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Cannabidiol prevents infarction via the non-CB1 cannabinoid receptor mechanism

Hayakawa, Kazuhide1; Mishima, Kenichi1; Abe, Kohji4; Hasebe, Nobuyoshi1; Takamatsu, Fumie1; Yasuda, Hiromi1; Ikeda, Tomoaki3; Inui, Keiichiro1; Egashira, Nobuaki1; Iwasaki, Katsunori1 2; Fujiwara, Michihiro1 2 CA

Neuropharmacology and Neurotoxicology

Cannabidiol, a non-psychoactive constituent of cannabis, has been reported as a neuroprotectant. Cannabidiol and Δ9-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 Δ9-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. Δ9-Tetrahydrocannabinol significantly decreased the rectal temperature, and the hypothermic effect was inhibited by SR141716. These results surely show that the neuroprotective effect of Δ9-tetrahydrocannabinol are via a CB1 receptor and temperature-dependent mechanisms whereas the neuroprotective effects of cannabidiol are independent of CB1 blockade and of hypothermia.

1Department of Neuropharmacology, Faculty of Pharmaceutical Sciences

2Advanced Materials Institute, Fukuoka University, Nanakuma 8-19-1, Fukuoka City, Fukuoka, 814-0180

3Department of Obstetrics and Gynecology, Miyazaki Medical College, University of Miyazaki, 889-1692

4Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Osaka 565-0871, Japan

CACorresponding Author: mfuji@fukuoka-u.ac.jp

Received 17 July 2004; accepted 18 August 2004

© 2004 Lippincott Williams & Wilkins, Inc.