Cannabidiol and neural correlates of threat anticipation in alcohol use disorder.

Hurzeler T.; Logge W.; Watt J.; McGregor I.; Suraev A.; Haber P.; Morley K. · Psychopharmacology · 2026

**Background & Methods** This cross-over, double-blind, randomized controlled trial investigated cannabidiol (CBD) as a potential pharmacotherapy for alcohol use disorder (AUD) by examining its effects on neural activity during threat anticipation. Non-treatment seeking individuals with DSM-V diagnosed AUD received either 800mg CBD or placebo while undergoing fMRI scanning during a fear anticipation continuous performance task (FCPT). **Key Findings** • CBD produced no statistically significant treatment effects on brain activity across region-of-interest or whole-brain analyses during high versus low threat anticipation stimuli, indicating the drug did not modulate neural responses to anticipatory threat processing in AUD patients. • Cognitive performance on the FCPT showed no main treatment effect; however, alcohol consumption the day before scanning was associated with longer response latencies, suggesting acute alcohol use may impair cognitive processing independent of CBD administration. • The absence of measurable neural or cognitive effects suggests that previously reported beneficial effects of CBD in AUD may operate through mechanisms distinct from anticipatory threat processing—potentially involving direct responses to salient stimuli rather than anticipation thereof. **Dosage & Administration** Single oral dose of 800mg cannabidiol or matched placebo administered prior to fMRI scanning during the fear anticipation continuous performance task. **Safety & Adverse Effects** Not reported. **Evidence Quality** This study represents a well-designed RCT with appropriate blinding and crossover methodology; however, several limitations reduce interpretability. The sample was small (n=14-16 for primary analyses), potentially underpowered to detect moderate effects. Participants were non-treatment seeking, which may limit generalizability to clinical AUD populations motivated for recovery. The single 800mg dose may not represent optimal therapeutic dosing or timing for neurobiological effects. The null findings are hypothesis-negative but do not exclude CBD efficacy through alternative mechanisms. The study provides Level 2 evidence and contributes to the mixed literature on CBD for AUD by narrowing the scope of putative mechanisms, though larger, adequately powered trials with treatment-seeking populations and optimized dosing regimens remain necessary to definitively establish CBD's therapeutic potential in AUD.

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