Can GLP-1s dull your joy?

As millions of people take GLP-1 medications for obesity and diabetes, some users have begun asking an unexpected question: Can these drugs dull your ability to experience pleasure?

Across social media and online forums, some people describe feeling emotionally “flat,” less excited by activities they once enjoyed. They also mentioned feeling less interested in favorite foods, alcohol, shopping, sex or other rewarding experiences while taking the medications.

The reports have sparked questions about whether GLP-1s can cause a reduced ability to experience pleasure, known as anhedonia. While the theory is biologically plausible, the research so far tells a different story.

What the research actually shows

Studies to date have not found convincing evidence that GLP-1 medications cause anhedonia. Instead, research has generally found improvements in depression, mental well-being and quality of life among people taking the drugs.

Trends point toward better quality of life, fewer symptoms of depression and greater feelings of self-worth and motivation among people taking these medications. Many patients also report experiencing less “food noise,” the constant thoughts about eating that can make weight management emotionally exhausting, which may contribute to an overall sense of improved well-being.

“The big meta-analysis would say that there’s a trend toward improvement in psychological symptoms overall,” said Josh Neal, M.D., chief of the MUSC Health Wellness and Human Performance Integrated Center of Clinical Excellence (ICCE) and an obesity medicine physician. “I would say, overall, I’ve seen people enjoy mostly an improvement in their mental health symptoms.”

Early in the rollout of GLP-1s, regulators investigated whether the drugs might increase the risk of suicidal thoughts after reports emerged in Europe between 2020 and 2022. However, the evidence has since been reassuring.

“There is no increased risk of suicidal ideation or suicidality in general,” Neal said, noting that both randomized controlled trials and large population-based studies have failed to confirm the initial concern.

When it comes to anhedonia specifically, however, the evidence is much thinner because most studies weren’t designed to evaluate anhedonia. Instead, they measured broader mental health outcomes such as depression. Since anhedonia is only one component of depression, researchers may not detect changes unless they ask targeted questions.

One small study out of the University of Toronto Health System addressed that gap by examining motivated behavior, a surrogate marker for anhedonia. The researchers reported that semaglutide actually improved motivated behavior in people with depression.

“ Basically, anhedonia got better in the people who had depression and who were on the GLP-1,” said Neal.

Why the theory still makes sense

Neal said the theory isn’t far-fetched from a biological standpoint. GLP-1 receptors act on areas of the brain involved in reward processing and on parts of the dopamine system that help to determine what feels pleasurable and motivating.

“The biological and the neurobiological mechanisms are totally plausible,” Neal said. “But we haven’t seen it in the data.”

The same brain pathways are also thought to contribute to the reduced cravings for alcohol and other substances that have been observed in some people taking GLP-1 medications.

“Good data suggests that people have less alcohol use, less other substance use, when they’re on this medicine,” Neal said. “So they feel less of that reward overall.”

More research specifically focused on anhedonia will be needed to determine whether a small subset of patients experience these effects that current studies have overlooked.

“If you really want to find that out, you probably have to specifically ask about it,” said Neal.

What patients should know

Individual experiences can differ even if the overall evidence is reassuring. Some patients report feeling all-around improvements while others simply don’t like how they feel on the medication and stop taking it. Neal said that if patients notice emotional changes, they should discuss them with their healthcare providers rather than dismissing them.

“Everybody’s experience can be really different,” he explained. “These medicines do have a very powerful effect on areas of the brain.”

This is likely to become an important area of future research as scientists begin studying reward function directly rather than relying only on depression questionnaires.

“There have been lots of case reports where somebody had symptoms of anhedonia and then came off the medication, and it cleared up, which is a good indicator that the medication might have been contributory.”