Hampson A J, Grimaldi M, Lolic M, Wink D, Rosenthal R, Axelrod J
Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, Maryland 20892, USA.
Ann N Y Acad Sci. 2000;899:274-82.
Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.
在暴露于毒性水平神经递质谷氨酸的大鼠皮层神经元培养物中，对大麻二酚及其他大麻素作为神经保护剂进行了研究。精神活性大麻素受体激动剂δ9-四氢大麻酚（THC）和大麻二酚（大麻的一种非精神活性成分）均能减轻N-甲基-D-天冬氨酸（NMDA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和红藻氨酸受体介导的神经毒性。神经保护作用不受大麻素受体拮抗剂的影响，表明其作用机制不依赖于（大麻素）受体。抗氧化剂可降低谷氨酸毒性。通过循环伏安法和基于芬顿反应的系统，证明大麻二酚、THC和其他大麻素是有效的抗氧化剂。作为大麻素可在神经元培养物中充当抗氧化剂的证据，已证明大麻二酚可降低神经元中的氢过氧化物毒性。在一项比较各种抗氧化剂预防谷氨酸毒性能力的直接对比试验中，大麻二酚在保护能力方面优于α-生育酚和抗坏血酸。最近在局灶性脑缺血大鼠模型中的初步研究表明，大麻二酚在体内可能至少与这些体外研究中所见的效果一样有效。
