CANNABIS :
OUR POSITION FOR A CANADIAN PUBLIC POLICY

REPORT OF THE SENATE SPECIAL COMMITTEE ON ILLEGAL DRUGS

VOLUME I : PARTS I and II


Chapter 7

Cannabis: Effects and Consequences

Cannabis, as we saw in Chapter 5, acts on the central and peripheral nervous systems in various ways. While research has established a fairly clear role for some of the components of cannabis, D9THC in particular, the main active component, we are less sure of the role of other chemicals. Similarly research, which is often conducted on laboratory animals or in an even more specialized manner on molecules extracted for experimental purposes, does not reflect the conditions under which the average user uses marijuana. We have seen that, in some cases, dosages used for experimental purposes on laboratory animals, in particular to determine the chronic effects of regular use, are dosages that are unimaginable for humans, the equivalent of 570 marijuana cigarettes a day. Since THC content varies greatly with the cannabis available on the market, since users make different use of the drug depending on the place and circumstance, and since individual characteristics interact with the actual effects of cannabis, knowledge of the effects is necessarily influenced.

From an even more technical standpoint, we should point out that a statistical association – that is, the fact that two facts are concomitant – in no way indicates causality. To infer causality, a certain number of methodological prerequisites must be satisfied. In addition to the statistical association, we must be able to dismiss chance and alternative hypotheses, and show that the causative factor does precede the inferred consequence. According to the WHO:

 

Causal inferences can be drawn from research findings by judging the extent to which the evidence meets widely accepted criteria. These include: strength of association, consistency of association, specificity, dose-response, biological plausibility, and coherence with other knowledge. These criteria are not sufficient to show that an association is causal but the more are met, the more likely it is that the association is causal. [1] 

 

Moreover, a strong tradition in the philosophy of science holds that you can never prove a hypothesis. The most you can do is falsify – that is, dismiss – alternative hypotheses.[2]

To try to meet the requirements of causality, researchers have developed sophisticated research methods, providing in particular for the random selection of subjects for a study, the random assignment to experimental conditions and non‑experimental conditions (control group), the use of double blind and placebo techniques, the careful control of intervening variables that could represent as many alternative hypotheses as researchers are trying to eliminate. This is how, for example, they usually try to test medications that are put on the market.

For most questions involving human behaviour, a fortiori in society, it is difficult and rarely possible to establish such a causality relationship for the simple reason that each of these methodological requirements can rarely be met. In our case, the effects of cannabis use, the methodological constraints are particularly obvious. We cannot gather a random sample of cannabis users since we don’t know the population. Therefore we must rely on alternative methods for selecting subjects (volunteers, for example). It is difficult to have people smoke cannabis who would otherwise never use it38 without running the risk of contravening certain rules of ethics, or even legal provisions. And if we resort to people who have already smoked it, there is necessarily contamination of the control group. The cannabis that is used in the lab may be completely different from that of users who buy it off the street. And controlled laboratory conditions definitely do not reproduce the methods of cannabis use, which we know are usually a form of social ritual. As for studies–and they are numerous–conducted on animals (monkeys, mice, rats…), they may be interesting, but the possibility of transposing their results onto humans is limited. Lastly, we note that, as most cannabis smokers also smoke tobacco and drink alcohol, it is difficult to separate the effects of one from the effects of the others.

Obviously that does not prevent researchers from conducting studies, and these studies are also necessary. However, it does require researchers to be as prudent as possible when interpreting their results, in particular with respect to the ability to generalize about all marijuana users and to draw causal inferences. This is a caution that we do not always find, far from it, as this chapter will repeatedly show.

Lastly, we should note the distinction between effects and consequences. Smoking cannabis has immediate effects, some physiological and some psychosocial, that we must describe. But smoking cannabis, especially repeatedly, can also have consequences, some immediate – for example, the ability to perform certain tasks or the ability to drive a vehicle – and others more distant – for example if smoking cannabis results in a greater risk of lung cancer and if it has a lasting effect on memory.

We are aware of just how arbitrary these distinctions can be insofar as a human being is a whole, an organism integrated into his emotional and social environment and into his ecosystem. The physiological, psychological and social effects interact with one another, infiltrate one another, influence one another and act together rather than separately. In some ways, these distinctions remain the reflection of our incompetence, or at least of our inability, to think about the various systems of a human being as a whole, from every angle. This same incompetence can, also in part, explain the difficulty we have in creating a drug policy. It is to be hoped that those who come after us will be able to develop an integrated, holistic approach. For now, we are forced to use the means at our disposal, our fragmented understanding.

One last preliminary note. We were constantly guided by the need to be rigorous. Be that as it may, our resources did not enable us to be completely thorough and to examine the studies one by one for all these questions. In total, we know that approximately ten thousand studies have been published on cannabis over the last forty years! However, as Nelson points out, “Although the total volume of this literature is somewhat daunting at first glance, a sampling of the material soon reveals that much is repetitive and a relatively small number of papers are continually referred to by most authors.” [4] Despite this repetition, we could not go without examining a certain number of these studies. That is why we commissioned the preparation of a summary report[5] and also examined the summaries of scientific literature that were prepared in recent years.[6]

This chapter is divided into five sections. The first is a collection of statements on the presumed effects of marijuana that the Committee heard or that it was made aware of through its research. The following three sections examine the acute effects of cannabis, followed in turn by the physiological and neurological consequences, the psychological consequences and the social consequences. Then, because of its significance and the central place it holds in social and political concerns, we turn our attention specifically to the question of dependence possibly arising from prolonged use of cannabis.

 

 


Effects and consequences of cannabis: what we were told

 

During the hearings, many witnesses told us what they knew about the effects of cannabis. Some of this knowledge came from their own research work. Other knowledge came from their professional experiences. And lastly, other knowledge was either their interpretation of scientific literature or anecdotes. In this section, we will not make distinctions between the testimony and we will not evaluate its validity. We only want to highlight the richness, as well as the complexity, of what we were told.

 

Message number one is that drugs, including cannabis, are harmful. (…) There is considerable misinformation about the physiological consequences of cannabis use. There is no doubt that heavy use has negative health consequences. The most important are in the following areas: respiratory damage, physical coordination, pregnancy and postnatal development, memory and cognition, and psychiatric effects. (...) [7]

 

Generally, marijuana (cannabis) and its derivative products are described in this context to distance the drug from the recognized harm associated with other illegal drugs. This has been a successful yet dangerous approach and contributes to the misinformation, misunderstanding and increasing tolerance associated with marijuana use. Marijuana is a powerful drug with a variety of effects. Marijuana users are subject to a variety of adverse health consequences that include respiratory damage, impaired physical coordination, problem pregnancy and postnatal deficits, impaired memory and cognition, and psychiatric effects. Marijuana use is associated with poor work and school performance and learning problems for younger users. Marijuana is internationally recognized as a gateway drug for other drug use. Risk factors for marijuana dependence are similar to those of other forms of drug abuse. (…) It was the consensus of the international community to put marijuana and other substances under international control. That decision was based on evidence of its harmfulness to human health and its dependence potential. [8]

 

I wish to briefly review two of what I believe are fairly well-established, harmful effects of marijuana, and a number of other areas where there is considerable contention. (…) By far the most consistent and clear-cut effect of marijuana is disruption of short-term memory. Short-term memory is usually described as "working" memory. It refers to the system in the brain that is responsible for short-term maintenance of information needed for the performance of complex tasks that demand planning, comprehension and reasoning. The relatively severe impairment of working memory may help to explain why, during the marijuana high, subjects have difficulty maintaining a coherent train of thought or conversation. (…) Obviously this is relevant if you are going to school stoned. (…) It is becoming increasingly clear that cannabis is a drug on which regular users become dependent, and that this adversely affects large numbers of people. [9]

 

Marijuana has been shown to be associated with reckless drivers and motor vehicle accidents. Evidence suggests that marijuana may contribute to an appreciable number of traffic deaths and injuries in Canada. It has been shown to negatively affect the academic and social development of some adolescents. Marijuana can cause emotional and medical problems. Chronic use may be associated with lung diseases such as bronchitis, emphysema and cancer. A psychosis may develop in some individuals while other psychiatric symptoms such as anxiety, low mood, depression and panic do occur. Marijuana is known to be addictive. Although the rate of addiction varies, it is between 5 per cent and 10 per cent. I should like to stress that addiction is a disease and marijuana has the potential to be addictive to a genetically predisposed group of individuals. [10]

 

The evidence was that 95 per cent of the marijuana users in Canada are low, occasional, moderate users. Their consumption of marijuana does not impact on their health as long as they are healthy adults. The other 5 per cent are chronic users, people who smoke one or more marijuana cigarettes per day. If they continue to do that, they will ultimately get chronic bronchitis from the smoking process. The same would be true if they were to roll up the grass off their lawns and smoke that. They would inhale heated material over their large airways and cause damage to them. There were three primary vulnerable groups: pregnant women, which we submit is something between the woman and her doctor; the mentally ill, particularly paranoid schizophrenics (…) then, most importantly, immature youth. Young people who become involved with marijuana - particularly on a regular basis - seem to suffer from a disruption of their studies and the maturation process. As is the case with most intoxicants, it is recommended that they not become involved with them until they have matured. [11]

 

I have one resource from the Center for Substance Abuse Prevention in the U.S., where recent marijuana research and a number of studies indicate some of the risks. We already know and accept that cannabis has negative effects on many systems - respiratory, motor skills, memory and immune - and that it creates drug dependency and tension. In addition, we now know from numerous research studies that there is a definite and acute withdrawal syndrome associated with chronic cannabis use. (…) There is research that suggests there are effects on the developing fetus. (…) I will speak to visual scanning, specifically, attention dysfunction in the form of impaired visual scanning and related functioning. Visual scanning develops particularly in early adolescence, so earlier onset is associated with some concerns there. [12]

 

There are a number of negative health effects that have been created in the lab or have been observed with long-term users (…). There are, of course, health risks and negative health consequences with using the substance, but the majority of those risks only occur under specific circumstances. The majority of the risks are associated with long-term persistent and frequent use, and therefore must be understood as such. There is at this point agreement that the so-called dependence or withdrawal symptom may arise with heavy chronic users, but it is very much limited to that small population. (…) a seminal report by Hall and colleagues from Australia (…) concluded that the major risks of cannabis use can be significantly reduced by avoiding driving under the influence, by avoiding chronic and daily use, and by avoiding deep inhalation. These were the key factors that allowed us to avoid many of the major harms and risks associated with it. [13]

 

In any event, we are talking about plant derivatives that contain a number of psychoactive alkaloids. The psychoactive effects are predominantly of mild euphoria and time distortion, though disorientation and panic attacks may occur. The appreciation of music, art and food are said to be enhanced, as is appetite, and this later function seems important for one of the claimed medical benefits in offsetting the effects of the chronic wasting syndrome in AIDS and the prolonged nausea that accompanies chemotherapy. (…) Because the drug is usually smoked, it has acute and chronic effects that are shared with tobacco. These include airway irritation, cough, and probably with chronic use, bronchitis, chronic obstructive pulmonary disease, and lung and pharyngeal cancers. Its impact on the immune system is generally to impair the function of the immune system, but the impact on human health of this impairment is probably minor. (…) The effects of cannabis consumption on reproductive health are negative in animal studies. (…) This obviously has some relevance to human health. However, human studies have yet to show any measurable adverse impact beyond some evidence of adverse behavioural and developmental impacts on the children of mothers who smoked cannabis heavily during pregnancy. (…) The impact of cannabis on cognition is well documented. Short-term memory is adversely affected and chronic use may lead to chronic measurable defects in cognitive functioning. However, this may be more the result of persistent chronic intoxication than impairment in the substance and the working of the brain. Psychomotor skills are adversely affected by cannabis use. Driving or operating heavy machinery when intoxicated is contraindicated. Again, in contradistinction to alcohol, cannabis intoxication tends to slow drivers down rather than increase their speeds. Similarly, cannabis smokers tend not to be involved in acts of physical violence and aggression, and violence and aggression when intoxicated is reportedly very rare. Cannabis use may provoke schizophrenic symptoms in those with active schizophrenia or schizophrenic tendencies. Panic attacks and dysphoria are also mentioned in the literature. There is an amotivational syndrome described in the literature and cannabis is said to induce it, but most researchers have discredited that over the last decade. (…) Concerns have legitimately been raised about the effects of cannabis consumption on adolescent development. As use tends to peak in late adolescence, this is an important consideration. The adverse effects that have been noted include an association with risk of discontinuation of high school, job instability and progression to the use of harder drugs. The degree to which these associations are causal is very controversial. Alternative hypotheses are that cannabis use, like adolescent alcohol use, early onset of sexual activity, and tobacco smoking, are in fact markers for other risks of adverse social conditions (…) All researchers agree, however, that intoxication interferes with academic prowess. Recent studies seem to demonstrate measurable though reversible drops in IQ associated with heavy, persistent cannabis use and that engagement in illicit activities carries substantial risks, especially perhaps for youth whose connections to the school community are tenuous at best. [14]

 

I would like to first focus on the acute effects and then on the chronic effects. "Acute effects" are those effects that you experience during the course of action of a single dose. In the nervous system that includes a period of several hours in which (…) you become "chemically stupid." Side effects include decreased arousal and drowsiness, which acts together with the drowsiness produced by alcohol and other central nervous system depressants. Other side effects are impaired short-term memory, slowed reactions, less accuracy in test performance and less selectivity of attention. (…) Low doses generally produce the effects that cause people to like smoking pot. They include mild euphoria, relaxation, increased sociability and a non-specific decrease in anxiety. However, high doses produce a bad mood, anxiety and depression. There can be increased anxiety to the point of panic or even an acute toxic psychosis which, fortunately, is of very short duration and goes away when the drug effect wears off. High doses cause impaired motor coordination, unsteadiness of control and decreased muscle tone, which is therapeutically useful. (…) With low doses, perception is enhanced. That is part of the pleasure. In high doses, the same action produces sensory distortion, hallucinations and the acute toxic psychosis to which I have already referred. (…) It does not seriously affect the cardiovascular system. (…) As to chronic effects, in the central nervous system there is impaired memory, vagueness of thought, decreased verbal fluency, and learning deficits in chronic, heavy users. I emphasize "heavy" because the social user does not, by and large, show any significant health effects. Neither does the social user of alcohol. (…) These effects on cognitive functions fortunately tend to go away if the heavy user stops, for whatever reason. As long as use continues, there is a chronic intoxication, apathy, confusion, muddled thinking, depression, and sometimes paranoia. (…) Cannabis dependence, as defined in the conventional diagnostic criteria for dependence as set out in the latest edition of the American Psychiatric Association, or the equivalent publication of the World Health Organization, has been well documented in regular, heavy users. Numerous studies now show that a significant percentage of regular users are dependent. In some studies in Australia of long-term heavy users, mainly daily users for periods of 15, 17, 20 years, 60 per cent or more of them met the diagnostic criteria (…). Tolerance has been shown. By and large, it is not a terribly serious effect, and the physical withdrawal syndrome is not severe. Nevertheless, it is there, which indicates that physical dependence, in addition to psychological dependence, occurs as well. [15]

 

The long-term chronic effects of cannabis essentially cause the following symptoms: memory loss, faulty attention and concentration, a slow-motivation syndrome of passivity and low initiative, increased risk of respiratory disease, more specifically asthma, bronchitis and emphysema and a higher risk of cancer. (…) There may be hormone problems causing low fertility in men and women. In men, this can cause the development of breasts which is very unesthetic (…). Finally, in the long-term, it can also cause lower resistance to infectious disease. [16]

 As we can see, opinions sometimes agree and often differ. They agree at least on the nature of the consequences that may be of concern. One by one, we have seen effects that were physiological (risks of cancer, effects on reproduction and the immune system, deterioration of brain cells), effects that were psychological (amotivational syndrome, risks of psychosis, impaired cognitive function and memory in particular), and effects that were social (affecting the family and work, as well as the ability to drive vehicles and operate machinery). Opinions differ primarily on the scope of the conclusions that can be drawn from this knowledge. To what extent, in fact, can we generalize about the effects we observe in often small and rarely random samples of subjects? Also, to what extent can we generalize about the data on chronic users who represent – as we saw in the previous chapter – only a small percentage of cannabis users? And especially, to what extent does this data allow us to establish causal relationships?

The Committee also finds that most witnesses stressed the negative aspects and rarely the positive. However, if people use drugs in general, and cannabis in particular, surely it isn’t just to destroy themselves or because these drugs have only negative effects. Given the limitations of making any comparison between substances, we can still draw a parallel with alcohol: most of us know the pleasure of sharing a glass of wine with friends over a good meal, just as we also know the dangers of alcohol abuse and alcoholism. The Committee also notes that it is difficult, even for the most experienced researchers, to sift through the knowledge without assigning it a valence relative to the direction public policy should take. The same knowledge may be interpreted negatively here and more moderately there, based on the interpreter’s preconceptions of the “best” choice for public policy. We are not immune to this bias. Moreover, we do not deny that we had preconceptions, derived from our personal histories, our reading, and the hearings we held in 1996 to review Canada’s drug legislation. Among these preconceptions, which oriented our reading of the testimony, at least at first, we note:

·               The conviction that the current system does not achieve its objectives, if only because of the increase in cannabis use, by young people in particular;

·               A preference for an approach that is more consensual and more in keeping with Canadian attitudes;

·               A preference for a harm-reduction approach as indicated by the wording of our first mandate;

·               A tendency to distinguish between soft drugs – including cannabis – and hard drugs (heroin, cocaine);

·               A certain lack of knowledge about the specific effects of cannabis, from the standpoint of the toxicological and pharmacological studies conducted in recent years.

This being said, we did not work in isolation. Not only were we accompanied by our research team – sociologists, lawyers, criminologists – throughout our work, not only were we also under the close surveillance of the witnesses in a way and of the public in a larger sense, but primarily, other committees, in other countries, have conducted similar reviews in recent years. Their work was a source of inspiration and knowledge and as well a benchmark against which to compare our own conclusions.

 

 

Acute effects of cannabis

 

In toxicology, acute effects are those that are produced immediately after use and while the psychoactive effects are being experienced. These effects also correspond to what has been called cannabis intoxication ever since Moreau de Tours in 1845.[17] The “real” effects – on biological systems – and the effects experienced by users can vary based on a set of factors, such as the user’s experience with cannabis and other drugs (including tobacco), the user’s expectations and the context of use. In fact, [translation] “the psychoactive effects of cannabis, more than any other substance, vary from one subject to another and, for the same subject, from one experience to another.”[18] Additionally, with no reliable method to measure THC content in plasma, it is difficult to link the duration and strength of effects to the various cannabis preparations, in particular because of variations in the composition of the substance and in the bioavailability of THC. It is even more difficult to attribute relatively rare effects (for example, the appearance of psychotic symptoms) insofar as it is hard to decide if the co-occurrence is coincidental, if these effects stem from other substances often associated with cannabis use or from very high doses of cannabis, or from interactions between these various factors.[19]

The acute effects of cannabis are relatively well documented. Research sometimes distinguishes between central and peripheral effects[20], sometimes between somatic effects and psychological or psychomotor effects[21], and sometimes is simply content to list the effects of one type or another.[22]

Cannabis intoxication is generally considered to consist of two main phases:

 


v    The first phase, the “high”, includes the following effects:

·               A change in general mood, accompanied by gaiety or even hilarity, talkativeness, and a carefree feeling

·               A change in physical experience, including a feeling of well-being and satisfaction, a feeling of calm and relaxation, sociability

·               Alteration of intellectual functions, including increased self-confidence, magical thinking (feeling of being able to perform tasks more easily), distorted perception of time, space and self-image

·               Sensory changes, marked by increased sensory perceptions (colours, sounds sometimes seem more intense), stronger tactile impressions.

 

v    The second phase, “coming down”, is characterized by a feeling of sluggishness or drowsiness that appears gradually a little while after use.

 

More specifically, depending on their type of action, a distinction is made between truly somatic effects and more psychological ones.

 

v    Somatic Effects:

·               Cardiovascular effects: approximately 10 minutes after use, heart rate, cardiac output and cerebral blood flow increase. Tachycardia (accelerated heart rate) can achieve increases of 20% to 50% compared to normal rhythm and could help trigger anxiety and panic attacks in some subjects. It can be responsible for palpitations, reduced exercise tolerance in subjects with heart conditions, and can even facilitate the development of heart problems in subjects who are at risk or are predisposed. A recent study suggests that the risk of myocardial infarction increases by 4.8 times in the first hour after using marijuana and is 1.7 times higher in the second hour, thus suggesting that cannabis may represent a risk in the 60 minutes following its use. Hypotension while the subject is lying down is also mentioned. These effects vary based on the dose and concentration of THC.

·               Bronchopulmonary effects: the effects are similar to those of tobacco. Bronchodilator activity in the 60 minutes following use is mentioned. However this does not prevent the inflammatory consequences of smoking cannabis nor the secondary bronchial hyperreactivity that is translated in particular by a cough that results from the action of the THC and the irritating potential of the products of combustion;

·               Ocular effects: redness of the eyes due to vasodilation and conjunctival irritation is mentioned;

·               Other somatic effects: dry mouth due to decreased saliva secretion, increased appetite due to hypoglycemia (drop in blood sugar level), and more rarely nausea and vomiting, diarrhea and urine retention.

 

v    Psychological and Psychomotor Effects:

·               Diminished short term memory (so-called “working” memory): remembering words, pictures, stories and sounds;

·               Disturbances in psychomotor performance, including diminished ability to pay attention and concentrate, diminished reflexes, slowed reaction time, problems with coordination of movements, and impaired and diminished ability to perform complex tasks. Thus, a study by Fant et al. describes diminished visual tracking in the central and peripheral fields of vision after 15 minutes, capable of lasting for more than 5 hours.[23] Moreover, we note that according to professor Roques, studies on the effects of cannabis on learning abilities, in particular short term memory and working memory, are open to criticism from the standpoint of methodology and their contradictory results, “the heaviest users were the least affected”.[24] [translation]

 

Somatic, cognitive and psychomotor effects are related to the amount of cannabis inhaled and the concentration of THC. Thus, according to INSERM:

 

A quantity that corresponds to 25 puffs impairs psychomotor skills and cognitive performance, and more markedly than consumption of 10 puffs or 4 puffs. Maximum plasma levels then rise from 57 ng/ml (for 4 puffs from a cigarette containing 1.75% D9THC) to 268 ng/ml (for 25 puffs from a cigarette containing 3.55% D9THC). Heishman et al. (1997) established an approximate equivalence between 16 puffs at 3.55 % D9THC and approximately 70g of alcohol. At these levels, memory, cognitive and psychomotor performance and mood are impaired. [25] [translation]

 

The cognitive and psychomotor effects may continue for more than five hours, and some cognitive impairment may extend for 24 hours.

At high doses, or with inexperienced users, cannabis may cause a certain number of negative reactions that can even include a genuine paranoid, hallucinatory, manic or hypomanic psychotic experience. However these experiences are brief. Some disorders documented with high doses include:

 


·               Anxiety, even panic attacks

·               Confusion or disorientation

·               Vertigo, nausea or vomiting

·               Convulsions

·               Depersonalization

·               Hallucinations

·               Paranoia

·               Acute psychosis

 

These phenomena are relatively rare (less than 1 in a thousand psychiatric admissions). Primarily, it is difficult to establish that cannabis was the cause. In fact, in most cases, the most likely hypothesis is that these subjects were already predisposed, or had even already had psychotic or schizophrenic experiences. Use of other substances, alcohol, other illicit drugs, or medications, could also play an important role.

 

The link between cannabis use and psychosis is a very controversial issue. At the moment, we lack a corpus of comparable, methodologically sound studies repeatedly yielding similar conclusions. The results of existing studies are often complex or ambiguous and the personal opinions of the researchers often interfere with the interpretations. Further deepening our scientific knowledge is still necessary. However, there is extensive, albeit incomplete, consensus on the ability of heavy cannabis consumption or intoxication to induce an acute transitory psychotic state in healthy subjects. The frequency of this condition is unknown and the mechanisms are hypothetical. [26]

 

In accordance with the collective expertise of INSERM, we can establish the following:

 

The psychotic disorders caused by cannabis use are brief psychotic episodes that last less than two months, even four months[sic], sometimes a week. The premorbid personality does not present a pathological aspect. Regular users are at greater risk than occasional users. Onset is abrupt, in two or three days, with or without a recent increase in the use of toxic agents, sometimes with a psychological or somatic precipitating factor. Some symptoms appear more specific: behavioural problems, aggression, visual hallucinations, polymorphic nature of the delirium along various themes, psychomotor disinhibition. (…) Compared to a schizophrenic disorder, subjects are younger, 20 to 30 years of age rather than 25 to 30, with a greater proportion of poorly socialized males. [27] [translation]

 

However, here too, the data are relatively contradictory and, according to professor Roques, there is support for the belief that usage is more widespread among people with previous mental disorders.[28]

Consequences of chronic use

 

Most of the works consulted in pharmacology, toxicology and psychiatry speak of chronic effects. For our part, we prefer to speak of consequences resulting from chronic use. There are two reasons for this. First of all, because these consequences result not so much from the substance itself as from the way it is used. Therefore we are not dealing with the effects of the substance, but rather with the consequences that may arise from repeated, or even heavy, use. The second reason is that, as we saw in Chapter 6, chronic cannabis users account for a small fraction (often less than 10%) of lifetime users of cannabis. As a result, the consequences in question in this section concern this small portion of the population of users and not the substance itself.

We feel this distinction is fundamental because it is common, at all levels of public discussion – whether involving politicians, the public at large, or experts – to blame the substance – here cannabis, there alcohol or medications, even other illicit drugs–when in fact we must learn to distinguish between patterns and methods of use. By that we mean at-risk behaviour, which varies with the substance of course, and which does not depend solely on the intrinsic properties of the substance, but stems, in an overall approach, from the relationship between the substance and its place in society (integrated or not) from the individual’s characteristics, and from the society in which the substance is used.[29] Of course by that it should be clear that we consider as separate, for cannabis as for alcohol, use, at-risk use and heavy use (or abuse)[30], and that we reject the equivalency often made between use and abuse where any form of use is perceived as abuse. At the same time, we are aware of the vagueness that continues to surround these various types of behaviour – or practices – and that there is no clearly defined boundary, even less a universal boundary, between use, harmful use and dependence. For the purposes of this chapter, the consequences in question in the following three sections refer, without being more specific, to chronic use (which then includes at-risk and heavy use).

 

Physiological consequences of chronic use

The main physiological consequences of the chronic use of cannabis dealt with in scientific literature concern the respiratory system and the carcinogenicity of cannabis, the immune system, the endocrine system and reproductive functions and, to a lesser degree, the cardiovascular system.

 

Consequences for the respiratory system

Except for the nicotine in tobacco and the cannabinoids in cannabis, the smoke of these two products shares common irritating, even carcinogenic, properties. Although not recent, a comparative analysis of these products has shown that the concentration of certain strongly carcinogenic ingredients such as benzopyrene and benzanthracene is higher in cannabis smoke than tobacco smoke.[31] A more recent study cited by INSERM confirms this higher concentration of benzopyrene: 2.9 micrograms/100 joints compared to 1.7 for 100 cigarettes.[32] Of course, it will be argued that tobacco users generally smoke many more cigarettes a day than even chronic users of marijuana, that it is the total volume of toxic substances inhaled over time that counts, and that it can be difficult to distinguish the effects of cannabis from those of tobacco since joints often contain both products and users of cannabis are also often tobacco smokers.[33]

However we note other worrisome characteristics with respect to the potential effects on the respiratory tract of smoking cannabis. First of all, the concentration of benzopyrene in marijuana tar is 70% higher than that in the same weight of tobacco tar. Furthermore, an equal product weight of cannabis provides up to 4 times more tar than a strong tobacco. According to a study cited by INSERM, tar from a joint varies between 40 and 56 mg/cigarette whereas the allowable dose for a European tobacco cigarette is 12 mg.[34] In addition, a marijuana cigarette is generally smoked much more completely than a tobacco cigarette, inhalation – an important part of the ritual – is deeper and the smoke is held in the lungs longer and the combustion temperature of cannabis is higher than that of tobacco. Consequently, the percentage of tar deposited in the lungs is higher after smoking cannabis (> 80%) than after inhaling tobacco (64%) and the deposits are even greater for cannabis with a lower concentration of THC, probably because smokers draw on the joint more.[35]

According to INSERM’s report, chronic use of cannabis “results in unquestionable bronchial disorders (…) chronic bronchitis with a chronic cough, expectorations and a sibilant rale”[36] [translation], a conclusion shared by the Institute of Medicine in the United States in its recent report on marijuana[37] as well as by the WHO.[38] Moreover, macrophages (cells that attack foreign bodies) in the pulmonary alveoli seem to lose their ability to neutralize bacteria when exposed to cannabis smoke, hence the greater susceptibility of the bronchi and lungs to bacterial infections. According to some authors, in theory, a cannabis cigarette could cause as much damage as 4 to 10 tobacco cigarettes.[39] This data on the reduced ability of alveolar macrophages to destroy bacteria also suggests that cannabis could have an immunosuppressive action that decreases the ability of the organism, here the lungs, to fight carcinogenic cells.

The work of Tashkin in particular, but also of other researchers, is not as confirmatory on the effects of cannabis on the respiratory tract. Thus a recent study by Tashkin on heavy cannabis smokers showed that there was no decrease in the forced expiratory volume in one second to vital capacity ratio, even for those who smoked 3 joints a day, compared to tobacco smokers who registered a significant decrease.[40] Tashkin’s team also questioned the development of emphysema in cannabis users and bronchiole obstruction.[41] Similarly, a study by the Kaiser Permanent Medical Care Program revealed that daily cannabis users who did not use tobacco were hardly more likely than non-smokers (36% vs. 33%) to consult for colds, the flu and bronchitis.[42] We also note that to date, studies are contradictory about the additivity of the effects of tobacco and cannabis.

 

Carcinogenic potential

With respect to the carcinogenic potential of cannabis, there is a distinction between the carcinogenic effects of cannabis smoke – a potential source of lung cancer in particular – and the mutagenic effects of THC on cells. According to the majority of authors, THC itself does not seem to be carcinogenic.[43] However, cannabis smoke, like tobacco smoke, does seem to be able to increase the incidence of cancerous tumors.

The work of Fliegel[44] indicates that the histological changes that are considered the precursors of carcinomata are present in chronic smokers of cannabis. This data is also supported by clinical cases of cancers of the upper aerodigestive tract in young adult cannabis smokers. These cancers are types rarely observed in young subjects. Namely:

·               Thirteen cases of brain and neck cancer in young adults under the age of forty, eleven of whom were daily cannabis smokers;[45]

·               Ten cases of cancers of the upper respiratory tract in young adults under the age of forty, seven of whom were probable regular users of cannabis;[46] and

·               Two cases of carcinoma of the tongue in men between 37 and 52 years of age for whom the only common risk factor was the regular and daily use of cannabis.[47]

 

We note first of all the small number of cases, especially when compared to the large number of cannabis users. These clinical cases also present a certain number of important limitations: none compares the prevalence of cancer with a control group or evaluates the use of cannabis in a standardized way. Interpretation is also limited by the fact that the patients also smoked tobacco and drank alcohol.

The data available seems to indicate that the consequences of chronic and intense cannabis use (several joints per day for several years) are similar to those of cigarettes in terms of carcinogenic risks for the respiratory tract as well as the mouth, the tongue and the esophagus.[48] THC is generally considered to alter the functions of certain cells, namely lymphocytes, macrophages and polymorphonuclear cells, especially in in vitro models. However conducting controlled studies is largely recognized as a research priority in this field.[49]

 

Consequences for the immune system

Apart from the possible consequences for the respiratory tract defense system essentially caused by smoke, there is no conclusive data regarding the effects of cannabis on the immune system. Some studies on rodents show that high levels of cannabinoids, including THC, alter cellular immunity. In some cases, the experimental activity of cannabinoids is immunosuppressive and in others it is stimulating. These variations depend on experimental factors such as the concentration of the substance, the time and duration of administration, and the type of cell function studied. Very little work has been done on humans. According to the WHO report, if it is clear that cannabinoids have immunomodulating effects, it is also clear that the immune system is resistant to this substance. Several of the effects are relatively minimal and completely reversible, and are only experienced at higher doses than those required for the drug’s psychoactive effect in humans. Lastly, still according to the WHO report, even with respect to the immunomodulating effects of cannabis smoke, the studies are not conclusive and it is hard to compare the doses used in experiments with animals to the doses used by humans. The report concludes that rigorous studies on this question are necessary.[50]

 

Consequences for the endocrine system and reproduction

Endocrine abnormalities are well documented in animals. In the male rat, decreased testosterone secretion with testicular atrophy, impaired production, mobility and viability of sperm, and changes in sexual behaviour have been noted with high doses. The ovulatory cycle of the female is altered. In humans, the results are contradictory, in particular because findings are not constant from one study to another, but also because similar changes occur following the absorption of prescription drugs. Furthermore, the changes observed are often borderline normal and their clinical consequences remain controversial.[51]

With respect to reproduction, the fact that the active ingredients in cannabis cross the placental barrier is well established. Nevertheless, the question of the potential effects of cannabis on the feotus is far from resolved, especially since the studies are methodologically poor. Thus, when studying pregnant women who are cannabis users, the women often come from low socio-economic backgrounds – and we know that socio-economic level is a determining factor in the size and weight of babies – and it is difficult to isolate the effect of other factors, including the use of tobacco and alcohol – which we know are risk factors for premature birth, lower weight and smaller size. In fact, studies on occasional cannabis smokers do not show any significant difference with respect to non-smokers. All in all, most studies did not observe any significant differences.[52] Nevertheless, reports from the WHO and the collective expertise of INSERM conclude that, despite methodological difficulties, there is reasonable evidence that cannabis use during pregnancy harms fetal development, in particular restricted growth and behavioural abnormalities, but that these abnormalities are rather minor.[53]

As for the neonatal consequences of cannabis use by mothers during pregnancy, longitudinal studies on cohorts of children conducted in Ottawa since 1978 by psychologist Peter Fried’s team[54] are not conclusive. All the measurements taken reveal more similarities than differences between the children of smokers and non-smokers. And when differences are observed, they are minor and it is impossible to dissociate the effects of the various substances, tobacco and alcohol in particular. Lastly, these studies involve a small sample of children and generalizations cannot be drawn from them. Another longitudinal study, reported by INSERM, involving 636 subjects, concluded [translation] “there is a significant relationship between behavioural problems at age 10 and prenatal exposure to cannabis.” However the report from INSERM also notes that [translation] “if the results from these two studies seem to converge well (…) we must remember nevertheless that the postnatal environment can play an important role in the continuation of behavioural abnormalities.”[55]

 

Consequences for the cardiovascular system

Chronic use of cannabis may lead to cardiovascular complications for predisposed individuals. In fact, the use of significant quantities can slow the heart rate. Also, cannabis can have similar effects to those of tobacco on heart function by increasing the muscle workload. Furthermore, some studies point out the role that the carbon monoxide found in cannabis smoke plays in the risk of cardiovascular complications.

 

Cognitive and psychological consequences

The main cognitive and psychological consequences of chronic cannabis use concern brain functions involved in memory and verbal and math skills; motivation; and psychiatric disorders.

 

Brain functions

We have seen that cannabis has acute effects on short-term memory, attention and concentration. Does chronic use eventually result in effects on cognitive function that may be irreversible? These questions first raise the question of the neurotoxicity of cannabis, defined as “a reversible or irreversible impairment of the structure and/or functions of the central (and/or peripheral) nervous system by physical, chemical or biological agents”[56] [translation]

According to professor Roques:

 

[translation] Cannabis dependence does not result in neurotoxicity (…). Thus old results suggesting anatomical changes in the brain of chronic cannabis users, as measured by tomography, have not been confirmed by precise modern techniques of neuro-imaging. Similarly, morphological changes in the hippocampus of the rat following administration of very high doses of THC (Landfield et al., 1988) have not been repeated (Slikker et al., 1992). (…) Several studies have been devoted to the effects of cannabis on evoked responses and on electroencephalograms of humans. Intermittent use produces reversible changes in a wave patterns in the frontal cortex, probably with respect to the state of drowsiness induced by THC. In the very long term (more than fifteen years) and with heavy daily use, d hyperfrontality and an increase in q frontal activity have been observed (Struve et al., 1990, 1994). The possible connection with behavioural changes and changes in neuropsychological tests is not in question, nor moreover is that which is possible with the anticonvulsive effects of THC. [57]

 

The results of studies reported by the collective expertise of INSERM are contradictory as some observe changes while others do not. Even when changes are observed, they are often of minor amplitude and are reversible after a period of abstinence. The INSERM report observes that studies using neuro-imaging techniques have not confirmed the neurotoxicity of cannabis in either man or baboon.[58] Therefore it is through observing functioning and behaviour that we are still best able to examine the question of the neurological effects of cannabis.

Unfortunately, studies are just as contradictory here and the results are inconclusive. Studies performed in the 1970s in countries where cannabis use is traditional (Jamaica, Costa Rica, India) did not point out any significant differences in cognitive functions of users and non-users, whereas more recent studies, in particular in Costa Rica in the 1980s, did show differences: [translation] “In particular, long-term users recalled fewer words on a list they had been shown earlier and response time was longer.[59] In the United States, studies conducted in the 1970s found contradictory results for memory functions, whereas more recent studies reported subtle deficits in cognitive functions of heavy users after a brief period of abstinence. Some studies also showed continued memory impairment in adolescents after six weeks of abstinence.[60]

Most studies tend to show that overall, ex-users recover all cognitive functions, but depending on the length of use, subtle impairments can persist, in particular with regard to the ability to process complex information.

Still according to the collective expertise of INSERM, the age when use begins can be a determining factor. Thus, a recent study shows the persistence of some visual scanning impairments (related to attention) in young people who began to use cannabis before age 16, whereas those who began use after age 16 show no difference from non-users.[61]

In all, we cannot really establish that cannabis use has negative consequences for brain functions, even in chronic users, unless use begins before age 16.

Motivation

Some studies suggest the presence of an amotivational syndrome in chronic cannabis users, a syndrome that could affect the performance of young people at school and employees in a professional environment in particular. In its 1997 report, the WHO pointed out that our knowledge has not advanced since its previous report in 1981: the amotivational syndrome has still not been clearly defined, its effects have still not been clearly distinguished from the effects of intoxication itself, and the data available comes from clinical case reports with no control group.[62]

In order to evaluate the impact of cannabis on motivation, Canadian researchers developed a study where subjects received cannabis in exchange for work performed. Even though it is not recent, the study is no less interesting. They observed that subjects worked less efficiently immediately after using cannabis. However, their level of productivity then increased rapidly and exceeded levels achieved during periods of abstinence. Although working fewer hours, the subjects using cannabis were not less productive because they worked harder. Furthermore, over the course of the period of heaviest use, the subjects organized a strike and successfully negotiated a “salary” increase, after which they worked even harder.[63] [64]

Studies do not enable us to establish if motivational problems, when observed, preceded or followed cannabis use, or if other emotional or psychosocial factors played a greater role, or were even determining factors in the chronic use or abuse of cannabis in young people in particular. These conclusions are shared by the collective expertise of INSERM and by the authors of the report submitted to the International Scientific Conference on Cannabis in March 2002.[65]

 

Psychiatric disorders

Various psychiatric disorders have been associated with chronic cannabis use: mood disorders and depressive episodes, anxiety disorders, personality disorders, as well as more severe conditions, such as psychoses and schizophrenia. For each of these situations, the conclusion drawn by the authors of the report on mental health and cannabis prepared for the International Scientific Conference on Cannabis generally applies:

 

There are three possible ways to account for the relationship between cannabis and mood disorders. First, both may share common risk factors, so that their relationship is not causal. Second, mood disorders may predispose people to use cannabis. Third, cannabis use may trigger or increase depressive symptoms. As yet, there is no clear answer to this question of “which comes first”. [66]

 

Specifically with regard to mood disorders, depressive states and anxiety disorders, it seems probable that they precede chronic use. However, study results are extremely disparate: for mood disorders in so-called dependent people, the prevalence varies (depending on study methods), from 10% to almost 50%; with respect to major depressive episodes in clinical populations, studies report percentages varying from 4% to almost 20%. INSERM’s report presents a review that we feel is much more enlightening with regard to the situation for adolescents:

 

[Translation] Acquiring new knowledge has allowed for a better assessment of the burden of “early onset depression” in terms of individual suffering and public health. Its prevalence, around 5% in adolescence, makes it one of the most common pathologies for this period. The risk of suicide is high, and the functional deficits inherent in depressive syndromes are a source of school and family problems, and cause withdrawal from peers, for which the psychosocial consequences can be severe, especially if the disorder is prolonged. Additionally, depression is rarely an isolated disorder in a young subject: anxiety or behavioural disorders often precede or accompany depressive episodes and can survive them; moreover, the existence of a depressive disorder is a risk factor for addiction (alcohol or any other psychoactive substance) and eating disorders. [67]

 

With respect to psychotic disorders and schizophrenia, the two subjects are controversial, the methodologies weak, the data contradictory and the interpretations are often based on simplistic models of causality. If, in certain circumstances, cannabis can trigger psychotic episodes, they are most often short and resolve rapidly. As for schizophrenia, if it is true that cannabis use is more prevalent in these subjects than in the general population, some feel that it is self-medicating behaviour while others feel that the chronic use of cannabis is a trigger for the schizophrenic process. We feel that the conclusion of professor Roques’ report agrees best with current data:

 

[Translation] No mental pathology directly related to the overuse of cannabis has been reported, which distinguishes this substance from psychostimulants such as MDNA, cocaine or alcohol, heavy and repeated use of which can give rise to characteristic psychotic syndromes. Similarly, cannabis does not seem to precipitate the onset of pre-existing mental dysfunctions (schizophrenia, bipolar depression, etc.). [68]

 

As it is, most scientific reports come to the same conclusion: more research is needed, with more rigorous protocols, allowing in particular for comparison with other populations and other substances.

Behavioural and social consequences

The main behavioural and social consequences examined in scientific literature deal with social and family adjustment, aggression, and the ability to perform complex tasks.

 

Social and family adjustment

According to some studies, chronic cannabis use could have consequences for social and family adjustment. Thus chronic users would have more difficulty keeping a job, would be unemployed more often and would have more interpersonal adjustment problems.[69]

However, most of these studies suffer from methodological problems and interpretation difficulties. Most studies involve samples of people who, by and large, come from underprivileged socio-economic backgrounds. Above all, beyond the statistical association, it is difficult to determine to what extent other factors play a preponderant role, of which cannabis is itself a symptom and not a cause.

 

Aggression

Unlike other psychoactive substances, alcohol and cocaine in particular, cannabis does not lead to aggression. When examining withdrawal symptoms once dependence is established, some authors note greater irritability; but this is even less significant proportionally than that caused by tobacco.

 

Performing complex tasks

No study on chronic cannabis use has been able to establish that cannabis causes long-term effects on the ability to perform complex tasks. This data is in keeping with cannabis’ lack of neurotoxicity.

 

Tolerance and dependence

 

When we think drugs we think drug addiction since, as F. Caballero states, a drug is [translation] “any substance likely to lead to addiction”.[70] In France and Europe, monitoring groups created in recent years are called monitoring centres for drugs and drug addiction. In Quebec, the advisory body created by the government is called the “Comité permanent de lutte à la toxicomanie” [standing committee on the fight against drug addiction]. The expression “drug addiction” is found everywhere: in legislation, in information documents, and in everyday language. However, since 1963, the WHO has recommended that we abandon this expression because it is imprecise and refer instead to states of physical and psychic dependence, defined as follows:

Psychic dependence is a “condition in which a drug produces a feeling of satisfaction and a psychic drive that requires periodic or continuous administration of the drug to produce pleasure or to avoid discomfort. Physical dependence is an “adaptive state that manifests itself by intense physical disturbance when the administration of the drug is suspended or its action is opposed by a specific antagonist. These disturbances, that is the abstinence or withdrawal symptoms, consist of physical and psychic symptoms and signs that are characteristic for each drug. [71][translation]

 

Furthermore, with the extension of the notion of drugs to other substances (pharmaceutical products, tobacco, alcohol), and with the extension of international control of substances to psychotropic drugs, in 1969 the WHO created a new definition for the term drug dependence that, though its application was initially limited to medication only, has come to be more widely accepted over time:

 

Drug dependence. A state, psychic and sometimes also physical, resulting from the interaction between a living organism and a drug, characterized by behavioural and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects, and sometimes to avoid the discomfort of its absence. Tolerance may or may not be present. A person may be dependent on more than one drug. [72]

 

But it is even more interesting for our purposes to quote even older definitions from the WHO dealing with habituation and addiction:

 

Drug habituation (habit) is a condition resulting from the repeated consumption of a drug. Its characteristics include:

1.      A desire (but not a compulsion) to continue taking the drug for the sense of improved well-being which it engenders;

2.      Little or no tendency to increase the dose;

3.      Some degree of psychic dependence on the effect of the drug, but absence of physical dependence and hence of an abstinence syndrome;

4.      Detrimental effects, if any, primarily on the individual.

 

Drug addiction is a state of periodic or chronic intoxication produced by the repeated consumption of a drug (natural or synthetic). Its characteristics include:

1.      An overpowering desire or need (compulsion) to continue taking the drug and to obtain it by any means;

2.      A tendency to increase the dose;

3.      A psychic (psychological) and generally a physical dependence on the effects of the drug;

4.      Detrimental effect on the individual and on society. [73]

This definition is important because, more than the previous two, it allows us to better distinguish between drugs that create primarily a habit and those that create an addiction, that is, the overwhelming need to use them. Now, as we will see in this chapter, cannabis corresponds much more to the criteria of a substance likely to create some degree of habituation and not an addiction.

In addition to drug addiction, thinking about drugs means also thinking about illicit substances. Now, as a wide range of works and an increasing number of practices have established, for practical purposes, the actual distinction is made on the combined levels of the substance’s toxicity (its dangers) and the uses (use, abuse, heavy use) that characterize it, not on the level of its legal and symbolic status.

 

Cannabis dependence

Let us first establish that animal studies on dependence and withdrawal are not very pertinent since most of them use doses that have nothing in common with the doses used by humans, even chronic users. Moreover, we note that studies on naïve animals (no experience with other drugs) have not been able to establish self‑administering behaviour and that is the only technique that allows for the direct assessment of the reinforcing properties of a molecule. One of the probable explanations stems from the long plasma half-life of D9THC, which we know is eliminated slowly by an organism (up to 25 days as we saw in the Chapter 5).[74] We also note that even after administration of very high doses of D9THC, somatic signs of spontaneous withdrawal were not observed in rodents, pigeons, dogs or monkeys.[75] Lastly, we note that all in all, we know little about the biophysiological and psychological mechanisms of dependence.

The idea of cannabis dependence has been the subject of criticism due to its overly medical aspect (having little regard for the differences in social context of the ways and situations in which it is used) and circular reasoning (for example, the fact that drugs are illegal means that their use is necessarily illegal, yet this is one of the criteria for dependence).[76] Nevertheless, when measured in accordance with the criteria of the DSM, a cannabis dependence syndrome presents no differences from an alcohol or heroin dependence syndrome. Furthermore, establishing the relative dangers of cannabis is not contrary to the objectives of public health.

The nosologic criteria of the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) of the American Psychiatric Association undoubtedly remain the most widely used in studies on dependence, especially since the majority of drug research is conducted in the United States and Commonwealth countries (England, Australia, Canada…) that use this instrument.

The DSM-IV distinguishes between criteria for substance abuse and criteria for dependence. We have reprinted them here in accordance with the INSERM report.

 

 

Diagnostic Criteria for Substance Abuse according to the DSM-IV

A.     A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:

1.       Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home;

2.       Recurrent substance use in situations in which it is physically hazardous;

3.       Recurrent substance-related legal problems;

4.       Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance.

B.     The symptoms have never met the criteria for Substance Dependence for this class of substance.

 

 

Diagnostic Criteria for Substance Dependence according to the DSM-IV

A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:

1.       Tolerance, as defined by either of the following:

a.       A need for markedly increased amounts of the substance to achieve intoxication or desired effect;

b.      Markedly diminished effect with continued use of the same amount of the substance.

2.       Withdrawal, as manifested by either of the following:

a.       The characteristic withdrawal syndrome for the substance;

b.      The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms.

3.       The substance is often taken in larger amounts or over a longer period than was intended;

4.       There is a persistent desire or unsuccessful efforts to cut down or control substance use;

5.       A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects;

 

6.       Important social, occupational, or recreational activities are given up or reduced because of substance use; 

7.       The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.

 

 

The existence of a cannabis dependence syndrome in humans can be inferred using various methods: epidemiological investigations and clinical studies (which usually use DSM criteria), and requests for treatment.

 

Epidemiological investigations

Some epidemiological studies show that cannabis use can lead to psychological dependence. In some cases, they estimate that half of chronic users would develop this kind of dependence.[77] People who use cannabis on a daily basis for several months would be at greater risk of becoming dependent.[78] Interpretation and intercomparison of the various studies is difficult because the denominator is not always common, or even specified (in some cases, it is the general population while in others it is cannabis users and in the latter case, there is not always a distinction among life-long, recent and regular users). The authors also do not always specify if the dependence is recent or life-long.

In the United States, several investigations were conducted into the frequency of use of various psychoactive substances and dependence. Through the Epidemiological Catchment Area study, close to 20 000 people were interviewed in five years during the 1980s. The prevalence (in the general population) of cannabis dependence was 4.4%.[79] The National Comorbidity Survey, an investigation to estimate the comorbidity between substance abuse and other mental disorders, undertaken between 1990 and 1992 and involving more than 8,000 subjects from the general population between the ages of 15 and 55, also estimated the prevalence of dependence. For the purposes of the investigation, DSM criteria were used and dependence was observed when respondents presented at least three of the nine criteria. According to this study, 4.2% of the 15‑54 year olds presented cannabis dependence (14% were dependent on alcohol and 24% on tobacco). Of those who had used cannabis at least once during their life (46%), 9% were considered dependent, compared to 32% for tobacco and 15% for alcohol. Cannabis dependence was more common in men than women (12% versus 5.5% of users), and in those 15-24 than in the others (15% versus 8%).[80] Combining the results of three large investigations into the use of psychoactive substances conducted on households (nearly 88,000 respondents aged 12 and up) Kandel et al.[81] observed that 8% of those who had used cannabis in the previous year (0.7% of the sample) were considered dependent.

 

In New Zealand, a longitudinal study involving a cohort of 1,265 children born in 1977 in an urban setting and followed since birth revealed that at age 21, not less than 70% had used cannabis. Of those, 13% had had a problem with dependence measured in accordance with the DSM-IV during their lifetime.[82] Another New Zealand study involving a cohort of 1,000 people found similar results: at age 21, 62% had used cannabis and at age 26, 70% had. The prevalence of dependence using DSM III-R criteria went from 3.6% at age 18 to 9.6% at age 21 (or nearly 15% of users).[83]

In Australia, an investigation involving more than 10,000 people from the general population who were over 18 years of age showed that approximately 1.5% of users during the previous year and 20% of current users showed signs of dependence based on the DSM-IV.[84]

In the Netherlands, a study involving a sample of the national population aged 18 to 65 (7,000 subjects) showed that 10% of users had had signs of dependence during their lifetime.[85]

 

Clinical studies

It is difficult to generalize based on the results of clinical studies, but it is interesting to see to what extent their results are similar to those of epidemiologic studies. Kosten examined the validity of DSM-III R criteria to identify syndromes of dependence on various psychoactive substances including cannabis. He observed that the criteria for syndromes of alcohol, cocaine and opioid dependence were strongly consistent. The results were more ambiguous for cannabis. A criterion-referenced analysis revealed that there were three dimensions to the cannabis dependence syndrome: (1) compulsion – indicated by a change in social activities attributable to the drug; (2) difficulty stopping – revealed by the inability to reduce use, a return to previous levels after stopping temporarily and a degree of tolerance of the effects; and (3) withdrawal signs – revealed by their disappearance with re-use and continuing use despite recognized difficulties.[86]

 

Studies on long-term users

In Canada, Hathaway conducted a study between October 2000 and April 2001 to identify problem use and dependence in long-term users based on the DSM-IV criteria.[87] The sample was made of 104 individuals (64 men and 40 women) aged 18 to 55 (mean age 34). 80% had used cannabis on a weekly basis, 51% on a daily basis during the preceding 12 months, and close to half (49%) had used one ounce (28 grams) or more per month. Reasons to use included: to relax (89%), to feel good (81%), to enjoy music or films (72%), because they are bored (64%) or as a source of inspiration (60%).

Respondents were asked if they had ever engaged in deviant activity related to cannabis use. The most frequent answer was to have been in an uncomfortable situation in order to get cannabis. Other activities included borrowing money, selling cannabis to support their own drug use, and taking on extra work to buy cannabis. Only 6% ever had recurring legal problems due to their use of cannabis. With respect to dependence, 30% reported a lifetime prevalence of three or more of the criteria, 15% during the 12 months prior to the interview.

 

In light of this finding, the most frequently encountered problems with cannabis have more to do with self‑perceptions of excessive use levels than with the drug’s perceived impact on health, social obligations and relationships, or other activities. Lending support to the highly subjective nature of his evaluative process, no significant correlations were found between amounts nor frequency of use and the number of reported DSM-IC items. For those whom cannabis dependency problems progress to the point of seeking out or considering formal help, however, the substantive significance of perceived excessive use levels cannot be overlooked. [88]

 

The comparative study by Cohen and Kaal presented in the previous chapter also included data on dependency symptoms. Between 21% and 24% of the subjects presented 3 or more DSM-IV criteria in their lifetime as the following table shows.

 

Number of positive DSM IV answers

Amsterdam, San Francisco, Bremen [89]

 

Ever experienced

Last twelve months

Number of criteria

Amsterdam

   N               %

San Francisco

   N                %

San Francisco

   N                 %

Bremen

   N               %

 

0

1

2

3

4

5

6

Total

Average incl. 0

Average excl. 0

 

   85              39

   37              17

   43              20

   19                9

   15                7

     9                4

     8                4

  216            100

           1,5

           2,5

 

  129              49

    53              20

    30              11

    28              11

    15                6

      7                3

      3                1

  265             100

              1,2

              2,3

 

  233               88

    17                 6

      9                 3

      3                 1

3                               1

 

 

265                            100

           0,2

           1,8

 

   43              78

     5                9

     4                7

     2                4

1                              2

 

 

55                          100

          0,4

          1,9

 

 

The authors observe a significant correlation between amount of cannabis use (in grams) during top period of use and the number of DSM-IV items ever experienced. However, no correlation was found between the amount of cannabis use during top period of use and number of criteria experiences in the last twelve months.

 

Requests for treatment

Lastly, we can examine dependence indirectly through requests for treatment. Obviously, this is a very indirect and definitely very imperfect means for several reasons. The very great majority of cannabis users use it irregularly and stop when they reach their twenties. Of those who continue and become regular users, we have just seen that between 10% and 20% will present the criteria for dependence. Most users do not think they need help, which their ability to stop without outside assistance would confirm. Lastly, those who ask for help could be influenced simultaneously by the availability of services as well as the interaction of other problem substances, alcohol, medication or other drugs, or other mental disorders. In fact, it seems that in a significant proportion of cases, requests for treatment related to cannabis come from people with multiple disorders.

Nevertheless, we have heard testimony to the effect that requests for treatment for problems with cannabis dependence are on the rise and that this increase could be related to the THC content.

 


In Europe, requests for treatment where the main problem is cannabis-related vary widely from country to country, ranging from 6% in Spain (one of the countries where use is most widespread and most tolerated) to 25% in Belgium. Sweden, which however has a relatively low rate of use, is at 14%, comparable to France (16%) which, however, has a much higher rate of use. In the United States, demand is just as variable depending on the state, from 5% to 30%.[90]

 

Severity of dependence

Severity of dependence has been evaluated in different ways. In the United States, a study examined approximately 1,100 subjects who had used cannabis more than six times and evaluated the severity of their dependence based on DSM-IV criteria. The level of dependence (low, intermediate or high) corresponded to the number of criteria met.[91] The following results were obtained:

 

 

Severity of cannabis dependence based on use[92]

 

Distribution of subjects based on type of use

 

Low

Intermediate

Heavy

Total

Dependence

(number of criteria)

 

T          A          C

 

T          A          C

 

T          A          C

 

T          A          C

 

Nil (0-2)

Low (3-4)

Moderate (5-6)

Severe (7-9)

 

18         88         85

28           8         11

34           3          2

19           1          3

 

14         45         53

30         22         21

39         15         14

17         17         12 

 

 5           8         35

22         12         34

51         19         23

23         61         17         

 

13         47         59

27         14         18

40         12         13

20         27         10

T = tobacco; A = alcohol; C = cannabis

 

 

We see a consistent situation in which the link between heavy use and dependence is lower for cannabis than for tobacco and alcohol, and in which, over all, dependence on cannabis is the lowest of the three substances.

For his part, professor Roques proposes three classes of products based on their dangers. The first includes heroin, cocaine and alcohol; the second psychostimulants, hallucinogens, tobacco and benzodiazepines; and cannabis is set apart in a separate class. He classifies the dangerousness of drugs using a diverse set of criteria. We have reprinted his table of the dangerousness of drugs on the following page.


 

Danger Factors of “drugs” (reprinted from Roques, B. (1999), page: 296

 

Heroin

Cocaine

MDNA

Psycho-stimulants

Alcohol

Benzo-diazepines

Cannabi-noids

Tobacco

Dopamine Overactivation

 

 

Hypersensi-tivity to Dopamine

 

Activation of Opioid System

 

Physical Dependence

 

Psychic Dependence

 

Neurotoxicity

 

 

General Toxicity

 

Danger to Society

 

Replacement Therapy

 

+++

 

 

 

++

 

 

++++

 

 

 

very high

 

 

very high

 

 

low

 

 

high

 

 

very high

 

 

yes

 

++++

 

 

 

+++

 

 

++

 

 

 

low

 

 

high but intermittent

 

high

 

 

high

 

 

very high

 

 

yes

 

+++

 

 

 

?

 

 

?

 

 

 

very low

 

 

?

 

 

very high ( ?)

 

 

possibly very high

 

low ( ?)

 

 

no

 

++++

 

 

 

+++

 

 

+

 

 

 

low

 

 

average

 

 

high

 

 

high

 

 

low (exceptions)

 

no

 

+

 

 

 

±

 

 

++

 

 

 

very high

 

 

very high

 

 

high

 

 

high

 

 

high

 

 

yes

 

±

 

 

 

?

 

 

+

 

 

 

average

 

 

high

 

 

0

 

 

very low

 

 

low

 

 

not researched

 

 

+

 

 

 

±

 

 

±

 

 

 

low

 

 

low

 

 

0

 

 

very low

 

 

low

 

 

not researched

 

+

 

 

 

?

 

 

±

 

 

 

high

 

 

very high

 

 

0

 

 

very high (cancer)

 

0

 

 

yes


In closing, we note that there is no known physical dependence on cannabis, even though in the most severe cases, withdrawal is sometimes accompanied by physical signs such as trembling, insomnia, irritability, etc.

 

Tolerance

From a technical standpoint, tolerance is defined as follows:

 

the property of the human organism to endure the administration of usually effective doses of a given substance without displaying a reaction. With respect to drugs, this tolerance can lead to increased doses in order to achieve the desired effect. [93] [translation]

 

Development of tolerance is associated with pharmacodynamic changes. In some animal studies, chronic administration of THC reduced the density of receptors in some regions of the brain[94] and increased it in others; these effects were reversible.[95]

In man as in animals, studies have observed the phenomenon of cannabis tolerance. However, the data must be interpreted with care insofar as some studies and clinical cases have also found that regular users needed less cannabis to achieve the desired effect.[96] Nevertheless, a study by Wiesbeck et al. involving 5,611 subjects reported that 16% of frequent cannabis users had a history of a withdrawal syndrome.[97]

It is tolerance of a substance that leads to withdrawal symptoms. In recent years, clinical data has been accumulated on withdrawal symptoms in heavy cannabis users (several doses per day in an ongoing manner for several years). The symptoms observed include agitation, loss of appetite, nausea, disturbed sleep, irritability or hyperactivity and an increased body temperature.[98] These symptoms appeared after 24 hours of abstinence, peaked after two to four days and diminished within seven days. The symptoms were markedly less severe and of shorter duration than with other psychoactive substances. Furthermore, clinical studies showed that most subjects continued to perform their daily activities in a normal fashion.

 

 

To summarize

In Chapter 6, we have seen that use does not follow a single pattern, even less so a pattern inevitably leading to increased use. Even in chronic users, the use of cannabis is sometimes irregular and involves periods of abstinence and of more intensive use. We have also seen that current epidemiological studies are not sensitive enough to the complex interactions between the multiple factors that influence patterns of use. These various difficulties make it more difficult to estimate the number of problem users, even more so the number of persons who may become dependent.

In our view, it is clear that the term addiction, severely criticized for its medical and moral overtones, is inadequate to properly describe the different forms of at-risk and problem uses. It is even less useful when it comes to cannabis, whose addictive potential is low. It is therefore of limited use to inform public policies aiming to prevent at-risk and problem use and to assist excessive users. Further, we are of the view that dependency is but one of the many consequences of excessive use of cannabis and that this possibility must not be overestimated.

For these reasons, we propose to distinguish between different uses on the basis of four criteria: context, quantity, frequency, and duration and intensity.   

 

Proposed Criteria for Differentiating Use Types

 

Environment

Quantity

Frequency

Period of use and intensity

Experimental / Occasional

 

Curiosity

 

Variable

A few times over lifetime

None

Regular

Recreational, social

Mainly in evening

Mainly in a group

A few joints

Less than one gram per month

A few times per month

Spread over several years but rarely intensive

At-risk

Recreational and occupational (to go to school, to go to work, for sport…) Alone, in the morning

Under 16 years of age

Between 0.1 and 1 gram per day

A few times per week, evenings, especially weekends

Spread over several years with high intensity periods

Excessive

Occupational and personal problems

No self regulation of use

Over one gram per day

More than once per day

Spread over several years with several months at a time of high intensity use

 

 

Given the poor knowledge base on use patterns in Canada, we have no choice but to speculate on the number of persons falling in each of these types of uses. We propose the following broad parameters:

 

v     In adults: we have estimated that approximately 100,000 persons over 18 would use cannabis daily.

·               If 30% to 40% use between 0.1 to 1 gram per day, this means that 30,000 to 40,000 may be at-risk;

·               If 5% to 10% use more than 1 gram per day, this means that 5,000 to 10,000 adults have excessive use patterns.

v     In youth 12 to 17, we have estimated that as many as 225,000 use cannabis daily.

·               If it is agreed that any use below the age of 16 is excessive use, and that youths 12-15 who use cannabis may represent approximately 25% of this group, then about 50,000 may uses excessively;

·               Of the remaining 175,000, if 30% to 40% use 0,1 to 1 gram per day, approximately 50,000 to 70,000 would be at-risk;

·               If 5% to 10% of the remaining 175,000 use more than 1 gram per day, then approximately 8,000 to 17,000 use excessively.

 

We are aware that these estimates do not account other variables, such as context and duration of use. We can only hope that future epidemiological studies, which must be undertaken regularly, will help further explain the complexity and variability of these uses.

 

 

Conclusions

 

In total, based on all the data from the research and the testimony heard regarding the effects and consequences of cannabis use, the Committee concludes that the state of knowledge supports the belief that, for the vast majority of recreational users, cannabis use presents no harmful consequences for physical, psychological or social well-being in either the short or the long term.

More specifically, this conclusion is based on the following conclusions.

 


 

Conclusions of Chapter 7

Acute effects of cannabis

 

 

 

Distinctions between uses

 

 

 

 

 

 

 

 

At-risk use and heavy use in adults

 

 

 

 

 

 

 

Any use in those under age 16 is high-risk use

 

 

 

 

 

 

Consequences of heavy use

Ø      The immediate effects of cannabis are characterized by  feelings of euphoria, relaxation and sociability; they are accompanied by impairment of short-term memory, concentration and some psychomotor skills.

 

 

Ø      For purposes of public policy, the Committee does not feel that the traditional distinctions between acute and chronic effects are useful.

Ø      Similarly, the Committee does not feel the dichotomy of use and dependence is useful.

Ø      The research data does not allow for a clear distinction between use, at-risk use and heavy use.

Ø      The amount consumed is an indicator, but other factors, psychosocial factors and factors relating to the context of use and the quality of the substance, are equally determining in the passage from use to at-risk use and heavy use.

 

Ø      Nevertheless, the Committee feels that for people over the age of 16, at-risk use lies within the range of 0.1 to 1 gram per day; anything more than that is heavy use, which can have negative consequences on the physical, psychological and social well-being of the user.

Ø      According to this distinction, and in accordance with the epidemiological data available, there is reason to believe that approximately 100,000 Canadians could be at-risk users and approximately 80,000 could be heavy users.

 

Ø      The Committee feels that, because of its potential effects on the endogenous cannabinoid system and cognitive and psychosocial functions, any use in those under age 16 is at-risk use;

Ø      Our estimation would suggest that approximately 50,000 youths fall in this category.

Ø      For those between the ages of 16 and 18, heavy use is not necessarily daily use but use in the morning, alone or during school activities;

 

Ø      Heavy use of smoked cannabis can have certain negative consequences for physical health, in particular for the respiratory system (chronic bronchitis, cancer of the upper respiratory tract).

Ø      Heavy use of cannabis can result in negative psychological consequences for users, in particular impaired concentration and learning and, in rare cases and with people already predisposed, psychotic and schizophrenic episodes.

 

Ø      Heavy use of cannabis can result in consequences for a user’s social well-being, in particular their occupational and social situation and their ability to perform tasks.

Ø      Heavy use of cannabis can result in dependence requiring treatment; however, dependence caused by cannabis is less severe and less frequent that dependence on other psychotropic substances, including alcohol and tobacco.

 

 

 



[1] World Health Organization (1997), op. cit., page: 3; on this question also see: Hall, W. (1987) “A simplified logic of causal inference” Australian and New Zealand Journal of Psychiatry, 21: 507-513.

[2]  On this subject, see the works of Karl Popper in particular (1978 for the French edition) The Logic of Scientific Discovery Paris: Payot, and (1985) La connaissance objective. Bruxelles: Complexe.

[3]  It is even a little ironic that the National Institute on Drug Abuse (NIDA) in the US finances studies that have people smoke when the Institute believes that cannabis is a gateway drug: for example, see the study by Haney, M. et al. (1999) “Abstinence symptoms following smoked marijuana in humans” Psychopharmacology, 141; 395-404.

[4]  Nelson, P.L. (1993) “A critical review of the research literature concerning some biological and psychological effects of cannabis” in Advisory Committee on Illicit Drugs (eds.) Cannabis and the law in Queensland: A discussion paper. Brisbane: Criminal Justice Commission of Queensland.

[5] Wheelock, B. (2002) op. cit.

[6]  In particular the previously mentioned INSERM report (2001), op. cit. and the report from the International Scientific Conference on Cannabis (2002); as well as the report from the National Institute of Medicine in the US and the book edited by Professor Kalant, one of our witnesses.

[7] Testimony of Michael J. Boyd, Chair of the Drug Abuse Committee and Deputy Chief of the Toronto Police Service, for the Canadian Association of Chiefs of Police, Special Senate Committee on Illicit Drugs, First Session of the Thirty-Seventh Parliament, Issue No. 14, page: 74.

[8] Testimony of Dale Orban, Detective Sergeant, Regina Police Service, for the Canadian Police Association, Special Senate Committee on Illicit Drugs, First Session of the Thirty-Seventh Parliament, Monday, May 28, 2001, Issue 3, page: 47. It should be immediately noted that the last statement is completely false as we will see in Chapters 19 and 12 on international agreements and Canadian legislation that have placed cannabis on the list of controlled drugs since 1924, with no knowledge of its physical or psychological effects at that time, and for completely different reasons, when there were any.

[9]  Dr. Mark Zoccolillo, Professor of Psychiatry and Assistant Professor of Pediatrics, McGill University and the Montreal Children's Hospital, Special Senate Committee on Illicit Drugs, Second Session of the Thirty-Sixth Parliament, October 16, 2000, Issue No. 1, page 77.

[10]  Dr. Bill Campbell, President, Canadian Society of Addiction Medicine, Special Senate Committee on Illicit Drugs, First Session, Thirty-Seventh Parliament, March 11, 2002, Issue No. 14, page: 56.

[11]  Mr. John Conroy, Barrister, Special Senate Committee on Illicit Drugs, First Session of the Thirty-Seventh Parliament, March 11, 2002, Issue No. 14, page 11.

[12]  Dr Colin Mangham, Director, Prevention Source BC., Special Senate Committee on Illicit Drugs, First Session of the Thirty-Seventh Parliament, September 17, 2001, Issue No. 6, page: 71.

[13]  Dr. Benedikt Fischer, Professor, Department of Public Health Sciences, University of Toronto, Special Senate Committee on Illicit Drugs, First Session of the Thirty-Seventh Parliament, September 7, 2001, Issue No. 6, page 9.

[14]  Dr. Perry Kendall, Health Officer for the Province of British Columbia, Special Senate Committee on Illicit Drugs, First Session of the Thirty-Seventh Parliament, September 17, 2001, Issue No. 6, pages 33-33.

[15]  Dr. Harold Kalant, Professor Emeritus at the University of Toronto, Special Senate Committee on Illicit Drugs, First Session of the Thirty-Seventh Parliament, June 11, 2001, Issue No. 4, pages 74-76.

[16]  Dr. Mohamed ben Amar, Professor of Pharmacology and Toxicology, University of Montreal, Special Senate Committee on Illicit Drugs, First Session of the Thirty-Seventh Parliament, June 11, 2001, Issue No. 4, pages 9-10.

[17]  Moreau de Tours, J., Du haschich ou de l’aliénation mentale, étude psychologique. Paris: Masson.

[18]  INSERM, op. cit., page 118.

[19]  See WHO, 1997, op. cit., 3.

[20]  For example, this is the case with the classification proposed by Ben Amar (at press).

[21]  This is the case with the collective expertise of INSERM (2001).

[22]  This is the case with most works: WHO, 1997; Swiss Federal Commission for Drug Issues (1999) Rapport sur le cannabis. Berne: Swiss Federal Office of Public Health; and the report by Wheelock (2002).

[23]  Fant, R.V. et al. (1998) “Acute and residual effects of marijuana in humans.” Pharmacology, Biochemistry and Behavior, 60: 777-784.

[24]  Roques, B. (1999) La dangerosité des drogues. Paris: Odile Jacob, page: 184.

[25]  INSERM, op. cit., page: 203.

[26]  Hanak, C. et al. (2002) “Cannabis, mental health and dependence.” in Pelc, I. (ed.), International Scientific Conference on Cannabis, Brussels.

[27]  INSERM, op. cit., page 124.

[28]  Roques, B., op. cit., page 186.

[29]  This question has been discussed more fully in Chapter 6. For now it is enough to refer the reader to the work of Reynaud et al. (1999) Les pratiques addictives. Usage, usage nocif et dépendance aux substances psycho-actives. Paris: La Documentation française.

[30]  We will more clearly establish the parameters we used to make this distinction in the next chapter on use and users. Further on in this chapter we will see that dependence is a consequence of heavy use.

[31]  Institute of Medicine (1982) Marihuana and Health. Washington, DC: National Academy of Sciences.

[32]  INSERM (2001), op. cit., page 222.

[33]  For example, those are the criticisms made by Zimmer L., and J.P. Morgan (2000 for the French version; 1997 for the American original) Marijuana. Mythes et réalités. Paris: Georg editor.

[34]  Ibid., page 221.

[35]  Ibid., page 221

[36]  Ibid., page 218.

[37]  Joy, J.E. et al., (1999) Marijuana and Medicine: Assessing the Science Base. Washington, DC: Institute of Medicine.

[38]  WHO (1997) op. cit.

[39]  Ben Amar (at press), op. cit., page 18.

[40]  Tashkin, D.P. et al., (1997) “Heavy habitual marijuana smoking does not cause an accelerated decline in FEV1 with age: a longitudinal study.” American Journal of Respiratory Critical Care, 155: 141-148.

[41]  See Zimmer and Morgan, op. cit., page 148.

[42]  Polen, M.R. (1993) “Health care use by frequent marijuana smokers who do not smoke tobacco.” Western Journal of Medicine, 158: 596-601.

[43]  In particular, see the conclusions of INSERM (2001), op. cit.; as well as the report by Wheelock (2002) op. cit. for the Senate Committee.

[44]  Fliegel S.E.G. et al., (1988) “Pulmonary pathology in marijuana smokers”, in Chesher G. et al. (eds.), Marijuana: An International Research Report, National Campaign Against Drug Abuse, Monograph 7, 43‑48, Canberra, Australian Government Publishing Service; and Fliegel, SEG et al., (1997) “Tracheo-bronchial histopathology in habitual smokers of cocaine, marijuana or tobacco” Chest, 112: 319-326.

[45]  Donald P.J. (1991) “Marijuana and upper aerodigestive tract malignancy in young patients”, in Nahas, G. and C. Latour (eds.), Physiopathology of Illicit Drugs: Cannabis, Cocaine, Opiates, 39-54, Oxford; and (1991) “Advanced malignancy in the young marijuana smoker”, in Friedman, H. et al., (eds.), Drugs of Abuse, Immunity and Immunodeficiency, 33-36, London.

[46] Taylor, F.M. (1988) “Marijuana as a potential respiratory tract carcinogen: A retrospective analysis of a community hospital population”, Southern Medical Journal  81: 1213-1216.

[47] Caplan, G.A. and B.A. Brigham (1990) “Marijuana smoking and carcinoma of the tongue: Is there an association?” Cancer 66: 1005-1006.

[48]  MacPhee, D., (1999) “Effects of marijuana on cell nuclei”, in Kalant, H. et al. (eds.), The Health Effects of Cannabis, Toronto: Addiction Research Foundation.

[49]  In particular WHO (1997), op. cit.; Hall, W. and N. Solowij (1998) “Adverse effects of cannabis” The Lancet, 352, no. 9140, page 6; INSERM (2001), op. cit.

[50]  WHO (1997), op. cit., page 26.

[51]  INSERM (2001), op. cit., page 219-220.

[52]  Wheelock, B. (2002), op. cit., page 29.

[53]  WHO (1997), op. cit., page: 24; INSERM, op. cit., page 237.

[54]  Fried, P.A. (1995) “Prenatal exposure to marijuana and tobacco during infancy, early and middle childhood: Effects and attempts at a synthesis.” Archives of Toxicology, 17; and Fried P.A. and B. Watkinson (1999) “36- and 48-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes and alcohol.” Journal of Deviant Behavior and Pediatrics. 11: 49-58.

[55]  INSERM (2001) op. cit., page 235.

[56]  Roques, B., (1999) op. cit., page 73.

[57]  Roques, B., (1999) op. cit., page 187.

[58]  INSERM, op. cit., page 206.

[59]  Ibid., page 204.

[60]  Ibid., page 205.

[61]  Ibid., page 206.

[62]  WHO (1997), op. cit., page 18.

[63]  Miles G.C. et al., (1974) An Experimental Study of the Effects of Daily Cannabis Smoking on Behavioural Patterns, Toronto: Addiction Research Foundation, Toronto.

[64]  Campbell, I. (1976) The Amotivational Syndrome and Cannabis Use With Emphasis on the Canadian Scene, Annals of the New York Academy of Sciences 282, 33-36.

[65]  INSERM, op. cit.; Hanak, C. et al., (2002) “Cannabis, mental health and dependence”, Pelc, I. (ed.), International Scientific Conference on Cannabis, op. cit., page 61.

[66]  Hanak, C. et al. (2002), op. cit., page 62.

[67]  INSERM (2001), op. cit., page 98.

[68]  Roques, B., (1999) op. cit., page 186.

[69]  INSERM, (2001) op. cit., pages 206-207.

[70]  Caballero, F. and Y. Bisiou (2000) Droit de la drogue. Paris, Dalloz, 2nd edition, page 3.

[71]  WHO (1964) Expert Committee on Addiction-Producing Drugs, Technical Report Series, no. 273, quoted in Caballero and Bisiou, op. cit., page 5-6.

[72]  WHO (1969) Expert Committee on Drug Dependence, Technical Report Series, no. 407, quoted in Caballero and Bisiou, (2000), op. cit., page 6.

[73] WHO (1952) Expert Committee on Drugs Liable to Produce Addiction, Technical Report Series, no 57, quoted in Caballero and Bisiou (2000), op. cit., page 4-5.

[74]  INSERM, (2001), op. cit., pages 274-275.

[75]  Ibid., page 270.

[76]  Cohen, P. testimony before the Senate Committee; also Alexander B.K., professor, Department of Psychology, University Simon Fraser, testimony before the Senate Committee on Illegal Drugs, Senate of Canada, First Session of the Thirty-Seventh Parliament, April 23, 2001, Issue 1.

 

[77]  WHO (1997) op. cit..

[78]  Channabasavanna, M, et al., (1999) “Mental and behavioural disorders due to cannabis use”, in Kalant H. et al. (eds.), The Health Effects of Cannabis, Toronto: CAMH.

[79]  Anthony J.C. and J.E. Helzer (1991) “Syndromes of drug abuse and dependence”, in Robins L.N. and D.A. Regier (eds.), Psychiatric Disorders in America, New York, Free Press, pages: 116-154.

[80]  Anthony, J.C . et al., (1994) “Comparative epidemiology of dependence on tobacco, alcohol, controlled substances and inhalants: basic findings from the National Comorbidity Survey.” Experimental and Clinical Psychopharmacology, 2: 244-268.

[81]  Kandel, D. et al. (1997) “Prevalence and demographic correlates of symptoms of last year dependence on alcohol, nicotine, marijuana and cocaine in the US population.” Drugs, Alcohol and Dependency, 44: 11-29. See also Kandel D. and M. Davies, (1992) “Progression to regular marijuana involvement: Phenomenology and risk factors for near daily use”, in M. Glantz and R. Pickens (eds.), Vulnerability to Drug Abuse, 211-253, Washington DC, American Psychological Association.

[82]  Fergusson, D.M. and L.J. Horwood (2000) “Cannabis use and dependence in a New Zealand birth cohort.” New Zealand Medical Journal, 113: 156-158

[83]  Poulton, R., et al., (2001) “Persistence and perceived consequences of cannabis use and dependence among young adults: implications for policy.” New Zealand Medical Journal, 114: 13-16.

[84]  Swift, W. et al., (2001) “Cannabis use and dependence among Australian adults: results from the National Survey of Mental Health and Well-being.” Addiction, 96: 737-748.

[85]  Van Laar, M., et al., (2001) National Drug Monitor. Jaarbericht 2001. Utrecht: NDM Bureau.

[86]  T.R. Kosten et al., Substance-use disorders in DSM-III-R, British Journal of Psychiatry, 151, 8-19, 1987.

[87]  Hathaway, A.D. (2001) “Cannabis effects and dependency concerns in long-term frequent users: a missing piece of the public health puzzle.” Transmitted to the Senate Committee on Illegal Drugs during the testimony of Professor Hathaway before the Senate Special Committee on Illegal Drugs, Senate of Canada, First session of the thirty-seventh Parliament, May 14, 2001, Issue 2.

[88]  Ibid., page 15.

[89]  Cohen, P.D.A. et H.L. Kaal, (2001) The irrelevance of drug policy. Patterns and careers of experienced cannabis use in the population of Amsterdam, San Francisco and Bremen. Amsterdam: University of Amsterdam, CEDRO, page 99.

[90]  Rigter, H. and M. van Laar (2002) “Epidemiological aspects of cannabis use.” in Pelc I., (ed.) International Scientific Conference on Cannabis. Brussels.

[91]  Woody G.E. et al., (1993) “Severity of dependence: Data from the DSM-IV field trials” Addiction 88, 1573-1579.

[92]  Reprinted from INSERM (2001) op. cit., page 73.

[93]  OMS (1969), in Caballero et Bisiou (2000), op. cit., page 6.

[94]  Rodriguez de Fonseca, F. et al., (1994) “Downregulation of rat brain cannabinol binding sites after chronic delta-9-THC treatment”, Pharm. Biochem. Behav. 47, 33-40.

[95]  Westlake, T.M. et al., (1996) “Chronic exposure to delta-9-THC fails to irreversibly alter brain cannabinoid receptors” Brain Research, 544, 145-149.

[96]  Beardsley, R.M et al., (1986) “Dependence on THC in rhesus monkeys”, Journal Pharmacol. Exp. Ther., 239 (2), 311-319.

[97]  Wiesbeck, G.A., et al., (1996) “An evaluation of the history of a marijuana withdrawal syndrome in a large population.” Addiction, 91 (10): 1573-1579.

[98]  Kouri, E.M. et al., (2000) “Abstinence symptoms during withdrawal from chronic marijuana use.” Experimental and Clinical Psychopharmacology, 8: 483-492.


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