gw-1000 and Lennox-Gastaut-Syndrome

Treatment-resistant epilepsy (TRE) affects 30% of epilepsy patients and is associated with severe morbidity and increased mortality. Cannabis-based therapies have been used to treat epilepsy for millennia, but only in the last few years have we begun to collect data from adequately powered placebo-controlled, randomized trials (RCTs) with cannabidiol (CBD), a cannabis derivative. Previously, information was limited to case reports, small series, and surveys reporting on the use of CBD and diverse medical marijuana (MMJ) preparations containing: tetrahydrocannabinol (THC), CBD, and many other cannabinoids in differing combinations. These RCTs have studied the safety and explored the potential efficacy of CBD use in children with Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). The role of the placebo response is of paramount importance in studying medical cannabis products given the intense social and traditional media attention, as well as the strong beliefs held by many parents and patients that a natural product is safer and more effective than FDA-approved pharmaceutical agents. We lack valid data on the safety, efficacy, and dosing of artisanal preparations available from dispensaries in the 25 states and District of Columbia with MMJ programs and online sources of CBD and other cannabinoids. On the other hand, open-label studies with 100mg/ml CBD (Epidiolex®, GW Pharmaceuticals) have provided additional evidence of its efficacy along with an adequate safety profile (including certain drug interactions) in children and young adults with a spectrum of TREs. Further, Phase 3 RCTs with Epidiolex support efficacy and adequate safety profiles for children with DS and LGS at doses of 10- and 20-mg/kg/day. This article is part of a Special Issue titled "Cannabinoids and Epilepsy".

Topics: Adult; Anticonvulsants; Cannabidiol; Cannabinoids; Child; Clinical Trials as Topic; Dronabinol; Drug Combinations; Drug Resistant Epilepsy; Epilepsies, Myoclonic; Humans; Lennox Gastaut Syndrome; Medical Marijuana; Young Adult

Cannabis sativa L. is an ancient medicinal plant wherefrom over 120 cannabinoids are extracted. In the past two decades, there has been increasing interest in the therapeutic potential of cannabis-based treatments for neurological disorders such as epilepsy, and there is now evidence for the medical use of cannabis and its effectiveness for a wide range of diseases. Cannabinoid treatments for pain and spasticity in patients with multiple sclerosis (Nabiximols) have been approved in several countries. Cannabidiol (CBD), in contrast to tetra-hydro-cannabidiol (THC), is not a controlled substance in the European Union, and over the years there has been increasing use of CBD-enriched extracts and pure CBD for seizure disorders, particularly in children. No analytical controls are mandatory for CBD-based products and a pronounced variability in CBD concentrations in commercialized CBD oil preparations has been identified. Randomized controlled trials of plant-derived CBD for treatment of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) have provided evidence of anti-seizure effects, and in June 2018, CBD was approved by the Food and Drug Administration as an add-on antiepileptic drug for patients two years of age and older with LGS or DS. Medical cannabis, with various ratios of CBD and THC and in different galenic preparations, is licensed in many European countries for several indications, and in July 2019, the European Medicines Agency also granted marketing authorisation for CBD in association with clobazam, for the treatment of seizures associated with LGS or DS. The purpose of this article is to review the availability of cannabis-based products and cannabinoid-based medicines, together with current regulations regarding indications in Europe (as of July 2019). The lack of approval by the central agencies, as well as social and political influences, have led to significant variation in usage between countries.

Topics: Anticonvulsants; Cannabidiol; Cannabinoids; Child; Child, Preschool; Dronabinol; Drug Combinations; Epilepsies, Myoclonic; Epilepsy; Humans; Lennox Gastaut Syndrome; Plant Extracts; Seizures