Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus

Background and PurposeWe evaluated the anti-emetic and anti-nausea properties of the acid precursor of (9)-tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models. Experimental ApproachWe investigated the effect of THCA on lithium chloride- (LiCl) induced conditioned gaping (nausea-induced behaviour) to a flavour, and context (a model of anticipatory nausea) in rats, and on LiCl-induced vomiting in Suncus murinus. Furthermore, we investigated THCA's ability to induce hypothermia and suppress locomotion [rodent tasks to assess cannabinoid(1) (CB1) receptor agonist-like activity], and measured plasma and brain THCA and THC levels. We also determined whether THCA's effect could be blocked by pretreatment with SR141716 (SR, a CB1 receptor antagonist). Key ResultsIn rats, THCA (0.05 and/or 0.5mgkg(-1)) suppressed LiCl-induced conditioned gaping to a flavour and context; the latter effect blocked by the CB1 receptor antagonist, SR, but not by the 5-hydroxytryptamine-1A receptor antagonist, WAY100635. In S.murinus, THCA (0.05 and 0.5mgkg(-1)) reduced LiCl-induced vomiting, an effect that was reversed with SR. A comparatively low dose of THC (0.05mgkg(-1)) did not suppress conditioned gaping to a LiCl-paired flavour or context. THCA did not induce hypothermia or reduce locomotion, indicating non-CB1 agonist-like effects. THCA, but not THC was detected in plasma samples. Conclusions and ImplicationsTHCA potently reduced conditioned gaping in rats and vomiting in S.murinus, effects that were blocked by SR. These data suggest that THCA may be a more potent alternative to THC in the treatment of nausea and vomiting.