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 $Δ$9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and $Δ$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.