In this long article Dhruv Khullar explains the surprisingly complex, powerful and often mysterious impacts that GLP-1 medications have on the human body. At one level, these medications seem to have the potential to cure a variety of things which ail human beings. At another level, what these medications are doing could be messing up the wiring of our brains so comprehensively that we stop being ourselves.
Mr Khullar begins by explaining that although the traditional use of GLP-1 medications so far have been for weight loss, it appears that these medications can also reduce our cravings for addictive substances:
“GLP-1 medications—colloquially known as GLP-1s—mimic a naturally occurring hormone called glucagon-like peptide 1, which scientists have historically associated with digestion. In the traditional telling, after a meal, GLP-1 attaches to receptors in the pancreas, the gastrointestinal tract, and the brain; it stimulates the release of insulin, slows the passage of food through the stomach, and signals to our brains that we’re full. It breaks down within minutes. But it’s increasingly clear that GLP-1 affects much more than eating. GLP-1 drugs, which bind to the body’s receptors for hours or days, are now being studied for all sorts of addictions.
The results from the trial that Mary participated in should come out later this year, but a small study published in 2021 showed that smokers given exenatide, the first GLP-1 on the market, were nearly twice as likely to stop smoking as those given a placebo. An analysis of hundreds of thousands of electronic health records found that people with an addiction to opioids who happened to be prescribed GLP-1s were forty per cent less likely to overdose. Some scientists think that the medications may even help with behavioral addictions, such as gambling and compulsive shopping. Research into GLP-1s, scientists hope, could deepen our understanding of what addiction is. “Essentially all addiction medications to date have been specific to a particular type of addiction,” Heath D. Schmidt, a neuroscientist at the University of Pennsylvania, told me. “GLP-1s might be telling us that there’s some kind of universal pathology when it comes to addiction. And that they’re part of how we fix it.””
So, we hear you say, what is the problem? The problem might be that GLP-1 medications not only reduce our cravings (whether it be for food or drugs or alcohol) but they impact our neural pathways so profoundly that we stop being ourselves. Dhruv Khullar explains this trade-off beautifully:
“Recently, I spoke with a fortysomething woman I’ll call Jessica, who struggled with untreated A.D.H.D. for decades. She told me that her “treatment” was food and alcohol. For much of her life, she binged on both; when she entered menopause, she started to put on weight. She saw an advertisement for a GLP-1 medication from a telehealth company and decided to try it out. A few days later, she received a box of syringes in the mail.
Jessica lost twenty pounds in the four months after she started injecting herself, but her drinking was largely unaffected. Meanwhile, she grew more anxious. Her husband noticed her mood worsening; she lost interest in activities she’d previously enjoyed. An avid gardener, she had planned to refresh her yard with six Japanese maple trees, but now she couldn’t bring herself to plant them. “That’s when I was, like, Whoa, this isn’t my normal,” she said. She covered the windows looking into her garden so that she wouldn’t have to see her withering plants. For her, the GLP-1 medication didn’t moderate so much as agitate and numb. Eventually, she decided that the psychological side effects weren’t worth the weight loss. She stopped taking the medication and regained the weight, but her mood improved. “It was pretty immediate—the return to feeling like myself,” she said.
Jessica seemed to be describing anhedonia, a struggle to experience pleasure. Last year, the New York Times interviewed two dozen people whose relationships were affected by GLP-1 drugs, including a woman who lost interest in sex. In “Magic Pill,” the journalist Johann Hari attributes a muted mood to Ozempic. “I didn’t feel as excited for the day ahead,” he writes. “I was often emotionally dulled.” On Reddit, users discuss numerous psychological changes. “I wasn’t enjoying my family at all, or myself, or my life,” one person wrote. “I don’t want to be a zombie.” Jens Juul Holst, a Danish scientist credited with helping discover GLP-1, worried, in 2023, that GLP-1 medications would make life “so miserably boring that you can’t stand it any longer and you have to go back to your old life.””
So powerful are the side-effects of GLP-1 on our brain that the European Union’s medicines agency initiated a safety review of the drugs. However, neither this agency nor anyone else has been nail down clearly what is going on in the brain when the human body consumes GLP-1. This is a big deal because at stake are billions of dollars of profits for Big Pharma and the lives of the millions of those around the world who are now taking GLP-1 medications. Mr Khullar writes:
“The [European] agency ultimately concluded that the available evidence did not establish a causal link between the medications and suicidal thoughts or behaviors. (The U.S. Food and Drug Administration noted in 2024 that it could not “definitively rule out that a small risk may exist,” but requested last month that suicide warnings be removed from GLP-1 drugs.) The data remain frustratingly ambiguous. Observational studies, which tend to be less precise than randomized controlled trials, have found that GLP-1s might harm or help a person’s mental health. The Nature network of journals recently published an article suggesting that GLP-1s reduce the risk of suicidal thoughts by more than half—and another article saying that they more than double the risk of suicidal behavior. Nearly all the experts I spoke with said that we needed more research.” [Text in brackets is ours.]
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