Tetrahydrocannabinol and Cannabidiol in Tourette Syndrome.

Background: Tourette syndrome is characterized by chronic motor and vocal tics. There is preliminary evidence of benefit from cannabis products containing Delta9-tetrahydrocannabinol (THC) and that coadministration of cannabidiol (CBD) improves the side-effect profile and safety. Methods: In this double-blind, crossover trial, participants with severe Tourette syndrome were randomly assigned to a 6-week treatment period with escalating doses of an oral oil containing 5 mg/ml of THC and 5 mg/ml of CBD, followed by a 6-week course of placebo, or vice versa, separated by a 4-week washout period. The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range, 0 to 50 [higher scores indicate greater severity of symptoms]). Secondary outcomes included video-based assessment of tics, global impairment, anxiety, depression, and obsessive-compulsive symptoms. Outcomes were correlated with plasma levels of cannabinoid metabolites. A computerized cognitive battery was administered at the beginning and the end of each treatment period. Results: Overall, 22 participants (eight female participants) were enrolled. Reduction in total tic score (at week 6 relative to baseline) as measured by the YGTSS was 8.9 (+/-7.6) in the active group and 2.5 (+/-8.5) in the placebo group. In a linear mixed-effects model, there was a significant interaction of treatment (active/placebo) and visit number on tic score (coefficient = -2.28; 95% confidence interval, -3.96 to -0.60; P=0.008), indicating a greater decrease (improvement) in tics under active treatment. There was a correlation between plasma 11-carboxy-tetrahydrocannabinol levels and the primary outcome, which was attenuated after exclusion of an outlier. The most common adverse effect in the placebo period was headache (n=7); in the active treatment period, it was cognitive difficulties, including slowed mentation, memory lapses, and poor concentration (n=8). Conclusions: In severe Tourette syndrome, treatment with THC and CBD reduced tics and may reduce impairment due to tics, anxiety, and obsessive-compulsive disorder; although in some participants this was associated with slowed mentation, memory lapses, and poor concentration. (Funded by the Wesley Medical Research Institute, Brisbane, and the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically-funded research organization at the University of Sydney, Australia; Australian and New Zealand Clinical Trials Registry number, ACTRN12618000545268.)