Exploring the Efficacy of Cannabidiol in Drug-Resistant Monogenic Epilepsies: Insights from a Multicenter Study

Genetic epilepsies account for about 30% of all epilepsies and are often marked by recurrent and severe seizures. Among these, monogenic epilepsies, such as Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex represent some of the most severe. These forms are particularly prone to drug-resistant epilepsy (DRE), which affects 20-30% of epilepsy patients, making seizures uncontrollable despite the use of at least two appropriate antiepileptic drugs. DRE is a significant clinical challenge, leading to a high risk for neurological complications. The limited efficacy of conventional therapies underscores the urgent need for new treatment options. In this context, highly purified cannabidiol (CBD), a non-psychoactive compound derived from cannabis, has shown promising anticonvulsant potential. Our study, conducted in 19 centers across Italy, enrolled 108 pediatric patients with confirmed monogenic epilepsies. CBD was administered at 5 mg/kg/day, increasing to a maintenance dose of over 10 mg/kg/day, with a follow-up of at least 6 months. Results showed a significant reduction in seizure frequency at 3 months, with further improvement at 6 months. Additionally, the number of antiepileptic drugs required decreased, indicating a positive impact on patient management. This study reinforces CBD’s role as a safe and effective option for DRE, highlighting the need for ongoing clinical monitoring to maximize long-term benefits.