Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ(9) -tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats.

BACKGROUND AND PURPOSE: The cannabinoid 1 (CB1 ) receptor inverse agonists/antagonists, rimonabant (SR141716, SR) and AM251, produce nausea and potentiate toxin-induced nausea by inverse agonism (rather than antagonism) of the CB1 receptor. Here, we evaluated two phytocannabinoids, cannabidivarin (CBDV) and Δ(9) -tetrahydrocannabivarin (THCV), for their ability to produce these behavioural effect characteristics of CB1 receptor inverse agonism in rats.

EXPERIMENTAL APPROACH: In experiment 1, we investigated the potential of THCV and CBDV to produce conditioned gaping (measure of nausea-induced behaviour) in the same manner as SR and AM251. In experiment 2, we investigated the potential of THCV and CBDV to enhance conditioned gaping produced by a toxin in the same manner as CB1 receptor inverse agonists.

KEY RESULTS: SR (10 and 20 mg·kg(-1) ) and AM251 (10 mg·kg(-1) ) produced conditioned gaping; however, THCV (10 or 20 mg·kg(-1) ) and CBDV (10 or 200 mg·kg(-1) ) did not. At a subthreshold dose for producing nausea, SR (2.5 mg·kg(-1) ) enhanced lithium chloride (LiCl)-induced conditioned gaping, whereas Δ(9) -tetrahydrocannabinol (THC, 2.5 and 10 mg·kg(-1) ), THCV (2.5 or 10 mg·kg(-1) ) and CBDV (2.5 or 200 mg·kg(-1) ) did not; in fact, THC (2.5 and 10 mg·kg(-1) ), THCV (10 mg·kg(-1) ) and CBDV (200 mg·kg(-1) ) suppressed LiCl-induced conditioned gaping, suggesting anti-nausea potential.

CONCLUSIONS AND IMPLICATIONS: The pattern of findings indicates that neither THCV nor CBDV produced a behavioural profile characteristic of CB1 receptor inverse agonists. As well, these compounds may have therapeutic potential in reducing nausea.