Epilepsy and cannabis: facing reality.

Abstract

EDITOR–Pediatric drug-resistant epilepsy (DRE) can have a devastating impact on the quality of life and daily functioning of the child and family. It also affects their health and development, and creates an ongoing heavy load for health services. Despite new antiseizure medication (ASM), occasional precision therapy, advances in epilepsy surgery and neuromodulation, and the use of various ketogenic diets, the population of patients with DRE has not decreased significantly.1, 2 Cannabidiol (CBD)-enriched cannabis may be of benefit to some of these children.3 CBD-enriched cannabis for (pediatric) epilepsy has notably been championed by both parents and the pharmaceutical industry. Indications for the FDA and EMA approved pure CBD (Epidiolex) are still limited to Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, partly based on pathophysiological reasoning but also because the approval process is faster and easier for such rare disorders. As neurologists, we are exposed to increasing (mostly low-level) literature on artisanal CBD's efficacy and safety, and we are increasingly asked by families to consider it as a therapy. Owing to various reasons (mainly economic and political), artisanal CBD has mostly escaped the systematic sound research process necessary to document the safety and efficacy of ASM before it comes to market. This has occurred in a context where various cannabis products are being marketed in many countries for medical and non-medical purposes, most of them produced using uncontrolled methods resulting in unreliable composition.4 Kirkpatrick and O'Callaghan provide important clues for clinicians and researchers to address the issue ethically and realistically, with insights stemming from a British perspective. In Israel, we worked together with the Ministry of Health on strict regulations of growing cannabis by approved growers/producers; controlling the oil extraction following a Good Manufacturing Practice-like process; selecting the correct compositions and requiring precise product content to be accurately measured and declared; moving the distribution of the products from the growers/producers to regular pharmacies; and defining guidelines on who is eligible to be treated:currently in Israel, this includes seizures which are refractory to at least four appropriate ASMs, which is more strict than the usual drug-resistant epilepsy definition. Meanwhile, we keep educating treating neurologists on the use of CBD in epilepsy, limiting the eligible dosages of CBD and tetrahydrocannabinol (THC) allowed, and disseminating knowledge on adverse effects and possible drug interactions. We also try to ensure consistency in the oil used by the patient (as there may be differences in the other compounds) and the follow-up of treated patients. At the same time, we should all try to continue promoting research in animal models and design placebo-controlled treatment trials with different compounds and formulations in various populations, and in addition accumulate as much data as possible on long-term effects.