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

ABSTRACT:

Background

Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5-21 years) with ASD.

Methods

We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and ?9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and ?9-tetrahydrocannabinol at the same ratio. Participants (N?=?150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI).

Results

Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n?=?45) versus 21% on placebo (n?=?47; p?=?0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n?=?34) versus 3.6 points after placebo (n?=?36); p?=?0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n?=?95); 23% and 21% on pure-cannabinoids (n?=?93), and 8% and 15% on placebo (n?=?94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results.

Conclusions

This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016, https://clinicaltrials.gov/ct2/show/NCT02956226.

SUBMITTER: Aran A 

PROVIDER: S-EPMC7860205 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature