The Ozempic Middle Way

On a recent Sunday morning, I sat on a cushioned mat across from Sister True Vow, a Buddhist nun at Blue Cliff Monastery. I had traveled two hours north from Brooklyn to Pine Bush, New York, to seek her perspective on the human tendency to want. “Desire and craving mean forever running and grasping after something we don’t yet have,” Sister True Vow told me, making gentle but unwavering eye contact. There was something else I wanted to know about desire, though. So I asked what she thought of Ozempic.

Before my visit to Blue Cliff, I had been thinking about how so many people taking GLP-1 medications find that, without even trying, they’ve suddenly released their desires for food, alcohol, tobacco, shopping, and more—and how Buddhists have been contemplating this exact transition for centuries. In his first sermon after reaching enlightenment, the Buddha taught that humans suffer because of our desires, and we must unshackle ourselves from them in order to become enlightened. And to some people who take Ozempic or other GLP-1 medications, the lack of cravings feels like freedom. For others, life becomes a little empty. If renunciation of desire is the key to enlightenment, why does the medication version of Nirvana seem relatively lackluster?

Roughly one in eight Americans has tried a GLP-1 drug, a number that could increase as pressure is put on companies to lower prices and generics enter the market. This means that millions of Americans could soon confront a changed relationship with their general sense of desire. It’s a rare chance to peer inside a mindset that’s usually reserved for the spiritually awakened, and discover what it’s like to stop wanting, and what achieving that state in a matter of weeks reveals about the nature of human desire.

GLP-1 drugs such as Ozempic, Wegovy, and Mounjaro mimic a hormone that not only stimulates insulin production, but also interacts with the brain’s reward circuitry. Scientists are still working out exactly how people respond psychologically. Despite some anecdotal reports of depression and anxiety, a recent study didn’t find an uptick in neuropsychiatric issues with semaglutide, the active ingredient in Ozempic and Wegovy, compared with three other antidiabetic medications; another found that the drugs are not significantly associated with increased suicidal thoughts. The question of desire is more subtle. Davide Arillotta, a psychiatrist at the University of Florence, recently led a study that analyzed tens of thousands of English-language posts about GLP-1 drugs on YouTube, Reddit, and TikTok and found that, unsurprisingly, many express enthusiasm about weight loss. But other people “reported a lack of interest in activities they once enjoyed, as well as feelings of emotional dullness,” he told me.

Anna, a 51-year-old in California who works in marketing—and who requested to withhold her last name to discuss details of her medical history—told me that several months after she started taking Mounjaro, she began to feel listless. Anna was diagnosed with depression 20 years ago, and treated her symptoms successfully. This was different. She still enjoyed aspects of her life: playing with her dog, spending time with her kids. “I still get joy out of them, but I have to force myself to do them,” she told me. In subreddits about GLP-1 drugs, others express similar concerns. “Does anyone feel depressed or feel lack of enjoyment of life while on ozempic ?” one person asked. From another: “Does the apathy fade?” “I just haven’t been finding much interest, joy, or motivation to do things. I haven’t been able to pinpoint why, exactly,” someone else wrote.

Desire, or wanting, is a discrete mental phenomenon that is driven by the neurotransmitter dopamine. In the 1980s, Kent Berridge, a neuroscientist at the University of Michigan, led a study demonstrating that the neurobiology of wanting was separate from liking. Wanting is the motivation to pursue a reward, whereas liking is the enjoyment we get from that reward. This wanting is different from a cognitive plan, like wanting to stop by the library later; it’s an urge to act. Berridge and others have shown that wanting involves different chemicals and areas of the brain than liking does. This means we can want what we don’t like, and enjoy what we don’t crave; for example, Berridge has argued that addiction stems from the triumph of desire over enjoyment. Anhedonia, the loss of pleasure in activities that used to be meaningful, is commonly understood to be a symptom of psychological conditions such as depression. A better term for what’s happening to some GLP-1 users, Berridge said, would be avolition—a loss of motivation and wanting.

The circuitry of desire can be surprisingly easy to manipulate. Berridge has shown that increasing dopamine can make rats seek out painful electric shocks. Some people who take dopamine-increasing Parkinson’s drugs develop compulsive gambling or shopping habits—an issue of too much wanting. Certain Tourette’s drugs, such as Haldol, lower dopamine levels, and can make life feel dull to some people. In his 1985 book, The Man Who Mistook His Wife for a Hat and Other Clinical Tales, the neurologist Oliver Sacks wrote about a man with Tourette’s named Ray, who said that when he took Haldol, he was “average, competent, but lacking energy, enthusiasm, extravagance and joy.” Ray’s solution was to take the drug during the week, then get his fix of exuberance on the weekends.

GLP-1 drugs affect dopamine pathways in the brain in ways that scientists are still working to understand. Kyle Simmons, who’s leading a clinical trial of GLP-1 drugs for alcohol-use disorder, told me that his team plans to pay special attention to participants’ potential loss in pleasure and their loss in wanting—and the difference between the two. Researchers still don’t know whether taking a GLP-1 drug reduces all cravings, or just the strongest ones, Berridge said. But the evidence from other desire-disrupting drugs and experiments can help illuminate why certain people on GLP-1 drugs end up feeling a bit blah. Some might have previously relied on food to regulate their emotions, and can’t eat at the same volume anymore. Others may feel lethargic simply because they’re eating less. And for a person who is used to strong feelings of wanting, “all of a sudden, that goes away, and you have to reestablish what your behavioral drivers should be,” Karolina Skibicka, a neuroscientist at Penn State who did some of the first studies on GLP-1 and dopamine in rats, told me.

This explanation mirrored what Sister True Vow said as she reflected on my questions about anecdotal reports of apathy and GLP-1 drugs. Buddhism recommends contemplating your cravings over a period of years in order to gradually loosen your grip on them in a deliberate way. Ozempic and its peers, by contrast, “do it in a chemical way, without the psychology of us coming along with it,” Sister True Vow said. When people strongly identify with their cravings, feeling them disappear over a matter of weeks can be jarring. But it can also be an opportunity to uncover the roots of our desire in order to eventually let them go in a more deliberate way, Sister True Vow said. This doesn’t mean people have to forgo enjoyment of the present moment—in fact, Buddhism encourages such pleasures.

The Buddha’s first sermon also described the Middle Way: a balance between the extremes of asceticism and indulgence. Enlightenment is approached not by breaking completely free from desire, but by gaining awareness of how and why you want things. After many months on the drugs, some GLP-1 users appear to be finding their own Middle Way. “I have had to learn more about what desire is, how it works,” Anna told me. When she meditated on what exactly she liked about her favorite hobby—collecting perfume—she realized that she is drawn to the infinite variety of scents, how they produce memories and smell differently depending on where on the body they’re applied. I told her she sounded a bit like a Buddhist.

Modern American life is often accused of overloading our dopamine system with TikTok swipes and Amazon Prime deliveries, to the point that influencers and psychologists alike have endorsed “dopamine fasting” to help people break their instant-gratification habits. Desire, in other words, is a monster to be tamed if happiness is to be achieved. Yet people’s emotional responses to GLP-1 drugs reveal that our relationship with wanting is more complex. If an overattachment to every craving can bring suffering, a total renunciation of them can be unsatisfying too.