MARIJUANA ,

.cv~-^
AND HEALTH A v\

Ninth Report
to the U.S. Congress
From the Secretary of
Health and Human Services
1982
National Institute on Drug Abuse
5600 Fishers Lane
Rockville, Maryland 20857

i
Presented by Professor
Hamid Ghodse
 Public Domain Notice

All material appearing in this volume

is in the public domain and may be
reproduced or copied without permission
from the Institute. Citation of the
source is appreciated.

DHHS Publication No. (ADM)82-1216

Printed 1982
 Statement by
C. Everett Koop, M.D.
Surgeon General of the U.S. Public Health Service

As Surgeon General, I urge other physicians and profes-

sionals to advise parents and patients about the harmful
effects of using marijuana and to urge discontinuation
of its use.

The health consequences of marijuana use have been the

subject of scientific and public debate for almost 20
years. Based on scientific evidence published to date,
the Public Health Service has concluded that marijuana
has a broad range of psychological and biological
effects, many of which are dangerous and harmful to
health.

On March 24, Secretary Schweiker transmitted a report,

Marijuana and Health - 1982 , the ninth in a series, to
the U.S. Congress reviewing the health consequences of
marijuana use.

Among the known or suspected chronic effects of mari-

juana use are:

impaired short-term memory and slowed learning;

impaired lung function similar to that found in

cigarette smokers (indications are that more serious
effects may ensue following extended use);

decreased sperm count and sperm motility;

interference with ovulation and prenatal develop-

ment;

impaired immune response;

possible adverse effects on heart function; and

by-products of marijuana remaining in body fat for

several weeks with unknown consequences. The
 storage of these by-products increases the possibil-
ities for chronic effects as well as residual effects
on performance even after the acute reaction to the
drug has worn off.

I am especially concerned about the long-term develop-

mental effects of marijuana use on children and
adolescents, who are particularly vulnerable to the
drug's behavioral and physiological effects. The
"amoti vational syndrome" has been attributed by some to
prolonged use of marijuana by youth. The syndrome is
characterized by a pattern of loss of energy, diminished
school performance, harmed parental relationships, and
other behavioral disruptions. Though more research is
required to clarify the course and extent, in recent
national surveys up to 40 percent of heavy users report
that they observe some or all of these symptoms in
themselves.

The Public Health Service review of the health conse-

quences of marijuana supports this major conclusion of
the National Academy of Sciences' Institute of
Medicine:

What little we know for certain

about the effects of marijuana on
human heal th--and all that we have
reason to suspect--justif ies serious
national concern.

iv
 MARIJUANA AND HEALTH — 1982
Executive Summary

This year's report on Marijuana and Health, the ninth in

a series, is based primarily on two major 1981 scien-
tific reviews of this issue: the first undertaken by
the Institute of Medicine (IOM) of the National Academy
of Sciences; and the second carried out by the Canadian
Addiction Research Foundation for the World Health
Organization (WHO). Summaries of both of these reviews
are appended to this report.

The Department continues to believe that marijuana use

is a major puolic health problem in the United States.
Nearly one-quarter of the total American population has
used the drug, representing a 30-fold increase in use
over the past 20 years. Approximately half of those who
try the drug once go on to use it again; and the age of
onset of use has been steadily going down over the past
decade. At its peak, daily or nearly daily use of
marijuana involved more than one in ten high school
seniors, with daily use of marijuana now substantially
more common than daily use of alcohol among this age
group.

A great deal has been learned about both the acute and
chronic effects of marijuana use. Acute intoxication
with marijuana interferes with many aspects of mental
health functioning and poses a major impediment to
classroom performance. The drug also has serious acute
effects on perception and skilled performance, both of
which are involved in driving and a number of other
tasks. Among the known or suspected chronic effects
are: impaired lung functioning; decreased sperm counts
and sperm motility; interference with ovulation and
prenatal development; impaired immune response; and
possible adverse effects on heart function. There is
also increasing concern about the long-term develop-
mental effects of marijuana use on children and
adolescents, who are particularly vulnerable to the
drug's behavioral and physiological effects.

v
The ninth report also notes that the marijuana in use
today is considerably more potent than that previously
available. In fact, there has been a five-fold increase
in potency during the past 5 years. This change may
have a substantial impact on the effects felt by current
users of the drug.

The report recommends increased Federal research on

marijuana. There are specific needs in this area which
seem most pressing: (1) research on the effects of
marijuana on children and adolescents; (2) research on
other groups which may be at a higher than average risk
for adverse effects of marijuana use, e.g., women of
childbearing age or offspring of women who used mari-
juana during pregnancy; (3) large-scale epidemiological
research, including both cross-sectional and longitu-
dinal studies.

There have been some hopeful findings this past year,

most notably the decrease in marijuana use noted for the
third consecutive year in the National High School
Senior Survey. Nevertheless, the Department feels it
must maintain a high level of concern about this drug
and plans to continue its research and national preven-
tion efforts. Those efforts are beginning to bear
fruit, but much work remains to be done.

yi
 MARIJUANA AND HEALTH — 1982

This is the ninth in the series of reports to the

Congress on Marijuana and Health from the Secretary of
Health and Human Services, required by the Marijuana
Reporting Act (Title V, P.L. 91-296) As with earlier
.

versions, the continuing aim is to answer the question:

"What are the health implications of marijuana use for
Americans?"

This year's report is based primarily on two major

scientific reviews conducted in 1981. One was under-
taken by the Institute of Medicine (IOM) of the National
Academy of Sciences at the request of former Secretary
of Health, Education, and Welfare, Joseph Califano, and
was conducted under the supervision of the National
Institutes of Health. The other was carried out simul-
taneously by the Canadian Addiction Research Foundation
(ARF) for the World Health Organization (WHO). Depart-
ment scientists were invited observers at both reviews,
but the reports were done independently. The summaries
of both reviews are appended.

These two comprehensive reviews of available scientific

knowledge provide strong evidence that the use of mari-
juana is a serious public health concern. This is based
on the following conclusions:

°
Nearly a quarter of the total American population
have used the drug--a 30-fold increase in use over
the past 20 years (IOM Report, Chapter 2; Director,
NIDA, Testimony of 10/21/81). This is an unprece-
dented level of illegal drug use in this country.

Of those who try the drug once, about one-half

continue its use. Most users are adolescents and
young adults who are most vulnerable to its effects
(Main Findings of the National Survey 1979, p. 48).

The age of first use has declined progressively over

the last decade (IOM Report, Chapter 2).

1
 The drug is readily available and much more potent
marijuana than bef ore--potency has increased five-
fold in the past 5 years (Marijuana Research
Findings: 1980, p. 12).

°
Acute intoxication with marijuana interferes with
mental functioning; learning and thinking are
impaired. It is a marked impediment to classroom
performance (IOM Report, Chapter 6; ARF/WHO Report,
p. 23).

°
Marijuana produces serious acute effects on percep-
tion and skilled performance, which impairs such
everyday tasks as driving and other complex tasks
involving judgment or fine motor skills (IOM Report,
Chapter 6; ARF/WHO Report, pp. 24-25).

Daily or near daily use--20 times/month or more--

involved more than one in 10 high school seniors at
its peak in 1978. There is good evidence that even 4
years after graduation nearly 9 out of 10 daily users
continue use, half of them on a daily basis. Daily
use among high school seniors is more common than
daily alcohol use and is much more readily concealed
(IOM Report, Chapter 2).

°
A significant number of serious or potentially
serious chronic effects are known or suspected.
Known effects include impaired lung function similar
to that found in cigarette smokers. Indications are
that more serious effects such as cancer and other
lung disease may ensue following extended use (IOM
Report, Chapter 3; ARF/WHO Report, pp. 11-12).

Reproductive effects may prove to be serious. Pre-

liminary findings include decreases in sperm count
and sperm motility in humans (which may affect male
fertility), and interference with ovulation in female
monkeys (a possible basis for concern in girls and
young women). The active ingredients in marijuana
readily cross the pi acenta--the connection between
the developing fetus and the mother—and preliminary

2
 evidence suggests possible effects on prenatal
development' (IOM Report, Chapter 5; ARF/WHO Report,
P. 22).

°
Long-term or irreversible effects on adult intel-
lectual and social functioning are still uncertain.
However, there is increasing concern about the long-
term developmental effects of marijuana use on
children and adolescents, who are particularly at
risk from the drug's disruptive behavioral and
physiological effects (IOM Report; ARF/WHO Report,
p. 48).

Like cigarette smoking, marijuana use may have

deleterious effects on heart functioning, and these
effects may manifest themselves as the user group
ages (IOM Report, Chapter 3; ARF/WHO Report, V 8).

If marijuana-induced decreases in the body's immune

response, which have been found in animals, occur in
humans (present evidence is inconclusive), even a
modest decrease could have widespread public health
implications (IOM Report, Chapter 5; ARF/WHO Report,
P. 12).

Marijuana's by-products persist in body fat for

several weeks following use. This may mean a con-
tinued interference with bodily functioning, though
definitive evidence for prolonged effects is still
lacking (IOM Report, Chapter 1; ARF/WHO Report, p.
38).

Because of the brevity of the American experience with

marijuana and the limited amount of research that has
been done, particularly on the long-term effects of use,
there remain many unanswered or only partially answered
questions about marijuana which are noted by both scien-
tific reviews. There are other countries where certain
groups have used marijuana over long periods of time.
However, their mode of use is often different from
present American patterns of use; and the American
pattern--widespread use by large numbers of children,
adolescents, and females in a highly demanding

3
industrialized society—is unprecedented. There are
disturbing clinical reports* of behavioral disruption
and loss of conventional motivation related to marijuana
use. In addition, significant percentages of daily
users in nationwide surveys report the presence of
components of the amoti vational syndrome. Although such
reports are not easily confirmed by traditional scien-
tific research methods, the Department tends to place
more reliance on these clinical reports as confirmed by
users' self-perceptions reported in national surveys
than does the WHO or IOM report. Individuals who are
experiencing difficulties while growing up may be
attracted to marijuana or other drug use as a means of
"escape" from their developmental difficulties. Also
their drug use may in time contribute to further
developmental difficulties, including alienation and
lack of self-esteem. Membership in a drug-using
subgroup may further serve to consolidate such patterns.
The consistency of the clinical observations and the
self-perception gives considerable credence to the
occurrence of an "amotivational " syndrome among heavy
marijuana users even though rigorous scientific
demonstration of the specific role of marijuana in
causing the syndrome has not yet been elicited.

The IOM report summarizes evidence concerning possible

therapeutic effects of marijuana or its constituents in
treating several medical disorders, including most
notably glaucoma and the nausea induced by cancer chemo-
therapy. In each instance, the findings are described
as preliminary. It is reported that marijuana and
delta-9-THC often produce troublesome psychotropic or
cardiovascular side effects that limit their therapeutic
usefulness, particularly in older patients. It is
concluded that the greatest therapeutic potential

^National Institute on Drug Abuse. Marijuana and

Youth: Clinical Observations on Motivation and
Learning. DHHS Pub. No. (ADM)82-1 1 86
. Washington,
D.C.: Supt. of Docs., U.S. Govt. Print. Off., 1982.

4
probably lies in the use of synthetic analogues of
marijuana derivatives with higher ratios of therapeutic
to undesirable effects. It should be emphasized that
possible therapeutic benefits in no way modify the
significance of the negative health effects of
marijuana.

Future Directions

Both the IOM and the ARF/WHO reports advocate increased

research and make several recommendations. The
recommendation for an increasing Federal marijuana
research effort is in line with the increase in the
departmental cannabinoid research dollars during each of
the past 3 years. Both reports underscore:

1. The critical need for research on the effects of

marijuana on children and adolescents who are
undergoing rapid development and may be particularly
vulnerable to the disruptive behavioral and
physiological effects of marijuana use.

2. The need to expand present research efforts to

include other groups which may be at a higher than
average risk, such as women in the childbearing
years. Such research should include the study of
the offspring of women who have used marijuana
during pregnancy. Other groups include those with
pre-existing medical or psychological conditions
that may be worsened by marijuana use (e.g., .

cardiovascular disorders and mental disorders).

3. The emerging need for large-scale epidemiological

research to better monitor drug use and its effects
in both general and special populations such as
prepubertal children and adolescents. These should
be both cross-sectional (i.e., studies of groups at
a particular point in time) and longitudinal. The
latter provide base rate comparisons against which
to assess possible deleterious effects of marijuana
use. Such studies may yield important clues as to
why some users become intensely involved with
marijuana and other drugs while others discontinue

5
 .

use, and to possible methods for preventing involve-

ment. Costs of such studies may be reduced by
employing already existing samples that have been
studied longitudinally or by collaborative efforts
with other groups and agencies.

In view of the high cost of large-scale prospective user

studies, especially at a time when patterns of use are
rapidly changing, the Department hopes to emphasize well
designed retrospective studies using previously studied
groups as the data base. It is anticipated that studies
of marijuana use with particular emphasis on those areas
outlined by the two review groups will become a larger
part of the total departmental research effort.

It undoubtedly require many years of research in

will
the laboratory, in the clinic, and through modern
epidemiological methods involving large populations to
define adequately the parameters of risk associated with
marijuana use. But if the history of abused drugs
demonstrates anything, it is that the initial optimism
that so often accompanies the discovery (or rediscovery)
of the "pleasure potential" of a drug is soon followed
by the more gradual recognition that the transient
"pleasure" is bought at enduringly high individual and
societal cost. While our understanding of marijuana is
still far from complete, the reviews abstracted here
make clear that marijuana is unlikely to be an
exception

In recent years, the Department has emphasized its

concern about the increasing use trends and the evidence
of possible long-term health consequences of marijuana
use in this country. It is gratifying to be able to
report that 1981 was the third consecutive year in which
the National High School Senior Survey showed a decrease
in marijuana use by this key age group, and that the
drop in daily use was greater this year than in both
previous years. Nevertheless, we must maintain a high
level of concern, despite this encouraging reversal of
trend. It is believed that overall drug use levels by
American teenagers continue to be close to or above the
highest use levels in any other Western developed

6
country. The Department will therefore continue that
combination of research and national prevention efforts
which, on the basis of recent decreases in incidence and
prevalence, is believed to be effective.

7
 Appendix A

SUMMARY

Report of an Addiction Research Foundation/World Health

Organization Scientific Meeting on Adverse Health and
Behavioral Consequences of Cannabis Use

Toronto, Ontario
March 30 - April 3, 1981

The acute use of moderate doses of cannabis produces a

state of intoxication. This is associated with a dose-
related impairment of the ability to drive a car or
operate complex machinery. In some situations, the user
may not feel the desired euphoric state but rather may
experience a short-lived dysphoric reaction which can
range in intensity and character from mild anxiety to an
acute psychosis. Other acute physiological effects are
also transient and do not appear to be of major signifi-
cance in individuals with no pre-existing disease.

Intermittent use of low-potency cannabis is not

generally associated with obvious symptoms of toxicity.
Daily or more frequent use, especially of the highly
potent preparations, can produce a chronic intoxication
which may take several weeks to clear after drug use is
discontinued. The seeming inconsistency of this obser-
vation throughout the world may reflect differing
exposures to THC because of the large variation of
potencies and smoking techniques, as well as different
cultural preferences for the route of administration.

Respiratory toxicity is observed in heavy users and is

probably related to smoke components other than THC.
Therefore its severity may depend more on the smoking
techniques employed by the user and the combustion
properties of the material, than on the THC content.

9
 .

Cannabis effects on the hormonal, reproductive, and

immunological status of these users is, as yet,
unclear

Chronic administration of cannabis results in the

development of tolerance to a wide variety of the acute
drug effects in both humans and experimental animals.
Though scientific opinion is more divided on the
question of dependence on cannabis, there is now
substantial evidence that at least mild degrees of
dependence, both psychological and physical, can occur.

Some individuals may be particularly susceptible to the

effects of cannabis for a variety of reasons. Adoles-
cents who are undergoing rapid developmental change and
elderly populations with decreased rates of drug
metabolism, increased prevalence of disease and a more
conservative and less flexible mental set may be more
sensitive to the effects of cannabis and other drugs.
The symptoms of patients with a variety of diseases
including various forms of mental illness, diabetes,
cardiovascular disease or epilepsy may be exacerbated by
cannabis use. Interactions with a variety of substances
including tobacco and alcohol may also potentiate the
observed effects.

The epidemiological studies necessary to assess the

frequency of adverse effects and to relate their occur-
rence to factors such as potency and amount of cannabis
used, length of exposure, set and setting have not, as
yet, been conducted. The low prevalence of adverse
effects observed in field studies of small numbers of
heavy users suggests that the adverse effects described
in many of the clinical reports occur relatively
infrequently in these carefully selected populations.
Given that millions of individuals are now using the
drug, even relatively infrequent but serious adverse
consequences could be of public health significance.

The results of experimental studies in animals have

consistently demonstrated toxicity at doses comparable
to those consumed by the human who smokes cannabis

10
several times per day. Respiratory toxicity, CNS
dysfunction, endocrinological di sturbances, reproductive
deficits, and immunosuppression have all been observed
after treatment with THC or cannabinoids in experimental
animals. Most, but not all, of these effects disappear
when treatment is discontinued.

In vitro studies have also been used to demonstrate

cannabis-induced cytotoxicity. The results of these
experiments are, for the most part, qualitatively
consistent with the in vivo observations, and may
provide valuable information about the mechanisms of
action of cannabinoids and other plant components or
products of pyrolysis.

11
 Appendix B

SUMMARY

Report of a Study by a Committee of the Institute of

Medicine, Division of Health Sciences Policy,
on Marijuana and Health

Washington, D.C.
December 1981

The Institute of Medicine (IOM) of the National Academy

of Sciences has conducted a 15-month study of the
health-related effects of marijuana, at the request of
the Secretary of Health and Human Services and the
Director of the National Institutes of Health. The IOM
appointed a 22-member committee to:

analyze existing scientific evidence bearing on

the possible hazards to the health and safety of
users of marijuana;

analyze data concerning the possible therapeutic

value and health benefits of marijuana;

°
assess Federal research programs in marijuana;

identify promising new research directions, and

make suggestions to improve the quality and use-
fulness of future research; and

°
draw conclusions from this review that would
accurately assess the limits of present
knowledge and thereby provide a factual, scien-
tific basis for the development of future
government policy.

This assessment of knowledge of the health-related

effects of marijuana is important and timely because
marijuana is now the most widely used of all the illicit

13
drugs available in the United States. In 1979, more
than 50 million persons had tried it at least once.
There has been a steep rise in its use during the past
decade, particularly among adolescents and young adults,
although there has been a leveling off in its overall
use among high school seniors in the past 2 or 3 years
and a small decline in the percentage of seniors who use
it frequently. Although substantially more high school
students have used alcohol than have ever used mari-
juana, more high school seniors use marijuana on a daily
or near-daily basis (9 percent) than use alcohol that
often (6 percent). Much of the heavy use of marijuana,
unlike alcohol, takes place in school, where effects on
behavior, cognition, and psychomotor performance can be
particularly disturbing. Unlike alcohol, which is
rapidly metabol ized and eliminated from the body, the
psychoactive components of marijuana persist in the body
for a long time. Similar to alcohol, continued use of
marijuana may cause tolerance and dependence. For all
these reasons, it is imperative that we have reliable
and detailed information about the effects of marijuana
use on health, both in the long and short term.

What, then, did we learn from our review of the

published scientific literature? Numerous acute effects
have been described in animals, in isolated cells and
tissues, and in studies of human volunteers; clinical
and epidemiological observations also have been
reported. This information is briefly summarized in the
following paragraphs.

Effects on the Nervous System and on Behavior

We can say with confidence that marijuana produces acute

effects on the brain, including chemical and electro-
physiological changes. Its most clearly established
acute effects are on mental functions and behavior.
With a severity directly related to dose, marijuana
impairs motor coordination and affects tracking ability
and sensory and perceptual functions important for safe
driving and the operation of other machines; it also
impairs short-term memory and slows learning. Other

14
acute effects include feelings of euphoria and other
mood changes, but there also are disturbing mental
phenomena, such as brief periods of anxiety, confusion,
or psychosis.

There is not yet any conclusive evidence as to whether

prolonged use of marijuana causes permanent changes in
the nervous system or sustained impairment of brain
function and behavior in human beings. In a few
unconfirmed studies in experimental animals, impairment
of learning and changes in electrical brain-wave
recordings have been observed several months after the
cessation of chronic administration of marijuana.
Widely cited studies purporting to demonstrate that
marijuana affects the gross and microscopic structure of
the human or monkey brain are not convincing, in the
judgment of the committee; much more work is needed to
settle this important point.

Chronic relatively heavy use of marijuana is associated

with behavioral dysfunction and mental disorders in
human beings, but available evidence does not establish
if marijuana use under these circumstances is a cause or
a result of the mental condition. There are similar
problems in interpreting the evidence linking the use of
marijuana to subsequent use of other illicit drugs, such
as heroin or cocaine. Association does not prove a
causal relation, and the use of marijuana may merely be
symptomatic of an underlying disposition to use psycho-
active drugs rather than a "stepping stone" to involve-
ment with more dangerous substances. It is also
difficult to sort out the relationship between use of
marijuana and the complex symptoms known as the
amotivational syndrome. Self-selection and effects of
the drug are probably both contributing to the
motivational problems seen in some chronic users of
marijuana.

Thus, the long-term effects of marijuana on the human

brain and on human behavior remain to be defined.
Although we have no convincing evidence thus far of any
effects persisting in human beings after cessation of

15
drug use, there may well be subtle but important
physical and psychological consequences that have not
been recognized.

Effects on the Cardiovascular and Respiratory Systems

There is good evidence that the smoking of marijuana

usually causes acute changes in the heart and circu-
lation that are characteristic of stress, but there is
no evidence to indicate that a permanently deleterious
effect on the normal cardiovascular system occurs.
There is good evidence to show that marijuana increases
the work of the heart, usually by raising heart rate
and, in some persons, by raising blood pressure. This
rise in workload poses a threat to patients with
hypertension, cerebrovascular disease, and coronary
atherosclerosis.

Acute exposure to marijuana smoke generally elicits

bronchodilation; chronic heavy smoking of marijuana
causes inflammation and pre-neopl astic changes in the
airways, similar to those produced by smoking of
tobacco. Marijuana smoke is a complex mixture that not
only has many chemical components (including carbon
monoxide and tar) and biological effects similar to
those of tobacco smoke, but also some unique ingredients
of its own. This suggests the strong possibility that
prolonged heavy smoking of marijuana, like tobacco, will
lead to cancer of the respiratory tract and to serious
impairment of lung function. Although there is evidence
of impaired lung function in chronic smokers, no direct
confirmation of the likelihood of cancer has yet been
provided, possibly because marijuana has been widely
smoked in this country for only about 20 years, and data
have not been collected systematically in other
countries with a much longer history of heavy marijuana
use.

Effects on the Reproductive System and on Chromosomes

Although studies in animals have shown that delta-9-THC

(the major psychoactive constituent of marijuana) lowers

16
the concentration in blood serum of pituitary hormones
(gonadotropins) that control reproductive functions, it
is not known if there is a direct effect on reproductive
tissues. Delta-9-THC appears to have a modest
reversible suppressive effect on sperm production in
men, but there is no proof that it has a deleterious
effect on male fertility. Effects on human female
hormonal function have been reported, but the evidence
is not convincing. However, there is convincing
evidence that marijuana interferes with ovulation in
female monkeys. No satisfactory studies of the relation
between use of marijuana and female fertility and child-
bearing have been carried out. Although delta-9-THC is
known to cross the placenta readily and to cause birth
defects when administered in large doses to experimental
animals, no adequate clinical studies have been carried
out to determine if marijuana use can harm the human
fetus. There is no conclusive evidence of terato-
genicity in human offspring, but a slowly developing or
low-level effect might be undetected by the studies done
so far. The effects of marijuana on reproductive
function and on the fetus are unclear; they may prove to
be negligible, but further research to establish or rule
out such effects would be of great importance.

Extracts from marijuana smoke particulates ("tar") have

been found to produce dose-related mutations in
bacteria; however, delta-9-THC, by itself, is not
mutagenic. Marijuana and delta-9-THC do not appear to
break chromosomes, but marijuana may affect chromosome
segregation during cell division, resulting in an
abnormal number of chromosomes in daughter cells.
Although these results are of concern, their clinical
significance is unknown.

The Immune System

Similar limitations exist in our understanding of the

effects of marijuana on other body systems. For
example, some studies of the immune system demonstrate a
mild, immunosuppressant effect on human beings, but
other studies show no effect.

17
Therapeutic Potential

The committee also has examined the evidence on the

therapeutic effects of marijuana in a variety of medical
disorders. Preliminary studies suggest that marijuana
and its derivatives or analogues might be useful in the
treatment of the raised intraocular pressure of glau-
coma, in the control of the severe nausea and vomiting
caused by cancer chemotherapy, and in the treatment of
asthma. There also is some preliminary evidence that a
marijuana constituent cannabidiol ) might be helpful in
(

the treatment of certain types of epileptic seizures, as

well as for spastic disorders and other nervous system
diseases. But in these and all other conditions, much
more work is needed. Because marijuana and delta-9-THC
often produce troublesome psychotropic or cardiovascular
side-effects that limit their therapeutic usefulness,
particularly in older patients, the greatest therapeutic
potential probably lies in the use of synthetic
analogues of marijuana derivatives with higher ratios of
therapeutic to undesirable effects.

The Need for more Research on Marijuana

The explanation for all of these unanswered questions is

insufficient research. We need to know much more about
the metabolism of the various marijuana chemical com-
pounds and their biologic effects. This will require
many more studies in animals, with particular emphasis
on sub-human primates. Basic pharmacologic information
obtained in animal experiments will ultimately have to
be tested in clinical studies on human beings.

Until 10 or 15 years ago, there was virtually no

systematic, rigorously controlled research on the human
health-related effects of marijuana and its major con-
stituents. Even now, when standardized marijuana and
pure synthetic cannabinoids are available for experi-
mental studies, and good qualitative methods exist for
the measurement of delta-9-THC and its metabolites in
body fluids, wel 1 -designed studies on human beings are
relatively few. There are difficulties in studying the

18
clinical effects of marijuana in human beings, partic-
ularly the effects of long-term use. And yet, without
such studies the debate about the safety or hazard of
marijuana will remain unresolved. Prospective cohort
studies, as well as retrospective case-control studies
would be useful in identifying long-term behavioral and
biological consequences of marijuana use.

The Federal investment in research on the health-related

effects of marijuana has been small, both in relation to
the expenditure on other illicit drugs and in absolute
terms. The committee considers the research partic-
ularly inadequate when viewed in light of the extent of
marijuana use in this country, especially by young
people. We believe there should be a greater investment
in research on marijuana, and that investigator-
initiated research grants should be the primary vehicle
of support.

The committee considers all of the areas of research on

marijuana that are supported by the National Institute
on Drug Abuse to be important, but we did not judge the
appropriateness of the allocation of resources among
those areas, other than to conclude that there should be
increased emphasis on studies in human beings and other
primates. Recommendations for future research are
presented at the end of Chapters 1-7 of this report.

Concl usions

The scientific evidence published to date indicates that

marijuana has a broad range of psychological and bio-
logical effects, some of which, at least under certain
conditions, are harmful to human health. Unfortunately,
the available information does not tell us how serious
this risk may be.

Our major conclusion is that what little we know for

certain about the effects of marijuana on human
health--and all that we have reason to suspect--
justifies serious national concern. Of no less concern
is the extent of our ignorance about many of the most
basic and important questions about the drug. Our

19
major recommendation is that there be a greatly intensi-
fied and more comprehensive program of research into the
effects of marijuana on the health of the American
people.

For information on obtaining copies of the full reports

on which Marijuana and Health--1982 is based, contact
the Addiction Research Foundation, Toronto, ON, Canada
for the Report on Cannabis Use , and the National Academy
Press, 2101 Constitution Avenue, N.W., Washington, D.C.
20418 for the Institute of Medicine's Marijuana and
Health.

20 * U.S. GOVERNMENT PRINTING OFFICE: 1982-36 1-166:388

 *

DHHS Publication No. (ADM) 82-1216

Printed 1982
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Alcohol, Drug Abuse, and Mental Health Administration