Published Online
on April 21, 2005

A more recent version of this article appeared on May 1, 2005

This Article Full Text (PDF) All Versions of this Article: 36/5/1071    most recent 01.STR.0000163083.59201.34v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mishima, K. Articles by Fujiwara, M. Search for Related Content PubMed PubMed Citation Articles by Mishima, K. Articles by Fujiwara, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Acute Cerebral Infarction

Submitted on December 22, 2004
Revised on December 22, 2004
Accepted on February 18, 2005

Cannabidiol Prevents Cerebral Infarction Via a Serotonergic 5-Hydroxytryptamine_1A Receptor-Dependent Mechanism

Kenichi Mishima PhD; Kazuhide Hayakawa; Kohji Abe PhD; Tomoaki Ikeda PhD, MD; Nobuaki Egashira PhD; Katsunori Iwasaki PhD; and Michihiro Fujiwara PhD^*

From the Department of Neuropharmacology (K.M., K.H., N.E., K.I., M.F.), Faculty of Pharmaceutical Sciences, and Advanced Materials Institute (K.I., M.F.), Fukuoka University, Japan; Department of Obstetrics and Gynecology (T.I.), Miyazaki Medical College, University of Miyazaki, Japan; Department of Medical Physics (K.A.), School of Allied Health Sciences, Faculty of Medicine, Osaka University, Japan; and Department of Drug Safety Evaluation (K.A.), Developmental Research Laboratories, Shionogi and Co, Ltd, Osaka, Japan.

^* To whom correspondence should be addressed. E-mail: mfuji{at}fukuoka-u.ac.jp.

Background and Purpose--Cannabidiol has been reported to be a neuroprotectant, but the neuroprotective mechanism of cannabidiol remains unclear. We studied the neuroprotective mechanism of cannabidiol in 4-hour middle cerebral artery (MCA) occlusion mice.

Methods--Male MCA occluded mice were treated with cannabidiol, abnormal cannabidiol, anandamide, methanandamide, cannabidiol plus capsazepine, and cannabidiol plus WAY100135 before and 3 hours after MCA occlusion. The infarct size was determined after 24 hours (2,3,5-triphenyltetrazolium chloride staining). Cerebral blood flow (CBF) was measured at, before and 1, 2, 3, and 4 hours after MCA occlusion.

Results--Cannabidiol significantly reduced the infarct volume induced by MCA occlusion in a bell-shaped curve. Similarly, abnormal cannabidiol but not anandamide or methanandamide reduced the infarct volume. Moreover, the neuroprotective effect of cannabidiol was inhibited by WAY100135, a serotonin 5-hydroxytriptamine_1A (5-HT_1A) receptor antagonist but not capsazepine a vanilloid receptor antagonist. Cannabidiol increased CBF to the cortex, and the CBF was partly inhibited by WAY100135 in mice subjected to MCA occlusion.

Conclusions--Cannabidiol and abnormal cannabidiol reduced the infarct volume. Furthermore, the neuroprotective effect of cannabidiol was inhibited by WAY100135 but not capsazepine, and the CBF increased by cannabidiol was partially reversed by WAY100135. These results suggested that the neuroprotective effect of cannabidiol may be related to the increase in CBF through the serotonergic 5-HT_1A receptor.

Key words: cannabidiol • cerebral infarction • middle cerebral artery • serontonin receptor • 5HT_1A

This article has been cited by other articles:

				K. Hayakawa, K. Mishima, M. Nozako, M. Hazekawa, S. Mishima, M. Fujioka, K. Orito, N. Egashira, K. Iwasaki, and M. Fujiwara Delayed Treatment With Minocycline Ameliorates Neurologic Impairment Through Activated Microglia Expressing a High-Mobility Group Box1-Inhibiting Mechanism Stroke, March 1, 2008; 39(3): 951 - 958. [Abstract] [Full Text] [PDF]

				K. Le Minh, K. Klemm, K. Abshagen, C. Eipel, M. D. Menger, and B. Vollmar Attenuation of Inflammation and Apoptosis by Pre- and Posttreatment of Darbepoetin-{alpha} in Acute Liver Failure of Mice Am. J. Pathol., June 1, 2007; 170(6): 1954 - 1963. [Abstract] [Full Text] [PDF]

				N. Lindenblatt, M. D. Menger, E. Klar, and B. Vollmar Darbepoetin-Alpha Does Not Promote Microvascular Thrombus Formation in Mice: Role of eNOS-Dependent Protection Through Platelet and Endothelial Cell Deactivation Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1191 - 1198. [Abstract] [Full Text] [PDF]

				S. A. Andrabi, N. S. Kim, S.-W. Yu, H. Wang, D. W. Koh, M. Sasaki, J. A. Klaus, T. Otsuka, Z. Zhang, R. C. Koehler, et al. Poly(ADP-ribose) (PAR) polymer is a death signal PNAS, November 28, 2006; 103(48): 18308 - 18313. [Abstract] [Full Text] [PDF]