Randomized Clinical Trial Tests Effects of CBD on Behavior in Boys with Severe Autism

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A recently published study examined the effects of cannabidiol (CBD) on severe autism spectrum disorder (ASD) symptoms in boys (1). As noted by the study, previous studies have suggested that CBD could have a therapeutic effect on symptoms, though controlled clinical trials have yet to be conducted on the safety and tolerability. The study, “Cannabidiol (CBD) Treatment for Severe Problem Behaviors in Autistic Boys: A Randomized Clinical Trial,” was published in May 2025 in Journal of Autism and Developmental Disorders. The CBD used in the study was Epidiolex, which has been approved by the Food and Drug Administration (FDA) for seizures in children, the study noted. The study was limited to males due to autism being more commonly recognized in boys, it added.

The double-blind, placebo-controlled crossover study involved 30 participants, ages 7–14, with moderate to severe autism. The participants were randomized into either a “placebo then CBD” or “CBD then placebo” group. The test period lasted eight weeks with a four week washout period. The dose for treatment Week 1 was 5 mg/kg per day, split into two doses; Week 2 increased to 10 mg/kg per day, split into two doses; and Weeks 3 to 8 increased to 20 mg/kg per day, split into two doses. Behavior measurements were taken at baseline and after treatment ended, along with blood samples.

Highlighted results include:

• Clinically evident improvement with the CBD treatment was seen in 68% of participants
• Reductions in aggressive behaviors and hyperactivity were most common, followed by improvements in communication, with some children using words for the first time
• Improvements on the Repetitive Behavior Scale-Revised (RBS-R) for the CBD group were nearly twice the improvements for the placebo group, but the differences were not significant between the groups
• Similarly, improvements in the Child Behavior Checklist (CBCL) questionnaire for both groups during the eight week trial, with no significant differences between them
• Only the placebo group showed improvements in Autism Diagnostic Observation Schedule-2 (ADOS-2) scores—which evaluated communication, social interaction, and imaginative play—but these disappeared once the children’s other medications were taken into the analysis

No THC was detected in the participants at any time, and reported side effects were mild. Limitations to the study included the potential effects on behavior from the COVID-19 pandemic, the lack of generalization of the results for girls with severe autism, and the lack of measurement for a dose-dependent effect of CBD. It was also suggested that some medications could affect CBD blood levels and outcomes.

“There were no significant effects of CBD over placebo on the primary outcome measures suggesting no global benefit of CBD in the treatment of boys with autism and severe behavioral problems,” the researchers stated in the discussion. “There was a prominent placebo effect found on all measures that may have dampened the ability to identify differences between groups.” Studies with larger groups of participants were recommended to examine differences that were seen between the groups.

Reference

1. Trauner, D.; Umlauf, A.; Grelotti, DJ.; Fitzgerald, R.; Hannawi, A.; Marcotte, TD.; Knight, C.; Smith, L.; Paez, G.; Crowhurst, J.; Brown, A.; Suhandynata, RT.; Lund, K.; Menlyadiev, M.; Grant, I. Cannabidiol (CBD) Treatment for Severe Problem Behaviors in Autistic Boys: A Randomized Clinical Trial. J Autism Dev Disord, 2025. DOI: 10.1007/s10803-025-06884-y.