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Repeated Treatment With Cannabidiol But Not Delta9-tetrahydrocannabinol

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Repeated Treatment with Cannabidiol but Not Delta9-tetrahydrocannabinol Has a Neuroprotective Effect Without the Development of Tolerance

Authors:

Hayakawa Kazuhide
Mishima Kenichi
Nozako Masanori
Ogata Ayumi
Hazekawa Mai
Liu An-Xin
Fujioka Masayuki
Abe Kohji
Hasebe Nobuyoshi
Egashira Nobuaki
Iwasaki Katsunori
Fujiwara Michihiro

From: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Fukuoka City, Fukuoka 814-0180, Japan.
Neuropharmacology

Publish Date: Mar 2007
ISSN: 0028-3908
Volume: 52
Issue: 4
Pages: 1079-87
Medium: Print
Language: English
Citation (JAMA): Hayakawa Kazuhide, Mishima Kenichi, Nozako Masanori, et al. Repeated Treatment with Cannabidiol but Not Delta9-tetrahydrocannabinol Has a Neuroprotective Effect Without the Development of Tolerance.. Neuropharmacology Mar 2007;52:1079-87

Abstract

Both Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol are known to have a neuroprotective effect against cerebral ischemia. We examined whether repeated treatment with both drugs led to tolerance of their neuroprotective effects in mice subjected to 4h-middle cerebral artery (MCA) occlusion. The neuroprotective effect of Delta(9)-THC but not cannabidiol was inhibited by SR141716, cannabinoid CB(1) receptor antagonist. Fourteen-day repeated treatment with Delta(9)-THC, but not cannabidiol, led to tolerance of the neuroprotective and hypothermic effects. In addition, repeated treatment with Delta(9)-THC reversed the increase in cerebral blood flow (CBF), while cannabidiol did not reverse that effect. Repeated treatment with Delta(9)-THC caused CB(1) receptor desensitization and down-regulation in MCA occluded mice. On the contrary, cannabidiol did not influence these effects. Moreover, the neuroprotective effect and an increase in CBF induced by repeated treatment with cannabidiol were in part inhibited by WAY100135, serotonin 5-HT(1A) receptor antagonist. Cannabidiol exhibited stronger antioxidative power than Delta(9)-THC in an in vitro study using the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical. Thus, cannabidiol is a potent antioxidant agent without developing tolerance to its neuroprotective effect, acting through a CB(1) receptor-independent mechanism. It is to be hoped that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.

Mesh Headings (Keywords): Analysis of Variance, Animals, Behavior, Animal, Body Temperature, Cannabidiol, Cerebral Infarction, Cerebrovascular Circulation, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Interactions, Drug Tolerance, Infarction, Middle Cerebral Artery, Male, Mice, Neuroprotective Agents, Piperazines, Piperidines, Pyrazoles, Serotonin Antagonists, Tetrahydrocannabinol, Time Factors


Source: Repeated Treatment with Cannabidiol but Not Delta9-tetrahydrocannabinol Has a Neuroprotective Effect Without the Development of Tolerance
 
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