2. Cannabis: broad perspectives **
4. Effects on man of using cannabis
5. Research needs
6. Research strategies
Pages: 11 to 19
Creation Date: 1972/01/01
The Bulletin on Narcotics, in consultation with the Pharmacological and Toxicological Division of the Secretariat of the Worm Health Organization, presents the following excerpts from the report of a WHO Scientific Group on the Use of Cannabis which was published recently. Attention is drawn to the full text of the report, which is published in the WHO Technical Report Series. *
2.1 The substance
Cannabis sativa L. is an annual plant normally occurring in male and female forms. It often grows to a height of about six feet, but under optimum conditions may reach 20 feet. It is probably indigenous to Central Asia (Bouquet, 1950) but now grows wild in most temperate to tropical areas; it is produced commercially in some places. It has a long history of cultivation, as a source both of fibre (hemp) and of psychoactive substances contained in its leaves and flowering tops. In the past, it was very often grown for fibre with apparently no local awareness of its psychoactive properties.
Botanically, only one species of cannabis is now recognized ( C. sativa L.), but in the past other designations were sometimes applied to plants found in different parts of the world (e.g., C. indica and C. americana).
There are, however, substantial differences in the amount of psychoactive material contained in what may be different varieties of C. sativa L. The amount is also influenced by variations in climate, weather, soil, time of harvest, and conditions and length of storage (Davis et al., 1963; Lerner and Zeffert, 1968; Joyce and Curry, 1970).
C. sativa L. produces a resinous substance which contains the major part of the psychoactive and intoxicating ingredients. It occurs primarily in the flowering tops and upper leaves and is sometimes separated from the rest of the plant for use as hashish. In a given plant the lower leaves contain less of these ingredients than do those at the top of the plant; the flowering tops contain the highest concentration. The stalk and seeds contain a negligible amount of psychoactive ingredients (Fetterman et al., in press; Valle, 1969)...
* Wld. Hlth Org. techn. Rep. Ser., 1971, No. 478. This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the World Health Organization.
** Note by the Editor: The chapter and paragraph references for these excerpts have been retained in this presentation for the convenience of those readers who wish to identify them in the context of the full report.
2.1.1 Recent advances in cannabinoid chemistry and measurement
The chemical constituents of C. sativa L. are quite complex. They include a unique group of chemicals called cannabinoids (Mechoulam, 1970) together with waxes, starches, terpenes, oils, and trace amounts of other as yet unidentified substances. The five most important cannabinoids, as far as the biological potency of cannabis is concerned, are the ( - )-Δ 9- trans-tetrahydrocannabinol (Δ 9-THC), 1 ( - )-Δ 8- trans-tetrahydrocannabinol (Δ 8-THC), 2 Δ 9- trans-tetrahydrocannabinolicacid (THC-acid), cannabinol (CBN), and cannabidiol (CBD). The first two are psychoactive when taken orally or by smoking. THC-acid is not active when taken orally, but is partly converted to the active Δ 9or Δ 8when smoked (Mechoulam, 1970). Knowledge of the extent of this conversion is incomplete. CBN and CBD have very little psychoactivity but are present in fairly large amounts. They appear to have an inverse quantitative relationship to the highly active Δ 9-THC and Δ 8-THC. Δ 8-THC, discovered by Hively et al. (1966), occurs in very small amounts as compared to Δ 9-THC, except in aged hashish (Lerner and Zeffert, 1968).
Δ 9-THC produces most of the effects of cannabis or extracts of cannabis in both animals and man. It is therefore believed, but not entirely proved, that Δ 9-THC accounts for most of the pharmacological activity of cannabis. At least thirty other cannabinoids have been isolated from cannabis (Mechoulam, 1970), but relatively little information about their biological activity is available. In addition, trace amounts have been reported of an alkaloid or alkaloids as yet chemically uncharacterized. The presence of an atropine-like substance and trigonelline in a commercial preparation of cannabis has been reported (Gill et al., 1970).
1. Also known as ( - )-Δ 1- trans-tetrahydrocannabinol (Δ 1-THC)
2. Also known as ( - )Δ 1-( 6-)- trans-tetrahydrocannabinol(Δ 1-( 1)-THC)
Δ 9-THC and Δ 8-THC volatilize readily when smoked (Manno et al., 1970) and are rapidly absorbed from human lungs. They are also absorbed, but more slowly, from the gastrointestinal tract.
In animals, both Δ 9-THC and Δ 8-THC are bound to serum protein. Only small amounts are found in the brain. They are metabolized in the liver, and the metabolites are excreted in the bile 3 and re-absorbed from the gastrointestinal tract; an enterohepatic circulation therefore exists. The metabolites of Δ 9-THC and Δ 8-THC first formed in the liver are 11-hydroxyl derivatives (11-OH-Δ 9-THC and 11-OH-Δ 8-THC). In later steps additional hydroxylations occur on the rings. The 11-hydroxyl derivatives of Δ 9-THC and Δ 8-THC possess pharmacological activity (Mechoulam, 1970), and it has been postulated, but not proved, that they, rather than the THCs themselves, are the compounds responsible for the pharmacological activity. The metabolites of the THCs persist in the bodies of animals for long periods of time. Δ 8-THC and Δ 9-THC disappear from blood rapidly, so that neither can be found in blood 15 minutes after intravenous injection (Klausner and Dingell, 1970). Δ 8-THC and Δ 9-THC are not excreted as such in the urine. These phenomena mean that present chemical methods for the detection of these THCs will not be useful for determining the presence of cannabis in man. Attention must therefore be turned to methods for detecting the metabolites rather than the THCs themselves. Radioimmune assays may prove useful.
For purposes of comparison, three of the older synthetic tetrahydrocannabinols deserve mention: (±)-Δ6a,10a-THC; (±)-Δ6a,10a-5- n-hexyl-tetrahydrocannabinol(called synhexyl or parahexyl); and (±)Δ6a,10a-5-dimethyl-octylheptyl-tetrahydrocannabinol (DHMP). The first is a synthetic tetrahydrocannabinol but possesses only about one-fourteenth of the biological activity of the natural Δ 9-THC (Loewe, 1950). The second (synhexyl) possesses marihuana-like activity (Loewe, 1950) and underwent a limited clinical trial as an antidepressant (Parker and Wrigley, 1950). The third (DHMP) is a very potent drug which, in doses of 1-2 mg orally in man, produces cannabis-like subjective effects, marked sedation, and profound postural hypotension (Isbell, unpublished data).
3. Ben-Zvi et al., 1970; Burstein et al., 1970; Foltz et al., 1970; Nilsson et al., 1970.
The chemistry of the major cannabinoids was investigated extensively from about 1936 to 1941 by Adams and co-workers in the USA (Adams, 1942) and by Todd and co-workers in the United Kingdom (Todd, 1940). These two groups of workers determined the chemical structure of cannabinol, cannabidiol, and tetrahydrocannabinol, except that neither group was able to establish the position of the double bond in the non-phenolic ring of either cannabidiol or tetra-hydrocannabinol. Mechoulam and Shvo (1963) identified the position of the double bond in natural cannabidiol as being located in the Δ 9position, and Mechoulam et al. (1967) and Petrzilka et al. (1967) developed two different methods for the synthesis of Δ 8-THC and Δ 9-THC.
It is now possible to determine the amount of Δ 9-THC, Δ 8-THC, CBD and CBN in the cannabis plant by gas-liquid chromatography (Lerner and Zeffert, 1968; Lerner, 1969). Cannabis grown in the same soil and the same climate from authenticated samples of seed collected in Canada, the USA and Western Europe have produced plants that, as a group, contain a low Δ 9-THC content (average 0.2% by weight) but a high cannabidiol content (Fetterman et al., in press). Seed from Mexico and Thailand, on the other hand, produced plants with a high content (1.5-2.0%) of Δ 9-THC. 4Some samples of naturalized or wild cannabis growing in the USA contain as little as 0.09% of Δ 9-THC, while a sample from Tailand contained 4.89% (Turk, 1970).
The Δ 9-THC content of cannabis preparations is influenced not only by the characteristics of the plant and the place and circumstances of its growth but also by such factors as the age and methods of storage of the harvested materials. All active substances contained in preparations of cannabis deteriorate with time, the Δ 9-THC being converted to cannabinol. Inactivation of Δ 9-THC is particularly rapid if the herbal material is exposed to or stored at high temperatures (Lerner, 1969). If cannabis preparations are stored at - 10°C, the Δ 9-THC content remains much the same for periods of at least two years (Isbell, unpublished data). It follows that the Δ 9-THC content of preparations in use in experimental work must be carefully and frequently monitored.
The average Δ 9-THC content of marihuana believed to be of Mexican origin and obtained from the illicit market is around 1%, although it varies widely (Lerner and Zeffert, 1968). The Δ 9-THC content of samples of hashish has ranged from 1% to 15%, with an average of about 5% (Lerner and Zeffert, 1968; Mechoulam, 1970; Turk, 1970). Very little information is available about the THC content of marihuana-type preparations available in many parts of the world or about ganja in India.
With the data available, however, it is possible to establish a rough scale of relative potency for the purpose of making broad or order-of-magnitude comparisons of the amounts of Δ 9-THC contained in the cannabis preparations commonly consumed. For this purpose, marihuana (bhang, kif, etc.), ganja, and hashish (charas) are assumed to average respectively about 1%, 3% and 5% by weight of Δ 9-THC...
4. The cannabis preparations analysed were marihuana without seeds, stalks, and main stems.
2.3 Relation to use of other drugs
Very broadly, there has been a tendency to use cannabis as the principal intoxicant in some regions (e.g., the Indo-Pakistan subcontinent and North Africa), and alcohol in others (e.g., North America, Europe, and many areas of South America). In many countries the current trend appears to be towards using both alcohol and cannabis preparations, although in only a very few countries is there anything approaching the use of both to an equal extent.
A large proportion of cannabis users frequently take in addition psychoactive dependence-producing drugs of the alcohol, amphetamine, barbiturate, hallucinogen, and morphine types (Eddy et al., 1965), either at the same time or consecutively. 5 This greatly complicates the task of attributing drug effects to a single substance. Multiple drug use is perhaps more frequent in parts of Europe and North America than in the Indo-Pakistan subcontinent and Africa. In nearly all areas where cannabis is used, however, numerous other factors complicate the identification of individual drug effects.
2.3.1 Progression to the use of other drugs
The assertion is commonly made that the use of cannabis leads to the use of other drugs. This "stepping-stone" theory holds that adolescents begin with marihuana and later proceed to other drugs, often including heroin, in search of greater thrills. Most observers discount any pharmacological action disposing the cannabis user to resort to other drugs.... It appears likely that important sociocultural and personal factors contribute to any apparent progression from cannabis preparations to other dependence-producing drugs. For example, many people who take marihuana frequently tend to limit their social life to the circle of drug-takers, particularly in areas where drug-taking is not socially acceptable. They are thus frequently given the opportunity to try other drugs (Goode, 1969). It is also possible that certain individuals have a greater personal need than others to experience the effects of drugs, and/or that chronic intoxication with cannabis contributes to a generally poor orientation to reality, especially among adolescents...
5. Goode, 1969; Kielholz and Ladewig, 1970; Popham, 1970; United Kingdom, Advisory Committee on Drug Dependence, 1968.
6. The psychoactive components of cannabis are insoluble in water, and are therefore ineffective by the intravenous route. Fur thermore, mixtures prepared from various preparations of cannabis contain macroscopic and microscopic particles and soluble pyrogens. A few attempts to inject suspensions of hashish or marihuana have been followed by severe physical symptoms (Gary and Keylon, 1970; Henderson and Pugsley, 1968; King and Cowen, 1969).
3.1 Manner of use (mode of consumption, frequency, amount, and duration)
The primary mode of consuming cannabis is by smoking, but it may be ingested as a food or beverage. 6India is the only country in which a significant amount is taken orally, in the form of a beverage made from bhang. Cannabis is also consumed in numerous confections and other food preparations, especially in India and sometimes in North Africa and other regions (Bouquet, 1951; Chopra and Chopra, 1939); however, in most parts of the world this mode of consumption is minor compared with smoking. The stronger preparations, e.g., ganja and hashish (or charas), are normally smoked in a pipe, which is sometimes so constructed that the smoke is first passed through water. The crude forms, which are less potent, may be smoked in either pipes or cigarettes...
A meaningful evaluation of the consequences of cannabis use for the individual and society must take into account the frequency, amount, and duration of use and the relative numbers of persons conforming to various usage patterns. Studies in the USA indicate that occasional users far outnumber those who use cannabis daily, 7whereas reports from the Indo-Pakistan subcontinent and North Africa are frequently concerned only with regular users; throughout the world, however, it appears that the majority of cannabis users take the drug occasionally rather than daily. 8 In countries such as India and Morocco, where cannabis use has been more or less accepted, the daily use is measured in grams and only amounts in the upper range are considered "excessive". In India, the usage is considered moderate if around 1-2 g of ganja per day, 9 or an estimated 30-60 mg of Δ 9-THC. 10The majority of daily users are reported to fall within the moderate range. Chopra and Chopra (1939) conclude that, in India, "moderate use is much more common and excessive use is exceptional". The Indian Hemp Drugs Commission (1894) similarly estimated that excessive users represented only about 5% of ganja smokers.
While the amount of cannabis used daily is usually discussed in terms of moderate and excessive (terms that have different meanings in different reports), the amounts consumed probably exhibit the same type of unimodal frequency distribution as alcohol consumption, i.e., the large majority fall within the low end of the continuum, and progressively smaller frequencies are obtained as the high end of the scale is approached... 11
7. Bromberg, 1934; Mayor's Committee on Marihuana, 1944; McGlothlin et al., 1970; United States, Select Committee on Crime, 1970.
8. Chopra and Chopra, 1939; Roland and Teste, 1958; Soueif, 1967.
9. Chopra, 1935; Chopra, 1940; Indian Hemp Drugs Commission, 1894.
10. Not all taken at once, and perhaps not in a single drug-taking session.
11. Ledermann, 1956; de Lint and Schmidt, 1968; Smart et al., 1970b.
The duration of cannabis use is important. Many authors imply that, once the use of cannabis is well established, it is likely to continue on a daily basis for many years and is not infrequently a lifetime practice (Bouquet, 1951; Chopra and Chopra, 1939). However, longitudinal data on representative samples of users are seldom if ever cited, and there is some indication that, in India and North Africa, the period of time over which cannabis is used by individuals may have been exaggerated (Soueif, 1967). In other parts of the world there are frequent references to discontinuation of its use after adolescence (Robins et al., 1970; South Africa, Interdepartmental Committee, 1952) and to intermittent use among others (Mayor's Committee on Marihuana, 1944). In one follow-up study of regular marihuana users in the USA, one-half were still using marihuana twice or more a week after 20 years (McGlothlin et al., 1970).
3.2 Reasons for starting and continuing to use cannabis
Association with other users, curiosity as to the effects of cannabis, and a desire for relaxation, relief from tension, or a pleasurable feeling are widely cited as reasons for starting to use cannabis.. 12
One of the more frequently stated reasons for continuing to use cannabis moderately is the sense of well-being, relaxation, and relief from tension experienced. 13It is used less frequently in an attempt to enhance sexual satisfaction 14 and to increase the enjoyment of music and food. 15 It is also reportedly taken to alleviate hunger (Chopra and Chopra, 1957; Indian Hemp Drugs Commission, 1894). Another stated reason for its continued use is relief from boredom, frustration, and depression (McGlothlin et al., 1970)...
Social reasons are adduced for the use of cannabis. Cannabis, more than any other intoxicant, is used throughout the world in small social settings, so that the desire to achieve a sense of belonging to an intimate group is undoubtedly a significant factor both in beginning and in continuing to use it. The social intimacy may be intensified by the precautions required to avoid legal sanctions (Becker, 1953; Goode, 1969).
12. California Legislature, 1970; Canada, Commission of Inquiry, 1970; Chopra and Chopra, 1939; Goode, 1969; Koppikar, 1948; Soueif; 1967.
13. Canada, Commission of Inquiry, 1970; Chopra and Chopra, 1957; McGlothlin et al., 1970; Roland and Teste, 1958; Tart, 1970,
14. See section 4.2.
15. Chopra and Chopra, 1957; Goode, 1969; McGlothlin et al., 1970; Tart, 1970.
16. Manheimer et al., 1969; Soueif, 1967; Watt, 1961.
17. Robins et al., 1970; Sigg, 1963; Soueif, 1967; Watt, 1961.
18. Mauer and Vogel, 1962; Mayor's Committee on Marihuana, 1944; Roland and Teste, 1958; Soueif, 1967.
3.3 User characteristics
... Cannabis use is related to age. It is generally most popular among adolescents and young adults; 16 however, consumption in India is said to show a fairly even age distribution at present (United Nations Economic and Social Council, 1957), while in Thailand it has reportedly been largely restricted to elderly persons (United Nations, Commission on Narcotic Drugs, 1965). At present initiation is most frequent during adolescence, 17 but Chopra and Chopra (1939) found that 40% of their sample of regular users began after the age of 30 years.
The extent of cannabis use is closely related to sex. Except in Europe and North America, the extent to which females use it is extremely low. Even in these areas, the extent to which it is regularly used among women is low compared with that among men...
Within the broad "normal" range, certain personality characteristics are associated with some cannabis users. Individuals who appear to enjoy the effects of cannabis tend to prefer an unstructured and spontaneous style of life, are relatively prone to take risks, value states of altered consciousness, and tend to seek such effects both through drugs and through other methods (Cohen, 1970; McGlothlin et al., 1970). Thus cannabis users are most frequently young, male, unmarried, and exhibit some instability with respect to residence, work, school, and goals. Individuals who have no taste for the cannabis experience per se (regardless of moral or other considerations) are more apt to exhibit a preference for a controlled, structured, rational, and secure approach to life.
Excessive use is associated with personality inadequacies. Persons who exhibit emotional immaturity, low frustration tolerance, and a failure to assume responsibility tend to be over-represented in samples of heavy cannabis users, 18In behavioural terms, these traits are manifested in an unrealistic emphasis on the present as opposed to the future, a tendency to drift along in a passive manner, failure to develop long-term disciplines and skills, and a tendency to favour regressive and magical to rational thinking.
3.4 Sociocultural factors
The taking of drugs, particularly cannabis, appears to be associated not only with certain individual and group beliefs and expectations about the effects but also with a broader system of beliefs and values concerning such matters as ( a) the relative worth of material possessions and of spiritual, cultural, and traditional beliefs and experiences; ( b) the respective importance of the rights, prerogatives, and responsibilities of the individual and of society; ( c) the nature of practices that are considered good and evil; and ( d) the meaning and value of life itself (Cameron, 1970)...
In summary, the epidemiology of cannabis use involves three factors: ( a) the personal characteristics of the actual or potential user, ( b) the sociocultural pressures on him, and ( c) the pharmacological properties of various cannabis preparations. The extent to which its use satisfies conscious (stated or unstated) or unconscious needs will help to determine whether or not the behaviour is sustained. The use of cannabis tends to "bind" the user to certain persons, while often "alienating" others.
4.1 Influence of different preparations, dose levels, and routes of administration
It is now generally believed that Δ 9-THC accounts for a large part of the pharmacological activity of cannabis preparations (see section 2.1). The percentage of Δ 9-THC in cannabis preparations varies markedly (see section 3.1). To a large extent, the potency of various preparations varies directly with their Δ 9-THC concentration.
To obtain the maximum effect from cannabis preparations they must be smoked by a technique that is somewhat different from that of smoking tobacco cigarettes and must be learned by practice. 19 When this technique is followed, about 50% of the Δ 9-THC in marihuana comes over in the smoke and most of the remainder is converted to CBN or CBD or both (Manno et al., 1970). Exhaled air contains practically no Δ 9-THC when the specified technique is used. It is thus assumed that roughly 50% of the Δ 9-THC content of a marihuana cigarette is absorbed by the lungs and constitutes the dosage actually delivered to the smoker (Manno et al., 1970). Available data on the amounts of Δ 9-THC delivered by smoking are relatively meagre; more research is needed on the variations in the dosage obtained from marihuana and other cannabis preparations when different smoking devices and techniques are used. Δ 9-THC is about 3 times as potent when smoked as when ingested (Isbell et al., 1967). The subjective effect begins very rapidly when Δ 9-THC or cannabis preparations are smoked, an experienced smoker being able to perceive subjective effects within a minute after one or two puffs of a potent preparation. The peak effects are probably reached within 20 - 30 minutes after smoking. In contrast, when Δ 9-THC or extracts of cannabis are taken orally, about 30 minutes elapse before subjective effects are perceived. The duration of action varies with the dose, but the effects of a single administration are usually dissipated 3 - 4 hours after smoking or about 8 hours after oral administration. 20The degree and duration of effect after smoking a given amount also probably vary with the speed of smoking.
19. Failure to use this technique may partly account for the apparent lack of effect when cannabis is first smoked by a novice (Becker, 1953).
20. Hollister et al., 1968; Isbell et al., 1967; Jones (unpublished data).
21. Hollister et al., 1968; Isbell et al., 1967; Manno et al., 1970.
23. Ibid.
4.2 Immediate effects
4.2.1 Usual symptoms and signs
... Symptoms after taking Δ 9-THC or cannabis preparations depend on the dose, 21as well as on the setting and the expectations and personality of the user. In experiments with one sample of Δ 9-THC, threshold doses of 50 μg/kg by smoking or 120 μg/kg orally, caused chiefly mild euphoria (Isbell et al., 1967). With doses of 100 μg/kg by smoking, or 240 μg/kg orally, some perceptual and sensory changes also occurred. Doses of 200 - 250 μg/kg by smoking, or 300 - 480 μg/kg orally, resulted in marked distortion of sensory perception, depersonalization, derealization, and both optical and auditory hallucinations...
The signs are few. They consist of injection of conjunctivae, a decrease in muscular strength, as measured with a finger ergograph, and an increase in pulse rate; these effects do not regularly occur with a placebo and the increase in pulse rate parallels the intensity of the subjective effects at peak time. Resting systolic and diastolic blood pressure, respiration rate, body temperature, threshold for eliciting the knee jerk, and pupil size are not affected... 22
Various doses of cannabis preparations produce some impairment of body and hand steadiness, which persists as long as the effects of the drug (Mayor's Committee on Marihuana, 1944)...
One preliminary study showed the smoking of two marihuana cigarettes to have little effect on the more complex task of operating a driving simulator (Crancer et al., 1969), although the subjects in that study reported achieving a " social high "....
The matter deserves further investigation, with attention to the effect of cannabis at various dose levels not only on psychomotor performance but also on the attention and judgement required of drivers (Kalant, 1969)...
Consistent reports of interference by cannabis with short-term and immediate memory function have focused experimental investigation on these and other cognitive areas...
Oral doses of cannabis (an estimated 20 mg of Δ 9-THC) given to "naive" subjects severely impeded a learning task that required the subject to discover and remember several associations via trial and error· It also significantly impaired reading comprehension (Clark et al., 1970). In experienced users the smoking of cannabis (an estimated 18 mg of Δ 9-THC), caused a pronouced decrease in the coherence, clarity, and time orientation of speech and an increase in free association and dream-like imagery (Weil and Zinberg, 1969). The impairment in performance of these more complex tasks appears to arise from difficulty in maintaining a logical train of thought...
In summary, cannabis significantly impairs cognitive functions, the impairment increasing in magnitude as the dose increases or the task is more complex or both.
4.2.2 Acute psychotoxic reactions
...Syndromes resembling acute intoxication may occur following relatively small doses of cannabis, e.g., after smoking one cigarette, especially among "naive" users. 23
Another type of acute psychotoxic reaction is seen in persons who appear to be overwhelmed by marked anxiety, fear, and panic (e.g., fear of death or of " going crazy "). Such persons are usually agitated and depressed, and occasionally withdrawn. There is usually very little or no evidence of disorientation, delusions, illusions, or hallucinations (Weil, 1970). The presence of a reassuring person significantly reduces the likelihood of this syndrome occurring and alleviates the symptoms if it does occur. Its duration may be from a few hours to, more rarely, a few days. This syndrome tends to occur after relatively small doses (e.g., the equivalent of one or two marihuana cigarettes), as well as after larger ones. It has been observed in persons who later insisted that it followed their first experience with cannabis. 24Newly initiated users are also reported occasionally to develop a depressive syndrome after small doses (Weil, 1970).
4.3.2 The question of psychoses
Various psychiatric conditions purportedly related to or associated with the use of cannabis have been described, covering a wide range of disorders and situations. 25They can be considered as comprising the following groups:
Specific cannabis disorders:
acute and subacute disorders
residual psychoses
personality deterioration following prolonged use
Other psychiatric disorders, precipitated or aggravated by the use of cannabis
Coincidental association of a psychiatric disorder with cannabis use...
23. Bromberg, 1934; Defer, 1968; Roland and Teste, 1958; Talbott and Teague, 1969.
24. Bromberg, 1934; Talbott and Teague, 1969; Weil, 1970.
25. Bromberg, 1934; Chopra and Chopra, 1957; Christozov, 1965; Dally, 1967; Defer and Diehl, 1968; Roland and Teste, 1958; Talbott and Teague, 1969; Watt, 1961.
26. Chopra et al.,1942; Christozov, 1965; Indian Hemp Drugs Commission, 1894; Roland and Teste, 1958; Warnock, 1903.
The literature often mentions the existence of a characteristic personality deterioration among older habitual users after prolonged "excessive" use. 26Such individuals are frequently described as showing a simple-minded, carefree state, the following terms being typically applied: "chronic, cheerful mania"; "kif-happy vagabonds"; and "hilarious and full of a sense of well-being ". No systematic scientific study has been made to assess their previous personalities, the social factors involved, and the occurrence of such a syndrome among non-users of cannabis. This syndrome could, in theory, be a primary specific cannabis disorder as well as a residual effect of a more acute disturbance...
4.3.3 Some psychosomatic aspects
... There is evidence that, under certain conditions, the regular use of cannabis for several years is associated with measurable deficits in a number of psychomotor and cognitive functions. In a study of 850 hashish users and 839 non-users as controls, drawn from a population of prisoners in Egypt, Soueif (unpublished data) showed differences between users and controls in a number of standardized objective tests. These assessed speed and accuracy of psychomotor performance, initial reaction time, memory for digits, and memory for designs. Comparisons were made between subgroups of test and control subjects equated for education. In most of the tests used, the hashish users had poorer scores than the controls. In general, the higher the level of education of the users and non-users the larger was the discrepancy between their respective test scores. It must be stressed that the association between cannabis use and the reported deficits does not necessarily indicate a causal relationship. The differences might pre-exist or might be related, for example, to changes in life style occasioned by regular participation in socially disapproved and unlawful activities.
A number of authors claim a fairly consistent association between "heavy" use of cannabis and a characteristic symptomatology, sometimes called the "amotivational syndrome ". It has been especially emphasized with cannabis use among young persons in Europe and the USA. Among the main characteristics usually cited are apathy, emphasis on the present rather than the future, preference for fantasy rather than rationality, child-like thinking, and preference for a loosely structured type of life rather than one that is well structured and goal-directed (McGlothlin and West, 1968). It has been suggested that the clinical picture resembles that of patients with an organic brain syndrome (Brill et al., 1970). However, the evidence might equally suggest a learned constellation of behaviour in which cannabis acts as a catalytic agent...
4.3.4 Cannabis and crime
The arguments purporting to relate cannabis use to crime fall generally into 3 categories:
Loss of control during cannabis intoxication may result in violence or other forms of impulsive behaviour.
Cannabis-induced lethargy may lead to loss of legitimate earnings and hence to petty thieving.
Cannabis may provide persons predisposed to criminality with the courage to commit antisocial acts.
The evidence in support of the first argument is generally anecdotal, although it appears that, of those cases coming to the attention of the authorities, violent and impulsive behaviour is not infrequent among persons with relatively acute psychotic reactions to cannabis. 27On the other hand, disruptive behaviour plays a significant role in determining whether or not an individual with an acute cannabis psychosis is hospitalized (Indian Hemp Drugs Commission, 1894; Peebles and Mann, 1914), so that those exhibiting violent behaviour are probably over-represented in the hospitalized samples. Some authors in the USA have attempted to establish the direct role of cannabis in violent acts, 28 but these reports are of little value because there is usually no effort to establish the validity of the claimed relationship, nor is information provided on the relative incidence of such cases among otherwise comparable populations of users and non-users...
4.4 Questions of tolerance and physical and psychic dependence
In a description of drug dependence of the cannabis (marihuana) type (Eddy et al., 1965) the following characteristics were listed: ( a) moderate to strong psychic dependence on account of the desired subjective effects; ( b) absence of physical dependence, so that there is no characteristic abstinence syndrome when the drug is discontinued; ( c) little tendency to increase the dose and no evidence of tolerance. These characteristics must now be re-examined because of subsequent findings.
4.4.1 Tolerance
... The question of tolerance to cannabis in man clearly deserves further investigation ...
4.4.3 Psychic dependence
This has been described as a condition in which a drug produces "a feeling of satisfaction and a psychic drive that require periodic or continuous administration of the drug to produce pleasure or to avoid discomfort" (Eddy et al., 1965).
27. Bouquet, 1951; Chopra et al., 1942; Christozov, 1965; Roland and Teste, 1958; Warnock, 1903;
28. Merrill, 1938; Munch, 1966; Wolff, 1949.
As in nearly all biological, and particularly behavioural, phenomena, there is no hard and fast line between a state of psychic dependence and its absence. Rather, there is a continuum of phenomena, at one end of which psychic dependence clearly does not exist, while at the other it clearly does. Between these extremes there is a zone of behaviour that is not sufficiently characteristic of either extreme for it to be said that psychic dependence does or does not exist. In judging the presence or absence of psychic dependence in an individual, it is important to ascertain how far the use of cannabis appears to be a life-organizing factor, or to take precedence over the use of other coping mechanisms, or both (Cameron, 1971). The Group was of the opinion that many regular (almost daily) users of cannabis exhibit psychic dependence, as do some less frequent but relatively "heavy" users, whereas the great majority of people who use it a few times on an experimental basis, or casually on a few festive occasions a year, could not be said to exhibit psychic or any other dependence on cannabis.
There is a substantial fund of knowledge about ( a) the properties of Cannabis sativa L. and its various psychoactive preparations, ( b) the general manner in which those substances are used in different parts of the world, ( c) some of the individual and sociocultural factors associated with their use, and ( d) the dose-related immediate effects on man of taking cannabis and 9-THC. There are, nevertheless, a number of important questions to be answered with respect to these areas.
... The Group considered it especially important to intensify substantially current research on ( a) major epidemiological problems in widely varying sociocultural settings, and ( b) the effects on man of using various cannabis preparations in differing amounts for specified, particularly prolonged, periods of time. Research on these problems has so far received less support than is warranted by their importance. International collaboration would greatly enhance the value of such investigations. The following are among the areas of highest priority:
5.1 Determination of the cannabinoid content of cannabis preparations in use in different parts of the world
An initial broad study, followed by selective monitoring, is needed for the purposes of comparative epidemiology. It is advisable that a large number of representative samples be collected in each area studied, taking into account the types of preparations and, where possible, their age and source. The minimum information required on the chemical constituents is the Δ 9-THC content. It would be desirable to determine also the content of 8-THC, 9-THC acid, CBN, and CBD.
5.2 Distribution of cannabis consumption in the populations of various countries
This requires attention to the modes and frequency of consumption and the average amount consumed on a given occasion (preferably expressed as Δ 9-THC content). Longitudinal data are also required on the proportion of the population who use and later discontinue use of cannabis and on those who continue to use it sporadically or gradually increase their level and frequency of consumption. The relation of cannabis use to the use of other drugs should be investigated in this connexion. Social and personality factors associated with non-use, as well as with use, in a given sociocultural setting should be studied. Finally, the drugs used by a particular culture for non-medical purposes should be evaluated in order to assess their relative impact on the individual and society. The regions selected for study should represent different levels of acceptance of cannabis use in a variety of sociocultural settings.
5.3 The effects of long-term cannabis use
It would be highly desirable to correlate studies on the effects of long-term use with the distributional picture indicated in section 5.2. That is, samples of users should be selected for special study who are representative of various levels of use as regards quantity and frequency. These samples should be studied with special reference to the occurrence of bronchopulmonary and cardiovascular diseases, chromosomal abnormalities, teratogenic effects, organic brain damage, deficits in cognitive and other skills, and social effects such as crime and other deviant behaviour. Evidence of changes in tolerance and characteristic abstinence symptoms and signs should also be sought. Comparisons should be made in all instances with suitable control samples of nonusers. Because of methodological limitations, causal relationships often cannot be established. Nevertheless, such studies are useful since they establish the maximum effects that can be attributed to various levels of drug use. For instance, it would be useful to know the maximum effect on a particular variable that could be expected from the daily consumption of 1 g of ganja for 20 years.
5.3.1 The relation of cannabis and psychoses
In section 4.32, stress is placed on the need for studies on the prevalence and incidence of various psychiatric disorders in different groups of cannabis users (in relation to level and frequency of use) and in matched controls. In addition, since one of the more frequently mentioned distinguishing features of the "cannabis psychosis" is its relatively short duration as compared to functional psychoses, a prospective study comparing length of hospitalization for psychiatric admissions with and without a history of cannabis use might be useful. Better information on the history of onset is also needed.
5.4 Pharmacological research
Although such research is not the main subject of this section, certain areas are mentioned because of their close connexion with the above topics. Since cannabis is frequently used in combination with other drugs, e.g., tobacco and alcohol, or closely following them, experimental studies of the effects of such combinations are desirable. Further clarification of the relationship of response to dose and to route of administration is needed, from the standpoint both of acute effects and of the development of tolerance. There is also a need to assess further the acute effects of cannabis on attention, judgement, and psychomotor and other skills related to driving or to operating machinery.
In view of the complexity and cross-cultural nature of some of the more important research needs that have been mentioned, a number of observations and recommendations are offered on ways in which investigations might be encouraged and facilitated, and their productivity enhanced.
6.1 Provision for research access to cannabis and cannabis users
Laws and regulations concerning the control of cannabis and its preparations should take account of legitimate research needs. Where not already in existence, provisions should be considered that would permit ( a) possession of needed research materials by accredited investigators, and ( b) epidemiological research (e.g., surveys of patterns of use) without legal hazard to the investigator or user.
6.2 Comparability of cannabis materials involved in research studies
There is great variability in the degree of psycho-activity produced by different cannabis plants and preparations (see section 2.1). The following means are recommended to ensure the maximum comparability of results from studies in which the potency of cannabis materials is an important consideration.
Standard materials of known chemical content should be available for experimental studies of acute and chronic effects. 29If such materials are prepared in different laboratories, there should be common agreement on the chemical and biological criteria of potency.
As noted in section 5.1, the cannabinoid content should be determined for cannabis preparations available in many parts of the world. It would be desirable for one organization to co-ordinate the collection and analysis of samples. Standard techniques of handling and analysing samples are essential.
Research workers should have ready access to means of monitoring, by commonly agreed methods, the chemical and biological potency of materials under investigation.
29. Substantial progress has recently been achieved in this field through the marihuana research programme of the National Institute of Mental Health in the U.S.A. (Miller, 1970; Waller, 1970).
30. In so far as possible, standard psychological and other test instruments and procedures should be identified that are relatively "culture-free" and capable of being adopted for local use in a variety of settings. They would not necessarily be the only tests used, but would provide a common bridge for purposes of comparison between projects.
6.3 Comparability of research approaches
... The following proposals are made for this purpose:
Provision should be made for the formation of a multidisciplinary group of research and other workers concerned with the epidemiology of cannabis use. These workers should be representative of each of the major areas of use in the world, and should meet periodically to develop common elements of approach, methods, and test instruments, 30and to share experiences and The use of cannabis 19 pool data from their respective geographic areas and fields of competence. The group might be assigned the additional task of preparing periodic statistical and interpretative reports on the use of cannabis. Finally, selected members of the group might be called upon from time to time to constitute a team to assist in the development of epidemiological studies or to carry out time-limited studies in a particular area.
Provision should be made for the convening of small groups of selected investigators who have entrée, in different regions of the world, to subcultures in which cannabis is used extensively. Discussions would centre on ( a) their experiences in data collection, ( b) the individual and social factors apparently associated with cannabis use and non-use in their localities, ( c) the feasibility of collecting data with reasonably comparable parameters, and ( d) the feasibility of establishing pilot programmes for cross-cultural collection and analyses of data
(3) Development of multidisciplinary research centres and information resources
The importance of a multidisciplinary approach to the entire field of drug dependence has been stressed by the WHO Expert Committee on Mental Health (1967). Research designed to further knowledge about the extent and consequences of cannabis use is no exception. To stimulate further the development of much-needed research on cannabis in many parts of the world, it is recommended that WHO consider designating centres and individuals in appropriate regions of the world to assist in such endeavours. The Organization would be in a unique situation to foster collaboration among these centres and individuals, and their co-operation with other individuals and organizations concerned.
