Can a drug already hailed for its ability to help with diabetes and promote weight loss also help people with alcohol use disorder reduce their cravings to drink?
That’s the focus of a National Institutes of Health-funded study being conducted by Joseph Schacht, PhD, associate professor of psychiatry at the University of Colorado School of Medicine and co-director of the Division of Addiction Science, Prevention, and Treatment.
Schacht is studying whether the pill form of the GLP-1 agonist drug Ozempic — known as semaglutide — can help curb cravings in those who have become addicted to alcohol.
“The thing that people most report when they take these drugs is that they're not hungry anymore, which is why they help you lose weight. They affect a hormone that makes you feel full,” Schacht says. “When longer-acting GLP-1 drugs like Ozempic were first approved for human use in the late 2010s, there also was an off-label effect where people were reporting that they were not interested in drinking and that they were not craving alcohol.”
Studying cravings
As craving is one of the core components of addiction, Schacht designed a double-blind trial — meaning neither the participants nor the researchers know who is getting semaglutide and who is getting a placebo — in which participants take a drug daily for two months and agree to be studied to see how their cravings are affected. Patients must have a body mass index of 25 or higher to account for the weight loss effects of GLP-1 drugs.
“Our primary outcome is if it reduces alcohol craving and how much people drink,” he says. “We're also doing brain imaging where we present pictures of alcohol to see if sematlutide reduces activation of brain areas associated with reward. Some of the approved medications for alcohol use disorder can reduce that. We're testing whether semaglutide has that same effect. If it does, that would suggest that the mechanism is through reducing craving and reducing the brain's response to reward.”
The researchers are looking at other measures of craving as well, including asking people what they drink most frequently, purchasing that alcohol, then pouring it in front of a participant, bringing it to their nose, and asking them to smell the liquid.
“We ask them to tell us how much they feel craving in that moment,” Schacht says. “We measure the brain response on the MRI scanner. We’re also measuring the concentration of the drug in the blood, as well as a biomarker of alcohol. We're asking people how much they drink, but we can also measure something called phosphatidyl ethanol, which is a chemical that increases in the blood if you're drinking heavily over a long period of time and decreases if you reduce your drinking or become abstinent.”
Benefits of cutting back
The results of the study won’t be available until later this year, but so far Schacht and his team have observed that participants are reducing their drinking but not becoming completely abstinent.
“That's consistent with what the drug does for food as well — people don't stop eating,” he says. “I would say that's a good outcome, if you drink less. There's a historical bias in alcohol and addiction treatment toward abstinence or nothing, but there’s a different approach called harm reduction, which says it's good if you do it less. If you can just reduce your drinking, you reduce your blood pressure, you sleep better, and you lose weight.”
A ‘Prozac moment’
Schacht says that between 10% and 15% of Americans meet the diagnostic criteria for alcohol use disorder, and that alcohol-associated deaths have significantly increased since the COVID pandemic. Alcohol is the third leading cause of preventable death in the United States, he says, after obesity and smoking. And though there are three FDA-approved drugs for alcohol use disorder, none of them is hugely effective.
“We've been looking for a more effective drug for a long time,” he says. “Our ultimate goal would be to conduct a larger phase three trial that would support an FDA indication; however, many drugs are used off label for other indications besides the ones they’re approved for. If there were data suggesting that these drugs were effective in reducing alcohol craving, we hope that physicians might start to prescribe them for that indication, even before a formal approval.
“I've been working in this area for 15 years, and this is the most exciting drug we've seen in that time,” he adds. “Some people are thinking of it as a potential ‘Prozac moment’ for alcohol and addiction. Prozac was a breakthrough drug, because it was the first effective antidepressant that was available broadly. And it seems like drugs in this class might have a similar effect for alcohol and addiction.”
People interested in being involved in the alcohol and semaglutide study can visit the enrollment link to schedule a screening phone call. Interested patients can also email alcoholstudy@ucdenver.edu or call (303) 724-2424 for more information.
