The side effects of medications are not always dangerous or bothersome. In some cases, they are even so positive that they go from being side effects to the medication’s primary use. That is what happened with GLP-1 agonists, a family of pharmaceuticals sold under the name of Ozempic. They were originally patented years ago to treat diabetes patients. They went on to become a miracle weight loss drug. And in recent months, they have become a generic cure for addictions.
The headlines about the drug are so glowing as to seem sensational. Ozempic went from appearing in scientific journals to gossip magazines in just a few months, demonstrating on the bodies of the rich and famous that its fame as a diet shortcut was more than justified. Patients who consumed the medication lost up to 15% of their body weight. Now many are beginning to call attention to another side effect: the reduction of alcohol consumption. It is still too early to confirm how GLP-1 agonists work in this regard, but the first scientific studies seem to shed light on some of the reasons behind their functioning, opening the possibility of treating all kinds of addictions.
“I stopped drinking,” says 52-year-old Toñi Venegas in a telephone conversation. “I’m from Seville, and here we’re used to going out to have a few beers. But when I started injecting myself, suddenly, I didn’t want to.” Toñi has been injecting a GLP-1 agonist for almost a year. She has lost 12 pounds. When she began with the diet and medication, she noticed her appetite decrease, but she did not expect to also lose her interest in drinking. Beer started tasting bad. Her body didn’t crave it anymore. So she went to talk to Cristóbal Morales, an endocrinologist at the Virgen de Macarena hospital in Seville, about the surprising side effect.
It wasn’t a surprise for Morales, who has conducted over 120 clinical studies with the drug and had heard the same story. “At first we attributed it to the slowing of gastric acids,” he explains. With GLP-1 agonists, the digestive rhythm decreased, so it was normal for patients to have less interest in drinking and eating. But in light of the latest studies, Dr. Morales explained to Toñi that what was happening was a side effect of the medication. “With time, its effect on the central nervous system and the pleasure center has become clear, showing that it affects alcohol and even other substances and addictive behaviors.”
The avalanche of anecdotes from patients like Toñi have paved the way for a handful of studies that confirm a scientific basis. Some show that the medications lead to rats receiving less dopamine from alcohol. Others stopped feeling attracted to cocaine. A species of African monkey with a tendency to drink stopped doing so.
Experiments in humans, however, are scarce and inconclusive. One of the most cited was conducted by Anders Fink-Jensen, a psychiatrist at the eUniversity of Copenhagen, on the consumption of alcohol in patients who were using a GLP-1 agonist called exenatide. “We saw that there was a dramatic decrease in the quantity of alcohol that they drank,” he confirms in a video call. “But that was only in some of the participants, and as there was also a group that was taking a placebo, when we looked at the total, no clear difference was seen.”
Intrigued by such disparate results, Fink-Jensen decided to screen the analysis according to certain criteria. He observed what happened to patients with a BMI of over 30, which is considered obese. “There we did see a significant decrease in alcohol consumption,” he explains. Fink-Jensen believes now that the drugs may have an effect on alcohol consumption, but not in all patients. The results of the study are promising, but not enough to affirm that the medication can end alcohol dependence, the psychiatrist says: “We need more studies to corroborate it.” Those studies are already on the way.
Fink-Jensen points out that three studies have begun in the United States, and he has just started one of his own, this time centered on obese patients and with semaglutide, a more modern version of the drug. The new studies have received financing from the Novo Nordisk Foundation, a dependent of the pharmaceutical company that makes the medications Ozempic and Wegovy.
Ending addiction without diminishing pleasure
María Inés López-Ibor, a psychiatry professor specialized in anxiety and substance use disorders, has closely followed the effects of GLP-1 agonists. Many of her patients began taking them after antidepressants caused them to gain weight. In a telephone conversation, she explains that the medication “acts on the brain level and can cause a modulation of several neurotransmitters.” One of them is GABA, which is related to anxiety. The other is dopamine, a substance that is released in response to a pleasure stimulus, whether it is a doughnut, a glass of wine or a line of cocaine. Semaglutide would control the pleasure and eliminate the anxiety. “That could help us to understand why it could have an effect on addictions,” López-Ibor says.
The idea that, with one injection a week, a drug promises not only to facilitate weight loss but also to help patients stop smoking, reduce alcohol consumption and eliminate other addictions could spark a revolution in the field of medicine. It would change forever how we relate to addictions. Until now, they have been treated more specifically, with, for instance, methadone for opioids and bupropion for tobacco. But GLP-1 agonists could change all that by attacking the problem at the root, altering the brain’s reward circuits.
The pleasures associated with food, alcohol and drugs are different, but the brain uses the same circuits to process the emotions they provoke. These drugs could modify them, radically changing the focus of the problem. Who would want to consume drugs that did not have an effect? Why choose a hamburger over a salad if they offer the same amount of pleasure?
Playing with dopamine and pleasure could have side effects that in the case of GLP-1 agonists have been totally discarded. “In thee clinical studies of obesity, we gave the patients suicide questionnaires because of the possibility of anhedonia,” explains Juan José Gorgojo, head of nutrition at the Alcorcón Foundation University Hospital in Madrid. Anhedonia is the general diminishment of the ability to experience pleasure. And those questionnaires are routine in psychiatric studies since a drug called Acomplia caused an increase in serious psychiatric disorders in 2006.
GLP-1 agonists do not have that effect. “Injecting does not decrease pleasure,” Dr. Gorgojo says. “It simply makes you not go too far.” The specialist believes that the effects that patients refer to “make scientific sense.” But he calls for caution, pointing out that one of the other possible side effects of GLP-1 agonists is the reduction of liquid consumption. The fact that patients drink less alcohol could be because patients drink less, in general.
After a year, Toñi drinks a beer or two from time to time. But she doesn’t feel like drinking like she did before. That doesn’t mean that she doesn’t go out or enjoy herself. “On the contrary,” she says, “when I was dieting, I tried not to go out to avoid temptation. Now I go out and have fun, because I know that I won’t want to drink or eat too much.”
GLP-1 agonists are changing thousands of people’s relationship with food. And now they promise new knowledge about the nature of pleasure and addictions. They could save millions of lives every year, between treating obesity and drug and alcohol consumption. They could even end the social stigma of those who struggle with addiction: if a drug can modify their behavior, it would show the medical nature of the problem, leaving moral or personal issues out of the equation. It may be early to imagine such outcomes, but it wouldn’t be the first surprise to come out of this drug.
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