2. Cannabis and Its Effects

CANNABIS AND OTHER DRUGS

Pharmacological Interaction

The interaction between cannabis and other drugs has only recently begun to be systematically explored. Most of the existing pharmacological research has been done on animals. Cross-tolerance among the cannabinoids has been demonstrated in some species.418 In rodent studies, some cannabinoids have been shown to prolong barbiturate sedative and hypnotic effects and, paradoxically, to intensify amphetamine stimulant activity, probably through metabolic interaction.211,225,346,491,616  Cannabis increases alcohol effects on behaviour in mice 192,240 but does not interact with diethyl ether (which is not metabolized in the body). 225 Recently it has been shown by Manno and associates399,400 and by Commission research,518' that in humans, cannabis and alcohol can have additive effects on certain psychomotor and physiological functions, and that marijuana may intensify the sedative properties of ethanol under some conditions. On the other hand, marijuana and alcohol may produce antagonistic effects on some subjective variables such as visual imagery. 146,149,251,518 (Commission research suggests that these interaction effects can occur in the absence of any change in alcohol absorption, metabolism or excretion .518 )

Evidence of interaction between cannabis and other drugs has led to speculation that even though cannabis itself has very low lethal toxicity, high doses taken concomitantly with large quantities of sedatives, such as barbiturates and alcohol. or opiate narcotics may increase the likelihood of overdose effects with the latter drugs.489,490 Fernandes found in animal studies  that cannabis had no significant effects on the lethal dose of alcohol, but increased sensitivity to barbiturate and morphine overdose, and reduced the toxicity of amphetamines.185' No cross-tolerance has been found between THC and LSD, mescaline, psilocybin or opiate narcotics in animal and/or human studies. 297,418,460 Cross-species generalizations from all of these reports must be limited, since the effects demonstrated may not apply to different animals or humans uniformly. Some cross-tolerance between cannabinoids and sedative drugs, such as barbiturates, minor tranquilizers and alcohol might exist in heavy chronic cannabis users, but these combinations have not been scientifically explored in man. The discovery that THC is progressively metaholized by the same nonspecific microsomal enzyme system in the liver as is involved in the biotransformation of many different substances, may be significant in the study of cannabis interactions with other drugs.

Stimulants are reportedly sometimes taken with cannabis to intensify certain effects and to negate the sedation some users experience with cannabis alone. It is said that DMT or DET are sometimes smoked in marijuana, but no such mixtures have been documented in Canada. Cannabis, as has been mentioned, is commonly taken with large quantities of tobacco in many countries, and in North America hashish is sometimes rolled into 'joints' with tobacco to facilitate burning. Possible interaction effects between cannabinoids and nicotine or other agents or irritants in the smoke from these plants have not been systematically examined. It is sometimes claimed that cannabis reduces some of the adverse aspects of opiate narcotic withdrawal,268,407 even though no significant cross-tolerance exists between these two classes of drugs. In addition, some 'speeders' reportedly smoke cannabis during their withdrawal to 'mellow the crash'. There is occasional mention in the 'underground subculture' that the juice from citrus fruit may counteract some aspects of the cannabis 'high'. The notion of a 'citrus antidote' to overdose effects is also mentioned in some of the older medical literature540 and reports from non-industrial countries, but has apparently not been systematically explored in the laboratory.

Patterns of Multiple-Drug Use

The majority of cannabis users studied in North America have had experience with a variety of other psychoactive drugs, alcohol and tobacco being the most frequently mentioned. The use of heroin, amphetamine and LSD is also much more common in cannabis users than in the general population.

Cannabis and alcohol. The relationship between cannabis and alcohol use has been the subject of much controversy. Some have suggested that cannabis may be a cure for society's alcohol ills. In general, survey studies of incidence of drug use find that those who use alcohol are much more likely than 'teetotallers' to use cannabis, and that most cannabis users still drink alcohol. In addition, heavy users of cannabis tend to drink more alcohol than light or infrequent users. 54,60,104,239,349,350,351,394,536,570,584,624 In a retrospective study of black males in St. Louis, a higher incidence of alcoholism and related problems was found among cannabis users than non-users.523 We have no information as to the effect cannabis had on an individual's drinking behaviour and overall alcohol intake in most of these studies, however.

Many researchers have mistakenly assumed that survey data indicating a positive between-subject correlation of cannabis and alcohol use, at a single point in time, implies a positive relationship between the use of the two drugs within an individual over time. which is the relationship of ultimate interest. This extrapolation is unjustified logically and statistically.117 Evidence of an association (either positive or negative) between the use of two drugs in a population at a given time provides little information as to the relationship (if any) between the use of the drugs within the individual members of the group. Changes in behaviour, over time, within an individuate must be studied directly. Even then, other secondary data in addition to drug use patterns must be considered in order to determine causal factors.

The bulk of the limited retrospective, within-subject data now available suggest that cannabis use may reduce or interchange with alcohol consumption in the user opulation. In many surveys, including several Commission studies, 238,239,351 a substantial proportion of cannabis users claimed that they have significantly reduced their consumption of alcohol or quit it since using cannabis.247,248,415,493,554,682  There is a reported tendency, with cannabis use, for a greater reduction in the use of hard liquor than of the milder forms of alcohol. The combined consumption of cannabis with wine or beer is common in some social circles. Anecdotally, in certain parts of the United States, alcohol sales in university areas have reportedly declined as marijuana use increased, in spite of generally spiralling alcohol sales across the country.472  Also of interest, five fraternities on a Midwestern campus reported that the proportion of social funds spent annually on alcohol had been reduced considerably since marijuana use became common. No indication of alcohol abstinence appeared in these fraternities, however. 438 None of these reports present definite, verifiable evidence of a reduction in alcohol use, and conclusions must be guarded.

Some cannabis users claim that alcohol effects dominate and, for that reason, they refuse to mix the drugs even if they enjoy each one separately. In several studies, however, where alcohol and cannabis were given separately or together in low doses under 'blind' conditions, some experienced cannabis users were not particularly proficient at identifying the predominant drug action.215,305,518  differentiation is easier at higher doses, however, and alcohol does appear to reduce some of the 'psychedelic' aspects of cannabis. 149,251,518

It would appear that individuals who actually quit alcohol use because of cannabis reflect a minority of users, and their choice of drugs may have more to do with their particular value systems than with the pharmacological properties of the drugs. The hostile attitude towards alcohol expressed by some cannabis-using youth is clearly not reflected in the majority of cannabis users. Combined use is apparently becoming increasingly common. Systematic prospective studies have not been done, and it is not clear from the data whether, on a large scale, cannabis would tend to replace alcohol as an intoxicant in the user population, or whether the use of these drugs would be additive without significant interaction, or if the use of one might potentiate or increase the consumption of the other.

Comparing the benefits and harms of alcohol and cannabis has become a popular and engaging activity. Due to the profoundly different social connotations, patterns of use, and scientific knowledge of these drugs, such a comparison must be made on limited and tenuous grounds. (In addition. only a few experimental studies have been done directly comparing cannabis and alcohol in humans. 108,267,282,305,308,397,440,518,573)

Cannabis and tobacco. In North America, marijuana use has traditionally been closely tied to tobacco use and there seem to be relatively few regular cannabis smokers who did not initially learn the technique of inhaling smoke from prior experience with tobacco cigarettes. In some areas of North America the majority of tobacco smokers have also used cannabis. While the smoking of tobacco leaf does not necessarily precede or lead to the similar use of cannabis, the temporal sequence is commonly observed and must be considered in any serious investigation of the proliferation of drug use today. A pharmacological "progression" from tobacco to cannabis has been suggested,531 but is not considered a likely direct causal factor, and there is no scientific evidence that one drug creates a need for another.

The importance of a "smoking barrier" in the spread of drug smoke inhalation has been given considerable attention.60,195,243 Because the inhalation of smoke is initially difficult and unpleasant for the novice and usually requires considerable practice and control of natural reflexes, the problems of learning the technique of smoking might be considered a general barrier against this mode of drug administration. Many observers feel that after one has acquired the seemingly unnatural and originally offensive practice of smoke inhalation and learned that the effects can be rewarding or pleasurable, the general "smoking barrier" is removed and the smoker is then more likely to try smoking other drugs.

Blum has presented considerable evidence that before the world-wide "epidemic" spread of tobacco use, the intentional inhaling of the smoke from burning substances, as a mode of drug administration, was not popular in most parts of the world. The smoking of opium in China and India, for example, only occurred after tobacco was introduced from the West to the Orient, and for some time opium was smoked in conjunction with tobacco.59 Cannabis, even today, is rarely smoked alone in Eastern countries. In India, hashish and marijuana are invariably mixed with large quantities of crude tobacco for smoking. 126,295 The smoking of cannabis was not common before tobacco was introduced. It would appear then, that although cannabis was previously consumed in other ways, the past and present practices of smoking cannabis in most cultures is directly and causally linked with the assimilation of tobacco smoking practices from the Western Hemisphere.

Progression to heroin and other drugs. In the past two decades, the relationship between cannabis and heroin has been the subject of heated controversy in Western literature. During this period, reports from the United States indicated that the majority of heroin users studied had previously used cannabis, although in certain sections of the country (noticeably the southeastern states) this was not the case.28 Before 1950, there was little evidence or serious discussion of a cannabis-to-heroin progression. Similarly, until recently in Canada, there appeared to be no relationship between the use of cannabis and heroin. Heroin users studied were generally heavy consumers of alcohol, barbiturates, and tobacco, but had little or no cannabis experience.588,671 The situation has apparently changed. and many young Canadian heroin users report previous and concomitant use of marijuana. amphetamines and LSD. 302

Several studies in the United States of persons arrested for cannabis offences, or noted for other delinquent behaviour, indicate that a significant number of these individuals were later arrested on heroin offences.99,228,506 In some instances, however, the critical contact with heroin users and sources came from a prison experience. Robins reported that one-fifth of a group of blacks in St. Louis who were users of cannabis in the 1940s had admitted to subsequent heroin use.523

Paton used a Bayesian formula employing various estimates of the incidence of cannabis and heroin use in the general population and in the sub-population of heroin users in England, to predict that seven to fifteen per cent of cannabis users will try heroin.488 The appropriateness and accuracy of the figures used in the formula and their applicability to the present situation are highly questionable. The proper use of Bayes' Theorem in this application requires accurate estimates of the incidence of drug use in the various populations described, at a single point in time. Good epidemiological data meeting these criteria were not available in England, and some researchers have suggested that if other, apparently equally justifiable, estimates had been employed, rather than those used by Paton, the resulting prediction of heroin use among cannabis users would have been substantially lower.243,544 In any event, even estimates derived from the proper use of the statistical formula can be considered valid only as long as the social and epidemiological conditions associated with the use of both drugs remain constant. These requirements call into question the general value of Bayes' Theorem in those areas of science dealing with rapidly changing social phenomena.

Studies based on lower-class and/or delinquent populations do not readily generalize to the present phenomenon of middle-class cannabis consumption. In middle-class cannabis users it would appear that only a small minority have experience with opium and even less with morphine and heroin. However, an increase in opiate narcotic use in the younger middle-class groups in Canada has been reported.

A similar controversy exists regarding the role of cannabis in the use of amphetamines and LSD. Most chronic users of these drugs report earlier experience with cannabis and illicit, heavy use of alcohol and tobacco, as adolescents.

In North American studies, peer group values and the establishment of contacts with illicit drug distribution networks have played a major role in concomitant and sequential illegal use of different drugs. Becoming accustomed to "breaking the barrier" of illegal drug use by the consumption of one illicit drug may reduce, in some individuals, inhibitions with respect to other such drugs, It has been proposed that cannabis often provides the initial drug in this context. Although previous heavy illicit use of alcohol during adolescence is common in adult chronic drug users, drinking by young people, even though illegal, is largely condoned and, to some extent, encouraged by our society; it does not have the legal significance that cannabis use has. Some have suggested that through the use of cannabis certain, perhaps predisposed, individuals may learn the use of drugs as a mode of coping or as a simple primary source of reinforcement and satisfaction, and that this lesson might later generalize to other drugs. Many argue that persons who ultimatel become dependent on opiate narcotics, 'speed' or other 'hard' drugs are strongly predisposed in that direction by personal, social and economic factors and that the use of cannabis as a transitional drug is of little causal significance. Attempts to identify and establish these predisposing factors have met with little success, however, and this interesting hypothesis has yet to be confirmed scientifically.

In summary, a positive statistical relationship exists between the use of cannabis and a variety of other psychoactive drugs. Marijuana is often the first illicit drug (other than alcohol and tobacco in adolescence) taken by multi-drug users. The role of cannabis, if any, in the progression to other drugs is not yet well understood; it is unclear whether it plays a specific predisposing role, or is causally unrelated to other drug use and is often used earlier simply because of its wider availability and social acceptance. Specific pharmacological properties of marijuana (or any other drug) which might lead to a need or craving for other drugs have not been discovered. It would appear that dynamic and changing social and personal factors play the dominant role in the multi-drug-using patterns reported, and that the specific pharmacology of the compounds involved is secondary.