The potential role of cannabinoids in epilepsy treatment

Abstract

Epilepsy is one of the world's oldest recognized and prevalent neurological diseases. It has a great negative impact on patients' quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs' side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention. Areas covered: This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system. Expert commentary: Despite the fact that cannabis has been used for many purposes over 4 millennia, the development of drugs based on cannabinoids has been very slow. Only recently, research has focused on their potential effects and CBD is the first treatment of this group with clinical evidence of efficacy in children with Dravet syndrome; moreover, other studies are currently ongoing to confirm its effectiveness in patients with epilepsy. On the other hand, it will be of interest to understand whether drugs acting on the endocannabinoid system will be able to reach the market and prove their known preclinical efficacy also in patients with epilepsy.

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science

“…There is medical evidence showing that CBD may be effective in treatment of a wide range of disorders including epilepsy (particularly medically‐refractory pediatric epilepsy syndromes), Alzheimer's disease, Parkinson's disease, MS, ‐ , Huntington's disease, ALS, anxiety disorders including PTSD, depression, dystonia, Meige's syndrome, schizophrenia and psychosis, stroke and hypoxic‐ischemic injury, antioxidant, TBI,…”

<p>Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects</p>

“…Most patients participating in the above-illustrated RCTs were enrolled in an open-label extension (OLE) study (GWPCARE5), including overall 630 subjects (264 with DS and 366 with LGS) treated with adjunctive CBD (maximal dose 30 mg/kg/day) for 1-3 years, with 12-week follow-up visits. 55,56 During the interim analysis period (after data cut in November 2016) CBD was discontinued by 75 DS patients and 67 LGS subjects (corresponding to a withdrawal rate of 28% and 18%, respectively), mainly due to adverse events (AEs) and parent/patient consent withdrawal. In the DS group, the responder rate was about 40% at each visit window, the reduction in convulsive seizure frequency in the first trimester was 37.5% and persisted throughout 48 weeks, whereas the frequency of all seizures decreased by 39-50%.…”

“…Its anti-convulsant properties have been documented in several animal models of acute seizures and SE, where it proved widely effective (except for pilocarpine-induced SE). 67 Like CBD, CBDV has little affinity for CB1 and CB2, and like CBD it is considered a "multi-target" drug, known to act as an agonist on TRPV1/2 and TRPA1 channels, and as an antagonist on TRPM8 channels. 68 It also inhibits DGLα, involved in endocannabinoid synthesis.…”

Cannabidiol Determination on Peripheral Capillary Blood Using a Microsampling Method and Ultra-High-Performance Liquid Chromatography Tandem Mass Spectrometry with On-Line Sample Preparation

“…In recent years, a broad spectrum of products containing CBD has emerged on the market although their effects are largely dependent on the purity, the preparation, and the concentration of CBD and other components [9,10]. A plant-derived pharmaceutical formulation of purified CBD oral solution (Epidiolex ® ) was approved in June 2018 by the US Food and Drug Administration (FDA) as treatment and in July 2019 by the European Medicines Agency as adjunctive therapy in conjunction with clobazam (CLB) for seizures associated with Dravet Syndrome (DS) or Lennox-Gastaut syndrome (LGS) for patients aged 2 years and older [11].…”