Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.
Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.
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DOI：
10.1111/epi.12631
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发表时间：
2014-06
期刊：
影响因子：
5.6
通讯作者：
Friedman D
中科院分区：
文献类型：
--
作者：
Devinsky O;Cilio MR;Cross H;Fernandez-Ruiz J;French J;Hill C;Katz R;Di Marzo V;Jutras-Aswad D;Notcutt WG;Martinez-Orgado J;Robson PJ;Rohrback BG;Thiele E;Whalley B;Friedman D
目前关于大麻素，大麻二酚（CBD）与癫痫和其他选定的神经精神疾病的相关性的科学证据的总结。我们总结了一次会议上的演讲，邀请与会者回顾了生理学，作用机制，药理学以及动物模型和人类受试者研究的相关方面。自古以来，大麻就被用来治疗疾病。Δ9-THC是大麻中主要的精神活性成分，大麻二酚（CBD）是大麻中主要的非精神活性成分。大麻和Δ9-THC在大多数动物模型中具有抗惊厥作用，但在一些健康动物中可能具有促惊厥作用。Δ9-THC的精神作用限制耐受性。CBD在许多急性动物模型中具有抗惊厥作用，但在慢性模型中的数据有限。CBD的抗癫痫机制尚不清楚，但可能包括对平衡核苷转运体的作用；孤儿g蛋白偶联受体GPR55；美拉西汀8型通道瞬时受体电位；5-HT1a受体；α3和α1甘氨酸受体；以及锚蛋白1型通道的瞬时受体电位。CBD具有神经保护和抗炎作用。CBD在人类中似乎具有良好的耐受性，但CBD在人类癫痫中的小型和方法学有限的研究尚无定论。最近关于高比例CBD：Δ9-THC医用大麻的传闻报道声称有功效，但研究没有受到控制。CBD在癫痫和其他神经精神疾病（包括焦虑、精神分裂症、成瘾和新生儿缺氧缺血性脑病）中的应用值得研究。然而，我们缺乏关于纯CBD对任何疾病疗效的有力的双盲随机对照研究的数据。最初的剂量耐受性和双盲随机对照研究侧重于目标顽固性癫痫人群，如患有Dravet和Lennox-Gastaut综合征的患者，正在计划中。其他治疗难治性癫痫的试验也可能是必要的。
To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regards to their relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. Δ9-THC is the major psychoactive ingredient and cannabidiol (CBD) is the major non-psychoactive ingredient in cannabis. Cannabis and Δ9-THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. Psychotropic effects of Δ9-THC limit tolerability. CBD is anticonvulsant in many acute animal models but there is limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of melastatin type 8 channel; the 5-HT1a receptor; the α3 and α1 glycine receptors; and the transient receptor potential of ankyrin type 1 channel. CBD has neuroprotective and anti-inflammatory effects. CBD appears to be well tolerated in humans but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ9-THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted.