KALANT, H. in chief cont. 1

A Yes, I do, Your Honour.

Q Doctor, let’s get now towards the report of the ARFWHO committee and the report of the meeting of 1981. Just before we go into that, there has been a later meeting of that committee?

A Yes, there is an updated report currently in preparation.

Q And that will reflect work done to what period of time?

A Essentially up to 1995.

Q Back to the 1991 report, firstly, can you tell us how cannabis should be classified as a pharmacologist, how would you classify cannabis?

A It’s not entirely clear, because cannabis has actions which are somewhat different from those of any other well-recognized class of drugs, but it depends to a large extent on the dose. At the doses that are typically used by most users for social purposes, it’s a mild sedative similar in some ways to the effects of alcohol and similar drugs. It’s not identical to them. It differs in some respects, but probably it’s closer to that than to any other category. In very high doses, it can produce—

Q Excuse me a minute, please—

Q I’m sorry, before I stopped you there, Doctor, you were telling us that at normal doses the effect of cannabis is that of a mild sedative or a sedative?

A Yes, that’s correct. It produces relaxation and elevation of mood, feelings of greater comfort and pleasure and it can also produce at the later stage of the effect drowsiness and it can enhance the sedative effects of alcohol and similar sedative drugs. In high doses it can produce hallucinations or altered perception and for that reason, some books classify it with hallucinogens, but I think it’s important to make clear that that’s only true at very high doses. It is not hallucinogenic in the levels that are normally used.

Q Thank you. Now, in the committee work, you arrived and for the sake of reference here, looking at page 3 of the ARFWHO report that is found in Exhibit 5 of the—which tab number was that?

Q Doctor, you defined—or the committee defined the term adverse effect as being one which may be considered to occur when such use produces impairment of an individual’s biological behavioural or social function, is that correct?

A That’s correct.

Q Was there a contextual reference to adverse effect?

A I’m afraid I don’t understand your—

Q Does the implication of the phrase adverse effect depend upon the context in which it is being used?

A Ahh. Yes, it does, in the sense that as pointed out in that paragraph, there can be disagreement about whether an effect should be called adverse or not, and I think it is quite clear that something which alters perception may have no adverse consequences if a person is simply sitting quietly and enjoying music or whatever; whereas the same effect could be adverse if a person were driving a car, so that the impairment of function does necessarily relate to what a person is doing, what the circumstances are and so on.

Q You also defined intoxication and toxicity?

A We attempted to define them, but recognized that it was not always possible to differentiate them. Intoxication ordinarily refers to the constellation of effects that a person experiences when taking the drug in the usual way for the usual purpose; whereas toxicity usually refers to unanticipated and undesired harmful effects to the extent that you can separate them. That’s the meaning, but sometimes for obvious reasons they can’t be separated because intoxication can result in toxicity.

Q The committee also—and when I say committee for the next little while I’ll be referring to the Addiction Research Foundation World Health Organization committee.

A Yes.

Q The committee also defined acute to refer to single doses and their effects?

A That’s correct.

Q Or to reactions or responses on single occasions of brief duration?

A That’s right.

Q Did you have the same level of precision with chronic?

A No. Chronic is used in different senses by different users. I don’t mean users of the drug, I mean users of the term. In animal experiments, for example, chronic can mean as few as five or six administrations. Clinicians ordinarily use chronic to mean long-term, months or years and there’s a convenient term, subacute or another subchronic that attempt to indicate various stages of difference between the acute and the clearly chronic, but they are not widely used.

Q Did you have success in finding the term rates of use or coming to agreement on what rates of use are?

A No. The trouble is that occasional, frequent and heavy moderate are all judgmental terms in a sense, and it’s better, if possible, to avoid those terms and simply specify frequency and amount in terms of actual numbers.

Q Is that what the committee did eventually when they had their meeting and the report was prepared?

A They attempted to. Unfortunately, habits often die hard and the term chronic use does come up frequently without specification but where possible, attempts were made to relate effects to known durations and amounts of use.

Q The next heading on page 4 of that report is General Toxicity of Cannabis Preparations. What can you tell the Court about the general toxicity of cannabis preparations?

A The term general toxicity usually refers to the production of organ damage or life-threatening functional change and in general, I think one can say that the toxicity of cannabis as measured in terms of the dose required to produce death, for example, which is a standard definition of toxicity for many drugs, such definitions would say that it is not a—not a severely toxic drug. There are no known deaths from cannabis alone and in animals one can cause death with enormous doses, but humans—in human experience there is no such toxicity because people don’t use doses of the order that are required to produce that in animals.

Q There are from your answer though, I understand that there are lesser levels of toxicity than lethality, being those which can have an effect on the organism?

A Yes. And most of the committee’s report is devoted to consideration of special toxicity in the sense of adverse effects on specific organ systems or functions, rather than on life or death.

Q That takes us to page 7 or reference cite. What is the—were the findings of respiratory toxicity in animals?

A At that time there was not very much experimental work on respiratory toxicity in animals. What was well-recognized was that single doses of cannabis can decrease the frequency and the depth of respiration much as other depressive drugs do and the effect of cannabis was at least additive with the similar effects of other drugs such as alcohol, barbiturates, general anaesthetics and so on. However, the studies on other characterizations of pulmonary pathology were not very extensive. There was some evidence that large amounts of cannabis smoke administered to animals could produce inflammation in the small airways and some changes in the lungs in terms of inflammatory cells collecting in parts of the lungs. That was not given a great deal of attention by the committee because they—again, the parameters of exposure of animals were not terribly clear in terms of how they related to human exposure.

Q Has that situation changed in the science since 1981?

A Yes, it has changed, not in the sense of animal studies but of much more refined studies in humans and perhaps you—I don’t know if you want me to go on to the human studies or not at this point.

Q Well, you can certainly do that. What has been learned since 1981 with respect to respiratory effects in humans?

A There has been a continuing series of studies by the group headed by Dr. Tashkin in California, very sophisticated studies with quite refined functional tests and one similar study by Bloom’s group in England somewhat later. They have not coincided completely in terms of their findings, but in general there has been very good agreement between them, and what they have shown is that chronic heavy use and by heavy in this case they meant essentially daily use, gives rise to inflammation of the what are called the proximal bronchials, that is the larger branches rather than the very fine terminal branches that lead right into the lung tissue.

Q Proximal are those closer to the mouth.

A Closer to the mouth.

Q And the—

A Distal are the ones—

Q -- distal are those furthest away.

A Closer to the final branching in the lungs, so the more proximal tubes have shown inflammatory changes, excessive production of mucous, alteration of the inflammatory cells, that is the cells that normally scavenge foreign material out of the bronchial tubes and the alveoli, the small air sacs in the lungs, and there have been changes in resistance of air flow through these tubes. The—probably the best term to use is a chronic bronchitis with reduced efficiency of air movement through the bronchial system to the lungs.

Q Has there been studies done, has there been a development in the science which would tell us what the cause of those apparent precancerous cellular changes is? Is it smoke, is it active ingredient in the substance that one would—

A No, that can be answered in the sense that it seems to be fairly clearly the smoke, polycyclichydrocarbons similar to those that occur in tobacco smoke and which produce the inflammatory and precancerous changes in the airways and the lungs. The tetrahydrocannabinol, the active, the psychoactive component of cannabis does not appear to be involved in the production of the precancerous changes or the inflammatory changes.

Q I’d like to just deviate here for a moment. Does there exist data which compares one to the other the risks of cancer between a tobacco smoker and a cannabis smoker?

A No, not specifically with respect to the risks of cancer, because there are not yet data which permit that type of assessment for cannabis. In terms of the inflammatory changes in the airways, yes, because the studies that I referred to have made quite a major point of including as closely as possibly matched groups of tobacco only smokers, of marihuana only smokers, of combined tobacco and marihuana smokers and of non-smokers, so that these studies do give some basis for assessing the relative contributions of the two types of smoke to the production problems and what is clear is that the patterns of change produced by tobacco smoke and by cannabis smoke are not identical but they’re additive. In all of the tests that have been examined, for example, the effect of the combined marihuana plus tobacco smoke was greater than the effect of either the marihuana or the tobacco alone and the reason why one cannot draw similar conclusions about the risk of cancer is that the data on which that risk is assessed for tobacco are of a very different type from the immediate clinical study that I’ve described. Those are public health, based on public health statistics in which one can assess the rates of cancer production according to the duration and the amount of smoking of tobacco and such data accumulated over twenty, twenty-five years or more, in fact over probably several generations of tobacco smokers have been the basis for the conclusions about the risk of cancer production in tobacco smoking and such data simply aren’t available yet, at least, for cannabis smoking.

Q And when would one expect those data to become available for cannabis smokers?

A I can only offer a personal opinion here. I think it will be probably—

Q Perhaps you shouldn’t.

A I think it will be at least thirty or forty years, for the following reasons. It depends upon the size of the population which is being observed and how accurate the data are concerning the extent of use, in terms of intensity and duration of use. With a legal drug such as tobacco, it’s much easier to get such data. With illicit drugs, it’s unlikely that one can accumulate such data for the simple reason that patients obviously—or I shouldn’t say patients, users are obviously reluctant to provide detailed information if it may be incriminating and also at current levels of use, cannabis is not used nearly as widely as tobacco and therefore it will take a much longer time to accumulate the data. For tobacco, as I said, it took twenty, twenty-five years of accumulation of such data and given the fact that the information on cannabis is much more limited, it will probably take correspondingly longer.

Q The next item in the report is on page 9 and that deals with cardiovascular toxicity in experimental animals. What was the results of the committee’s work on that, Doctor? Page 8, excuse me.

A The committee came to the conclusion that there was really minimal evidence to suggest any cardiovascular risk. What is recognized is an acute effect of two kinds. Cannabis tends to—the smoking of cannabis tends to increase the heart rate and therefore in theory someone who has impairment of coronary circulation could have—could experience a risk of heart attack because of an increase in heart rate elevating the demand for oxygen while the coronary circulation is unable to supply that extra demand. But that’s a purely theoretical or a hypothetical suggestion because there were no data to describe cases in which that had actually occurred.

Q Now, you were dealing then with humans, you’d gone from experimental animals into humans?

A Yes. Experimental animals show the increased heart rate which is accompanied by an increased work load because of an increased output of blood attributable to the increased rate. There is mention in the animal section of a finding which has subsequently been confirmed in humans, there have been a couple of studies in humans confirming the increased blood flow through the large vessels of the brain. It should be pointed out this is generally considered an interesting finding but it’s impossible to say whether it’s beneficial or detrimental. The way it’s studied in humans is to give a tracer which can be combined with a PET scan or a single positron emission scanning of the brain and the tracer is injected intravenously and then as long as it remains in the circulation you can measure the tracer isotope output, at least the emission from the isotope, over different parts of the brain and thus show an increased flow of blood through those parts of the brain, and that occurs together with the psychoactive effects. It is—in the case of other drugs it is taken to mean that the blood is going through the large vessels and shunting back to the veins, rather than going through the brain tissue itself, but it really—one can use it only as an index of the drug activity but it’s impossible yet to attribute either beneficial or harmful effects to that.

Q The next topic dealt with—

Q Has there been any change in the science on this since 1981, Doctor?

A In terms of cardiovascular?

Q Yes.

A No. The only major change has been the use of these tracers for studying cerebral flow. There has been no further evidence to implicate cannabis in terms of cardiac damage.

Q The next topic that I would like to direct your attention to appears on page 9 of the report under growth and body weight and the conclusion of the committee was that as of 1981 there was little or no information on possible long-term effects of cannabis on growth, development and maturation of humans, is that right?

A Yes. That was the conclusion then.

Q That has changed?

A That has changed. There have been contradictory findings in various studies, but perhaps the best longitudinal studies, that is those which follow subjects over a period of years and re-examine them, relate to the possible—I may be jumping a topic here, but I think this is the most appropriate place to bring it, relate to the effects of prenatal exposure, that is the fetus exposed in the uterus to cannabis smoked by the mother and there have been a number of studies showing that babies born to mothers who have used cannabis through substantial part of the pregnancy are small for their birth age, that is for their gestational age, the length of time that they’ve been developing in the uterus. That has been shown in several studies and they, according to perhaps the largest of these studies, that by Freed et al in Ottawa, the infants are small, hyperirritable, don’t feed as well after birth, but they recover over the next six months or so and by a year they’re back to normal size for—size for age in terms of body weight and growth. The animal studies have consistently shown that high doses of cannabis do inhibit appetite and therefore impair growth over short periods of time, but there is a good possibility that tolerance develops to that effect, as it does to the similar effect of morphine, for example, and long terms studies therefore would be needed and have not been carried out in this -- no, I must retract that. There has been one good long term study by the toxicology group in Arkansas which showed that in—after a year’s exposure, there was no appreciable impairment of the growth or development of animals exposed regularly to cannabis, so the implication must be that there was tolerance developed to the initial inhibitory effect on appetite.

Q Have there been studies done on the additive effects of the use of cannabis with other drugs at the prenatal stage?

A Yes. The same studies that I referred to have shown that the effects of cannabis are similar to those of the effects of tobacco smoking. It -- the evidence is suggestive of an additive effect of the two. It’s more difficult to state with certainty that that is the case compared to the respiratory studies in which the populations are well-matched. In the prenatal studies, the matching is more difficult because many of the mothers who used cannabis also used other drugs for which good controls are not as easy to obtain.

A I have to recall here something that our professor of pathology said when we were medical students. This is the famous Professor William Boyd, who talked about his experience as a medical student in Edinborough when there his professor of medicine took the group to the window and said, "What are those birds on the roof over there?" And one of the students said, "Sparrows." And he said, "Of course they’re sparrows. You don’t expect to see canaries in Edinborough. But remember that canaries would be rare except when they happen to you." So that something like a—well, reference is made here to pathogenic fungi such as Aspergillus which produces a very serious disease in the lungs which has been described in AIDS victims smoking contaminated cannabis, that would be rare but I suppose to the person to whom that happens, it’s not insignificant. Other than that, I would say yes, in statistical terms they are insignificant.

Q I skipped over a gastrointestinal section. I understand that there does not appear to be any adverse effects in the gastrointestinal—

A That’s correct.

Q -- situation.

A And that’s—that has not changed in the years since that first report.

Q Going back then to the miscellaneous toxic manifestations, has there been any change since 1981 on that topic?

A No, not really. The other thing that was mentioned there was allergic phenomena and there have not been any additional reports to suggest that this is in any way a significant problem.

Q The next heading on page 10 is toxicity related to unusual methods of cannabis exposure, and what do you or would the committee have described as an unusual method of exposure or administration?

A Well, the one which was given the greatest attention was the accidental exposure to very large amounts by people who swallowed balloons or condoms filled with hashish or hashish oil to avoid detection by the police and in the very few cases in which the container ruptured inside the gastrointestinal tract, the person was then exposed to sudden administration of a very large amount and the toxic reactions that are referred to in that paragraph refer to such episodes. Those are obviously purely random events and cannot be considered meaningful in terms of public health considerations.

Q What type of reactions would those individuals typically suffer?

A They suffered a sharp fall in blood pressure, coma, fallen body temperature, similar to those described in the toxicity studies in experimental animals with very large doses, but it’s again the case that none of those resulted in fatality.

Q Let’s proceed then to the topic cellular toxicity on page 10 and what was the view of the committee on the cellular toxicity of cannabis?

A The committee at that time was unable to come to any firm conclusion. There were reports that cannabis tested on isolated cells in a test tube was mutagenic, that is produced mutations and drugs which are mutagenic are by definition harmful to the nuclear material of the cell and many mutagens are also carcinogenic, that is they can produce cancer. That’s not invariably true, but many mutagens are carcinogens. The problem is that these studies were done in isolated cells and when one looked to see if there was evidence for that happening in humans who smoked cannabis, the results are conflicting. Some studies reported increased frequencies of anomalies in such as what are called chromatid exchange, a breakage and then rejoining in an abnormal fashion, that is not the original fashion in that cell of chromosomal fragments or other changes in cell function by isolated inflammatory cells and some studies showed that there were such changes in increased numbers and others did not. Therefore, the conclusion was that this is an area which requires further study, it requires more precise examination of frequencies and doses used to give rise to such findings and preferably longitudinal studies following smokers to see whether such changes occurred with increasing frequency or not, as they continued to use the drug.

Q The committee studied reports, experiments on among others for rodents on this, did they not?

A Yes. Yes.

Q And what types of dose would be given to rodents typically in studies of this nature?

A The doses given to rodents are always very substantially larger than the doses given to humans but the—

Q Why is that? Why is that?

A Well, I was just going to explain that there are two considerations that come in. The first is that the dose that you give to—to any species to produce comparable degrees of exposure has to be related to the body size and shape because to produce equivalent effects, the dosage should not be expressed in terms of body weight, but ratio of body surface to body mass. The reason for that is that the smaller the animal, the higher the ratio of the surface to body mass, the greater the metabolic rate, the faster the drug is eliminated and the more drug you need to produce a comparable effect, so that with any drug you can find, for example, that in terms of body surface to mass ratio, if you equate them you’re giving an elephant a much smaller dose per unit of body weight to produce the same change that you would produce in a human with a larger dose per unit of body weight and in a rat or a mouse with a very much larger dose per unit of body weight, but all would be comparable in terms of surface area to mass ratio.

Q Is that a generally accepted principle for testing in this area?

A That’s a well-known principle of pharmacology, yes. Yes, that’s—that’s a principle which dates from very early toxicity studies that therefore you must not compare, for example, the dose of the same amount per unit of body weight in a mouse as in a human to look for comparable effects. You need about twenty to thirty times as much in a rat as you do in a human to get comparable drug effects, but the other reason for using much larger doses in rodents is that the rodent studies look deliberately to see the complete range of effects from very small to the largest you can possibly give and you can’t do that in humans for ethical reasons, so that the range of doses you examine in rats tends to go to often hundreds of times what you would give in a human for the combination of the two reasons and the problem is whether the differences between the studies in humans and in rodents are due solely to the difference in requirements of different species or whether they also reflect differences in the objectives.

Q Is the use of rodents as a testing method a commonly accepted way of studying things in the pharmacological field?

A I would say it is almost mandatory. It’s almost always the first step. If you’re dealing with a drug which has therapeutic uses, you then have to use other species as well in order to study the generality of the effects that you find for licensing of a new drug for a therapeutic use, for example, you have to do it in species other than rodents, preferably in primates, that is in monkeys or chimpanzees and then in the later stage of drug testing, of course, it has to be done in humans, but you begin almost invariably in small animals in order to scan the whole spectrum of effects, focus down on those that you are most interested in for therapeutic or other purposes and then see how defined the quantitative relationships and then see how those change in other species.

Q Has there been any change in the science since 1981?

A Of the methods of studying?

Q Of the methods of studying and—

A No, the methods of studying, I think, are still essentially the same.

Q And the committee’s views on cellular toxicity?

A No, I would say that has not changed in the sense that the uncertainty that was expressed by the committee in the 1981 meeting was still expressed by the committee in the 19 -- well, the committee that was charged with preparing the current report that’s in progress by the World Health Organization. In the sense that it was still confirmed that there are with high doses of -- or high concentrations of cannabis increased frequencies of breaks in the nuclear material, but there is still not agreement or not certainty as to what the functional implications of that are for humans with respect to, for example, inflammatory cells or the cells that may give rise to cancer.

Q Okay. I should just insert now that with respect to the 1995 meeting you performed a similar role for the Addiction Research Foundation and the World Health Organization as you did in 1981, did you?

A Not quite identical, because the 1993 to current committee is entirely a World Health Organization committee, not a joint ARFWHO committee, so that my role was not as an ARF member but as a member of the ad hoc committee by the World Health Organization. My role has been to chair that meeting and also to chair the editorial committee that is preparing the report.

Q And are you following the same method of developing a consensus on the document as you did for the 1981 meeting?

A It’s rather wider in the sense that the consensus was reached by the committee. Then the committee’s draft report was circulated to I believe something like eighty experts in various countries in different agencies or different scientific disciplines for their reactions. The reactions were fed back to the committee for discussion and response. The response was in many cases to make modifications to the report that the committee felt were improvements, clarifications, the reviewers had suggested. In some cases the committee did not agree with the comments made by the reviewers and gave the reasons for their disagreement when they resubmitted the report to the WHO and it is now in a stage of final review by the outside experts and will presumably be published sometime later this year.

Q The next heading in the 1981 committee report is the immune system. What were the findings of the—

A I’m sorry, you’re regarding carcinogenicity in the 1981 report as already having been dealt with or—

Q I thought that we had, but please continue, we’ll go back to carcinogenicity.

A Right. The only thing that has differed since the ‘81 report is the question of the case reports that have been published of cancers of the upper airways or upper digestive tract meaning the pharynx and esophagus in people who were heavy smokers of cannabis, and the committee—the current WHO committee reviewed those as well and concluded that while they’re only scattered case reports, they are—they provide grounds for concern in that while most of the subjects in whom these cancers occurred were smokers of both cannabis and tobacco, there were a very small number of cases in which they were smokers of cannabis only and not of tobacco and had not been smokers of tobacco, plus the fact that a number of these occurred in quite young people, people in their late teens or early twenties at an age at which one does not ordinarily see such cancers due to tobacco alone and therefore the committee felt there was legitimate reason for concern of the—either the cannabis alone or the combination of cannabis plus tobacco posed—may pose a greater risk of carcinogenicity than that attributable to tobacco alone.

Q Thank you.

Q Should I direct your attention to anything in the impairment of the macromolecule synthesis?

A No, we’ve already covered that.

Q Or possible biomechanical mechanisms?

A Biochemical mechanisms. No, that section on possible biochemical mechanisms has proven to be, I think, a non-productive lead. The newer work on biochemical mechanisms relates much more to the discovery of cannabis receptors or cannabinoid receptors and their possible cellular functions and I think the work described in that section on page 13 of the 1980 -- report of the 1981 meeting has probably not panned out. It shouldn’t be given much importance now.

Q The next topic then is the immune system. What were the findings of the 1981 committee on adverse effects related to the immune system?

A The literature that was reviewed by the committee for the 1981 report indicated that cannabis or cannabinoids in fairly high concentrations, in fact quite high concentrations, could suppress the function of immune cells either examined in the test tube or in animals such as rats or mice. What was looked for in the test tube was the ability to activate the immune cells to start producing antibodies or to act as scavengers that would pick up foreign material including bacteria and so on and what was looked for in mice was the ability to impair an immune response to a known antigen that should evoke an immune response. Those effects were again considered suggestive but not conclusive and it was recognized that the possible role of the cannabinoids had to be defined more exactly in quantitative terms, in terms of specific functions of immune cells because it was known that immune cells are of different types and have different functions and that these had to be examined in living animals or humans in much more detail before one could conclude that it was a meaningful effect. So that this was regarded as something for requiring further investigation.

Q I’m sorry, Doctor, I didn’t hear the—

A It was suggested by the committee then, the section called biological significance, that it might be of greatest importance, a possible suppression of immune function might be of greatest importance in individuals whose immune function was already impaired by other disease and that in such people it might be a significant consideration. That was as far as the committee felt able to go with a conclusion at that time.

Q Has there been any development in the science since 1981 on that point?

A Yes, there has been—there have been several developments. Not enough to resolve the doubts completely, but certainly there has been considerably more work defining the effects of the cannabinoids on the individual functions of immune cells of different types, both in the test tube and in the living organism. It’s been shown, for example, that the cannabinoids can inhibit the production of what are called cytokines—

Q How do you spell that please?

A C-y-t-o-k-i-n-e-s. These are substances that activate immune cells and cause them to initiate their immune functions, including both what are called humoral, that is antibody functions, production and release of antibodies and their ability to attack foreign organisms such as bacteria or fungal cells or particles of foreign material such as smoke condensates depositing in the lungs and it’s been shown that in fairly good studies that this is indeed a significant effect of cannabinoids in high concentrations and that these are mediated in substantial part by the cannabinoids themselves, rather than by smoke because there are cannabinoid receptors—I should perhaps deviate here for a moment to explain that development. It was referred to in court yesterday, but I think that it is important to repeat it, that the newer work has been—demonstrate that the cannabinoids act through specific chemical receptors on the surfaces of various types of cells in the body. There’s one type of receptor which is found in brain cells and another type which is found on immune cells in the spleen and other parts of the immune system and the rest of the body, so that actions of this type which are initiated through cannabinoid effects on the receptors in immune cells can be considered true effects of cannabinoids themselves, rather than effects of smoking.

Q What is the effect of this discovery? What have we found the effects on the immune system then to be since 1981?

Q The next topic appears on page 16, Cannabis as an Allergen. Did the committee have any concerns about possible or probable adverse effects of cannabis as an allergen in 1981?

A No, there was no—oh, in ‘91 it had some concern that there had been reports of allergic responses as demonstrated by skin tests and by the appearance of antibodies, but there has been no new information that has been published since then that we have encountered or that suggests that a major importance of this aspect of cannabis effects.

Q On page 17 of the summary of the committee report is the topic Effects on Endocrine Function. Did the committee come to any conclusions about possible adverse effects or probable adverse effects on the endocrine function?

A In the ‘81 again?

Q In 1981.

A Yes. The committee felt that there was again reason for some possible concern that required further study, but there was no definite evidence of significant impairment of function. What they found was some studies which indicated that in the short term the administration of rather large amounts of cannabis in animal studies and in one or two human studies suggested a decrease in the production of testosterone, a decrease in sperm count in the human subjects in whom the testosterone levels were reduced and in females, an increased possibility of what are called anovulatory cycles, in other words menstrual cycles in which no release of egg cells occurs. These were all short term observations and there was no evidence on which to conclude whether that had any long-term significance or not.

Q Has there been any development in the science since 1981?

A A small amount, not much. There has been demonstration that luteinizing hormone—

Q Would you spell for the sake—

A -- which is a—

Q -- of the person who will have to type the transcript?

A Yes. L-u-t-e-i-n-i-z-i-n-g, or luteotropic, l-u-t-e-o-t-r-o-p-i-c hormone which is the hormone that’s released by the pituitary gland that stimulates production of sex hormones in the testes for the male or in the ovary for the female is diminished by cannabis smoking or has been shown to be diminished in some experimental studies with humans that involve smoking over a period of weeks; however, again this led to no long-term conclusion on—or rather no conclusion about long-term significance because there is a suggestion in both humans and animals that tolerance may develop to this effect and that the levels may return to normal, despite continued smoking of cannabis, so that there is less concern now by the committee, the current committee than there was by the previous committee in terms of possible effects on the endocrine system.

Q That should take us then to page 21, Reproduction and Development.

Q Which committee—

A I’m referring here to the current WHO committee.

Q You mentioned different tests being applied in different times or different stages of a child’s development. Is that in accordance with the usual types of procedure in these kinds of cases?

A Yes, this is in accordance with what is conventionally done in child psychology because the types of tests that you can apply at different ages depend on functions which mature to different degrees at different ages, so that you don’t test a baby for verbal skills but you test a five-year-old for verbal skills and therefore, tests of this kind become meaningful when the child is old enough to be normally expected to have developed those skills to a point where they can be quantitatively tested.

Q Did the 1995 committee make any recommendations specifically or express any—or would you expect them to express any specific concerns about this variation shown in the latest Freed report?

A Yes. The committee did in its draft report did say this was an area which required follow-up, that its—the degree of its significance to the development of those children would need to be assessed by monitoring of them through subsequent stages of their school careers and it did indicate that this was one of the areas which warranted continued study.

Q Doctor, we’re still dealing with the committee report from 1981. I would ask you to direct your attention to page 23 at the bottom of the page, topic 7, affects on nervous system function.

A And you would like me to summarize?

Q Would you please tell us what the committee found with respect to the effects of cannabis on—the acute effects on intellectual functions?

A The—there is a fairly extensive description on pages 23 through to bottom of page 26. I’ll attempt to summarize those very briefly. Cannabis at that time was recognized to have, in terms of its acute effects, to have a characteristic time pattern in which the initial effects for the first fifteen minutes or so were mainly excitatory, that’s the period in which the heart rate increased, the period in which people are animated, talkative. In experimental animals there’s increased movement and increased physical activity and then there’s a gradual transition over into a period of sedation in which people become quiet, relaxed and animals become less actively moving and in the first phase, the excitatory effect is additive with that of amphetamine or cocaine while in the quiet phase that follows, the effect is additive with that of alcohol, barbiturates or tranquillizers.

Q Would one expect to find similar reactions from people heavily involved with other psychoactive drugs such as alcohol or cocaine or anything you might name?

A No. The pattern of effects with cocaine or amphetamine or stimulant drugs is quite different. With alcohol, yes, chronic alcohol consumption does tend also to reduce motivation, but it was felt to be more marked with cannabis because the duration of the drug and of its actions is longer than that of alcohol that would produce a comparable degree of acute maximum effect. In other words, alcohol is cleared from the body more rapidly than cannabis; therefore, someone who uses cannabis daily can be to some extent under the influence of cannabis virtually all the time, whereas a person who drinks alcohol daily to produce the same acute effect tends to be sobering up for enough of the next day to be able to work and to maintain a job, so that the effect of chronic alcohol use on employment and performance is perhaps not as marked as that of cannabis for comparable degrees.

Q Where were you going when I interrupted you there?

A Well, I was going to say simply what the changes or—

Q Okay.

Q Is it fair to describe synapsis being something like an intercellular pathway or messageway for electric impulses or—

A Yes.

Q -- nervous impulses?

A Yes, that’s exactly what synapse means. A synapse is a contact of the fibre coming out of one nerve cell that carries impulses to a receiving fibre or part of the cell body of the cell to which that information is being transmitted. It is in the great majority of cases a chemical transmission. The nerve impulse causes release of a chemical at the synapse that then passes over to the next cell and activates a receptor on the second cell in the chain and those synapses are recognized by electron—in electron microscopy as tiny protuberances from the fibres that can be actually stained and counted and the synaptic density, that is the number of synapses that an individual nerve cell makes has been shown to be markedly decreased by high—chronic high dose treatment with alcohol and Dr. Fehr’s work suggests that the same would happen or does happen with chronic high dose administration of cannabis, of THC.

Q Does the work indicate whether that is an effect of smoke or of the THC?

A No, that’s because of THC because this was not administered as smoke, as the pure chemical.

Q Does that then take us to page 25, acute effects on driving skills and driving performance?

A Yes. Yes, because the—the same effects on attention, arousal, alertness and so on that had been described in the general performance tests are of obvious relevance to driving and people interested in driving accidents have done a lot of work not only with cannabis but with alcohol, with benzodiazepine tranquillizers, with cocaine, with a variety of other drugs, to see what their effects are on level of alertness, on attention span, on the ability to monitor, pay attention to several different sources of information at the same time, this is referred to as divided attention tasks, on speed of reaction, on accuracy of judgment of distances and speeds, on risk-taking and on motor control, accuracy of response, ability to steer, to move a control lever or a drive wheel accurately to keep on target, and these have shown unequivocally, I mean all observers agree that cannabis in socially-used doses in humans impairs most of these functions in a manner comparable to that of alcohol and additive with that of alcohol.

Q Can I just ask a question for clarification of these. In those studies that found the presence of both cannabinoids and alcohol in the urine tests, was there any way of measuring the level of THC active in the human body at the appropriate time?

A No. That was another problem with those studies because the cannabinoid metabolites, that is the substances to which THC or tetrahydrocannabinol is converted in the body and which are no longer pharmacologically active are excreted in the urine for hours or days and in some cases possibly weeks after the last known use of cannabis so there’s not a good correlation between positive test results in those instances and the blood levels of the active material at the relevant time.

Q Does your earlier evidence about the additive effect of cannabinoids and alcohol have any relationship to the evidence that you have just given?

A No, because those were done after the actual administration of known amounts of the cannabis and/or alcohol with testing during the period of a few hours immediately following that, so that both were known to be present in active concentrations during that time. That’s why experimental studies are much easier to interpret than statistical studies gathered from post hoc or after the fact information from highway drivers or accident victims.

Q Okay. Thank you. Please continue.

Q Now, you have explained the difficulty of proving that very hazard. Do similar difficulties exist in demonstrating the effect on psychomotor operations and cognitive functions in people who are impaired at impaired type levels of THC?

A No. No, no. As I explained, where you are measuring the effects during a known period after the administration of a known amount of cannabis for a time during which one knows what the time course of concentration in the blood or in the brain may be, then that worry does not apply. One knows that the drug, period of drug action is associated with a period of measurable impairment of those functions. All the driving simulator studies, for example, or flying simulator studies are done in that manner.

Q The—has the science advanced since 1981 on this point?

A Yes, there have been better tests developed, more refined and more exacting tests of attention and of visual or functional visual attention, the use of perimetry for noting how small or how large a part of a total possible visual field the person actually pays attention to is a recent development and things of this kind have been used in the study, not only of cannabis but of alcohol and other drugs and have served to fairly consistency lower—fairly consistently lower the concentration that has been found to produce measurable impairment, in other words, the more sensitive the test, the easier it is to show a significant impairment at a given blood level.

Q And that applies to which types of drugs again?

A That applies to all of these drugs. The same reasoning applies to the consistently lower levels of drug that are found to impair flying skills compared to driving skills, because flying is a more demanding task. One has to monitor more sources of information currently and make more rapid critical responses and the driving studies have shown impairment of cannabis—or rather the flying studies have shown impairment by cannabis more readily than driving studies have, that is lower doses and for longer periods of time.

Q Did the 1995 World Health Organization address this issue of impaired operation of vehicles?

A Yes, it did.

Q And was their conclusion any different from that of the 1981 committee report?

A Only in the sense that it was more emphatic, that there was clear demonstration of impairment of a wide range of driving or flying-related skills and that there was now at least better suggestive evidence of actual implication in real life accidents, as shown by the kind of epidemiological study that I referred to, that is in non-fatal cases and measurement of levels in plasma rather than in urine.

Q Have you had an opportunity to read in any detail or to—the Robbe report on a driving study done in the Netherlands recently?

A No. I saw—I had a chance to look at it briefly but not to read it in detail. The only things that I looked—had a chance to look for specifically were the doses that were used in that study and the rationale for the selection of those doses and the authors gave as the reason for selecting one hundred, two hundred and three hundred micrograms per kilo, the fact that these produced blood levels which corresponded to what regular experienced users considered to be mild, moderate or good psychic effects. The three hundred was the one that corresponded to the effects which they attempted to produce in themselves by choice. So that it would be comparable to alcohol levels that might correspond to two or three drinks and I think that from my very brief reading, I gather that that was the reason for them comparing the doses of cannabis that they did to the doses of alcohol that they did.

Q Have you dealt in your earlier evidence on the effects of the dose in studying the motor capacities of an individual? In other words, what I’m trying to say is have you described for us the differences in results that come from different doses of THC when a person is trying to perform complex motor skills?

A I haven’t—I don’t believe I did—

Q Would you deal with that now please?

A Certainly. It’s—I think all that needs to be said is that all investigators who have examined various doses have found that the effects, as one would expect, are dose-related. This is not unique for cannabis. This is a general principle of pharmacology. All measurable drug effects other than allergic or host-related reactions rather than drug-related reactions, all of those characteristic drug effects are dose-dependent. When you study the action of a drug, you always do a dose response curve. You give a range of doses and measure the effects of each of the doses so that you can say how much effect is predictable from how much of the drug and that is true, just as true of cannabis as it is of alcohol or morphine or digitalis or any other drug.

A They were—they were fairly comparable. My recollection is that they used one or two cannabis cigarettes. I don’t remember the concentration. That may be -- no, I don’t believe—it was described in Dr. Klonoff’s paper in the complete volume, but I don’t believe it was mentioned in the executive summary. No, it isn’t. But it would have been comparable to the doses that were used in the Robbe study because they also used, as I recall, either different potencies or different numbers of cigarettes to achieve the three different levels of concentration in the plasma.

Q The next topic is on page—starts on page 26, but I direct your attention to page 27 and Mr. Conroy is directing my attention to the clock. It would appear to be the noon hour, Your Honour.

Q I’d like now, Dr. Kalant, to direct your attention to the report of the committee of 1981, page 33. There’s a heading there Psychiatric Consequences. I would like to ask you whether or not the committee came to any conclusions about the potential psychiatric consequences of cannabis use.

A In the 1981 report, no, it did not come to a very clear conclusion. They recognized that the things which had been described as cannabis psychosis in the older literature dating from the 19^th century on, were questionable, that the case descriptions were not very good and that there was a tendency to take any case that in a psychiatric hospital in which the patient was known to have used cannabis to attribute the illness to cannabis and this was not a very valid procedure.

Q Scapegoating is a word that comes to mind.

A Yes, basically scapegoating.

Q All right.

A And they concluded that this was something which required further investigation, but they were not in a position to offer any clear judgment about it other than that the term cannabis psychosis they felt was probably not a meaningful term.

Q Was there any change in the conclusions of the World Health Organization committee from 1995, was there any difference—

A Yes.

Q -- in those?

Q We have heard of a study done with some members of the Swedish military, I believe it was. Is this that same study?

A It grows out of the same study. The trouble was that in the study of the conscripts, they had no way really of being certain of the relationship between cannabis use and schizophrenia other than that those who smoked cannabis when they were conscripted and were followed up subsequently, a higher proportion developed schizophrenia than among those who weren’t smoking cannabis, but the study that I’m referring to then took actual cases with significant clinical histories that permitted sequential following of events in the individual cases and therefore was able to come to a conclusion with more certainty and in—diagnosed individual cases of what the sequence of drug use versus onset of schizophrenia had been.

Q So do I understand then that there was some significant difference in the methodology of the two studies?

A Yes.

Q And when was that later report approximately, do you recall?

A It was about 1993. I can check that to be certain.

Q That would have been between then the time of the Hall report and the time of the World Health Organization—

A Yes.

Q -- committee—

A Yes, that’s correct.

Q -- or would it have preceded the Hall report?

A I believe that was—no, I think that was mentioned in the Hall report.

Q Thank you.

A I’ll just double check that, but I believe it was. I’m afraid it’ll be more difficult to find here because there isn’t a heading on psychiatric—

Q It’s not—I don’t see it as being especially—the timing as being especially important in any event, Doctor.

A But I’m fairly sure I can find it here in my—in the draft of the—

Q Let’s not worry about that, Doctor.

A Okay.

Q We can go on to the next topic, I think. The next topic is a quick return to the heading epidemiology which is found on pages 34 and 35 of the committee report and there are two items that you and I discussed over the break. The first has to do with what types of studies are going to be needed to show various things. Can you give us your view of the committee’s report on that aspect, please? I’m directing your attention, please, to page 35, the paragraph that begins with, "For this reason ..."

A Oh, yes. The point here was simply that statistics, the shortcoming in statistics at the time that this report was prepared was first of all that the shortcomings were that first of all there was grossly unequal quantity and quality of statistical information from different countries. Some countries had a large amount of information over a relatively long time and others had very little, except spotty, occasional, random checks.

A Well, yes. Yes, you want to know the rates of use in the population because that, in part, will determine how large an—how large a population must be observed in order to get meaningful figures. For example, if you have a population in which .5 per cent of the people use a particular substance and another population in which 50 per cent use, you stand a much better chance of discovering connection between use and health consequences in the population of which 50 per cent are users than you do in the one in which .5 per cent are users.

Q I’d like to go back to our discussion earlier on the neurological system and I would like you to explain to us the difference and the significance in the state of scientific knowledge between functional and structural effects of a substance such as cannabis.

A I’m sorry, this is in relation to which system?

Q The nervous system.

A Nervous system.

Q Excuse me.

A Yes. The point I was making earlier, and I think it bears repetition, is that what one is interested in is for most population purposes is the effect on function. Effect on structure represents often extreme cases. In other words, if you look for signs of cell loss in the brain, we know from the alcohol model that we’re there looking only at extreme cases. Overt brain damage produced by alcohol, loss of cells in specific parts of the brain is seen in severe alcoholics usually after many years of very heavy drinking and often presents difficulty in sorting out the influence of the alcohol, the influence of head injury while drunk, the influence of nutritional deficiencies. Those are cases which have practical importance in hospitals that treat such cases, but from a public health point of view, one is more interested in consequences that alter function, that alter performance.

Q Is it necessary, as a matter of pharmacology or medical science, for there to be structural changes in order for there to follow functional changes?

A No. No, functional changes can occur from altered cellular function without actual microscopically demonstrable cellular injury. Most cases of intoxication, for example, in which there is altered function, are not accompanied by any overt or demonstrable cell injury.

Q Is there anything else that you had wanted to add to that?

A Simply that this explains why the more recent studies have found alterations of performance, things such as memory, abstract reasoning, learning, at levels of intake of cannabis that in earlier studies were not described as producing any change, which was thought to depend upon cell damage, brain injury. For example, there’s a test called the trail-making test, which is taken as a sign of organic change in the brain and that has not shown alteration from which earlier investigators concluded that there was no evidence of brain injury by long-term cannabis use. But with more sensitive functional tests, it is possible to show differences which can outlast by a considerable time the actual period of cannabis use.

Q Okay. Now, in the course of the evidence in this case we have heard something about a course taken by one Western country, the Netherlands, with respect to the way that they deal with cannabis use. Are you familiar through the literature, through your work or as a member of either the Addiction Research Foundation World Health Organization committee or the World Health Organization committee with the—with whether or not there are statistical records of what rates of use may have been prior to the change in the Netherlands approach, both in the Netherlands and in other European countries? That’s a two-part question. Firstly, are you familiar and if so how and then we’ll get on to the balance.

A Yes, I have had occasion to read publications on that topic in preparation for the current World Health Organization committee report, and there are two points that I feel competent to make, that I think are worthy of consideration. One is that the committee did not have any available data on levels of use prior to the adoption by the Dutch authorities of their policy of non-punished sale in coffee houses, so that it would be unwarranted to attribute the relatively low rate of use in the Netherlands to that policy, since there’s nothing to compare it with. In other words, there were no previous figures so that one can say—that would enable one to say whether that policy had caused a change in the level of use.

Q Now, you said that one study showed that. Was that study one of many or was it a study that was inconsistent with other studies? Can you tell us that?

A No, it’s the only one I know of.

Q Okay. And I ask you that because I take it from your earlier evidence that rates of use can be important from a health point of view when one wants to assess and measure risks, is that a correct statement?

A Yes. The assessment of risk depends upon—or requires knowledge of two things: what percentage of -- or what level of use is necessary to produce a particular health problem; and secondly, how many people in the population of potential users do use and use at such levels. So that one needs to know not only the mechanistic connection between use and a particular consequence, but also how many people put themselves at risk of such a consequence by using the necessary levels.

Q From what you told us yesterday, Doctor, and from looking at your curriculum vitae, it is obvious that you have spent a considerable amount of time in your professional career studying the effects of alcohol.

A That’s correct.

Q And is there a particular disease or health problem that flows from alcohol use that you look for in coming to your conclusions on the prevalence of alcohol as a health factor?

A There are a number of diseases which correlate in a population with the level of alcohol use, but the one that has been most widely used is the morbidity and mortality rate from alcoholic cirrhosis of the liver.

Q Do you, as a result of your training and your experience, have knowledge of the rates of cirrhosis and morbidity due to cirrhosis of the liver from in the United States from 1900 to the present?

A Yes, there was a study by Klatscan (phonetic) which presented those data and which we have used in one of our own publications to illustrate the influence of other factors on the prevalence of cirrhosis and on the death rate from cirrhosis.

Q What I’m going to ask you to do would be to just give us the trends and identify any years that show a beginning and end of trends.

A From the beginning of the century up to about 1916, there was a slow, gradual decrease in the death rate from cirrhosis. Then in 1916 it dropped very abruptly. This was the time at which the American government and various state governments used—took advantage of existing interstate commerce regulations.

Q All I want you to do is to just give us the—

A The times.

Q -- times and—

A All right.

Q -- the results that you could see as a scientist without trying to tie them to any cause.

A All right. There was a sharp decrease beginning in 1916. It was maintained until 1932, and then after 1932 the death rate began to rise again fairly steadily, right up to about the late 1980’s.

Q You said there was a sharp decrease maintained from 1916 to 1932?

A Yes, the decrease, and I’m sorry I’m not explaining that very well, there was a sharp decrease. The low level which was achieved at about two years after 1916 was then maintained ‘til 1932 and after that, the level began to increase again.

Q And did—was there any change after 1945?

A I can cite Ontario figures for that.

Q All right.

A In the Province of Ontario, similar records of death rate from cirrhosis have been kept for an equivalent time, almost as long as the American ones, and the cirrhosis death rate dropped very sharply in 1932, 1930 to ‘32. It fell until 1939 or ‘40, then began to rise gradually and then post-war, from 1945 until about the late 1980’s rose much more rapidly for a period of about twenty years and then levelled off, and in the last few years has begun gradually to drop.

Q I’d like to direct your attention now to what we have been describing as the Hall report. It’s Exhibit 5 and it’s found in Volume 1 at tab 3. Do you have that before you?

A I have a copy of the Hall report.

Q A copy of the Hall report?

A Yes.

Q Okay. Would you direct your attention please to the executive summary, IX.

A Oh, in the report itself, is this what you’re referring to, executive summary?

Q Yes, page—

A There’s no Roman Numeral on the front of that.

Q It has a heading on the copy that I have that’s printed large for folks like me, so I’ll know where to go.

A Executive summary. Yes.

Q Do you have it?

A Yes. This is the page which begins, "The following is a summary of a major adverse health and psychological effects ..."

Q That’s right. Let’s just wait for my friend to find his copy.

A No, I would have no quarrel with any of the items listed here.

Q The next heading is Chronic Effects and it is divided into two categories, the first being major probable adverse effects and the second being major possible adverse effects. I would ask you to direct your attention firstly to that category listed as major probable adverse effects. Is there anything listed under that category which in your professional opinion is not consistent with the current state of scientific knowledge?

A No, I would agree with all of those.

Q The next heading is the major possible adverse effects of chronic heavy cannabis use which remain to be confirmed by further research and before you answer the question that I’ve already asked three times, can you tell the Court whether or not the Hall report defined the terms major possible adverse effects of chronic heavy cannabis use?

Q The major possible adverse effects of chronic heavy cannabis use are listed and you can see them. Does that—is there anything in the statements that are contained in that paragraph and the possible adverse effects that is not consistent with the current state of scientific knowledge?

A The only one that I think there is not a very compelling reason to continue entertaining as a real possibility is the leukemia among the offspring of women who used cannabis during pregnancy. If I may come back, Your Honour, to the question you asked, I think the next item, decline in occupational performance, may help clarify what I was trying to get across. There is ample observation, there are many observations that chronic heavy, and by that I mean daily and often multiple daily use, users who at that level do show impaired school performance, impaired work performance. What makes this a possible adverse effect is the possibility that the cannabis use is the cause rather than a coincidental phenomenon. The phenomenon is real, but the question that is being asked is the possibility that—of the causal link between the use and the observed behaviour.

Q Would it be fair to describe that as being the identification of an area where there is enough evidence to justify further investigation?

A Yes.

Q Nobody is suggesting that these things are proved.

A That’s right. I was just going to say, the things that are considered probable also warrant further investigation, but the possibles are ones in which there is enough uncertainty about a causal link but enough real concern about the event itself to warrant a look, a closer research to establish whether there is a causal link or not.

Q Doctor, did the 1994 World Health Organization committee on possible adverse—or adverse effects of cannabis, what was the correct name of that committee, please?

A It’s the Committee on Health Implications of Cannabis Use.

Q And can I just address that as the 1995 committee, is that all right? Did the 1995 committee deal with the possible adverse effect of an increased risk of leukemia among offspring exposed while in utero?

A It was discussed at the meeting and considered not sufficiently convincing to warrant being mentioned as a seriously-entertained risk in the report.

Q Overleaf, at page X, there are a list of high risk groups. Is there—are the listings of high risk groups contained on that page which include and in fact are described generally as adolescents, women of child-bearing age—no, let’s do it one at a time so it’s a little more fair, I think. Certain adolescents are identified in the Hall report as being at a high risk group. And two categories are identified there. Is that still consistent with the state of scientific and medical knowledge?

A Yes. I think that’s a valid statement.

Q Okay. Are there any other groups of adolescents that have been added in there since the Hall report?

A No, I don’t think so.

Q The next high risk group identified is women of child-bearing age; that describes two groups. Now, does the Hall report there still accurately reflect the state of scientific and medical knowledge?

A The 1995 committee agreed with the first one of the risks that may be consequent upon the mother smoking cannabis during pregnancy or during critical periods of fetal development. There was not much support for the idea that smoking of cannabis at the time of conception might pose a significant risk.

Q The third category is persons with pre-existing diseases and there are four subcategories of that. Does that list of categories still reflect the state of scientific and medical knowledge?

A They reflect the present state of medical and scientific concern, I wouldn’t say knowledge, because as I pointed out, the first one, individuals with cardiovascular diseases such as coronary artery disease, there’s really been no significant body of evidence presented that such individuals are, in fact, at risk. It’s a theoretical or a hypothetical risk.

Q Does that remain then a valid hypothesis?

A Mm hmm.

Q And the others?

A The others, I think, are consistent with current thought.

Q During the course of preparing for this case, I asked you—one of us asked you fairly recently if you would have available to you statistics relating to the current potency rates of cannabis and you obtained rates of potency for the Ontario region, is that right?

A Yes. That’s correct. These were from the Ontario Laboratory of Health Canada, the Health Protection Branch sample control office.

Q The numbers that you have produced come from 1975 through to 1996, is that right?

A That’s correct.

Q And the document that you have given to me, was that produced by you or was it produced by Health Canada?

A That was produced by Health Canada.

Q There are some handwritten numbers on the bottom of the document for the years 1995 and 1996.

A Yes, that’s my handwriting, because I have another document from Health Canada which gave figures separately for 1995 and ‘96, which included not only marihuana which is what the first sheet deals with, but also some information on cannabis resin and cannabis resin liquid, hash oil, and I took the marihuana data and added them to the list of the other marihuana data to make a single composite.

Q That second document you’re referring to is similar to the one I’m holding up now?

A That’s correct.

Q The only way that the first document has changed is that you have—

A Transcribed.

Q -- transported the information from it from part of the second document to the first?

A That’s correct.

Q For convenience sake.

MR. DOHM: I’m going to tender the two documents jointly as the next exhibit, please.

Q I’m going to ask you to just quickly deal with these, Doctor. Firstly, I’d ask you to direct your attention to the year 1975, and the average THC sampled for 1975 in Ontario appears to have been .5 per cent. Do you have a comment on that?

A Yes. That’s a bit on the low side, because the samples which I obtained from the R.C.M.P. for purposes of extraction to use in our own experiments had a content about 1 per cent. The samples varied from a little below to a little above 1 per cent, so the .5 per cent seems a bit too low and particularly since the high is shown only as 0.6 per cent, I suspect that that must have been a small number of samples that were not typical of what was generally available.

Q One might perhaps make a similar comment about the average recorded for 1976?

A Yes, which was even lower. But perhaps significantly, the higher point is much more in keeping with the range that we found, which was 1.2 per cent.

Q Are the balance of the figures then commensurate with your experience?

A Yes. The remaining figures are all fairly consistent with what I or my colleagues at the ARF or in other research labs have found and with the samples that NIDA was distributing for experimental use in the United States. They’re all for the next few years, they’re all around or above 1 per cent.

Q Up to about 1983, they stayed around 1 per cent then, I would take it?

A Yes.

Q I take your evidence to be. And there’s been a fairly steady growth with some anomalies in—since then?

A Yes. It’s—one shouldn’t be surprised by some anomalous values, occasional fluctuations, because this is after all seized material and it depends to a considerable extent on where that material came from, how the material was handled after seizure, how long it was between seizure and analysis and so on, so that some variation is not unexpected, but the overall trend has been upwards.

Q Anybody interested in playing with these numbers could develop some pretty strong multipliers by comparing, for example, the 1975 averages with the 1996 high, but that would be distorted?

A That would be distorted.

Q Simply, to look at it from about 1980 to currently, we have on the average an increase in potency of how many times?

A About four and a half times.

Q You have had an opportunity to read Exhibit 27, being the manuscript that Dr. Morgan presented during the course of his evidence?

A Oh, yes. Yes, I have.

Q Is there anything in the Zimmer and Morgan manuscript which would cause you to rethink your understanding of the combined scientific opinions expressed in the 1991 committee report, the Hall report or the 1995 report?

A I can’t think of anything that would cause me to change my interpretation. There were understandably differences of interpretation between Dr. Morgan’s handling of the data and my interpretation, but I don’t think that that in itself requires any change of assessment of the overall body of evidence summarized in the three reports.

Q Were you present yesterday when Dr. Morgan described cannabis as being—I’ll paraphrase here, but the most studied drug in the universe in the last twenty years?

A Yes, I heard that statement.

Q Do you agree with that?

A No, I don’t.

Q Why do you not agree with that?

A I—as part of my response to the Hall report, I was asked to write a critique for the British Journal of Addiction and my overall response was that it was a very good report, but that it was disappointing how little really fundamental new research there had been in the long interval since the previous WHO report, and in preparation or in justification of that statement, I counted all the publications listed in the cumulative index medicus, which is an index that lists virtually all of the publications in the world in the clinical and scientific literature—

Q Would that include editorials and opinions?

A Yes, it includes editorials and opinions, but principally it includes published studies and the total of all of them, that is studies and opinions and comments and so on, I graft in—on page 763 of this collection of commentaries on the Hall report there’s—

Q Do we have a copy of this for the Court? I do believe that Mr. Conroy has a copy.

Q You’re going to direct us, Doctor, to—

A Page 763.

Q And what do you have to tell us about what is now Exhibit 30 at page 763, Doctor?

A The graph, Figure 1, illustrates the number of publications dealing with cannabis each year from 1971 up to 1994, which was the time of the Hall report and the thing to pay attention to is the dramatic increase in the number of publications from a hundred and fifty in 1971 to between three hundred and fifty and four hundred in 1976 and then the sharp drop again after 1977 back down to a level of—that has drifted up and down between a hundred and a hundred and fifty a year, and the slight apparent increase from 1990 onwards is in part fictitious because in that year the index medicus adopted a different system of cross indexing, so that the same paper might be listed twice under two different indexing terms, so that the slightly increased figures after 1990 are probably not valid. The publication rate has, in fact, remained at or below a hundred and fifty a year.

Q So does that have any relationship to the current degree of—the current status of scientific and medical knowledge in the area in your view?

A Yes, I think it is directly related. I think that the reason that many questions remain unanswered is that there has not been the degree of stimulus to and support for research on these questions that would be necessary to answer many of the questions.

Q I’m getting to the point where I’m going to be summarizing Dr. Kalant’s evidence, so I haven’t been paying any attention to that device behind me and I’ll leave that to others. The—Doctor, there are main areas of concern that appear from your evidence to be common to the medical scientific community when it comes to the adverse consequences of cannabis.

A Yes.

Q Can you briefly just list those and summarize them?

A Yes. In terms of acute effects, I would