SLPRCTMolecular autism2021

Cannabinoid treatment for autism: a proof-of-concept randomized trial.

Adi Aran, Moria Harel, Hanoch Cassuto and 6 others

PMID 33536055

WHAT IT FOUND

Whole-plant cannabis extract improved disruptive behaviors on clinician ratings compared to placebo, but showed no benefit on the primary parent questionnaire.

Pure cannabinoids were not significantly better than placebo. Somnolence was common.

Key findings

01On the clinician-rated primary outcome, 49% of participants receiving whole-plant extract responded compared to 21% on placebo, a significant difference.

02The other primary outcome, a parent-rated questionnaire of noncompliant behavior, showed no significant difference between whole-plant extract, pure cannabinoids, and placebo.

03Somnolence was the most frequent adverse event, reported by 27% of participants on whole-plant extract and 24% on pure cannabinoids, compared to 7.5% on placebo.

STILL TO COME

How it was doneWhat they foundWhat it means for SLPs

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What it does not show

The study was a proof-of-concept with a crossover design that failed due to order effects, limiting the analysis to the first period and reducing power. Discrepancy between primary outcomes: The clinician-rated measure showed benefit while the parent-rated measure did not, raising questions about the robustness of the finding. Many standardized questionnaire items were not applicable for lower-functioning participants, leading to missing data and reduced statistical power. The study did not assess long-term safety, pharmacokinetics, or the impact of genetic factors. High placebo response was observed, which is common in ASD trials and complicates interpretation.

Declared interests

The study was funded by BOL Pharma, an Israeli company that produces the cannabis extract used in the trial, and the National Institute for Psychobiology in Israel.

The easy way to misread this

Do not conclude that cannabinoids are an effective treatment for ASD core symptoms. The benefit was seen only on a clinician-rated global impression of behavior, not on the primary parent-reported measure of noncompliance, and pure cannabinoids failed to show significant benefit over placebo. The study was underpowered due to design issues, and the funding source had a commercial interest in the product.

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