A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome

Abstract

Introduction: Both Δ⁹ Tetrahydrocannabidiol (THC) and cannabidiol (CBD) components of cannabis, have been shown to have anticonvulsant effects. Cannabis oils are used to treat seizures in drug-resistant epilepsy (DRE). Recent trials provide data on dosing, side effects, and efficacy of CBD, yet there is a paucity of information on THC in epilepsy. Primary objective was to establish dosing and tolerability of TIL-TC150 - a cannabis plant extract produced by Tilray^®, containing 100 mg/mL CBD and 2 mg/mL THC- in children with Dravet syndrome. Secondary objectives were to assess impact of therapy on seizures, electroencephalogram (EEG) and quality of life.

Methods: Twenty children received add-on therapy with TIL-TC150. The dose ranged from 2 to 16 mg/kg/day of CBD and 0.04 to 0.32 mg/kg/day of THC. Patients were monitored for tolerability and adverse events, and secondary objectives.

Results: Nineteen participants completed the 20-week intervention. Mean dose achieved was 13.3 mg/kg/day of CBD (range 7-16 mg/kg/day) and 0.27 mg/kg/day of THC (range 0.14-0.32 mg/kg/day). Adverse events, common during titration included somnolence, anorexia, and diarrhea. Abnormalities of liver transaminases and platelets were observed with concomitant valproic acid therapy. There was a statistically significant improvement in quality of life, reduction in EEG spike activity, and median motor seizure reduction of 70.6%, with 50% responder rate of 63%.

Conclusions: TIL-TC150 was safe and well tolerated in our subjects. TIL-TC150 treatment resulted in a reduction in seizure counts, spike index on EEG, and improved quality of life measures. This study provides safety and dosing information for THC-containing cannabinoid preparations.

Figure 1

Study participant flow chart.

Figure 2

The doses of CBD (A) and THC (B) achieved for all participants during the intervention period. The Boxplots show mean values, with 25th and 75th percentiles. The whiskers denote the minimum and maximum doses.

Figure 3

Change in reported somnolence during intervention period, in 4‐week blocks. Rates of reported somnolence were high, and increased in the first 8 weeks during TIL‐TC150 titration, subsequently dropping during the remaining weeks. There was a reduction in somnolence during the last 4‐week period (weeks 17–20) when compared with the first 8 weeks (r = −0.97).

Figure 4

Percentage change in Seizure frequency. Each bar represents a study participant. Bars represent the percentage change in frequency of motor seizures during the primary end point period (17–20 weeks), compared with the pre‐intervention period (−4–0 weeks) measured by seizure diary. The red line represents the mean percentage change across the entire 20 weeks. Percentage changes for each participant are sorted from highest to lowest values. 2 participants were seizure free during the last 4 weeks.

Figure 5

Mean number of seizure free days in each 4‐week period comparing pre‐intervention (week −4–0) with each 4 week block of intervention period (weeks 1–20). The mean (bar) and standard deviation (tail) are shown below for all 19 participants. *P < 0.05; **P < 0.01