Cannabidiol attenuates precuneus activation during appetitive cue exposure in individuals with alcohol use disorder

Alcohol use disorder (AUD) is a prevalent psychiatric condition characterised by problematic alcohol consumption and craving, necessitating the exploration of novel therapeutic interventions. Cannabidiol (CBD), a non-psychoactive component of cannabis, has shown potential in modulating neural processes associated with substance use disorders including AUD. This study aimed to investigate the effect of CBD on alcohol cue-induced activation of neurocircuitry associated with alcohol craving, and impact on mood, craving, and cognitive functioning in individuals with AUD. In a cross-over, double-blind, randomized trial, 22 non-treatment seeking individuals (M = 29 years) diagnosed with AUD (DSM-V) received either 800 mg of CBD or a matched placebo, completing two respective fMRI sessions. The primary outcome was neural activation in response to alcohol versus control visual cues, measured using a functional magnetic resonance imaging (fMRI) alcohol cue reactivity task. Secondary outcomes included assessments of mood, craving, and cognitive functioning. Region of interest analyses showed no differences in alcohol cue-elicited activation between the CBD and placebo conditions. However, exploratory whole-brain analysis indicated a significant treatment effect of CBD in the precuneus which was independent of cue specificity. There were no significant treatment effects of CBD compared to placebo on acute craving, mood, or cognitive functioning. In non treatment seeking individuals with AUD, CBD modulates precuneus activity during alcohol cue exposure. Further studies examining the effect of CBD on treatment-seeking AUD individuals are warranted.