Objective:

To evaluate the efficacy of pharmaceutical-grade cannabidiol (CBD) in reducing seizures and co-morbid anxiety symptoms in pediatric epilepsy, and to examine changes in circulating endocannabinoids and related lipid biomarkers pre- and post-treatment.

Background:

Children with epilepsy frequently experience comorbid anxiety, yet pharmacologic options targeting both conditions remain limited. Epidiolex®, an FDA-approved CBD formulation, is effective for seizures associated with rare pediatric epilepsies and has shown anxiolytic effects in adults.

Design/Methods:

In this open-label exploratory study, 12 participants (ages 2-25; 6 female) received Epidiolex® for 4-6 weeks (5-20 mg/kg/day, titrated to therapeutic response). Caregivers completed seizure diaries, the Spence Children’s Anxiety Scale, and the Pediatric Epilepsy Side Effects Questionnaires at baseline and study end. Primary outcomes were changes in seizure frequency and anxiety symptoms. Blood samples were collected at baseline and 4 weeks to assess safety labs and changes in plasma endocannabinoids and other lipid biomarkers. 

Results:

Post-treatment, 73% of participants showed reductions in both seizure frequency and anxiety symptoms. Mean anxiety scores decreased from 17.1 at baseline to 8.2 at study end. Side effects were minimal, with participants generally reporting fewer negative side effects (e.g., drowsiness) from baseline to study end. Plasma concentrations of the endocannabinoid 2-arachidonoylgylcerol (2-AG) significantly increased from baseline to study end, with higher post-treatment 2-AG concentrations associated with greater reductions in anxiety symptoms. Plasma prostaglandin E2 (PGE2) significantly decreased, with lower post-treatment PGD2 associated with greater seizure reduction.

Conclusions: