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

Br J Pharmacol. 2013 Oct;170(3):641-8. doi: 10.1111/bph.12316.


Background and purpose: We evaluated the anti-emetic and anti-nausea properties of the acid precursor of Δ(9) -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.

Keywords: CB1 receptor; SR141716; THC; THCA; conditioned gaping; vomiting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiemetics / blood
  • Antiemetics / pharmacology*
  • Behavior, Animal / drug effects*
  • Body Temperature Regulation / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Cannabinoid Receptor Antagonists / pharmacology
  • 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
  • Shrews
  • Time Factors
  • Vomiting / blood
  • Vomiting / chemically induced
  • Vomiting / prevention & control*
  • Vomiting / psychology


  • Antiemetics
  • Cannabinoid Receptor Antagonists
  • Cnr1 protein, rat
  • Receptor, Cannabinoid, CB1
  • Dronabinol
  • delta(9)-tetrahydrocannabinolic acid
  • Lithium Chloride