Background

Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A plant-derived, highly purified CBD formulation with a known and constant composition has been approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome, Lennox–Gastaut syndrome, and tuberous sclerosis complex. In the European Union, the drug has been authorized by the European Medicines Agency for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome, in conjunction with clobazam, and is under regulatory review for the treatment of seizures in patients with tuberous sclerosis complex.

Objectives

This systematic review aimed to summarize the currently available body of knowledge about the use of this US Food and Drug Administration/European Medicines Agency-approved oral formulation of pharmaceutical-grade CBD in patients with epileptic conditions, especially developmental and epileptic encephalopathies other than Dravet syndrome and Lennox–Gastaut syndrome.

Methods

The relevant studies were identified through MEDLINE and the US National Institutes of Health Clinical Trials Registry in October 2020. There were no date limitations or language restrictions. The following types of studies were included: clinical trials, cohorts, case-control, cross-sectional, clinical series, and case reports. Participants had to meet the following criteria: any sex, any ethnicity, any age, diagnosis of epilepsy, receiving plant-derived, highly purified (> 98% w/w) CBD in a sesame oil-based oral solution for the treatment of seizures. Data extracted from selected records included efficacy, tolerability, and safety outcomes.

Results

Five hundred and seventy records were identified by database and trial register searching. Fifty-seven studies were retrieved for detailed assessment, of which 42 were eventually included for the review. The participants of the studies included patients of both pediatric and adult age. Across the trials, purified CBD was administered at dosages up to 50 mg/kg/day. In a randomized double-blind controlled trial in patients with tuberous sclerosis complex, CBD was associated with a significantly greater percent reduction in seizure frequency than placebo over the treatment period. Open-label studies suggested the effectiveness of CBD in the treatment of children and adults presenting with other epilepsy syndromes than those addressed by regulatory trials, including CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences. The most common adverse events observed during treatment with CBD included somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.

Conclusions

The currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies. The existing evidence can provide preliminary support for additional research.

中文翻译：

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用于癫痫治疗的高纯度大麻二酚：对 Dravet 综合征和 Lennox-Gastaut 综合征以外的癫痫病症的系统评价

背景

大麻二酚 (CBD) 是大麻植物的主要成分之一，具有抗癫痫作用，不会产生欣快或侵入性副作用。美国食品和药物管理局已批准一种来自植物的、高度纯化的、具有已知和恒定成分的 CBD 制剂，用于治疗与 Dravet 综合征、Lennox-Gastaut 综合征和结节性硬化症相关的癫痫发作。在欧盟，该药物已获得欧洲药品管理局的授权，可与氯巴占一起治疗与 Dravet 综合征和 Lennox-Gastaut 综合征相关的癫痫发作，并正在接受监管审查，用于治疗结节性硬化症患者的癫痫发作复杂的。

目标

本系统评价旨在总结目前可用的关于使用美国食品和药物管理局/欧洲药品管理局批准的药物级 CBD 口服制剂治疗癫痫病患者的知识体系，尤其是除 Dravet 综合征以外的发育性和癫痫性脑病患者和 Lennox-Gastaut 综合征。

方法

相关研究于 2020 年 10 月通过 MEDLINE 和美国国立卫生研究院临床试验注册中心确定。没有日期限制或语言限制。包括以下类型的研究：临床试验、队列研究、病例对照研究、横断面研究、临床系列研究和病例报告。参与者必须满足以下标准：任何性别、任何种族、任何年龄、癫痫诊断、接受以芝麻油为基础的口服溶液中的植物来源、高度纯化 (> 98% w/w) CBD 治疗癫痫发作. 从选定记录中提取的数据包括疗效、耐受性和安全性结果。

结果

通过数据库和试验注册检索确定了 570 条记录。检索了 57 项研究进行详细评估，其中 42 项最终被纳入审查。研究的参与者包括儿童和成人年龄的患者。在整个试验中，纯化的 CBD 的给药剂量高达 50 mg/kg/天。在一项针对结节性硬化症患者的随机双盲对照试验中，与安慰剂相比，CBD 与治疗期间癫痫发作频率的降低百分比显着相关。开放标签研究表明，CBD 在治疗患有其他癫痫综合征的儿童和成人方面的有效性比监管试验所解决的那些癫痫综合征，包括 CDKL5 缺乏症和 Aicardi、Dup15q 和 Doose 综合征，SYNGAP1 脑病和伴有肌阵挛缺失的癫痫。在 CBD 治疗期间观察到的最常见的不良事件包括嗜睡、食欲下降、腹泻和血清转氨酶升高。

结论

目前可用的数据表明，在各种癫痫疾病和病因的患者中可以看到对高度纯化的植物衍生 CBD 油基溶液的治疗反应。现有证据可为进一步研究提供初步支持。