The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice.
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.
Bolognini
Daniele
D
Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Costa
Barbara
B
Maione
Sabatino
S
Comelli
Francesca
F
Marini
Pietro
P
Di Marzo
Vincenzo
V
Parolaro
Daniela
D
Ross
Ruth A
RA
Gauson
Lisa A
LA
Cascio
Maria G
MG
Pertwee
Roger G
RG
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
D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C003403:tetrahydrocannabivarin 9; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013759:Dronabinol; D000242:Cyclic AMP