Research Group Clinical and Experimental Psychopathology, Department of General and Social Psychiatry ZH West, Psychiatric University Hospital Zurich, Zurich, Switzerland.
World J Biol Psychiatry. 2010 Mar;11(2 Pt 2):208-19. doi: 10.3109/15622970801908047.
Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the principal psychoactive constituent of the Cannabis sativa plant, and other agonists at the central cannabinoid (CB(1)) receptor may induce characteristic psychomotor effects, psychotic reactions and cognitive impairment resembling schizophrenia. These effects of Delta(9)-THC can be reduced in animal and human models of psychopathology by two exogenous cannabinoids, cannabidiol (CBD) and SR141716. CBD is the second most abundant constituent of Cannabis sativa that has weak partial antagonistic properties at the CB(1) receptor. CBD inhibits the reuptake and hydrolysis of anandamide, the most important endogenous CB(1) receptor agonist, and exhibits neuroprotective antioxidant activity. SR141716 is a potent and selective CB(1) receptor antagonist. Since both CBD and SR141716 can reverse many of the biochemical, physiological and behavioural effects of CB(1) receptor agonists, it has been proposed that both CBD and SR141716 have antipsychotic properties. Various experimental studies in animals, healthy human volunteers, and schizophrenic patients support this notion. Moreover, recent studies suggest that cannabinoids such as CBD and SR141716 have a pharmacological profile similar to that of atypical antipsychotic drugs. In this review, both preclinical and clinical studies investigating the potential antipsychotic effects of both CBD and SR141716 are presented together with the possible underlying mechanisms of action.
德尔塔(9)-四氢大麻酚（Delta(9)-THC）是大麻植物的主要精神活性成分，以及中枢大麻素（CB(1)）受体的其他激动剂，可能会引起类似精神分裂症的特征性精神运动效应、精神病反应和认知障碍。在精神病病理的动物和人类模型中，两种外源性大麻素，大麻二酚（CBD）和 SR141716，可以减少 Delta(9)-THC 的这些作用。CBD 是大麻中第二丰富的成分，对 CB(1)受体具有弱的部分拮抗特性。CBD 抑制内源性 CB(1)受体激动剂花生四烯酸的再摄取和水解，并具有神经保护抗氧化活性。SR141716 是一种有效的、选择性的 CB(1)受体拮抗剂。由于 CBD 和 SR141716 都可以逆转 CB(1)受体激动剂的许多生化、生理和行为效应，因此有人提出 CBD 和 SR141716 都具有抗精神病特性。动物的各种实验研究、健康的人类志愿者和精神分裂症患者的研究都支持这一观点。此外，最近的研究表明，大麻素如 CBD 和 SR141716 具有与非典型抗精神病药物相似的药理学特征。在这篇综述中，介绍了 CBD 和 SR141716 潜在抗精神病作用的临床前和临床研究，以及可能的作用机制。
