Cannabidiol and neural correlates of threat anticipation in alcohol use disorder

Psychopharmacology (Berl). 2026 Sep 1. doi: 10.1007/s00213-026-07148-y. Online ahead of print.

ABSTRACT

RATIONALE: Cannabidiol (CBD) has previously been suggested to be an emerging pharmacotherapy for Alcohol Use Disorder (AUD), however, results from clinical studies remain mixed and potential mechanisms remain elusive.

OBJECTIVES: The aim of the present study is to investigate the potential for CBD to modulate neurobiological, cognitive and psychological processes during anticipation of threatening stimuli.

METHODS: In a cross-over, double-blind, randomized trial, non-treatment seeking individuals diagnosed with AUD (DSM-V) were recruited to receive either 800mg of CBD or matched placebo, completing two respective fMRI sessions. Region of interest (ROI) and whole-brain analysis were utilized to examine treatment effects on neural activity in response to high vs low threat anticipation stimuli during a fear anticipation continuous performance task (FCPT).

RESULTS: Sixteen participants contributed complete FCPT data and fourteen contributed analysable fMRI data. No main treatment effects were observed across cognition, regional or whole-brain activation. Drinking the day before the scan was associated with longer latencies in responses on the continuous performance task.

CONCLUSION: The present findings indicate that CBD did not produce measurable effects on brain activity or cognitive performance during threat anticipation in individuals with AUD suggesting that previously reported neural effects may be more closely related to direct responses to salient stimuli rather than anticipatory processes.

PMID:42678517 | DOI:10.1007/s00213-026-07148-y