Abstracts

Rationale: Both delta-9 Tetrahydrocannabidiol (THC) and cannabidiol (CBD), components of the cannabis plant, have been shown to have anticonvulsant effects. Mixed CBD/THC oils are currently being used to treat seizures in children with drug-resistant epilepsy (DRE). Recent clinical trials have provided data on dosing, side effects, and anticonvulsant efficacy of the CBD component, yet there is a paucity of comparable information on THC. The primary objective of this study was to establish dosing and tolerability of TIL-TC150 - a cannabis plant extract produced by Tilray® a licensed Canadian producer of medical cannabis, containing 100 mg/mL CBD and 2 mg/mL THC- in children with DRE due to Dravet syndrome. Secondary objectives were to assess the impact of therapy on seizures and quality of life. Methods: Twenty children received add-on therapy with TIL-TC150. The dose ranged from 2 mg/kg/day to 16 mg/kg/day of CBD and 0.04mg/kg/day to 0.32 mg/kg/day of THC. Patients were monitored for tolerability and adverse events. Impact on seizure frequency, and quality of life measures were determined. Results: Nineteen participants completed the 20-week intervention period. The mean dose achieved was 13.3 mg/kg/day of CBD and 0.27 mg/kg/day of THC. Adverse events were common but did not lead to participant withdrawal. Most were transient, seen during the titration phase and included somnolence, anorexia, and diarrhea. Laboratory abnormalities observed included elevation of liver enzymes and lowered platelets predominantly in those on concomitant valproic acid therapy. Til-TC150 administration was associated with a statistically significant improvement in quality of life was seen as well as a statistically significant reduction in clinical seizures, with a mean seizure reduction of 47.4%. In addition, analysis of prolonged electroencephalogram (EEG) recordings revealed a statistically significant reduction in spike activity. Conclusions: TIL-TC150 was safe and well tolerated in our subjects with DRE due to Dravet Syndrome. TIL-TC150 treatment resulted in a reduction in seizure counts and spike index on EEG, and improvements in quality of life measures. This study adds to the evidence for the efficacy of cannabinoids in the treatment of DRE and provides safety and dosing information for THC-containing cannabinoid preparations. Funding: This study was supported by funding from Tilray® and The Little Rocky Project.