Division of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Via Ferrata 9, 27100, Pavia, Italy.
IRCCS Mondino Foundation, Pavia, Italy.
Drugs. 2019 Sep;79(13):1435-1454. doi: 10.1007/s40265-019-01171-4.
Cannabidiol (CBD) is a major active component of the Cannabis plant, which, unlike tetrahydrocannabinol (THC), is devoid of euphoria-inducing properties. During the last 10 years, there has been increasing interest in the use of CBD-enriched products for the treatment of epilepsy. In 2018, an oil-based highly purified liquid formulation of CBD (Epidiolex) derived from Cannabis sativa was approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). The mechanisms underlying the antiseizure effects of CBD are unclear but may involve, among others, antagonism of G protein-coupled receptor 55 (GPR55), desensitization of transient receptor potential of vanilloid type 1 (TRPV1) channels, and inhibition of adenosine reuptake. CBD has complex and variable pharmacokinetics, with a prominent first-pass effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat/high-calorie meal. In four randomized, double-blind, parallel-group, adjunctive-therapy trials, CBD given at doses of 10 and 20 mg/kg/day administered in two divided administrations was found to be superior to placebo in reducing the frequency of drop seizures in patients with LGS and convulsive seizures in patients with DS. Preliminary results from a recently completed controlled trial indicate that efficacy also extends to the treatment of seizures associated with the tuberous sclerosis complex. The most common adverse events that differentiated CBD from placebo in controlled trials included somnolence/sedation, decreased appetite, increases in transaminases, and diarrhea, behavioral changes, skin rashes, fatigue, and sleep disturbances. About one-half of the patients included in the DS and LGS trials were receiving concomitant therapy with clobazam, and in these patients a CBD-induced increase in serum levels of the active metabolite norclobazam may have contributed to improved seizure outcomes and to precipitation of some adverse effects, particularly somnolence.
大麻二酚（CBD）是大麻植物的主要活性成分，与四氢大麻酚（THC）不同，它没有引起欣快感的特性。在过去的 10 年中，人们对使用富含 CBD 的产品治疗癫痫的兴趣日益增加。2018 年，美国食品和药物管理局批准了一种源自大麻的 CBD 油基高纯度液体配方（Epidiolex），用于治疗与 Dravet 综合征（DS）和 Lennox-Gastaut 综合征（LGS）相关的癫痫发作。CBD 抗癫痫作用的机制尚不清楚，但可能涉及 G 蛋白偶联受体 55（GPR55）的拮抗作用、瞬时受体电位香草酸型 1（TRPV1）通道的脱敏作用和腺苷再摄取的抑制作用。CBD 的药代动力学复杂且多变，具有明显的首过效应和低口服生物利用度，当 CBD 与高脂肪/高热量膳食一起服用时，其生物利用度增加四倍。在四项随机、双盲、平行组、附加治疗试验中，每日两次分两次给予 10 和 20mg/kg 的 CBD 被发现优于安慰剂，可降低 LGS 患者的跌倒发作频率和 DS 患者的癫痫发作频率。最近完成的一项对照试验的初步结果表明，疗效也扩展到治疗与结节性硬化症相关的癫痫发作。在对照试验中，将 CBD 与安慰剂区分开来的最常见不良事件包括嗜睡/镇静、食欲下降、转氨酶升高和腹泻、行为改变、皮疹、疲劳和睡眠障碍。在 DS 和 LGS 试验中纳入的患者约有一半正在接受氯巴占的联合治疗，在这些患者中，CBD 诱导的活性代谢物去甲氯巴占血清水平升高可能有助于改善癫痫发作结局和引发一些不良反应，尤其是嗜睡。
