Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol in rats and shrews

Rationale The interaction between two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), which have been reported to act as a 5-hydroxytryptamine 1A (5-H[T.sub.1A]) agonist and antagonist, respectively, was evaluated. Objective To evaluate the potential of CBG to reverse the anti-nausea, anti-emetic effects of CBD. Materials and methods In experiment 1, rats were pre-treated with CBG (0.0, 1, 5, and 10 mg/kg, ip), 15 min prior to being treated with CBD (experiment 1a: VEH or 5 mg/kg, ip) or 8-OH-DPAT (experiment 1b: VEH or 0.01 mg/kg, ip). Thirty minutes later, all rats received a pairing of 0.1% saccharin solution and LiCl (20 ml/kg of0.15 M, ip). Seventy-two hours later, the rats received a drug-free taste reactivity test with saccharin to evaluate the effects of the treatments on the establishment of conditioned gaping reactions (a model of nausea). As well, conditioned saccharin avoidance was measured. In experiment 2, Suncus murinus were injected with CBG (5 mg/kg, ip) or VEH 15 min prior to CBD (5 mg/kg) or VEH and 30 min later were injected with LiCl (60 ml/kg of 0.15 M, i.p.), and the number of vomiting episodes were measured. Results CBD (5 mg/kg) suppressed conditioned gaping in rats and vomiting in shrews, which were reversed by pretreatment with all doses of CBG. CBG also prevented the anti-nausea effects of 8-OH-DPAT. Conclusions Interactions between moderate doses of CBG and CBD may oppose one another at the 5-H[T.SUB.1A] receptor in the regulation of nausea and vomiting. Keywords Nausea * Vomiting * Cannabinoids * Cannabigerol * Cannabidiol * Serotonin * 5-H[T.sub.1A] * Phytocannabinoid