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 unsatisfied.
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.
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