Clinical evidence has long suggested that the use of GLP-1 medications is linked to lower substance use. It’s also been speculated among patients taking the medications. Social drinkers, for example, contend that they no longer have the urge to order that glass of wine when they’re out with friends and smokers are finally able to stop.

Now a larger body of research shows what physicians and their patients have long noticed: Taking GLP-1 medications seems to significantly prevent and reduce addiction and substance use disorders. In a study published recently in The BMJ, researchers followed about 600,000 veterans with type 2 diabetes and found that GLP-1s prevented and treated substance use disorders when taken over a 3-year period.

The Most Surprising Aspect of GLP-1s

The most surprising outcome was that GLP-1s seem to reduce bad outcomes in those with a substance use disorder. Specifically, the study showed a 50% reduction in drug-related deaths and 40% reduced risk for drug overdoses. Researchers noted significantly fewer drug-related hospitalizations, drug-related emergency department visits, and suicide attempts.

“Reports of patients who started taking GLP-1s and lost interest in smoking, alcohol, and other substances without effort led us to wonder if these drugs were doing more than just quieting food noise, treating obesity, and treating diabetes,” said Ziyad Al-Aly, MD, study author and a clinical epidemiologist at the Washington University School of Medicine in St. Louis.

He said that as a result of these observations, researchers devised a study to look at whether GLP-1s prevented new addiction disorders as well as whether the medications treated and prevented the outcomes of addiction across all substances including alcohol, nicotine, opioids, and cocaine.

“It’s clear that GLP-1s seem to be reducing the risk of developing new onset addiction disorders across all substances and this is unique because there’s currently no other addiction medicine that works across the board,” said Al-Aly.

How GLP-1s Work to Reduce Addiction?

Researchers don’t know what’s happening in the brain to reduce addiction, but they have some ideas, said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.

“There are thoughts that it has to do with certain areas of the brain dealing with dopamine pathways and the impact on cravings and reward centers of the brain, but we don’t really have it figured out yet,” said Francavilla.

Different substances affect the brain in different ways. While alcohol is working on your gamma-aminobutyric acid receptors and tetrahydrocannabinol binds to cannabinoid receptors, for example, GLP-1 medications seem to stave off cravings that affect all of them in the reward pathways of the brain.

A study published in the Medical Sciences found that GLP-1 medications function as a “neuromodulator” that affects neuronal activity distributed in the brain, including in the hypothalamus and nucleus accumbens, a brain region that’s important for reward, motivation, pleasure, and addiction. But researchers need more high-quality data to really understand what’s going on.

How GLP-1s Reduce Death as a Result of Addiction?

Again, researchers don’t know the whole story, but they do know that if patients are using less substances, there are fewer opportunities to have an overdose or a death from them. In addition, if they’re not on substances, they’re less likely to be driving under the influence or participating in other risk-taking behaviors that might result in injury or death.

“If you’re using the substances less, then you’re less likely to experience negative repercussions from them,” said Francavilla.

Interestingly, The BMJ study found that the medications reduced the risk for suicide, which contradicts an earlier warning on the label that they actually increased the risk for suicide ideation. In January, the FDA requested the removal of a suicidal behavior and ideation warning on GLP-1 medications because the data no longer substantiated the risk.

Addiction causes people to feel poorly when they’re not taking the substance, and if they’re taking less of them, their mood is likely to stabilize. Some studies have shown that GLP-1s seem to improve mood and mental health in some of the patients taking them, although research on mental health and GLP-1 medications is very mixed.

More Work to Be Done on GLP-1s and Substance Use

While this is a very active area of research, it’s important to note that there’s still a lot we don’t know, said Daniel J. Drucker, MD, an endocrinologist at Mount Sinai Hospital and Lunenfeld Tanenbaum Research Institute, Toronto, Ontario, Canada, renowned for his breakthrough discoveries on the actions of the hormone GLP-1.

“The reduction in death is surprising and really positive, but we don’t have a lot of detail about what was causing the deaths before and what caused a reduction in them,” said Drucker.

He adds that we had similar thoughts about taking GLP-1s and a reduction in dementia, but when we actually did the randomized controlled studies, we sadly found that there was no effect.

“Real-world reports like this one generate exciting hypotheses, but so far, we still haven’t had one large randomized controlled trial or even a smaller trial that clearly shows that using a GLP-1 medication significantly changes rates of consumption,” said Drucker. “This study included only patients with type 2 diabetes, and we don’t know what would happen in patients without the condition,” he added.

Additionally, Francavilla contends that taking these medications and drinking too much can be a really dangerous combination for patients who are not eating enough and heavily drinking their calories. It can cause serious vitamin deficiencies and malnutrition, something Francavilla has seen in her practice.

“For patients who have substance use disorders, we can’t yet rely on these medications to solve that problem, these patients need extra care and monitoring when they’re on GLP-1 medications,” said Francavilla. This includes meeting with them more often and asking direct questions about alcohol consumption.

Still, the research is promising because again the medications seem to work across all substances rather than on a specific substance. Nicotine patches contain nicotine for smoking addictions, methadone, buprenorphine, and naltrexone work for opioid addictions, but researchers have never seen a medication that seems to affect all of them.

“These GLP-1s seem to be working on the brain in a way that they’re quieting these cravings,” said Al-Aly.