Ozempic: A Promising Drug for Addiction and Brain Disorders

Ozempic was the most prominent word in biomedicine this year.

The drug’s effectiveness in treating diabetes, which it has FDA approval for, and obesity astonished doctors. It became a “miracle” weight-loss drug in the year’s zeitgeist on social media, as it can help people lose weight easily—for health or for vanity.

It’s understandable. Diet pills have a troubled and long history. From “rainbow pills” loaded with amphetamine to the infamous fen-phen and its fatal consequences in the heart and lungs, these pills have a lethal reputation.

Scientists have been looking for a pill that safely and effectively suppresses appetite without harmful side effects. Ozempic is closer to meeting that criteria than any other drug. It mimics the body’s natural reaction after a filling meal—it makes the user feel satiated. The pounds disappear without the need to fight constant hunger.

The drug could save the lives of many people who suffer from obesity. Excess weight increases the risk of stroke, heart and liver disease, sleep apnea, joint issues, and some cancers. A large clinical trial this year involving tens of thousands of overweight people who don’t have diabetes showed that semaglutide, Ozempic’s main ingredient, lowered the chances of stroke and heart attack, as well as death from cardiovascular problems.

The drug is also gradually shifting how society views obesity—it’s not a lack of self-control, but a treatable chronic medical condition.

But Ozempic and similar drugs—like Wegovy, another semaglutide-based medication that has FDA approval for weight loss—are ready for the next challenge: addressing various brain disorders, such as Alzheimer’s and Parkinson’s. Clinical trials are in progress for addiction, and the drugs show early signs of success against bipolar disorder and depression.

Gut to Brain

How can drugs that help with diabetes and weight loss also benefit mood, addiction, and neurodegenerative diseases?

It depends on how Ozempic and Wegovy work. They both contain semaglutide, a substance that imitates a hormone called glucagon-like peptide-1, or GLP-1. When our gut detects an influx of nutrients after a meal, cells in the intestine secrete the hormone. GLP-1 instructs the stomach to slow down the rate at which it empties its contents. It also stimulates the pancreas to produce more insulin to regulate blood sugar—maintaining a metabolic state that’s essential for brain health.

But here’s the key. GLP-1 doesn’t just stay in the gut; it also easily accesses the brain.

The brain often blocks large molecules that could harm its delicate neurons with a tight cellular barrier, but it welcomes GLP-1. The hormone activates neurons in various brain regions, including the “reward center” and hippocampus, which are crucial for mood and memory regulation.

This makes neuroscientists curious: Can GLP-1 modify brain function to enhance neurological or mental health?

Addiction

One intriguing consequence of people using drugs similar to GLP-1 is that they have less desire for alcohol and other psychoactive substances. The reason for this is not clear, but it may be because the hormone weakens reward circuits in the brain. One study, for instance, offered alcoholic monkeys (yes, that exists) an open bar for four hours a day. These monkeys adore their booze. Living in the Caribbean, they are infamous for stealing alcoholic beverages from tourists. After two to five weeks of treatment, those who received injections of drugs similar to GLP-1 decreased their alcohol consumption even when faced with unlimited alcohol. Instead, they eagerly drank plain water. GLP-1 analogs may also help reduce smoking addiction.

A small clinical trial in 2021 found that smokers, while wearing nicotine patches, easily quit smoking when injected with an early version of a GLP-1 drug. Almost half of the participants treated with GLP-1 stopped smoking—a success rate nearly twice that of a control group that only wore nicotine patches. As with any new drug, the results are not conclusive.

One study for alcoholism using an early version of a GLP-1 analog found little difference in people undergoing behavioral therapy. Both groups reduced their alcohol intake, but the GLP-1 drug did not further enhance recovery. A trial using the drug for cocaine addiction also found minimal effects. That said, semaglutide is much more effective than early versions of GLP-1 analogs. Clinical trials are in progress, some using brain-imaging to see how the brain responds to the drug in real time.

Mood Disorders

Depression and other mood disorders are also potential targets for GLP-1 analogs. Mood is often seen as purely neurological, but it is closely connected to other parts of the body, including the gut. People with depression often experience changes in appetite and gut hormone levels—including GLP-1. An analysis of six trials with over 2,000 participants found that drugs mimicking GLP-1 relieved their depression. Another trial involving 29 people with bipolar disorder or depression found that the drugs stabilized mood swings for at least six months after treatment.

The drugs could work by altering neural connections in the brain. Neurons resemble trees, with large trunks that process information and branches that “communicate” with neighbors. These branches shrivel in a depressed brain, making it hard for neurons to connect to each other and form healthy networks. Moreover, the hippocampus—a brain region vital to memory—has difficulty producing new neurons, which help maintain memory and mood. All these changes contribute to mood disorders.

Traditional antidepressants and newer treatments, including ketamine, reverse depressive symptoms by helping neurons grow back their branches. Initial studies in mice suggest that drugs similar to GLP-1 also rewire brain regions that contract with depression and ease manic symptoms in bipolar mice. While still preliminary, these results open the way for further testing in humans.

Alzheimer’s Disease

Dementia is a harrowing journey for those who suffer from symptoms and their families. Neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease, gradually erode memories, reasoning, and eventually take lives. Chronic inflammation, which harms neurons and blood vessels and is linked to unregulated levels of blood sugar, is a major factor. Because Ozempic and similar drugs lower blood sugar, they could also potentially reduce inflammation in the Alzheimer’s brain and slow the loss of cognition. A few trials are underway. Novo Nordisk, the Danish pharmaceutical giant behind Ozempic and Wegovy, started two clinical trials in 2021 to see if semaglutide slows cognitive decline in Alzheimer’s patients. First results are expected in 2025. Meanwhile, several companies, including Neuraly and Kariya Pharmaceuticals, are testing whether drugs mimicking GLP-1 can restore cognition in Parkinson’s disease.

The mechanism of these drugs in the brain is still unclear. They might change cholesterol metabolism—a vital process for neurons to build their protective coatings. GLP-1 also modifies the way neurons communicate with each other to create functional networks, which might be the way Ozempic and similar drugs affect the brain. The duration of the effects is another unknown. Early findings for obesity indicate that GLP-1 analogs are not “permanent drugs,” as the patients’ weight partially returns after stopping the treatment. What about the brain? Only time will reveal.