Semaglutide and other similar drugs are widely known for being able to regulate appetite and food intake to encourage weight loss. Now, scientists are researching whether these same drugs could be used to reduce cravings for other substances, including alcohol and nicotine — something that could open new avenues for addiction treatment.

How weight-loss drugs could treat addictive behavior

Semaglutide, which is branded as Ozempic for diabetes and Wegovy for obesity, as well as tirzepatide, which is branded as Mounjaro, have gained popularity in recent months as effective weight-loss treatments. Both drugs are glucagon-like peptide-1 (GLP-1) receptor agonists, which mimic the GLP-1 hormone to target areas of the brain that regulate appetite and food intake.

Although these drugs were originally intended to reduce patients' food cravings to facilitate weight loss, anecdotal evidence from both patients and providers suggests that they may also reduce other cravings, including for alcohol, coffee, and even shopping.

"The consistency that I'm hearing from all across patient groups is gain of control, whereas previously, there was a loss of control," said Gitanjali Srivastava, an internist and director of the obesity medicine program at Vanderbilt University Medical Center. "All of a sudden, there is a calm. It's like the calm after the storm."

According to Srivastava, patients have described a feeling as if "a valve was turned off" on several different behaviors after taking GLP-1 drugs, not just uncontrolled eating. "All of a sudden they're able to step back and say, 'oh, well I had this shopping phenomenon that was going on, gambling, addiction, or alcoholism, and all of a sudden, it just stopped,'" she said.

So far, research on how GLP-1 drugs impact addictive behavior is limited, but some animal studies have suggested that they may suppress consumption of certain substances. For example, studies on liraglutide found that the drug suppressed or reduced alcohol consumption in rats and African vervet monkeys. Studies on exenatide also found that it decreased nicotine intake in mice. The results on opioid-related behaviors were mixed.

Research into GLP-1 drugs is expanding

Currently, it's unclear how semaglutide and other GLP-1 agonists impact behaviors such as drinking and smoking, and researchers are in the early stages of studying their precise mechanisms in humans.

According to Daniel Drucker, from the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, the mechanisms behind the potential addiction curbing effects of GLP-1 drugs "are not very well-delineated," but are potentially related to dopamine availability.

"GLP-1 will suppress either the amount of dopamine or dopamine transporters, implying, indirectly ... that somehow we're not getting as much pleasure or not getting as much reward, because dopamine is induced by many of these substances that we take, which is part of the pleasure in taking them," Drucker said.

GLP-1 drugs may also impact GABA, a neurotransmitter that is targeted in certain medications for alcohol use disorder. In a recent study from Lorenzo Leggio and colleagues from the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, semaglutide reduced "binge-like" alcohol drinking in mice and alcohol dependence in rats.

"[W]e showed that the semaglutide is hitting some of the key factors related to addiction in our brain, such as dopamine and GABA," Leggio said. "So it's another piece of the pie, another proof of evidence that the semaglutide is working on those systems in the brain that we know are important for addiction."

Another potential explanation is that GLP-1 drugs may just blunt pleasure responses in the brain overall, which may make certain activities less appealing to people.

"It's not entirely surprising that some people might feel like they're not getting pleasure out of activities that they were getting pleasure out of before," said Jody Dushay, an endocrinologist at Beth Israel Deaconess Medical Center. "It may just be the case that ... it's just not scratching the itch anymore."

Health experts have also warned about the potential negative mental health impacts of anhedonia, or the reduced ability to feel pleasure, that may be caused by GLP-1 drugs. Currently, Wegovy contains a warning about suicidal ideation, and providers are advised to avoid prescribing it to patients with a history of suicidal thoughts.

"This is exactly why we have to do double-blind placebo-controlled studies, to look not only at the efficacy, as we hope, but also safety, in particular because people with alcohol use disorder and addiction in general often have a comorbidity with other mental health problems, including depression," Leggio said. He also stressed the importance of closely monitoring for depressive symptoms in these studies.

So far, data on GLP-1 drugs and how they affect addictive behavior is limited, but researchers are hoping to expand gather more evidence in the future, including by running randomized controlled trials in humans.

"Do you think that the semaglutide is going to dramatically save the world from addiction? The answer is no," said Leggio. "If you asked me, 'do you think that semaglutide is a promising medication to help people with alcohol use disorder?' I think the answer is yes." (Putka, MedPage Today, 6/2; Szalavitz, New York Times, 6/4)