Drug Abuse

5. Cannabis Psychosis

N. H. Rathod, St. Christopher's Day Hospital, Horsham, England.

INTRODUCTION

The relationship between use of cannabis and psychosis has been under discussion for over a century, but opinion still remains divided. The drug has been implicated as the cause of psychiatric disorders it is claimed to cure,and many more besides.

Some (e.g. 3, 5, 10, 11, 12, 13, 17, 30, 33, 42) are convinced that not only does it cause psychoses but the syndrome is distinctive. Others (e.g. 18, 37) question these views. And of course, there are others still, (e.g. 2, 6, 7, 44, 48) who give qualified assent. Rates of hospital admission vary between 3 per cent to 27 per cent.

The literature on the subject is extensive and varied. Differences in samples, varying authenticity of evidence, cursory attention to clinical details and other factors make valid conclusions difficult.

It may be fruitful to view the subject in terms of historical perspective (mid-nineteenth to mid-twentieth century), to examine the more recent literature with reference to some of the basic requirements of clinical research and to propose some ideas for research in the immediate future.

HISTORICAL

It was in 1828 that O'Shaughnessy(38) observed cataleptic reactions amongst patients receiving liquid extract of cannabis. In his paper published in 1843 he presents detailed observations on one of his three patients suffering from rheumatism developing catalepsy while being treated with cannabis. In the same paper he gives an account of the experimental administration of the drug to animals and humans. The drug produced no harmful effects. Cannabis produced euphoria followed by sleep.

In 1844 Jacque-Moreau, according to Oriana Kalant (28), published detailed accounts of effect of experimental as well as therapeutic administration of cannabis. Amongst other effects he observed varied hallucinatory phenomena. He likened these to dreaming whilst awake. He also drew attention to the subject having insight into these experiences and his ability to control the effects, and noted the relationship between dose and effect. He also treated psychotics with benefit and 5 of his 7 manic patients treated with fatty extracts of cannabis recovered. Kalant observes that these two 'contributions, almost simultaneous and independent of each other, constituted the beginning of modern scientific and medical study of cannabis' and, indeed, of experimentally induced psychoses.

In 1894, i.e. 50 years later, the Indian Commission on Hemp Drugs (24) published its report. Their enquiries into social aspects of the use of cannabis (insanity) psychosis are to date unsurpassed in scope, meticulousness and detail. They questioned over 400 doctors and 700 other witnesses, made on the spot enquiries in mental hospitals, and also asked for supplementary evidence from sources other than medical. They drew attention to (a) dangers of observer bias, (b) need to check clinical claims and (c) relationship between dose and effect. 222 of the 1344 admissions to mental hospitals in 1892 were attributed to cannabis. The Commission accepted that only in 98 the use of hemp drugs 'may be reasonably regarded as a factor'. When mixed cases, i.e. cases in which the hemp drugs were only one of the 'several possible causes', were omitted the Commission was left with 61 cases. Regarding these 61 cases the Commission commented with commendable caution: 'Even in regard to the remaining 61 cases, it must be borne in mind that it is impossible to say that the use of the hemp drugs was in all, the sole cause of insanity or indeed part of the cause'. The number is reduced by a further 22 because corroborative information was impossible to obtain. Thus a large part of clinical claim was found to be invalid, as, of the 222 reported cases, it was only in 39 cases that cannabis may have been the factor in or cause of insanity. (Pages 239-241). Recently a contribution of Baker and Lucas (4) reveals a parallel situation in the U.K. They scrutinised the records of 79 patients in whose admission cannabis was claimed to be a factor. In 51 or over 60 per cent of cases the role of cannabis was either assessed as irrelevant or the evidence was very inadequate. The strictures of the Indian Hemp Commission on clinical opinion may be found to be as relevant in 1974 as they were in 1894. They say (p.233 'The most striking feature of the medical evidence is perhaps the large number of practitioners of long experience who have seen no evidence of any connection between hemp drugs and disease, and when witnesses who speak of these ill effects from the moderate use are cross examined, it is found that:

(a) their opinions are based on popular ideas on the subjects;
(b) they have not discriminated between the moderate and excessive use of the drug;
(c) they have accepted the disease as being induced by hemp drugs because the patient confessed to the habit.'

No wonder they felt that the claim for hemp insanity was exaggerated.

As to classification of disorders attributed to cannabis , mania was the commonest, followed by toxic insanity and these accounted for 81 of the accepted 98 cases, melancholia was seen in 3 and dementia in 4.

In 1933 Bromberg (7) from New York published detailed observations on toxic confusional states and psychotic reaction amongst 10 cannabis users. He repeatedly stressed the role of the patient's personality and made a plea for precision in diagnosis. His clinical investigations were thorough and accounts detailed. He divided the clinical picture into three categories - Intoxication alone, Reactive states accompanying intoxication, and Toxic psychoses - an admixture of intoxication and basic cyclothymic or schizophrenic reaction. Intoxication (i.e. toxic confusional state) formed the common denominator of all the reactions .

In 1939 (11) the Chopras reported on years of their research into varieties of issues related to cannabis. They commented on the epidemiological aspects and estimated the incidence of psychoses amongst chronic users as ranging between 0.5 per cent to 2 per cent amongst the 1,238 subjects they studied. They also differentiated between effects of moderate and heavy use and referred to the popular use of the drug by physicians in indigenous medicine in India for many illnesses.

It is interesting that the possible therapeutic value of cannabis, and harmlessness of the substance if used in 'moderation' have received inadequate attention in contemporary scientific literature. The literature is heavily weighted in favour of 'adverse effects of the drug'.

In 1944 the first broadly based controlled study of the clinical effects of cannabis came from the Mayor of New York's Commission of Enquiry (36). Referring to the existing literature they were prompted to observe, 'Relationship to varying dosage, to the subject's personality and background and to the environment when the drug was taken is given little or any attention', - remarks so true even today.

Their sample was drawn from prison population and included both sexes, negroes and whites. Five of them were novices and 72 had a history of variable abuse of different drugs. DOse-related effects in clinical as well as social settings were studied. Patients were used as their own controls; nine patients developed psychotic reactions; 5 of them were novices. Of these six patients developed psychotic reactions with evidence of confusion which terminated as the drug wore off, and 3 patients developed psychosis after being sent back to prison. Fear, suspiciousness, restlessness were the commonest effects. The role of dose and setting on clinical effect is made obvious by their meticulous attention to details, (e.g. cases of E.C., sex male, novice, H.W. sex male, novice p.47). Allentuk and Bowman (2) have summarised the findings:- 'Characteristic marihuana psychosis does not exist. Marihuana will not produce a psychosis de novo in a well integrated stable person. It may precipitate a psychosis in an unstable, disorganised personality when it is taken in an amount greater than he can tolerate. Under such circumstances the previously mentioned physical and psychic manifestations become quantitatively greater and new events arise,' e.g. assuming grotesque statuesque positions and auditory hallucinations.

In 1946 Freedman and Rockmore (16) reported that none of the 310 chronic users (7 years +) they studied had a history of hospitalisation for psychiatric disturbance.

In 1946 Williams, Himmelbach and Wikler (49) reported withdrawal effects on 12 prisoners who were allowed ad lib use of the natural substance or of synthetic compound 'Parahexyl' under controlled experimental setting. The main feature of withdrawal effect was disorientation. In 1949 Fraser (17) described 9 cases of withdrawal syndrome amongst Indian troops fighting in South-east Asia. The patients showed unpredictable violence. The behaviour was waxing and waning and lasted up to 5 weeks.

The studies mentioned so far had between them pointed to many ground rules for the study of psychoses in a clinical setting - rules which are by and large ignored. Briefly stated they point to:

1. The need to ensure reliability of the evidence.
2. The need for meticulous attention to clinical details.
3. The need for precision in diagnosis.
4. The dangers of assuming cause and effect relationships too readily.
5. The relationship between amount (or dose) and effects.
6. The value of controlled studies.
7. The value of epidemiological approach.
8. The possibility of withdrawal 'syndrome'.

IMPLICATIONS

The term 'Cannabis Psychosis' has three important implications:

1. Therapeutic
2. Scientific
3. Social

1. Therapeutic. In a clinical setting diagnosis is based as much on existing knowledge about evidence as on the unique inter-action between the clinicians and the patient. Its primary function is to plan therapy and its implications therefore are limited to the individual patient, e.g. on medical advice he may have to abstain from using cannabis, or reduce its consumption, or ignore its role in the psychiatric disturbance altogether.

2. Scientific. The situation alters materially when the term is used as an aid to scientific knowledge. Its implications are far reaching and crucial to knowledge. Data need to be reliable and uniform; capable of scrutiny by others; and criteria of diagnosis clearly documented. If these points are not met, it is difficult for others to validate them and much worse, faulty conclusions may result. Judging from the literature such approaches are not popular. (e.g.3, 4, 5, 6, 11, 12, 13). Contributors often use evidence collected by others in day to day clinical practice. Meticulousness and uniform standards cannot be guaranteed. The reader is left with the task of drawing valid conclusions when the data does not lend itself to such an exercise. Instead of detailed clinical history and observations authors (e.g. 5, 12) use summary terms such as schizophrenia, depressive mania, aberrational and oneiretic states, and many others; without adequate criteria. This is done, possibly with the misplaced assumption that the reader will comprehend what the author has in mind, but which is not made explicit. It is only in the presence of detailed evidence that the reader is in any position to make evaluative judgment, e.g. the evidence produced by Campbell and Evans et al (8), enables us to suggest that factors other than smoking cannabis may have contributed to the clinical picture. Head injury and more than occasional use of L.S.D. by some of their subjects may be relevant factors. We also learn that their diagnostic instruments are not adequate to warrant diagnosis of organic brain damage. Kolansky and Moore (33), stated that 'The symptomatology seen in 13 patients imply biochemical or structural change in cerebral cells as a result of chronic cannabis use.' Clinical evidence does not warrant such implications - as no biochemical studies or investigations for organic damage were undertaken. Similarly, it becomes clear that many of their subjects were either showing signs of psychosocial disturbance, and/or were using other hallucinogens before starting regular use of cannabis. These examples illustrate the relevance of detailed evidence.

3. Social Significance. Choice of the least dangerous and at the same time most satisfying intoxicant is not easy for the ordinary person. He looks up to 'experts', e.g. clinicians and scientists, for guidance. These prestige groups have a responsibility in advising society - under-estimation of risks is hazardous and over-estimation is likely to cause undue anxiety, and also devalue their authority and authenticity. Furthermore social statements need to be relative, i.e. stating the relative dangers or benefits of various intoxicants in use. In this context it is interesting that the professional literature on cannabis is heavily weighted in favour of its dangers, and reports comparing its effects with others in common use, e.g. L.S.D., amphetamines and alcohol are few, (e.g. 22, 26, 41).

CLASSIFICATION OF 'PSYCHOTIC' EFFECTS:

Cannabis related psychotic phenomena can be divided into three groups:

1. Dose related acute psychotoxic reactions (e.g.50). They invariably show evidence of organic confusion. This is usually associated with anxiety, suspiciousness, restlessness and maybe violence, and perceptual disturbance. Their duration is measured in hours or days and recovery is complete. They are reported equally in Eastern and Western literature. (e.g. 4, 13, 16).

2. Idiosyncratic reactions: (e.g. 44, 48). These have features similar to acute psychotoxic reactions, except that (A) organic confusion is not always found. (B) Anxiety or panic states dominate the picture; and (C) subjects are usually novices and the amount consumed may be very little.

3. Other psychiatric disorders: Almost all major psychiatric disorders have been ascribed to cannabis. They range from psycho-neuroses, functional psychoses (e.g. Mania/Schizophrenia) to dementia and personality deterioration.

Frequency of such diagnoses varies, e.g. schizophrenia was diagnosed in 5 per cent of cases in an Indian study (12) and in between 58 to 60 per cent of cases in a Swedish study (6), and in a Nigerian one (3). On the other hand, Weil (48) claims that marihuana does not seem to trigger true psychotic reaction except in persons with a history of psychoses or hallucinogenic drug experimentation. Duration is equally variable and course unpredictable. They occur predominantly or solely amongst chronic users - and therefore African and Eastern literature is rich in such reports.

The existence of the first two conditions has been observed repeatedly in clinical practice and confirmed by controlled studies. (e.g. 3, 4, 21, 25, 31, 36, 44, 46, 48). However, it is relevant to point out that cannabis is not unique in giving rise to dose related toxic states or idiosyncratic reactions. They occur with many other drugs. The controversy really centres around psychiatric disorders in group (3) i.e. other than toxic states and idiosyncratic reactions. I have chosen to look at the more recent clinical research in this controversial area keeping in mind the historical guide-lines mentioned above.

While much of the disagreement may in part be due to defective research techniques, it is worth stressing that clinical research in this field is hampered by practical constraints over which the clinician may have
little control, e.g. selection of the sample, availability of reliable witnesses or such witnesses (e.g. parents) not having much knowledge of patients' drug habits. The following discussion is meant only to highlight some of the problems encountered in clinical research in this field.

THE TERM

Term Cannabis Psychosis presupposes that:

1) The claimed use of cannabis is valid and that it is the only drug involved;

2) There is agreement on criteria for diagnosing psychosis;

3) Cannabis causes the psychosis.

Patients' claims should be viewed with some scepticism specially in countries where cannabis is available only through illegal or underground sources. What the patient believes he has bought and used may not be what he has
been sold, e.g. Patterson (39) reports that nearly one-third of the samples purchased by users contained no cannabis. In other words, even if the patients' claims are reliable, they need not be valid. The amounts of active ingredients also vary (50). There is also the problem of cannabis being used concurrently or alternatively with L.S.D. and effects of the two drugs being similar.

Furthermore, L.S.D. flashbacks are similar to those caused by cannabis and cannabis may precipitate such flashbacks, ( e.g. 29, 30, 32). In India, Datura (Stramonium) is often mixed with cannabis. It too can cause psychotic reactions. By and large little attempt is made to checking the validity of patients' claims.

Agreement about Psychosis: Diagnosis in psychiatry is hampered because evidence is often ambiguous. Agreement between independent raters is difficult to achieve because criteria for a particular diagnosis are not uniform and due to individual clinician bias. Diagnosis is also influenced by other factors, e.g. as Hollingshead and Redlich (20) point out, people from lower social classes are more likely to be diagnosed as suffering from psychosis such as schizophrenia than others; and the majority of the cannabis smokers in the Middle East and India belong to the lower strata of society.

But an even greater cause for concern about diagnosis is the lack of enough attention to its significance. Discussing the issues involved, Per Dalen (14) observes:- 'The theoretical importance of diagnoses is not heeded. They are not treated as hypotheses to be subject to test, but rather as conventions or intuitively and implicitly defined concepts of classification.' But even when diagnoses are put forth as hypotheses one needs to guard against personal prejudice because it can affect research design and outcome. In the words of Weil, Zinberg and Nelson (47) 'the researcher who sets out with prior conviction that hemp is psychotomimetic or a mild hallucinogen is likely to confirm his conviction experimentally, but he could probably confirm the opposite hypothesis if his bias were in the opposite direction.'

In summary: Reliable and agreed diagnoses, although important, are unlikely to obtain in the absence of uniform criteria, detailed evidence and independent assessment of evidence to exclude personal bias.

CAUSALITY

Given the history of use of cannabis, cause-effect relationship between the drug and various psychiatric disturbances is too readily assumed. Undoubtedly psychiatric disorders do occur amongst cannabis users, but the implication that cannabis is the or the major cause is more often than not unwarranted. To illustrate: In 1970 I sent a questionnaire to 20 Senior Psychiatrists in India. Twelve replied and estimated that between 1 - 3 per cent of all hospital admissions were due to cannabis psychosis. In 1971 I had an opportunity to see 18 of these people individually in India. Asked, if in the absence of history of cannabis use would they have been able to claim that the psychoses was due to the drug - the answer was 'NO. They could not.' In the same year I visited a well known mental hospital in Northern India. I was shown a ward of 40 males, which housed 10 'typical' cannabis psychosis patients. Their clinical picture and history of cannabis use was similar to twenty or so others in that ward who were not diagnosed as suffering from cannabis psychoses. No explanation was forthcoming to explain this discrepancy.

ROLE OF ANTECEDENTS OTHER THAN CANNABIS

Little or scant attention is paid to family history, life experiences, and patients' personality (e.g. 3, 6, 5, 30, 33, 44). This is surprising in view of their role in development of psychiatric disorders, including functional psychoses and amotivation syndrome. Cannabis may, in some circumstances, precipitate psychiatric disturbance. In this sense it possibly acts as a non-specific stress like many others, e.g. trauma, intercurrent infections, personal tragedies, etc. This non-specificity does not receive attention. In order to confirm the role of cannabis as a specific precipitant it is necessary to exclude all other probable factors which may lead to a similar reaction, specially the role of other intoxicants, e.g. use of amphetamines, Lysergic acid diethylamide and other hallucinogens. It is at times surprising to find that history of such use is not given sufficient weight, (e.g. 3, 30). The above observations only go to show the dangers of accepting the immediate and the obvious - as the cause. In the words of Sir Aubrey Lewis (34): 'Interpretations which explain the phenomena too readily lead to a feeling of certainty which closes the mind to further enquiry and makes the believer hostile to any breath of sceptisism.' Similarly in the case of amotivational syndrome varieties of non-drug factors (e.g. Social alienation, Chronic privation and lack of opportunities, etc.) may play a crucial role. (e.g. 43, 50).

DOSE AND DURATION
Another difficulty arises from insufficient attention paid to dose and duration of use. Eastern authors (such as Chopras and Benabud) assert that moderate use (e.g. UP to 1.3 g per day in India) is harmless. Observations
of Tart (45) on chronic users in the West seem to support such contention. This may imply that in terms of harmful effects what matters is the amount used over a period of time, and not just the use. Relationship between dose
and effect has been repeatedly confirmed in controlled studies. (e.g. 20, 25, 31). The role of a dose-frequency and duration may therefore be very significant because of the possibility of cumulative effect (40). Data on these variables in clinical reports is very meagre. Bernhardson and Gunne (6) present data on duration and dosage and find that duration is of little consequence to effects, but they do not discuss the relation between dose and duration combined on one hand and effects on the other.

The hypotheses that cannabis causes psychosis will be much strengthened if it could be shown that:

a. the frequency of psychoses amongst users is greater than observed in comparable group of non-users; and that this difference cannot be attributed to chance.
b. administration of cannabis under controlled conditions will result in predictable recurrence of psychosis amongst those volunteers who have recovered from cannabis psychoses. Such an experiment using double blind technique is permissible as the risk of fatality and sequelae is negligible. Relapsing patients should provide suitable subjects and may not be difficult to find. (3, 6, 13). The procedure will have the benefit of the patient being his own control, (36) and of monitoring dose and the setting if not the mental set.

In summary. Evidence in support of causal connections between cannabis use and psychosis is defective on the basis of:

1. Non-critical acceptance of evidence.
2. Short-comings of diagnostic procedures.
3. Scant attention to other probable causes.
4. Concept of single aetiology.
5. Lack of statistical support.
6. Absence of controlled studies.

ROLE OF EPIDEMIOLOGY

Epidemiological aspects of cannabis psychoses have attracted insufficient attention - a point made by Le Dain Commission in Canada (9). Statistical data based on mental hospital admissions or other special groups can
never mirror the actual occurrence or absence of psychoses amongst the users. If anything they must underestimate the phenomena as many who are affected may never come to the notice of the medical profession. In the absence of field studies, incidence of psychoses amongst users is impossible to assess. Chopra (11) estimate of 0.5 to 2 per cent for Indian users, and Benbud's (5) of 0.5 per cent for the Moroccan Kif smokers are difficult to confirm or challenge because of methodological problems. Recent attempts to document the frequency of, adverse effects and their recurrence, in the absence of drug use ('Flashbacks') may be of help. (1, 15, 19, 29, 32). It is, however, not clear from these accounts if the adverse reactions were of such a nature or degree that the users required professional or other assistance or deterred the subjects from further use at least for a period.

CONTRIBUTIONS OF RECENT RESEARCH

In the last 6 or 7 years we have seen a resurgence of experimental research into the effects of cannabis. Even though this renewed research has, as Hollister (23) puts it, 'added little not previously known about the clinical syndromes produced by the drug'; it should provide a healthy stimulus to further clinical research.

It has

(a) made it possible to assess the amount of active ingredient in cannabis; (50)
(b) established the relationship between amount of active ingredients and effects;
(c) established the basic characteristics of the effects of the drug; thus confirming the claims of users, of folklore and of past observers; (e.g. 21, 25, 51, 31, 32, 41, 47, 52, 53).
(d) reminded us of the role of important non-drug factors, such as mental set, the setting (22, 27, 47), and placebo effect (35) in reactions to the use of cannabis.

In other words, laboratory studies have provided the field workers, e.g. clinicians and epidemiologists with the basic pre-requisites for field studies. For as Hollister (23) says, 'the clinical effects in regard to social questions about marihuana such as possible deleterious effects from chronic use cannot be answered by laboratory experiments. They must be settled by close observations made on those who experiment on themselves.' Thus he has put the responsibility where it belongs - on to the shoulders of field workers.

Some ideas for future research. I would suggest that:

1. We re-examine the usefulness of the term psychosis;
2. We examine the possibility of establishing facilities to study the clinical effects of cannabis.

When the term cannabis psychosis is beset with so many difficulties, e.g. definitional one, questions whether it exists, if it exists what is its nature and whether it is a specific or non-specific entity and so on and so forth -
one wonders why we retain it at all - why does one have to fit in all adverse reactions into a pre-conceived frame work? I personally cannot see the advantage except that of tradition - and the ease with which we can pigeon-hole those affected if these can be called advantages. I would like to suggest that we freeze the term psychosis for the time being and start at the beginning by just documenting the effects (adverse or otherwise) according to their form and degree, and functional consequences on the 'life' of the users and others, in an agreed and uniform manner. It would certainly make communication and understanding between workers much easier, and may help confirm or reject the possibility or a syndrome or syndromes - provided of course that there is prior agreement, (a) about the operational definition of adverse effects, and (b) about the criteria to be used. We should be able to establish facilities on national or regional levels to study the adverse effects of cannabis under controlled conditions on volunteers who have suffered from these and have come to the notice of helping professions. I have already referred to this idea. One would expect this facility to carry out extensive clinical, biochemical and psychosocial investigations, and long term follow-up studies on the subjects studied. Unless such or other similar steps are taken sterile arguments as to whether or not cannabis does cause psychosis will continue.

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DISCUSSION

Discussion on the topic of Cannabis Psychosis ranged widely and can be conveniently brought together under the following headings.

THE CONCEPT OF CANNABIS PSYCHOSIS

As well as Dr Rathod, Drs Smart, Cameron and Miles, and Mr Hastleton were in favour of dropping the term 'cannabis psychosis' in the present state of knowledge and Professor Soueif and Dr Cameron stressed the need to look at symptoms and signs and define these rather than using syndromes which are not adequately delineated. In general it might be better to talk about adverse or unpleasant reactions. Dr Smart reported that half the high school students who reported adverse reactions or recurrences refused to characterise them as unpleasant and thought that the term psychosis should be restricted to a toxic psychosis on the carb on tetrachloride model. Dr Tinklenberg reported one subject's description of 'cosmic vomiting' and some participants were in favour of talking about 'unusual reactions' or 'atypical reactions'.

Dr Edwards drew attention to the possibility that other drugs were also being used, the influence of age and personality and the need to establish the precise pathological mechanism. He highlighted the particular problem of explaining how a psychosis could continue for a long time after withdrawal from a drug.

CELL PATHOLOGY
Professor Paton, when asked to comment on the question of establishing a pathology, thought that it was too early to relate concepts of cell pathology to clinical findings and that if such a pathology existed it was likely to be found in the field of neuropathology and to affect the finest structures such as dendrites.

DEFINITION OF SPECIFIC SIGNS AND SYMPTOMS

Dr Rubin noted that 'all research is fraught with difficulties. I think Dr Rathod has made an important contribution in pointing out the kind of problems that seem to plague cannabis research particularly. It
seems at times, to me, that cannabis is the current sin to which every thing is being attributed. I think the important contribution is in trying to establish the research methodology that will be able to distinguish between correlation and cause. The Royal Indian Hemp Commission still remains, to my mind, a model of scientific research. The time has come in cannabis research when we need some international agreements on parameters, so that the data can be comparable. Otherwise we are dealing with too many unknowns.'

Dr Cameron was concerned about the lack of tools for research, and urged further attention to this
aspect. Professor Soueif reported that in his researches, of 120 items collected from classical symptomatology and including behavioural changes, inter-observer reliability had been established in 70 items at a correlation of 0.7 or better.

Dr Rathod stressed the need for observers to agree on an operational definition of signs and that a distinction should be made, if possible between direct drug effects and cultural and social effects of expectation and motivation.

POPULATIONS TO BE STUDIED

Dr Rubin observing that the fact of illegality influences signs and symptoms stressed the importance of looking at countries where cannabis use is traditional. Dr Cahal stressed 'the need to go to countries where only cannabis is used is becoming a matter of some urgency because more and more countries, as they develop and as communications improve, are beginning to use drugs other than cannabis.' This point was generally agreed. Professor Paton pointed out that since population in Jamaica, India, and South Africa were not characteristic of industrial users, there was a danger of generalisation from researches carried out in them.

STRATEGY OF RESEARCH - THE CONTRIBUTION OF EPIDEMIOLOGY

Dr Edwards said that he felt that the sort of questions to which the epidemiologist is asked to address himself are often increasingly inappropriate. 'The epidemiologist can only really apply his art when he has some likelihood of describing the distribution through time or through populations of reliably describable entities, syndrome or behaviours. The difficulties of measurement and analyses are such that we should be very wary indeed of mounting new epidemiological studies before we are really certain that we can accurately measure what we want to measure. Research will go forward in this area most effectively by the close definition of hypotheses and close testing of these hypotheses by the most appropriate and economic scientific means available. The most economic means will relatively seldom be the large sample epidemiological enquiry.'

PRIORITIES FOR RESEARCH

In general, participants agreed with Dr Rathod's suggestion that the priority, at the moment is to develop a reliable check-list of signs to discover which signs, both usual and unusual, occurred across cultures, and which signs were culture-specific.

Dr Cameron supported this view saying: 'I don't feel constrained to attribute a diagnosis nor to attribute a cause. I would just like to know if we can see any major differences between groups of heavy users and non-users. I don't get particularly interested in a phenomenon until the phenomenon has been demonstrated. And that is where I think we are, looking at signs and symptoms. It seems particularly difficult to get a population frame from which to draw these two user/non-user groups. We may have to look at more than one population frame in order to get a cross-section. Some population groups have been examined with comparison groups from the same population, but those populations are sometimes very circumscribed and we can't generalise from those.'

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