Effects of Cannabidiol on Auditory Mismatch Negativity in Autistic Children

Pharmacological treatments targeting core autistic features remain limited. In neurotypical adults, cannabidiol (CBD) alters mismatch negativity (MMN), an electrophysiological marker of automatic auditory deviance detection that has been associated with autistic traits. The effects of CBD on MMN, as measured using electroencephalography (EEG), in autistic children remain unknown. This secondary analysis of a pilot randomised, double-blind, placebo-controlled crossover trial examined the effects of 12 weeks of oral CBD oil on MMN during a duration-deviant auditory oddball task. We hypothesised that CBD would produce more negative MMN amplitudes and shorter peak latencies relative to placebo. Nineteen autistic children (6-12 years, 8 female) received CBD (dose) and placebo in randomised order, separated by an 8-week washout. Age-adjusted linear mixed-effects models tested Time (baseline, follow-up) x Treatment (CBD, placebo) effects on mean MMN amplitude and peak latency separately at Fz and FCz. Exploratory Spearman correlations examined baseline associations between MMN and Developmental Behaviour Checklist-2 (DBC-2) Social Relating scores. At FCz, latency decreased following CBD but increased following placebo but did not survive FDR correction (p = .029, pFDR = .058) and no other interactions were significant. Higher baseline DBC-2 Social Relating scores were associated with more negative MMN amplitude at FCz (rho = -.58, pFDR = .028) and Fz (rho = -.59, pFDR = .028). These findings provide tentative evidence that CBD may modulate MMN latency in autistic children. Larger trials should clarify CBDs effects on MMN and further examine the association between MMN amplitude and social-relating difficulties.