Efficacy and Safety of Cannabidiol in a Single-Center Pediatric Drug-Resistant Epilepsy Cohort: A Retrospective Study

Ambra Butera^1,2Giulia Spoto³Graziana Ceraolo²Maria Grella²Ivana Giunta²Maria Ludovica Albertini²Carla Consoli²Caterina Sferro⁴Maria Spanò⁴Gabriella Di Rosa^3*Antonio Gennaro Nicotera⁴

• ¹Unit of Child Neurology and Psychiatry, Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
• ²Division of Child Neurology and Psychiatry, Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, Messina, Italy
• ³Department of Biomedical, Dental and Morphological and Functional Imaging Sciences, University of Messina, Messina, Sicilia, Italy
• ⁴Unit of Child Neurology and Psychiatry, Maternal-Infantile Department, University of Messina, Messina, Italy

Background: Pharmacoresistance to conventional anti-seizure medications has been described in approximately 30% of the pediatric epileptic patients, making pharmacological management particularly challenging for physicians. Currently, cannabidiol (CBD) is approved as an adjunctive therapy in combination with clobazam for Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS), and as adjunctive treatment for Tuberous Sclerosis Complex (TSC). Studies on drug-resistant epilepsy (DRE) suggested that CBD antiepileptic properties may benefit a wider range of pharmacoresistant epilepsy syndromes.Objective: Our observational, retrospective, monocentric study aimed to evaluate the effect and safety of CBD in a real-world pediatric cohort with DRE.Methods: We recruited fifteen pediatric patients (7 females, 8 males; mean age: 12.33 ± 4.37 years) affected by pharmacoresistant epilepsy treated with CBD as adjunctive therapy. Inclusion criteria required a diagnosis of DRE, initiation of CBD treatment before 18 years of age, and at least 6 months period of follow-up after CBD initiation. Clinical, demographic, and instrumental data were retrospectively extracted from the medical records and caregivers’ reports. Based on seizure reduction, patients were stratified into “responders” (≥50%), “partial responders” (30-50%), and “non-responders” (<30%) groups.Results: CBD was used as an add-on therapy in 8/15 patients on-label (for DS, LGS, and TSC) and in 7/15 off-label. The maximum dose of CBD administered was 21 mg/kg/day, with an average dose of 16.5 mg/kg/day. 11/15 patients showed a reduction in seizure frequency: 7 were responders (2/7 seizure-free) and 5 were partial responders. Additionally, 11/15 patients showed improved social and environmental participation, as assessed using the Clinical Global Impression scale. Interestingly, brain magnetic resonance imaging revealed structural abnormalities in 5/15 patients, with 6/15 showing malformations of cortical development (4/6 responders, including 1 seizure-free).Conclusions: CBD demonstrated a good safety and tolerability profile and appeared to be a promising therapeutic option for the management of DRE. It offers a valuable alternative for seizure control and has a positive impact on social interaction, with overall improvement in the quality of life for patients and their caregivers.