Background and purpose: The phytocannabinoid, Δ9-tetrahydrocannabivarin (THCV), can block cannabinoid CB1 receptors. This investigation explored its ability to activate CB2 receptors, there being evidence that combined CB2 activation/CB1 blockade would ameliorate certain disorders.
Experimental approach: We tested the ability of THCV to activate CB2 receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB2 (hCB2) receptors; (ii) it stimulated [35S]GTPγS binding to hCB2 CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB1 or CB2 receptor antagonist.
Key results: THCV inhibited cyclic AMP production by hCB2 CHO cells (EC50= 38 nM), but not by hCB1 or untransfected CHO cells or by hCB2 CHO cells pre-incubated with pertussis toxin (100 ng·mL−1) and stimulated [35S]GTPγS binding to hCB2 CHO and mouse spleen membranes. THCV (0.3 or 1 mg·kg−1 i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB2 receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg·kg−1, and in both phases of this test at 5 mg·kg−1; these effects of THCV appeared to be CB1 and CB2 receptor mediated.
Conclusions and implications: THCV can activate CB2 receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB1 and/or CB2 receptor activation.
This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x