Exploring the Potential of GLP-1 Drugs in Addiction Treatment

In April, neuroscientist Sue Grigson received a heartfelt email from a man who shared his challenging journey to overcome addiction—first opioids, then the very medication intended to aid his recovery.

This individual discovered Grigson’s research which indicated that specific anti-obesity medications might help reduce rats’ dependence on drugs like heroin and fentanyl. Encouraged, he tried quitting again, this time using semaglutide, commonly recognized as Ozempic. “That’s when he reached out to me,” Grigson recalls, noting that he finally felt drug- and alcohol-free for the first time as an adult.

Such stories have been on the rise in recent years, surfacing across online platforms, weight-loss clinics, and news outlets. People taking diabetes and weight-loss medicines like semaglutide (also known as Wegovy) and tirzepatide (branded as Mounjaro or Zepbound) report newfound abilities to combat long-standing addictions to various substances, including alcohol and cigarettes. Recent clinical data seems to support these experiences.

Earlier this year, a team led by psychologist Christian Hendershot at the University of Southern California released findings from a significant randomized trial showing that weekly doses of semaglutide reduced alcohol consumption, indicating that GLP-1 drugs might positively influence addictive behavior in those dealing with substance-use disorders. There are over a dozen randomized clinical trials underway worldwide, with results anticipated soon.

Researchers are investigating how these weight-loss drugs impact addiction by working on hormone receptors in brain regions tied to cravings, rewards, and motivation. Evidence is emerging that GLP-1 therapies can lessen urges for alcohol, opioids, nicotine, and cocaine through similar brain pathways that manage hunger and overeating. “Essentially, the neurobiological system activated by rewarding substances—like food and drugs—operates within the same framework,” says Roger McIntyre, a psychopharmacologist at the University of Toronto. Some researchers are even examining if these drugs could help alleviate conditions like dementia and depression.

However, experts caution that this research is still in its infancy. “We need to determine if it’s both effective and safe,” notes W. Kyle Simmons, a neuroimaging specialist at Oklahoma State University who leads a GLP-1 trial focusing on alcohol reduction.

Nonetheless, enthusiasm is building. Elisabet Jerlhag Holm, an addiction biologist at the University of Gothenburg, emphasizes that no new class of addiction treatments has gained regulatory approval for decades. If GLP-1 drugs prove effective in larger trials, she suggests it could represent a significant breakthrough.

A Journey from Lab Research to Public Attention

It hasn’t been an overnight sensation for GLP-1 drugs in addiction treatment. Initially developed to regulate blood sugar levels in people with type 2 diabetes, these drugs mimic the hormone GLP-1. As it turned out, they had the added benefit of suppressing appetite and promoting weight loss. They target hormone receptors in the pancreas and gut to regulate blood sugar and signal feelings of fullness, but they also act on critical brain regions involved in motivation and reward, decreasing cravings for high-calorie foods.

In the early 2010s, Jerlhag Holm contemplated whether these drugs might suppress other cravings. She conducted several studies revealing that they could reduce cravings in rats and mice addicted to substances like alcohol, nicotine, and stimulants. Her research also indicated that GLP-1 therapy could lower behaviors resembling relapse in animals who had previously abstained from drugs.

Despite her findings initially flying under the radar, they eventually caught the attention of Lorenzo Leggio, a physician-scientist at the NIH. In 2015, he and Jerlhag Holm began exploring the connection between GLP-1 and alcohol dependence in humans, discovering links between GLP-1 receptor gene variants and increased drinking behaviors.

Using post-mortem brain tissue, Leggio uncovered elevated levels of GLP-1 receptors in reward-related brain areas of individuals with alcohol-use disorders. He suspects this may be an adaptive response to the body’s reduced GLP-1 production due to alcohol consumption.

The mounting evidence catapulted GLP-1’s association with addictive behavior into public discourse this past May, sparked by an article in The Atlantic. The headline asked if scientists had inadvertently developed an anti-addiction treatment, marking a pivotal moment that led to increased media interest.

Nevertheless, early trials yielded unsatisfactory outcomes. A 2022 study from Denmark found that the first-generation GLP-1 compound, exenatide, didn’t significantly lessen heavy drinking days for patients with alcohol dependence. Another recent Swiss trial found that dulaglutide, another older GLP-1 drug, failed to aid those attempting to quit smoking.

However, other outcomes hinted at potential benefits. In one study involving 20 individuals with opioid-use disorders, Grigson and psychologist Scott Bunce found that liraglutide reduced opioid cravings by about 40%. Additionally, Fink-Jensen’s research using fMRI revealed lower activity in reward-related regions while participants viewed alcoholic drink images during exenatide treatment.

It’s worth noting that the first-generation drugs used in these studies are much less potent than newer agents like semaglutide or tirzepatide. These second-generation compounds bind more effectively to GLP-1 receptors and maintain longer activity in the body, showing tremendous promise across various health conditions. This begs the question: could these newer formulations effectively alter the behaviors of those battling substance misuse?

Anticipation for New Trials

Researchers are currently engaged in numerous clinical trials to explore this potential further. Fink-Jensen and his team have tested how a high dose of semaglutide, approved for weight loss, impacts alcohol consumption in a trial involving 108 participants with alcohol-use and obesity challenges, expected to report results in early 2026.

In the United States, Leggio and Simmons are spearheading their own parallel randomized trials examining semaglutide in moderate-to-heavy drinkers diagnosed with problematic drinking behaviors. Leggio’s trial will involve 52 participants, and Simmons’s will include 80, with Schacht at the University of Colorado also testing the oral version of semaglutide in his own alcohol trial.

Interestingly, Schacht points out that while pills may be less potent than injections, they might appeal more to those recovering from alcohol addiction, some of whom may have a history of using injectable substances. “People can hesitate with needles, as it connects to their past experiences with injection drug use,” he notes.

As these trials progress, researchers are utilizing fMRI to capture brain activity before and after treatment, observing how semaglutide changes responses to alcohol-related stimuli. This could provide insights into how well the drug disrupts the acute “wanting” that drives addiction and potentially reveal brain activity patterns indicating who might benefit most from GLP-1 therapy.

Understanding the Reward System

Scientists are beginning to form a clearer picture of how GLP-1 drugs affect the brain’s reward system. Animal studies have shown that addictive substances like alcohol, nicotine, and opioids activate similar neural pathways. This involves deep brain structures like the ventral tegmental area, where dopamine-producing neurons reside, linking to the nucleus accumbens, the pleasure center that responds to dopamine signals.

GLP-1 receptors are found throughout this network and, when activated, they may reduce both dopamine flow and other chemical signals, making rewarding experiences less compelling. Drugs like semaglutide mimic GLP-1’s actions, decreasing the dopamine response and, in turn, diminishing the urge to engage in addictive behaviors.

Stress responses also come into play. Studies indicate that when GLP-1 receptors are activated in regions like the amygdala, they help suppress the stress hormones associated with anxiety, withdrawal, and cravings. This dual action, calming the craving and the stress, may elucidate why these therapies appear to help reduce both substance consumption and relapse rates—at least in animal studies.