This is a bonus article that will not be included in my weight loss book, unless I decide to update it with a second edition.
People taking new weight-loss drugs say they curb cravings for booze, drugs, and nicotine. Did scientists inadvertently create an addiction-busting drug?
Shannon Hinderberger was just hoping to lose some weight when she began taking a GLP-1 receptor agonist drug in August of 2022. And over the course of 14 months, she did lose more than 60 pounds. But she ended up with a surprising result: She lost her desire for alcohol.
“Looking back, I was mildly dependent on alcohol to self-medicate for stress—I’d crave a glass of wine when I got home from work and I’d consume three-quarters of a bottle at a time, four times per week,” says Hinderberger, 49, a mother of two and a marketing consultant in Bend, Oregon. Now, the taste of alcohol no longer appeals to her. “It was a totally welcome side effect,” she says.
Side effects of drugs are typically considered a bad thing. But there are exceptions. Consider the seemingly miraculous glucagon-like peptide 1 agonist (GLP-1) drugs like Ozempic and Wegovy (semaglutide): They have helped countless people achieve dramatic weight loss, while curbing their hunger and interest in food. That was the drugs’ intended purpose but unexpected results are also being reported: Many people say their interest in drinking alcohol, smoking, or using recreational or illicit drugs diminished while they were using a GLP-1.
Now scientific evidence is mounting in support of these reports. In a study in the May 2024 issue of Nature Communications, researchers examined electronic health records from 83,825 people with obesity and found that those using semaglutide had more than a 50 percent lower risk of alcohol use disorder over a 12-month follow-up period; people taking other weight-loss drugs, such as naltrexone or topiramate, didn’t experience the same effect.
Another study in the August 2024 issue of eClinical Medicine found that semaglutide use for type 2 diabetes was associated with reduced nicotine overuse. And a new study in the journal Addictionfound that people with an alcohol use disorder had a 50 percent lower rate of drinking to the point of intoxication if they were taking a GLP-1 receptor agonist. Similarly, those with an opioid use disorder had a 40 percent lower rate of overdose while taking these drugs.
If further research supports these effects on substance overuse, these drugs could revolutionize the treatment of addiction, experts say.
Some people aren’t waiting for that to happen. As more people learn about the unexpected side effects of these drugs, some have begun to seek them out specifically to help with drinking or other substance use issues. But it’s important to remember that these medications are not yet approved for substance use disorders, says Patricia “Sue” Grigson, a behavioral neuroscientist and professor and chair of the neural and behavioral sciences at the Penn State College of Medicine.
Why does Ozempic curb alcohol cravings?
How can drugs that are designed to help people lose weight help with substance use challenges? That’s of course the million-dollar question, and the answer isn’t fully understood.
This much is known: “GLP-1 agonists influence dopamine pathways in the brain, particularly within the reward system,” says Fares Qeadan, co-author of the study in Addiction and an associate professor of biostatistics at the Loyola University Chicago Parkinson School of Health Sciences and Public Health. “By modulating these pathways, GLP-1 agonists seem to dampen cravings and reduce the reinforcing effects of addictive substances.”
But the effects on dopamine signaling may not be the whole story, experts say. “In addition, it is possible that the mechanisms related to satiety with food may relate to alcohol as well,” says Lorenzo Leggio, a physician-scientist at the U.S. National Institutes of Health and clinical director at the National Institute on Drug Abuse. In other words, these drugs may reduce the amount of food or alcohol it takes for someone to feel satisfied.
The theory is that these effects would occur regardless of whether the substance is alcohol, drugs, or nicotine.
In addition, “the GLP-1 agonists may make some drugs more aversive or unpleasant,” says Luba Yammine, an associate professor of psychiatry at UTHealth Houston who is currently the principal investigator of a clinical trial evaluating a GLP-1 agonist as a potential treatment for smoking cessation and post-cessation weight management. “For example, the person may get nauseated while smoking.”
In a previous study, Yammine and her colleagues examined the effects of an extended-release GLP-1 agonist, along with nicotine replacement therapy, in helping people who had prediabetes or were overweight quit smoking. The participants were randomized to receive a placebo or the drug, in addition to the nicotine patch. After six weeks of treatment, those who received the GLP-1 drug were more likely to abstain from smoking and experience fewer craving and withdrawal symptoms.
The biggest questions scientists are asking
So far, the results of studies in animals on the use of GLP-1 drugs for substance use are very encouraging and the early data in humans is also positive, says Kyle Simmons, a neuroscientist and professor in the department of pharmacology and physiology and the director of Oklahoma State University’s Biomedical Imaging Center.
“But we don’t have the gold standard randomized, controlled trials to say with confidence that this is a safe and efficacious medication for alcohol use disorder,” says Simmons.
In addition to the issue of efficacy, other questions remain. “We have a lot to learn about which formulation and which regimen will work best for which substance and which individual,” says Grigson.
Experts like Leggio also want to gain insights into how these drugs affect brain circuitry when someone is faced with temptation. Clinical trials to investigate these issues and others are underway at the National Institutes of Health and other medical institutions.
(It’s also too soon to know what role these drugs could play for people who don’t have a diagnosed substance use disorder but do want to cut back on drinking or smoking.)
In the meantime, there are three FDA-approved medications to treat alcohol use disorder. “There are many people who could benefit from these medications but aren’t receiving them,” Simmons. The same is true of medications to help people kick opioid or nicotine dependence. Right now, experts recommend turning to these first.
Treating both weight loss and addiction
Even though it’s too early for the GLP-1 medications to be used on a widespread basis for substance use problems, there are exceptions. “These medications are used clinically for the treatment of diabetes or for weight management,” Yammine says. “So if someone is taking a GLP-1 agonist for diabetes or weight management and they have co-occurring substance use issues, they may be helped by these medications.”
Steven Klein, an addiction medicine fellow at the Caron Treatment Centers’ residential treatment facility in Pennsylvania, prescribes these drugs to patients for this dual purpose.
“My personal experience has really molded my professional practice,” says Klein, who got sober from alcohol and drug use in 2016. During his subsequent medical residency, he gained 40 pounds. “I always struggled with my weight and I turned to food to deal with the stress of the pandemic—I used food in the same way I used drugs and alcohol,” he says.
In 2022, Klein started taking Mounjaro and lost 40 pounds. What’s more, the drug reinforced his sobriety. “I haven’t had a craving for alcohol or drugs in years,” says Klein. “It’s been transformative.” He sees a similar effect in patients to whom he prescribes drugs for concurrent obesity and substance abuse. “What I hear from people taking the GLP-1 drugs is they can feel their bodies change—their cravings for food and substances decrease,” says Klein.
“As an addiction medicine provider,” Klein adds, “I think of addiction as a record playing—our job is to lift the needle off the record long enough to teach them a different song.” So far, he says, the GLP-1 drugs seem to be having that effect, at least anecdotally.
Michael Cupps discovered that firsthand. In 2023, the father of two from Dallas told his doctor he wanted to stop drinking. “I had been questioning my relationship with alcohol for some time—it was my way of coping with stress,” says Cupps, 58, who works in the software industry. Because his doctor wanted him to drop some weight, she suggested that he try semaglutide. After Cupps started taking it, alcohol lost its pull on him. Eventually Cupps stopped drinking entirely and started going for walks to relieve stress. He also lost 20 pounds.
The future of addiction treatment?
With the benefit of further research, especially randomized, controlled trials, experts are hoping the GLP-1 drugs will broaden their arsenal of weapons against addiction.
“If it turns out these GLP-1 medications are effective for treating alcohol use disorder, right out of the gate they will become the most widely used medication for addiction treatment,” predicts Simmons.
Simmons sees the potential for GLP-1 drugs to treat addiction as being similar to the way SSRI antidepressants like Prozac became a major breakthrough for depression in the 1990s.
“That Prozac moment radically changed how we treat depression and how people see depression,” Simmons says. “It helped people see depression as a biological process, which reduced the stigma. Addiction is also a biological process. We may be on the verge of having a semaglutide moment for addiction—and that’s got to be a good thing.”
Ozempic and Mounjaro have another benefit: treating inflammation
A new study in mice shows that popular weight loss drugs can lower inflammation. What might this mean for the treatment of other diseases and neurodegenerative conditions?
Ozempic, Mounjaro, and similar drugs have dominated headlines in recent years as research has shown how effective they are for treating type 2 diabetes and obesity. But a new study reveals this class of drugs, known as GLP-1 agonists, may also reduce inflammation throughout in the body. That finding suggests they may be useful for treating a wide range of diseases, such as Alzheimer’s or Parkinson’s, or at least inspire research into new ways to treat neurodegenerative or autoimmune diseases.
The new study, published in Cell Metabolism in December, suggests that one major way the drugs work is by causing the brain to send signals to reduce inflammation throughout the body.
This has “broad implications” in part because of how widely used these drugs are, says Mike Schwartz, an endocrinologist at the University of Washington in Seattle who was not involved in the study.
We think about using these drugs to treat obesity and type 2 diabetes, but maybe there are other ways we can use them, says Schwartz.
Inflammation refers to the immune system response to perceived threats in the body. Good inflammation occurs when the immune system gears up to fight a pathogen, such as a bacteria or virus, but metabolic diseases, such as type 2 diabetes and obesity, involve unhealthy inflammation that can injure tissues.
“We need that good inflammation to fight infection,” says senior author Daniel Drucker, an endocrinologist at the Lunenfeld-Tanenbaum Research Institute and University of Toronto in Canada. “But we don’t want inflammation to persist over time, particularly if we have these metabolic conditions, because it will cause heart disease, it will cause diabetes, it will cause obesity complications.”
It has long been known that inflammation decreases when people take GLP-1 agonists, but no one knew why or how.
Beyond weight loss and diabetes
GLP-1 stands for glucagon-like peptide 1, a natural hormone made in the body that has a varied range of effects, including stimulating the release of insulin, slowing the digestion process, reducing appetite, and even blunting the brain’s interest in food.
GLP-1 agonist drugs that mimic this hormone—such as Ozempic and Mounjaro—were initially developed to treat type 2 diabetes, but clinical trials then revealed their potential to treat obesity. Ozempic, whose active ingredient is semaglutide, was later approved as Wegovy to treat obesity; and Mounjaro, whose active ingredient is tirzepatide, was recently approved as Zepbound to treat obesity. Another GLP-1 agonist used in this study, exenatide, is a diabetes medication known by the brand names Bydureon and Byetta. Clinical trials have continued to explore ways these drugs might improve other conditions.
For example, a major trial at the end of 2023 revealed that semaglutide reduced risk of heart attacks, stroke, and cardiovascular deaths. Other trials have shown that semaglutide may improve fatty liver disease and chronic kidney disease. Yet more clinical trials are in progress to investigate GLP-1 agonist effects on depression, alcohol use disorder, and nicotine addiction, as well as Alzheimer’s and Parkinson’s diseases.
But even as researchers try to learn the many ways these drugs may affect different human diseases, they’re also trying to learn how these drugs work.
Inflammation in the body
Drucker wanted to figure out how GLP-1 agonists reduce systemic inflammation in the body, as a decade of research has shown they do.
GLP-1 agonists act by triggering GLP-1 receptors, proteins on the surface of certain cells. When these receptors receive a signal from the GLP-1 hormone, it prompts the cell to complete all GLP-1 functions. Most of the cells with a lot of GLP-1 receptors are in the pancreas—the location of insulin producing cells—and in the brain, which curbs appetite and controls the body’s food reward system. But there are cells throughout the body that also have fewer GLP-1 receptors and respond to the hormone.
Despite recent trials showing that GLP-1 agonists reduce cardiovascular disease, the heart doesn’t have many GLP-1 receptors, Drucker says. Similarly, despite studies showing GLP-1 agonists improve liver and kidney disease, those organs don’t have loads of GLP-1 receptors either, raising questions about how GLP-1 agonist drugs have such significant effects on those organs.
White blood cells—inflammatory cells of the immune system—do have GLP-1 receptors, but “it was clear that GLP-1 agonists damped down inflammation likely more than was occurring just by their effect directly on white blood cells,” says Eva Feldman, a neurologist at the University of Michigan. There just aren’t enough GLP-1 receptors in white blood cells to account for how much these drugs reduced inflammation.
As Drucker’s team conducted various experiments, they eventually deduced that GLP-1 “must be working at least partly indirectly,” possibly through the nervous system, “because what’s the one system we have that can talk to every part of our body?” Drucker says. “It’s our brain and nervous system. It can send signals everywhere.”
Can the brain reduce inflammation everywhere?
To test that hypothesis, the researchers first induced inflammation in mice.
In one experiment they triggered inflammation with synthetic chemicals; in another they used a mixture of bacteria. Then they gave these mice exenatide, semaglutide (Ozempic), or tirzepatide (Mounjaro) and measured the subsequent reductions in inflammation from each drug.
In the next experiment the scientists bred several different strains of mice that were genetically engineered to lack GLP-1 receptors in various parts of the body: in white blood cells, in various organs, and in the brain.
Again, the researchers induced inflammation in each of these mice, gave them exenatide, semaglutide or tirzepatide, and observed whether the drugs suppressed inflammation.
“When we blocked the GLP-1 receptors in the brain,” Drucker says, “we no longer suppressed inflammation” in other parts of the body. The mice missing GLP-1 receptors in the brain had substantially more inflammation than the other mice after all received the drug.
That suggests that the absence of GLP-1 receptors in the brain prevents the GLP-1 drugs from reducing inflammation as effectively as they did in the other mice, which just lacked the receptors in other cells or organs.
The finding is surprising because “the general perception is that that’s not really how inflammation works,” Schwartz says. Conventional ideas about inflammation suggest that the damaged tissue sends out signals telling the immune system what to do, and it’s still likely that occurs as well. But these findings show “that the brain actually is playing a role and can be targeted therapeutically,” Schwartz says.
Next steps
There were already other known ways that GLP-1 agonist drugs may have been reducing inflammation. One was by decreasing glucose and fat tissue since high glucose levels and fat cells both cause inflammation. Another is that the sparse GLP-1 receptors that do exist in various organs may indeed play a role. But neither of those two mechanisms was sufficient to explain the drop in inflammation.
“I think this is the third piece to the puzzle,” Drucker says. “Maybe part of the story is that the brain is instructing these other tissues and organs to dampen down the inflammation.”
Drucker remains cautious about what these findings mean. “I don’t want to pretend this is the entire answer,” he says, but the study has “opened a new way of thinking about how GLP-1 benefits us long term.”
The next steps are to figure out how the brain is lowering inflammation, perhaps through experiments that, for example, direct specific nerves to reduce inflammation. Research published in 2000 from the lab of neurosurgeon Kevin Tracey, for example, has shown that the vagus nerve can turn off inflammation. But the body has a lot of different nerve pathways.
“I think over the next few years, you’re going to see a whole lot of additional experiments digging down to try and identify more precisely those pathways,” Drucker says.
One hope is that a better understanding of how GLP-1 agonists reduce inflammation in the brain could reveal possible therapies for neurodegenerative diseases like Alzheimer’s.
It’s well-established that inflammation in the brain likely contributes to Alzheimer’s, and inflammation has therefore emerged as a therapeutic target for the disease in recent years.
“But how best to alter that inflammation and whether changing it will change the course of the disease, that’s less well understood,” Feldman says. Drucker’s findings “could be really good for neurodegenerative disease, but the jury’s out.”
Drucker is similarly cautious about what these findings mean for conditions like Alzheimer’s that have eluded effective therapies for so many years.
Similarly, although inflammation plays a role in Parkinson’s disease, it’s far too early to know whether GLP-1 agonists could slow the disease’s progression, especially when mouse studies have been far less predictive of success in the areas of neurodegenerative disease than they been in inflammation and metabolism. The broader implication of these findings is that scientists may want to consider investigating whether the brain can be targeted to treat not only metabolic diseases but inflammatory disease states as well. “I’m not saying it will work,” Schwartz says, “but it opens the door pretty wide.”
Like any good scientific discovery, says Tracey, president and CEO of the Feinstein Institutes for Medical Research in New York, the study answers some questions while raising many more. “I think it will accelerate more interest in the important question of what else we have to do to know how this works to treat inflammation and to potentially see the launching of more clinical trials that might help a lot of people.”
Translating findings from mice to humans
A major caveat of Drucker’s study is that it was done in mice.
“There’s always a gap between what is possible to know in humans and what we infer from animal models,” Schwartz says. But the data here are strong enough, he says, “that if someone wants to come along and say, well, that’s just not true in humans, then the onus is on them to show why it isn’t true.”
Tracey agrees that some mice studies translate better to humans than others, and this is one of the more translatable ones.
“I’ve been impressed in the last 30 years with how much is actually translatable between mice and humans in the fields of inflammation and metabolism,” Tracey says. But he and other scientists remain cautious about what this means specifically for the use of GLP-1 agonist drugs. “We’re still learning the benefits and risks to a new class of drugs,” Tracey says. “These things take a long time before we really understand how they work and how to use them.”
Resources
nationalgeographic.com, “Ozempic has a surprising side effect: Drinking less alcohol.” By Stacey Colin; nationalgeographic.com, “Ozempic and Mounjaro have another benefit: treating inflammation.” By Tara Haele;
Weight Loss Articles
https://common-sense-in-america.com/2023/04/12/losing-weight-leads-to-better-health-not-necessarily/
https://common-sense-in-america.com/2023/04/25/hormones-that-control-your-appetite/
https://common-sense-in-america.com/2024/07/02/the-unexpected-health-benefits-of-ozempic-and-mounjaro/
https://common-sense-in-america.com/2024/10/04/ozempic-quiets-food-noise-in-the-brain-but-how/
https://common-sense-in-america.com/2024/11/26/obesity-drugs-would-be-covered-by-medicare-and-medicaid-under-biden-proposal/
https://common-sense-in-america.com/2024/12/05/ozempic-has-a-surprising-side-effect-drinking-less-alcohol/