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

• Published in: British journal of pharmacology Vol. 170; no. 3; pp. 641 - 648
• Main Authors: Rock, E M, Kopstick, R L, Limebeer, C L, Parker, L A
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2013
• Subjects: Animals; Antiemetics - blood; Antiemetics - pharmacology; Behavior, Animal - drug effects; Body Temperature Regulation - drug effects; Brain - drug effects; Brain - metabolism; Cannabinoid Receptor Antagonists - pharmacology; CB1 receptor; conditioned gaping; Disease Models, Animal; Dronabinol - analogs & derivatives; Dronabinol - blood; Dronabinol - pharmacology; Lithium Chloride; Male; Motor Activity - drug effects; Nausea - blood; Nausea - chemically induced; Nausea - prevention & control; Nausea - psychology; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - drug effects; Receptor, Cannabinoid, CB1 - metabolism; Research Papers; Shrews; SR141716; THC; THCA; Time Factors; vomiting; Vomiting - blood; Vomiting - chemically induced; Vomiting - prevention & control; Vomiting - psychology; conditioned gaping; SR141716; CB1 receptor; THCA; THC; vomiting
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.12316

Background and Purpose We evaluated the anti‐emetic and anti‐nausea properties of the acid precursor of Δ9‐tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models. Experimental Approach We 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 cannabinoid1 (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 Results In rats, THCA (0.05 and/or 0.5 mg·kg−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 0.5 mg·kg−1) reduced LiCl‐induced vomiting, an effect that was reversed with SR. A comparatively low dose of THC (0.05 mg·kg−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 Implications THCA 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.