The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice

Authors


Professor RG Pertwee, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. E-mail: rgp@abdn.ac.uk

Abstract

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

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