Effects of Marihuana in Laboratory Animals and in Man

Abstract

1The pharmacological potencies of the resins from three different samples of Brazilian marihuana (A, B and C) were determined through corneal areflexia in rabbits, decrease of spontaneous motor activity and induction of catatonia in mice, and decrease of rope climbing performance of rats. 2 The A9 -tetrahydrocannabinol (A9 THC) content of the marihuanas, measured by gas chromatography, was 0.82, 2.02 and 0.52%, respectively, for samples A, B and C. Approximately 2% cannabinol was present in samples A and B whereas the content of cannabidiol was approximately 0.1%. 3 The petroleum ether extraction of the samples A, B and C yielded, respectively, 12.06, 14.56 and 4.26% of resin. 4 In all animal tests resin B was nearly twice as active as resin A, whereas C was the weakest. 5 The smoke of the marihuana samples was inhaled by 33 human subjects, under a double-blind standardized procedure. Pulse rate, a time production task and an evaluation of psychological effects were recorded. 6 The smoke of 250 mg of sample B provoked disruption of the time production task, increased pulse rate, and induced strong psychological reactions in four of the six subjects who received it. Similar effects, although slightly smaller, were obtained with 500 mg of sample A. On the other hand, 500 mg of sample C did not differ from placebo. 7 It is suggested that it is possible by means of animal tests to predict the potency of a marihuana sample in man. 8 In parallel experiments, A9-THC was administered to other human subjects and to laboratory animals in a manner similar to that in which the marihuana samples were administered. 9 Comparison of the results between the marihuanas and A9 -THC showed that in man and in the laboratory animals marihuanas A and B induced effects two to four times greater than expected from their A9 -THC content.

SEDATIVE ACTIVITY OF CANNABIS IN RELATION TO ITS Δ‘‐trans‐TETRAHYDROCANNABINOL AND CANNABIDIOL CONTENT

“…The results agree with those from our cataleptic work with THC, herb and extracts (Fairbairn & Pickens, 1981) and with those of Carlini et al, ( 1974) (7) (7) (7)…”

“…I have attempted to discover whether the 0007-1188/81/040649-08 $01.00 sedative action of 'whole' herb and extracts is related to their THC contents measured by gas-liquid chromatography (g.l.c. ) analysis, by the method of Fairbairn & Liebmann (1973), as previous work has shown that the herb and extracts are at least two or four times more active than one would expect from their THC content (Carlini et al, 1974;Fairbaim & Pickens, 1981). The effect of aspirin on sedative action and its reversal by prostaglandin E2 (PGE2) has also been determined since previous work showed that the cataleptic effects of herb and extracts were antagonized by aspirin and restored by PGE2 (Fairbaim & Pickens, 1979;1981).…”

“…Extracts of cannabis and THC also have a sedative effect in mice, measured as a decrease in spontaneous motor activity (Carlini, Karniol, Renault & Schuster, 1974). I have used Tuck No.…”

ACTIVITY OF CANNABIS IN RELATION TO ITS Δ‘‐trans‐TETRAHYDROCANNABINOL CONTENT

“…and because of the large biological variation which accompanies cannabis work (Carlini et al, 1974) and which is confirmed from our data (see Table 1) where the lowest score was zero (from a non-reacting mouse) and the highest score 270. One way of overcoming the difficulty is to study those factors which cause the 'day to day' variance and this we have done for the ring test (Fairbaim & Pickens, 1980).…”

“…Similarly in animals it has never been possible to explain all the effects of the crude material in terms of THC alone (Mechoulam, Ben-Zvi, Shani, Zemler, Levy, Edbury & Grunfeld, 1972;Carlini, Masur, Karniol & Leite, 1972). However, in both man (Isbell, 1971;Carlini, Kamiol, Renault & Schuster, 1974) and in animals (Carlini et al, 1974) the activity of the herb and extracts is proportional to their THC contents. In an attempt to establish the ratio of the content of THC to the biological activity we have made use of the fact that the cataleptic effect of very small doses of THC given orally can be measured in mice and that the cataleptic effect is dependent on the availability of prostaglandins E2 (PGE2) (Fairbairn & Pickens, 1979;.…”