Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 14 - Trang 8268-8273 - 1998
Aidan J. Hampson1, M. Grimaldi1, J Axelrod1, David A. Wink1
1Laboratory 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

Tóm tắt

The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (−)Δ 9 -tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl- d -aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl- d -aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or α-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 14

8268-8273

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