Cannabidiol blood metabolite levels after cannabidiol treatment are associated with broadband EEG changes and improvements in visuomotor and non-verbal cognitive abilities in boys with autism requiring higher levels of support

TL;DR

CBD treatment in boys with autism may improve cognitive and motor skills, with effects linked to blood metabolite levels and EEG changes.

Contribution

This study is the first to use FDA-approved purified CBD in children with high-support autism and examine aperiodic EEG biomarkers.

Findings

CBD metabolite levels correlated with changes in aperiodic EEG measures across the scalp and occipital regions.

Higher CBD metabolite levels were associated with improved receptive vocabulary, nonverbal intelligence, and visuomotor coordination.

CBD treatment showed mixed effects, with some children experiencing cognitive and behavioral improvements.

Abstract

Oral cannabidiol (CBD) treatment has been suggested to alleviate severe symptoms of autism spectrum disorder (ASD). While many CBD preparations have been studied in clinical trials involving ASD, none has used purified CBD preparations or preparations approved by the U.S. Food and Drug Administration, nor have they focused on children with ASD with higher support needs. Previous studies have identified several candidate electrophysiological biomarkers of cognitive and behavioral disabilities in ASD, with emerging biomarkers including periodic (oscillatory) and aperiodic measures of neural activity. We analyzed electroencephalography (EEG) recordings from 24 boys with ASD and higher support needs (aged 7–14 years) from a prior double-blind, placebo-controlled, crossover Phase II Clinical Trial (NCT04517799) that investigated whether 8 weeks of daily CBD treatment (up to 20 mg/kg/day) improved severe behavioral problems, measured at baseline, post-CBD, post-placebo, and post-washout. Using linear mixed effect models, we found that aperiodic EEG measures varied with CBD metabolite levels in blood, as evidenced by a larger aperiodic offset across the scalp and a decreased aperiodic exponent across occipital electrodes. Furthermore, CBD metabolite levels in blood had a positive association with receptive vocabulary, nonverbal intelligence and visuomotor coordination. Our data suggest that this daily CBD preparation and administration schedule produced mixed effects, with some children showing improvements in cognitive and behavioral abilities while others demonstrated limited changes. Our findings support the inclusion of aperiodic EEG measures alongside traditional oscillatory EEG measures as candidate biomarkers for tracking the variable clinical impact of purified CBD treatment in children with ASD.

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