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

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.

• Authors: E M Rock, R L Kopstick, C L Limebeer, L A Parker
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 170 Issue 3 Pg. 641-8 (Oct 2013) ISSN: 1476-5381 [Electronic] England
• PMID: 23889598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The British Pharmacological Society.

Chemical References

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

Topics

• Animals
• Antiemetics (blood, pharmacology)
• Behavior, Animal (drug effects)
• Body Temperature Regulation (drug effects)
• Brain (drug effects, metabolism)
• Cannabinoid Receptor Antagonists (pharmacology)
• Disease Models, Animal
• Dronabinol (analogs & derivatives, blood, pharmacology)
• Lithium Chloride
• Male
• Motor Activity (drug effects)
• Nausea (blood, chemically induced, prevention & control, psychology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Cannabinoid, CB1 (drug effects, metabolism)
• Shrews
• Time Factors
• Vomiting (blood, chemically induced, prevention & control, psychology)