Did Scientists Accidentally Invent an Anti-addiction Drug?

Mai 19, às 16:18


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Did Scientists Accidentally Invent an Anti-addiction Drug?People taking Ozempic for weight loss say they have also stopped drinking, smoking, shopping, and even nail biting.Illustration by The AtlanticMay 19,...
Did Scientists Accidentally Invent an Anti-addiction Drug?

Did Scientists Accidentally Invent an Anti-addiction Drug?

People taking Ozempic for weight loss say they have also stopped drinking, smoking, shopping, and even nail biting.

Animation of neurons lighting up
Illustration by The Atlantic

May 19, 2023, 10:37 AM ET

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All her life, Victoria Rutledge thought of herself as someone with an addictive personality. Her first addiction was alcohol. After she got sober in her early 30s, she replaced drinking with food and shopping, which she thought about constantly. She would spend $500 on organic groceries, only to have them go bad in her fridge. “I couldn’t stop from going to that extreme,” she told me. When she ran errands at Target, she would impulsively throw extra things—candles, makeup, skin-care products—into her cart.

Earlier this year, she began taking semaglutide, also known as Wegovy, after being prescribed the drug for weight loss. (Colloquially, it is often referred to as Ozempic, though that is technically just the brand name for semaglutide that is marketed for diabetes treatment.) Her food thoughts quieted down. She lost weight. But most surprisingly, she walked out of Target one day and realized her cart contained only the four things she came to buy. “I’ve never done that before,” she said. The desire to shop had slipped away. The desire to drink, extinguished once, did not rush in as a replacement either. For the first time—perhaps the first time in her whole life—all of her cravings and impulses were gone. It was like a switch had flipped in her brain.

As semaglutide has skyrocketed in popularity, patients have been sharing curious effects that go beyond just appetite suppression. They have reported losing interest in a whole range of addictive and compulsive behaviors: drinking, smoking, shopping, biting nails, picking at skin. Not everyone on the drug experiences these positive effects, to be clear, but enough that addiction researchers are paying attention. And the spate of anecdotes might really be onto something. For years now, scientists have been testing whether drugs similar to semaglutide can curb the use of alcohol, cocaine, nicotine, and opioids in lab animals—to promising results.

Semaglutide and its chemical relatives seem to work, at least in animals, against an unusually broad array of addictive drugs, says Christian Hendershot, a psychiatrist at the University of North Carolina at Chapel Hill School of Medicine. Treatments available today tend to be specific: methadone for opioids, bupropion for smoking. But semaglutide could one day be more widely useful, as this class of drug may alter the brain’s fundamental reward circuitry. The science is still far from settled, though researchers are keen to find out more. At UNC, in fact, Hendershot is now running clinical trials to see whether semaglutide can help people quit drinking alcohol and smoking. This drug that so powerfully suppresses the desire to eat could end up suppressing the desire for a whole lot more.

The history of semaglutide is one of welcome surprises. Originally developed for diabetes, semaglutide prompts the pancreas to release insulin by mimicking a hormone called GLP-1, or glucagon-like peptide 1. First-generation GLP-1 analogs—exenatide and liraglutide—have been on the market to treat diabetes for more than a decade. And almost immediately, doctors noticed that patients on these drugs also lost weight, an unintended but usually not unwelcome side effect. Semaglutide has been heralded as a potentially even more potent GLP-1 analog.

Experts now believe GLP-1 analogs affect more than just the pancreas. The exact mechanism in weight loss is still unclear, but the drugs likely work in multiple ways to suppress hunger, including but not limited to slowing food’s passage through the stomach and preventing ups and downs in blood sugar. Most intriguing, it also seems to reach and act directly on the brain.

GLP-1 analogs appear to actually bind to receptors on neurons in several parts of the brain, says Scott Kanoski, a neurobiologist at the University of Southern California. When Kanoski and his colleagues blocked these receptors in rodents, the first-generation drugs exenatide and liraglutide became less effective at reducing food intake—as if this had eliminated a key mode of action. The impulse to eat is just one kind of impulse, though. That these drugs work on the level of the brain—as well as the gut—suggests that they can suppress the urge for other things too.

In particular, GLP-1 analogs affect dopamine pathways in the brain, a.k.a the reward circuitry. This pathway evolved to help us survive; simplistically, food and sex trigger a dopamine hit in the brain. We feel good, and we do it again. In people with addiction, this process in the brain shifts as a consequence or cause of their addiction, or perhaps even both. They have, for example, fewer dopamine receptors in part of the brain’s reward pathway, so the same reward may bring less pleasure.

In lab animals, addiction researchers have amassed a body of evidence that GLP-1 analogs alter the reward pathway: mice on a version of exenatide get less of a dopamine hit from alcohol; rats on the same GLP-1 drug sought out less cocaine; same for rats and oxycodone. African vervet monkeys predisposed to drinking alcohol drank less on liraglutide and exenatide. Most of the published research has been conducted with these two first-generation GLP-1 drugs, but researchers told me to expect many studies with semaglutide, with positive results, to be published soon.

In humans, the science is much more scant. A couple of studies of exenatide in people with cocaine-use disorder were too short or small to be conclusive. Another study of the same drug in people with alcohol-use disorder found that their brain’s reward centers no longer lit up as much when shown pictures of alcohol while they were in an fMRI machine. The patients in the study as a whole, however, did not drink less on the drug, though the subset who also had obesity did. Experts say that semaglutide, if it works at all for addiction, might end up more effective in some people than others. “I don’t expect this to work for everybody,” says Anders Fink-Jensen, a psychiatrist at the University of Copenhagen who conducted the alcohol study. (Fink-Jensen has received funding from Novo Nordisk, the maker of Ozempic and Wegovy, for separate research into using GLP-1 analogs to treat weight gain from schizophrenia medication.)  Bigger and longer trials with semaglutide could prove or disprove the drug’s effectiveness in addiction—and identify whom it is best for.

Semaglutide does not dull all pleasure, people taking the drug for weight loss told me. They could still enjoy a few bites of food or revel in finding the perfect dress; they just no longer went overboard. Anhedonia, or a general diminished ability to experience pleasure, also hasn’t shown up in cohorts of people who take the drug for diabetes, says Elisabet Jerlhag Holm, an addiction researcher at the University of Gothenburg. Instead, those I talked with said their mind simply no longer raced in obsessive loops. “It was a huge relief,” says Kimberly Smith, who used to struggle to eat in moderation. For patients like her, the drug tamed behaviors that had reached a level of unhealthiness.

The types of behaviors in which patients have reported unexpected changes include both the addictive, such as smoking or drinking, and the compulsive, such as skin picking or nail biting. (Unlike addiction, compulsion concerns behaviors that aren’t meant to be pleasurable.) And although there is a body of animal research into GLP-1 analogues and addiction, there is virtually none on nonfood compulsions. Still, addictions and compulsions are likely governed by overlapping reward pathways in the brain, and semaglutide might have an effect on both. Two months into taking the drug, Mary Maher woke up one day to realize that the skin on her back—which she had picked compulsively for years—had healed. She used to bleed so much from the picking that she avoided wearing white. Maher hadn’t even noticed she had stopped picking what must have been weeks before. “I couldn’t believe it,” she told me. The urge had simply melted away.

The long-term impacts of semaglutide, especially on the brain, remain unknown. In diabetes and obesity, semaglutide is supposed to be a lifelong medication, and its most dramatic effects are quickly reversed when people go off. “The weight comes back; the suppression of appetite goes away,” says Janice Jin Hwang, an obesity doctor at UNC School of Medicine. The same could be true in at least certain forms of addiction too. Doctors have noted a curious link between addiction and another obesity treatment: Patients who undergo bariatric surgery sometimes experience “addiction transfer,” where their impulsive behaviors move from food to alcohol or drugs. Bariatric surgery works, in part, by increasing natural levels of GLP-1, but whether the same transfer can happen with GLP-1 drugs still needs to be studied in longer trials. Semaglutide is a relatively new drug, approved for diabetes since 2017. Understanding the upshot of taking it for decades is, well, decades into the future.

Maher told me she hopes to stay on the drug forever. “It’s incredibly validating,” she said, to realize her struggles have been a matter of biology, not willpower. Before getting on semaglutide, she had spent 30 years trying to lose weight by counting calories and exercising. She ran 15 half marathons. She did lose weight, but she could never keep it off. On semaglutide, the obsessions about food that plagued her even when she was skinny are gone. Not only has she stopped picking her skin; she’s also stopped biting her nails. Her mind is quieter now, more peaceful. “This has changed my thought processes in a way that has just improved my life so much,” she said. She would like to keep it that way.

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