Overview

• The eight-day, placebo-controlled study of 64 participants used an fMRI stop-signal task to show that tolcapone increases activation in the prefrontal cortex during inhibitory-control challenges.
• Greater engagement of the inferior frontal gyrus under tolcapone correlated with stronger response inhibition and reduced alcohol consumption among people with AUD.
• Tolcapone enhances dopamine levels in the prefrontal cortex by suppressing the enzyme catechol-O-methyltransferase, an effect linked to improved self-control.
• Authors propose shifting AUD pharmacotherapy toward boosting cortical dopamine to rescue impaired inhibitory circuits rather than solely targeting craving or withdrawal.
• Journal leadership and researchers stress that these mechanistic findings are preliminary and call for larger, longer trials to establish safety and therapeutic efficacy.