitters. Domino et al . (41) recently 



reviewed the effects of delta-9-THC on acetylcholine (ACh) . In two strains 
of mice, increasing doses of delta-9-THC reportedly produced a statistically 
significant increase in whole brain acetylcholine; correspondingly, at least 
two dose levels (10 and 32 mg/kg) delta-9 antagonized hemicholinium induced 
reduction of ACh. Expansion of these results to an analysis of effects on ACh 
release from the cat cortex revealed that, although increased variability was 
apparent with small doses, larger doses of delta-9, as expected, seemed to 
cause a progressive decrease in ACh release. These results, it was amply 
pointed out, are complicated by the fact that most central nervous system 
depressants increase acetylcholine levels at doses producing sedation and 
comatose state. 

A preliminary report (113) indicated that changes in gamma-aminobutyric acid 
(GABA) levels occur in the mouse brain after delta-9-THC. Leonard, in a series 
of comprehensive articles on the effects of psychotropic substances in the 
brain amines (112, 113, 114), reported that a large dose (100 mg/kg i.p.) of 
delta-9-THC, producing pronounced behavioral effects in rats, caused a slight 
decrease in brain and blood tyrosine and brain GABA levels, although the levels 
and turnover of other important amines appeared unchanged (113). 

In the last two years with increased information about the effects of delta-9- 
THC on biogenic amines in the brain, it has become evident that this is a very 
complicated area of investigation. In addition to the complex pharmacological 
profile of delta-9-THC and the marihuana extract, the central nervous system 
is a dynamic system with intricate mazes of biochemical events. Levels of 
biogenic amines are maintained by multifactorial events including uptake of 
precursor amino acids, activity of synthetic and degradative enzymes, uptake 
and release mechanisms, as well as the interaction of various functional 
neuronal systems in the brain. Evidence is increasingly accumulating to show 
that delta-9 -THC and marihuana extract influence both steps directly involved 
with maintenance of amine levels as well as related steps (91, 134). Inter- 
pretation of the data now tends to emphasize changes in the overall balance 
of levels of biogenic amines (84) rather than discrete changes in the whole 
brain levels. 



Neurophysiological Effects 

Additional studies of the neurophysiological and neuropharmacological effects 
of cannabinoids in various species, rats (160), cats (176), rabbits (58), 
and baboons (100) have been reported in the past year. 

Evaluation of the effects reported in the different studies is, as usual, 
different since various dose levels, routes and experimental conditions were 
used. When one considers, however, the results obtained by the IV route, a 
typical pattern of marihuana effects on the EEG seems to emerge. As shown 
by Segal (176), it appears to consist of a triphasic EEG response character- 
ized by an early stimulation and increase in arousal, then depression shown 
as cortical synchronization simultaneous with or followed by high voltage 
spiking activity. Cortically, the effect seems to be more intense in the 
frontal than in the posterior areas. Subcortically, the cannabinoids produce 

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definite changes in the "old brain" areas. In the hippocampus, changes in 
rhythm (117, 19), epileptiform spikes, slow waves (127, 117), and fast, high 
amplitude spindles (85, 19) have been reported. Spindles were also seen in 
the amygdala and hypothalamus (85). The effect of cannabinoids on the septal 
region is mixed, with sometimes stimulation (fast spindling activity) and at 
other times depression (slowing with sharp waves) (78, 19). The marked effect 
of the cannabinoids on these areas is not surprising in view of the auto- 
radiography findings showing high concentrations of delta-9-THC or its metabo- 
lites in these subcortical areas (83) . 

In rodents, delta-8-THC produces the same effects as delta-9-THC (145), but, 
in the cat, delta-8-THC produced EEG depression rather than the activation 
seen with delta-9-THC (176, 191). Repeated daily administration showed some 
tolerance developing to the EEG changes in voltage but not to the spike-like 
activity (117, 160). Although this spike-like activity has been a consistent 
finding in most studies (117, 191, 176, 42, 127), there has been no report of 
seizure activity after acute administration of cannabinoids, even at high dose 
levels. It has even been shown (100) that small doses of 5-160 micrograms per 
kilogram of delta-9-THC, which produce changes in spectral power density dis- 
tribution of resting EEG patterns in the baboon, can block photomyoclonic 
evoked seizures, corresponding to the findings of Sofia who has reported an 
anticonvulsant effect of cannabinoids (179). 

The neuroendocrine effects of marihuana on the hypothalamo -hypophyseal -adrenal 
axis have been reemphasized. Oral or i.p. administration of hashish to rats 
produces an increase in plasma corticosteral levels in plasma corticosterone 
and depletion of adrenal ascorbic acid and cholesterol content (37) . This 
corticosterone elevation by delta-9-THC had previously been shown to be 
centrally mediated (108). Others investigated the effects of orchidectomy 
and testosterone pretreatment on responses to marihuana (22) . These experi- 
ments demonstrated that responses to marihuana may be altered by changes in 
hormonal balance. 



In Vitro Effects 

A. Liver 

Delta-9-THC strongly affects rat liver mitochondria in vitro . 

"At concentrations of 15-60 nanamoles/mg of mitochondrial protein, 
THC uncoupled state IV respiration and decreased respiratory con- 
trol and ADP / ratios. Energy-linked changes in fluorescence of 
8-anilino-l -naphthalene sulfonate were prevented or reversed by 
THC. THC also produced large amplitude swelling of mitochondria 
and release of matrix enzymes. These effects were greatly poten- 
tiated by Mg . Likewise, flocculation of mixed phospholipid 
micelles by Mg was potentiated greatly by low concentrations of 
THC. Studies with micelles prepared from purified phospholipids 
suggest that THC may specifically destabilize the cardiolipin in 
mixed micelles , " 

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It also increases ATPase activity (17). In vivo , 'delta-9-THC increases the 
activity of two liver enzymes, tyrosine-alpha-ketoglutarate transaminase (FKT) 
and tryptophan-pyrrolase (TPO) . 

B. Lung 

Addition of marihuana to 'cigarettes has been shown to produce a smoke which 
evokes morphological and cytochemical alterations in epithelioid cells of lung 
explants such as atypism, mitosis and DNA synthesis to a significantly greater 
degree than does smoke from cigarettes without marihuana (115) . In isolated 
perfused lungs, delta-9-THC decreased perfusion flow rate, indicating pulmonary 
vascular constriction and increased tidal volume, probably by primary action on 
the alveoli (182). 

C. Red Blood Cells 



Delta-9-THC protects red blood cells against hypotonic hemolysis. This 
protection increases with increasing THC concentration. Lowering of either 
pH or temperature enhances the stabilizing effect. Addition of albumin to the 
hypotonic solution decreases stabilization. This protective effect of THC is 
probably due to its highly lipophilic character and low water solubility, which 
probably help it to bind erythrocytes membranes (16) . 



METABOLISM 



Intensive efforts continue in the studies of cannabinoid metabolism. In addi- 
tion to attempting to learn about the absorption, distribution and fate of the 
drugs themselves, far more information about the pharmacologic properties of 
their metabolites is required to understand clearly the overall effects of 
Cannabis and its derived products. Various aspects of Cannabis metabolism 
have been reviewed since last year's report (148, 148a, 190). Absorption, 
distribution, metabolism and excretion will be discussed separately. 

A. Absorption . Little new information concerning the relative efficiency of 
various routes of administration has appeared. It is commonly accepted now 
that administration by inhalation (smoking) and intravenous injection are the 
most effective routes, with oral and intraperitoneal not as good. Studies 
using intracerebral injections (21) indicate more accurately the central 
effects of the parent drug as they have also shown that little if any metabolism 
takes place in vitro in the brain tissue (21). One must regard these results 
with caution, however, as the drug passes freely out of the brain into the 
circulating system where it can be metabolized and the metabolite can enter 
the brain. 

Other water-soluble derivatives suitable for oral and parenteral administration 
have been reported (196). The most promising of these is the l-(4-morpholino)- 
butyrate ester of delta-9-THC (SP-111A) . It apparently hydrolyzes rapidly and 
gives effects nearly identical to the parent THC given in the usual emulsified 
form. 

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B. Distribution . Of continuing concern is the effects of Cannabis use during 
pregnancy. A number of studies on the distribution of THC and its metabolites 
in mice and pregnant mice have been reported (56, 75, 96, 170) By using 
whole-body autoradiography and measurement of radiolabeled drugs in isolated 
tissues, it has been unequivocally shown that THC penetrates the placental 
barrier and accumulates in the fetus and the cotyledons (153) . The actual 
levels in the fetus are low, as they are also in the maternal brain and muscle, 
in comparison to the high levels in maternal fat, liver, spleen, lungs, adrenal 
and mammary glands, placenta and corpus luteum. At high doses, the fetal 
levels become high enough, however, to cause embryonic and fetal deaths (75). 
No differences were found between the distribution of delta-8- and delta-9- 
THC (170) . The levels of THC in the brain following IV injection never attain 
a maximum, whereas the 11 -hydroxy metabolites show a maximum at about 15 min- 
utes (67, 170). Their half-lives in the brain, from a single dose, are 36 to 
40 hours, respectively. The blood levels of THC and metabolites show a bi- 
phasic pattern of decline, with a second phase half-life of about 20 to 25 
hours (170). 

In the rat, repeated subcutaneous injections of delta-9-THC showed accumula- 
tions of THC and 11-hydroxy and 8, 11-dihydroxy metabolites in (in decreasing 
order of levels): fat, liver, lung and brain (105). After a single injection 
the concentrations in body fats were ten times higher than any other tissue 
and persisted up to two weeks. 

C. Metabolism . There are now at least twenty-two known metabolites of mari- 
huana constituents. Of these there are eight each for delta-8-and delta-9-THC 
and three each for CBD and CBN. Many of these metabolites have been isolated 
or identified from human or animal administration, but a number have only been 
found to date from in vitro microsomal preparations. There is some variation 
in the pattern of metabolism in various species and this is an important factor 
to be considered when comparing the biological effects of the cannabinoids in 
different species For example, from male dog liver, delta-8-THC was found 

to give rise to side-chain hydroxylated metabolites (132). In the rabbit, 
delta-9-THC was found to give in the urine 11-carboxylic acid metabolites with 
side-chain hydroxylation (5) In rats, from urine and feces, some glucuronide 
of delta-9-THC was found along with CBN, and 8,ll-hydroxy-delta-9-THC was 
found in the urine as well (140) . An unidentified diacetate metabolite was 
found in the bile. These studies, as are others, were conducted using a gas 
chromatography-mass spectrometry technique that can detect minute amounts of 
metabolites present in biological media but does not always permit their iso- 
lation and complete characterization. 

In a recent study of the metabolism and excretion of delta-9-THC in the rat, 
experiments in which the bile duct was cannulated showed that as much as 60 
percent of the IV dose was excreted via the bile, less than 10 percent in 
the urine and only 3 percent in feces (38) Oral administration gave over 
40 percent of the excreted drug and very little metabolite in the feces, 
strongly indicating that at least one-third of the oral dose was not absorbed. 
This further confirms the role of enterohepatic circulation, as demonstrated 
earlier (101). 



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Of particular concern is the selection of a suitable animal species to serve 
as a model for man. From a metabolic standpoint, it would appear to date 
that this is best satisfied with the rhesus monkey. A comparison was made 
between the rhesus and squirrel monkey, but the latter was found to exhibit 
quite a different pattern of metabolism and excretion than the rhesus, which 
was quite similar to man (195) . A study on the brain levels of THC and metabo- 
lites in the brains of squirrel monkeys has been reported, however (83). At 
thirty minutes after IV administration, about 4 percent of the dose was located 
in the brain, of which 84 percent was THC and 8 percent the 11 -hydroxy metabo- 
lite. These levels went to 70 and 15 percent, respectively, at four hours. 

Many of the findings about marihuana metabolism in animals are slowly being 
confirmed by studies in humans. This is important since studies in man are 
considerably more difficult and expensive to carry out. 

Further support has been reported for the earlier hypothesis that the 11- 
hydroxy metabolite is the active form of the THC's (67, 111, Ilia). A study 
of the blood levels following administration of delta-9-THC to twelve long- 
term marihuana smokers by IV, oral and inhalation routes showed that over 90 
percent of the oral dose was absorbed and its metabolites gave a peak blood 
level at three hours (Ilia) . The peak of metabolites by inhalation was over 
a range of 10 to 140 minutes, with an average of 70 minutes, demonstrating 
the extent of individual variation. These levels of metabolites correlated 
quite closely to the psychologic effects. In a study of the principal metabo- 
lite itself, ll-hydroxy-delta-9-THC gave psychological and pharmacological 
effects that were similar to THC, and lasted for several hours (111) . The 
disposition and metabolism of the metabolite mimicked that of delta-9-THC as 
well. These studies were carried out with only three normal male volunteers 
and may require further confirmation before the question of the active species 
of drug is completely resolved. From a repeated dose study in man, it was 
reported that there was no significant accumulation of THC or metabolites ap- 
pearing in the urine (87) . 

A study of the ability of the human intestine to metabolize delta-9-THC shows 
that this is another important site, in addition to liver and lungs, for 
metabolism (73). Because of its secretion in bile and with portal reabsorp- 
tion, this site of metabolism must be considered significant regardless of the 
route of administration. 

It seems from the metabolism studies to date that delta-8- and delta-9-THC 
and their 11 -hydroxy metabolites are all active to varying degrees and account 
collectively for the overall effects observed after smoking or on administra- 
tion of delta-9-THC. 



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TOXICITY 



Comprehensive reviews of the toxicology of marihuana have been published 
recently (3, 52, 53, 147, 148, 148a). 



Acute Toxicity 

In rodents, it has again been confirmed that the therapeutic ratio of lethal 
dose to pharmacologically effective dose of delta-8- or delta-9-THC is very 
large (35). That study also showed that the choice of compounds used to sus- 
pend these insoluble substances is important as definite differences in pharma- 
cological and even lethal effects were found when various suspending agents 
were used. A systematic study of the various solvents or suspending agents 
which can be used to administer cannabinoids by various routes, especially in 
the higher concentrations necessary for toxicity studies, has been published 
this year (169). 

Two interesting Russian articles reported in detail the functional and mor- 
phological changes noted in experimental acute poisoning of fourteen healthy 
adult and young dogs given high lethal doses (1.5 - 4.0 grams/kg of body 
weight) of resin prepared from Yujnochuisk Cannabis (44). Stimulation alone 
or alternating with depression happened within thirty minutes and vocaliza- 
tion was followed by depression within two hours after administration. Im- 
paired motor coordination, tremors, muscular rigidity, catalepsy and hyper- 
kinesia were noted. Reportedly, acute Cannabis resin poisoning, whatever the 
dosage, affected the central nervous system and led to severe impairment of 
the animals' behavior and to the development of neurological symptoms. These 
symptoms were most intense in the early days, after which their severity de- 
creased. Morphological changes in the brain were distinguished by disorders 
of the vascular circulation, which were a main constituent of the histo- 
pathological process. Degenerative changes such as hydropic degeneration 
and caryocytolysis, which could lead to the death of the cells, were seen in 
the cerebral cortex, medulla oblongata and cerebellum. The overall evalua- 
tion of histological experiments on acute Cannabis resin poisoning is that 
the pathological process is of the nature of toxic encephalopathy. Analysis 
of EKGs showed considerable and varied cardiovascular disturbance. Electro- 
cardiographic and haemodynamic shifts which were observed during the first 
one to two hours - tachycardia, bradycardia, pronounced sinus arrhythmia, 
symptoms of coronary insufficiencies and reduced arterial pressure - were re- 
portedly the results of damage to the vegetative centers and not to a direct 
toxic effect on the myocardium. Pathological changes were observed in the 
liver, kidneys and adrenal glands. 

Clinical chemistry showed a decrease in red blood cells and an increase in 
leucocytes. Blood sugar, cholinesterase activity, and blood plasma protein 
levels rose and fell at different times. 

Although the authors mention that these effects are similar to those of Indian 
Cannabis and their results in basic agreement with the findings of Chopra (18) 

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and Loewe (118), it is difficult to compare these findings with those of our 
American marihuana, as no analytical determination of the potency of the resin 
was made. Furthermore, the vehicle in which the resin was given is not men- 
tioned and there do not seem to be any controls included in the experimental 
design 

Another paper reported the first stage of a study on mice of the effects of 
chronic exposure to the smoke of marihuana or its resin-free residue (34). 
There were no significant differences in death rates of mice exposed to smoke 
from marihuana or residue and the LD50 was around two grams. Deaths were 
attributed to carbon monoxide poisoning. 

Since delta-9-THC, like amphetamine, possesses some stimulating properties, 
the influence of conditions of housing on the toxicity of delta-9-THC was 
studied under different conditions. It was found that the lethal activity of 
a single intraperitoneal injection of delta-9-THC was significantly enhanced 
in isolated mice. Conversely, the toxicity of d-amphetamine was greater in 
aggregated mice while the mortality rate of chlorpromazine and phenobarbital 
was unaffected by housing conditions (179) . 



Chronic Toxicity 

In view of the behavioral reversal from sedation to hyperactivity and ag- 
gressiveness found in our previous toxicity studies after chronic administra- 
tion of even the lowest dose of delta-9-THC, i.e., 50 mg/kg, the National 
Institute of Mental Health decided to start a new and longer (six-month) 
chronic toxicity study of delta-9-THC in rats, orally, at lower dosage levels 
of 2, 10 or 50 mg/kg (28). After one month of chronic administration, the 
results were as follows: 

Approximately 60 percent of animals on 10 mg/kg and 100 percent on 50 mg/kg 
displayed CNS depression in the first week of treatment. A dose-related 
decrease in respiration rate occurred. With the onset of tolerance in the 
second week, hyperactivity and passivity became prevalent and CNS depression 
was reduced. Irritability and fighting occurred at higher doses in the third 
week and the intensity of aggression was associated with the emergence of a 
dominant animal in each cage. Territorial aggression was manifested pre*- 
dominantly in male rats and was more apparent at 10 mg/kg than 50 mg/kg, 
probably due to the continuing tranquilizing effect of the higher dose. A 
poikilothermic effect was observed in response to higher ambient room tempera- 
tures. Anorexia and diminished water consumption in conjunction with a 
decline in growth rate occurred in the second and third weeks but were re- 
versed in the fourth week at the highest dose. At necropsy, no drug related 
gross pathology was observed. Histopathology, hemotology and urinanalysis 
parameters were essentially normal. At high doses of delta-9-THC, adrenal 
weights were elevated in both sexes and the pancreas in the male. Apparent 
decreases in prostate and uterine weights were discerned with the possibility 
of a similar change in female pituitary weights as well. Neurochemical 
changes were somewhat variable and did not reveal any serious biochemical 
lesions in brain. It has been demonstrated for the first time that oral doses 

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of delta-9-THC (10 rag/kg) equivalent to those present in hashish evoke pro- 
found effects on the CNS manifested by fighting, starting within fourteen 
days after chronic administration. 

After chronic LV.treatment of monkeys with high doses of THC, O2 uptake was 
measured in slices of cerebral cortex, midbrain, medulla, cerebellum and lungs 
in the absence and presence of succinate by conventional Warburg manometry. 
Endogenous respiration increased 16-30 percent in the brain cortex at doses 
above 4 mg/kg but not at higher doses. No change occurred in medulla. An 
apparent decline in endogenous lung respiration was not significant. Exoge- 
nous succinate consistently stimulated oxygen uptake, more so for tissues with 
low endogenous respiration, indicating no impairment of oxidative capacity 
This alteration in oxygen was only related to chronic intoxication with high 
doses of THC. This study also confirmed an earlier report that chronic 
parenteral administration of delta-9-THC, either by the intravenous or the 
subcutaneous route, produce edema, ulceration and fibrosis at the injection 
site, due to the caustic properties of cannabinoids (3, 184). 

Very recently, toxic effects of marihuana tar in the mouse have been found. 
Confiscated marihuana was rolled into cigarettes and artificially puffed in 
a smoking machine. The smoke was collected and condensed, producing tar 
which was used for painting mice skin. A positive control group receiving 
benzo-( a )pyrene, a known carcinogen, was included in the experimental design. 
Marihuana tar, like benzo-( a )pyrene or cigarette smoke condensate in equal 
concentrations showed complete metaplasia of all sebaceous glands in mouse 
skin. The authors conclude that "since metaplasia of all sebaceous glands in 
the target area correlates well with carcinogenicity, it may be an indication 
that Cannabis tar will prove to be carcinogenic" (29) . These findings confirm 
an earlier report by Magus (121) and indicate that smoking crude marihuana 
produces tar which, like that of tobacco and other plant materials, can be 
demonstrated to be carcinogenic by this type of technique. On the other hand, 
a comparative evaluation of the carcinogenic potential of the major cannabi- 
noids of marihuana in another test system (transformation of cultures of rat 
embryo cells by combined action of murine leukemia virus and cannabinoids) 
showed that these compounds have a weak oncogenic activity compared to that of 
methycholanthrene (164). 

In view of these conflicting reports, a long-term study of the potential 
oncogenic effects of cannabinoids seems in order. 

Effects on Pregnancy, on the Fetus and the Newborn 

One of the important questions regarding marihuana use in the population, which 
was clarified in the past year, concerns the effects of repeated dosage of 
cannabinoids during pregnancy and after birth in the mother, the fetus and the 
newborn. 

As mentioned previously (125, 126), experiments in animals had produced con- 
flicting results, with some authors reporting reduced fertility (142), stunting, 
fetal resorptions or malformations after administration of marihuana extracts 

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by various routes (64, 65, 75, 155, 156). Others (153), however, using 
delta-9-THC or extracts at dose levels ranging from 0.01 to 200 mg/kg for 
delta-9-THC, 20-40 mg/kg for delta-8-THC and 200-300 mg/kg of a marihuana 
extract containing 17.1 percent delta-9-THC, in a large number of experiments 
failed to find any abnormalities in offspring. In these studies, cannabinoids 
were injected at different times of gestation, using various solvents (olive 
oil suspensions, rat or rabbit serum or plasma plus propylene glycol) and two 
different species (rats and hamsters) in attempts to duplicate the experimental 
conditions used in the previously reported studies. The only adverse effect 
was that at high dose levels of 100 mg/kg and above, postnatal mortality was 
high in all groups as compared to controls. A cross -fostering experiment 
demonstrated that agalactia, i.e., lack of milk production in the mother, was 
primarily responsible for the death of pups, since placing some treated off- 
spring with a control lactating female lowered the mortality rate, while the 
mortality rate of the control offspring placed with the delta-9-THC treated 
females was increased. Some of the offspring that survived were bred and the 
data indicate that there was no fertility impairment in the F-^ and F2 genera- 
tions and no development of abnormalities in the offsprings. Unfortunately, 
the subcutaneous route of administration was used in this study. It has since 
been shown to be a rather poor route of administration for repeated adminis- 
tration of cannabinoids since repeated injections produced erythema, edema 
and granulomas at the injection site due to the caustic properties of the 
cannabinoids (3) . There is also some doubt regarding complete absorption of 
cannabinoids by this route, although the authors had previously shown that 
delta-9-THC affected the rats' spontaneous activity and depressed bar pressing 
within 10 minutes after s.c. administration at the same dose levels (144). 

In view of these conflicting reports a year ago, the National Institute of 
Mental Health initiated a comprehensive study of the effects of delta-9-THC 
and a crude marihuana extract in two species to determine their teratogenic 
potential as well as the effects of these compounds on reproductive functions 
and on the newborn. These studies were made in rats and rabbits, at dose 
levels which do not markedly affect the body weight gain of normal animals. 
This is important and was not carefully controlled in other studies which 
have instead used doses as high as 1/2 of the LD50. In such cases, effects 
on reproduction and fetal development become confused with general toxicity. 
The NIMH studies were conducted according to the Food and Drug Administration 
Guidelines and divided into three phases: prenatal (Phase I), potential for 
teratogenicity (Phase II) and postnatal effects (Phase III). Phases I and 
III were conducted in rats only, Phase II in rats and rabbits. Rats were 
dosed with 0.5 mg. , 1.5 mg. and 5.0 mg. of delta-9-THC/kg. of body weight 
given either as the pure compound or as an extract containing 16 percent of 
delta-9-THC. Dosing was initiated sixty days prior to mating for males and 
fourteen days prior to mating for females in the Phase I studies, and on day 
15 of gestation in the Phase III studies. Drug administration to the parent 
animals was continued until sacrifice. The results were as follows: 

A slight depression in body weight gain was observed among rats given 5 mg/kg. 
Behavioral reactions observed among rats from all treatment groups included 
inactivity, irritability, pallor and pupillary constriction. The severity 
and direction, but not the incidence, of these reactions were dose related. 

-102- 



An apparent tolerance was manifested by a decrease in the severity and dura- 
tion but not complete absence of these reactions. There were no treatment 
related mortalities. Mating and fertility indices were similar for the con- 
trol and all treatment groups. At the interim sacrifice, on the fourteenth 
day of pregnancy, the numbers of corpora lutea, implantation sites, and live 
fetuses were similar for all groups. The average numbers of pups delivered 
and viable at birth did not differ among treatment and control groups. There 
were no statistically significant differences in the number of live pups on 
lactation days 1, 4, 12 or 21. 

To determine the teratogenic potential of delta-9-THC and of marihuana 
extract, pregnant rabbits were dosed orally from days 6 through 18 of gesta- 
tion with 0.5, 1.5, 5.0 or 15 mg. delta-9-THC/kg body weight from either 
source. Pregnant rats were dosed orally from days 6 through 15 of gestation 
with 5, 15 or 50 mg/kg delta-9-THC/kg body weight. A positive control group 
treated with 37.5 mg/kg of Thalidomide was included in the experimental design. 
Sedation and depression of body weight gains was seen in females at the high 
dose level. The number of live rabbit fetuses per 100 implantation sites was 
similar in control and treated groups. Similar findings were observed in pups 
from treated and control dams. Examinations of external, internal and skele- 
tal development disclosed no effects which could be related to prenatal ex- 
posure of fetuses to the cannabinoids (74, 94) . 

Although doses used in this experiment are much smaller than those used in 
previous experiments, they are behaviorally active doses as shown by the ob- 
served behavioral changes listed above. When compared to the average oral 
active dose in man of 500 microgram/kg, the 5-50 mg/kg doses represent 10-100 
times the effective human dose. 

At high dose level of 200 mg/kg i.p., which is almost 1/2 of the LD50 by this 
route (158), delta-9-THC was shown to significantly increase resorptions in 
mice especially if administered during early organogenesis, on days 8 and 9 
of gestation, The developing organism appears to be less sensitive to toxic 
effects of delta-9-THC during late organogenesis or the period of fetal 
maturation (75). In the same study, delta-9-THC also significantly reduced 
the body weight of the surviving fetuses and this effect was most pronounced 
when delta-9-THC was administered between days 10 and 13. 

In conclusion, the NIMH studies confirm the report of Pace (153) that, at 
doses 10-100 times the effective human doses, synthetic or natural marihuana 
does not appear to have serious deleterious effects during pregnancy, on the 
fetus, the mother, or, after birth, on the newborn. 



BEHAVIORAL EFFECTS 



This part of the preclinical section will summarize some of the effects of 
cannabinoids on the behavior of animals reported for the most part in the 
last two years. The use of animal subjects to study drug-behavior interac- 
tions has many advantages. The investigator can know precisely the genetic 

-103- 



and behavioral history of the animals as well as systematically control their 
behavior. Before going into the experimental results, however, it might be 
well to point out some important background aspects. 

Methodological Considerations 

Interpretation of data obtained from behavioral studies of cannabinoids must 
take into consideration the type of behavior measured (learned or spontaneous) 
the behavioral tests used, as well as the type of subjects (species and strain) 
and route of administration. In common with other drugs, it has been shown that 
the behavioral effects of cannabinoids may be significantly altered by varia- 
tions in the route of administration and testing situation (123). 

During the past year, investigators studying cannabinoid -behavior relation- 
ships used paradigms to test both learned and unlearned performance. In con- 
trast to the earlier literature, investigators now use learned tasks more 
frequently than unlearned tasks to evaluate the effects of marihuana on be- 
havior. This is probably because of the tighter degree of specificity and 
control available in learned paradigms. General motor performance and open- 
field activity have been used to characterize unlearned behavior of mice and 
rats while maze performance has been used extensively to measure simple learned 
behavior. A number of other operant conditioning techniques have been employed 
to measure more complex behaviors. Such methods have included the use of simple 
and multiple schedules of reinforcement baselines, active and passive avoidance 
paradigms, conditioned emotional response (CER) tests and timing tasks. 

The species used to study behavioral effects of cannabinoids have varied from 
fish, birds, mice and rats to squirrel and rhesus monkeys, chimpanzees and 
great apes. By far the greatest number of experiments reported in the litera- 
ture employed rodents as subjects. This choice is based largely upon the 
economy of rodent laboratories, the efficiency with which mice and rats can be 
used in group experimental designs, and the wealth of baseline data already 
available detailing the behavior of rodents in comparable test situations. 

During the past year, there has been an upsurge in the use of primates as 
experimental subjects. Squirrel monkeys, rhesus, macaques, and great apes 
have been employed to study the effects of cannabinoids. The use of chimpan- 
zees is of particular interest since some of the preclinical data collected on 
them is quite similar to that reported in clinical studies of human volunteers. 
The use of primates, while involving greater expenditures can certainly be 
justified in terms of the data generated, as they provide the opportunity to 
study the effects of drugs in more complex test situations. In addition, the 
analysis is usually focused upon the behavior of single individuals, an alter- 
native approach to group designs. 

In general, the route of administration varied with the species. In birds 
(pigeons), administration of cannabinoids was usually by the parenteral (intra- 
muscular) route. In rats, the intraperitoneal (i.p.) route was used in about 
90 percent of the studies and the oral route in the remaining ones. Contrary 
to metabolic studies, for instance, the intravenous (IV) route of administration 

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was used in only one experiment. Mice were given cannabinoids either i.p. or 
IV. In primates, the oral (gavage, baited fruit, or smoking) or IV routes 
were used equally. 

This review will describe experimental results derived from a variety of tech- 
niques in the following areas: (a) gross behavioral observations, (b) aggres- 
sion and social competition, (c) avoidance and aversive control, (d) schedules 
of reinforcement and (e) timing behavior. 



Gross Behavioral Observations 

Studies in the area of gross behavioral observation can be divided methodologi- 
cally into two categories, nonsystematic and systematic, Nonsystematic studies, 
as the name implies, place no restriction on the type or quantification of 
behavior recorded. Therefore, these studies yield descriptive, unquantitative 
impressions of an animal's gross behavior under the influence of a drug. In 
contrast, systematic studies rely upon preplanned scales or measures to record 
selected aspects of an animal's behavior. Certain patterns or types of be- 
havior are preselected to observe, measure and quantify a drug effect. 
Despite their underlying methodological difference, both systematic and non- 
systematic studies measure unlearned behavior. Of necessity, a full evaluation 
of the effects of cannabinoids on behavior includes both types of studies. The 
nonsystematic studies have been often reported and are summarized in the sec- 
tion on pharmacological profile of the cannabinoids. The systematic studies 
will be considered in more detail. 

Systematic studies with cannabinoids have used a number of different parameters 
to quantitate drug effects. Habituation experiences, vocalization, motor tasks, 
and open-field behavior have been measured. 

Brown (4) reported that mice which received IV doses of delta-8-THC immediately 
prior to an habituation experience (pre-exposure to a cage where latency to 
drink would later be measured) did not appear to be significantly different 
from non-habituated vehicle-treated mice. The results suggest that delta-8- 
THC inhibited the habituation and may be similar in action to anti-cholinergic 
drugs (scopalamine, atropine, and ditran) . These results indicate that the 
effects of delta-8-THC may be mediated via an anti-cholinergic mechanism. 

Henriksson and Jarbe (79) observed vocalizations of rats when squeezed behind 
the forelimbs after administration of delta-8- or delta-9-THC via i.p. or oral 
routes using different vehicles or after inhalation of marihuana smoke. They 
concluded that vocalization might be a useful indicator of cannabis effects at 
relatively low doses of the drug. Cohn et al . (23) used a scaled set of motor 
tasks in addition to vocalization to measure the effect of marihuana extract 
administered orally to rats. The results showed that drugged rats had sig- 
nificantly higher scores than controls (the drugged animals were more sluggish); 
with drugged female rats significantly more affected than drugged males. These 
results indicate the possible role of sex difference in responses to marihuana 
extract (MED) . 



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In addition to these studies, Masur et al . (129) evaluated the effects of 
intra-peritoneally administered cannabis extract and delta-9-THC using an 
open-field technique. Decreases in bolus production, rearing and grooming 
behaviors were found in the treated rats, However, ambulation was not sig- 
nificantly different from controls. The work of Drew et al . (43) confirms the 
findings cited above. These investigators measured the effects of intra- 
peritoneally administered delta-9-THC on behavior or rats in an open-field 
testing situation. Results indicated that drugged tats exhibited reductions 
compared to controls in the 'following behavioral measures: rearing, grooming, 
sniffing, and bolus production. However, these investigators found that ambu- 
lation was reduced, a result which differs from Masur et al . (129). 

Aggression and Social Competition 

Studies in this area are unique in that the focus of analysis shifts to the 
interaction between animals. Paradigms used to study aggression can be divided 
into four categories as follows: predatory, shock induced, starvation induced, 
isolation induced. With few exceptions, studies of the relationship between 
cannabis and aggression employ rodents (mice and rats) as the subjects of choice. 
Two recent studies of aggressive behavior cannot be conveniently included in 
one of the categories listed above. An experiment by Gonzalez et al . (69) 
studied the effects of marihuana extract on the aggressive behavior and ritual 
displays of Siamese fighting fish ( Beta splendens ). The investigators found 
that delta-9-THC or cannabis extract decreased the number of fighting episodes 
between paired males. This reduction in aggressive behavior and the general 
profile was similar to that reported when the fish were tested under the in- 
fluence of hypnotic drugs. Display and aggressive behavior of the drugged fish 
became similar to control subjects after nine consecutive days of treatment 
with cannabis. 

Kilbey et al . (99) evaluated the effects of attack behavior of mice on passive 
mice in a T maze testing situation after the experimental animals had received 
intravenous injections of delta-9-THC. The results of the experiment indicated 
that the drug reduced aggression and agree with the data of Santos et al . (172) 
who reported that an extract of marihuana reduced isolation induced aggression. 

A. Predatory Aggression 

The typical behavioral situation observed in this form of aggression is 
the attack and killing behavior of rodents (rats) when they are presented with 
a frog or a turtle in their home cage. Kilbey et al . (97) measured the effects 
of intravenously administered delta-9-THC on frog killing behavior by rats and 
found a dose related increase in the latency to attack and kill frogs immediately 
after receiving the drug. In a second study, Kilbey et al . (98) investigated 
the time course of the drug effect and found that the latencies to kill were 
longest when measurements were taken 0, 15, and 30 minutes post injection. The 
peak of the drug effect.3 was found to occur between 0-15 minutes after drug 
administration. Another study by McDonough et al . (135) investigated the 
effects of delta-9-THC i.p. (6.4 mg/kg) on the turtle killing behavior of rats. 
The results of this experiment indicated that the percentages of attacks at 1 
and 2 hours post injection were significantly less on drug days. At 4 and 8 
hours after drug administration, attack behavior could not be distinguished 

-106- 



from placebo administration. These data are in general agreement with the 
findings of Kilbey et al . (97) and Kilbey et al . (98), cited above. 

B. Shock Induced Aggression 

In this paradigm as the name implies, the fighting behavior in pairs of 
rats is induced via electric shocks that both animals receive while they are 
in the observation arena. Two sets of studies employed this paradigm to in- 
vestigate the relationship between aggression and cannabis. Carder and Olsen 
(8) found significant increases in shock induced fighting if either or both 
of a pair of rats was administered marihuana extract (MED) intraperitoneally. 
The increase was found to be dose dependent and occurred at doses of 0.12, 
0.25, 0.50 mg/kg; at doses of 1.0 and 2.0 mg/kg fighting behavior was shown 
to decrease when compared to control animals On the next two days of test- 
ing, fighting was not observed to increase at any dose of marihuana. In a 
subsequent control study these investigators found that familiarization with 
either the drug or the testing situation was sufficient to prevent the drug 
from increasing fighting behavior. Manning and Elsmore (124) found that rats 
given dose levels of delta-9-THC i.p. ranging between 0.64-6.4 mg/kg showed 

no increase in fighting behavior over control animals. The conflicting re- 
sults between the two studies may be attributed to the fact that in Manning 
and Elsmore' s study the rats received extensive pre-training in the apparatus 
before being given the drug. This is just the type of condition which Carder 
and Olsen' s study indicated would preclude drug effects from being observed 

C Starvation Induced Aggression 

In this paradigm rats are administered intraperitoneal injections of 
cannabis extract while they are maintained on a food deprivation schedule. 
The behavior measured is fighting between pairs of rats receiving this treat- 
ment regime. Two early papers by Carlini and Masur (10, 11) described the 
basic experimental situation. Carlini et al . (12) investigated some of the 
factors that may contribute to starvation -marihuana induced aggression. The 
results of the study suggested that the stress of hunger is the factor which 
facilitates the development of aggressive behavior by chronic administration 
of marihuana. A recent report, however, has described aggressiveness in 
normally fed rats after receiving cannabinoids for 4 or 5 weeks (3) . 

Neto and Carlini (149) found that when p-chlorophenylalanine (PCPA) and 
dihydrophenlalanine (DOPA) were administered separately to food deprived 
pairs of rats which received marihuana extract, each drug potentiated the 
fighting behavior. When the drugs were given in combination the potentiation 
was greater than either of the drugs given alone. The drugs had no effect if 
the rats were not treated with marihuana or if they were fed ad libitum . 
Carlini and Gonzalez (13) found that THC given during morphine withdrawal 
induced aggressiveness in rats so treated but this effect was observed only 
after 60 days of treatment with morphine. While d -amphetamine was also shown 
to induce aggression, THC was found to be more efficient in that it induced 
aggressiveness sooner. 



-107- 



D. Social Competition 

A study by Masur et al . (128) found that rats treated with delta-9-THC in 
a situation where they competed for food won more encounters than those not 
so treated; when "loser" rats were subsequently treated with the drug in the 
same testing situation (straight alley) they prevailed over the former "win- 
ners." When the testing apparatus was changed from a straight runway to a T 
maze, those rats given THC were mostly "losers" in the competitive encounters. 
In a second study Masur et al . (130) showed that rats empirically rated as 
"losers" became "winners" when treated with 10 mg/kg of cannabis extract prior 
to a contest in a straight alley food competition test. Masur et al . (131) 
also showed that when pairs of rats were tested in operant bar pressing situa- 
tions (VI and CRF schedules were used) that marihuana extract could induce a 
shift in the social hierarchy and this change is partially dependent upon 
environmental contingencies. These data support the results of Masur et al. 
(130, 131) cited above. 



Avoidance and Aversion Control 

A number of recent studies which employed avoidance paradigms and aversive 
control were used to study cannabinoid effects. 

A. Conditioned Food Aversion 

A study by Elsmore and Fletcher (46) investigated the effects of delta-9- 
THC using a conditioned food aversion paradigm. Rats were administered doses 
of delta-9-THC either orally or intraperitoneally immediately after drinking 
a saccharine solution. A subsequent 2-bottle preference test between water 
and saccharine indicated an inverse relationship between drug dose and sac- 
charine preference. These data suggest that delta-9-THC in doses of 2 mg/kg 
or above is an aversive substance for rats and that investigators should take 
into account this fact when interpreting any behavioral effects of the drug. 
A second study by Elsmore (47) using the conditioned aversion paradigm indi- 
cated that little if any of the effect observed is due to the unfamiliarity 
of the unconditioned stimulus. 

B. Acquisition, Retention and Extinction of Avoidance 

A study of acquisition and retention of a conditioned emotional response 
(CER) by Gonzalez et al . (70) indicated that acute administration i.p. of 
10 mg/kg of Cannabis extract partially blocked the acquisition of the response, 
When measured in a retention test, the CER was significantly attenuated by 
Cannabis extract (10 mg/kg) given either acutely or chronically. These data 
suggest that cannabis acts on the process underlying acquisition and reten- 
tion of a CER and thus mimics the action of some CNS depressants (reserpine 
and chlordiazapoxide) which are able to block CER acquisition 

Henriksson and Jarbe (80) studied acquisition of an avoidance response by 
rats in a shuttle box and found that rats administered delta-9-THC i.p. 
showed a significantly reduced acquisition of the avoidance response. In 

-108- 



addition results from this study indicated symmetrically state dependent 
learning under the influence of synthetic cannabinoids. In a series of studies 
using several avoidance paradigms Robichaud et al . (168) found that delta-9- 
THC given i.p. to mice reduced avoidance responding in some test situations 
but not others. In addition he found that delta-9-THC did not appear to 
generally inhibit acquisition of a CER. A study by Kubena and Barry (106) 
found that fats were able to use drugged (delta-1-THC) and undrugged states as 
discriminative stimuli for approach and avoidance behavior. A study by Jaffe 
and Baum (90) found that rats which received hashish and were tested in an 
avoidance task made significantly more extinction and spontaneous recovery 
responses than controls. Such data indicate that Cannabis may interfere with 
the inhibition process in extinction. 

C. Avoidance and Tolerance Effects 

Harris et al . (77a) studied the effects of IV doses of delta-9-THC on dis- 
criminated avoidance performance of rhesus monkeys and found that the monkeys 
exhibited an increase in shocks received but a rapid tolerance to the drug 
developed by the third and fourth session respectively for the two monkeys 
tested. Krasnegor and Elsmore (103) studied Sidman avoidance in rhesus 
monkeys and found a positive relationship between dose of delta-9-THC and 
total shocks on day 1 and an inverse relationship between drug dose and 
response rate on day 1. By day seven at each dose studied both monkeys showed 
a return to control levels on both dependent variables indicating the possible 
development of tolerance to the effects of the drug. 



Schedules of Reinforcement 

The schedules of reinforcement used to study the effects of cannabis included: 
fixed ratio (FR) ; fixed interval (FI); variable interval (VI); and time out 
(TO). These schedules were studied separately and as components of multiple 
schedules. Rats, pigeons, monkeys, and chimpanzees were used as experimental 
subjects. The literature supports the generalization that FR responding is 
markedly reduced by Cannabis. Studies by Henriksson and Jarbe (79), Pradhan, 
Bailey, and Ghosh (163), Peterson et al . (157) and Frankenheim et al . (55) 
all reported reduced responding in their subjects in experiments where the 
responding of the animals was controlled by fixed ratio schedules of rein- 
forcement. Similar results were reported by Frankenheim et al . (55) and 
Krasnegor (104) who studies the effects of Cannabis on fixed ratio responding 
in pigeons. In primates, Harris et al . (77a) reported that the monkeys in 
his study showed a marked reduction in FR responding after intravenous admin- 
istrations of delta-9-THC. In chimpanzees however Ferraro et al . (48) re- 
ported that cannabis had a variable effect on fixed ratio responding. In 
addition both Ferraro and Billings (49) and Pradhan et al . (163) reported that 
post -reinforcement time was affected by the drug. 

Responding on fixed interval reinforcement schedules was also found to be sub- 
stantially reduced under the influence of Cannabis. In studies using both 
rats and pigeons, Manning and Elsmore (124), and Frankenheim et al . (55) 
showed that cannabis reduced responding controlled by fixed interval schedules 
of reinforcement . 

-109- 



D. 

A study by Masur et al . (128) found that rats treated with delta-9-THC in 
a situation where they competed for food won more encounters than those not 
so treated; when "loser" rats were subsequently treated with the drug in the 
same testing situation (straight alley) they prevailed over the former "win- 
ners." When the testing apparatus was changed from a straight runway to a T 
maze, those rats given THC were mostly "losers" in the competitive encounters. 
In a second study Masur et al . (130) showed that rats empirically rated as 
"losers" became "winners" when treated with 10 mg/kg of cannabis extract prior 
to a contest in a straight alley food competition test. Masur et al . (131) 
also showed that when pairs of rats were tested in operant bar pressing situa- 
tions (VI and CRF schedules were used) that marihuana extract could induce a 
shift in the social hierarchy and this change is partially dependent upon 
environmental contingencies. These data support the results of Masur et al . 
(130, 131) cited above. 



Avoidance and Aversion Control 

A number of recent studies which employed avoidance paradigms and aversive 
control were used to study cannabinoid effects. 

A. Conditioned Food Aversion 

A study by Elsmore and Fletcher (46) investigated the effects of delta-9- 
THC using a conditioned food aversion paradigm. Rats were administered doses 
of delta-9-THC either orally or intraperitoneally immediately after drinking 
a saccharine solution. A subsequent 2-bottle preference test between water 
and saccharine indicated an inverse relationship between drug dose and sac- 
charine preference. These data suggest that delta-9-THC in doses of 2 mg/kg 
or above is an aversive substance for rats and that investigators should take 
into account this fact when interpreting any behavioral effects of the drug. 
A second study by Elsmore (47) using the conditioned aversion paradigm indi- 
cated that little if any of the effect observed is due to the unfamiliarity 
of the unconditioned stimulus. 

B. Acquisition, Retention and Extinction of Avoidance 

A study of acquisition and retention of a conditioned emotional response 
(CER) by Gonzalez et al , (70) indicated that acute administration i.p. of 
10 mg/kg of Cannabis extract partially blocked the acquisition of the response, 
When measured in a retention test, the CER was significantly attenuated by 
Cannabis extract (10 mg/kg) given either acutely or chronically. These data 
suggest that cannabis acts on the process underlying acquisition and reten- 
tion of a CER and thus mimics the action of some CNS depressants (reserpine 
and chlordiazapoxide) which are able to block CER acquisition 

Henriksson and Jarbe (80) studied acquisition of an avoidance response by 
rats in a shuttle box and found that rats administered delta-9-THC i.p. 
showed a significantly reduced acquisition of the avoidance response. In 

-108- 



addition results from this study indicated symmetrically state dependent 
learning under the influence of synthetic cannabinoids. In a series of studies 
using several avoidance paradigms Robichaud et al . (168) found that delta-9- 
THC given i.p. to mice reduced avoidance responding in some test situations 
but not others. In addition he found that delta-9-THC did not appear to 
generally inhibit acquisition of a CER. A study by Kubena and Barry (106) 
found that rats were able to use drugged (delta-1-THC) and undrugged states as 
discriminative stimuli for approach and avoidance behavior. A study by Jaffe 
and Baum (90) found that rats which received hashish and were tested in an 
avoidance task made significantly more extinction and spontaneous recovery 
responses than controls. Such data indicate that Cannabis may interfere with 
the inhibition process in extinction. 

C. Avoidance and Tolerance Effects 

Harris et al . (77a) studied the effects of IV doses of delta-9-THC on dis- 
criminated avoidance performance of rhesus monkeys and found that the monkeys 
exhibited an increase in shocks received but a rapid tolerance to the drug 
developed by the third and fourth session respectively for the two monkeys 
tested. Krasnegor and Elsmore (103) studied Sidman avoidance in rhesus 
monkeys and found a positive relationship between dose of delta-9-THC and 
total shocks on day 1 and an inverse relationship between drug dose and 
response rate on day 1. By day seven at each dose studied both monkeys showed 
a return to control levels on both dependent variables indicating the possible 
development of tolerance to the effects of the drug. 



Schedules of Reinforcement 

The schedules of reinforcement used to study the effects of cannabis included: 
fixed ratio (FR) ; fixed interval (FI) ; variable interval (VI) ; and time out 
(TO). These schedules were studied separately and as components of multiple 
schedules. Rats, pigeons, monkeys, and chimpanzees were used as experimental 
subjects. The literature supports the generalization that FR responding is 
markedly reduced by Cannabis. Studies by Henriksson and Jarbe (79), Pradhan, 
Bailey, and Ghosh (163), Peterson et al . (157) and Frankenheim et al . (55) 
all reported reduced responding in their subjects in experiments where the 
responding of the animals was controlled by fixed ratio schedules of rein- 
forcement. Similar results were reported by Frankenheim et al . (55) and 
Krasnegor (104) who studies the effects of Cannabis on fixed ratio responding 
in pigeons. In primates, Harris et al . (77a) reported that the monkeys in 
his study showed a marked reduction in FR responding after intravenous admin- 
istrations of delta-9-THC. In chimpanzees however Ferraro et al . (48) re- 
ported that cannabis had a variable effect on fixed ratio responding. In 
addition both Ferraro and Billings (49) and Pradhan et al . (163) reported that 
post -reinforcement time was affected by the drug. 

Responding on fixed interval reinforcement schedules was also found to be sub- 
stantially reduced under the influence of Cannabis. In studies using both 
rats and pigeons, Manning and Elsmore (124), and Frankenheim et al . (55) 
showed that cannabis reduced responding controlled by fixed interval schedules 
of reinforcement. 

-109- 



Responding on variable interval (VI) schedules was reported to be reduced at 
high doses of Cannabis (12-18 mg/kg and 25 mg/kg) . Thus both Grisham and 
Ferraro (73a) and Carlini (9) reported complete suppression of variable inter- 
val responding of rats after high doses were administered i.p. At low doses 
of the drug conflicting data were reported. Grisham and Ferraro (73a) indi- 
cated that at doses of 0.25-8.0 mg/kg, variable interval responding was facili- 
tated in rats, while Masur et_al. (131) reported that rats in their experiment 
showed a decrease in VI responding at comparable low dose levels. This dis- 
crepancy may be partially due to the different forms of cannabis used in the 
two studies. 

Responding in the time out phases of multiple schedules was found to be un- 
affected by administration of delta-9-THC Ferraro et_al. (48) and Ferraro 
and Billings (49). 

Timing Behavior 

Timing behavior was studied in both rodents (rats) and great apes (chimpan- 
zees and orangutan) using a schedule of responding known as differential 
reinforcement of low rates of responding (DRL) . In all the animals studied 
the drug produced an increase in the frequency of short interresponse times 
(IRT's). Pradhan et_al. (162) found that delta-9-THC increased overall re- 
sponse rate in rats responding on a DRL schedule for food. At low doses of 
the drug (5 mg/kg and below) an increase in the frequency of shorter IRT's 
was observed. A similar finding was reported by Cole et al . (24) who studied 
the DRL performance of chimpanzees and an orangutan. A slight shift to 
shorter IRT's was reported to occur after the animals smoked cigarettes con- 
taining delta-9-THC. A dose related shift to shorter IRT's was also re- 
ported by Conrad et al . (25) in three chimpanzees after the animals received 
oral doses of delta-9-THC. Effects of the drug were reported at dose levels 
(0.25 mg/kg) that produce deficits in performance of human volunteers after 
they smoked cigarettes containing marihuana. Two additional studies, 
Ferraro et al . (48) and Ferraro and Billings (49) reported a shift in re- 
sponding to shorter IRT's in chimpanzees which responded on a DRL controlled 
schedule of reinforcement. 

Data of the type reported above must be interpreted cautiously. Although one 
may be tempted to speculate that a drug induced increase in shorter IRT's may 
be indicative of over estimation of temporal intervals, one should also be 
cognizant of the fact that the drug in the doses studied has a general facili- 
tatory effect on responding in the DRL situation. Thus, at least in several 
of the studies cited, there was an overall drug induced increase in responding. 
Such an effect would have the net result of increasing the total number of 
short IRT's but would not necessarily be indicative of a timing deficit. 



-110- 



Implications and General Conclusions 

Great care must be exercised in generalizing preclinical behavioral results 
to humans. Using this caution as a guide we shall attempt to relate some of 
the results from the animal studies reviewed to the clinical literature of 
marihuana research. 

In addition to reductions in gross behavioral indices, the literature also 
supports the conclusion that food reinforced scheduled controlled performance 
is depressed under the influence of the drug. Thus across species, routes of 
administration, dose levels, and forms of cannabis, it was found that fixed 
ratio responding was depressed or almost suppressed to a near zero rate. 
Similar results were found for responding controlled by fixed interval sched- 
ules of reinforcement. 

These results may relate to two clinical studies of marihuana smoking and work 
in human volunteers. A study of smoking and operant performance undertaken 
by the Marihuana Commission (Mendelson et al .)(139) indicated that when casual 
and heavy users of the drug were allowed to work to obtain marihuana cigarettes 
no difference was seen in their performance. Subjects earned the maximum 
number of points available throughout the drug period and showed no consistent 
change in their working patterns that could be systematically related to mari- 
huana. In contrast to these results, the preliminary findings of the Le Dain 
Commission study (6) indicated when human volunteers were required to consume 
large doses of marihuana after long periods of abstinence, work performance 
tended to become depressed. When the group required to consume high doses 
of marihuana was compared on its work output to a group which consumed only 
the amounts of the drug that they desired, the forced group showed a dramatic 
reduction in average productivity. Thus the two studies agree that when sub- 
jects are allowed to choose how much of the drug they will consume, no demon- 
strable changes in work performance was noted. However, when the subjects 
were forced to consume large quantities of the drug, decrements were observed. 
This finding is possibly related to the preclinical findings cited above and 
may suggest that when the dose of the drug is not under the control of the 
subject or above the level that would be self -administered on an ad libitum 
basis that marihuana has a suppressive effect on behavior. 

A second finding of interest was the fact that the drug itself under certain 
circumstances may be aversive. Thus two studies support the conclusion that 
delta-9-tetrahydrocannabinol when administered either orally or intraperito- 
neally produced a conditioned food aversion in rodents. Such data should 
serve as a reminder for experimenters that they must take into account the 
possible aversive effects of the drug when making interpretations of behavioral 
results. These preclinical findings are of interest also because preliminary 
data from the Le Dain (6) study indicate that human volunteers found cannabis 
to be aversive when they were forced to consume large doses of it for long 
periods of time. The subjects reported the drug was subjectively unpleasant 
and in the highest dose condition studied, most subjects requested to stop 
using the drug. The drug was so unpleasant for some that they indicated they 
would no longer participate in the study if forced to continue smoking the 
high doses required. 

-Ill- 



The data on timing performance indicate that the drug does have an effect on 
spaced responding. Thus both rodents and primates show a shift in inter- 
response times (IRT) on a schedule termed differential reinforcement of low 
rate of responding (DRL) . As was indicated above, such data, although they 
are suggestive of timing deficits reported in human studies, must be dealt 
with cautiously. However, one study in particular Conrad et al. (25) is sug- 
gestive of a timing change. The study is important for two reasons. First, 
it was able to demonstrate alterations in spaced responding at dose levels of 
delta-9-tetrahydrocannabinol that are well within the range of psychoactivity 
reported for humans. Second, the study suggests that chimpanzees may be the 
animals of choice to study certain effects of marihuana (e.g., timing and 
chronic behavioral effects), and that the results of such studies may be 
generalized to man. 

Since there is a lack of clinical data relating the effects of marihuana to 
human aggression, it would be unwarranted to speculate about this drug- 
behavior relationship. The only clinical reports on this problem are some 
preliminary results from the Le Dain (6) Commission where the investigators 
reported that the: . . "drug did not seem to induce hostility or aggression, 
and no evidence was found of social deterioration. . ." 

In summary, a good deal of the animal behavioral data correlates well with 
clinical investigations of the behavioral effects of marihuana in man and thus 
substantiates the predictive and confirmatory value of preclinical behavioral 
analysis of cannabis. 



-112- 



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181. Spaulding, T.C., Dewey, W.L. and Harris, L.S. The pharmacological 
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Monkey brain and lung respiration after chronic I.V. treatment with 
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185. Tonge, S.R. and Leonard, B.E. The effect of some hallucinogenic drugs 
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Identification in hashish of tetrahydrocannabinol, cannabidiol and 
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1972. 



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EFFECTS IN MAN 



Acute Effects 



The prominent acute pharmacological effects of marihuana, namely, the char- 
acteristic but- individually variable subjective "high" and the invariable 
physiological effects, including an increase in pulse rate and reddening of 
the eyes, have already been clearly established (56, 44, 33). In the past 
year the continuing research concentrated on studying the less obvious but 
potentially important effects of marihuana, of delta-9-THC, and of its 
metabolites utilizing sophisticated psychological and physiological methodology, 

The Question of the Active Ingredient 

Since the major psychological and physiological effects of marihuana can be 
reproduced by the administration of synthetic delta-9-THC, the majority of 
the studies continued to utilize this compound, and relatively slow progress 
has been made in exploring the effects of the other, chemically identified 
ingredients that may play a role either in modifying the effects of delta-9- 
THC or producing some pharmacological effects of their own. 

One of the double-bond isomers of delta-9-THC is delta-8-THC which occurs in 
relatively small quantities in natural marihuana, and on the basis of animal 
experiments it has been suspected to possess pharmacological activity compa- 
rable to that of delta-9-THC (12, 20). 

Orally or intravenously administered delta-8-THC to six human experimental 
subjects has been shown by Hollister (32, 33) to produce marihuana-like psycho- 
logical and physiological effects, but it was somewhat less active than delta-9- 
THC. Its relative potency, both as judged following oral and intravenous 
administration, is 2:3. In view of this lesser potency, the qualitatively 
similar clinical effects to delta-9-THC and the relatively low content of this 
isomer in most cannabis samples, it seems unlikely that varying amounts of 
this material could account for differences in clinical effects sometimes 
reported from various cannabis samples. 

Two other cannabinoids: cannabinol and cannabichromone, isolated from hashish, 
were found to be inactive in man. Doses up to 2,000 mcg/kg or 2,500 mcg/kg, 
respectively, of the two compounds administered orally produced no discern- 
ible subjective or physiologic effects (38). Cannabidiol in relatively 
large smoked doses (25 mg) produced a slight but detectable change in sub- 
jective state and increased pulse rate similar to the effects of low doses 
(2-3 mg) of THC (40). 

There have been claims made in a recent paper that the content of delta-9-THC 
does not explain all biological activity of some Brazilian marihuana samples 
(42). In this report reference was made to an unpublished clinical study of 
a Brazilian sample of marihuana which seemed to be about three times more 
active than would be expected from its delta-9-THC content. Several possible 

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explanations for this discrepancy were offered, the most likely being that a 
major portion of the originally present delta-9-THC was converted to canna- 
binol by the time the chemical analysis was made. 



Dose and Route of Administration 

While it is generally acknowledged that smoking is the most common way to 
consume marihuana in this country, researchers who would like to study dose- 
effect relationships are still troubled by the fact that when marihuana is 
smoked an uncertain and variable fraction of THC is lost through burning, by 
being left in the "butt" or "roach", by escaping in the smoke between puffs 
or by being exhaled following incomplete absorption from the respiratory dead 
space (44, 83). 

Because of these difficulties, many researchers prefer oral or intravenous 
routes of administration so that at least the delivery of a given dose can 
be assured. Although 90-95% of the orally administered delta-9-THC and 100 
percent (by definition) of the intravenously administered drug is absorbed (50), 
both of these routes of administration have problems of their own. The speed 
and degree of absorption of an oral dose of delta-9-THC seems to be greatly 
influenced by the vehicle used for the preparation (64) . Even when the same 
vehicle was used, absorption of the orally administered drug varied signifi- 
cantly among individuals. 

For intravenous administration delta-9-THC is dissolved in absolute ethanol 
and is injected either through the tubing of a rapidly flowing intravenous 
infusion of five percent dextrose in water (48, 50, 32) or, after the alco- 
holic solution is first dispersed in 25 percent human serum albumin and then 
slowly infused intravenously (65) . The first mentioned intravenous technique 
is preferred when the measurement of dynamic characteristics of distribution 
and biological half life of a tracer amount of the drug is the primary goal 
of the investigation (48, 50, 47). The second technique appears to be pre- 
ferred when larger doses of THC are to be given intravenously or when the 
effects of a metabolite of THC with unknown potency are to be studied with 
maximum possible safety (65). 



Metabolism of Delta-9-THC 

Work continued in the past year to identify the metabolites of delta-9-THC 
in the plasma, urine and feces of subjects after oral injections or intra- 
venous administration of the radioactive labeled drug and to study the 
metabolic pattern of delta-9-THC or ll-hydroxy-delta-9-THC. 

At least three monohydroxylated metabolites of delta-9-THC have now been 
positively identified either in human plasma, urine or feces (64, 85). 
Besides the already known ll-hydroxy-delta-9-THC, 8-A- and 8-B-hydroxy- 
delta-9-THC have also been identified although they represent a very small 
portion of the total cannabinoids found in biological specimens at any time 
after administration of the parent compound (64). 8,ll-dihydroxy-delta-9-THC 

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has also been identified in plasma samples by gas and liquid chromatography- 
mass spectrometry (86) and appears in plasma in relatively larger amounts than 
the monohydroxylated metabolites, especially after oral administration of 
delta-9-THC. Several unidentified metabolites, most likely 11-carboxy acids 
of various degrees of hydroxylation in free and conjugated form have been 
found in the urine comprising the majority of the metabolites. These acids 
are also found to some extent in the feces, but are not found in measurable 
quantity in the blood. 

As far as the relative amounts of the metabolites by the two major routes of 
excretion are concerned, there seems to be a consensus that the bulk of the 
metabolites is excreted via the feces, while only about 15 -20 percent of the 
orally, and 20-30 percent of the intravenously administered drug can be found 
in the urine as metabolites after 72 hours of collection (64, 48) . Approxi- 
mately 20-35 percent of the total dose, however, was still in the various 
tissues at the time the investigators ceased taking samples. 

A curious observation about the metabolic fate of delta-9-THC was made by 
Perez-Reyes et al . during their studies of blood levels of delta-9-THC after 
oral administration of the drug (64). At the peak of the psychological "high" 
the plasma levels of delta-9-THC and ll-hydroxy-delta-9-THC were relatively 
low, the levels of the dihydroxy metabolite and other, more polar, unidentified 
metabolites were relatively high. Twelve hours after the injection of delta-9- 
THC, when the subjects no longer experienced any significant drug effects, the 
plasma levels of delta-9-THC, surprisingly, increased more than twofold, while 
the plasma levels of the other metabolites decreased substantially. High 
levels of delta-9-THC in the plasma without corresponding pharmacological 
effects suggest that the circulating delta-9-THC is not active, possibly due 
to strong binding to plasma lipoproteins. The sudden increase several hours 
after injection is explained by the possibility of mobilization of delta-9-THC 
from the gall bladder, as bile is secreted following food ingestion and the 
drug is reabsorbed from the intestines. This view is supported by animal 
experimental data demonstrating the existence of entero-hepatic circulation 
for delta-9-THC and its metabolites (13). 

The question, whether or not a metabolite is responsible for the psychological 
activity of delta-9-THC, has been explored in the past year by two groups of 
investigators (65, 49). Lemberger et al . administered labeled 11-hydroxy- 
delta-9-THC (1 mg) to three volunteers intravenously using the dextrose in- 
fusion technique (49). Psychologic and pharmacologic effects (heart rate, 
ECG) were continuously evaluated during and after the administration of the 
drug or the vehicle. Urinary and fecal excretion of total radioactivity and 
of the unchanged drug were also followed. Characteristic heart rate increase 
was observed and marihuana-like psychologic symptoms were reported by all 
three subjects indicating that most of the pharmacologic effects attributable 
to delta-9-THC or marihuana can be produced by ll-hydroxy-delta-9-THC in man. 
Perez-Reyes et al . have infused intravenously the same metabolite or delta-9- 
THC to 12 subjects using the serum albumin technique mentioned earlier (65). 
The infusion proceeded slowly until the subjects asked for termination of 
infusion as soon as they felt they had arrived at their derived level of 
"high" (the subjects were experienced marihuana users, and had also partici- 
pated in another THC study previously) . Heart rate and respiration were 

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constantly monitored during the experiment. The results indicate that the 
two compounds are not significantly different in pharmacological activity 
when injected intravenously in man. 

Since ll-hydroxy-delta-9-THC showed a disappearance rate from plasma and excre- 
tion rate in the urine and feces similar to those of delta-9-THC, the conclu- 
sion was drawn that after the administration of marihuana or hashish, delta-9- 
THC is first converted to the 11 -hydroxy metabolite and that this metabolite 
is responsible for the majority of the pharmacological effect of marihuana 
and hashish (49). This conclusion is consistent with the findings of Galanter 
et al . (23) who found that the time course of blood levels of THC, after 
smoking it in a spiked placebo, correlated more closely with the time course 
of the pulse increment than with the time course of the subjective experience. 
Both pulse increments and THC levels peaked 15 minutes post smoking, while the 
subjective effects, presumably elicited by the 11-hydroxy metabolite, appeared 
later, peaked about one hour post smoking and dissipated in the course of about 
four hours , 



Subjective Effects of Marihuana and THC 

Conclusive evidence from two controlled studies shows that delta-9-THC is 
indeed the major psychoactive component of marihuana (23, 19). Galanter et al . 
(23) administered natural marihuana, synthetic delta-9-THC (both in 10 mg 
doses) and a placebo cigarette to 12 volunteers on separate days each, a week 
apart according to a balanced order double blind design. Subjective drug 
effects were assessed by a 62-item questionnaire essentially developed by 
Waskow (87). Other physiological and psychomotor tests were also performed. 
The relative frequency of subjective symptoms in the marihuana and delta-9-THC 
states indicated a marked similarity in the subjective experiences. In the 
placebo states the subjective ratings were somewhat similar in constellation, 
but only about one third as intense as those reported in active drug states. 
This suggests a strong learned component in the marihuana response. In the 
other controlled study, Frank et al . (19) compared three active doses of 
synthetic delta-9-THC with natural marihuana (containing similar doses of 
delta-9-THC) and placebo in ten normal volunteers giving each dose a week 
apart in a random order, double blind design. Among the 17 various psycho- 
logical and physiological measures, the highest dose-response correlations 
were found in the subjective "high" estimates of the subjects on a to 7 
scale. Both studies found natural marihuana somewhat stronger than synthetic 
delta-9-THC in terms of the intensity of the subjective effects, but the 
differences were not large enough to suggest any significant role of compo- 
nents other than delta-9-THC in the natural marihuana. 

Some controversy still exists as to the role of the pharmacological effects 
of delta-9-THC (versus the social setting) and learning in the subjective 
manifestation of the marihuana "high." Indications are that the effect is 
very much dependent upon the dose of THC consumed. 

In relatively high doses, THC invariably produces psychotomimetic or hallucino- 
genic effects: paresthesias, altered perceptions, difficulty with thinking, 

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concentrating or speaking, and depersonalization (38, 34). However, in lower, 
more typical social doses, smoking of marihuana or appropriately prepared THC 
produces a level of intoxication which is variable, and allows the attitude 
of the subject, his set and expectations, the setting, and his past experi- 
ence to interact in a complex way to determine how the subjective state will 
be labeled and reported (39). Reese Jones maintains that many people have 
uncritically accepted the belief that marihuana has specific effects on 
behavior and experience and that these can be readily identified. Such an 
erroneous model, he continues, has been accepted by both users and profes- 
sionals and is continually reinforced by the media. Although at high doses 
such a model may be valid, as the general consensus of experts on the halluci- 
nogenic properties of high doses of THC suggests, at the doses most youthful 
drug users are discussing there is ample evidence that the effects of mari- 
huana on behavior and subjective experience are often unpredictable from the 
drug's pharmacologic profile (39). 

Other investigators, using moderate doses of smoked or oral marihuana in 
double blind studies, came to somewhat similar conclusions (11, 67). 

Marihuana intoxication, these studies indicate, is not totally a pharmaco- 
logical state but rather a state very much affected by the subject's expecta- 
tions and subjective interpretation of drug effects that he is experiencing. 
The interpretation is based on long-term social learning rather than simply 
influenced by the social setting. Moreover, the impairment in functions 
experienced as part of the intoxication can be enhanced or overcome depending 
on the subjects' motivation (11). The results of these studies also suggest 
that the frequent marihuana user is better able to control and compensate 
for the subjective effects as a consequence of a learned response pattern 
acquired after extended experience with the drug (67) . 

Physiological Effects 

In view of the consistent pharmacological effects of THC and marihuana on 
pulse rate, further in-depth studies of this cardiovascular response seemed 
warranted. 

Weiss et al . (88) gave delta-9-THC (0.3 mg/kg) orally to eight male volun- 
teers and monitored carefully the various parameters relevant to cardio- 
vascular functions. Recumbent and upright heart rate, recumbent mean 
arterial blood pressure, forearm blood flow, and calculated forearm conduc- 
tance all increased significantly following drug administration. Signifi- 
cant shortening of ventricular pre-ejection period and attenuation or aboli- 
tion of reflex vasoconstriction in response to deep breath were also seen. 
Mean arterial pressure decreased transiently with head-up tilt and was 
associated with presyncope in seven subjects although cardio-acceleratory 
response and forearm arteriolar constriction remained intact. Several of 
the cardiovascular effects seen appear to be consistent with increased sym- 
pathoadrenal activity rather than a direct effect of delta-9-THC on the heart 
itself. The augmented epinephrine secretion during the six-hour period fol- 
lowing delta-9-THC administration, but not during a similar control period, is 

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consistent with this interpretation. From the data available, however, it 
cannot be excluded that additional factors, including the subject's psychic 
responses, may have influenced circulatory functions (88). 

The increase in pulse rate and peripheral blood flow induced by cannabis seems 
to involve beta-adrenergic mechanisms, since pretreatment with propranolol, a 
beta-adrenergic blocker, prevented these cardiovascular responses to mari- 
huana (88, 2). Marihuana -induced tachycardia, however, cannot be the result 
from an atropine-like effect on efferent vagal activity since it could still 
be evoked in a sustained fashion in subjects who were clinically atropinized (2) 

These findings have several clinical implications. The age group most fre- 
quently involved in traffic accidents is also the one that most commonly smokes 
marihuana. A persistently high cardiac rate in a patient in an accident, not 
adequately explained by the clinical situation, might be related to cannabis 
smoked before the accident. Also, administration of atropine or local anaes- 
thetic containing epinephrine in such patients could enhance and prolong this 
tachycardia for a dangerously long period (2). 

The effect of marihuana on the intraocular pressure, referred to briefly in 
last year's report on Marihuana and Health, has been further investigated and 
compared to the effects of synthetic delta-9-THC in a double blind study by 
researchers at UCLA (19, 18). 

Thirty healthy subjects, 21-29 years of age, most of them occasional users of 
marihuana were selected on the basis of a strict psychological and medical 
screening process from the large number of students who volunteered for the 
study. Each subject returned for intoxication and examinations, a total of 
eight separate occasions, one week apart, receiving natural marihuana and 
delta-9-THC spiked placebo marihuana in a cigarette of approximately half 
gram size containing 0, 1, 2 and 4 percent THC in a random order. Evaluation 
was done on a double blind basis, using applanation tonometry, a precise 
ophthalmological technique to measure intraocular pressure (18). 

The results confirmed the preliminary report, i.e., marihuana decreases intra- 
ocular pressure in normal subjects and the effect is dose-related The maxi- 
mum average decrease observed was about 36 percent after the highest dose of 
natural marihuana. Furthermore, it was also demonstrated that delta-9-THC, 
the main psychoactive ingredient of marihuana, is also the main active com- 
ponent in the effect on the intraocular pressure (18). 

The obvious practical significance of this effect of THC would be its poten- 
tial utility as a therapeutic agent in open angle glaucoma, where pathologi- 
cally increased intraocular pressure due to some impediment of the outflow 
facility is a cardinal sign. Preliminary evidence from one glaucoma patient 
suggests that pathologically increased intraocular pressure can indeed be 
reduced to normal levels for a few hours by the administration of marihuana 
(31). 

The results of this study, however, cannot be generalized to other situations, 
such as the street use of marihuana. Before natural or synthetic marihuana 

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can be deemed safe and efficacious for treating this disease, further studies 
and testing are required. 

In view of the frequently reported respiratory difficulties such as bronchitis 
and asthma in chronic heavy cannabis smokers (54, 82, 30) detailed studies on 
the acute effects of smoked marihuana and oral delta-9-THC on pulmonary func- 
tions have been undertaken (19) . 

Nineteen healthy, experienced marihuana smokers, who also participated in the 
intraocular pressure study at UCLA discussed above, were tested by whole body 
plethysmography before and following acute intoxication with smoked marihuana 
of similar strength to that used in the intraocular pressure study (80) , In 
12 subjects the same tests were performed before and after oral administration 
of placebo, 10 mg, 15 mg and 20 mg delta-9-THC using a random, double blind 
crossover design. Whole body plethysmography is a relatively sensitive test 
which is capable of measuring the effect of any irritant on airway resistance 
within the respiratory passages. The results of this double blind study indi- 
cate that both smoked marihuana and oral delta-9-THC cause significant broncho- 
dilation in normal healthy volunteers resulting in a decrease in airway resis- 
tance. This bronchodilation appears to be produced by a mechanism other than 
beta-adrenergic stimulation since the effect could not be blocked by intra- 
venous pre-treatment of propranolol (0.2 mg/kg) (80). This unexpected airway 
resistance finding needs confirmation by independent investigators and the 
study will have to be extended to the effects of chronic administration of the 
drug before its role in pulmonary and respiratory functions can be adequately 
assessed. 



Neurological Effects 

It is generally agreed that the acute effects of THC or marihuana is unde- 
tectable by simple though expert visual inspection of EEG records (84, 71). 
Application of sophisticated computerized methodology in combination with 
EEG, however, can reveal some subtle but potentially important effects, 
especially after high doses of THC (84, 51, 72) In a scalp EEG record an 
increase of alpha activity can usually be demonstrated (84, 71) Certain 
components of both auditory (72) and visual evoked responses (51) from scalp 
electrodes show amplitude attenuation or peak delay prolongation after high 
doses of THC. These results are interpreted as THC acting on brain levels 
higher than the brain stem reticular activating system (51). THC thus seems 
to act differently from sedatives or alcohol which act primarily at the brain 
stem level in the central nervous system. 

A unique observation on the possible electrophysiological correlates of the 
marihuana "high" was made by Heath in a patient who, for other medical 
reasons, had chronically implanted electrodes in various deep structures of 
his brain (29). The patient, who had a three year history of drug abuse, 
was asked to smoke a marihuana cigarette on four occasions while his EEG 
was recorded from the indwelling electrodes. The development of euphoria 
was associated with the appearance of more distinct high aplitude slow wave 
activity focally in the septal region. No significant changes in EEG activity 

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were observed at other deep sites, over the cortex or over the scalp. Nor 
were similar changes observed in the EEG from deep sites of the brain of the 
same patient when effects of amphetamine, alcohol and tobacco were studied for 
comparison with changes induced by marihuana. Since EEG changes in the septal 
region, in past studies, have been correlated with the pleasure response, it is 
suggested by Heath that the results in this case probably also reflect func- 
tional changes produced by marihuana in the pathways essential to expression of 
emotion and feeling (29). 

Anecdotal reports in the marihuana literature on the occurrence of dreamlike 
and hallucinatory states resembling dreams, prompted the suggestion that THC 
might enhance dreaming sleep (34, 36). Since dreaming has been associated 
with REM (Rapid Eye Movement) sleep, several groups of investigators initiated 
studies of orally administered THC on all night EEG recordings (19, 68, 21, 1, 
41, 37). 

Although these studies are still under way, some preliminary data on limited 
number of subjects have been reported (68, 21, 1, 41). These indicate that, 
contrary to expectations, on THC nights there was some decrease in time spent 
in REM sleep with a "REM rebound" to the normal level on the following nights, 
apparently irrespective of whether THC continued to be given or the drug was 
withdrawn. The acute effect of THC on the stage 4 type of non-REM sleep was a 
slight increase in the first night (68, 1) but if THC was given on several 
consecutive nights, a progressive and apparently significant decrease in this 
measure was observed (1). Since there seems to be no quick "rebound" of this 
sleep stage after discontinuation of THC, it may be a sign of long-term effect 
of chronic administration of THC, but any speculation regarding its signifi- 
cance must await additional confirmation and further studies of this particular 
phenomenon. 

In view of the continuing debate on the relative toxicity of alcohol and mari- 
huana, it was of interest to investigate the effect of marihuana on the ves- 
tibular system which plays an important role in maintaining the equilibrium 
of the body. As it is well known, alcohol and several other drugs can produce 
serious impairment of this system resulting in ataxia and a loss of equilib- 
rium. In a controlled study, two doses of marihuana (7.5 and 15 mg THC) and 
a placebo cigarette were given on separate occasions in a random fashion a 
week apart to 72 volunteers (half of them occasional, half heavy users of 
marihuana) (78). A sensitive technique, electronystagmography was the main 
tool of the study but other, clinically routine, vestibular function tests 
were also performed before and twice after smoking the test cigarette. The 
results indicate no significant effect on these vestibular function tests by 
any of the test substances. 

In another study seven volunteers were given two doses (0.2 and 0.3 mg/kg) 
of THC orally on separate occasions and various physiological and neurological 
tests were performed (37). Typical subjective effects and pulse rate responses 
were recorded for several hours after ingestion. A modified Romberg test 
showed no impairment when the test was performed with the eyes open. However, 
when visual cues were absent (with closed eyes) the ataxia and equilibrium 
impairment were marked after the higher dose of THC. Other tests, such as 

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reaction time, visual evoked responses and sleep patterns on continuous EEG 
showed no drug-related changes (37). Some of the discrepancies between this 
and the other studies may be related to methodological differences or, espe- 
cially in the results of the sleep studies, to the small number of subjects 
which made the results and conclusions relatively uncertain. 



Effects on Mental and Motor Performance 

There have been several controlled studies performed in the past year to define 
the areas of mental and motor activities that are affected by marihuana or THC 
and to establish the role of chronic smoking in the actual performance variables 
after either smoking (70, 15, 19, 22, 58) or orally ingesting marihuana or THC 
preparations (66, 19). Carefully controlled conditions were deemed necessary 
for two major reasons already alluded to: first, because of the confounding 
effects of set and setting had to be partialled out so as to establish the 
effects of the drug itself, and second, because the effects of marihuana on 
many of the performance tests are relatively small and could be clearly demon- 
strated only in well-controlled situations. 

A deficit in short-term memory has again been clearly demonstrated in all of 
the studies which included an appropriate test of this function in their 
assessment battery (70, 22, 58, 66). 

In several other simple or moderately complex psychomotor tasks the reported 
findings are still mixed. Reaction time is more frequently reported to be 
affected by marihuana or THC (32, 66, 51) than not to be affected (22). Tap- 
ping speed or Reitan's trail -making is either not affected by the drug (66, 58) 
or affected only to a moderate degree (66, 15). 

Evidence is accumulating more clearly indicating that more complex tasks may 
be detrimentally affected by marihuana or THC (66, 19, 58). Some of the dis- 
crepancies in the reported effects of this drug on psychomotor performances 
may be related to the findings that occasional and frequent users perform 
differently under the influence of the drug, with the frequent users showing 
better performance and a clearer dose response curve than occasional users (66). 

Research on the theoretically as well as practically important issues of the 
possible interaction between THC and other drugs has just begun. It is pri- 
marily of theoretical interest, for example, that propranolol, a beta- 
adrenergic blocking agent, seems to block the cardioaccelerating action (80) 
or the disruptive effects of the drug on recall and performance tests (15). 

It is of more practical interest that THC and alcohol seem to have additive 
effects on heart rate and conjunctival injection ratings (58), as well as on 
performance measures of various psychomotor tasks (55, 58, 10). However, 
alcohol seemed to have no effect on the subjective phenomena produced by THC 
(except for visual imagery) which were possibly antagonized by the simul- 
taneous ingestion of alcohol (58). 



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Driver Performance 

It is of considerable practical interest whether or not automobile driving 
performance is adversely affected by marihuana smoking and s if so, how does 
the impairment produced compare to that produced by alcohol drinking. During 
the past year several studies have been performed and published both in this 
country and abroad. One of the studies involved actual driving (right after 
smoking) over a predetermined driving course. The driving task included both 
slow forward and backward maneuvering and higher speed (about 25 mph) straight 
and curved sections, marked out with wooden poles and plastic cones (58). The 
subject's driving was scored on: hits of cones and poles, rough handling and 
speed. Supplementary physiological and psychological measures were also ob- 
tained during each session. The sessions were designed to give performance 
data on driving impairment under four experimental conditions, according to a 
double blind design: placebo smoked; two levels of marihuana (21 and 88 meg 
delta-9-THC per kg body weight); and one dose of ethanol (producing an average 
blood alcohol level of 0.07 percent - the equivalent of about three cocktails). 
Both the alcohol and the higher dose of cannabis were found to result in poorer 
car handling performance. Driving speed, on the other hand, was affected only 
by the higher dose of cannabis, being slightly but consistently slower (about 
7 percent) . Driving speeds in the alcohol and low cannabis conditions were 
not significantly different from placebo. In a second driving trial, about 
three hours after smoking (or drinking) driving speeds as well as car handling 
performance scores were statistically indistinguishable from each other under 
all four conditions, suggesting a temporary effect of the drugs lasting for 
less than three hours (58) . 

In another study, using a simulated driving test after orally administered 
doses of delta-9-THC (350, 400 or 450 meg/kg) and a placebo according to a 
double blind design, somewhat similar conclusions were reached except that the 
effect lasted longer (5-6 hours) in these cases (43). THC significantly im- 
paired adaptation to rapidly changing situations in the driving test. At 
times when rapid decisions and actions were required, prolongation of reaction 
time, and an increased frequency of wrong and inadequate responses were ob- 
served. The degree of impairment seemed to depend on the initial personality 
structure and/or individual effects of the drug on basic word and attitude. 

The aspect of risk taking in driving after marihuana smoking has been studied 
in a simulated passing task by Dott (14). Twelve marihuana users operated an 
optical driving simulator under a nonsmoking condition and under three condi- 
tions after smoking crude marihuana leaf. The estimated dosages of delta-9- 
THC in the smoking conditions were mg. , 11.25 mg. , and 22.5 mg. During each 
session, each subject was given the opportunity to pass a lead car with the 
assistance of a passing aid device under conditions of varying risk. During 
several of these passing trials, there arose an emergency condition that 
required immediate response in order to avoid an accident. No differences in 
performance were noted between the nonsmoking and placebo (0 mg. THC) condi- 
tions. Subjects under the influence of marihuana completed fewer passes and 
took more time to make the elective decision as to whether to pass. It would 
appear that a subject under the influence of marihuana was less likely to 
accept the increased risk of attempting to complete the passes that were more 

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hazardous. Marihuana did not affect the number of attempted passes or the 
number of, "accidents" in a significant manner (14). 

A comparison with another experiment - in which the same experimental model 
was used, but with alcohol as the impairing agent - is of considerable interest 
(52). Enough alcohol was administered to 16 subjects to achieve a mean blood 
alcohol level of .089 mg percent, and they performed the same simulated passing 
study. The results indicate that drivers under the influence of alcohol were 
more aggressive in their behavior and made more errors of judgment than did 
control subjects. Subjects under the influence of alcohol attempted and com- 
pleted fewer passes. There were no significant differences noted in the number 
of attempts or "accidents." Both the alcohol and the marihuana subjects' 
decision-reaction times were prolonged in elective type passes. Alcohol also 
affected the lateral position of the vehicle and the tracking range during 
passes. Marihuana did not (14). 

In regard to the mechanisms involved, Dott offers the interpretation that 
marihuana does appear to reduce vigilance, but the person under its influence 
is able to compensate effectively in a high stress situation. Alcohol subjects 
are not able to achieve this compensation. In this respect, it would appear 
that alcoholic intoxication is more hazardous for traffic safety than is mari- 
huana intoxication (14). In view of the different conclusion drawn by Kielholz 
(43) from his study of marihuana on the compensation ability of the subjects in 
a stressful situation, these results should be interpreted with caution pending 
further investigations. 

With the controversial findings in tests using real or simulated driving, it 
is important that the effects of marihuana on various basic perceptual and 
motor functions, which are involved in the complex task of driving an automo- 
bile, be further elucidated in rigidly controlled experiments. 

Moskovitz et_al. (59) have reported three sets of experiments designed to com- 
pare alcohol and marihuana effects on visual functions. The first set of 
experiments examined drug influences on the detection of peripheral lights 
under three levels of central visual information processing demands. The second 
set studied drug effects on autokinesis (apparent movement of a stationary 
point source of light) and the third set examined drug effects on visual acuity, 
dark adaptation and ocular motor control. Each set of experiments used a group 
of 12 subjects and the drug dosages were either 200 meg THC per kg of body 
weight (a relatively high level of social usage) and placebo or three doses of 
alcohol: zero, 0.414 and 0.828 grams per kg of body weight, each on a separate 
occasion with a minimum of three days apart. The evaluation of the various 
visual functions were done on a double blind basis. The results can be sum- 
marized as follows: 

Marihuana produced a large decrement in peripheral signal detection under 
three different conditions of central visual information load, including that 
condition where no central information processing was required. In addition, 
errors in the central vision task increased under marihuana. Alcohol, on the 
other hand, did not impair peripheral vision when central vision did not re- 
quire information processing by the brain. A dose related, significant 

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impairment of the peripheral vision under both alcohol doses was observed 
when central information processing was required by the brain (59, 60). 

The effect of alcohol is interpreted as a deficit in the ability to divide 
attention or "time-share," while the effect of marihuana was suggested to be 
due to momentary lapses of attention - attention in the sense of concentration 
upon a specific task (59) . 

The results of the autokinesis studies revealed again a striking difference 
in the effects between the two drugs. Alcohol produced only an insignificant 
change in this measure, while marihuana produced a considerable and statisti- 
cally significant increase in the mean distance of the apparent movement of 
a stationary light source (74, 59) 

Dark adaptation, as measured by the Goldman-Weekers adaptometer was not af- 
fected by any of the drug treatment situation (placebo, alcohol or marihuana) 
(59). This finding is in conflict with earlier, admittedly preliminary find- 
ings of difficulties in dark adaptation under marihuana as reported in terms 
of increased amount of time required to recover from glare (17) . Marihuana 
as well as alcohol produced no effects on visual acuity or on binocular vision 
and only a small impairment on oculomotor functions (59) . 

The significance of these studies on visual functions lies in the fact that 
without understanding the mechanisms inducing the visual deficits in complex 
perceptual functions found under marihuana, it is difficult to estimate the 
degree of impairment likely to be found in man-machine interactions such as 
flying or driving. Only by understanding the mechanisms involved can we at- 
tempt to predict marihuana's impact on a host of variables out in the more 
complex work situation (59). 

In an effort to throw some light on the complex interplay between the altered 
perceptual processes and motor functions, the effects of smoked marihuana and 
ethanol on human schedule controlled behavior have been compared (10). The 
behavioral task involved a differential reinforcement of low rate schedule 
in which subjects were required to space key-press responses at least 20 
seconds apart in order to receive a small monetary reinforcement. Another 
feature of the schedule was that reinforcement was available for a limited 
period ranging from 0.5 to 4.0 seconds. Subjects received immediate feedback 
indicating whether a response was premature, correct or late. In a Latin 
square design, 12 subjects performed the designated task after consuming 
marihuana cigarettes containing a total of 0, 4, 8 or 16 mg of delta-9- 
tetrahydrocannabinol, and 12 additional subjects were tested following 0, 0.48, 
0.72 or 0.96 g/kg of ethanol. There was a dose-related decrement in rein- 
forced responses after marihuana. Moreover, a reliable shift toward errors 
of premature responding was observed with increasing doses. Ethanol had no 
reliable effects on the schedule controlled behavior at any dose. The results 
indicate that marihuana, in contrast to alcohol, interferes with temporally 
controlled responding even when there is a maximum of feedback concerning 
response accuracy. A placebo effect on behavior was found with marihuana but 
not with ethanol (10) . 



-140- 



From these studies it is clear that marihuana at levels of typical social usage 
does impair visual perceptual performance as well as temporally controlled 
responses to a significant degree and potential users should be warned that 
driving under its influence may lead to accidents. 

Jamaican Study 

Since cannabis use on a large scale is a relatively recent phenomenon in this 
country, it is difficult to find populations of chronic users who can be 
studied for possible adverse effects of long-term use. Another difficulty in 
studying cannabis users in this country is that many of them use other drugs 
as well, making it difficult to sort out possible adverse effects attributable 
solely to cannabis In order to avoid some of these difficulties, the National 
Institute of Mental Health supported an intensive study of chronic cannabis 
users in Jamaica (73). This study was undertaken to assess the possible 
physical and mental effects of cannabis in adult males who had been heavy 
smokers for many years. Because various portions of this Jamaican study will 
be referred to in the following sections on the adverse physical and psycho- 
logical effects of cannabis, we will describe here some relevant aspects of the 
study design, the sample characteristics, and the level and duration of cannabis 
usage. 

The subjects were from the lower socioeconomic class of Jamaican society and 
were mainly farmers and fishermen from rural areas* and unskilled laborers from 
the Kingston area. Sixty subjects, thirty chronic cannabis smokers and thirty 
matched controls, were hospitalized for six days. During this time detailed 
medical histories and physical examinations were performed, chest X-rays and 
electrocardiograms taken, respiratory function tests performed, and a variety 
of blood chemistry tests were done to assess renal, liver, and hematological 
function. In addition, thorough psychological and psychiatric assessments were 
carried out, including psychological testing and EEGs . 

The age range of the subjects was from 23 to 53 years, with an average age of 
34. Age at first cannabis smoking experience varied from 8 to 36 years. Total 
years of regular cannabis smoking ranged from 7 to 37 years, with a mean of 
17.5 years. The number of marihuana cigarettes smoked per day ranged from 1 
to 24, with an average of 7. Potency of cannabis preparations in Jamaica 
varies but analysis of samples submitted by the subjects revealed a relatively 
high delta-9- tetrahydrocannabinol content ranging from 0.7 percent to 10.3 per- 
cent, with an average of 2.96 percent. 

In general, the users and controls seemed well-matched. All but 3 of the canna- 
bis users also smoked tobacco, whereas 8 of the controls did not use tobacco. 
Alcohol consumption appeared to be roughly the same for both groups. 



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Chronic Physical Effects 

Past reports of the effects of chronic use of cannabis have described a variety 
of conditions ranging from minor physical effects such as congestion of the 
ciliary vessels of the eye to organic brain damage. The many problems involved 
in proving a causal relationship between the chronic use of any drug and a re- 
sulting illness have been described in previous reports to Congress (56). Also, 
the importance of the level of usage of cannabis has been emphasized. In gen- 
eral, there has been little evidence that occasional light use of cannabis has 
deleterious physical effects. Most reports in the literature of chronic physi- 
cal effects were of heavy users of cannabis. In this country most usage would 
be considered light compared to levels common in some Eastern countries where 
very potent preparations such as hashish are regularly used. Therefore, ex- 
posure to toxic substances in cannabis preparations may vary many fold from 
population to population and chronic physical effects are likely to be dose de- 
pendent. Thus, to be meaningful, discussions of toxic physical effects must 
take into consideration the level of exposure. Almost every drug will have 
chronic physical effects if given in large enough doses over a sufficient period 
of time. There is no totally "safe" drug. The safety of a drug only has mean- 
ing if discussed in the context of level and characteristics of common usage of 
the drug 

Recently a new report in this country has described the occurrence of gyneco- 
mastia (breast enlargement) in chronic marihuana users (28) . Three cases of 
young males in their twenties with gynecomastia associated with heavy marihuana 
use for from two to six years were observed. Extensive examinations were per- 
formed to rule out other causes such as liver disease or an endocrinological 
abnormality, however no evidence of other disorders was found. The authors 
speculate that the chemical similarity between delta-9 -tetrahydrocannabinol and 
the feminizing hormone, estradiol, may have played some role in this phenomenon. 

Although some authors have previously reported evidence of liver dysfunction, 
others have been unable to confirm this finding and in some cases have described 
liver abnormalities in chronic marihuana users who were later discovered to also 
be heavy users of alcohol. In the Jamaican study comparisons were made between 
cannabis users and controls on a number of blood chemistry tests which can indi- 
cate liver malfunction. No significant differences were present and no evidence 
of liver disease was observed in the cannabis users. In Canada, in a prelimi- 
nary report of a study of 200 regular cannabis users, Oki and Sisson report 
that there seemed to be no significantly increased incidence of liver disorders 
in cannabis users as compared to a similar non-cannabis using population (9) . 

Since the liver seems to be important in the metabolism of the active consti- 
tuents of cannabis, such as delta-9 -tetrahydrocannabinol, there is considerable 
interest in the possible deleterious effects of cannabis on liver function. 
Such effects occurring at the levels of chronic usage common in the Western 
Hemisphere have not been demonstrated. 

Respiratory difficulties have in the past been reported in chronic, heavy smokers 
of cannabis preparations. In last year's Report to Congress it was concluded 
that there was some evidence to support these observations. In the past year 

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further case reports and observations have appeared which lend increased credi- 
bility to the earlier reports, Henderson et al . report on 200 cases of chronic 
hashish smokers in the U.S. Army in West Germany who sought treatment for a 
variety of upper and lower respiratory tract complaints (30) . Over 90 percent 
of these patients additionally smoked cigarettes. Use of hashish was very 
heavy and ranged up to 600 grams per month. Most of the complaints were rela- 
tively minor ones such as sore throat and rhinitis, but 20 of these patients 
were diagnosed as having bronchitis. In the bronchitis patients chest X-rays 
were normal except for increased bronchopulmonary markings but pulmonary vital 
capacity was reported to be 15-40 percent below normal. Six of the bronchitis 
patients underwent bronchoscopy and biopsy. All of these patients used greater 
than 50 grams of hashish monthly. Although no gross lesions were seen for 
biopsy, all samples showed microscopic epithelial alterations such as loss of 
cilia, hyperplasia, and presence of atypical cells. The authors felt that such 
abnormal findings were similar to those usually seen in heavy cigarette smokers 
in an older age group. In a further report from this group, they describe the 
finding of bronchial biopsies on 17 additional heavy hashish smokers (26) . 
Microscopic abnormalities were observed in every biopsy and included epithelial 
changes similar to those described above. 

In a recent study of the effects of marihuana and tobacco smoke on human lung 
explants, Leuchtenberger et al . found an increased incidence of cellular ab- 
normalities in both the cultures exposed to marihuana and tobacco as compared 
to control cultures (89). Initially, the cellular changes were more severe in 
the tobacco smoke exposed cells than in marihuana smoke exposed cells; however, 
after this initial period marihuana appeared to produce the same abnormalities 
as tobacco smoke. However, the marihuana smoke was administered at twice the 
level of tobacco smoke in this study. — — 

In the Jamaican study, spirometric and arterial blood gas tests of pulmonary 
function revealed no major statistical differences between cannabis smokers 
and controls. However, several trends were of interest. There was a tendency 
for a proportional decrease in the forced expiratory volume, the forced vital 
capacity, and the peak flow as the number of years and quantity of cannabis 
and tobacco cigarettes smoked increased. The arterial oxygen of cannabis 
smokers tended to be lower than that of the controls. However, these trends 
are difficult to evaluate because a larger proportion of the cannabis smokers 
also smoked tobacco. In addition, cannabis in Jamaica is often smoked as a 
mixture with tobacco. For these reasons it was felt that these findings may 
be more a result of smoking per se than of marihuana smoking as such. 

In addition, the Jamaican study showed statistically significant differences 
in the blood hemoglobins of cannabis users versus controls. Cannabis users 
had elevated hemoglobin levels and elevated packed red blood cell volumes. 
Although carboxymethemoglobin levels were not obtained, it was felt that this 
might be the most reasonable explanation of these findings and the low arterial 
oxygen. In other words, these findings could be due to an increased production 
of hemoglobin and red blood cells as a result of a functional hypoxia induced 
by chronic smoking. 

The possibility that chronic cannabis use might cause brain damage is one that 
has stirred concern and controversy in this country. During the past year 

-14?- 



several articles have been published which are relevant to this issue. 

Kolansky and Moore have described a series of 13 adults who were regular users 
of cannabis (three to ten times per week) and who were referred to them for 
psychiatric r evaluation and care because of various psychiatric symptoms (46). 
These authors feel that their observations reflect a specific pathological 
organic response in the Central Nervous System to cannabis and speculate widely 
on the possible biochemical and structural brain lesions that might accompany 
such a syndrome. They describe a common core of symptomatology which they feel 
characterizes this syndrome and which includes such things as apathy, mental 
sluggishness, loss of interest in personal appearances, flattening of affect, 
sense of well-being, mental confusion, slowed time sense, difficulty with recent 
memory, and an incapability of completing thoughts during verbal communication. 
They report that the intensity of symptoms seemed to be related to the level of 
cannabis use and that in most cases there was either total or partial remission 
of symptoms after the patient stopped using cannabis. All of these patients 
were felt to be relatively normal psychologically prior to using cannabis al- 
though the authors did not observe this normal baseline but conclude on the 
basis of clinical history taking that this was the case. The authors strongly 
feel that the psychological phenomena they observed are causally related to a 
toxic effect of cannabis on the brain. 

Although this report tries to make a causal connection between cannabis and an 
organic brain syndrome, there are limitations on the conclusions which can 
validly be drawn by an uncontrolled case report of this sort. While clinical 
case reports are very useful in medicine in alerting other physicians to possible 
new syndromes and etiological agents, they cannot provide definitive evidence 
because of their inherent sampling bias and their lack of control over a multi- 
tude of independent variables that may account for the phenomena observed. A 
number of the symptoms described as part of this cannabis syndrome are not too 
different from the effects of acute marihuana intoxication, whether these 
patients may at times have used cannabis before seeing their psychiatrist or 
may have been chronically intoxicated is unknown, but some sort of objective 
knowledge of the drug status of the individual is needed before conclusions 
about brain cell damage as the cause of these symptoms can be made. Unfortu- 
nately, simple body fluid tests for the presence of cannabis products are not 
yet available to physicians. Hopefully such tests will be available in the 
future so that the presence or absence of cannabis or other intoxicants such as 
alcohol and barbiturates can be easily ascertained by the physician who sees 
such symptomatology. Although these cases were all felt to have had an absence 
of psychopathology prior to cannabis use, one must wonder why many of them became 
psychologically dependent on cannabis since only a small fraction of users become 
chronic users. There is some reason to believe that a high level of pre-existing 
psychopathology exists in many of those who do become dependent. That these 
patients got better when they gave up cannabis use is suggestive that cannabis 
may have been playing some role in their difficulties but other factors may have 
also played a role. For instance, some of them received psychotherapy and all 
of them were told that their use of cannabis was causing their difficulty and 
that they should stop the cannabis use in order to get better. Thus, suggestion 
on the part of the therapist may have played some role in their improvement. 
Finally, these authors report no attempt to corroborate their subjective clinical 

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impressions of brain damage with more objective tests such as EEG's and bat- 
teries of neuropsychological tests. While these alternative explanations of 
their observations may be incorrect, they serve to illustrate the sorts of 
variables that can complicate any attempt to arrive at definite causal rela- 
tionships on the basis of clinical case reports. 

Tennant and Groesbeck have recently published their observations of the psychi- 
atric complications of 720 hashish smokers in the U.S. Army in West Germany (81). 
A total of 110 of these patients heavily used hashish, smoking it several times 
a day to the point that they were chronically intoxicated. The authors were 
able to prospectively follow 9 of these heavy users for periods of up co two 
years. These patients eventually discontinued hashish use. In six of these 
patients, memory, alertness, concentration, and calculating ability appeared to 
return to normal in two to four weeks after stopping hashish. Three of the nine 
continued to exhibit intermittent symptoms which were felt to be analogous to 
those of organic brain damage. With time these episodes became less severe and 
less frequent. Twenty-three of these 110 patients were first observed during 
chronic intoxication but later quit the use of hashish. Ten of these 23 con- 
tinued to exhibit intermittent episodes of memory loss, inability to concentrate, 
and confusion. These patients denied further use of drugs except alcohol though 
the authors report no objective corroboration of the patient's drug use such as 
urine or blood testing during this period. 

In a study in Egypt of 850 hashish users compared to 839 nonuser controls, both 
drawn from a population of prisoners, Souief found differences between users 
and nonusers on a number of tests which assessed cognitive and psychomotor per- 
formance (77). In general the users had poorer scores than the controls. How- 
ever, these differences may have predated cannabis use or may have been a result 
of the long-term existence in a particular life style necessitated by partici- 
pation in the hashish subculture in Egypt. 

In the Jamaican study extensive efforts were made to assess the possibility of 
brain dysfunction in the subjects. EEG's were recorded and every subject re- 
ceived an elaborate battery of neuropsychological tests and a neurological 
examination. The striking finding in this study was the absence of any signifi- 
cant difference in any of these parameters between the chronic cannabis users 
and their matched controls. There was no evidence of organic brain damage in 
any of the subjects in the study, and the psychosocial functioning of the regular 
cannabis users matched well with the controls and with social expectations for 
those from that stratum of Jamaican society. ««. 

In a study of chronic hashish users in Greece, there were no significant dif- 
ferences between users and a matched control group in the prevalence of EEG 
abnormalities (16) . — 

In a Canadian study, Campbell studied the EEG's of a group of cannabis users 
who had become psychotic and compared them with a group of cannabis users who 
had no psychiatric impairment, and a group of schizophrenic and neurological 
patients (8). Both the cannabis groups had a high incidence of abnormal EEGs . 
However, this was a small sample and the cannabis use among these groups was 
quite variable. 

_ l *±^_ 



Genetic and Birth Defects 

In last year's Report to Congress we indicated that in a small number of pre- 
liminary studies on the effect of cannabis on human chromosomes there was little 
evidence that cannabis caused chromosomal aberations. Also, the number of re- 
ports of birth defects in children of mothers who used cannabis was very small. 
During the past year such reports have continued to be very rare. In a single 
case report Bogdanoff , et al . reported the birth of an infant with multiple 
central nervous system abnormalities to a 19 year old mother who had smoked 
marihuana and had taken multiple drugs including LSD and amphetamines through- 
out her pregnancy C5) . No conclusion can be reached about the role of cannabis, 
if any, in this case. 

There have been further reports of cytogenetic studies on the effects of canna- 
bis on human chromosomes. Stenchever, et al . recently studied the in vitro 
effect of delta-9-tetrahydrocannabinol on the chromosomes of human lymphocytes 
(79). In their study, human leucocytes from healthy blood donors were exposed 
to several concentrations of delta-9-tetrahydrocannabinol in tissue culture. 
They found no increase in the incidence of chromosome breaks or other defects 
in any of the cannabis exposed cultures when compared to controls. In the 
Jamaican study the chromosomes of peripheral blood lymphocytes were examined 
and comparisons were made between cannabis users and nonusers. No significant 
differences were found in the incidence of chromosomal abnormality between 
cannabis users and controls. 

At the present time there continues to be little evidence from human case re- 
ports and research studies that cannabis preparations have either a signifi- 
cant teratogenic effect or have any significant effect on chromosome breakage. 
Case reports of children with birth defects born to mothers that used cannabis 
continue to be very infrequent and almost always are complicated by the use of 
other drugs. In vitro studies of the effect of delta-^9-tetrahydrocannabinol 
on human chromosomes as well as studies of chromosomes from chronic cannabis 
users have so far failed to indicate that cannabis causes chromosomal abera- 
tions. However, it must be kept in mind that such effects may be dose related. 
It is possible that very heavy use of cannabis preparations might have a 
detectable effect. Thus far there have been few reports of cytogenetic studies 
of very heavily using populations. In addition, the limited findings reported 
to date need to be confirmed, particularly by other studies of chronic cannabis 
abusers. In the meantime, caution dictates that care be exercised in the use 
of cannabis especially during the reproductive years and by young women during 
pregnancy. 

Evidence from recently conducted animal research provides no indication that 
marihuana, even under conditions of chronic use, is mutagenic or teratogenic. 
Nevertheless, there is no way to be completely certain that under some condi- 
tion of use, possibly in interaction with that of other drugs, adverse conse- 
quences might not ensue. 



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Acute Physical Toxicity 

As was summarized last year, death, from overdose of cannabis is a very rarely 
reported event. Case reports of death from cannabis overdose continue to be 
extremely infrequent. This fact, plus evidence from animal toxicity studies 
indicates that the ratio of lethal dose of cannabis to psychologically ef- 
fective dose is very large and is much more favorable than that of drugs such 
as alcohol and many common over-the-counter drugs. This may not be the case 
for the intravenous injection of a cannabis preparation since a majority of 
the severe physical reactions to cannabis reported in this country have fol- 
lowed this mode of administration. 

Although in the past isolated reports have associated marihuana with exacerba- 
tions of certain chronic illnesses such as epilepsy and diabetes, a causal 
role has not been established and thus far the deleterious effect of marihuana 
in these illnesses has not been confirmed. One acute pharmacologic effect of 
cannabis that has been repeatedly demonstrated in humans is a tachycardia. 
Some investigators have suggested that the use of cannabis derivatives by 
people in middle age or people with cardiac illnesses might present some 
hazard (61) . Others have suggested the possibility that there might be a 
deleterious interaction between cannabis derivatives and various vasoactive 
compounds used in medical practice (2). So far there have been few case re- 
ports in this country which would confirm these concerns. 

Cannabis and Psychopathology 

Previous reports to Congress have pointed out that marihuana use may be asso- 
ciated with certain less severe psychological reactions such as depressive 
and panic reactions, particularly in inexperienced users. Also, there seemed 
to be some evidence that the sudden exposure of an individual to greater 
amounts of cannabis than that to which he was tolerant might cause a toxic 
psychosis. These psychoses appeared to be relatively infrequent and self- 
limited, usually resolving in a few days to a few weeks when exposure to 
cannabis was terminated. Although cannabis has been claimed to be a cause of 
chronic psychoses and an amotivational syndrome, there appeared to be little 
well-controlled evidence to support this though systematic investigation in 
this area was rare. 

In the past year a number of case reports have appeared which have described 
psychiatric problems in association with cannabis use. Tennant and Groesbeck 
have reported on the psychiatric phenomena associated with hashish use among 
U.S. Army personnel in West Germany (81) . They received 720 referrals of 
hashish smokers from a population of 36,000 soldiers. Of these patients, 392 
were occasional users and limited their use to 10 to 12 grams monthly. In 
these light users there were no indications of adverse psychological or be- 
havioral effects and their major complaints centered around minor respiratory 
problems such as sore throats. Eighteen patients were seen because of a 
panic reaction or toxic psychosis after a single high dose of hashish. Psy- 
chotic manifestations in these patients dissipated within three days following 
treatment with phenothiazines. Eighty-five other patients were referred for 

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treatment of an acute toxic type psychosis after use of hashish, and other 
drugs in combination. These other drugs included alcohol, various hallucino~ 
gens, amphetamines, and sedatives. In 115 patients a psychosis similar to 
schizophrenia occurred and progressed to a chronic psychotic phase similar to 
chronic schizophrenia. Almost all of these patients were very heavy hashish 
users (several times daily) . Finally, 110 of these patients were very heavy 
users of hashish who were referred for evaluation because of being in a 
chronically intoxicated state which seriously interfered with their psycho- 
social functioning. These subjects appeared to be analogous to chronic alco- 
holics. It must be emphasized that these levels of usage are extremely high 
compared to common American usage, and the authors estimate that they may be 
equivalent to as much as 500 to 6,000 marihuana cigarettes per month of the 
street variety found in the United States. The authors conclude that 10 to 12 
grams or less per month of hashish was without apparent adverse mental effects 
while heavier levels of usage and simultaneous use of other psychoactive drugs 
may produce a variety of adverse mental effects ranging from toxic psychoses 
to a chronically intoxicated state. 

In Scandinavia, Bernhardson and Gunne investigated the number of cases of 
psychosis seen in association with cannabis use (4) . They mailed question- 
naires to psychiatric clinics and mental hospitals throughout Sweden and found 
66 cases of psychosis in cannabis users. Of these, 20 were excluded because 
of the predominant use of other drugs and little use of cannabis. Of the re^ 
maining 46 cases of psychosis, 24 were of an acute nature CI to 5 weeks) and 
22 were chronic (greater than 4 months and continuing at the time of the 
study) . Hashish was the preparation of cannabis most commonly used and use 
was quite high by American standards C2 to 15 grams daily). A majority of the 
chronic psychoses occurred in individuals who had a history of psychosis prior 
to cannabis use and almost all of these cases appeared to be chronic schizo*- 
phrenia. Only two of the 24 patients who had an acute psychosis, however, had 
had a previous history of a psychotic episode. In many of those who had an 
acute psychotic episode there had been a considerable increase in cannabis use 
just prior to the psychosis. 

Geerlings et al . report a survey of acute adverse drug reactions seen in the 
emergency room of the major hospital in Amsterdam C24) . Adverse reactions to 
alcohol were the most frequent problem with reactions to psychotomimetics, 
stimulants and cannabis following in that order. In general, the reactions 
to cannabis were not severe and consisted mostly of panic reactions though 3 
cases were seen in which hallucinations or paranoid ideation was present. 

In a recent report, Heath has described the occurrence of high amplitude, 
slow-wave EEG activity recorded from an electrode implanted in the septal area 
of the brain (29). These recordings were made while the subject smoked mari^ 
huana and described his subjective state as one of euphoria. The same author 
has previously reported recording abnormal EEG activity in the human septal 
area in psychotic patients. The implications of this finding are as yet unclear, 

Since case reports rarely make it possible to determine a causal association 
between cannabis and a particular psychiatric syndrome, those studies which 
have examined the relationship of cannabis use to the level of psychological 
health of the user are of interest. 

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Linn sent questionnaires to 1000 randomly picked university students (53) . 
These questionnaires gathered information on the individual's drug history and 
also included a psychiatric symptom checklist. On the basis of drug history 
the students fell into four categories; those currently using marihuana, those 
who had used in the past but were not now using, those who were nonusers but 
who had had the opportunity to try marihuana, and those who were nonusers and 
had never had an opportunity to try marihuana. Cannabis use correlated well 
with high scores on the psychiatric symptomatology checklist. Also nonusers 
who had never had an opportunity to try marihuana but who indicated they would 
like to use it had higher scores on the symptom checklist than those who said 
they would not use marihuana even if it were available to them. Although this 
seems to suggest that the presence of psychiatric symptoms may predispose to 
marihuana use there was some support in the study for a different interpreta- 
tion. For example, students who had the strongest introspective-psychological 
identification (e.g., "psychological mindedness") were those most likely to be 
users and nonusers with no opportunity to try marihuana who had high scores in 
"psychological mindedness" were also those most likely to be willing to use 
marihuana if it was available. This suggests that marihuana users may be 
people who are more likely to describe themselves using psychological concepts 
and thus the high symptomatology scores may not reflect real psychopathology. 

Harmatz et al . in a study of young adult applicants to a drug research program 
found that more users than nonusers were found among those who showed psychi- 
atric impairment (27) . Shearn and Fitzgibbons compared the frequency of drug 
use (including marihuana) of 167 young psychiatric in-patients with the fre- 
quency of drug use in college students (75) . There was a much higher frequency 
in the psychiatric patients. Burke and Eichberg in a study of the personality 
characteristics of adolescent users of non-narcotic drugs of abuse found a 
broad spectrum of psychopathology (7). 

Klapper et al . studied the cognitive performance of subjects who had experi- 
mentally received a synthetic derivative of delta-9-tetrahydrocannabinol (45) . 
They selected a group of drug sensitive subjects and a group of drug resistant 
subjects based on their cognitive performance after receiving the drug. They 
found significant personality differences as measured by the Minnesota Multi- 
phasic Personality Inventory, between drug sensitive and resistant subjects. 
This study seems to confirm and correlate well with previous studies which 
have indicated the importance of psychological set in the effects of cannabis. 

One possible adverse psychological effect of cannabis that has received wide- 
spread attention is the so-called amotivational syndrome. Clinical case re- 
ports continue to appear from time to time describing an association between 
cannabis and a deviation from conventional motivation (3) . For instance, the 
13 cases described by Kolansky and Moore seem to have as one of their common 
features (in addition to the previously discussed organic symptoms) a decrease 
in conventional motivation. Several of these patients seemed to lose interest 
in their profession or occupation, acquire new, less competitive values, and 
become interested in various political, philosophical, or religious systems. 
The interpretation of this sort of change is very difficult since illicit drug 
use in the United States is often closely associated with a counterculture 
movement that emphasizes just such values as these as being preferable to 

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conventional ideas. It is practically impossible to tell from anecdotal case 
reports whether cannabis caused the change in behavior and values or whether 
the change in values and behavior caused the individual to become involved 
in cannabis use. So far, well controlled studies to examine this problem are 
virtually non-existent. The results of the Jamaican study indicate that such 
an amotivational syndrome is not associated with regular cannabis use in that 
society. These results suggest that factors other than cannabis may be im- 
portant in causing the changes described in this country. 

A further problem in defining an amotivational syndrome is in delineating it 
from states caused by intoxication with the drug. It is quite possible that 
cannabis may decrease motivation if the individual is chronically or even 
frequently intoxicated by it. Some experimental evidence to support this 
comes from a study conducted by the Addiction Research Foundation of the be- 
havioral consequences of administration of marihuana in a controlled setting 
(9). They found that when subjects were forced to consume larger daily quanti- 
ties of cannabis than they wished, there was a decrease in work productivity. 
Mendelson and Meyer, however, in their study of experimental administration 
of marihuana did not find any consistent alteration in pattern of work over a 
21 day period (57). However, most authors who describe the amotivational 
syndrome do not seem to be talking about a direct result of frequent intoxica- 
tion but rather emphasize some lasting change in behavior and personality pre- 
sumably due to permanent or semi-permanent organic brain changes. For this 
reason, the fate of the entity, amotivational syndrome, will probably ulti- 
mately depend on the demonstration or lack of demonstration of specific organic 
brain lesions which can be causally related to cannabis. The continued use 
of uncontrolled anecdotal reports to support the existence of this syndrome 
will probably add little to clarifying the situation. 

In summary, the acute psychoses reported by Tennant and Bernhardson after 
sudden increase in cannabis use or a single high dose seem to be compatible 
with previous reports of a cannabis toxic psychosis which is usually short- 
lived, self— limited, and without apparent lasting psychological consequences. 
Tennant' s and Geerling's reports suggest that such acute psychoses due to 
cannabis alone are not frequent occurrences. The acute psychoses occurring 
after use of hashish in combination with other drugs emphasize the possibility 
of synergistic interactions of various drugs of abuse. The chronic psychoses 
which occurred in association with cannabis use seem, for the most part, to 
be little different from chronic schizophrenia. In Bernhardson ' s study, a 
majority of those with chronic psychosis had a psychosis prior to cannabis 
use, thus making it doubtful that cannabis was a cause. Most of those 
chronic patients in both Tennant 's and Bernhardson' s reports who did not 
have prior psychoses come from the age group that is at highest risk for the 
onset of schizophrenia; therefore, some sort of appropriate control population 
would have to be examined before an association between cannabis and chronic 
psychosis could be established. Even this would not establish a causal rela- 
tionship. Therefore, cannabis as a sufficient cause of chronic psychosis 
seems to remain unproven. This, of course, does not rule out the possibility 
that heavy cannabis use may play a role in precipitating or aggravating chronic 
schizophrenic psychoses. 

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A number of studies have suggested that cannabis use in this country, par- 
ticularly heavy use and use in conjunction with other drugs, is associated 
with considerable psychopathology and that this psychopathology may predate 
the drug use. Further studies are needed to clarify this issue. The existence 
of an amotivational syndrome continues to be reported. In the absence of evi- 
dence from controlled studies Csuch as the Jamaican study) that such a syndrome 
is causally related to cannabis, it remains a condition whose existence and 
characteristics will probably be in doubt unless an association between it and 
organic brain changes due to cannabis can be unequivocally demonstrated. 



-1! 



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(9 



13/ Rubin, V. , Research institute for the study of man, United States 
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January 12, 1973. 



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FUTURE RESEARCH DIRECTIONS 



As this and the earlier editions of the Marihuana and Health Report readily 
attest, we have had an exponential increase in our knowledge of marihuana in 
recent years. Characteristically, as our knowledge has increased so has aware- 
ness of our ignorance in many areas and of the need for additional data. The 
purpose of this section is to briefly outline some of the important research 
issues that require study in the future. For convenience we will discuss these 
needs from a psychosocial and biomedical standpoint. 

There is a need for more focused studies on the epidemiology of marihuana use 
and especially on the family, institutional and peer influences on use patterns. 
One difficulty with much of the work that has been done in the past is that it 
has examined drug use at a particular point but not over a period of time. 
Longitudinal studies over a period of several years or more can contribute much 
to our presently limited understanding of the implications of cannabis use. It 
would be very useful to know, for example, what happens with respect to drug 
use and other aspects of life style as the youthful user passes through the edu- 
cational process and becomes involved with the demands of adult life and a 
career. 

Longitudinal studies would go a long way toward clarifying the extent to which 
drug use and changes in conventional motivation that have been alleged to re- 
sult from it are related. Almost certainly the number of users who "drop out" 
of more conventional society is small and what evidence exists suggests a pre- 
existing disenchantment with more conventional values. Even among this group, 
however, little is known about life histories and the degree to which there is 
a return to more conventional pursuits following a period of estrangement. 

One of the problems that has made data from various parts of the country and 
from different studies difficult to compare has been a lack of consistency in 
methods of data collection and interpretation of results. While few, if any, 
studies now limit themselves to examining whether the respondents have simply 
"ever used" marihuana, it is important that current patterns of use be examined 
in a way that permits more sophisticated analysis of use patterns along many 
dimensions. Efforts are currently underway to encourage more thoughtful data 
collection and more sophisticated epidemiological approaches to examining drug 
use patterns. 

While our understanding of the nature and extent of marihuana use has increased 
tremendously in the past several years, there are still a number of specific 
areas in which increased knowledge is greatly needed. Relatively little is 
known about the extent of on-the-job use of marihuana in industry although 
there have been reports that such use is occurring with greater frequency. 

A systematic knowledge and understanding of marihuana use in various minority 
groups would be valuable and might also enhance our understanding of the ways 
in which different groups informally cope with the issue. It is well known 
that attitudes toward the use of alcohol, for example, vary greatly among dif- 
ferent ethnic groups and that these attitudes play a role in the level of abuse 

-161- 



that occurs. A better understanding of the genesis of attitudes toward use 
and the user in different groups may help us to discourage drug abuse whether 
of marihuana or of other drugs. 

Although the difficulties of setting up well controlled studies of cannabis use 
overseas remain formidable, there is a continuing need to do so. It will be 
many years before the number of long term domestic users has increased to the 
point where large scale assessment of chronic risk is possible. In order to 
detect possible infrequent hazards it is necessary that we study larger popula- 
tions than has been done in the past. Such studies, incorporating both bio- 
medical and social science research techniques, can also give us significant 
insights into the types of drug user, the methods of induction into different 
use patterns, factors governing persistent use and those psychosocial factors 
that encourage or discourage excessive cannabis use. 

The introduction of marihuana use to new groups in countries where its use had 
been indigenous has resulted in an expansion of scientific interest within 
many of those countries. In addition to our own direct efforts, we hope to 
encourage increased research on cannabis use by investigators in other countries. 
Such research, especially in those countries in which use has been widespread 
for generations, will do much to increase our understanding of patterns of cul- 
tural diffusion and the role of marihuana use within different cultural contexts. 
If the longitudinal study of users in many countries can be accomplished, it will 
better assist us in understanding some of the rather contradictory reports of 
the implications of use. While reports of socially deteriorated functioning 
related to marihuana use received wide publicity in the past, we have no way of 
knowing what percentage of users are affected in this way or, indeed, to what 
extent such deterioration is directly related to cannabis use. As use increases 
in the United States such knowledge will be valuable in assessing the size of 
the public health problem that is likely to develop from marihuana use and may 
enable us to minimize it. 

There are a number of important chemical and biomedical research issues that 
are important in continuing to assess the health implications of marihuana use 
in the United States. One technical problem is that of developing relatively 
uniform methods of analysis of cannabis so that the results of one laboratory's 
assay can be accurately compared to that of another. This is especially impor- 
tant when comparisons are being made between results obtained in the United 
States and in other countries. At present a collaborative program is underway 
in which ten analytical laboratories doing cannabis assays are reporting their 
findings on standard cannabis samples to the National Institute of Mental Health. 
By evaluating the variations in findings and methodology, we can expect to 
develop more valid and reliable measures that will facilitate comparisons. 

The development of a simple, easily carried out test for marihuana use and in- 
toxication has not yet been achieved. Such a test would be invaluable in 
determining the extent of marihuana intoxication for both clinical and research 
purposes. Work is continuing on this problem, and it is hoped that such a test 
can be developed this year. 



-162- 



Continuing studies of the various products formed during the metabolism of 
marihuana in the body and of the process by which the drug acts are important 
to our understanding of marihuana's health implications. This area of study 
is likely to assist us in anticipating possible drug interactions that may 
occur as marihuana is used in conjunction with other drugs widely available in 
our society. Systematic pharmacokinetic studies are needed to better define 
absorption in the various organ systems of the body and the excretion process. 
As has been suggested in other sections of this report, the interaction of 
marihuana with such drugs as alcohol, nicotine, caffeine, barbiturates and 
stimulants is of particular importance. Such studies have been begun and will 
continue. 

There is evidence in animals that regulation of body temperature may be dis- 
turbed by marihuana. Possible effects of exposure to cold while under the 
influence of marihuana should be examined as well as its role when used in 
association with febrile illnesses. 

Possible toxic effects of cannabis on specific organ systems should continue 
to be examined with care. Increasing reports of respiratory difficulties asso- 
ciated with heavy smoking of cannabis and the possible effects of marihuana 
smoking on lung tissue require especially careful examination. 

Because clinical reports of adverse effects typically cannot distinguish the 
role of marihuana from that of other drugs or other aspects of life style, it 
continues to be important to follow-up these reports by more systematic animal 
and human studies. 

A variety of preclinical animal research data has been accumulated which also 
requires systematic study in humans. In the past the maximum length of studies 
of systematic administration in man has been limited to thirty days. As a 
result of recently completed toxicity studies, it will be possible to extend 
this period which will permit systematic study of the effects of clearly de- 
fined doses of marihuana and its principal psychoactive ingredient, Delta-9- 
Tetrahydrocannabinol , over more lengthy periods of use. Such studies should 
include a wide range of areas of psychological and physiological functioning. 

The possibility of developing a marihuana antagonist - that is, a drug that 
will block or reverse the action of marihuana - is worth pursuing. Such a drug 
may be of value in treating cases of acute intoxication and preventing chronic 
intoxication. 



-163- 



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HV MARIHUANA AND HEALTH; 
5822 THIRD ANNUAL REPORT 
.M3U53 
1973 

Library 

P.O. Box 5180 
Baltimore, MD 21224 



3 1496 01031 6951 



DHEW Publication No. (ADM) 74-50 
Printed 1974 



IWin tollX T OF HEALTH, EIHIOl ION, AKII WELi <AKE 
IMHELIC HEALTH SEKVIEE 
jHOL.OKIM; AKIISE.ANlt AtENTAL HEALTH AOAMNISTKATION 
NATIONAL INSTITUTE OK IIIHIO AIHISE 






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