>> even includes at least one CB1R antagonist <<
er......... well.......
Br J Pharmacol. 2013 Jul 31. doi: 10.1111/bph.12322. [Epub ahead of print]
Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and ?9 -tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats.
Rock EM, Sticht MA, Duncan M, Stott C, Parker LA.
Department of Psychology and Neuroscience Graduate Program, University of Guelph, Guelph, Ontario, Canada.
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 ?9 -tetrahydrocannabivarin (THCV) for their ability to produce these behavioural effects characteristic 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 LiCl-induced conditioned gaping, whereas ?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. |
