UCL NIHR BRC Great Ormond Street Institute of Child Health, Guilford St, London, WC1N 1EH, UK; Great Ormond Street for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK; Young Epilepsy, Lingfield, Surrey, UK.
Institute of Molecular and Clinical Sciences, St George's University of London, SW17 0RE, UK; Atkinson Morley Regional Epilepsy Network, St George's University Hospitals NHS Foundation Trust, Blackshaw Road, London, SW17 0QT, UK.
Neuropharmacology. 2020 Jun 15;170:107861. doi: 10.1016/j.neuropharm.2019.107861. Epub 2019 Nov 23.
With the licensing of cannabidiol for drug resistant seizures in Dravet and Lennox Gastaut syndromes in the United states in 2018, interest in the potential for cannabis-based-medicinal products to meet currently unmet needs for people with epilepsy continues to grow. This review summarizes current knowledge and discusses the implications for future research and practice. Both cannabidiol and tetrahydrocannabinol, the main components, have been extensively studied in animal models, with multimodal mechanisms of action proposed. Only pure cannabidiol formulations have been rigorously evaluated in controlled trials thus far, with modest but significant improvements in motor seizures. Adverse effects include diarrhoea, somnolence and reduced appetite, with mostly acceptable tolerability, but a not insignificant (up to 1 in 23) risk of serious adverse events. Recognized drug interactions include with valproate (increased risk of hepatotoxicity) and clobazam (contributing to somnolence, increased secretions, probably chest infections, and potentially efficacy). Whilst there is public (and producer) interest in products also containing tetrahydrocannabinol, clinicians have justifiable concerns about exposing a group already vulnerable to mental health and neurobehavioural comorbidities to the associated additional risks in these domains. Artisanal preparations, with often inconsistent/unknown constituents are frequently used but not recommended. A gulf exists between the actual evidence, including a lack of comparative studies and public beliefs, fuelled by media and anecdote. Continued education of the public, policymakers, researchers and healthcare providers about what is and isn't yet known, together with on-going good quality research is essential to mitigate against future potential risks, particularly in relation to vulnerable populations. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
2018 年，美国批准将大麻二酚用于治疗德拉维氏症和 Lennox-Gastaut 综合征的耐药性癫痫发作，人们对基于大麻的药物产品是否有可能满足癫痫患者目前尚未满足的需求的兴趣持续增长。这篇综述总结了当前的知识，并讨论了对未来研究和实践的影响。大麻的两种主要成分，即大麻二酚和四氢大麻酚，已在动物模型中得到广泛研究，提出了多种作用机制。迄今为止，只有纯大麻二酚制剂在对照试验中得到了严格评估，运动性癫痫发作有适度但显著的改善。不良反应包括腹泻、嗜睡和食欲减退，耐受性大多可接受，但严重不良事件的风险不容忽视（高达 1/23）。已认识到的药物相互作用包括与丙戊酸（增加肝毒性风险）和氯巴占（导致嗜睡、增加分泌物，可能导致胸部感染，并可能降低疗效）。虽然公众（和生产者）对含有四氢大麻酚的产品感兴趣，但临床医生有理由担心，将一个已经容易受到精神健康和神经行为合并症影响的群体暴露于这些领域的相关额外风险中。经常使用但不推荐使用手工制作的制剂，其成分往往不一致/未知。实际证据与包括缺乏对照研究和公众的信念之间存在差距，这是由媒体和传闻推动的。继续向公众、政策制定者、研究人员和医疗保健提供者进行关于已知和未知内容的教育，以及开展持续的高质量研究，对于减轻未来的潜在风险至关重要，特别是对于弱势群体。本文是题为“21 世纪的新型癫痫治疗方法——从抗癫痫药物到预防、改变和治愈癫痫”的特刊的一部分。
