Summary: A randomized, double-blind crossover trial from the Center for Medicinal Cannabis Research at UC San Diego School of Medicine evaluated the safety and behavioral effects of cannabidiol (CBD) in boys with severe autism spectrum disorder (ASD). The study found CBD to be safe and well tolerated and clinicians reported meaningful improvements in many participants—particularly in aggression, hyperactivity, and communication—despite a substantial placebo response and no clear advantage on broad standardized behavioral scales.
Researchers enrolled boys aged 7–14 years with severe behavior problems related to autism. Participants were randomized to receive eight weeks of plant-derived CBD (up to 20 mg/kg/day) followed by a four-week washout and eight weeks of placebo, or the reverse sequence. Behavioral assessments were completed before and after each treatment phase, and plasma CBD concentrations were measured. Thirty participants completed the full crossover trial.
Key findings
- Safety and tolerability: CBD was well tolerated and caused no serious adverse events. Most participants were able to take the medication without major difficulty.
- Clinician-observed benefits: Blinded clinical impressions indicated that roughly two-thirds of the children showed behavioral improvement during CBD treatment, with commonly reported gains in reduced aggression and hyperactivity and improved communication in nearly 30% of participants.
- Standardized measures: On primary outcome measures—the Repetitive Behavior Scale-Revised (RBS-R), Child Behavior Checklist (CBCL), and the Autism Diagnostic Observation Schedule-2 (ADOS-2)—both CBD and placebo phases showed improvements. Differences between CBD and placebo were not statistically significant on the RBS-R or CBCL. ADOS-2 scores improved only in the placebo group, but that effect did not persist after accounting for other medications the children were taking.
- Placebo effect and medication interactions: The trial revealed a prominent placebo effect: both treatment arms improved over time. Additionally, concurrent behavioral medications appeared to affect CBD blood levels and may have influenced outcomes.
Overall, the study suggests that CBD has an acceptable safety profile and that clinicians observed clinically meaningful improvements in many participants. However, the lack of clear superiority over placebo on key standardized behavioral scales means efficacy is not firmly established. The pronounced placebo response highlights the need for rigorous, placebo-controlled designs in psychopharmacology research for autism.
These results add to the growing but still preliminary body of evidence around cannabidiol as a potential intervention for challenging behaviors in autism spectrum disorder. They emphasize two important points for clinicians, families, and researchers: first, CBD appears safe for short-term use in this population under study conditions; second, larger studies with careful control for concomitant medications, longer follow-up, and refined outcome measures are necessary to determine whether CBD provides reliable, clinically meaningful benefit beyond placebo.
Implications for practice and research
- Clinicians should interpret early positive reports of CBD cautiously because strong placebo effects can make small, uncontrolled studies misleading.
- Future trials should stratify or control for other medications that may alter CBD metabolism or clinical response.
- Researchers should consider combining clinician-rated impressions with sensitive, disorder-specific outcome measures targeted to aggression, hyperactivity, and communication to capture areas where CBD may provide the most benefit.
The study was conducted by investigators at UC San Diego School of Medicine and published in the Journal of Autism and Developmental Disorders. Lead investigators included Doris Trauner, M.D. (Departments of Neurosciences and Pediatrics) and Igor Grant, M.D. (Department of Psychiatry).
About this CBD, Autism, and psychopharmacology research news
Author: Miles Martin
Source: UCSD Health
Contact: Miles Martin, UC San Diego
Image: Image credit: Neuroscience News
Original Research (open access): Cannabidiol (CBD) Treatment for Severe Problem Behaviors in Autistic Boys: A Randomized Clinical Trial — Doris Trauner et al., Journal of Autism and Developmental Disorders. DOI: 10.1007/s10803-025-06884-y
Abstract (condensed)
Previous open-label and observational studies suggested that cannabidiol might reduce problematic behaviors in autistic children, but randomized controlled data were lacking. This double-blind, placebo-controlled crossover study evaluated plant-derived CBD (Epidiolex®) up to 20 mg/kg/day in boys with severe behavior problems aged 7–14. Primary outcomes included changes on the RBS-R, CBCL, and ADOS-2. Both CBD and placebo phases produced improvements on the RBS-R and CBCL without significant differences between treatments. ADOS-2 improvement occurred only in the placebo group and lost significance when controlling for concomitant medications. Blinded clinical impressions favored CBD—about two-thirds of participants showed clinician-rated improvement during CBD treatment. A strong placebo effect was evident. CBD demonstrated an acceptable short-term safety profile, but clear effectiveness across broad behavioral measures was not established. Further controlled research is needed to clarify CBD’s therapeutic role in autism and to explore interactions with other medications.