# CBD attenuates amygdala response to negative emotional stimuli in individuals with alcohol use disorder – a randomized controlled trial

## TL;DR

CBD reduces amygdala activity in response to negative emotions in people with alcohol use disorder, potentially lowering craving and relapse risk.

## Contribution

This is the first study to show CBD's effects on amygdala reactivity and subjective craving in individuals with AUD.

## Key findings

- CBD reduced bilateral amygdala reactivity to angry and fearful faces in individuals with AUD.
- Amygdala response correlated positively with subjective alcohol craving and negatively with CBD plasma levels.
- CBD had no effect on amygdala activation during neutral stimuli.

## Abstract

Negative affect is a key factor in Alcohol Use Disorder (AUD) associated with craving and relapse risk that is insufficiently treated by approved medications. Cannabidiol (CBD) has shown promising effects on negative affect, indicating its potential for addressing the neurocircuitry underlying negative affect in AUD.

This study investigates CBD’s effects on neural response to negative emotional stimuli and subjective alcohol craving in individuals with AUD.

We conducted the first neuroimaging study investigating CBD’s effects on neural responses to negative emotional stimuli and craving in AUD. The study was designed as two armed, 1:1 randomized, double blind, parallel group neuroimaging trial, enrolled N = 28 individuals with AUD. It compared the effects of 800 mg oral CBD versus matched Placebo (PLC) on blood oxygenated level dependent (BOLD) response in the amygdala during a validated emotion processing task and explored associations with CBD plasma levels and subjective alcohol craving.

CBD versus PLC attenuated bilateral amygdala reactivity to angry and fearful faces (pFWE <.05, small volume corrected), while CBD showed no effect on amygdala activation during the presentation of neutral shape stimuli. Amygdala response to negative emotional stimuli correlated positively with the extent of subjective alcohol craving (rLeft Amygdala =.52, pFDR =.01; rRight Amygdala =.52, pFDR =.01) and negatively with CBD plasma levels (rLeft Amygdala = -.68, pFDR = 0.002; rRight Amygdala = -.65, pFDR = 0.002).

In summary, CBD’s effects on amygdala reactivity to negative emotional stimuli in individuals with AUD support CBD’s potential for modulating emotion-processing circuits in AUD and CBD’s treatment potential for craving and relapse driven by negative affective states.

The online version contains supplementary material available at 10.1007/s00213-025-06860-5.