Lippiello Pellegrino, Balestrini Simona, Leo Antonio, Coppola Antonietta, Citraro Rita, Elia Maurizio, Russo Emilio, De Sarro Giovambattista
Department of Science of Health, School of Medicine, University of Catanzaro, Via T. Campanella, 115; 88100 Catanzaro, Italy.
Curr Pharm Des. 2016;22(42):6426-6433. doi: 10.2174/1381612822666160831122722.
Several antiepileptic drugs (AEDs), about 25, are currently clinically available for the treatment of patients with epilepsy. Despite this armamentarium and the many recently introduced AEDs, no major advances have been achieved considering the number of drug resistant patients, while many benefits have been indeed obtained for other clinical outcomes (e.g. better tolerability, less interactions). Cannabinoids have long been studied for their potential therapeutical use and more recently phytocannabinoids have been considered a valuable tool for the treatment of several neurological disorders including epilepsy. Among this wide class, the most studied is cannabidiol (CBD) considering its lack of psychotropic effects and its anticonvulsant properties.
Analyse the currently available literature on CBD also in light of other data on phytocannabinoids, reviewing data spanning from the mechanism of action, pharmacokinetic to clinical evidences.
Several preclinical studies have tried to understand the mechanism of action of CBD, which still remains largely not understood. CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures; beneficial effects were reported also in animal models of epileptogenesis and chronic models of epilepsy, although not substantial. In contrast, data coming from some studies raise questions on the effects of other cannabinoids and above all marijuana.
There is indeed sufficient supporting data for clinical development and important antiepileptic effects and the currently ongoing clinical studies will permit the real usefulness of CBD and possibly other cannabinoids. Undoubtedly, several issues also need to be addressed in the next future (e.g. better pharmacokinetic profiling). Finally, shading light on the mechanism of action and the study of other cannabinoids might represent an advantage for future developments.
目前临床上有大约25种抗癫痫药物（AEDs）可用于治疗癫痫患者。尽管有这样的药物库以及许多最近推出的AEDs，但考虑到耐药患者的数量，并未取得重大进展，不过在其他临床结局方面（如更好的耐受性、更少的相互作用）确实有诸多益处。大麻素长期以来一直因其潜在的治疗用途而受到研究，最近植物大麻素被认为是治疗包括癫痫在内的几种神经系统疾病的有价值工具。在这一广泛类别中，考虑到其缺乏精神活性作用和抗惊厥特性，研究最多的是大麻二酚（CBD）。
根据关于植物大麻素的其他数据，分析目前可得的关于CBD的文献，回顾从作用机制、药代动力学到临床证据的数据。
多项临床前研究试图了解CBD的作用机制，但目前仍大多未明。CBD主要在急性癫痫发作动物模型中显示出显著的抗惊厥作用；在癫痫发生动物模型和慢性癫痫模型中也报道了有益作用，尽管不显著。相比之下，一些研究的数据对其他大麻素尤其是大麻的作用提出了疑问。
确实有足够的支持数据用于临床开发，且有重要的抗癫痫作用，目前正在进行的临床研究将证实CBD以及可能其他大麻素的实际效用。毫无疑问，未来还需要解决几个问题（如更好的药代动力学特征分析）。最后，阐明作用机制以及对其他大麻素的研究可能对未来发展具有优势。
