Objective:

To evaluate cannabidiol (CBD) in pediatric patients with autism spectrum disorder (ASD), fluent verbal language and an estimated full-scale IQ of 80 or above.

Background:

Preliminary evidence suggests CBD may ameliorate challenges associated with ASD. Whether CBD benefits pediatric ASD without accompanying intellectual or language impairment remains unknown.

Methods:

We enrolled 23 participants, ages 7.8–17.8 (Mean [M] = 11.3 ± 2.8) with ASD and IQ ≥ 80 in a 6-week Phase-2 open-label trial of ≥98% CBD (Epidiolex^®, 100 mg/mL) at 3, 6, or 9 mg/kg/day using a Bayesian optimal interval dosing design. The primary endpoint was the CBD dose associated with the highest response rate (i.e., Clinical Global Impression Scale-Improvement [CGI-I] score = 1 or 2) on a target symptom domain designated individually based on informant report, standardized scales, and clinical observation. Secondary endpoints were effect sizes of changes from baseline in measures assessing ASD core and associated symptoms, and global functioning. Adverse events (AEs) were assessed weekly. Plasma CBD levels and clinical labs were obtained at the final visit.

Results:

All 23 enrolled participants completed the trial. The highest response (62%) was observed at 9 mg/kg/day (N = 8). Overall, 10 of 23 patients (44%) were responders. Response varied across domains: Irritability/Tantrums (N = 5, 60%), Social (N = 8, 50%), Anxiety (N = 5, 40%), Restricted, Repetitive Behaviors (N = 4, 25%), and Sleep Problems (N = 1, 0%). Dose correlated with individualized CGI-I (r = −0.42, N = 23, p = 0.04).

Individualized domain CGI–Severity scores improved from pre-(M = 4.6 ± 0.5) to post-(M = 3.9 ± 0.8) treatment, t₍₂₂₎ = −4.36, p ≤ 0.001; d = 0.91; 95%CI [0.37,1.03]. Social Responsiveness Scale-2 Total-Score (SRS2-T) had the largest effect size (p ≤ 0.001; d = 1.36, 95% CI [0.78–1.93]).

Of 222 reported AEs, 27 unique AEs were considered treatment-related. Most AEs (93%) were mild and expected (82%); none was severe. The most frequent related AEs were increased salivation (30%), increased sleep duration (39%), sleepiness/sedation (26%), increased dream activity (35%), and polyuria (22%). Vital signs, physical exams, weight, liver function tests, and complete blood counts were unaffected. CBD plasma levels did not correlate with response.

Conclusions:

In this preliminary study, CBD was well tolerated; AEs were mild–moderate. Mean SRS2-T and subscores decreased significantly with large effect sizes, shifting from the severe to the moderate range.

Clinical Trial Registration:

ClinicalTrials.gov Identifier NCT03900923.