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|Major Studies of Drugs and Drug Policy|
|The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs - 1972|
The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs - 1972
2. Cannabis and Its Effects
ADVERSE PSYCHOLOGICAL REACTIONS
The term adverse reaction, as traditionally applied to the medical use of drugs, refers to significant undesirable or negative side-effects of the drug. The distinction between main or desired effects and the multitude of other side effects which the drug may have is not absolute in any sense, and the application of these terms generally depends on the conditions of drug use. In the medical use of drugs, the desired and undesired effects are relatively easy to define in a specific treatment context, although the labels may change with the aims of the therapy.
Drug adverse reactions in the medical context are not at all unusual. In one recent study in Montreal, a total of 524 psychiatric patients experienced 730 adverse reactions to psychotropic drugs administered them for therapeutic purposes.535 This represents an overall incidence of close to 10% of the more than 5,000 patients studied over a one-year period. Predominant adverse reactions included central nervous system effects, behavioural effects and autonomic physiological effects.
In the area of the non-medical use of drugs, defining adverse reactions becomes considerably more complicated. With cannabis, for example. personal and social attitudes and norms often dominate in the interpretation of drug effects. What may be a desirable or pleasurable effect to one individual in a certain situation may be considered an adverse response or a side effect in another situation or to another individual. For example, cannabis effects that are subjectively considered "psychedelic" or "peak" by certain persons are often defined as "psychotic" by others. Feelings of increased sensitivity to humour, reported by some users, may be viewed as "unnatural hilarity" or "loquacious euphoria" by other individuals. What some would consider "exploration of inner consciousness" might alternatively be called "escape from reality". Clearly, the labelling of certain aspects of a drug experience as adverse, neutral or positive is often a function of individual and social constructs and concepts of normality, morality and reality, and generally implies a definite value judgement beyond the objective reporting of behaviour and experience.232 In a survey of physicians regarding adverse reactions to LSD, one respondent stated, "From my understanding of the effects, I would consider all reactions to LSD as 'adverse' regardless of the immediate subjective response."625 Clearly, not all LSD users or other observers share this opinion. As Bialos indicates, in discussing some of the difficulties with defining marijuana adverse reactions:
Tart has proposed two criteria for selecting what he believes would be unequivocally negative effects:
(1) The effect is clearly unpleasant,
(2) it has no redeeming value, other than as a possible lesson to the user. 598
While most observers might agree in principle with the approach, considerable conflict among individuals would undoubtedly arise in the application of these criteria in many practical situations.
Even if agreement is reached as to whether a particular drug-associated condition is positive or negative, in practice one is often left with the difficult task of determining whether the behaviour or condition under consideration is in fact a response to the drug, whether the drug use is the result of the condition, whether the two are merely randomly coincident, or if a combination or interaction of these possible situations might exist. Some observers contend that only those with serious psychiatric disorders become heavily involved in non-medical drug use, while others might argue from the same data that the drug is primarily responsible for the pathology. Alternatively, some investigators have suggested that the "cannabis psychosis" often noted in Eastern literature, for example, is merely endogenous schizophrenia occurring in the drug-using population, independent of drug use.
In spite of these ambiguities, a number of rather specific concerns have developed regarding possible adverse psychological reactions to cannabis. Some of these alleged effects, which will be examined in detail below, include acute adverse reactions such as depression, anxiety, panic or psychotic-like, short-term responses cannabis augmentation of pre-existing neuroses. character disorders and adjustment problems; functional psychoses in which cannabis might serve as a precipitating or complicating factor; long-term changes in personality, behaviour or life style associated with chronic use (for example, the so-called "amotivational syndrome"); a specific "cannabis psychosis" or dementia of a chronic nature caused primarily by the drug and "flashbacks" or recurrences of previous drug effects.
Because of the potentially serious nature of these alleged acute or chronic effects and the current vociferous controversy regarding both the validity and frequency of such occurrences, the literature concerning adverse reaction will be reviewed in considerable detail below.
ADVERSE PSYCHOLOGICAL REACTIONS TO CANNABIS IN THE EAST AND IN NON-INDUSTRIAL COUNTRIES
A vast literature exists describing complications of chronic cannabis use in the Middle and Far East, where the drug has been consumed for centuries. Generally, moderate use seems to be the rule, with little evidence of harmful effects in the majority of users. However, cannabis has long been implicated in serious psychiatric problems in some chronic heavy users, who reportedly constitute a population similar to the derelict skid-row alcoholics of this continent. There are a variety of problems with interpreting these reports and generalizing their conclusions to North American conditions of cannabis use.
It has often been said that many of these countries are underdeveloped scientifically and medically as well as economically. Consequently. few studies exist which are even marginally adequate by present scientific standards of clinical research. As discussed earlier. medical and psychiatric diagnostic and treatment practices vary greatly from country to country. In addition, in most non-industrial countries, psychiatric institutions are grossly understaffed and suffer from a serious lack of modern treatment and diagnostic facilities. The majority of subjects in most of the Eastern studies were illiterate, impoverished and malnourished. Furthermore, the potency, form, and mode of administration of cannabis (and the presence of other psychotropic drugs), as well as the extent, patterns of use and social and religious meaning, differ greatly from conditions in North America.
The 1971 United States Health, Education, and Welfare Marihuana and Health report states that:
In spite of these limitations, certain studies clearly merit attention and may provide clues as to possible consequences of increasing cannabis use and of changing patterns of consumption in the West.
A number of articles in the nineteenth century and early part of the twentieth. reported that cannabis was responsible for 20 to 50 per cent of the mental hospital admissions in India. Egypt and other Eastern and Middle Eastern countries.121,173,652 A different picture has been presented by other researchers.
The Government of India, in 1893, appointed the Indian Hemp Drugs Commission to investigate and report on the economic, social and medical aspects of the cannabis (hemp drugs) situation in India. 215 The different forms of the drug. bhang, ganja and charas (hashish), were to be studied separately. The Commission was asked to "...ascertain whether, and in what form the consumption of the drugs is either harmless or even beneficial as has occasionally been maintained." Although the inquiry, in many respects, does not meet modern optimal research standards, it remains one of the most thorough general studies of cannabis ever conducted.313,320,433
In investigating the effects of hemp on mental health, the Indian Hemp Drugs Commission found much of the medical testimony and hospital records and reports defective and unreliable. In many instances, the primary hospital data regarding the patients' histories and diagnoses were taken from the "descriptive role" which was generally filled out prior to referral to the asylum. often by non-medical personnel such as policemen or magistrates. The Commission stated:
The Commission concluded:
Since this report. many observers have challenged the conclusion that even excessive use can be a major cause of "insanity".'196,235,406,458 On the other hand, two Indian members of the original Commission felt that a stronger statement should have been made. and indicated that the majority of medical witnesses felt that the use of hemp drugs was deleterious. They recommended that both charas and ganja be prohibited but that the use of bhang should continue to be permitted. Their dissenting opinion is summarized by the following statement:
In a series of articles. Chopra and associates have discussed mental and physical effects of chronic cannabis use India .124,126,127 Much of their data is based on a study of over one thousand cannabis users. The major project represents one of the few attempts to investigate a large group of cannabis users who were not selected from an obviously pathological or deviant population (that is, not psychiatric patients or prison inmates). The researchers report that among regular users of the potent ganja and charas a small percentage suffered from serious psychiatric disorders, and that minor emotional problems, including impairment of judgement and memory, were observed in these subjects. According to the authors, a significant proportion of this group had pre-existing neurotic tendencies which may have contributed to their problem of drug use. In some instances, cannabis use was seen as an attempt at self-medication in response to these disorders rather than as the cause. Heavy users were often observed to show marked inactivity, apathy and self-neglect. The majority of those who took small doses of any of the cannabis preparations felt that the overall consequences of their drug habit were harmless or beneficial. while the majority of those who chronically took heavy doses, thought the practice harmful. These subjective judgements were generally consistent with the clinical observations reported.
In a separate study, the Chopras 124,127 carried out a survey of:
Four hundred cases were found in which the authors felt that the cannabis habit was the only clear cause of insanity. In the remaining two hundred cases, a variety of other factors such as heredity or indulgence in other drugs, were considered important as well. They describe a variety of acute mental disorders which they feel are attributable to the use of cannabis drugs. including confusional, maniacal, depressive and delusional disorders. Chronic disorders were less common but reportedly took the form of a toxic mania. schizophrenia or dementia. Unfortunately, no control group of nonusers of similar socioeconomic background was studied by the Chopras in this series of investigations, but their data do allow some comparisons within the types of users studied.
Recently, G.S. Chopra reported on 200 cases of psychotic reactions to cannabis seen between 1963- 68.123 The subjects fell into three main categories: Group I (34%) no previous history of mental disorder; Group II (61%) most were on the "threshold of psychosis"; Group III (5%) chronic psychotics with cannabis intoxication superimposed.
Dube has conducted a general epidemiological study of health and mental illness in a North-Indian town and surrounding rural area.163,165 General drug use was very low in this district. Significantly more psychiatric disorders were found among the cannabis users than among the non-drug-using subjects. Although the author does not conclude that drugs were the direct cause of the pathology observed in these cases, he has described elsewhere a cannabis toxic psychotic reaction with schizophrenia-like features, and a dull lethargy in some chronic users.164
A few cases of cannabis-associated anxiety or psychotic reactions of varying duration have also been recently reported among North Americans visiting or living in India.245 The Commission has been informed of several such occurrences, as well.438 These cases have typically involved the use of very potent cannabis materials under generally unusual, unfamiliar and, in some respects, stressful circumstances.
A Moroccan study by Roland and Teste (also presented by Benabud in 1957 45) has received considerable attention in discussions of "cannabis psychosis".529 The report, based on a study of hospital records, provides a variety of subcategories of psychotic reaction to cannabis. The majority of cases were reported to be acute reactions to "sharp toxic overdose" associated with heavy use and were not as long-lasting as functional psychoses. The average duration of hospitalization was about six weeks. The investigators also felt that heavy cannabis use may mobilize or aggravate schizophrenia in predisposed individuals and may also interact negatively with malnutrition, alcoholism and other disorders. The problem chronic users in this study smoked enormous quantities of cannabis. "The average number of pipes smoked is between twenty and thirty, but figures of forty to fifty are not infrequent." A similar and more recent report has been presented by Defer and Diehl. 151 Other authors writing on the Moroccan situation include Sigg and Christozov.560,131 In these studies, the majority of the severe chronic problems occurred in illiterate and impoverished slum dwellers. Moderate users, especially in the country districts, showed little sign of untoward effects.
After visiting some of the hospitals involved in the above reports, Mikuriya has challenged the validity of the clinical and diagnostic data in Morocco.434 Few of the patients were seen by professional psychiatric personnel. diagnoses and case histories were often not based on adequate information, and many standard neurological and physiological tests and post mortern facilities were unavailable. Murphy states that:
In Egypt, Soueif studied two groups of hashish users, and two control groups of non-users.583 While hashish takers were found to be more anxious than the controls, no significant differences were found in other personality variables. No cases of psychosis or serious deterioration were noted. Moderate negative correlations were obtained between the amount of hashish consumed and the number of hours worked per day. Soueif is presently conducting a much larger study of imprisoned hashish smokers but has not yet published a full report.414,584 Preliminary information suggests more impairment in cognitive and psychomotor function in these individuals than in non-hashish-using prisoners.
Bouquet of Tunisia argued that chronic intoxication with hashish leads to mental and physical deterioration.70,71 Chronic users of raw hemp or inarijuana. however, apparently rarely attain a condition of dementia, hut reportedly show a reduced capacity I'or work and a tendency towards anti. social acts.
There were a number of papers published on cannabis in Nigeria in the 1950s. Fifteen to twenty per cent of some mental hospital admissions were attributed to the drug.23,66,347 While a variety of psychiatric disorders are reportedly linked to cannabis consumption, a clear picture of a specific "cannabis psychosis" does not appear. Lambo commented:
Also in Nigeria. Boroffka states:
Boroffka does report that cannabis can precipitate schizophrenia-like toxic psychoses in certain individuals and may contribute to psychopathology in other forms.
The South African Government Report on the Abuse of Dagga [cannabis] notes that:
In 1939, Stringaris published a small monograph on various aspects of the "hashish habit". 590 Considerable attention was given to adverse psychiatric reactions illustrated by case histories observed in Greece. Miras has more recently described a chronic hashish smoker syndrome which he feels has an organic base.442 A preliminary report of a major study of 31 Greek hashish smokers, with an average history of chronic use of almost three decades, suggests no gross behavioural deviations or neurological disorders.189 All of thesee subjects were gainfully employed at the time of the study. Further controlled comparisons and analyses are underway.
The history of cannabis in South America has been reviewed by Wolff,674 and Cordeiro de Farias.142 These writers feel strongly that cannabis contributes heavily to mental and physical deterioration in South America, but others disagree. Adequate epidemiological and psychiatric data are lacking, however.312,453
Prince and associates report that of 106 male admissions to the mental hospital in Jamaica, 24 per cent used ganja once a day or more, 40 per cent had never used it and the rest were occasional users.513 This pattern of cannabis consumption was not different, however, from the estimates of cannabis use (based on a "key informant technique") in the communities from which the patients came. Acute toxic confusional states due to ganja were rarely seen in hospitals. The authors conclude that: "A so called 'ganja psychosis' is simply schizophrenia occuring in the ganja using population."
Beaubrun, who is currently conducting research (for the United States National Institute of Mental Health) on the chronic effects of cannabis use in Jamaica, reported that about 20 patients per year were admitted to the mental hospital with acute psychotic reactions alledgedly due to ganja, and few of those became chronic. He concluded that:
Recently. Spencer, also from the Carribean, reported nine cases of psychotic reaction in "patients who are known to have taken cannabis." The symptomatology displayed was reportedly different from "classical schizophrenia and manic-depressive illness".
In summary, reports from the East and other non-industrial countries have tended to concentrate on chronic heavy users of hashish or other potent cannabis preparations, such as ganja. The subjects of these reports have usually been illiterate and impoverished, and were often contacted through medical or criminal-legal channels. Few of the studies have adequate controls. Most investigators report that users of bhang, or marijuana, show few physiological and psychological ailments compared to chronic consumers of the more potent hashish. It is not clear, however, if the various forms of cannabis have differential effects on health. Moderate use is the general rule and heavy chronic use the exception. There is agreement that heavy cannabis use can, in certain circumstances, elicit an acute toxic psychotic reaction. and the contention is often made that such a response might precipitate a schizophrenia-like rejection in certain redisposed individuals. Other subtypes of psychotic reaction lasting from one week to two months have been frequently noted. There is no consensus regarding the existence of a "cannabis psychosis" as a specific syndrome, clearly differentiated from endogenous or natural psychotic states, and although many investigators feel that persistent toxic doses can potentiate a variety of psychological disorders in certain individuals. others do not consider this a likely occurrence.
There is frequent mention in this literature that chronic excessive use is often associated with a lack of ambition, drive, ability to make and carry out long-term plans, etc. (often called an "amotivational syndrome" in the West), although the relative cause and effect roles of the drug, pre-existing personality, and socioeconomic and nutritional conditions have not been fully clarified. Reference has often been made to chronic dementia and deterioration in a small fraction of individuals with a long history of excessive use, but again causal factors have not been well established.
It is not clear whether or not severe psychological disorders are any more common in the cannabis-using population than in non-using individuals of similar socioeconomic background. Thorough, controlled studies in these countries, which isolate the long-term effects of cannabis from the powerful and pervasive sociocultural, economic, nutritional and hygienic conditions described have yet to be reported.
ADVERSE REACTIONS IN NORTH AMERICA
Clinical Reports From North America
In the past few years there have been numerous clinical reports of a variety of adverse psychological reactions to cannabis use in North America after nearly three decades of relative absence of such papers in the literature. The majority of these clinical reports display many of the methodological problems seen in the bulk of the Eastern literature. Pre-drug personality, cause and effect relationships, and details of both the general patient group and the overall catchment population from which the subjects were drawn are rarely adequately explored and presented. Some reasonably well-documented reports have appeared, however, and certain recurring patterns and situations of adverse reactions are becoming apparent.
Among the first reports of adverse psychological reactions to cannabis in North America were two papers presented by Bromberg in 1934 85 and 1939.86 Thirty-one psychiatric patients who had experienced "psychotic reactions following the use of cannabis were described. Conditions characterized included acute intoxication (which might manifest manic-like features), emotional reaction to the somatic and psychological intoxication effects (lasting from hours to days), and toxic psychoses often due to an admixture of drug effects and basic functional psychoses such as schizophrenia (lasting for weeks to months). The validity of the role of cannabis in some of these cases has been challenged by several researchers.243,458 In a separate study, Bromberg found no psychoses among 67 marijuana users.86 The author observed that the chronic dementia and deterioration attributed to long-term cannabis use in some Eastern papers had not been observed in North America.
Keeler has presented several papers on the characteristics of acute adverse reactions to marijuana.323,325 In one report, 11 cases from a student population were described with symptoms including gross confusion, depersonalization, inipairment of recent memory. depression, paranoia, anxiety and panic, and recurrence of unpleasant effects. None of the cases required hospitalization. The author suggested that "...dissolution of ordinary adaptive and defensive psychological structure may have led to the emotional disturbances observed."323 In addition, there were two other individuals whose life style changed after the use of marijuana, and four others who developed schizophrenic symptoms subsequent to the combined use of marijuana, LSD and amphetamines. Keeler also reported that multi-drug-using patients frequently admitted having experienced some kind of paranoid thinking at some time during a marijuana experience, usually taking the form of "law enforcement paranoia" or suspicions as to the motivation of friends.325 Keeler also considered the rewarding aspects of marijuana use in the patients:
In a separate paper, Keeler and associates reported that four individuals, in a drug-free state, experienced a "spontaneous recurrence of marijuana effects329 (that is, unusual visual or somatic sensations previously experienced during acute marijuana reaction). In two cases, the occurrences precipitated severe anxiety, while in the others, no distress was elicited by the experience. The authors point out that the recurrence of a drug effect (or "flashback") is not necessarily an adverse reaction and should be classified as such only if it precipitates anxiety of interferes with function. "Spontaneous recurrences are tolerated by some and enjoyed by others." They also note that the recurrence of clinical psychopathology that was present during the drug reaction is not a spontaneous recurrence of the drug effect, but should be considered an adverse reaction. The diagnosis is complicated when an individual has had similar reactions to more than one hallucinogenic drug since, in this situation, recurrences cannot be clearly assigned to either.
It would appear that discrete recurrences may be on a continuum with more subtle effects of cannabis use. For example, Keeler notes that some subjects claim that their perceptual awareness was increased by marijuana and that some degree of this enhancement remained with them after use.329 Perhaps also related is the 'contact high', or the experience reported by some users of reeling somewhat 'high' without the drug when in the presence of others who were 'high'. Although these various aspects of post-intoxication responses may be in some respects related psychologically and perhaps physiologically, it, Most situations they cannot be considered the same phenomena. The lack or clear agreement as to essential definitions in these areas prevents simple interpretation of the very limited data available. Definitions of "flashbacks" or "spontaneous recurrences' rarely accompany clinical reports in the literature.
Weil has presented a classification of marijuana adverse reactions which he connsiders statistically uncommon, but clinically valid.657,659 These include: panic reactions, simple depressive reactions, recurrence of effects ("flashbacks"), precipitation of delayed psychotic reactions to hallucinogenic drugs, and atypical reactions in ambulatory schizophrenics. Over 200 cases were studied and the majority (over 75%) were considered panic reactions in which the person interpreted the acute physical or psychological effects of the drug to mean that he was becoming insane or perhaps dying. Except in rare instances, these reactions were self-limiting and of short duration. Weil stresses that labels such as "psychotic reaction" and "toxic psychosis" are often erroneously applied to such cases.
As will be elaborated upon later, the majority of the acute adverse reactions which come to medical attention apparently occur in novice, inexperienced users and generally, but not always, involve relatively high doses. These short term panic reactions, which rarely result in hospitalization and usually last only a few hours, or at most a day or two, are hardly mentioned in the literature of countries where cannabis use has been common for long periods of time. These reactions are either too infrequent or are not considered significant enough to require medical attention and discussion. The "acute" cases discussed in the Eastern literature are generally more severe and may persist for days or weeks.
Becker has proposed an explanation for the North American pattern of short-term anxiety reactions, which is gaining considerable support. 39,40,42 While the effects of low doses of cannabis are in some respects similar to the familiar alcohol 'high' in our culture, larger doses of cannabis produce effects which are qualitively different from those a non-user is likely to expect or have experienced before. In many instances, it is the interpretation or meaning which the user attaches to these radically different experiences which determine the subsequent emotional response. Effects which are considered tolerable or even interesting or pleasurable to experienced users, may be frightening to a novice, who may fear a permanent derangement of his mind. Cannabis sometimes produces transient waves of mild anxiety or paranoia, which the regular user usually correctly attributes to the drug and has learned to control. These same effects may convince the novice that he is insane and bring on a severe panic. The response of others to this fear is of great importance-if they are not alarmed, and reassure him that the effects are not unusual or permanent, the anxiety reaction may be minimized. On the other hand. non-users, including some police and medical personnel, may react with alarm. and reinforce the notion that the person is at least temporarily insane (psychotic). thereby adding to his alarm. Becker's hypothesis would predict that as familiarity with the acute effects of cannabis in our culture increases. the frequency of short-term panic reactions among users will decrease.
In the past two years, a number of clinical reports have appeared which suggest that the chronic use of cannabis in North America may be causally associated with a variety of psychological problems of a more prolonged nature than the generally accepted acute reactions discussed above.34,318,345,441,448,496,499,500,543,550 Similar clinical reports have come from other industrial countries.50,148,593,623 In most of the cases described, considerable prior psychopathology existed. although this is reportedly not always the case. and there are numerous reports of adverse psychological effects in individuals without obvious previous pathology. There have been a few individuate reports in which cannabis use may have been associated with suicide, but a possible role of the drug is unclear in these cases. Suicidal thoughts do sometimes occur in a small proportion of users while under the influence of the drug, but there is little indication that such notions are carried through.249
Lundell has related some of his clinical experiences over the past few years with adolescent patients involved in the non-medical use of a variety of drugs in Montrea1.383,385 Although no systematic, controlled study has been done, over a period of three years he has seen "thirty to forty cases drift into and out of treatment". Of a group of twenty of these patients, all "started on" cannabis, 16 used LSD or speed, and five used heroin. All had been "school drop-outs at some stage", three had been hospitalized for treatment, and two had experienced acute psychotic-like breakdowns. Since this initial report, five more "acute toxic reactions" have been observed.383 Lundell reports that his patients exhibited problems in perceptual and motor organization (on the Bender-Gestalt Test), inconsistency of social values, lack of judgement, impaired memory, change in appetite and personal appearance, paranoia, irritability, violence, hepatitis, "philosophical meanderings", and decreased interest and motivation. He stresses the importance of pre-drug use personality adjustment in problem cases, and notes that serious psychological difficulties preceded drug use in many of these instances. In discussing LSD and cannabis (which he considers the "disdainful dysphoriant"), Lundell points out the need to:
Lundell considers drugs to be "dynamite" for adolescents going through a variety of identification and adjustment problems, and urges a cautious approach to cannabis until a systematic study has elucidated the possible causal role of the drug in the adolescent adjustment disorders he has observed.
Recently, in a widely publicized and highly controversial paper, Kolansky and Moore have described 38 young people who were "moderate-to-heavy" users of cannabis (but not other illegal drugs), and displayed a variety of serious psychological disturbances which the authors attributed to marijuana. 311,344 These patients had been observed usually once or twice, as part of a consultation service which included about 500 psychiatric patient referrals over a five-year period. Features present in the 38 individuals, who reportedly had shown no pre-marijuana signs of significant psychopathology, included psychosis, paranoia, anxiety, confusion, apathy, depression, disturbances in visual perception, suicide attempts and pregnancy. The majority were not hospitalized, but were referred for treatment on an outPatient basis. The authors state:
The report has been heavily criticized by scientists and clinicians on a number of grounds.189,198,425,465,551 Doubts have been expressed as to the adequacy of the pre-drug personality inquiry and case history constructions; objections have been raised as to the logic of broad conclusions and generalizations based on a restricted referral patient sample in the absence of normative or control data; and the unequivocal and perhaps oversimplified cause and effect statements presented have been criticized. Jones306 and Benson46 have suggested that the article on the misuse of health statistics,381 which followed the Kolansky and Moore paper in the journal "... should be read with the first in mind". Many have argued that the chronic use of drugs is more often a sign of underlying psychopathology than a cause of it. In addition, it has been frequently pointed out that the initiation to drug use usually occurs in age groups where functional psychosis and other disorders typically become manifest regardless of drug use. In response to such criticism, Kolansky and Moore argue that other clinicians have reported similar cases, and go on to say:
While many scientists question the statement that clinical data can yield as reliable results, the authors do raise a number of important questions regarding the heavy use of cannabis by adolescents in their report. Because of the seriousness of the charges made, these hypotheses should be explored in a systematic and thorough fashion.
Although no adequately controlled studies have yet been published on the behavioural effects of chronic cannabis use in North America, a number of clinicians have described an "amotivational syndrome" in some chronic marijuana users on this continent. McGlothlin and West report that clinical impressions suggest that heavy use of marijuana may contribute to some characteristic personality changes, including apathy, loss of effectiveness. reduced drive and ambition. diminished capacity or willingness to carry out complex long-term plans, to endure frustration, to follow routines or to successfully master new material.416 David Smith has described a similar condition in a small proportion of chronic users, "The picture in terms of social consequences is then similar to that of a chronic alcoholic, but without the physical deterioration."576 As discussed earlier, a similar syndrome has been described in long-term excessive users of hemp in a number of Eastern countries.
Thurlow has described a transient lack of drive and motivation in a small group of university students in Ontario, who were regular users of cannabis and, more rarely, LSD. The condition generally responded rapidly to drug withdrawal and routine treatment.607 A similar condition was described by Scher and Mirin.111,113
Although no systematic studies have been done, some observers warn that chronic cannabis use may cause prolonged disruption of cognitive functioning and school performance in the university student population.89,103,177,511 As noted in a previous section, no major consistent differences have been found between cannabis users and non-users on college rmance, althou h some negative correlation is often reported between cannabis use and grades. It would appear that the general "amotivational" condition is not prominent among college student cannabis users. It may exist in a minority of users, however.
While an association between chronic heavy cannabis use and an "amotivational" behaviour pattern in some persons in North America is generally acknowledged, the complexity of untangling any causal relationship between the heavy use of cannabis and the general life style has resulted in considerable controversy regarding the essential etiology of the syndrome. Gay has proposed that the role of marijuana in such cases may often be more symbolic than pharmacological.216 Others have suggested a definite organic basis.83,383,550 Unwin considers that "the so-called amotivational syndrome" may in most cases be a "masked depression".637 Lecker felt that such a syndrome might represent an "operant conditioning state" during which the chronic user aims at the quickest way to get pleasure, and may revert more and more to the drug for instant gratification. 351 McGlothlin has suggested that cannabis use by persons appearing "amotivational" was perhaps continued and intensified when the drug effects were compatible with their natural personality characteristics and preferred life style. He indicated that separating the various social, psychological and pharmacological components would be an arduous task. The issue is further complicated by the fact that heavy cannabis users in North America are usually regular consumers of other drugs, such as LSD. 414
A study by Suchmann suggests a close association between the use of marijuana in some young people and adherence to what is termed the "hang loose" ethic. Central to this notion is the questioning of such traditional aspects of authority, behaviour and belief as conventional educational, religious and political institutions, pre-marital chastity and the accumulation of wealth. The investigator contends that while the "hang-loose" ethic may represent antagonism to the conventional world, it does not appear to create apathy and withdrawal, and that the smoking of marijuana is often part of the behaviour pattern associated with this ethic rather than the cause of it.511 In contrast, however, some individuals have suggested that cannabis and other drugs may have a "cultogenic" influence on susceptible users. and thereby contribute significantly to the growth of what they consider to be an undesirable subculture in North America." A recent WHO report states:
In summary, mild, transient phases of anxiety and paranoia occur in some inexperienced and regular users of cannabis in North America. More severe panic reactions, especially among inexperienced users, have been reliably reported. The notion that cannabis may, under certain circumstances, precipitate a more prolonged psychotic reaction in predisposed individuals is gaining some support in the clinical literature, although there is no consensus as to the exact nature of the "predisposition" or its prevalence in the general
population. Other more prolonged adverse psychological reactions to chronic use (including personality changes and an "amotivational syndrome"), in some instances in apparently previously normal individuals, have been cited, but there is considerable controversy as to the validity and general applicability of many of the clinical reports presented. It is not yet clear what role cannabis plays in such chronic syndromes. Additional aspects of these questions are presented in later sub-sections. Given that a variety of adverse psychological conditions may be associated with or caused by cannabis use, the next step, and perhaps the most important one socially, is to determine the frequency and severity of such reactions in the population of users in North America, and to consider what might be expected in the future.
The Incidence of Adverse Reactions in Patient Samples
Although no proper epidemiological studies of adverse reactions to cannabis have been done, some impression as to the frequency of such cases in North America can be obtained from a number of limited surveys of clinicians and treatment services. These studies have generally inquired vaguely about instances of cannabis use which have come to professional attention, and typically encompass a range of undifferentiated cases covering a variety of social, psychological and physiological conditions. They often even include non-medical involvement in cases arising, for example, from parental concern over adolescent usage, rather than from any direct drug effect per se. In general, little information can be gained about the 'normal' user of drugs through patient or treatment service sampling, since the subject population is defined a priori as pathological. Treatment facilities make contact with relatively few people who are not patients, and their resulting experiences and attitudes are generally biased accordingly.
With few exceptions, hospital records are not kept in a form which enables an efficient search of treatment cases. In addition, ethical considerations regarding the patients' right to privacy often impose restrictions on easy access to data. Furthermore, the reliability and validity of psychiatric diagnosis, especially in drug-related cases, is often not adequate for survey purposes. Polling individual clinicians and simply counting cases seen medically in a community can be misleading since many such patients are referrals, seen by different doctors, and consequently may appear several times in the final totals. In addition, many clinicians are not well informed in the area of non-medical drug use, and surveys of such individuals often reflect personal attitudes as much as the epidemiological aspects of the situation. Since most cases of adverse reaction to cannabis are probably not brought to medical attention, even accurate diagnostic and treatment statistics must be considered underestimates of the overall incidence of the less severe conditions. Most acute reactions are probably easily handled by friends and other non-professionals. Fear of legal repercussions undoubtedly prevents many from seeking formal assistance. In any event, the number of drug related cases must ultimately be interpreted in terms of the overall patient population, and more importantly, in terms of the extent and patterns of drug use in the general population from which the patients were drawn.
Unfortunately, these methodological requirements are rarely met in clinical reports.
During the 1930s and 40s a few reports were published on marijuana use in the United States Army.119,201,202,213,401,561 Perhaps the best known of these papers was the Panama Canal Zone Report of 1933.561 In these various reports a total of 589 marijuana users were studied, almost all of whom were selected from patient or special counselling populations. More than three-quarters were black, and the subjects in these studies were typically in their early twenties, had poor educational and socioeconomic backgrounds, were below average in intellectual ability, and usually had a long history of deviant or delinquent behaviour. They had generally been using marijuana for several years and many averaged two to five cigarettes daily, with some using twenty. No tolerance or signs of physical dependence were reported, although indications of "psychological dependence" were noted in a number of subjects. Almost none of the men used opiate narcotics, but most used tobacco and alcohol. Although there were frequently noted behavioural and personality disorders among these individuals, and generally poor adjustment to army life, only a few cases of psychosis were observed, and in only one was cannabis use considered a possible cause. The importance of long-standing underlying personality disorders was generally stressed with respect to deviant or delinquent behaviour. There was little connection between cannabis use and violence or serious crime. In none of these studies were control groups employed, so generalizations and conclusions are limited. Extreme chronic pathology is not to be expected among military personnel since such individuals would normally be screened out by entrance examinations.
Probably the most thoroughly investigated population of drug users in North America are college students. Murphy and associates surveyed the health services and student counselling centres in 126 colleges in Canada and the United States in 1966, asking about drug-related problems seen over the previous 18 months. Replies were received from 66 counselling centres and 80 health services. In total, 67 cases of acute cannabis adverse reactions were reported, 60% of which were considered panic states and 10% psychotic episodes. The majority of schools reported no cases.457
In 1966-67 Blum and associates surveyed the student health services at five West Coast schools in the United States. Drug adverse reaction cases seen made up less than 0.1% of the overall student population. Cannabis problems were not specifically mentioned. Based on student surveys, the investigators cautiously estimate that perhaps 14 "bad outcomes" occur in the student population for each one noted in official health records.60
Keeler at the University of North Carolina reported that 28 of 40 multidrug-using patients seen for psychiatric reasons (not necessarily drug-related) admitted having experienced paranoid thinking at some time during a marijuana experience. In most cases the effect was not severe and all of these patients were continuing cannabis USe.325
Bialos has reported eleven cannabis adverse reactions seen at the Yale University Health Department during the academic year 1968-69. The school has a population of 8,500.52 Pillard noted that:
Durham found no instances of "marihuana induced psychosis" at the Student Health Centres at the University of California at Berkeley and at Stanford University. In 1968 these schools had a combined student population of over 40,000."' Hochman reports that:
Furthermore, a large survey of University of California undergraduates in Los Angeles found no difference between marijuana users and non-users in the frequency of psychiatric treatment or a variety of other psychiatric variables. 276 The University of California at Los Angeles has approximately 25,000 students, over one-half of whom have tried cannabis.
Schwarz has reported that six cases of acute cannabis intoxication were admitted to the University of British Columbia Infirmary over a two-year period ending in spring, 1970. One patient was hospitalized three days, the others were kept overnight. None were diagnosed as being psychotic. Schwarz has also seen 14 cases of cannabis-associated psychological problems which did not require hospitalization, and cautions that his figures are probably low since some students may have been treated off campus. In 1970, the University of British Columbia had approximately 25,000 students, of whom probably close to one-half had used marijuana or hashish.549
Surveys of clinicians' experiences in the general community have uncovered considerably more instances of cannabis-user contact with treatment facilities than are reflected in the student figures. Apparently few of these cases have required hospitalization, however.
In a 1968 study primarily concerned with LSD, Ungerleider surveyed 2,700 clinicians in Los Angeles County, asking for reports on drug adverse reactions, broadly defined as "a drug-induced state which had led individuals to seek professional help". Fifty-nine per cent replied, reporting 1,887 cannabis cases which had come to their attention over an 18 month period. 625
Unfortunately, no further information was obtained regarding the nature or severity of the cases, treatment required, referrals, other drug use, or the total patient population.
Studying much the same catchment population in California, Lundberg and co-workers surveyed (by computer) 701,057 consecutive admissions to the Los Angeles County USC Medical Centre from 1961 to 1969 and found only nine cases of marijuana-induced hospitalization during the entire period. Five cases followed intravenous use of a crude cannabis extract, one followed ingestion and three involved smoking. The latter four subjects were hospitalized for one day, and the others were released within eight days. The researchers felt that, because of the general "open door" policy and the enormous size of this general medical and psychiatric complex, the patient population seen represented accurately the spectrum of diseases occurring in the metropolitan community of almost seven million people which it served. They indicate:
D. Smith reported that:
Durham found no cases of "marihuana induced psychosis" at the Stanford-Palo Alto Hospital.166 More recently, D. Smith has reported a variety of less severe, and infrequent, adverse reactions to cannabis in the Haight-Ashbury area of San Francisco. Such cases included acute toxic reactions and confusional states with anxiety, paranoia, disorientation, nausea and, more rarely, short-term psychotic breakdowns. Smith feels that chronic heavy marijuana use is often associated with social maladjustment and an "amotivational syndrome." 576
At a large psychiatric hospital in New York, Hekimian and Gershon carefully studied 112 persons chosen randomly from the patient population admitted with a history of "drug abuse" over a seven-month period in 1967. This latter group made up 5% of total admissions. Eight of these patients were admitted in a toxic psychotic condition related to cannabis use. Of these eight, six had used LSD, seven had had previous psychiatric hospitalization or treatment, six described "primary or secondary symptoms of schizophrenia prior to smoking marihuana", one had been diagnosed a "schizoid Personality" and the last was considered "depressive" prior to cannabis use. Four did not show rapid improvement and were further detained. Cannabis cases, like the eight described, apparently made up less than 0.4% of the 20,000 annual admissions to the hospital. The authors note that, "Our patients did not display a characteristic marihuana psychosis." [P. 179] They concluded:
Keup studied 126 of 165 patients admitted to a Brooklyn Hospital in 1968 "with a history of drug abuse". Over two thousand patients were admitted during the same period. "Fourteen patients were found to have suffered, at some time from cannabis induced psychotic behaviour of a more serious nature. In two Patients, cannabis seemed to be the direct cause of admission (less than 0.1% of all admissions); in four cases, the drug contributed to the events leading to hospitalization and, in the remainder, cannabis had caused serious difficulties in the past. Keup stressed the varied symptomatology of cannabis-related pathology and the difficulties in relying on hospital diagnoses only one of the cases was labeled "toxic psychosis" in the admitting diagnosis. Almost all of the cases had had considerable prior pathology, and six were considered schizophrenic in some cases "mobilized or aggravated" by cannabis. In addition, most were multi-drug users. "In our series ... none of the cases was pure enough to qualify as a cannabis case...... " 331 Even in some of Keup's primary cases, the role of cannabis in the disorder is highly questionable.
In the 1967 trial Commonwealth of Massachusetts v. Leis & Weiss,405 presided over by Judge G. Tauro, much attention was directed to the possible role of marijuana in mental illness. There was a consensus among medical witnesses that acute panic or psychotic reactions to cannabis did occur in certain circumstances. Furthermore, manv witnesses noted cannabis-related problems of a more prolonged and subtle nature, often complicated by multiple-drug use. The information presented indicates that, at that time, severe or chronic cases of adverse reaction to cannabis rarely came to medical attention. No systematic studies or formal data were provided, however. In his testimony, H. Brill, director of a large New York State mental hospital which houses about 10,000 patients. reported that he:
Regarding the incidence of hospitalization due to marijuana use, Fort194 told the court:
Louria testified that at Bellevue Hospital in New York, he had seen only a "minuscule" number of patients who had been admitted with a "marihuana psychosis". He estimated that one per cent or less of marijuana users would experience an acute panic reaction.378 Malleson knew of only four cases over a three-year period at the University of London Health Service where cannabis was a compounding factor in admission. He felt that cannabis use may make psychological problems more difficult to deal with, but "...I believe the excessive smoking of cannabis is a consequence of the trouble and not the cause in all cases that I have heard of."391 Farnsworth testified that ten cases of psychotic episodes due to cannabis use had been seen by his staff at the Harvard University Health Services, but he had "...not seen anyone with a permanent psychotic injury with marihuana", nor had he seen any persons committed to a hospital as a result of "marihuana psychosis".176
In 1969, the Committee on Youth of New York5 surveyed by mail 1,253 pediatricians regarding their attitudes toward marijuana. Responses were obtained from 755. Most of the respondents felt that marijuana was psychologically and socially harmful. About one-third had seen patients in the past year who used marijuana, and of these, 80 reported 337 patients in whom marijuana usage was part of the presenting complaint. No description was given of the nature or the severity of these symptoms, however.
All psychiatric hospitals in England were asked to report cases of admissions related to drug dependence in 1966. Out of a total national psychiatric admission population of 163,980 for the year, 82 cannabis cases were reported. On the basis of a subsequent analysis of these case reports, the investigators felt that in at least 37 instances, cannabis played a clear role in admission to the hospital. An increase in cannabis-related cases was reported in 1967.26,27
The Narcotic Addiction Foundation464,537 surveyed medical practitioners in the Province of British Columbia in 1969 asking if they had ever had to treat a patient for his non-medical use of drugs. Of the 1,100 physicians who replied (42% return), 109 reported seeing 335 cases involving the use of marijuana. the majority appearing since 1966. Without being specifically requested to do so, in 90 of these cases the doctors volunteered the information that there were no adverse reactions associated with the case, or that the main concern seemed to be the anxiety of parents rather than any direct medical problem in the patient. A similar report of "parental referrals" has been made by Smith and Mehl.576 These findings call into question any simple interpretation of survey tabulations of marijuana cases seen by physicians. A similar proportion of non-adverse reaction cases may be present in other medical surveys. The 245 adverse reaction cases reported in the British Columbia study should be considered in the context of the population of over 100,000 persons in the province who had used cannabis in 1970.349,350, 351 No further details were obtained from the physicians as to the nature or severity of the adverse reactions reported.
In 1970, the Hamilton Academy of Medicine surveyed its members regarding their attitudes toward, and experiences with problems arising from the non-medical use of drugs. Although no precise estimate of the number of drug adverse reactions was obtained, physicians did rate alcohol, LSD, amphetamines, heroin. barbiturates, solvents, cigarettes (tobacco) and marijuana with respect to their effects upon the health of their patients. While cannabis was definitely not considered harmless, marijuana was rated as having the least harmful effect upon health of the drugs mentioned.250 This finding would suggest that the incidence of serious cannabis problems is relatively low in the Hamilton region.
In 1970, the Newfoundland Department of Health and the Newf'oundland Medical Association surveyed the practising physicians of the province.470 Physicians were asked about instances in which they "...may have been consulted by individuals with 'drug problems' or by concerned parents." No time interval was specified. Of seventy-two replies (approximately 20% return), there were sixty-two marijuana cases re ported. The nature of the consultation involved was generally not specified.
Silver, head of a drug emergency project at the Montreal Jewish General Hospital, reported that of approximately 100 adverse drug reactions of various kinds seen monthly during 1971, there were "amazingly few cannabis complications" and those that did appear were practically always novices to the drug who had become frightened. None of these people required hospitalization or medication for his anxiety reaction. 562
Because of various administrative and communication problems, the statistics of the federal Poison Control-Drug Adverse Reaction Program can provide little epidemiological information regarding the non-medical use of drugs. It is interesting to note, however, that in 1970, 75 cases of adverse reaction were reported as attributable to cannabis. In the majority of these cases, cannabis was part of a general multiple-drug problem. The list contained twice as many males as females, and most of these individuals were under 24 years of age. Incomplete data for part of 1971 indicate 14 "pure" cannabis cases, including one instance of intravenous use of hashish extract, and 13 multiple-drug combinations. The most frequent cannabis combinations involved LSD, alcohol or amphetamines. 107,463
In the spring of 1971, the Commission conducted a pilot study in the Ottawa-Hull area of physicians' contact with, and attitudes toward, persons involved in the non-medical use of drugs over the preceding 12 month period. 439 All physicians who were listed in the telephone book as general practitioners, psychiatrists, neurologists, pediatricians, or who had no specialty listed, were contacted. Two mail surveys were done and a number of selected telephone and in-person follow-up interviews were conducted. A general inquiry regarding the full spectrum of drugs was followed by a survey focussing on adverse reactions to cannabis. On the basis of this experience. tentative plans for a representative cross-national mail survey of physicians were abandoned. It became clear from this preliminary project that detailed and accurate data regarding the frequency and nature of drug treatment cases could not be gained from this type of investigation without enormous expenditure of time and money, if at all. Treatment records were generally not easily accessible, either to researchers or the physicians' staff, and responses were generally, at best, rough approximations, and in many cases were grossly inconsistent and contradictory within respondents. Although physicians were generally co-operative, in many instances a significant lack of knowledge or familiarity with the identification, diagnosis and treatment of problems related to non-medical drug use was revealed-even in persons with significant numbers of patients presenting drug-related problems.
In the cannabis survey, 57% of the 214 questionnaires sent out were returned. Because of incomplete data and obvious errors in the replies, as well as the other difficulties described above, accurate estimates as to the frequency of various cannabis adverse reactions cannot be easily obtained from this study. Other more general findings are of interest and can provide at least some broad information regarding physician contact with cannabis-using patients. This pilot study, at best, gives impressions of physicians' personal opinions and attitudes. and some glimpse of the epidemiological aspects of the treatment picture. It also makes clearer the limitations of similar previous surveys.
Of the drugs mentioned in the general survey, alcohol was responsible for the largest number of cases, followed by amphetamines, multi-drug combinations, cannabis. hallucinogens, barbiturates and minor tranquilizers and opiate narcotics. There appeared to be a greater tendency to attribute adverse effects to cannabis when no alternatives were specifically presented than when other or multi-drug options were available on the questionnaire form.
Sixty-five per cent of the physicians reported having seen patients whom they knew used cannabis, but only about one-half of these had seen or treated any patients in connection with their cannabis use. Cannabis-using patients ranged from 10 to 47 years of age with a modal age of 18. One-third of the physicians reported having seen patients because of parental, school, legal, or other external concern rather than concern expressed by the patient himself. Approximately three-quarters of the doctors who saw cannabis-using patients because of such social pressures had not had to treat any of these persons for adverse reaction to cannabis. This information is in agreement with the situation described by Russell537 and Smith and Mehl 576 and clearly indicates that doctors are frequently involved in social consultation of little medical significance, and casts further doubts on simple tabulations of "cannabis cases seen" by clinicians.
A general picture of multi-drug use emerged in the majority of patients requiring treatment or attention. Three-quarters of the physicians who had seen patients in connection with their use of cannabis noted that other drugs were often equally or secondarily involved. Many of the patients seen for cannabis-related problems had serious prior or concomitant personal or social difficulties not attributable to the drug and, in many instances, patients' misuse of cannabis was seen as a symptom rather than a cause of underlying psychological disorder.
Almost one-fifth of all respondents reported having seen one or more patients with cannabis-related problems who had required psychiatric treatment. Several psychiatrists had patients referred to them, whom they felt did not require psychiatric attention. About one-fifth of the physicians had patients who had been seen by another physician because of referrals.
Almost one-fifth of the physicians had seen one or more patients with anxiety or acute panic reactions. Other adverse reactions, listed in order of decreasing frequency, include: prolonged depressive reactions, acute Psychotic reactions, cannabis-induced recurrences ("flashbacks") of previous (non-cannabis) drug experiences, recurrences of previous cannabis effects, acute depressive reactions and prolonged psychotic reactions. Other drugs in addition to cannabis were involved in many of these cases. Almost one-fifth Of the doctors indicated that they occasionally used drugs in the treatment of cannabis-related problems. Five to ten per cent of the respondents reported having seen one or more patients who had been hospitalized because of cannabis adverse effects. The majority of these were for less than one week. although two respondents noted cases in which hospitalization lasted for months.
Fourteen per cent of the doctors reported having seen some patients who had serious chronic social and psychological problems attributable to cannabis use which did not actually require hospitalization. Fifteen per cent of the respondents noted having seen patients whom they believed were suffering from persistent problems of thinking and cognition attributable to chronic cannabis use, and, in a few cases, organic neurological symptoms were suggested. Seventeen per cent of the doctors reported having seen one or more patients who displayed signs of psychological dependence on cannabis. One-quarter of the respondents reported having seen one or more patients whose school or work performance was thought to be adversely affected by cannabis use. Among these patients was noted some evidence of an "amotivational syndrome" or apathy and lack of energy and drive which was attributed to cannabis use.
Qualitatively, the overall findings of this feasibility study are in general agreement with the bulk of clinical reports of adverse effects of cannabis in the North American literature, and suffer from much of the same limitations and drawbacks previously discussed. Few conclusions can be drawn regarding the accuracy of the physicians' memories or the validity of the diagnoses and case histories involved. The high incidence of multi-drug use in problem cases complicates any cannabis-specific interpretation, but the study does give some general information as to the current drug treatment picture in this area. The study clearly points out limitations in the interpretation of other clinician or therapist surveys in the literature, and suggests that further work of this type would probably be of little additional value. Careful, intensive study of systematically selected cases and control subjects would be of considerably greater epidemiological import.
The Commission conducted a study of youth-oriented innovative services, drop-in centres, hostels, and 'street clinics' across the country.528 Mailed questionnaires, and telephone and in-person follow-up interviews with staff were involved. Of 80 organizations on our original mailing list, about one third were able to provide information relevent to this discussion. All of the organizations reported that cannabis use was either very prevalent or common in the populations they served, but none of the facilities reported having had to treat anyone as a result of cannabis use. These data present an interesting contrast to the reports from the physician survey discussed above. This apparent discrepancy is probably a product of differences in the populations served and the functions played by the respondents in the two studies, as well as substantial differences in personal experiences, attitudes and beliefs regarding cannabis use.
The Commission also conducted a general survey of the diagnostic records of psychiatric hospitals across the country in the spring of 1971.528 All psychiatric hospitals in Canada were included in the survey with the exception of those specializing in the treatment of alcoholism, emotionally disturbed children. mental defectives, and aged and senile patients. Rehabilitation hospitals were also excluded, as were general hospitals with psychiatric wards (with the exception of British Columbia). Hospital record librarians were asked to report the frequency with which various drugs eared as rimar or secondary factors in the official diagnoses of the patients resident in the hospital on the date of the inquiry. This effort was intended to serve only as a general barometer and gross preliminary inquiry into the extent to which the nonmedical use of drugs had imposed upon the country's hospital system, and was not expected to provide a precise index of the actual number of drug-related cases in treatment. Of 56 psychiatric hospitals included in the survey, 51 were able to describe their resident populations.
In general, alcohol was the drug most commonly implicated in psychiatric disorders, followed by LSD and other hallucinogens, amphetamines, cannabis, opiate narcotics, and barbiturates. Of a total of 22,827 psychiatric in-patients from all provinces except British Columbia, cannabis was mentioned as a primary factor in 20 cases and as a secondary factor in 18 (representing a combined total of 0.17% of the patient population).
In British Columbia there are few psychiatric hospitals, and the largest such institution was only able to provide admissions records. Consequently, non-psychiatric hospitals with psychiatric wards were also surveyed in that province. Because of the different sample and data base for British Columbia, comparisons with the other provinces are limited. Twelve of thirteen hospitals contacted provided resident sample information. Cannabis appeared as a primary factor in 5 cases and as a secondary factor in 15. This represents 1.4 and 4.3%. respectively, of the 351 psychiatric ward inpatients in these institutions. At the major psychiatric institution (3,000 beds) there were no cannabis-related cases among 226 consecutive admissions for the month of April, but information on resident patients was unavailable. It is difficult to interpret the relatively high proportion of cannabis-related patients in the psychiatric wards compared to the consecutive admission pattern in British Columbia, and the general residential picture for the rest of the country. While extent and patterns of drug use specific to British Columbia may be a factor, the relatively small numbers involved and the limited nature of the data base and sampling procedures used complicates further comparisons.
Interpretation of even the general national figures is obviously not straightforward. nor was it expected to be. All hospitals which had reported cannabis-related cases were asked for specific case history summaries. A total of 40 case history reports were received in which cannabis was considered a primary or contributing factor in the admission. The age of these patients ranged from 14 to 27 years, and 73% were males. In spite of the limitations of secondary analysis of often condensed and incomplete case history reports, some general impressions of these patients emerge, and information was revealed which sets clearer limitations on the interpretation of the general statistical data obtained. Even though the initial inquiry specifically requested only the number of patients with drugs mentioned in the official diagnoses, in many instances hospital staff went well beyond diagnostic information and interpreted the request as a more general quaere regarding drug involvement in the patient population. Unfortunately, hospitals were not consistent in their interpretation of the request and may have also applied differential criteria for the various drugs. The cannabis-related case histories revealed that most of these patients had intense involvement with other drugs. including alcohol, speed and LSD and, in some cases, had only passing or occasional experience with cannabis. It appears that in many instances drups were considered primary or secondary factors essentially because of general information that the individual was a user, either in the past or at the time of hospital admission. The inclusion of such cases would undoubtedly give an inflated estimate of the role of cannabis in psychiatric disorder. On the other hand. as Keup has shown, many patients with drug-related problems are not detected in the admitting diagnoses and can only be identified by intensive background exploration. 330,331 Consequently, diagnostic record sampling is bound to miss certain valid cases. Almost one-half of the patients in the follow-up study had been diagnosed schizophrenic at some time, and a high proportion of personality disorders and adolescent adjustment problems were also noted. In those patients in which further data were available, the duration of hospitalization ranged from a few days to several months.
In general, the cannabis picture in this study, which admittedly is only partially revealed, again reflects the bulk of the North American clinical literature. Hospital resident sampling techniques tend to detect more chronic cases than do consecutive admissions surveys, for example, and, as would be expected, these individuals generally showed considerable prior and concomitant psychiatric disorder and, typically, frequent or chronic use of other drugs. In only three instances did hospitalization appear to be the direct result of an acute reaction to cannabis use. No clear cases of "cannabis psychosis" were identified, although it appeared that in some instances the chronic use of cannabis may have contributed significantly to the condition which resulted in hospitalization. The data from this study do not allow firm conclusions regarding the causal role of the drugs in the cases described, and is subject to the limitations of incomplete case history reports described earlier. The data do suggest, however, 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. Significant changes in the extent and patterns of cannabis use in North America will undoubtedly alter the treatment picture, and such changes should be carefully and systematically monitored.
The Incidence of Adverse Reactions in Non-Patient Samples
In studying psychiatric patient populations we have a priori defined the group under study as pathological. Consequently, only limited information can be gained from tabulating the pathology within such groups. There have been a number of studies of marijuana users among prison populations. While such subjects are not necessarily pathological, they have clearly been selected for deviant behaviour and cannot be considered representative of marijuana users in general. Few controlled studies exist of cannabis users who were selected on some non-pathological or non-deviant basis. It would be preferrable to compare a cross-sectional sample of marijuana users with a control group of non-users with similar social, economic, and educational backgrounds. Even this type of investigation can only demonstrate factors which are associated with the use of cannabis. It cannot indicate causality.
Long-term prospective studies would be most useful, but are extremely difficult and expensive to undertake.
The Mayor's Committee of New York studied 48 marijuana-using prisoners who had been smoking regularly for 2 to 17 years with a mean of 8 years. The number of marijuana cigarettes smoked per day ranged from 2 to 18 with a mean of 7. The investigators concluded that there was no evidence that the marijuana users had suffered any mental deterioration as a result of their use of the drug.407 Bromberg examined 67 prisoners who were marijuana users@ none were psychotic, although neuroses and personality disorders were frequently found. There were no signs of chronic dementia or deterioration.86
The Addiction Research Foundation of Ontario conducted a study of 232 confirmed marijuana users in Toronto in 1968 and 1969.481 Prison and court referrals provided about one-half of the subjects and the remainder were volunteers not contacted through criminal-legal channels. The majority came from middle-class or upper middle-class homes, and 16 per cent were students. The average age was 22 (range: 15-42), and males outnumbered females four to one. The average duration of marijuana use was 2.7 years (range: 1-20).
Preliminary analyses suggest the following characteristics in this sample: the subjects tended to be multiple-drug users (tobacco and alcohol were used by almost all of the subjects, more than one-half had tried LSD and speed, and one-third had tried opiate narcotics); cannabis was generally used about twice a week in the company of friends, accompanied by passive rather than active behaviour. Almost all subjects found the usual effects favourable, although about one-third had had at least one acute unpleasant experience (physiological or psychological) with the drug; only 5% had experienced more than a few 'bad trips', and a similar proportion had experienced one or more unpleasant cannabis reactions lasting more than one day; about one-half felt that cannabis had improved their lives, while a much smaller proportion thought it had made things worse; the subjects "tended to be underactive physically, engaging in passive pursuits"; about one-third believed in the "Protestant work ethic", while almost as many rejected it, more than one-half were thought by a psychiatrist to be psychologically unstable or disturbed. Twelve per cent regularly experienced a "contact high" or a "flashback" to their drug experience, 17% never experienced either of them, and slightly more than one-half experienced one of these at least occassionally. It is unfortunate that these two concepts were considered together as a single item since they are not clearly defined. and, as discussed earlier. are not necessarily related.
The researchers stress that their findings demonstrate an association, and not necessarily a causal relationship, between the regular use of cannabis and other characteristics described in this sample. The lack of a comparable matched control group precludes certain generalizations. and the frequent use of other drugs by these subjects limit conclusions specific to cannabis use. A complete report of this study will be published in the near future.
The majority of studies of cannabis users not selected from deviant Populations have concentrated on college or high school students. In several of these, psychiatrically oriented questions were asked and in a few studies some psychometric data were obtained as well. There are often serious problems with applying, to cannabis or LSD users, conventional psychiatric tests (for example, the MMPI) which have been developed and standardized on populations without psychedelic-drug, experience, since in many instances the subject's response to a test item will be altered by his drug experience even if no residual direct effects exist. We have been unable to find any cross-sectional studies of cannabis users in which intensive direct clinical observations were involved. Correlational studies can, of course, only provide information regarding characteristics of cannabis users, and cannot establish causal relationships.
Several studies using personality questionnaires or inventories have found that cannabis users (especially chronic users and those involved in the regular use of other drugs) tend to obtain more deviant scores than non-users.84,103,181,507 Some investigations have found no appreciable differences between cannabis users and non-users on pathological dimensions, 244,408,570,682 although other personality correlates have been noted. On the basis of such studies, cannabis users have been described as more open to experience, unconventional, individualistic, spontaneous, adventuresome, socially poised, impulsive, suggestible, rebellious, alienated, pleasure-seeking, antiauthoritarian, creative, aesthetically oriented, opinionated, unreligious, socially maladjusted, dissatisfied or depressed than non-users. On most variables, however, no consistent differences have been found between those who use cannabis and those who do not.59,84.2 32.244,247,2 77,408,415,476,5 5 3,650,682 It should be noted that the majority of users in these studies were students without extensive, heavy or long-term cannabis use. Most were light or intermittent smokers. There is apparently a greater tendency to find pathology among regular chronic users than persons with more casual involvement with the drug. It is not clear from any of these studies whether the personality attributes described lead to the use of cannabis or vice versa.
Robins and associates reported the first study of the long-term outcome of marijuana use in a group not selected for deviant behaviour. The subjects were 235 black men who had gone to public elementary schools in St. Louis, Missouri in the early forties. While the characteristics of such a population may have questionable applicability to present marijuana use in Canada, this careful retrospective study should be considered. Persons in this sample who had used marijuana (and no other drugs except alcohol and tobacco) differed significantly from the non-marijuana users in that the users had more often: drunk heavily enough to create social or medical problems, failed to graduate from high school, reported their own infidelity or fathering of illegitimate children, received financial aid, had adult police records for non-drug offences, and reported violent behaviour. While these findings indicate an association between marijuana use and these other behavioural characteristics in this population, causal variables have not been identified. The heavy use of alcohol in these subjects complicates the interpretation considerably. Among the subjects who used only marijuana and alcohol, almost half had medical or social problems attributable to drinking and more than one-third were definitely considered alcoholics. When those subjects who were classified as alcoholics were eliminated from the data, the only statistically significant difference between the marijuana users and non-users with with respect to financial aid received in the past five years. Subjects who used 'harder drugs' (for example, heroin. amphetamines and barbiturates) in addition to marijuana and alcohol were significantly more deviant than non-users, even after the alcoholics had been eliminated from the sample. Almost one-half of the subjects who had used marijuana also had some experience with the 'hard' drugs.
In a survey of University of California at Los Angeles undergraduates (half of whom had tried marijuana) no differences were found between users and non-users on history of psychological or psychiatric treatment. or a variety of other psychiatrically oriented survey variables.275 Similarily, in a Commission study of 108 adult cannabis users and 34 matched control subjects, no differences were found between the two groups in psychological problems reported or visits to a psychotherapist.239 By contrast, two studies of adults in the San Francisco area found that cannabis use was more common among those who had seen a professional psychotherapist.299,393 In a study of Harvard seniors, Walters and associates found more visits to a psychiatrist among those students who were users of marijuana or hallucinogenic drugs. However, in half of these cases, the individuals were not users at the time they saw the psychotherapist. Few felt that marijuana use was related to their seeking psychiatric help.659
Smart and Fejer of the Addiction Research Foundation have recently conducted two surveys which have examined the relationship between cannabis use and experience in psychotherapy. Among high school students in a semi-rural area of Ontario,181 for all drugs (including alcohol and tobacco) significantly more users than non-users had received treatment for psychological problems. Non-users who had received treatment noted family or school problems most frequently as the reason for treatment. Users of illicit drugs most often gave depression as the reason for therapy. It is difficult to ascertain the role of marijuana use in these data since the incidence of psychotherapy generally increases with age, as does drug use. The investigators point out that age differences may be a confounding factor in the correlation between marijuana use and treatment. As well, we do not know whether the treatment preceded or followed marijuana use. In presenting the difference between treatment frequency in users and non-users, there is no control for the use of other drugs, and many of these individuals are multi-drug users.
In their survey of adults in Toronto,570 these same investigators found that, overall, more cannabis users than non-users had been treated for psychological problems. However, when age was controlled, only in those over 30 was there a significant relationship between experience with cannabis and treatment. Marijuana users more often reported feelings of depression than did non-users. Again, neither the order of these occurrences, nor possible causal links were determined.
In Tart's study of regular marijuana users, about one-third had witnessed at least one person experiencing an "emotional crisis" with marijuana and slightly fewer had actually experienced a 'bad trip' themselves. The subjects were also asked during what percentage of the times they had gotten 'high' had they witnessed a 'bad trip'. More than two-thirds estimated that such occurrences happened in less than 0.1% of the sessions. Two per cent of the sample indicated that 'bad trips' occurred in 5-10% of sessions. In the vast majority of the 'bad trips', friends and other non-professionals provided help or the incident subsided by itself. In approximately ten per cent of the adverse reactions some contact was made with professional treatment facilities. 598
Campbell interviewed 144 cannabis-using young people. About one-third reported having had some "bad" or unpleasant experience with the drug; 5.7 per cent had experienced moderately severe reactions and 2.8 per cent had had what were called severe reactions.105 In a Commission study of adult cannabis users239 one-quarter of the subjects reported having had experienced some negative reaction to cannabis in the past. Unpleasant experiences were listed as among the reasons for quitting or reducing cannabis use in a small percentage of former users in several studies, including Commission surveys.53,349,359,351,415,449
In Smith's sample of patients seen at the Haight-Ashbury Clinic in San Francisco, one-third of those who used marijuana had experienced some adverse reaction at one time or another. Few of these instances were ever presented for treatment, however.575 Similarly, in a study of high school students in Ontario about one-third of the cannabis users reported having experienced, at least once. "confusion, anxiety or other unpleasant effects" from the drug. In addition, one-quarter of the users reported that they had experienced a recurrence of some aspect of cannabis effects while not using the drug. The quality, intensity or the general nature of these recurrences were not determined, however. 21
Halikas found that 16 out of 100 regular cannabis-using subjects reported that they "usually" experienced at least one acute or post-intoxication unpleasant effect, and about one-half "occasionally" experienced some adverse effects such as anxiety, confusion or memory impairment. Two per cent "usually" experienced "anxiety flashes" as an after-effect, 22% have "occasionally" experienced this and 76% had experienced it "once or never". It is not clear if these responses coincide with the "flashbacks" occasionally noted in the clinical literature.249
In his study of West Coast United States schools, Blum has broken down "bad outcomes" into several categories and generally found relatively fewer acute adverse reactions to cannabis than to alcohol. Very few of the cannabis reactions described were severe enough to require professional treatment, and typically included such things as headache, nausea. emotional upset, sensitivity to criticism. and difficulty in thinking. Blum calculates that only about one in 14 adverse reaction cases actually are seen for treatment.60
Goode found a tendency for women to report negative aspects of the cannabis 'high' more often than men. Less than 10% of male users reported sometimes feeling paranoid. while this was true of 21% of the women. Women more often noted that they had experienced depression (6% for met, and 15% for women) and depersonalization (8% vs. 16%) at least once with cannabis.232
Although many gaps exist in the epidemiological picture of cannabis adverse effects, studies based on non-medical samples provide little evidence at this time that cannabis causes a significant degree of pathology in the general population of users studied in North America. Some unpleasant aspects of cannabis effects are acknowledged by most users and it would appear that a significant proportion have experienced at least one generally unpleasant 'high' from the drug. Very few of these negative reactions require n edical assistance. Although cannabis users in some populations may differ from non-users on a variety of personality variables, the majority of the findings are within the general range of normality, no uniform or consistent picture has emerged and causal relationships have not been established.
AMERICAN EXPERIENCE IN VIETNAM
In the past several years a number of reports have appeared of adverse reactions to cannabis among U.S. soldiers stationed in Vietnam. Surveys suggest that 25-68% of the hundreds of thousands of U.S. soldiers involved in the war have smoked the potent, inexpensive, and readily available Vietnamese marijuana.51,138,255,597,630 Cannabis use was reportedly higher in a psychiatric population than in other patients in 1968. 115, 509 The use of opium, both alone and mixed with marijuana, has also frequently been reported among U.S. soldiers and some investi ators claim that half of the cannabis contraband seized contains opiates.319,597 However, good statistical evidence on the extent of drug use or its purity in Vietnam is not currently available.
Talbott and Teague reported that in 1967-68, persons suffering from acute, self-limiting psychosis associated with cannabis use and environmental stress, were appearing for medical treatment at the rate of one or two per month, from an overall population of about one-half million individuals. The authors described 12 cases appearing with acute symptoms including anxiety and fear, impaired cognitive functioning and memory, excited and disorganized behaviour, paranoia and other delusions, hallucinations, aggression (in one case, homicide was involved). A "definite toxic, organic quality" was noted. Ten patients recovered within three days and the other two within a week and one-half. In all cases, the situation described was reportedly the patient's first experience with marijuana, and in only two individuals was there significant evidence of previous psychiatric disorder.597
More commonly, reports from Vietnam have dealt with regular or heavy cannabis users with generally poor premorbid psychological adjustment. Fidaelo reported that in 1968, approximately five per cent of psychiatric admissions at an army hospital were cannabis-related psychotic reactions, generally in heavy users. This incidence is essentially the same as that noted by Talbott and Teague. In discussing a minority of cases which did not clear Up in a few days, the author states:
Colbach and Crowe reported that out of a catchment population of 45,000 soldiers in 1969, about five cases per month (approximately ten per cent of the patients seen) appeared with schizophrenia-like psychoses usually associated with a history of heavy marijuana use. These individuals were characterized hv a prior "borderline personality organization". No cases were seen in which marijuana was the primary cause of aggression directed to the self or toward others.138,139
Marijuana was apparently often used by soldiers after a battle as a tranquilizer.509 Bev and Zechinelli have further suggested that chronic marijuana use may be a form of attempted self-treatment in some disturbed individuals in Vietnam. They described 20 consecutive soldier patients, all habitual users, who were hospitalized for 24-72 hours for acute psychotic reactions. "It was observed that all of these men had serious characterological problems and could be classified as 'borderline personalities'." The authors contend that:
After reviewing some of the U.S. marijuana experience in Vietnam, and related literature, Hauschild concluded that cannabis:
J. Kaplan recently described a general problem of heavy multi-drug use (including opiate narcotics) in the military patient population. The majority of the problem patients had severe underlying personality and character disorders. A number of chronic drug users who smoked heavily "day in and day out" reportedly suffered from an "amotivational syndrome", characterized by passive behaviour, loss of complex goals, withdrawal from activities, procrastination, poor concentration, and reduced ambition. 319
It has frequently been pointed out that the set and setting of cannabis use by U.S. military personnel in Vietnam may approach the ultimate situation for producing 'bad trips'. One medical officer, after returning from Vietnam, voiced the opinion that:
The actual frequency of adverse reactions to cannabis in Vietnam is uncertain. Because of the frequent lack of confidentiality of medical records in the U.S. military. and the potentially severe penalties for illicit drug use, which. until recently. potentially included the complete loss of war veterans benefits,319 a significant number of acute cannabis reactions. especially of the less severe variety, are undoubtedly never brought to medical or official attention and, consequently, will not appear in official statistics. The cases reported to date, although clinically significant, represent a low percentage of the psychiatric population treated and a very small proportion of cannabis using soldiers.
Several observers have pointed out that even though drug reactions are now seen more frequently than in past wars, battle fatigue and psychosis, other acute war reactions, and psychiatric admissions in general are considerably lower among soldiers in Vietnam than in World War II or in the Korean War. 243,597,608 It has been suggested that many of the marijuana cases seen medically may represent combat reactions complicated by, or coincident with, cannabis use. It has further been suggested that the high incidence of drug use among soldiers in Vietnam may possibly be masking, or to some extent, even protecting that population from traditional wartime reactions, although a variety of other factors such as improved training, treatment, and personnel turnover might well account for the differences reported.243 It should be noted that acute reactions have been described in individuals without obvious prior pathology, and in military personnel not actually working under combat conditions. Some observers have suggested that the recently increased number of psychiatric cases in Vietnam might be a function of drug use problems.138
Clearly, a thorough and systematic investigation of the U.S. military experience with cannabis in Vietnam is indicated. Firm conclusions regarding essential questions as to the nature and the extent of cannabis-related psychiatric problems associated with the Vietnamese War cannot be made on the basis of the evidence presently available. Furthermore, the applicability of any such findings to present conditions of cannabis use in North America is limited, although it is clear that general conditions of physical and psychological stress are by no means restricted to military operations.
LABORATORY REPORTS OF ADVERSE REACTIONS
A major difficulty in interpreting clinical reports of adverse reactions to illicit drugs is that one rarely has adequate information regarding the quantity, quality and often. even the general identity of the drug involved. In the East, cannabis, when smoked, is invariably taken with tobacco and is, in some situations, mixed with other potent psychotropic compounds as well. Such practices obviously complicate clinical interpretation. Because of continual rumours of 'spiked' or adulterated cannabis in North America, it has been suggested that some of the adverse reactions described in the clinical literature may not have involved pure cannabis, but might be attributable to some other unknown drug. As discussed earlier, however, samples of cannabis mixed or adulterated with other psychotropic compounds have rarely been documented by chemical analysis in North America. Cannabis is usually what it appears to be, or may be diluted or cut with inactive plant substances. Adverse reactions to pure cannabis, both in the laboratory and in the Community, have been documented. For example, the Commission has investigated two cases of acute panic or psychotic reaction in Ontario and found, by chemical analysis, that the marijuana involved was uncontaminated and of high purity and potency. Interestingly, marijuana from the same original batch was used by over one hundred other persons, totalling well over one thousand individual instances of use without serious adverse reaction. The two cases described occurred simultaneously in the same session. Smith and Mehl have reported similar cases of idiosyncratic adverse response. 576
Several experimental reports have contained descriptions of acute panic or psychotic reactions which have occurred under controlled laboratory conditions with pure cannabis compounds. It must be stressed, in this context, that scientific laboratory conditions often do not provide a particularly pleasant setting for drug consumption, or one which generalizes readily to normal social conditions of drug usage. Subjects, even in non-drug studies, are often apprehensive about being experimented upon. Consequently, one might expect to see a higher incidence of drug adverse reactions in some .neutral' scientific laboratory or psychiatric hospital experimental settings than under conditions of normal social usage.
The Mayor's Committee of New York (1944)407 conducted experiments with 77 persons-72 of whom were inmates of various New York prisons. Forty-eight of these subjects had used marijuana previously and some had been heavy users of opiate narcotics. Cannabis concentrate was given orally in generally large doses and ordinary marijuana cigarettes were administered in various quantities. Using admittedly high doses, the researchers reported nine cases of psychotic reaction in the prisoners studied. In six instances, acute or short-term adverse reactions characterized by "...mental confusion and excitement of delirious nature with periods of laughter and anxiety" occurred and rapidly cleared. Three cases of "true" psychosis appeared to be associated with the experiment.
The precise role of marijuana in the psychotic states of the three unstable persons is not clear ... [in the first subject] the psychotic episode was probably related to epilepsy .... In the case of the second and third subjects, the fact that they were sent back to prison to complete their sentences must be considered an important, if not the main factor in bringing on the psychosis.407
None of the nine individuals had previously been a regular user of cannabis. The researchers indicate that:
Isbell, and co-workers gave various doses of isolated THC to a group of former opiate narcotic addict prisoners. With the higher doses "marked distortion in visual and auditory perception, depersonalization, derealization and hallucinations. both auditory and optical, occurred in most patients. Delta-9 THC, therefore, is a psychotornimetic drug and its psychotornimetic effects are dependent on dose." Such occurrences may also appear in some individuals as "idiosyncratic" reactions at lower doses. It has been noted that many of the symptoms which Isbell labelled 'psychotomimetic" might be called 'psychedelic' by scientists with different attitudes or theoretical orientation. Euphoria was consistently noted in most subjects, but in two individuals, the drug experience was definitely unpleasant, and they were released from the study.296,298
Ames, in South Africa, administered cannabis concentrate orally, in moderate to high doses. to ten apparently cannabis-naive medical staff volunteers. including herself. In a thorough report, the author drew many parallels between the cannabis-induced state and natural psychosis. Some transient anxiety and confusional reactions were noted among the subjects.16
In South America, Cordeiro de Farias demonstrated noxious marijuana symptoms in a group of cannabis-naive medical personnel, after a series of trials in which the marijuana dose was repeatedly increased until significant acute adverse effects occurred. In the final test, quantities up to 5.6 gm of marijuana were smoked, and confusion and anxiety resulted in some subjects. In spite of the intentions of the experimenters, and the very large doses administered to inexperienced persons, no persistent adverse effects were reported. 142
In all of the laboratory examples of adverse reactions discussed above, subjects were given doses which exceeded, in some cases, many times their preferred or regular doses, or were cannabis-naive medical personnel given large initial quantities of the drug. Many of the other subjects tested were prisoners and former opiate narcotic addicts. None of the individuals described were typical cannabis users given socially relevant doses.
In Commission laboratory experiments (including pilot projects), 65 "normal" cannabis-using individuals were tested under a variety of conditions a total of 180 times with smoked cannabis doses ranging from approximately 0.5 to 15 mg THC. The 'joints' were smoked completely and more rapidly than normal, using techniques which maximize THC delivery and absorption, although the doses given are within the general range of usual consumption in Canada. In three instances, acute anxiety or panic reactions occurred, which cleared within hours and left no residual symptoms. Although transient, these reactions were highly unpleasant and disturbing for the subjects and experimenters involved. The three subjects were young men, all occasional cannabis users, without experience with LSD or other potent hallucinogens, who presented no clear signs of prior psychopathology. It should be stressed that considerable individual differences exist in drug sensitivity and desired levels of intoxication. In addition, questions of tolerance may enter the picture. (See later section on Tolerance and Dependence.) In all three cases, the subjects were asked to consume more than they wished, and would have undoubtedly avoided the anxiety reactions had they been left to smoke to a personally selected optimal level of intoxication. One subject was under considerable psychological and physical stress at the time of the experiment, and this may have contributed to his reaction. No npn-laboratory factors were identified in the other two persons.
A number of researchers in North America have indicated to the Commission that similar acute reactions have occurred in subjects in their laboratories as well, and several such cases have recently been mentioned in the literature.111,156,307,398.431,436 It would appear that the administration of cannabis to inexperienced or infrequent users under laboratory or hospital conditions, in doses exceeding 10 mg THC (efficiently and rapidly smoked) or 30 mg THC given orally, entails a small but significant risk of acute anxiety reaction in some individuals (although considerably higher doses have frequently been given without untoward effects). Complications may also arise when cannabis is given in combination with alcohol or tobacco. No indication of persisting effects arising from a laboratory cannabis experience has been reported.
Since there have been few chronic or sub-chronic laboratory studies of cannabis effects in humans, experimental data pertaining to possible chronic adverse psychological effects are limited. In 1946, Williams and associates reported an increase in lassitude and indifference, and a lack of productive activity in prisoners given large doses of marijuana cigarettes (or Pyrahexyl) ad libitum daily for over a month. Unfortunately, no control group was run, so interpretation of these data are difficult. 670
The Addiction Research Foundation's continuing experimental study of the effects of daily marijuana smoking has focussed considerable attention on the subjects' personal and socioeconomic behaviour.436 (This research program is summarized in Annex B at the end of this chapter.) Experimental and control subjects, who were "normal" cannabis-using volunteers, were studied for several months under various drug conditions while living in a model "micro-economy" system in an experimental hospital ward. Subjects were given the opportunity of earning a living (in cash equivalent tokens) by constructing stools and weaving belts.
When large daily mandatory doses of marijuana were introduced after long periods of abstinence in the laboratory, work productivity tended to be depressed. Discontinuation of marijuana use after a prolonged period of forced daily smoking of high doses resulted in an increase in productivity. When the work ouput of subjects on a mandatory high dose was compared to that of subjects who consumed only the amounts they desired (which were, in fact, relatively small quantities) the forced-dose group showed dramatically lower average productivity, which was most pronounced in the first few weeks of testing. Some behavioural adaptation or tolerance to this effect of the drug seemed to develop over the course of the experiment, and differences between the mandatory and free-purchase groups were minimal toward the end of the experimental period. The researchers suspect that this productivity decrement is due more to a reduction in time spent working, rather than to inefficient performance.
No gross behavioural changes appeared during the experiments and there was no evidence of social deterioration, or a decline in concern over personal hygiene or physical condition. No intellectual deterioration was detected and chronic mood modification was not reflected in either staff ratings or the subjects' self reports. Repeated daily administration of the higher mandatory doses was considered unpleasant by the subjects, and a few acute anxiety reactions occurred. Psychiatric tests and examinations found no chronic adverse effects as a result of cannabis use in these experiments.
The relationship between some of the effects observed here and the socalled "amotivational syndrome", sometimes noted in clinical reports of chronic heavy users, is not clear, but the data do lend support to the notion that cannabis, in certain circumstances. may reduce motivation for performing certain normally conducted tasks. Some characteristics of data of this type are very like1y determined to a significant degree by the nature of the general living environment and the tasks involved. In this program, labour was of a repetitive, handicraft nature. Effects on work of a more intellectual or artistic variety, or on tasks of the subjects' own choosing, might yield different results, and should be explored. In addition, the stress or boredom of institutional living undoubtedly had some influence on the data, and conclusions must be limited accordingly.
SUMMARY AND DISCUSSION OF ADVERSE PSYCHOLOGICAL REACTIONS TO CANNABIS
A number of apparent conflicts exist in the North American literature on adverse reactions to cannabis. During the past few years there have been numerous clinical case reports of individuals who were suffering from a variety of acute and chronic psychological disabilities allegedly associated with cannabis use. Some writers have gone so far as to suggest that such a picture may be expected to be the typical outcome of regular cannabis consumption. On the other hand, surveys of hospital admissions and resident patients in North America have uncovered an almost insignificant number of patients with primary cannabis problems. Even university counselling and health services have a dearth of systematic records of serious cannabis difficulties. Although studies of college treatment facilities deal with a very select sub-group of the population, these statistics are interesting in that one can generally define the catchment population of students served by the counselling and health services, and often considerable information is available on drug use patterns in the population. Several limited surveys of private practitioners and clinicians in the general community provide some bridge between the apparently conflicting views presented by the clinical case reports and hospital and treatment facility records. In spite of severe methodological difficulties, studies of individual practitioners indicate that a significant number of cannabis-related cases do come to medical attention for a variety of reasons, although the role of the drug in the conditions described is often uncertain, and such patients apparently represent a minimal proportion of users. Cannabis cases are rarely referred to a hospital, suggesting a relative absence of major debilitating chronic problems in North America today. Available evidence strongly suggests that serious adverse reactions are infrequent and that only a small proportion of the adverse reaction cases which do occur ever come to medical attention.
Intensive psychiatric studies of cannabis users selected from non-patient populations are rare@ reports of comparisons with proper control groups are, at this time, virtually non-existent. The few studies which approach these criteria have not demonstrated the existence of serious complications with cannabis use.
In conclusion, existing limited information suggests that cannabis use in North America has, so far, rarely led to reactions requiring hospitalization. Nearly all of the cases which have been hospitalized were acute, and were released in a matter of days. Severe chronic cases of "cannabis psychosis" have not been scientificallv documented, although there is some evidence that cannabis may contribute to chronic conditions in certain individuals. Lesser problems do come to the attention of clinicians often enough to cause concern, althouoh there is no indication that cannabis reactions requiring medical treatment occur in more than a small fraction of users, and the nature of the problems presented are yet to be elucidated. It should be stressed, however. that treatment on an occasional or out-patient basis does not necessarily indicate that the disorder is not serious or that it is insignificant. The majority of severely disturbed individuals in North America are not hospitalized, and out-patient psychiatric care is becoming increasingly common in all areas of psychotherapy. Changes in the extent and pattern of cannabis use in North America will undoubtedly alter the epidemiological picture of adverse reactions as well. To date, long-term heavy cannabis use has been relatively rare on this continent.
The Eastern literature, by contrast, is much more suggestive of a link between heavy cannabis use and more prolonged psychological disorders. It should be restated, however, that in the East, moderate use is the rule and has not been shown to lead to serious psychological and physiological problems. The strongest evidence of adverse effects generally involves the exceptional chronic user, living under conditions of poverty, who reportedly consumes what seems to be an incredible amount of potent cannabis. Scientific and medical difficulties in interpreting the Eastern literature and generalizing from the social, economic and philosophic conditions involved to the present situation in North America have been discussed in detail earlier. In spite of these major difficulties, this literature cannot be discarded or considered irrelevant. If one assumes, for purposes of analysis, that the often-suggested cannabis-psychopathology link in the Eastern literature has some validity, significant contradictions appear when one compares the Eastern and Western-industrial situations.
Many observers have argued that the major reason we have not seen adverse effects comparable to those reported in some other countries is that most of what is consumed as cannabis in North America is weak or inactive marijuana. often cut with a variety of inactive substances. They further contend that if potent cannabis material were freely available, the North American picture would more closely approximate that presented in the Eastern literature. The recent experiences of North Americans in Vietnam lends some support to this view. The factors of availability and potency may well account for some of the East-West differences discussed above, but other social and economic, as well as scientific and medical factors complicate such a simple interpretation of the overall picture.
In the United States, marijuana is the most common form of cannabis and is generally brought up from Mexico and distributed across the continent. Until recently, hashish was considered a rarity in the United States. In Canada, however, with the exception of the West Coast, where marijuana apparently comes north through California, the use of hashish has been quite common for several years. Furthermore. it appears that in the past few years marijuana has become relatively less available in Canada, and in some areas. cannabis is most commonly seen in the form of hashish. Hashish used in Canada is generally of reasonable potency. Analysis of recent police seizures and 'street' samples indicates that the marijuana available is usually mild. but definitely psychotropic. Consequently, one must conclude that much of the recent Canadian cannabis experience has been with potent material, but of usually limited availability. This is also the case in England.235 It has frequently been noted that the heavy chronic user in both the West and the East often uses other potent substances as well as cannabis. The role of other drugs in the pathological conditions often described is as yet unclear.
The vast majority of problem cases reported in the East were daily, long term users who consume many times the amount of cannabis used by chronic smokers in North America. There are relatively few persons with a long history of heavy, chronic use on this continent. This is probably a significant factor in the differential treatment pictures presented. On the other hand, even in the Eastern literature most of the acute psychiatric hospital admission cases related to cannabis are relatively young men and, consequently, have had a limited duration of cannabis usage as well. Consequently, the chronicity of use factor, alone, cannot account for all of the discrepancies in the literature.
In the East, usually the lower classes have been studied. Subjects were mostly impoverished, irregularly employed, illiterate, malnourished and often from urban slums. In the West, especially in the recent literature, focus has been on middle-class, affluent users-often college students with above average drive and intelligence. Some of the older United States literature, which deals primarily with lower-class, urban slum-dwelling minority groups, presents a picture perhaps more similar to the Eastern problem user, although there is not enough accurate data for detailed comparison.
Some modern controlled studies of cannabis use in non-industrial countries are now underway, and will undoubtedly further clarify the factors involved in the apparent East-West cannabis paradox.38,74,189 It should be noted that Jamaica, which has had a long history of widespread use of very potent ganja, has not produced many reports of cannabis adverse reactions. In fact, recent Jamaican studies have shown little indication of cannabis-related problems in chronic users.
There a tendency in much of the Eastern literature to differentiate between the effects of marijuana or bhang and the more potent, concentrated forms of cannabis such as hashish or charas. It would appear that chronic heavy cannabis users prefer the more potent compounds and are also more likely to be mentioned in studies of adverse effects. It is not clear. however, if the more potent preparations are per se any more or less likely to produce adverse effects in the long run than are the milder materials. A similar distinction. based on potency, has traditionally been made in the alcohol literature. with more serious consequences often attributed to the use of distilled liquor than to the consumption of weaker drinks such as beer or wine. 450 Recent studies299,508,596' have shown, however, that even though acute poisoning with alcohol may occur more frequently with distilled spirits, longterm effects of chronic alcoholism are related to total alcohol consumed and not to the form or potency of the individual drinks. An analogy might exist between the alcohol and marijuana experience. While it is generally much easier to consume massive quantities of cannabinoids in the form of hashish rather than marijuana (and this might make acute adverse reactions more likely with hashish), until further pharmacological studies are done, it would be premature to assume that one cannabis preparation is more likely than another to produce chronic adverse effects in the long run. It should be noted, however, that marijuana and hashish generally differ in relative cannabinoid proportions as well as overall THC concentration (in that the ratio of CBD and CBN to THC is usually significantly higher in hashish see Table 2).
If attention is focussed on the North American literature alone, one is still left with an apparently paradoxical situation. If concern is directed to isolated (and, more recently, grouped) clinical case reports only, the impression is gained that there is, or soon will be, an epidemic of serious cannabis-induced psychopathology on this continent. On the other hand, attempts to locate severe chronic cases, starting from a broad population of users, or even a narrower population of general psychiatric patients and hospital admissions, have met with little success. This would strongly suggest that "cannabis psychosis" or other severe cannabis-related disorders requiring in-patient treatment are statistically rare in North America. This does not mean that isolated case reports are not clinically valid, however.
Based on what we now know from clinical and experimental reports, it would appear that given a certain set and setting, and sufficient dose, it would be possible to produce a marijuana 'bad trip' in a significant proportion of users. Furthermore, it has been established that in some individuals and circumstances, a severe and horrifying acute panic reaction can occur. What follows the acute panic reaction is less clear. In most instances the main adverse effects disappear as the ordinary symptoms of the 'high' recede, and few residual symptoms persist. There are, however, a few clear clinical reports of more prolonged psychotic reactions lasting days or, more rarely, weeks and months in individuals with little or no identifiable prior psychopathology. Prolonged reactions in chronically maladjusted individuals are more often reported, but still cannot be considered frequent. Some aspects of the conflicting views developing in the literature may be reconciled by the following analysis.
Alleged cannabis-related psychoses are often considered to be schizophrenia-like, and the "cannabis psychosis" syndrome is often defined with respect to "classical" schizophrenia as a standard. The opinion is frequently voiced that cannabis use may aggravate, mobilize or precipitate schizophrenia in borderline personalities. On the other hand, many investigators have argued that "cannabis psychoses" are just naturally occurring schizophrenic disorders in the cannabis-using population. 193,406,458,513 Consequently, it would seem worthwhile to explore the schizophrenic syndrome, as it might relate to cannabis use, in more detail.
There is general agreement in the non-drug psychiatric literature that psychotic reactions can occur in predisposed individuals in response to emotional and physical stress. The ideal case of the good premorbid or reactive schizophrenic is a good example. A typical picture is one of acute psychotic breakdown, elicited by some specific and identifiable traumatic stress stimulus. Prognosis is generally good and reasonable recovery can be expected. This situation can he contrasted with that of the poor premorbid or process schizophrenic, at the opposite end of the scale where there is no clearly identifiable precipitating event, or acute onset of illness but instead a more insidious and gradual process of dementia of long duration, with poor prognosis. This latter case more clearly corresponds to dementia praecox and the classical psychiatric notions of schizophrenia which pervade the older European literature and, significantly, seem to predominate in Eastern and Middle-Eastern psychiatric circles. The more acute psychotic reactions, which would likely be called schizophrenia in North America, are generally not considered "true" schizophrenia by clinicians of this latter theoretical orientation. In most cases of schizophrenia, onset of psychotic symptoms occurs in youth. Some borderline individuals may have displayed very few signs of psychopathology prior to the first psychotic break. In many instances pre-schizophrenic persons appear to manifest character disorders.
It is conceivable that a severe panic reaction to cannabis might serve as a precipitating stimulus for a more prolonged schizophrenic reaction in a borderline pre-psychotic individual. Such a hypothetical reaction might be expected to be of relatively short duration compared to the classic process or poor premorbid case. A number of case reports which fit this model have appeared in the North American literature. In addition, much of the Eastern literature on short- to medium-length cannabis-related psychotic reactions, which are often designated as being of shorter duration than "classical" schizophrenia, seem to follow this pattern. Whether or not such individuals would have experienced a schizophrenic break at some time, in the absence of drug-related stress, is an important, but difficult, question. There is no good evidence from which we can answer, but many observers feel that a significant number of borderline, schizoid or "compensated" schizophrenics may go through life without ever developing a full-blown psychosis.
There are no good estimates of the incidence of various kinds of endogenous psychosis in society-gross differences in diagnostic categories and practices preclude accurate data. Estimates usually range from 0.5 to 3% of the total population. Since schizophrenia itself is not a well-defined entity, and is probably a heterogenous group of perhaps etiologically different disorders with areas of common symptomatology, the picture is even more complicated.
If the assumption is made that one per cent of the general population might at some time display "schizophrenic behaviour" some interesting hypothetical conditions can be explored. The high risk period for initial schizophrenic breakdown is between the ages of 15 to 35, with perhaps half the cases initiating before the age of 25. This means that the onset of schizophrenic symptoms is most likely to occur in the same age groups that are presently the most frequent users of cannabis and other illicit drugs in North America.
In the following (admittedly over-simplified) hypothetical exercise, assume a city with a population of one million, with 150,000 persons between the ages 15-25, an incidence of ten per cent regular cannabis use in that age group, and an incidence of schizophrenia-like conditions in 0.5 per cent of that sub-population (0.05 per cent would be expected to show initial schizophrenic breakdown per year if reactions were evenly distributed throughout the ten-year period). By multiplying through the various probabilities, one can predict that seven to eight cases of schizophrenia per year would occur among cannabis-smoking young people, even if no interaction existed between the drug and the disorder, and any overlap being merely random coincidence. Such cases undoubtedly exist and must present a difficult and challenging diagnostic and therapeutic problem.
It should be pointed out that schizophrenia is only one of many serious psychological problems which commonly emerge in adolescence, and a variety of other forms of psychological disorder would also be expected to occur by chance in a cannabis-using population. Some observers estimate that 10-30% of adolescents experience temporary or long-lasting psychological disorders or adjustment problems. Consequently, one would expect to see on a chance basis alone, a significant number of young people who were psychologically disturbed and using cannabis at the same time. In a small number of these individuals, the onset of both acute psychological problems and cannabis use would be expected to coincide.
While the above hypothetical exercise was focussed primarily on schizophrenia as an example, a similar analysis could be made for a variety of other personality and behavioural patterns which have been associated with cannabis use at different times in the literature.
Although good epidemiological data are lacking, many observers feel that the frequency of psychopathology in the chronic cannabis-using population is higher than would be expected by chance. If this were true, at least three reasonable explanatory hypotheses might be adequate, each with some current data for its support:
(1) Pathological persons may be more likely to use cannabis (or to use it heavily)-especially when use is statistically unusual or deviant. This might. for example, represent acting-out or rebellious behaviour, attempted self-treatment, poor judgement, or an inability to find pleasure by other means.
(2) Cannabis use may lead to an increased incidence of psychopathology. This could be a direct neurological effect, or, for example, the drug might conceivably precipitate or complicate a schizophrenic reaction in a predisposed person as discussed above.
(3) Other factors may influence both psychopathology and cannabis use (for example. social alienation. socioeconomic conditions, and family relations).
A fourth possible interaction between cannabis and psychopathology has been suggested by several authors.193,243,458 It is possible that cannabis use may mask and compensate for chronic pathology and reduce overt symptoms in certain individuals. This would lead to a lower incidence of pathology in some cannabis-using groups than in comparable members of the general population. This interesting hypothesis has not been adequately tested. although cannabis has been used as a tranquilizer in many cultures.
The clinician, in treating cases of concomitant drug use and psychological disorder, is left in a very perplexing position. Armed with diagnostic and therapeutic concepts and techniques which are of questionable reliability and validity in even traditional non-drug cases, he must attempt to untangle the undoubtedly intricate and multidimensional causal and predisposing factors. It is clear that highly systematic and carefully controlled clinical research will be necessary to partial out causal variables, since there is no evidence so far that cannabis produces an easily-identifiable chronic condition of psychopathology. If such chronic conditions exist, they are likely to be shaped as much by the prior personality of the individual as by the specific pharmacological effects of the drug. It is unlikely that important questions will be answered by more anecdotal clinical reports of psychopathology or personality change coincident with cannabis use in ill-defined sub-groups of patients, especially in the present emotionally-charged atmosphere in North Arnerica. However. accurate clinical reports, put into proper population context, can provide valuable clues for subsequent systematic study.
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