Could Weight Loss Drugs Be a Psychiatric Tool?

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Obesity and type 2 diabetes mellitus (T2DM) are two of the most pressing dangers to public health facing the United States today. This should come as no surprise, as these interrelated conditions have been affecting an ever-growing number of Americans for several decades.

One piece of good news has been the development of medicines such as glucagon-like peptide 1 (GLP-1) receptor agonists. This class of drugs includes semaglutide (Ozempic, Wegovy), liraglutide (Victoza), and dulaglutide (Trulicity), and they have proven to be remarkably effective in assisting patients with weight management, oftentimes allowing them to lose significant amounts of weight even when the treatment is not paired with lifestyle interventions. They are also being prescribed frequently, with as many as one in five individuals with T2DM using these drugs as of 2022.

Reducing obesity levels can lower the risk of developing high blood pressure, cardiovascular disease, and numerous other complications associated with T2DM. However, it appears that these drugs can also help treat pathologies that do not seem to be closely tied to obesity. Preliminary research suggests they can reduce the severity of COVID-19 symptoms (though it does not reduce the risk of infection), and that they may be useful in treating psychiatric conditions and even preventing the progression of neurological disorders like Alzheimer’s disease and possibly Parkinson’s disease.

How GLP-1 Agonists Work: Insulin, T2DM, and Obesity

Synthetic GLP-1 agonists mimic the hormone GLP-1, which is released in the gastrointestinal (GI) tract after eating. GLP-1 triggers the release of insulin, which helps regulate blood glucose levels by encouraging cells to absorb glucose and use it for energy.

Patients with T2DM either do not make enough insulin to properly regulate their blood glucose levels or have developed insulin resistance (meaning their cells are less sensitive to insulin signaling). Since this does not occur concurrently, most people experience years of prediabetes (typically caused by either genetics, sedentary lifestyle, or a diet high in sugary and overly processed foods), as their cells develop a greater tolerance to insulin, eventually turning into insulin resistance. It is only after their pancreas is unable to produce sufficient insulin to maintain a healthy blood glucose level that a patient becomes diabetic.

By encouraging the release of insulin, GLP-1 agonists can help individuals with T2DM better manage their blood glucose levels and avoid complications associated with the disease, such as chronic inflammation, nerve damage, and diseases affecting the kidneys, eyes, and cardiovascular system.

Fortunately, researchers realized early on that the benefits of GLP-1 agonists were not just limited to the treatment of T2DM; they also helped patients lose weight. Consequently, for years, these findings led many medical professionals to use GLP-1 agonists off-label as a means of weight management. More recently, however, the Food and Drug Administration (FDA) approved their use in the treatment of obesity, as they not only help stimulate the release of insulin but also slow down the digestion of food, leading to prolonged feelings of satiety.

GLP-1 Agonists and Addiction

But that doesn’t appear to be the whole story.

GLP-1 agonists also appear to act on certain parts of the central nervous system (CNS), most notably the parts of the brain in charge of appetite and eating behaviors, as well as the reward centers of the brain (especially what is known as the mesolimbic reward pathway). In other words, these drugs don’t just affect the organs in the GI tract; they also appear to act on areas of the CNS that are deeply tied to emotion and motivation, altering individuals’ psychological relationships with rewarding activities and modifying reward behavior accordingly.

This change is something that patients consciously notice and report. After starting treatment with GLP-1 agonists, many describe not only a reduction in appetite, but a psychological change in their relationship with food. Most importantly, they describe being less burdened by preoccupations centering on food. Known colloquially as “food noise,” examples include a persistent fixation on food (especially energy-dense and extremely palatable foods), the temptation to repeatedly check food delivery applications, and thinking about the next meal they will eat while in the process of eating a meal. GLP-1 agonists make these preoccupations or “noise” quieter and easier to ignore.

Researchers have found that this kind of “noise” also affects individuals with a history of substance use disorders. Though preliminary, several studies have found that GLP-1 agonists can promote abstinence among patients with alcohol use disorder, cannabis use disorder, and opioid use disorder. They even appear to help individuals quit smoking.

GLP-1 Agonists and Dementia

Even more recently, a study not yet published has found that GLP-1 agonists can help slow cognitive decline in patients with Alzheimer’s disease (AD). According to study chief Paul Edison of Imperial College London, who presented at the Alzheimer’s Association International Conference on July 30, 2024, patients with AD who were given liraglutide had nearly half the volume loss in areas of the brain associated with memory, language, and executive function, as measured by MRI. Over 12 months, the liraglutide group also reported an 18 percent slower decline in cognitive function when compared with the placebo group in the study.

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What remains an open question is how these drugs confer their neuroprotective qualities in patients with AD. While the cause of AD is believed to center on the abnormal buildup of plaques and protein tangles around neurons that ultimately become toxic and metaphorically suffocate brain cells, research has found that GLP-1 drugs do not directly result in the clearance of these buildups. What is more likely is that GLP-1 agonists reduce neuroinflammation by counteracting insulin resistance in the brain, much as they counteract insulin resistance in the periphery, and that the resultant reduction in blood glucose levels prevents inflammation and slows disease progression.

If this research is validated, GLP-1 agonists may improve the disease course for a host of neurological and psychiatric disorders tied to inflammation, providing relief to millions of patients.