Delta 9-tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication

Studies of the discriminative stimulus effects of delta 9-THC are reviewed. The results of generalization studies in rats trained to discriminate delta 9-THC from nondrug provide evidence for the pharmacological specificity of the delta 9-THC stimulus. Only cannabinoid analogs of delta 9-THC substitute fully for delta 9-THC. The ability of cannabinoids to produce delta 9-THC-like discriminative stimulus effects appears to predict delta 9-THC- or marihuana-like effects in humans. Of the 11 cannabinoids tested in rats and humans, the results with 9 are in complete concordance, and results with the remaining two are inconclusive. This concordance provides evidence for the validity of delta 9-THC discrimination in rats as an animal model of cannabis intoxication. A number of natural and synthetic cannabinoids have delta 9-THC-like discriminative stimulus effects. They represent a 5,600-fold range of relative potencies. Micromolar potency estimates and relative potencies to delta 9-THC for these compounds are provided. Correlations between these values and potencies for cellular actions of cannabinoids can be used to establish the neural substrates of cannabis intoxication.