31297
A Placebo-Controlled Trial of Cannabinoids in Children with ASD
Objectives: To assess safety, tolerability and efficacy of cannabinoid treatment, in children with ASD, in a double-blind, randomized, placebo-controlled trial.
Methods: Children with ASD were randomly assigned to receive 1 out of 3 treatments for 12-weeks and cross-over to another treatment in a second 12-week period. Treatment options were: (1) oral placebo, (2) cannabis extract, contains cannabidiol and Δ9-tetrahydrocannabinol in a 20:1 ratio, at a cannabidiol dose of 10 mg per kilogram of body weight per day (maximum 420 mg) and (3) pure cannabidiol and Δ9-tetrahydrocannabinol in the same ratio and dose. The two treatment periods were separated by a 4-week washout period. The primary comparison was between the cannabis extract and the placebo. Secondary comparisons were between the pure cannabinoids and placebo and between the cannabis extract and pure cannabinoids treatments. The primary outcome measures were the clinical global impression of improvement (CGI-I) and the home situation questionnaire- ASD (HSQ-ASD) that taps disruptive behavior. The secondary outcome measures included the social responsiveness scale (SRS) that taps core ASD symptoms. A positive response to the treatment was defined as a rating of much improved or very much improved on the CGI-I scale, at least a 25 percent decrease in the HSQ total scores and at least a 15 percent decrease in the SRS score. We conducted a conservative parallel group analysis of cannabis extract versus placebo treatments for the first treatment period only.
Results: A total of 150 children (120 boys; mean [±SD] age, 11.82±4.1 years) were enrolled. ASD symptoms severity were in the high range in 78.7% of the children according to the Autism Diagnostic Observation Schedule (Comparison score = 8-10) and adaptive level in the Vineland behavior scales was "low" (standard score ≤70) in 88%. Fifty participants were randomly assigned to receive each of the 3 treatments, 45 in each group crossed-over to the second treatment and 44 in each group completed the study (12% attrition). In the first treatment period. The rates of a positive response to the placebo and cannabis extract respectively were: 21% and 49% on the CGI-scale (p=0.005); 44% and 53% on the HSQ-ASD and 22% and 50% on the SRS (p=0.015). The rates of positive response to each treatment in the first and second periods were not significantly different. The rates of positive response to pure cannabinoids and cannabis extract were not significantly different. Adverse events that were more prevalent in the active treatment groups included: somnolence, decreased appetite and disturbed sleep. There were no treatment related severe adverse events. The average number of adverse events during a 3-month period was 4.28, 5.02 and 4.87 for participants in the placebo, pure cannabinoids and cannabis extract groups, respectively.
Conclusions: Among children with ASD, the addition of cannabinoid treatment to conventional regimen resulted in greater reductions in the core- and co-morbid ASD symptoms than placebo, but was associated with higher rates of adverse events.