Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ9-tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats

Background and PurposeThe 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 (9)-tetrahydrocannabivarin (THCV), for their ability to produce these behavioural effect characteristics of CB1 receptor inverse agonism in rats. Experimental ApproachIn 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 ResultsSR (10 and 20mgkg(-1)) and AM251 (10mgkg(-1)) produced conditioned gaping; however, THCV (10 or 20mgkg(-1)) and CBDV (10 or 200mgkg(-1)) did not. At a subthreshold dose for producing nausea, SR (2.5mgkg(-1)) enhanced lithium chloride (LiCl)-induced conditioned gaping, whereas (9)-tetrahydrocannabinol (THC, 2.5 and 10mgkg(-1)), THCV (2.5 or 10mgkg(-1)) and CBDV (2.5 or 200mgkg(-1)) did not; in fact, THC (2.5 and 10mgkg(-1)), THCV (10mgkg(-1)) and CBDV (200mgkg(-1)) suppressed LiCl-induced conditioned gaping, suggesting anti-nausea potential. Conclusions and ImplicationsThe 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.