Interactions between THC and cannabidiol in mouse models of cannabinoid activity

Rationale: Interest persists in characterizing potential interactions between Delta(9)-tetrahydocannabinol (THC) and other marijuana constituents such as cannabidiol (CBD). Such interactions may have important implications for understanding the long-term health consequences of chronic marijuana use as well as for attempts to develop therapeutic uses for THC and other CB1 agonists. Objectives: We investigated whether CBD may modulate the pharmacological effects of intravenously administered THC or inhaled marijuana smoke on hypo-activity, antinociception, catalepsy, and hypothermia, the well characterized models of cannabinoid activity. Results: Intravenously administered CBD possessed very little activity on its own and, at a dose equal to a maximally effective dose of THC (3 mg/kg), failed to alter THC's effects on any measure. However, higher doses of CBD (ED50 = 7.4 mg/kg) dose-dependently potentiated the antinociceptive effects of a low dose of THC (0.3 mg/ kg). Pretreatment with 30 mg/ kg CBD, but not 3 mg/ kg, significantly elevated THC blood and brain levels. No interactions between THC and CBD were observed in several variations of a marijuana smoke exposure model. Either quantities of CBD were applied directly to marijuana, CBD and THC were both applied to placebo plant material, or mice were pretreated intravenously with 30 mg/ kg CBD before being exposed to marijuana smoke. Conclusions: As the amount of CBD found in most marijuana strains in the US is considerably less than that of THC, these results suggest that CBD concentrations relevant to what is normally found in marijuana exert very little, if any, modulatory effects on CB1-receptor-mediated pharmacological effects of marijuana smoke.