Annex A - Preliminary Summary of Commission Cannabis and Alcohol Experiments

Cannabis

The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs - 1972

2. Cannabis and Its Effects

ANNEX A

PRELIMINARY SUMMARY OF COMMISSION CANNABIS AND ALCOHOL EXPERIMENTS

The Commission has undertaken four experimental projects concerning the acute effects of cannabis and, in some cases, of alcohol on humans. These experiments were designed to fill gaps in the literature in certain critical areas. We were especially interested in the acute effects of cannabis on the functioning of 'normal' users at doses that are socially relevant for Canada today. The purpose of this summary is to supplement the presentation of the findings in the text. The reader is referred to the previous sections of this chapter for discussion, conclusions, general perspective with respect to past literature, current projects, and areas of future attention related to these research areas. Of particular relevance is the previous discussion of dose. This preliminary summary deals with the major aspects of our experimental program. Although the primary results of these experiments have been established. further comprehensive analysis is underway, and a final detailed description of the experiments (with complete statistical procedures"') will appear in a supplement to this report.

One experiment was designed to provide a quantitative comparison of the effects of synthetics, ' THC and natural marijuana in humans, and to establish dose- and time-response relationships with these substances on a number of physiological and psychological measures.' A second experiment sought to determine the effects of cannabis and alcohol on some automobile driving tasks.'5' The purpose of the third study was to examine the effects of cannabis, alcohol, and their combination on psychornotor tracking performance."' The fourth project was concerned with the effects of cannabis on visual signal detection (attention and vigilance) and, secondarily, the recovery of visual acuity after exposure to glare.

"" In all four experiments, subjects were paid volunteers, mostly university students. The subjects were psychiatrically screened, and those with detectable pathology were excluded. Subjects were all experienced with alcohol and cannabis, but not heavy users of either, and had had minimal experience with other psychoactive drugs. No heavy tobacco smokers were included.

A common supply of marijuana, kept frozen under nitrogen. was used for all experiments. Each cigarette was packaged in a nitrogen-filled container and kept frozen until being administered to the subject. Many other conditions of our experiments were standardized and were common to all these proj ects, thereby allowing considerable between-study comparison and a common data base for certain variables.

EXPERIMENT 1: A COMPARISON OF A' THC AND MARIJUANA EFFECTS IN HUMANS"

A variety of chemical and pharmacological data support the contentio . n that A I THC is the principal active constituent in cannabis (at least in part via metabolites). There has been an almost complete reliance on the @@` THC

content of cannabis to provide the basis for standardizing various samples and comparing the results of different experimental and social studies, even though the pharmacological equivalence of different cannabis preparations accomplished by this process has not been adequately tested. In fact, no direct quantitative comparison of the effects of relatively pure isolated or synthetic THC and crude cannabis preparations or other cannabinoids has previously been conducted in humans. Furthermore, there are increasing suggestions in the literature that a single isomer of THC may not account for all of the major effects of cannabis.

This project was designed to compare the effects of high purity synthetic AI THC with natural marijuana as a further step in determining the active constituents of marijuana in humans. Of comparable interest, acute dose- and time-response functions were obtained on a number of subjective, behavioural and physiological measures.

Procedure

Fourteen male subjects each attended eight weekly experimental sessions which were six hours in duration. Each subject was assigned a specific time and day of the week for all sessions. After a no-drug practice session, seven experimental conditions were given to all subjects in a double-blind Latin square design as follows: Placebo (extracted alfalfa); three levels of marijuana (9,21, and 88 mcgA' THC per kg body weight, giving average doses of 0.7, 1.5, and 6.2 mg A 9 THC); three equivalent doses of high-purity synthetic A9 THC on extracted alfalfa. Subjects always received a standard 0.4 gram cigarette containing a varying ratio of cannabis to extracted alfalfa material, as appropriate to the condition. The highest marijuana dose was intended to approximate the effects typically sought by regular cannabis users in North America. The lowest quantity was given in an attempt to establish a threshold dose, as suggested by pilot studies and evidence in the literature.

Considerable problems were encountered in obtaining adequate quantitative cannabinoid content figures on the two drug samples. Delta-9 THC values obtained from a variety of authorized laboratories in Canada and the United States differed in the extreme by several hundred per cent. Discrepancies in THC content estimates were finally resolved in an apparently satisfactory manner and the experimental work was begun.IPJ Delta-9 THC made up more than 90% of the cannabinoids in the marijuana sample. Consequently, the study cannot provide information regarding cannabinoids other than THC or possible cannabinoid interactions.

The smoking technique employed was standardized and closely controlled. A five second smoke inhalation was followed by a brief air inhalation period, and the smoke was retained in the lungs for a total of 25 seconds. A 20second rest period followed exhalation. This cycle was repeated until the entire cigarette was consumed including the butt. On the average, this took about ten minutes. On the basis of available evidence, it would appear that with our standard administration technique nearly all of the THC delivered in the smoke was absorbed. Subsequent to the pharmacological studies. 24 cigarettes, comparable to those used in the main experiment, were smoked by machine using the same timing schedule."" This experiment suggested that

the actual THC delivered to the subjects in the smoke was 53% and 481TI, of' I a cigarettes, r

that originally in the marijuana and THC-alfalf espectively. Consequently. in spite of the fact that the cigarettes in the THC and marijuana conditions contained matched quantities ofA' THC, there was apparently a 10% difference in the dose delivered. This discrepancy has been taken into'account in the following discussion.

On the basis of a review of the literature and preliminary laboratory work. a condensed test battery was constructed to assess most of the major acute cannabis effects previously indicated and to attempt to tap some of the prominent features of the 'high' as reported by users. The time required to complete the test battery wasjust over two hours, and with the exception of a few measures, the battery was repeated four hours after smoking. The various tests were given in the same order in all conditions. While there are certain practical and statistical advantages to this fixed procedure, it means that the differential sensitivity of the various measures to cannabis effects is confounded with time-response effects. Certain tests, given near the end of the battery, in which little or no change was detected may have shown changes if they had been given immediately after the drug administration. In most cases, however, the major part of the 'high' resulting from the highest dose lasted throughout the first testing period of the test battery.

The following measures were included in the test battery: heart pulse rate; salivation; conjunctival injection (reddening of the eyes); finger temperature; tonic skin conductance of the fingers (a measure of sweat gland activity); visual imagery (visual impressions with eyes closed in total darkness); autokinetic movement (apparent movement of a stationary point of light in an otherwise dark room); two-flash fusion threshold (the shortest time interval between two brief light flashes at which they are still perceived as two),- spiral after-effect (the duration of visual distortion which follows viewing a rotating spiral); time production (the ability to specify 15-second intervals during a distracting task) and time estimation (the perceived duration of the visual imagery, painting and speech tasks); one-minute sustained finger grip; maximum momentary strength of hand grip; maximum tapping speed (the total number of taps made with a hand-held pencil-like stylus in a one-minute period); short-term serial position memory (after a series of nine different digits were presented, a tenth digit was given and the subject was asked to note the position in which that number appeared in the original series); digit symbol substitution (the number of correct code and symbol substitutions written during a 90-second interval); finger painting (scored with respect to a variety of psychiatric, graphic, and aesthetic variables); speech sample (a three-minute description of TAT pictures data not yet fully analysed); Clyde Mood Sea JeI15 (a questionnaire which measures six different mood dimensions)@ Royal Highness Inventory (RHI) (a multiple-choice questionnaire des igned to assess some subjective effects of cannabis); How High Scale (a rating form on which the subject rates his usual "high" and how "high" he currently is on a scale between "not high" and the "highest you have ever been", successive points are recorded by the subject on a single graph at several times throughout the experimental session so that a time-response curve of the intensity of the subjective "high" is plotted); post-Session Questionnaire and Morning-After Questionnaire (a variety of items relating

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Canadian Government Commission of Inquiry - Cannabis Report