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|Major Studies of Drugs and Drug Policy|
|Canadian Senate Special Committee on Illegal Drugs|
|Volume I - General Orientation|
Chapter 7 - Cannabis: Effects and Consequences
Tolerance and dependence
we think drugs we think drug addiction since, as F. Caballero states, a drug is
[translation] “any substance likely to
lead to addiction”. 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. [translation]
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. 
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
Drug addiction is a state of periodic or chronic
intoxication produced by the repeated consumption of a drug (natural or
synthetic). Its characteristics include:
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.
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.
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). 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. 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).
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.
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.
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 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. People who
use cannabis on a daily basis for several months would be at greater risk of
becoming dependent. 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.
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%. 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%). 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. 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. 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).
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.
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.
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.
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. 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. 
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
Amsterdam, San Francisco, Bremen 
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
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
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%.
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. The following results were obtained:
T = tobacco; A = alcohol; C
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.
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.
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.
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. 
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 and increased it in others; these effects were reversible.
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. 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.
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. 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.
 Caballero, F. and Y. Bisiou (2000) Droit de la drogue. Paris, Dalloz, 2nd edition, page 3.
 WHO (1964) Expert Committee on Addiction-Producing Drugs, Technical Report
Series, no. 273, quoted in Caballero and Bisiou, op. cit., page 5-6.
 WHO (1969) Expert Committee on Drug Dependence, Technical Report Series, no.
407, quoted in Caballero and Bisiou, (2000), op. cit., page 6.
 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.
INSERM, (2001), op. cit.,
 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.
 WHO (1997) op. cit..
 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:
 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.
 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.
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
 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
 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.
 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.
Van Laar, M., et al., (2001) National
Drug Monitor. Jaarbericht 2001. Utrecht: NDM Bureau.
 T.R. Kosten et al., Substance-use disorders
in DSM-III-R, British Journal of
Psychiatry, 151, 8-19, 1987.
 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.
 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.
 Rigter, H. and M. van Laar (2002)
“Epidemiological aspects of cannabis use.” in Pelc I., (ed.) International Scientific Conference on
 Woody G.E. et al., (1993) “Severity of
dependence: Data from the DSM-IV field trials” Addiction 88, 1573-1579.
 Reprinted from INSERM (2001) op. cit., page 73.
 OMS (1969), in Caballero et Bisiou (2000), op. cit., page 6.
 Rodriguez de Fonseca, F. et al., (1994)
“Downregulation of rat brain cannabinol binding sites after chronic delta-9-THC
treatment”, Pharm. Biochem. Behav.
 Westlake, T.M. et al., (1996) “Chronic
exposure to delta-9-THC fails to irreversibly alter brain cannabinoid
receptors” Brain Research, 544,
 Beardsley, R.M et al., (1986) “Dependence on
THC in rhesus monkeys”, Journal
Pharmacol. Exp. Ther., 239 (2), 311-319.
 Wiesbeck, G.A., et al., (1996) “An
evaluation of the history of a marijuana withdrawal syndrome in a large
population.” Addiction, 91 (10):
 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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