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Harold Kalant, M.D., Ph.D., F.R.S.C.

Professor Emeritus, Department of Pharmacology, University of Toronto
Research Director Emeritus, Centre for Addiction and Mental Health*

Toronto, Ontario

June 11, 2001

*Note: The views expressed in this submission are those of the author and do not necessarily represent the policies of the Centre for Addiction and Mental Health. 

address: Department of Pharmacology
Medical Sciences Building
University of Toronto
Toronto, Ontario M5S 1A8
telephone: (416) 978-2730
facsimile: (416) 978-6395
e-mail: harold.kalant@utoronto.ca


1. No potent psychoactive substance can ever be completely safe, because every active drug is capable of causing various types of harm to the individual user, to those in contact with the user, and to society at large. To minimize the harm, all societies control the extent of use of such drugs, by a combination of different means, including laws and law enforcement, regulations, traditions, societal norms of behavior, education, price and taxation. Although the choice of policy options is often presented as a sharp dichotomy between legalization and prohibition, there is in fact a rather broad range of variable mixtures of these different means available, aimed at achieving the optimum balance of greatest social benefit at the lowest social cost. Individual and collective values and value judgments are important components of the process.

2. The nature of the controls and their enforcement differs for medical use vs. non-medical use, and it is appropriate that this is so. The costs and benefits pertaining to the two types of use are quite different. Expert knowledge and scientific judgment play a major role in designing controls on medical use, whereas ideologies, traditions, social values, and judgments about individual vs. collective good predominate in relation to controls on non-medical use. The difference is well illustrated by the fact that medical use of heroin and of cocaine is permitted and approved, but is not seen as a justification for the free availability of these drugs for non-medical use. Cannabis is a major exception, for which the distinction between the appropriate controls for medical and non-medical use is frequently overlooked, or even deliberately blurred.

3. Medical use of cannabis has a long history, but in North America it decreased steadily in the first part of the 20th century, well before over-the-counter cannabis preparations were made illegal. This was due mainly to poor standardization of these cannabis preparations, variable composition, uncertain dosage, and instability (poor shelf life) of the products, and the clinical superiority of new drugs that were pure compounds of exact composition and dosage. However, isolation of the pure active ingredients of cannabis (cannabinoids), identification of their receptor molecules in brain and other tissues, and synthesis of derivatives with greater selectivity of action, have revived interest in the potential therapeutic uses and benefits of these drugs. Much work remains to be done in the area of clinical tests to establish the proper dosages for specific medical purposes, the safety margin, and the comparative efficacy of these compounds relative to other recognized treatments for the same medical conditions.

4. The smoking of crude cannabis is not an approved form of therapy for any disease in any of the major countries of the world, because crude cannabis is an imprecise agent, and smoking poses health risks in chronic users. Although marijuana is relatively safe compared to a number of other drugs, it does carry various risks of potentially serious health and safety problems. During a single occasion of use, the main risks are: (1) impaired alertness, accuracy, coordination and judgment in operating motor vehicles or other heavy machinery, and (2) occasional panic states or toxic psychoses caused by overdose. With regular heavy use the major risks are: (1) chronic inflammation of the bronchi, (2) possible cancers of the upper airways, (3) impaired memory and other cognitive functions, (4) cannabis dependence, (5) precipitation of relapse in schizophrenic patients, and (6) possible mild but permanent changes in memory and learning in children of mothers using cannabis during pregnancy.

5. The future of medical use of cannabis-related materials will almost certainly involve pure single cannabinoids, administered by various methods free of the risks of smoking. However, as an interim measure there are some individuals for whom the short-term use of smoked cannabis may be beneficial and justifiable. These are mainly experienced users who have smoked it for non-medical purposes, and can easily continue to use it for medical reasons. The specific therapeutic purposes for which this might be warranted are discussed in Dr. Mary Lynch's submission.

6. To permit the necessary clinical trials, including comparisons of smoked cannabis with oral and other routes of administration of pure cannabinoids, it is necessary to be able to offer protection from legal penalties and harassment, both to the clinical researchers conducting the studies and to the subjects taking part in them. This should be seen as a completely separate issue from the political, ethical and value judgments that the whole population must take part in, with respect to any change in the legal status of non-medical use.

1. Psychoactive drug use: external controls versus personal choice

1.1 Why do controls exist?

It is a basic truth of pharmacology that there can be no such thing as a totally harmless drug. Every substance that has pharmacological activity is capable of causing harm, by excess of its action, by unusual individual sensitivity or allergy in the user, by unforeseen interaction with other drugs, or by situational circumstances in which its usual action for some reason becomes dangerous (e.g., antihistaminic drugs with sedative effects that impair driving). Some drugs are more dangerous than others, but no drug is without risk. The harm caused by psychoactive drugs may be to physical or mental health, to interpersonal relations, to school or work performance, or to the smooth human or economic functioning of society. The untoward effects may be to the individual user (for example, alcoholic liver disease, tobacco-induced lung cancer, suppression of breathing by heroin overdose, etc.), to those around the user (for example, violence caused by "crack" cocaine, failure to provide for the well-being of the user's family, etc.), or to society at large (for example, lost productivity due to drug-impaired work performance, accidents caused by impaired drivers, increased expense to the health care system due to illnesses caused by drug use, loss of billions of dollars annually to foreign suppliers of illoicit drugs, etc.).

There is abundant evidence that the total amount of such drug-related harms is proportional to the total extent of use of the drugs. Therefore, in order to minimize the frequency and severity of the harm, every society imposes various types of controls on the level of use.


1.2 What types of control measure does society use to reduce or limit drug use?

The choice of policy options for control of drug use is often presented as a sharp dichotomy, a choice between legal prohibition, with its attendant reliance on police, courts and prisons, and full legalization of drugs, with reliance on individual judgment and choice to limit use to safe and enjoyable levels. In fact, no such simple dichotomy exists. Controls are of many different types, including not only legal sanctions, but also regulations governing such things as places and hours of sale, legal purchasing age, etc,; society's traditions and shared values concerning acceptable and unacceptable levels and patterns of use; price; taxation policy; educational programs; and other means of shaping attitudes toward drug use in both children and adults. All of these methods are used in varying degrees, for both legal and illegal drugs.

1.3 Do these control measures really work?

It is often argued by opponents of legal controls that prohibition of drug use, or heavy taxation of the drugs (tobacco, alcohol, etc.), do not really work, because people use the drugs in spite of these controls. There is abundant evidence that this view is quite mistaken. No control measure can ever be expected to be 100% effective: speed limits do not prevent all speeding, raising taxes on cigarettes does not stop all smoking, and laws against theft and murder do not totally prevent these crimes. Nevertheless, such measures help to shape, as well as reflect, society's attitudes towards what behaviors are acceptable or unacceptable. The best evidence of their effectiveness is to be seen in the changes in behavior that occur when the control measures are changed. When Prohibition was instituted in the USA (de facto in 1916, and de jure in 1920), the consumption of alcohol dropped by over 50% and the death rate from alcoholic cirrhosis of the liver fell sharply. The per capita consumption of tobacco and of alcohol in Canada have both varied inversely with their price relative to income and cost of living. When the legal drinking age was lowered from 21 to 18 years in several provinces, there was an abrupt increase in the proportion of drinking-driving accidents contributed by 16- and 17-year-old drivers.

There are many more such examples that demonstrate that control measures do have a significant effect on levels of use, and on the adverse consequences of excessive use. The problem is that the control measures themselves can also have adverse consequences. Society therefore has to assess the benefits and the harms caused both by drug use and by the measures used to control drug use.

1.4 Cost/benefit considerations in the choice of drug control policies.

The main benefit of medical use of drugs is the treatment of disease or the relief of its symptoms, whereas the main costs are the financial costs to the individual and to the health care system, the risk of adverse drug effects, and the risk of deviation of certain drugs into the illicit drug market. The main benefits of the drug control system are the guarantee of purity, safety and efficacy of the drugs, and protection against their misuse; on the other hand, the main costs of the control system are the risk of excessive delay in making new drugs accessible, and the burden and financial cost of "paper work" in the handling of controlled drugs. The cost/benefit balance is a relatively simple one, the goal of which is to maximize the access to safe and effective drugs at the lowest financial and procedural cost.

In contrast, the main benefit of non-medical drug use is personal pleasure, or reduction of discomfort of various types. The costs of drug use include the various types of harm mentioned in section 1.1. The main benefit of control measures is the prevention or reduction of drug-related harm, whereas the costs of control measures include the massive expenditures on police, courts, and prisons, the lasting harm that a criminal record may cause to the career and personal life of the convicted offender, the restriction of individual freedom of choice, social disunity, and the indirect promotion of illicit drug traffic. These costs do not refer only to legal and punitive controls. For example, imposition of high taxes on alcohol or tobacco creates conditions that favour smuggling or bootlegging. On the other hand, reducing price or increasing the ease of purchase from legal suppliers increases the extent of use, and hence increases the health and social damage caused by the drugs themselves.

The challenge, therefore, is to find the optimal combination of control measures that will achieve the greatest social benefit at the lowest total social cost. This concept is developed in greater detail in the book chapter that is attached as Appendix 1 to this submission. 


2. Different controls for medical and for non-medical use.

2.1 Why are these different?

Although there are some who feel that even medical use of drugs should be left completely to individual judgment and choice in a free market (e.g., Dr. Thomas Szasz, in Our Right to Drugs: The Case for a Free Market)), the vast majority of people recognize that treatment of disease requires expert knowledge and experience, and they generally prefer to entrust the therapeutic decisions to physicians or other health specialists. Since all drugs used in treatment have appreciable risks of adverse effects, the public has also left to the health care system, including governmental agencies in the health field, the responsibility for ensuring that the drugs really do have the desired quality and actions, that their risks are smaller than their possible benefits, that the appropriate doses are established by scientific methods, and that the drugs are used responsibly and monitored continuously for unpredicted adverse effects. To this end, the controls consist of such measures as the requirement for preclinical and clinical trials before licensing, availability of many drugs only on medical prescription, the keeping of adequate records by pharmacists, post-marketing monitoring for infrequent adverse effects, reporting of production and sales figures to the government, regulations governing standards of purity, and so forth. Even over-the-counter drugs that can be freely purchased and self-administered without medical prescription must first pass careful examination for purity, efficacy and safety before they can be marketed, and experts are expected to carry out this type of control for the protection of the public.

In contrast, non-medical use of drugs serves primarily for the pleasure of the user, and sometimes for the alleviation of discomfort that is perceived as a personal rather than a medical problem. The potential harms, however, are both to the user and to the rest of society, in many different forms, as noted in section 1.1 above. The considerations that enter into the choice of optimal control policy are therefore much more diverse than for the controls over medical use.


2.2 Value judgments in selecting the optimal control policy.

It should be readily apparent that the definition of "optimal" depends not only on a sound basis of factual information concerning all the effects of drug use and of the various possible control measures, but also on a series of value judgments. Labelling any given effect as a cost or a benefit already implies a value judgment; the same effect may be considered good (hence, a benefit) by one person and bad (i.e., a cost) by another. Weighing relative costs and benefits also involves value judgments: for some people, freedom of choice to use or not use drugs is more important than reduction of health care costs to society; for others, reduction of health care costs is much more important, and freedom to use drugs is a negligible benefit or even a threat. In effect, we have to make a very difficult value judgment: how much pleasure or freedom is worth how much risk or cost to the individual and to society. Such judgments involve many factors that are impossible to weigh objectively but that enter in an important way into the shaping of individual and collective value systems: religious views, traditions, political philosophy, personal preferences and tastes, peer group fashions, etc. All of these contribute to forming our views on what kind of a society we want to live in. In a democratic society, that kind of judgment is not a matter for experts, but for the whole public to decide.


2.3 Medical usefulness is totally irrelevant to control policy for non-medical use.

Control policies are not directed toward particular drugs, but toward particular ways of using drugs. In other words, the same drug can be subject to two different sets of control measures, one dealing with its medical use and one with non-medical use, and the two sets have nothing at all to do with each other. This is well illustrated by the fact that heroin and cocaine still have recognized (though limited) medical uses, for which they are legally available on medical prescription, whereas their non-medical use is strictly forbidden. Nobody argues that their medical uses justify making them freely and legally available for non-medical use. The major, or perhaps sole, exception to this accepted separation of roles is in the case of cannabis. Whether it is due to confused thinking, or to deliberate blurring of the distinction for strategic or political purposes, numerous advocates have argued that the possible therapeutic usefulness of cannabis or cannabinoids is a reason for completely legalizing cannabis for all uses.


3. How useful is cannabis in the treatment of disease?

3.1 History of medical use of cannabis

Medical use of crude cannabis, in the form of solid or liquid extracts taken by mouth, has a centuries-long history in traditional medicine in several parts of the world, but also for at least 150 years in Western Europe and North America. Many of the uses were similar to those for which it is now being studied in scientific medicine. Nevertheless, the medical use of cannabis declined steadily after 1900, and had largely died out even before over-the-counter cannabis preparations were made illegal in 1923. Physicians were still permitted to prescribe it, but so few did so that manufacture ceased by the 1950s. The reason was to be found in the variability of composition and potency of the pharmaceutical preparations, their poor shelf-life, the consequent unreliability of therapeutic effect, and the appearance of new, synthetic drugs of known purity, stability and potency (opiates, barbiturates, aspirin, etc.) that rapidly gained medical favor and increasingly replaced cannabis in medical practice.

This change was not unique to cannabis. Medical history demonstrates for all drugs an evolution away from crude mixtures of natural products, towards pure synthetic compounds of exactly known composition, strength, dosage, and selectivity of therapeutic effect. This evolution permitted major improvements in drug therapy, including more specific targetting of drug actions for particular uses, and decreases in unwanted side effects.


3.2 Current status of cannabis and cannabinoids in medical treatment.

Renewal of medical interest in cannabis has arisen primarily because of the isolation of pure cannabinoids from the crude cannabis, synthesis of newer derivatives with greater specificity of action, and elucidation of the cellular mechanisms by which these pure compounds act in the body. These developments are summarized in the accompanying submission by Dr. Mary Lynch, and in Appendix 2 to the present submission. Like all new drugs, these pure cannabinoids will have to undergo the same testing to establish their effectiveness, safety, appropriate dosage, best methods of administration, range of side effects, etc., as for all new drugs. The great bulk of medical and scientific studies on the use of cannabis-related drugs has involved pure _9-tetrahydrocannabinol (THC), the main active component of crude cannabis, and two closely related derivatives, nabilone and levonantrodol. However, in the near future there will be increasing numbers of published studies with newer, wholly synthetic cannabinoids.


3.3 What is the medical role of smoked cannabis (marijuana)?

The smoking of crude cannabis is not now, and never has been, an approved form of medical therapy for any disease, in any of the major countries of the world, even when cannabis was in the British Pharmacopoeia and the US Pharmacopeia prior to 1932 and 1941 respectively. The reasons are not difficult to understand. Despite the undeniable fact that the onset of drug action is much faster when cannabis is smoked than when it is taken by mouth, the duration of action is also much shorter, which is a significant disadvantage in the treatment of longer-lasting diseases or symptoms. The technique of smoking the drug, and therefore the delivery of drug from the lungs into the bloodstream, varies greatly from one user to another. Finally, the introduction of smoke into the lungs has harmful effects (see below) which are undesirable in the treatment of patients. Therefore the great preponderance of medical opinion is against the smoking of cannabis for medical purposes, except in a few special circumstances summarized later in this submission. However, if there are some patients for whom smoked cannabis is to be considered as a form of treatment, it is also necessary to do clinical studies to compare systematically the effectiveness of smoked cannabis with that of pure cannabinoids given by other routes than smoking, as well as with that of other currently available treatments for the same conditions.


4. Potential risks of cannabis use for either medical or non-medical purposes.

4.1 How safe is marijuana use?

Marijuana is often claimed to be a harmless substance. Although, as pointed out above, there is no such thing as a totally harmless drug, it is true that in some respects cannabis is relatively safer than a number of the other drugs that are commonly used non-medically, in that no known fatalities have occurred in humans as a result of overdose of cannabis alone. Nevertheless, its use does carry a number of serious risks to health, safety, and effective functioning. These risks can be divided into acute risks, i.e., those occurring during a single occasion of use, and chronic risks, i.e., those arising from repeated use over a period of many months or years.


4.1 Acute risks of cannabis.

The main risk arising during a single episode of use is the intoxication that accompanies the pleasurable "high" for which the drug is used non-medically. This intoxication, like that produced by alcohol, includes reduction of alertness, attention, accuracy, coordination and judgment in operating motor vehicles or other complex machinery. Despite claims to the contrary, there is in fact abundant evidence that driving ability is reduced. Many impaired drivers in whom cannabis is found in the blood or urine also have alcohol present. The rather illogical argument has been raised that therefore the impairment was due to the alcohol and not to the cannabis, but the only scientifically valid conclusion is that both substances were contributing to the impairment. The main other acute risk is the precipitation of acute panic reactions or acute toxic psychosis, caused by overdose. This occurs mainly, though not exclusively, in inexperienced users.

Both of these acute risks can occur when the drug is taken either by mouth or by smoking. However, they are more common during smoking, because the onset of action is more rapid and more intense after smoking than after the same dose taken by mouth.


4.2 Chronic risks of cannabis.

With regular heavy use (e.g., smoking cannabis several times daily over prolonged periods of time) there are a number of major health hazards. (1) The irritating properties of the smoke produce a chronic bronchitis in a high percentage (over 60% in some studies) of long-term users. (2) Related to this are pre-cancerous changes in the cells lining the airways, and recent reports indicate an increased risk of cancer of the upper airways. (3) Higher mental functions, including memory, learning ability, verbal ability, problem solving, and motivation, have been found repeatedly to be impaired in chronic heavy users, leading to poor school or work performance. Fortunately, these changes usually disappear if use is discontinued. (4) The occurrence of cannabis dependence, which was formerly denied by those who advocate the legalization of cannabis, has now been well demonstrated in numerous studies, and is seen in a high percentage of long-term heavy users. It is usually mild and not life-threatening, but may be sufficiently intense to cause continuation of use in a significant percentage of those who would like to stop using the drug. (5) In compensated schizophrenics (i.e., those who have responded to treatment well enough to resume functioning in society), cannabis use increases the risk of relapse. (6) The findings of a long-term study in Ottawa suggest that the children of mothers who used cannabis during pregnancy may have mild but permanent changes in memory, verbal ability, attention and learning. The literature on these and other adverse effects of cannabis use is reviewed in greater detail in the manuscript attached to this submission as Appendix 2.


5. Potential therapeutic applications of cannabis and cannabinoids.

For the reasons set out above, the future medical use of cannabis-related drugs will almost certainly involve the pure cannabinoids, either THC or the newer synthetic compounds with greater selectivity of action, that are water-soluble and can be administered by mouth, by injection or by inhalation in forms that do not require inhaling the smoke of combusted plant material. Nevertheless, for the next few years, until the development and testing of these other compounds and methods of administration are completed, there are some patients who may benefit from the smoking of crude cannabis for medical reasons. These patients are likely to be experienced marijuana smokers who have been using it for non-medical purposes, who find its effects pleasurable rather than unpleasant, and who now find that it also relieves symptoms of recent onset. The specific diseases or symptoms for which it may be beneficial are reviewed in the submission by Dr. Mary Lynch.

The few studies in which smoked cannabis has been systematically compared with pure THC given by mouth have not revealed any clear superiority of one over the other. Pure THC is already legally available on prescription in the form of capsules for oral use, for the treatment of nausea and vomiting, or the stimulation of appetite and weight gain, in patients being treated for AIDS or cancer. However, for the few who do not respond well to oral THC, the smoking of marijuana may be effective. If the disease in such patients is likely to be of short duration, or if their life expectancy is short because they are in the very late stages of a fatal illness, there would be no reason to worry about the long-term harm that might result from chronic smoking of cannabis, and it would be humane to allow them to use it. In contrast, if the illness is one which is likely to last for many years or for the rest of the patient's life, such as multiple sclerosis or epilepsy, it would be ethically unjustifiable to recommend the use of a treatment that might give rise to complications more serious than the symptoms that are being treated.


6. Changes in drug laws for medical versus non-medical use.

As discussed by Dr. Lynch, a number of changes in current drug laws and law enforcement practices are required, to facilitate the carrying out of the clinical trials needed for assessing and comparing scientifically the therapeutic usefulness of herbal marijuana and of pure THC and other cannabinoids. These changes are required for the protection of the patients taking part in these studies, as well as of the clinicans carrying them out. However, it must be emphasized again that such changes in the laws and regulations surrounding the clinical use of these substances should be seen as a completely separate matter from any change in the legal status of non-medical use of cannabis or other drugs. The latter involves political, ideological, ethical and very complex and difficult value judgments that must respect the views, feelings and aspirations of the whole population (for a fuller discussiom see Appendix 3).  



Appendix 1. La question des drogues au XXIe siècle: une responsabilité gouvernementale ou individualle? (Drug policies for Canada in the 21st century: government controls or individual responsibility?) Chapter 8 from Pierre Brisson, ed.: L'Usage des Drogues et la Toxicomanie, Gaëtan Morin, Éditeur, 1994.

Appendix 2. Medicinal use of cannabis: History and current status. Pain Research and Management, in press, 2001.

Appendix 3. Drawing a Balance (À la recherche d'un équilibre). Chapter 9 from Harold Kalant and Oriana Josseau Kalant: Drugs, Society and Personal Choice, General Publishing Co., 1971 (Drogues, Société et Option Personnelle, Les Éditions La Presse, 1973).

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