Pharmacological Specificity of the Discriminative Stimulus Effects of Delta(9)-Tetrahydrocannabinol in Rhesus-Monkeys

Abstract

Delta(9)-Tetrahydrocannabinol (Delta 9-THC) discrimination has been used as an animal model of cannabis intoxication in humans. While numerous studies have examined the discriminative stimulus effects of cannabinoids in rats and pigeons, studies with monkeys have been rare. In the present study, rhesus monkeys, trained to discriminate Delta(9)-THC from vehicle in a two-lever drug discrimination procedure, were tested with a variety of psychoactive drugs, including cannabinoids as well as drugs from other classes. Results showed that Delta(9)-THC discrimination showed pharmacological specificity, in that none of the non-cannabinoid drugs fully substituted for Delta(9)-THC. In contrast, the classical cannabinoids, Delta(9)-THC and Delta(8)-THC, and the novel cannabinoids, WIN 55212-2 and 1-butyl-2-methyl-3-(1-naphthoyl)indole, produced full dose-dependent substitution for Delta(9)-THC in ail monkeys. A heptyl indole derivative failed to substitute for Delta(9)-THC, but it also did not displace [H-3] CP 55940 from its binding site. These findings are consistent with those of previous cannabinoid discrimination studies with rats and suggest that results of Delta(9)-THC discrimination studies in rhesus monkeys may be predictive of the subjective effects of cannabinoid drugs in humans