The object of the experiment was to verify whether cannabidiol (CBD) reduces the anxiety provoked by delta 9-THC in normal volunteers, and whether this effect occurs by a general block of the action of delta 9-THC or by a specific anxiolytic effect. Appropriate measurements and scales were utilized and the eight volunteers received, the following treatments in a double-blind procedure: 0.5 mg/kg delta 9-THC, 1 mg/kg CBD, a mixture containing 0.5 mg/kg delta 9-THC and 1 mg/kg CBD and placebo and diazepam (10 mg) as controls. Each volunteer received the treatments in a different sequence. It was verified that CBD blocks the anxiety provoked by delta 9-THC, however this effect also extended to marihuana-like effects and to other subjective alterations induced by delta 9-THC. This antagonism does not appear to be caused by a general block of delta 9-THC effects, since no change was detected in the pulse-rate measurements. Several further effects were observed typical of CBD and of an opposite nature to those of delta 9-THC. These results suggest that the effects of CBD, as opposed to those of delta 9-THC, might be involved in the antagonism of effects between the two cannabinoids.

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The interaction of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabinol (CBN) was studied in man. Five male volunteers were given placebo, 50 mg CBN, 25 mg Δ⁹-THC, 12.5 mg Δ⁹-THC + 25 mg CBN, and 25 mg Δ⁹-THC + 50 mg CBN (orally). Administrations were spaced 1 week apart. With physiological measures, Δ⁹-THC produced an increase in heart rate while CBN did not. When combined, no change of the Δ⁹-THC effect occurred. No changes occurred on the electrocardiogram, blood pressure, or body temperature. With psychophysical measures no changes occurred in pain thresholds or skin sensitivity as a function of drug treatment. In time estimates of the passage of 1 minute, Δ⁹ -THC alone produced underestimates of the passage of 1 minute and CBN alone had no effect. In combination the two drugs had a tendency to produce significant overestimates and underestimates of the passage of 1 minute. On a 66-item adjective-pair drug reaction scale, the volunteers reported feeling drugged, drunk, dizzy, and drowsy under the Δ⁹ -THC condition, but not under the CBN condition. With combined drug treatment, volunteers reported feeling more drugged, drunk, dizzy, and drowsy than under the Δ⁹-THC condition alone. None of the drug treatments produced significant changes on other items which included items on perception, emotion, cognition and sociability. It appears that CBN increases the effect of Δ⁹-THC on some aspects of physiological and psychological processes, but that these effects are small and cannot account for the greater potency which has been reported when plant material is used.

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.