Effects on variable-interval performance in rats of delta 9-tetrahydrocannabinol and cannabidiol, separately and in combination.

The objective of this investigation was to study the influence of the dose ratio between cannabidiol (CBD) and delta 9-tetrahydrocannabinol (delta 9-THC) on the effects of mixtures of the two cannabinoids on variable-interval (VI) schedule performance in rats. The effect on VI performance of a control solution, 10 mg/kg CBD, delta 9-THC (0.125, 0.5, 2 and 8 mg/kg) and a mixture of 10 mg/kg CBD + delta 9-THC (0.125, 0.5, 2 and 8 mg/kg) was investigated in 10 rats, with a different sequence of treatments for each animal. The results were expressed in terms of rate-dependency. The control solution, 10 mg/kg CBD, 0.125 mg/kg delta 9-THC, or 10 mg/kg CBD + delta 9-THC (0.125 mg/kg) did not cause rate-dependent effects. Delta 9-THC (0.5 and 2 mg/kg) produced rate-dependent effects. The dose of 8 mg/kg delta 9-THC almost suppressed responding. The combination of 10 mg/kg CBD + 0.5 mg/kg delta 9-THC did not cause rate-dependent effects but produced a response pattern similar to that obtained with 0.125 mg/kg delta 9-THC. At these doses CBD antagonized delta 9-THC. The combination of 10 mg/kg CBD + 2 mg/kg delta 9-THC caused rate-dependent effects. The rate-dependent regression line determined by this mixture was parallel to that produced by 2 mg/kg delta 9-THC. However, the lower intercept of the mixture with the y axis suggested potentiation of the depressant effects of delta 9-THC by CBD.(ABSTRACT TRUNCATED AT 250 WORDS)