Mary Boyer, a 41-year-old tech worker, started taking the drug Mounjaro last October to treat obesity. She has since lost more than 40 pounds, going from 267 when she started to 221 when she weighed herself recently. “I’m losing, like, a pound and a half a week pretty steadily,” she said.
For decades, she was preoccupied with dieting, hunger and cravings. Now that obsession is gone. “I just straight up lost my sweet tooth,” she said. She still sometimes turns to pizza or tacos to stanch emotions, but less often. “What happens now is either I get them and I have a little bit and I’m satisfied or I’m just like, ‘You know, I don’t really need that,’” she said.
Mounjaro — like the better-known Ozempic — is one of a new class of diabetes and obesity drugs that work differently from earlier medications in ways that are not yet fully understood. Unlike stimulants, which can be addictive, these drugs may fight addictions and not just those related to food. Newer, stronger versions are on their way.
Discovering how the new weight loss medications alter appetite and the compulsive behavior that can be associated with it could offer new insight into the nature of pleasure and addictions. Adjusting brain systems that regulate desire may also affect the stigma that society pins on people with conditions that can lead to loss of control. When drugs can significantly ease weight loss or addiction recovery, it’s hard to argue that the problem is moral rather than medical.
The new weight loss drugs are called GLP-1 receptor agonists. They do much of their work in the brain, reducing the way that hunger centers attention on seeking food. This affects one of our two primary types of pleasure, which Kent Berridge, a professor of psychology and neuroscience at the University of Michigan, has labeled “wanting.” The positive side of wanting is feeling empowered and focused on getting what you desire; the negative side, of course, is craving that goes unsatiated.
The second kind of pleasure, which Dr. Berridge calls “liking,” is linked with the satisfaction and comfort of having achieved your goal. While there is less downside here, if people felt forever satisfied, they’d probably lack motivation to do much. The psychiatrist Donald Klein eloquently distinguished the two joys as the “pleasures of the hunt” and the “pleasures of the feast.”
Dr. Berridge and his colleagues showed how wanting and liking rely on distinct but connected circuitry. In his theory of addiction, he argues that wanting escalates as drug use increases, while liking plateaus or diminishes, leaving people frantically seeking something that no longer provides much, if any, satisfaction. Although he was previously skeptical of food addiction, recent research has convinced him that some people respond to food the way others crave drugs.
The blisses of eating, of sex and of drugs feel different. But the brain processes many emotions via the same circuitry. The wanting circuits tend to rely on the neurotransmitter dopamine, while liking is more associated with the brain’s natural opioids. Having these common currencies of emotion allows our brains to modulate what we want, depending on what it perceives as our most pressing needs.
When this circuitry works harmoniously, wanting and liking are tuned down after a need is satisfied. This is why, for most people, once they are full, more food is unappealing. The result is that pleasure is relative and context dependent — and sadly, what makes them happy now may not do so later, whether it’s a drug, a new outfit or a relationship.
These facts have inspired the design of drugs to fight addictions. Some, like methadone and buprenorphine, satiate opioid craving by providing a consistent level of a drug similar to the one that is wanted, without the chaos that can prevent people with addiction from living well.
When people take these medications consistently in appropriate doses, they are not impaired or high because they have become tolerant of those effects. Their brain receptors are now accustomed to certain levels of opioids and are occupied and activated when taking the medications. Consequently, people can get on with their lives, with a 50 percent or greater reduction in their risk of dying from overdose.
Other medications, like naltrexone, do the opposite and prevent opioid receptor activation. This, however, means that they can interfere with non-drug-related liking pleasures also mediated by these receptors, like those associated with socializing. Not surprisingly, patients overwhelmingly prefer drugs that satiate desire rather than reduce pleasure.
A third group of medications — antipsychotics, which block some dopamine receptors in the wanting circuitry and are used to treat schizophrenia — has also been tried for addiction. But these medications aren’t selective. For some people, they reduce the thrill of the chase so dramatically that motivation is minimized and life feels empty. Some of the newer antipsychotics seem to cut alcohol craving; however, they may also worsen stimulant addictions and are notorious for causing weight gain.
GLP-1 drugs act differently. They modulate the motivational dopamine systems but apparently not in a way that dampens desire overall. According to Randy Seeley, a professor of surgery at the University of Michigan School of Medicine who has been funded by drug companies for some of his research, they lower the body’s set point, or the weight it has determined it should be.
“Millions of years of evolution have told you that at some point food is the most important thing and at some point it’s not,” said Dr. Seeley, explaining how the brain makes choices about whether food or something else, like sex, should be desirable at any given time. He added, “It’s not a system that was designed to just accede to your force of will.”
Because these drugs act so specifically on a person’s set point, Dr. Seeley suspects that, despite the parallels between food and other addictions, the drugs may not work to treat substance problems. Food and fluid intake are heavily regulated by the brain through many complex mechanisms because they are critical to survival. But it’s not yet clear if these systems can also create signals that say no to more drugs and, if so, how this varies among individuals.
So far, the data on using GLP-1 drugs for substance addictions is mixed. Some studies showed positive results in animals and humans, but others found no effect.
Dr. Nora Volkow, the director of the National Institute on Drug Abuse, is funding research on these medications for drug addictions. She said that they might work “by interfering with that urge to have more.” It will be fascinating to learn whether it’s possible to alter or even create a set point that signals that “enough” drugs have been taken. People with alcohol problems seem to lack such an off switch, while those who drink moderately report clearly knowing when to stop.
Dr. Berridge noted that while neuroscientists know a lot about how to change the intensity of cravings, they don’t yet understand what controls the focus of desire. This could be how GLP-1 drugs work, by reducing the value that motivational systems place on getting more food now, thereby cutting hunger. In other words, they don’t block pleasure but shift attention. And this could help tame many types of obsessions. Some people who are taking these drugs already report ending compulsive shopping and nail biting.
But perhaps one of the greatest benefits of the widespread availability of drugs that make losing weight or kicking addictions easier is the reduction of stigma. People with obesity or drug addictions are often seen as selfish, shamefully lacking in willpower and lazy. Both are derided for apparently abandoning themselves to indulgence, even though research shows that they are more likely to be trying to ease emotional pain.
Seeing people change with ease on medication after years of struggle could help the public recognize that these are truly medical issues. Simply by working the way they do, GLP-1 medications suggest that the difference between addicted people and others is chemistry, not choices.
Alternatively, some advocates for fat acceptance worry that such drugs will actually add stigma, increasing pressure to change rather than encouraging society to value those of all sizes. Others are concerned about the persistence of the idea that making change without hard work is cheating, like taking steroids to gain muscle.
It is long past time to stop shaming people with disorders of appetite in a futile attempt to tame our own fears of loss of control. Whatever condition is being treated, we all deserve the easiest possible path to recovery. Understanding how wanting, liking and attention are regulated by the brain could lead to better self-control for many, across diagnoses.
Maia Szalavitz (@maiasz) is a contributing Opinion writer and the author, most recently, of “Undoing Drugs: How Harm Reduction Is Changing the Future of Drugs and Addiction.”
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