Abstracts

Rationale: Studies indicate that treatment with Cannabidiol (CBD) improves seizure control. This large, open-label, single-center study evaluates the combined effects of a pharmaceutical formulation of CBD (Epidiolex® provided by GW Research Ltd) on seizure frequency (SF) and severity (Chalfont Seizure Severity Scale; CSSS). Methods: 24-month data were included in the analyses. Included in the analysis of the effect of CBD dose on SF were 132 subjects (62 adults and 70 children); 131 subjects (62 adults and 69 children) were included in the analyses of CSSS and in the combined SF/CSSS analyses. SF (diary) and CSSS (interview) were collected at baseline and at all appointments after initiating CBD at 5mg/kg/day with adjustments as tolerated q2 weeks by 5mg/kg/day up to a maximum of 50mg/kg/day. Other AEDs were adjusted as needed (especially clobazam and valproate). Response models were tested to provide best fit (mixed vs. compound symmetry structure covariance model).  The CBD dose and SF/CSSS relationships were identified by matching the CBD dose used after controlling for the baseline variables. Results: SF: The compound symmetry structure covariance model where the outcome was the percentage of total seizure frequency at baseline showed that for every unit of CBD dose increase there was a 0.00648 (t value=-3.94, p0.05). CSSS: The autoregressive covariance structure model where the outcome was the percentage of total CSSS at baseline showed that for every unit of CBD dose increase there was a 0.01184 decrease in the percentage of the baseline CSSS score in all participants.  The estimate of the coefficient of CBD dose for the adults was 0.01344 (t value=-8.63, p < .0001) and for children 0.00649 (t value=-3.92, p < .0001).  Finally, combined SF/CSSS analysis using the fit mixed models with the outcomes being the percentage change from baseline of the SF and CSSS measures revealed for all participants the coefficient of CBD dose being -0.01041 (t value=-7.80, p < .0001) indicating that for every unit increase in CBD dose there is a 0.01041 decrease of the product of the percentage of SF at Baseline and the percentage of total CSSS at baseline. For the adults, the estimate of the coefficient of CBD dose was -0.01094 (t value=-7.08, p < .0001) indicating that for every unit increase in CBD dose there was a 0.01094 decrease in combined SF/CSSS. For the children, the estimate of the coefficient of CBD dose was -0.00901 (t value=-3.77, p=0.0002) indicating that for every unit increase in CBD dose there was a 0.00901 decrease in the combined measure of SF/CSSS. Conclusions: The findings in this compassionate use, open-label study suggest that treatment with CBD improves both SF and CSSS in children and adults. Funding: State of Alabama