Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity

Background: Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Delta(9)-tetrahydrocannabinol's (THC) effects. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism. Methods: In Experiment 1, CBD (0, 10 or 30 mg/kg) was administered 15 min before THC (0, 1.8, 3.2, 5.6 or 10 mg/kg), and rats were tested for antinociception and locomotion 15-360 min post-THC injection. In Experiments 2 and 3, CBD (30 mg/kg) was administered 13 h or 15 min before THC (1.8 mg/kg); rats were tested for antinociception and locomotion 30-480 min post-THC injection (Experiment 2), or serum samples were taken 30-360 min post-THC injection to examine CBD modulation of THC metabolism (Experiment 3). Results: In Experiment 1, CBD alone produced no antinociceptive effects, while enhancing THC-induced paw pressure but not tail withdrawal antinociception 4-6 h post-THC injection. CBD alone increased locomotor activity at 6 h post-injection, but enhanced THC-induced hypolocomotion 4-6 h post-THC injection, at lower THC doses. There were no sex differences in CBD-THC interactions. In Experiments 2 and 3, CBD did not significantly enhance THC's effects when CBD was administered 13 h or 15 min before THC; however, CBD inhibited THC metabolism, and this effect was greater in females than males. Conclusions: These results suggest that CBD may enhance THC's antinociceptive and hypolocomotive effects, primarily prolonging THC's duration of action; however, these effects were small and inconsistent across experiments. CBD inhibition of THC metabolism as well other mechanisms likely contribute to CBD-THC interactions on behavior.