Cannabidiol prevents infarction via the non-CB1 cannabinoid receptor mechanism.
Cannabidiol, a non-psychoactive constituent of cannabis, has been reported as a neuroprotectant. Cannabidiol and Delta(9)-tetrahydrocannabinol, the primary psychoactive constituent of cannabis, significantly decreased the infarct volume at 4 h in the mouse middle cerebral artery occlusion model. The neuroprotective effects of Delta(9)-tetrahydrocannabinol but not cannabidiol were inhibited by SR141716, a cannabinoid CB1 receptor antagonist, and were abolished by warming of the animals to the levels observed in the controls. Delta(9)-Tetrahydrocannabinol significantly decreased the rectal temperature, and the hypothermic effect was inhibited by SR141716. These results surely show that the neuroprotective effect of Delta(9)-tetrahydrocannabinol are via a CB1 receptor and temperature-dependent mechanisms whereas the neuroprotective effects of cannabidiol are independent of CB1 blockade and of hypothermia.
Hayakawa
Kazuhide
K
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Fukuoka City, Fukuoka, 814-0180, Japan.
Mishima
Kenichi
K
Abe
Kohji
K
Hasebe
Nobuyoshi
N
Takamatsu
Fumie
F
Yasuda
Hiromi
H
Ikeda
Tomoaki
T
Inui
Keiichiro
K
Egashira
Nobuaki
N
Iwasaki
Katsunori
K
Fujiwara
Michihiro
M
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002185:Cannabidiol / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000627:therapeutic use; D004347:Drug Interactions; D005334:Fever / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology; D000077285:Rimonabant; D013778:Tetrazolium Salts; D013997:Time Factors
D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013778:Tetrazolium Salts; D002185:Cannabidiol; D013759:Dronabinol; C009591:triphenyltetrazolium; D000077285:Rimonabant