Cannabidiol demonstrates safety, mixed efficacy for severe behavior problems in autistic boys

Cannabidiol demonstrates safety, mixed efficacy for severe behavior problems in autistic boys | Image Credit: © EKKAPON - stock.adobe.com.

A double-blind, placebo-controlled crossover trial led by researchers at the University of California San Diego School of Medicine found that purified cannabidiol (CBD) may be safe and tolerable in boys with autism spectrum disorder (ASD) and severe behavior challenges, but its efficacy in reducing core behaviors remains inconclusive. The study was published in the Journal of Autism and Developmental Disorders and represents the first controlled clinical trial evaluating the effects of purified CBD in this population.^1,2

“CBD was safe and well-tolerated in boys with severe autism and behavioral problems—participants were able to take the drug without difficulty and there were no serious adverse events,” the authors reported.

The trial enrolled 39 boys aged 7 to 14 years with confirmed diagnoses of moderate to severe ASD and persistent aggressive, self-injurious, and/or stereotyped behaviors. Participants were randomized to receive either eight weeks of oral CBD (up to 20 mg/kg/day) followed by eight weeks of placebo, or vice versa, separated by a four-week washout period. Epidiolex, a purified plant-derived CBD oral solution, was used as the study medication.

Primary outcomes included scores from the Repetitive Behavior Scale–Revised (RBS-R), the Child Behavior Checklist (CBCL), and the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). While both treatment groups showed improvement, the differences between CBD and placebo were not statistically significant on primary endpoints.

“While no significant differences were found between CBD and placebo on broad measures of behavior, clinician impressions suggested that approximately two-thirds of participants showed evidence of clinical improvement with CBD,” the study team wrote.

Blinded clinician observations indicated that 68% of children who completed the full 20-week study experienced behavioral improvements during the CBD phase. Reported improvements included reductions in aggression and hyperactivity as well as increased verbal communication in approximately 30% of participants. The placebo group also demonstrated marked improvements, underscoring the strong placebo effect observed in the study.

The researchers noted that the mean improvement in RBS-R scores was approximately twice as large in the CBD group compared with placebo (Cohen’s d = –0.44 vs –0.22), although this difference did not reach statistical significance (p = .095). Similar trends were seen in CBCL outcomes.

Plasma concentration analysis confirmed adequate systemic exposure to CBD and its active metabolite, 7-hydroxy-CBD. No tetrahydrocannabinol (THC) or related compounds were detected in any participant. Adverse events were generally mild and evenly distributed between the CBD and placebo phases. No serious adverse events were attributed to the study drug.

Of note, concomitant use of medications such as antipsychotics, alpha-2 agonists, and selective serotonin reuptake inhibitors was associated with lower CBD plasma levels and may have influenced outcomes. Sensitivity analyses accounting for these medications revealed stronger effects of CBD in participants not receiving behavior-modifying drugs.

While the authors emphasized the trial’s limitations, including small sample size, limited treatment duration, and the heterogeneity of autism, they concluded that purified CBD may hold therapeutic value for a subset of autistic children with severe behaviors.

“Our results underscore the importance of rigorous, controlled trials in evaluating the efficacy of novel treatments for autism,” the authors stated. “A study utilizing the same placebo-controlled and blinded approach but with a larger number of children, more targeted objective measures, and controlling for other medications used may be able to more definitively answer the question of whether CBD reduces problem behaviors in children with autism.”

The trial was funded by the Ray and Tye Noorda Foundation and the Wholistic Foundation. Epidiolex and placebo were provided by GW Pharmaceuticals (now Jazz Pharmaceuticals), which had no role in the study design, conduct, or analysis.

References:

1. University of California San Diego. Research alert: CBD might help children with autism, but more research needed. June 23, 2025. Accessed July 10, 2025. https://www.eurekalert.org/news-releases/1088388
2. Trauner D, Umlauf A, Grelotti DJ, et al. Cannabidiol (CBD) Treatment for Severe Problem Behaviors in Autistic Boys: A Randomized Clinical Trial. Journal of autism and developmental disorders. Published online Winter 2025:10.1007/s10803-02506884-y. doi:https://doi.org/10.1007/s10803-025-06884-y