Study identifies a promising new strategy for treating alcohol use disorder

Existing pharmacological treatments for AUD are modestly effective and primarily target alcohol craving or withdrawal symptoms. Researchers have identified a promising new approach for treating alcohol use disorder (AUD). A novel study found that the dopamine-boosting drug tolcapone increases activity in the prefrontal cortex (PFC) during self-control tasks. Greater activation of the inferior frontal gyrus, part of the PFC, was linked to improved behavioural control and reduced alcohol consumption. The findings from the study, published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, suggest that medications with a similar mechanism could potentially be used to treat AUD in the future.

The study involved 64 participants with AUD who were randomly assigned to receive either tolcapone, an FDA-approved medication that increases dopamine in the PFC by suppressing catechol-O-methyltransferase (COMT), an enzyme that degrades dopamine, or a placebo for eight days. Participants completed a behavioural control task called a “stop signal” task while undergoing functional neuroimaging (fMRI), during which they had to try to stop themselves from pressing a button on certain trials. This task reliably elicits activation of regions of the PFC that underlie response inhibition. Analysis showed that tolcapone increased activation of cortical areas implicated in inhibitory control, as assessed by the fMRI blood oxygenation response.
Joseph P. Schacht, PhD, Senior Author in the Department of Psychiatry at the University of Colorado School of Medicine, commented, “Our study shifts the focus to ‘rescuing’ impaired inhibitory control, which is the brain’s ability to stop unwanted thoughts or actions, a function often compromised in AUD. Our study suggests that medications that increase prefrontal dopamine are an important lead to pursue.”
Lead author Drew E. Winters, PhD, Department of Psychiatry, University of Colorado School of Medicine, added, “Based on previous studies, we anticipated that greater inferior frontal gyrus activation would be associated with better behavioural control, but we were pleasantly surprised to find that it was also associated with reduced alcohol consumption. This association validates the importance of impaired control in the pathophysiology of AUD.”
Source: Winters, D. E., & Schacht, J. P. (2025). Effects of COMT suppression in a randomized trial on the neural correlates of inhibitory processing among people with Alcohol Use Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.