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Throughout her life, Victoria Rutledge always considered herself to have an addictive personality. Her first addiction was alcohol. After achieving sobriety in her early thirties, she turned to food and shopping, which became constant obsessions. She would spend $500 on organic groceries, only to let them spoil in her fridge. “I couldn’t stop myself from going to that extreme,” she confessed. Whenever she went to Target, she would impulsively add extra items like candles, makeup, and skincare products to her cart.
Earlier this year, however, Victoria began taking semaglutide, also known as Wegovy, after her doctor prescribed it as a weight-loss treatment. (Colloquially, it is often referred to as Ozempic, though that is just one brand of semaglutide used for diabetes treatment.) Surprisingly, not only did her thoughts about food quiet down and she started losing weight, but she also noticed a significant change in her shopping habits. One day, while leaving Target, she realized her cart contained only the four items she originally came to purchase. “I’ve never done that before,” she remarked. The desire to shop had vanished. What’s more, the desire to drink, which she had successfully extinguished before, did not resurface as a replacement addiction. For the first time in her life, she felt free from all cravings and impulsive behaviors. It was as if a switch had been flipped in her brain.
As semaglutide has gained popularity, patients have reported curious effects that go beyond appetite suppression. They have found themselves losing interest in a range of addictive and compulsive behaviors, such as drinking, smoking, shopping, nail-biting, and skin-picking. While not everyone experiences these positive effects, addiction researchers have taken notice of the abundance of anecdotes. And these stories might hold some truth. Scientists have been studying whether drugs similar to semaglutide can reduce the use of alcohol, cocaine, nicotine, and opioids in laboratory animals, with promising results.
Semaglutide and its chemical counterparts seem to have a broad effect on various addictive substances in animals. Christian Hendershot, a psychiatrist at the University of North Carolina at Chapel Hill School of Medicine, explains that current treatments for addiction are usually specific to one substance, such as methadone for opioids or bupropion for smoking. However, semaglutide and similar drugs may have the potential to transform addiction treatment by altering the brain’s fundamental reward circuitry. While the science is not yet conclusive, researchers are enthusiastic about exploring this further. Hendershot has initiated clinical trials at UNC to assess whether semaglutide can help individuals quit drinking alcohol and smoking. This drug, originally designed to suppress appetite, could potentially suppress much more.
The development of semaglutide has been filled with surprises. Initially created for diabetes treatment, semaglutide stimulates the release of insulin by mimicking a hormone called GLP-1, or glucagon-like peptide 1. Older GLP-1 analogs like exenatide and liraglutide have been used to treat diabetes for over a decade. Doctors quickly noticed that these drugs caused weight loss as a side effect. Semaglutide, heralded as a more potent GLP-1 analog, is expected to produce similar weight-loss effects.
Experts now believe that GLP-1 analogs, including semaglutide, affect more than just the pancreas. While the exact mechanisms involved in weight loss are still unclear, these drugs likely suppress hunger through various methods, such as slowing down digestion and preventing blood sugar fluctuations. Importantly, they also target and act directly on the brain.
Scott Kanoski, a neurobiologist at the University of Southern California, explains that GLP-1 analogs appear to bind to receptors on neurons in different regions of the brain. When these receptors were blocked in rodents, the first-generation drugs exenatide and liraglutide became less effective at reducing food intake, suggesting that this mechanism plays a vital role. However, the impulse to eat is just one type of impulse. Since these drugs act on the brain, in addition to the gut, they could potentially suppress other urges as well.
Specifically, GLP-1 analogs affect the brain’s dopamine pathways, which are involved in the reward circuitry. In simple terms, dopamine is released in response to pleasurable activities such as eating and sex. People with addiction have alterations in this brain process, resulting in fewer dopamine receptors and reduced pleasure response. In animal studies, GLP-1 analogs have been shown to modify the reward pathway. For example, mice treated with a version of exenatide experienced reduced dopamine release from alcohol, while rats on the same drug sought out less cocaine and oxycodone. Even African vervet monkeys predisposed to alcohol consumption drank less when given liraglutide and exenatide. Most research in this area has been conducted using the older GLP-1 drugs, but positive studies on semaglutide are expected to be published soon.
Human studies on the impact of GLP-1 analogs are still limited. Short and small studies on exenatide in individuals with cocaine-use disorder failed to provide conclusive results. Another study using the same drug in people with alcohol-use disorder found that their brain’s reward centers were less activated when shown images of alcohol while undergoing an fMRI scan. However, the overall drinking behavior of the participants did not change significantly, although those with obesity in the study saw some improvement. Experts suggest that if semaglutide proves effective in treating addiction, its efficacy may vary depending on the individual. Anders Fink-Jensen, a psychiatrist at the University of Copenhagen who conducted the alcohol study, emphasizes that he doesn’t expect the drug to work for everyone. (Fink-Jensen has received funding from Novo Nordisk, the manufacturer of Ozempic and Wegovy, for separate research on using GLP-1 analogs to treat weight gain resulting from schizophrenia medication.) Larger and longer trials involving semaglutide will provide more clarity on its effectiveness for addiction treatment and identify which individuals may benefit the most.
Patients taking semaglutide for weight loss reported that the drug did not dull all pleasure in their lives. They could still enjoy a few bites of food or experience the thrill of finding the perfect dress; the only difference was that they no longer felt compelled to overindulge. Elisabet Jerlhag Holm, an addiction researcher at the University of Gothenburg, affirms that cohorts of people taking the drug for diabetes have not shown signs of anhedonia, a decreased ability to experience pleasure. Instead, those she interviewed said their minds were no longer trapped in obsessive thought loops. “It was a huge relief,” says Kimberly Smith, who used to struggle with moderating her food consumption. For patients like her, the drug curbed behaviors that had reached unhealthy levels.
Patients on semaglutide have reported unexpected changes in both addictive and compulsive behaviors. Although there is limited research on GLP-1 analogs and non-food compulsions, the brain’s reward pathways governing addiction and compulsion likely overlap. Semaglutide may have an impact on both. For example, Mary Maher noticed that after a couple of months on the drug, the skin on her back, which she had compulsively picked for years, had healed. She used to bleed so much from her picking that she avoided wearing white. Maher hadn’t even realized she had stopped picking until it had already been weeks. “I couldn’t believe it,” she exclaimed. The urge had simply vanished.
The long-term effects of semaglutide, especially on the brain, are still unknown. Ideally, semaglutide is intended as a lifelong medication for diabetes and obesity, and its most pronounced effects dissipate when the drug is discontinued. “The weight comes back; the appetite suppression diminishes,” explains Janice Jin Hwang, an obesity specialist at UNC School of Medicine. Further research involving larger and longer trials will shed more light on semaglutide’s effectiveness in addiction treatment and its impact on various individuals.
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