Cannabidiol Prevents Cerebral
Infarction
Via a
Serotonergic 5-Hydroxytryptamine1A Receptor–Dependent Mechanism ©
2005 American Heart Association, Inc. from
Stroke Journal. Kenichi Mishima, PhD;
Kazuhide Hayakawa; Kohji Abe, PhD; Tomoaki
Ikeda, PhD, MD; Nobuaki Egashira, PhD; Katsunori
Iwasaki, PhD; Michihiro Fujiwara, PhD
From the Department of Neuro-pharmacology (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.
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-hydroxytriptamine1A (5-HT1A)
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-HT1A
receptor. (see
original article here!)
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