SUMMARY

In this, the first detailed report to the Congress on Marihuana and Health, an attempt has been ma de to accurately describe the present state of. our scientific knowledge concerning this issue. Not unlike a rather elaborate jigsaw puzzle, however, there are many research "pieces" whose relation to one another is not obvious. Moreover, many of the most important pieces that are required are not yet available. Some of the technical data that have been accumulated remain obscure for the present, particularly in providing a picture comprehensible to the layman. The ultimate meaning of past, present and future research will only become clearer as the various parts can be related to an emerging whole. .

The purpose of this summary is to try to translate the present disparate elements into as reasonable an answer as can currently be framed to the question : What are the health implications of marihuana use for the American people? It does not attempt to evaluate broader legal, economic or social issues including the consequences of law enforcement for personal marihuana use even though they are important and must be considered in a complete discussion of the overall problem.

As we examine the drug in its various natural and synthetic forms, it becomes evident that the deceptively simple question posed is really highly complex in that marihuana is not a single, simple substance of uniform type. It consists of varying mixtures of different parts of the plant, Cannabis sativa, with psychoactive properties ranging from virtually nonexistent to decidedly hallucinogenic in its stronger forms and at higher doses. Unfortunately, much of the discussion in lay and sometimes scientific forums ignores this very basic and important fact. Most. of our American experience has been limited to the widespread relatively infrequent use of a rather weak form of marihuana. Early research dealing with the drug is inevitably faulted by the fact that it is difficult to be certain just what potency material was involved and at what dose level. Although the principal active ingredient in the plant is thought to be Delta-9-tetrahydrocannabinol, much remains to be learned about the chemistry of marihuana and related substances.

Even the form in which the drug is consumed may make a difference in the consequences of use. It is quite possible, for example, that when smoked the material taken into the body differs significantly from orally consumed drug. The route of absorption, whether through the lungs or the digestive tract, may also make a significant difference in the consequences of use.

Virtually all of the American data indicate that use of marihuana has rapidly increased over the past several years. While the number of those who have tried the substance at some point in their lives re- mains a minority of the population it is continuing to increase rapidly. In some high school or college settings it is virtually certain that a majorty have at least tried marihuana. By the end of 1970 about one college student in seven was using it on a weekly or more frequent basis. High school use has generally lagged behind that of colleges and universities, although in areas of high use as many as a third to a half have experimented with it. While comparable data are not available for non-school attending youth, there is reason to believe that their levels of use are at least comparable and for school dropouts are probably higher. In some west coast high schools which have had relatively high levels of use there is evidence that the increase in use may be decelerating and even declining. The likelihood of continuing, per- sistent use over an extended period of time by large numbers s not known at the present time.

Middle class users have tended to be individuals from higher income families attending larger, non-religiously affiliated urban universities rather than small, denominational colleges. However, as the number of users increases they become less clearly distinguishable from the more general youthful population. As use becomes more widespread there is reason to believe still younger as well as older populations are becoming involved.

Rather than being restricted to our own affluent society, marihuana use as a recent source of concern is a problem in many countries of the world. In at least three other English-speaking countries this concern has led to the appointment of commissions to examine the problem and to issue reports (Canada, England and New Zealand). While in 1956 the United Nations Commission of Narcotic Drugs estimated that over two hunded million people made regular use of cannabis, it is very likely the number is now substantially ff

The bulk of this report makes clear thaalthough there is much yet to be learned about cannabis, there is a substantial body of information presently available. Much of it is however, of only limited immediate relevance to the question of the is, health implications of use.

SUBJECTIVE EFFECTS

A range of studies have been conducted of the drug's acute effects. As is true of other drugs, generally the effects are closely related to the amount that is consumed. There is general agreement that at the usual levels of social usage the typical subjective effects are : Alteration of time and space perception, sense of euphoria, relaxation, well being and disinhibition, dulling of attention, fragmentation of thought, impaired immediate memory, an altered sense of identity, exaggerated laughter and increased suggestibility. Other less common effects are dizziness, a feeling of lightness, nausea, and hunger. As doses higher than the typical social dose are consumed more pronounced thought distortions may occur including a disrupted sense of one's own body, a sense of personal unreality, visual distortions sometimes hallucina- tions and paranoid thinking. The more marked distortions of reality or psychotic-like symptoms become increasingly common if the dosage used becomes extremely high. Most users smoke to the point of "high" which they find pleasurable and at which they are able to control the i effect. It s, however, difficult to predict individual reactions. Rarely, individuals may become quite anxious or panicky on even low doses. When eaten, effects are less predictable and more difficult for the user to control.

In addition to the amount of the drug that is consumed, the set and setting of use are important factors in determining marihuana's subjective effects. Set refers to the attitudes mood, expectations and beliefs which the individual brings • to the drug using experience. Setting represents the external circumstances surrounding the experience. Thus a relatively emotionally neutral laboratory setting may evoke very different responses at a given dose level than might a more typical settlep! of social nsage surrounded by other druo; users. A situation in which the individual is depressed or apprehensive about the drug's effects differs markedly from one in which the user is more sanguine and looks forward to the drug experience with eager anticipation. Degree of personality integration, psychological rigidity and the presence or absence of psychopathology are all important contributors to one's subjective reactions to marihuana or other psychoactive drugs.

These psychological aspects also play a role in what is often referred to as the 'placebo effect." The placebo effect is the response to a substance based not on its pharmacological activity but on the totality of expectations brought about by the set and setting of use. It is not uncommon for individuals consuming a psychoactively inert material to experience subjective effects which they erroneously attribute to an active drug. The placebo effect may complicate results in a laboratory setting. Particularly at low doses it may be difficult to be certain to what extent an effect is .brought about by the.drug itself or placebo effects.

PHYSIOLOGICAL EFFECTS OF ACUTE MARIHUANA USE

Physiological changes accompanying marihuana use at typical levels of American social usage are relatively few. One of the most consistent is an increase in pulse rate. Another is a reddening of the eyes at the time of use. Dryness of the mouth and throat are uniformly reported. Although enlargement of the pupils was an earlier impression, more careful study has indicated that this does not occur. Blood pressure effects have been inconsistent. Some have reported slightly lowered blood pressure while others have reported small increases. Basal metabolic rate, temperature, respiration rate, lung vital - capacity and a wide range of other physiological measures are generally tmchanged over a relatively wide dosage range of both marihuana and the synthetic form of the principal psycho-active agent, Delta-29--THC.

Neurological examinations consistently reveal no major abnormalities during marihuana intoxication. However, some investigators have found a small decrease in leg, hand and finger strength at higher dosages. Some decrease in hand steadiness and the ability to maintain balance occurs as dosages increase. Although users often report enhanced sensory awareness in the drugged state, objectively measurable improvements in visual acuity, brightness discrimination, touch discrimination, auditory acuity, olfactory threshold or taste discrimination have not been found. Some small changes in electroencephalograph (EEG) findings have been detected but the significance of these results is in doubt.

From the standpoint of lethality, cannabis products must be counted among the safer of the drugs in widespread use. Death directly at- tributable to the drug's effects is extremely rare even at very -high doses.

ACUTE PSYCHOTIC " EPISODES

Acute psychotic episodes precipitated by marihuana intoxication have been reported by a number of inveStigators. These appear to occur infrequently, usually at high dosages, but may occur, even at levels of social usage, in particularly susceptible individuals. Heightened susceptibility appears to be more likely in those who have previously had a marginal psychological adjustment especially in the presence of excessive stress.

INTELLECTUAL AND MOTOR PERFORMANCE

Changes in time sense have definitely been shown to take place during marihuana intoxication. There is a tendency to overestimate the pas-, sage of time particularly while engaged in some activity.
A wide range of tests of intellectual functioning and of psychomotor performance (the ability to precisely coordinate sensory pereeption and muscular performance) have been carried out under conditions of intoxication. As might be expected, the degree of impairment is dose related. It also varies during the period of intoxication.

Generally, the more complex and demanding the task to be performed the greater is the degree of impairment. Simple and very familiar tasks such as reciting the alphabet or repeating a brief series of numbers are least likely to be affected at relatively low dose levels. As the task becomes more complicated, however, decrements in performance do become apparent. Inexperienced users tend to show greater decrements than do experienced marihuana users. -

Because of the importance the automobile assumes in our society, the effect of marihuana on driving performance is of fundamental interest. One widely reported finding using a driver simulator was that the performance of marihuana using drivers was equal on the average to that of a non-intoxicated control group. It is, however, important to note that this was based on a single study of intoxicated drivers under test conditions that might be expected to be highly motivating. In addition, half the drivers in the experimental group did more poorly than did the control group. This suggests that the ability to compensate for the effects of marihuana—to suppress the "high"—may differ markedly from individual to individual. The relevance of this work to more typical driving conditions is not known.

It is noteworthy that in another series of studies not directly concerned with driving, marihuana intoxicated subjects consistently answered, "No !" when asked, "Do you think you could drive a car now?". Preliminary results of a study of attention skills believed to be among the best predictors of actual driving performance have shown performance decrements under marihuana use similar to those found when drivers have consumed moderate amounts of alcohol. Additional much needed research on driver performance and other complex motor tasks is currently in progress.

Marihuana users consistently report that their short-term and immediate memory while under the influence of the drug is interfered with. Systematic research evaluation generally confirms this. More complex functions such as learning a -number code, using such a code for encoding a series of numbers, understanding a written paragraph or spoken speech are all interfered with even at the moderate levels of typical American social usage. This is believed to reflect difficulty in retaining, coordinating and indexing over time those memories, per- ceptions and expectations demanded by the task being performed.

MARIHUANA AND BIRTH DEFECTS

A basic concern with any drug substance coming into wide use is the possibility that it may affect fetal mortality or fetal development (i.e. may he teratogenic) in such a way as to bring about abnormal offspring of pregnant users. It may also conceivably affect unborn generations by causing chromosomal changes (i.e. may be mutagenic) that persistently alter the genetic heritage. Thus far there is little evidence that marihuana or related materials do this. While preliminary studies of the effects of injecting relatively large quantities of cannabis or related substances have found some indication of fetal abnormalities in rats, other researchers have been unable to duplicate such findings. There is no evidence to suggest that marihuana use in humans affects fetal development. Despite the present absence of such evidence, it is obviously unwise for anyone to use any drug of unknown teratogenic or mutagenic properties during the child bearing years. Use during pregnancy is particularly unwise.

EFFECTS OF LONG-TERM CHRONIC USE

While a good deal is known about the acute effect of cannabis use and the laboratory findings to date generally correlate well with user reports, much less is known about the implications of long term chronic use. Marihuana has been administered to humans for extended periods in only a few experimental studies. The periods of administration have been limited to at most a few weeks. In addition, early studies of both acute and chronic use have provided no indication of the exact amounts of psychoactive material involved and so it is difficult to compare earlier findings with those of contemporary research. During a period of just under six weeks, one investigator found only small physiological changes in a group of prisoners who were permitted to consume the drug freely in whatever quantity they chose. A daily mean of 17 cigarettes each was consumed. There was some mild confusion during the period of continued intoxication with slight impairment of performance on general intelligence testing during the period. While mild changes in electroencephalograph findings were found, these returned to normal five days after discontinuance of the drug. There was no evidence of withdrawal effects (i.e. physical symptoms precipitated by discontinuance of the drug) after this duration of use.

It should be emphasized that early attempts at evaluating the effects of long-term use of cannabis suffer from multiple scientific defects. Whether they tend to indict or to absolve cannabis from causing chronic physical or psychosocial consequences, it is difficult to be certain of the validity of their observations. The Indian Hemp Commission Report, for example, although a careful, systematic study for its day (the 1890's), can hardly be regarded as meeting modern epidemiological research standards. Subsequent studies such as those of the group appointed by the then Mayor LaGuardia in New York can also be easily faulted for their scientific deficiencies. While psychoses presumably resulting from heavy cannabis use have been reported, these studies do not generally meet modern scientific standards.

The fact that there are many worldwide reports of heavy, chronic cannabis use resulting in loss of conventional motivation and in social indifference is of particular interest in that there are now some reports of somewhat similar findings among American heavy users of marihuana. Unfortunately, American use patterns are frequently contaminated by the use of other drug substances, making interpretation difficult. It is not certain to what degree this "amotivational syndrome" is the result of marihuana use per se or of a tendency for those who lack conventional motivation to find drugs unusually attractive. If one confines his use of the term to a description of the present American scene one must conclude that present evidence does not permit the establishment of a causal relationship between marihuana use and the amotivational syndrome. There is, however, increasing evidence that frequent, heavy marihuana use is correlated with a loss of interest in conventional goals and the development of a kind of lethargy. Research in humans is being conducted in an attempt to determine to what extent this observed correlation is due to an alteration in brain functioning.

The issue of long-term mental deficit is an exceedingly complex one. The lack of sufficiently sophisticated methodology may be crucial. The problem of determining harmful effects of chronic drug use and especially psychological harm is very difficult. Unless the type of deficit is distinctive or dramatic, it is likely that the same symptoms will be exhibited by many non-drug users. Furthermore, if the harm done to the user is not so gross as to be noticeable in a higher percentage of users, it may readily be attributed to such other factors as poverty or poor nutrition. Tobacco furnishes an apt example of the difficulties encountered in determining even the physical hazards of use. It was only after many years of use by a substantial segment of the population that the role of smoking in the development of various types of diseases was recognized. It should be noted, that concern has been expressed that marihuana when smoked in large quantities might be expected to have similar carcinogenic effects to those associated with cigarette smoking. There is, however, no present evidence to suggest that marihuana is cancer-producing.

MARIHUANA AND THE USE OF OTHER DRUGS

It is generally conceded that marihuana use does not necessarily lead directly to the use of other drugs. On a worldwide basis there is little evidence of a progression from the use of marihuana to that of opiates or hallucinogens. However, those who find use of marihuana highly attractive, may also be attracted to the use of other drug substances which may be popular among their peers. These may include stronger hallucinogens, amphetamines and the opiates. While it is true that a high percentage of heroin addicts have used marihuana as well, most marihuana users both here and abroad do not appear to be attracted to the use of heroin.

FUTURE RESEARCH DIRECTIONS

It is evident that much remains to be learned about marihuana, hashish and related materials. Little is as yet known about the implications of chronic use particularly at lower dose levels and less frequent intervals. Although much can be learned from animal research, in the final analysis the most crucial information with respect to long-term human use can only be obtained by careful observations of chronically using groups here and abroad. Such research is currently being carried out.

It is important that we learn more about the possible interactions between marihuana and a wide range of other drugs. These include not only such drug substances as caffeine, tobacco and alcohol, but also other drugs of abuse and a wide spectrum of therapeutically employed drugs. As use of marihuana comes to include a wider spectrum of the population it is important that we learn its effects on those whose physiological functioning is to some degree impaired or who suffer from physical or psychological disabilities. Such effects must be studied over a wide dosage range and in various use patterns.

From a psychosocial point of view it is essential that we come to better understand the different patterns of drug use, their implications for social functioning and those factors which contribute to such use. These include parental attitudes, child rearing practices and peer pressures as well as those aspects of subcultural and cultural practices that may affect use. Finally, it is imperative that we determine what are the more effective prevention and education techniques that may serve to avert drug abuse of all types including that of marihuana.