title: The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bolognini
authors.forename: Barbara
authors.initials: B
authors.lastname: Costa
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.forename: Francesca
authors.initials: F
authors.lastname: Comelli
authors.forename: Pietro
authors.initials: P
authors.lastname: Marini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Daniela
authors.initials: D
authors.lastname: Parolaro
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Ross
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Gauson
authors.forename: Maria G
authors.initials: MG
authors.lastname: Cascio
authors.forename: Roger G
authors.initials: RG
authors.lastname: Pertwee
mesh_terms: D000818:Animals; D016466:CHO Cells; D002461:Cell Line, Transformed; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000150:complications / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
chemical_list: D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C003403:tetrahydrocannabivarin 9; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013759:Dronabinol; D000242:Cyclic AMP