Abstracts

Rationale: Studies indicate that treatment with cannabidiol (CBD) improves seizure control. The relationship between seizure control and CBD level remains largely unexplored. In this large, open-label single-center study, we evaluated the relationship between the dose of a pharmaceutical formulation of highly purified CBD (Epidiolex®), CBD level, and seizure control. Methods: Patients participating in the UAB CBD Expanded Access Program (EAP) were approached for participation in this cross-sectional study. All participants had treatment refractory epilepsy, defined as failing =4 AEDs, including a trial of 2 concomitant AEDs. All AEDs must be at a stable dose 1 month prior to study enrollment (all inclusion and exclusion criteria are listed at uab.edu/cbd). CBD dosing was weight-based and could be increased every 2 weeks by 5 mg/kg/day up to a maximum dose of 50 mg/kg/day depending on tolerance and seizure control. Seizure counts were obtained at every clinic visit with frequency calculated per 2-week periods. Peak levels of CBD were drawn around noon for all participants (~4 hours after dosing) and were sent to a reference laboratory (NMS Labs, Willow Grove, PA). Results: 56 adults and 40 children (96 total; 52 female) received CBD levels (2 participants had incomplete data). Decreases in seizure frequency were noted for the entire sample from 72.4±191 seizures per period prior to CBD therapy to 35.0±104.5 (p=0.003) on CBD; for adults from 46.8±129 to 16.0±21.5, p=0.056; for children from 110.0±253.7 to 63.1±159, p=0.02. There was strong linear correlation between CBD dose (range from 5-50 mg/kg/d) and CBD level (range 7.1-1,200 ng/mL) in all participants r=0.648 (p0.158). When comparing all participants with ≥50% seizure reduction (N=51) to those with <50% seizure reduction (N=43), the level of CBD was significantly higher in responders vs. non-responders in the entire cohort (324±285 vs. 177±184 ng/mL; p=0.005), adults (394±314 vs. 233±231 ng/mL; p=0.042), and children (195±164 vs. 112±67 ng/mL; p=0.043); the CBD dose was also different between the groups (28mg/kg/d vs. 21.0mg/kg/d; p=0.017; 31mg/kg/d vs. 23mg/kg/d, p=0.060 for adults and 23mg/kg/d vs. 19mg/kg/d, p=0.271 for children). CBD doses and levels were typically lower in children when compared to adults: CBD dose 28.4 vs. 20.5mg/kg/d (p=0.013); CBD level 327 vs.151 ng/mL (p=0.001), respectively. However, the decreases in seizure frequency were not different between groups (p=0.541). Findings reported in this study are specific to Epidiolex and cannot be extrapolated to other CBD products. Conclusions: This analysis suggests that higher levels of CBD are associated with higher chance for seizure improvement (higher response rate) and that children may respond to lower doses of CBD than adults. Funding: Serina Therapeutics, Inc., Epidiolex was provided by GW Research Ltd, UAB EAP is supported by AL Department of Commerce (“Carly’s Law”)