Health Protection Branch

One of the major areas of concern surrounding cannabis pertains to its physiological and psychological effects, especially under conditions of heavy or prolonged use. Unfortunately, several important hypotheses have only begun to be explored, the scientific literature is riddled with inconsistent, methodologically questionable and unreplicated research, and North American-based long-term studies have yet to commence. Further, in some areas the proponents and opponents of cannabis law reform are locked in a prolonged and unproductive debate as to the meaning, significance and epidemiological implications of reported effects. As Griffith Edwards (1974:8) has commented: "in this polarized situation, objectivity becomes the casualty."

For the past decade, however, there has been an intensive international effort to determine what, if any, biomedical liabilities result from the use of cannabis. There remains much to be learned, but a considerable body of reliable knowledge of cannabis effects — adverse and otherwise — has accumulated. A review of these materials for the Health Protection Branch has been prepared by Dr. Leo Hollister, a California pharmacologist and one of a very small number of universally respected researchers in this field. We have also received advice and assistance in this area, especially as it relates to the Canadian context, from Dr. Ralph Miller, former Research Director of the Le Dain Commission of Inquiry into the Non-Medical Use of Drugs.

The evidence to date suggests that cannabis is relatively safe, but we must proceed on the assumption that it is not a unique drug in having no detrimental effects on health. Indeed, there are a number of possible health hazards which must be addressed.

Recent controlled field studies (all of which were conducted outside of North America) have generally failed to detect any major health consequences from long-term heavy cannabis use, but in certain circumstances the research techniques were too limited and the samples too small for accurate epidemiological predictions regarding unusual or statistically rare conditions. If cannabis is at all like alcohol or tobacco in its health hazards, broader-based epidemiological studies will be necessary before any final conclusions can be reached in certain areas.

Since there is little evidence of any significant health problems caused by moderate use of cannabis by normal young adults, attention in this review is placed primarily on possible effects of heavy, chronic use, and on use by particular subgroups of Canadian society who may have specific susceptibilities to any potential health problems. Impairment of psychomotor functioning, and its relationship to the safe operation of motor vehicles, is one issue of major importance to public health, but discussion of this problem will be deferred to a later section on safety-related concerns associated with cannabis use. First, we will focus on physiological effects. Later in this section, we will deal with the psychological and mental health aspects of cannabis use.

It seems to be generally agreed that the most likely health problem associated with cannabis use derives from its most common mode of administration (smoking) and the consequent risk of bronchial or pulmonary damage. It appears that heavy cannabis use may have effects similar to tobacco in this regard. This problem is especially exacerbated by the additional risk that some samples of marijuana may be contaminated by paraquet, an herbicide which may be extremely toxic when inhaled. Consequently, cannabis smoking by persons with impaired pulmonary function appears to be hazardous; frequent, chronic use of the drug in this way should be avoided. However, at present it is much more difficult to find evidence of clinically important pulmonary insufficiency among cannabis smokers than for example, among those who regularly smoke tobacco.

Concern about other probable health hazards is primarily focused on particular subgroups of society. The acute effects of cannabis, including increased heart rate and other ordinarily minor cardiovascular effects may have deleterious consequences for those suffering from arteriosclerosis of the coronary arteries, congestive heart failure or other cardiovascular disorders. Possible effects on the hepatic enzyme system may be problematic for persons with preexisting liver disorders.

There are other areas where the degree of risk involved in cannabis use is less certain than in those discussed above, but nonetheless deserve careful appraisal. Three of these again apply to special population groups: pubescent boys, pregnant women and diabetics.

Concern about cannabis use by young boys initially arose from some contradictory clinical observations of decreased serum testosterone levels in male cannabis smokers. Experimental studies have been similarly suggestive, but inconsistent. Although the evidence is not clear and its potential significance yet to be determined, the limited endocrine changes indicated, although probably of relatively little consequence in adults, could be of major importance in the prepubertal male.

Cannabis, like many other drugs, crosses the placental barrier, and although there is no demonstrated association between its use during pregnancy and fetal abnormalities, such occurrences, if they exist, are likely to be statistically rare and might easily be missed. Use during pregnancy should therefore be discouraged, although, as Dr. Hollister has noted, the "...current admonition against using cannabis during pregnancy is based more on ignorance than on definite proof of harm."

It has been suggested that large doses of THC might aggravate diabetes through deterioration of glucose tolerance. Such a relationship has not been clinically demonstrated, but the paucity of clinical evidence may be due to the relatively low doses commonly consumed by users or to some development of tolerance to this particular pharmacologic effect.

Other hypothesized, but so far unresolved, health hazards apply to the cannabis-using population as a whole. Impairment of cell-mediated immune responses has been suggested by some studies, but the experimental evidence is inconsistent and greater disease susceptibility in cannabis smokers has not been observed. . If such reductions do occur, they may well be transient, or so small that the capacity of the body to resist challenge is not sufficiently depleted to be cause for concern. The issue, nonetheless, warrants further research. The controversy over chromosome damage also remains to be resolved for cannabis, and, for that matter, a variety of commonly used drugs, including aspirin. In the absence of clinical evidence of harm, the significance of any abnormalities which may emerge is doubtful, but current uncertainty will only be assuaged by further experimental work. Similarly, research into the effects of cannabis on cell physiology and metabolism has failed, as yet, to provide us with satisfactory information on the role of the drug as a potential cause of lung cancer. Some findings suggest that the tars in cannabis smoke might be carcinogenic. Other cell studies indicate that THC might be therapeutically useful in the treatment of malignancies.

In the light of recent research findings, some issues which were once considered important do not now seem to warrant particular concern. An early study which reported brain atrophy in cannabis users has not been confirmed by newer and more reliable techniques, and epidemiological surveys have been generally unable to find clear evidence of impaired brain function in heavy cannabis users. It also appears unlikely that the high lipid solubility of THC implies that sequestered quantities of the drug might be later released in an active form. Many widely used drugs, including diazepam (Valium®) are highly lipid soluble, but this does not necessarily mean that the drug is accumulated in any active form or causes problems as a result of this characteristic per se. However, high lipid solubility, in this case, must be seen as grounds for continued, careful observation.

Dr. Hollister has come to the conclusion that "... general toxicity studies of cannabis and its constituents lead to the inescapable conclusion that it is one of the safest drugs ever studied in this way."

Turning now to the area of mental health and psychological functioning, it has been suggested that there might be some risk in the use of cannabis by psychologically troubled persons, whose psychiatric problems might be unmasked or aggravated by the drug. Tolerance to the effects of cannabis and definite, although mild, signs of physical dependence have been experimentally observed. These occur at much higher levels of consumption than those which characterize typical recreational cannabis use, but we cannot ignore the possibility that certain persons may be prone to compulsive use of this drug, as with any drug with attractive psychopharmacological characteristics.

One of the most common concerns is that cannabis use may precipitate basic changes in the personalties of users, whereby they become less motivated to work or strive for success. This so-called "amotivational syndrome," although observed in some young people who have become preoccupied with drug-taking and have radically changed or abandoned traditional life goals, is difficult to attribute directly to cannabis, especially when multiple drug use is present. In contrast to pharmacological hypotheses regarding such occurrences, other researchers have suggested that lack of motivation is really a manifestation of concurrent depression for which cannabis may be a self-prescribed treatment. No clear evidence exists for either mechanism, however. It has also been found that family background and relationships, as well as social values, are much. stronger predictors of dropping out of college than is drug use. Participation in the illicit drug subculture and "amotivation" may both be symptomatic of the same underlying problem. It is clearly impossible to ascertain if these lifestyle changes, when they do occur, are caused by the pharmacological properties of cannabis.

Whether or not cannabis has the ability to evoke sociopathic, depressive or schizophrenic states is highly uncertain, but there is little empirical evidence that this is a significant risk. There is no doubt that, in certain situations, it can produce acute anxiety or panic reactions. Although such transient reactions occur infrequently, if at all, in regular users, they are probably the most common adverse psychological effects of the drug. Fortunately, these reactions are rapidly reversible as the effects of the drug wane. Toxic delirium and acute paranoid states, more serious and more rare, are similarly self-limiting. "Flashback" reactions tend to be mild and require no specific treatment. At the present time, it would appear that psychopathology may predispose certain people to problematic cannabis use, rather than being caused by it. As mentioned above, it is reasonable to assume that it might unmask latent psychiatric disorders in those who are particularly vulnerable, but it does not appear that this is a significant occurrence in the general population.

Evidence from the available health statistics suggests the limited scope of cannabis-related psychological problems. For example, roughly one hundred cases involving cannabis are reported each year to the National Poison Control Program, representing 0.1%-0.2% of all reported poisonings. Even then, the figure is probably inflated, since patient reports are accepted without independent chemical verification. A 1975 study in a Toronto emergency ward indicated that adverse cannabis reactions (chiefly acute panic reactions) were concentrated among young, and probably naive, users; less than 3% of the alcohol and other drug-related emergencies requiring institutional intervention involved cannabis. Similarly, cases involving cannabis constituted less than 4% of all 1976 "crisis contacts" at the Calgary Information and Crisis Centre. This represented less than one-tenth of the number of cannabis cases reported there in 1972, despite a steady increase in the prevalence of cannabis use during the intervening period.

While 19% of all psychiatric admissions in Canada are classified as due to "drug dependence" by the Mental Health Division of Statistics Canada, all but 2% were attributable to alcohol, the cannabis-related admissions constituting 0.03% of the country's psychiatric case load. (About 30 cases per year over the past six years). Further, most cannabis-related admissions result in very brief hospital stays, usually measured in days or weeks, and some admissions may be attributed to cannabis in lieu of other more appropriate diagnostic assignments. Despite considerable increases in the using population, the proportion of psychiatric admissions attributed to cannabis has not risen accordingly. These more recent data seem to reinforce the Le Dain Commission's 1972 conclusion that:

...cannabis does appear as a secondary or complicating factor in psychiatric admissions in Canada, although such cases do not represent a significant proportion of either cannabis users in general or of the psychiatric hospital patient population in particular. (Le Dain, 1972:90)

There is no currently accepted medical use of cannabis in Canada, outside of the experimental context, although it appears that therapeutic prescription by physicians is not prohibited by law. Production of the last cannabis-containing pharmaceuticals was discontinued in 1954 and no new supplies have been made available through traditional channels. While cannabinoids, over the centuries, have been reported to produce an incredible array of possibly useful medicinal effects, the majority of the alleged effects are either complicated by undesirable side effects or can be duplicated by other more readily available and convenient drugs. Recent advances in the synthesis of natural cannabinoids and related compounds has led to a new generation of clinical testing. Some potentially important therapeutic uses have been discovered and a few interesting leads from the earlier literature have yet to be adequately followed up using modern techniques.

Of primary interest is the ability of THC to lower intraocular pressure in glaucoma, a major cause of blindness, and its capacity to suppress the often debilitating nausea and vomiting associated with cancer chemotherapy. Areas where cannabinoids are currently being investigated for possible, but less likely, clinically useful effects include its use as a bronchodilator in the treatment of asthma, as a tumour growth inhibitor in cancer treatment, and as an appetite stimulant in anorexia disorders. Other more tenuous uses include possible anticonvulsant and analgesic applications.

Major health hazards of cannabis have not readily appeared in either field studies or clinical practice, but we cannot rule out the possibility of statistically rare or as yet unforeseen occurrences. Like tobacco cannabis smoke contains tars which can be damaging to the lungs, and paraquat-contaminated materials are likely to be quite toxic. Until definitive research results are obtained concern will continue over the use of cannabis by people with heart, lung, or liver problems, diabetics, pregnant women, and young boys. Although our mental health and toxic reaction statistics would indicate that cannabis is of relatively little importance in precipitating problems in these areas, use by certain emotionally unstable people may be unwise. Overall, the risks to health connected with cannabis use appear, at present, to be less significant than those related to the use of the more common recreational drugs, but until further research has been conducted, caution and vigilance would be recommended.