Preliminary Prospective Study of Pharmaceutical-Grade Cannabidiol for Seizure Frequency, Anxiety, and Comorbid Symptoms in Pediatric Epilepsy: Associations With Circulating Endocannabinoids and Lipid Biomarkers

Anxiety commonly co-occurs with childhood epilepsy, yet treatments targeting both are limited. Epidiolex (cannabidiol, CBD) is an FDA-approved treatment for seizures associated with rare pediatric epilepsies and may have anxiolytic effects. We evaluated its effects on seizures and anxiety in pediatric patients with refractory epilepsy, representing diverse seizure etiologies and circulating endocannabinoids and related biomarkers. Twelve participants (12.17 ± 5.17 years; 6 female) initiated Epidiolex for 4-6 weeks. Caregivers completed pre- and post-treatment seizure diaries; validated anxiety and quality-of-life assessments; and plasma endocannabinoids, related lipids, and CBD metabolites-including 7-hydroxycannabidiol (7-OH-CBD)-were measured. Post-treatment, 73% of caregivers reported improvements in anxiety and seizure frequency with minimal side effects and improved sleep. Plasma 2-arachidonoylglycerol increased from baseline to study end, with greater elevations in those with lower baseline concentrations. Plasma 7-OH-CBD increased from baseline to study end, confirming systemic CBD exposure. Epidiolex may provide anxiolytic benefits across pediatric epilepsy, potentially involving endocannabinoids.