Scientists from the CU Anschutz School of Medicine have identified a new method to treat alcohol use disorder (AUD), using a drug that boosts dopamine in the prefrontal cortex, potentially offering a novel approach to managing the condition.
In a groundbreaking study, researchers at the University of Colorado Anschutz School of Medicine have identified a new approach to treating alcohol use disorder (AUD). The innovative method could revolutionize how AUD is managed, offering new hope to millions struggling with addiction.
Currently, AUD treatments function primarily in two ways: by reducing the euphoria associated with alcohol consumption or by lessening the cravings for alcohol.
“Those are important things for alcohol and substance use disorders — reducing how good the drug makes you feel or how much you want to use it,” corresponding author Joseph Schacht, an associate professor of psychiatry at CU Anschutz, said in a news release.
However, Schacht and his colleague Drew Winters, a research associate in the CU Anschutz Department of Psychiatry, hypothesized that targeting a different part of the brain could yield another effective treatment avenue.
Their research, published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, tested this theory with promising results.
Focus on the Prefrontal Cortex
“The current medications for AUD target the neurotransmitter dopamine in the reward-related parts of the brain,” Schacht added. “But we were interested in understanding how dopamine might act in a different part of the brain — the prefrontal cortex — and how its action there might affect a different behavior, which is behavioral control.”
By focusing on the prefrontal cortex — the brain region associated with decision-making and impulse control — the researchers aimed to improve behavioral control in individuals with AUD.
They turned to tolcapone, an FDA-approved drug initially designed for Parkinson’s disease, which increases dopamine levels in the prefrontal cortex.
Promising Results
In the randomized study, participants with AUD were given tolcapone or a placebo before performing a computer-based “stop signal task.”
This test required them to stop a particular action when signaled, assessing their impulse control capabilities.
Remarkably, those who took tolcapone performed better on the task.
“You have a greater number of trials where you just press the space bar,” added Winters. “You’re already primed to hit the space bar, then when a different signal comes up, you have to stop yourself and not press anything. We were measuring if they can stop, and we also want to see, when they make an error, are they making corrections afterward?”
MRI scans showed increased activation in the prefrontal cortex during the task, corroborating the belief that tolcapone enhances dopamine levels in this brain region.
Furthermore, participants reported drinking less alcohol in the week they were on the medication.
“Greater prefrontal cortex activation was associated with less drinking during that week, suggesting that the mechanism of increased control was having an effect on their behavior in the real world,” Schacht added.
“It was very gratifying to see that this medication is working in the ways that we expected it to, and that there were actually changes in the brain that associate with behavior,” added Winters. “That connection is really important.”
What’s Next?
While tolcapone has been phased out for Parkinson’s treatment, the findings open the door for developing new drugs that operate similarly to treat AUD and other substance use disorders.
Schacht, who has also researched the effects of GLP-1 agonist drugs like Ozempic on AUD, is now exploring tolcapone’s impact on patients with both AUD and attention-deficit/hyperactivity disorder (ADHD).
“Those patients are the ones who might especially benefit from being able to control their behavior more,” he said. “Because they have not only AUD, which is impairing the ‘brakes,’ but also this disorder related to difficulties with controlling impulsivity.”
The breakthrough provides a hopeful avenue for future treatments, potentially transforming the landscape of addiction therapy.
“I’ve worked in AUD medication development for a long time, and I’ve tested many medications with different mechanisms of action,” Schacht added. “It was very fulfilling to see that one that works in a different way could also be effective. It suggests that we might be able to broaden the space for what medications might be useful in this condition.”