This study evaluated the safety and efficacy of cannabidiol (CBD) transdermal gel in children with developmental and epileptic encephalopathies (DEEs).

The most severe group of epilepsies, DEEs, are characterized by frequent epileptiform activity that contributes to severe cognitive impairment and often, behavioral disturbances. Patients are typically drug-resistant and frequently have severe to profound disability; comorbidities include autism spectrum disorder, cerebral palsy, gait abnormalities, respiratory disorders and infections, gastrointestinal problems, and an increased mortality risk.

Of the 48 participants (26 male) enrolled and analyzed for safety, 46 were evaluated for efficacy in the initial 26-week treatment period. Median (range) age was 10 (3-16) years. Twenty-nine (60.4%) participants had ≥1 related adverse event over 26 weeks; 93% were mild or moderate. The most frequent were application site dryness, application site pain, and somnolence. From month 2-6, participants experienced ≥44% median reduction in the number of focal impaired awareness, focal to bilateral tonic-clonic, and generalized tonic-clonic seizures; ≥42% experienced ≥50% improvement in frequency of these seizures. Caregivers reported improvements in alertness, awareness, or energy in 58% of participants.

CBD transdermal gel reduced seizure frequency and was well tolerated in medically fragile children and adolescents with DEEs. This positive benefit-risk profile supports further study of CBD transdermal gel in DEEs.