Cannabidiol (CBD) Treatment for Severe Problem Behaviors in Autistic Boys: A Randomized Clinical Trial.

Open-label and observational studies suggest cannabidiol (CBD) reduces problematic behaviors in autistic children. No controlled clinical trials have addressed safety, tolerability, and efficacy. We conducted a double-blind, placebo-controlled crossover study of plant-derived CBD (Epidiolex®) to determine safety, tolerability, and behavior effects in autistic boys. Autistic boys with severe behavior problems age 7-14 years were randomized to eight weeks of CBD up to 20 mg/kg/day and eight weeks of placebo separated by a four-week washout. Behavioral assessments were completed before and after each treatment phase. Plasma concentrations of CBD were quantified. Primary outcomes were changes in total score of the Repetitive Behavior Scale-Revised (RBS-R), Child Behavior Checklist (CBCL), and Autism Diagnostic Observation Schedule-2 (ADOS-2). Both groups improved on the RBS-R and CBCL, with no significant difference between groups. ADOS-2 scores improved in placebo group only, but this improvement disappeared when other medications taken by the children were included in the analyses. Blinded clinical impressions showed almost 2/3 of the participants had behavioral improvements with CBD; 1/3 showed either no change or improvement on placebo. A strong placebo effect was observed. CBD had an acceptable safety profile. We did not find CBD to be clearly effective at reducing the broad range of behaviors characterized by the primary outcome measures. There was clinically evident improvement with CBD in 2/3 of participants. A prominent placebo effect demonstrates the importance of placebo control in treatment studies. Medications taken for behavior may reduce blood levels of CBD and may affect outcome measures.Trial Registration https://clinicaltrials.gov NCT04517799 start date 6/1/2020.