The Plant Cannabinoid Delta9-tetrahydrocannabivarin Can Decrease Signs of Inflammation and Inflammatory Pain in Mice

Br J Pharmacol. 2010 Jun;160(3):677-87. doi: 10.1111/j.1476-5381.2010.00756.x.

Abstract

Background and purpose: The phytocannabinoid, Delta(9)-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors. This investigation explored its ability to activate CB(2) receptors, there being evidence that combined CB(2) activation/CB(1) blockade would ameliorate certain disorders.

Experimental approach: We tested the ability of THCV to activate CB(2) receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB(2) (hCB(2)) receptors; (ii) it stimulated [(35)S]GTPgammaS binding to hCB(2) 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 CB(1) or CB(2) receptor antagonist.

Key results: THCV inhibited cyclic AMP production by hCB(2) CHO cells (EC(50)= 38 nM), but not by hCB(1) or untransfected CHO cells or by hCB(2) CHO cells pre-incubated with pertussis toxin (100 ng.mL(-1)) and stimulated [(35)S]GTPgammaS binding to hCB(2) 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 CB(2) 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 CB(1) and CB(2) receptor mediated.

Conclusions and implications: THCV can activate CB(2) receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB(1) and/or CB(2) receptor activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line, Transformed
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Dronabinol / therapeutic use
  • Edema / drug therapy
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Male
  • Membranes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pain / complications
  • Pain / drug therapy*
  • Pain Measurement / methods
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / agonists*
  • Spleen / drug effects
  • Spleen / metabolism

Substances

  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • tetrahydrocannabivarin 9
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Dronabinol
  • Cyclic AMP