This is your brain on GLP-1s

For many people, the first noticeable change after starting a GLP-1 medication isn’t necessarily the number on the scale — it’s the quiet in their head. The volume dial on their constant mental chatter about food gets suddenly turned way down, giving them more time to focus their thoughts on other things. 

But for some, the impact GLP-1s have on their brain goes even further: Researchers are learning more and more about how GLP-1 medications may influence mood, compulsive behaviors, substance abuse, and more. Many of the findings are still preliminary, but here’s what experts currently know about the possible mental health impacts of GLP-1 medications — and what questions remain unanswered.

It makes a lot of sense that medications like semaglutide and tirzepatide could impact the mind when you look at how they work to control hunger: by targeting hormone receptors in both the gut and the brain. There are GLP-1 receptors in the hypothalamus that are involved in hunger and satiety (fullness), and by impacting those receptors, the medications can reduce your appetite so you eat less.

But there are GLP-1 receptors in other parts of the brain as well. “They are in regions of the brain that modulate reward, and in those regions commonly thought to be involved with numerous mental health conditions including substance use disorders, binge eating disorder, and depression,” says Robyn Pashby, Ph.D., a clinical health psychologist and spokesperson for The Obesity Society. Plus, receptors in the hypothalamus (where the GLP-1 impacts hunger) are also involved in emotional responses, sexual drive, and sleep. 

In other words, the same biological processes that allow GLP-1s to influence appetite may also mean they can impact mood and behavior — and in some pretty surprising ways. This is something not surprising to many obesity medicine specialists: “As both a psychiatrist and an obesity medicine physician, I believe mental health and metabolic health are inseparable,” says Dr. Christine Glenn, D.O., clinical assistant professor in the department of psychiatry and behavioral sciences at the University of Kansas Medical Center.

It’s well known that GLP-1s help reduce overeating, but both anecdotal and scientific evidence suggests they could help control overconsumption of other sorts. “GLP-1 drugs activate receptors in the limbic system, which is responsible for mood and emotions,” says Pashby. As a result, less dopamine is released in areas of the brain associated with the drive to seek out food or drugs. Suppressing dopamine makes the lure of a reward — like donuts in the break room, a clickbait video in your social feed, or another glass of wine — feel less powerful. “GLP-1s turn down the volume on cravings,” explains Glenn, “and it appears this may apply not just to food but also alcohol, nicotine, and other substance-abuse cravings.” 

In a phase 2 clinical trial last year, participants with diagnosed alcohol use disorder who took a low dose of semaglutide didn’t stop drinking altogether — they weren’t necessarily trying to quit — but they reported reduced alcohol cravings and consumed significantly fewer drinks on the days they did have alcohol, compared to those on a placebo. Bonus: The smokers in the group also smoked fewer cigarettes per day during the trial. More recent research in U.S. veterans with type 2 diabetes found that taking any GLP-1 medication was associated with a lower risk of developing substance use disorders involving alcohol, cannabis, nicotine, cocaine, or opioids. And it reduced the risk of drug overdoses and other emergencies in participants with preexisting substance use disorders.

Since GLP-1 medications appear to dampen our hunger for pleasurable things, there’s a theoretical concern that the effect could go too far and lower mood across the board. And some research and anecdotal reports have born that out, finding an increase in depression and suicide risk associated with taking GLP-1s. Yet other studies show the exact opposite: that these medications seem to distinctly improve mental health-related quality of life. In fat, this past January the FDA asked manufacturers of GLP-1s to remove a warning about suicidal ideation from the medications’ labels after a comprehensive analysis of the data found no increased risk (the warning was based on reports in older weight loss medicines). There’s even some very early evidence to suggest that GLP-1 drugs could potentially work as a treatment for depression and anxiety.

Complicating this mixed bag of results is the two-way relationship between mental health and obesity itself. “We know that metabolic syndrome increases the risk of depression and having depression increases the risk of metabolic syndrome,” says Glenn. This is likely owing to the low-grade inflammation, stress hormones, and disrupted gut-brain communication that exacerbate both conditions. “GLP-1 receptor agonists may lower inflammation, reduce stress hormones, and help the brain and body communicate better,” says Glenn. “When these body signals are regulated, this can improve emotional health.”

While GLP-1s can directly impact the brain through these pathways, the weight loss they cause can affect mindset too. “People often experience improvement in self-esteem and anxiety and mood after weight loss,” says Pashby. “On one hand, they may feel and experience less judgment that often accompanies living with a larger body. On the other hand, reductions in inflammation and pain, the ability to engage in more physical activity, and improved sleep also are likely to benefit mood.”

What if you already have a mental health condition? The latest research indicates that semaglutide, for one, is more likely to lower the chance of it worsening — not raise it. “It is safe for people with mental health conditions to take GLP-1 medications for obesity or diabetes,” says Glenn. “I would recommend following closely with both an obesity medicine specialist and mental health provider; for patients on certain mental health medications, closer laboratory monitoring may be necessary.”

In another area of promising research, studies over the past several years suggest a connection between GLP-1 medications and Alzheimer’s disease, especially in people with diabetes, obesity, or both. These conditions are known to increase the chances of developing dementia, so it stands to reason that managing or reversing them could potentially reduce the risk. But GLP-1s may go one step further than other obesity and diabetes medications by improving not just weight and blood sugar, but also inflammation in the brain and additional dementia risk factors like cardiovascular disease, smoking, alcohol use, and depression. 

In two large 2024 studies, people with type 2 diabetes taking semaglutide were 48% less likely to be diagnosed with dementia and 67% less likely to be diagnosed with Alzheimer’s over the next one to three years, compared to those taking other diabetes medications. Likewise, in a study last year of people with obesity and type 2 diabetes, those taking either semaglutide or tirzepatide had a 37% lower risk of dementia over the seven-year follow-up versus those taking other diabetes drugs — women, people over 60, and those with a BMI between 30 and 40 saw the most benefit.  

But that doesn’t mean GLP-1s are a slam dunk for treating dementia. A phase 3 clinical trial published this year showed that taking 14 mg of oral semaglutide daily did not slow the progression of Alzheimer’s disease in people with mild dementia. The researchers suggest it may be that GLP-1s are better at helping to prevent cognitive decline before it starts — especially in people with obesity or diabetes — as opposed to treating it.

So could GLP-1 medications someday be prescribed specifically for mental health, even in people without diabetes or excess weight? Maybe, but for now, the science is still evolving. “Although GLP-1 medications have been in use for some time, we are really just in the early stages of exploring their utility specifically for mental health conditions,” says Pashby. “These are powerful medications that directly impact our brains, and I strongly encourage anyone to make sure that they have mental health support when taking them — not necessarily because there is a high risk, but because we are still unclear about how the benefits and risks vary by person given their individual history.” 

While researchers are increasingly optimistic about the potential psychological and cognitive benefits of GLP-1 medications, they’re continuing to sort out which effects come directly from the drugs themselves versus the broader health improvements that can accompany weight loss and better metabolic health. Currently, the best way to manage a mental health condition is to seek professional help and, if recommended, medication that is FDA-approved to treat your diagnosis.

GLP-1 medications are approved to treat obesity and diabetes, but their benefits may extend far beyond appetite and blood sugar. While more research is needed, early evidence suggests medications like semaglutide and tirzepatide could potentially support emotional, behavioral, and cognitive health — underscoring the growing understanding that treating metabolic health may have positive impacts throughout the body and mind.

All in all, whether or not you’ll get an emotional boost from your weight loss meds varies from one individual to the next. “For one person, taking a GLP-1 medication could mean improvements in food noise, anxiety (especially as related to eating and weight concerns), mood, and energy,” says Pashby. “However, these are not universally experienced outcomes.”