《neuroprotective antioxidants》.pdfVIP

Proc. Natl. Acad. Sci. USA Vol. 95, pp. 8268–8273, July 1998 Medical Sciences 9 Cannabidiol and () -tetrahydrocannabinol are neuroprotective antioxidants † ‡ § A. J. HAMPSON * , M. GRIMALDI , J. AXELROD *, AND D. WINK *Laboratory of Cellular and Molecular Regulation, National Institutes of Mental Health, Bethesda, MD 20892; ‡Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; and §Radiology and Biology Branch, National Cancer Institute, Bethesda, MD 20892 Contributed by Julius Axelrod, April 27, 1998 ABSTRACT The neuroprotective actions of cannabidiol reduce the toxic reactive oxygen species (ROS) formed during and other cannabinoids were examined in rat cortical neuron ischemic metabolism. Cannabinoids like ( )9-tetrahydrocan- cultures exposed to toxic levels of the excitatory neurotrans- nabinol (THC) and its psychoactive analogues also have been mitter glutamate. Glutamate toxicity was reduced by both reported to be neuroprotective against glutamate toxicity in cannabidiol, a nonpsychoactive constituent of marijuana, and vitro (7). Cannabinoids have been suggested to prevent gluta- the psychotropic cannabinoid ( )9-tetrahydrocannabinol mate neurotoxicity by activating cannabinoid receptors (7, 8), (THC). Cannabinoids protected equally well against neuro- which can reduce calcium influx through voltage sensitive toxicity mediated by N-methyl-D-aspartate receptors, 2-ami- calcium channels (8, 9). A synthetic cannabinoid (HU-211) no-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid recep- also has been demonstrated to be neuroprote