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

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

Author information

1
Department of Psychology, University of Guelph, Guelph, ON, Canada.

Abstract

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

PMID:
23889598
PMCID:
PMC3792001
DOI:
10.1111/bph.12316
[Indexed for MEDLINE]
Free PMC Article

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