Side effects from medications aren’t always dangerous or bothersome. In some cases, they are even so beneficial that they go from being side effects to primary use of drugs. That’s what happened with GLP-1 agonists, a family of drugs sold under the name Ozempic. They were originally patented years ago to treat diabetic patients. They have become a wonder drug for weight loss. And in recent months they have become a generic cure for addictions.
The drug headlines are so brilliant that they seem sensational. Ozempic went from appearing in scientific journals to gossip magazines in just a few months, proving on the bodies of the rich and famous that its reputation as a diet shortcut was more than justified. Patients who consumed the drug lost up to 15% of their body weight. Now many are starting to draw attention to another side effect – the reduction in alcohol consumption. It’s still too early to confirm how GLP-1 agonists do this, but early scientific studies seem to shed light on some of the reasons why they work, opening up the possibility of treating all kinds of addictions.
I stopped drinking, says Toi Venegas, 52, in a telephone conversation. I’m from Seville and used to go out here for a few beers. But when I started injecting myself, all of a sudden, I didn’t want to. Toi has been injecting himself with a GLP-1 agonist for nearly a year. He has lost 12 kilos. When he started on the diet and medications, he noticed that his appetite diminished, but he didn’t expect that he would lose his interest in drinking as well. The beer started to taste bad. His body didn’t want him anymore. So she went to talk to Cristbal Morales, an endocrinologist at the Virgen de Macarena hospital in Seville, about the surprising side effect.
It came as no surprise to Morales, who has conducted more than 120 clinical trials with the drug and had heard the same story. At first we attributed it to the slowing down of stomach acids, he explains. With GLP-1 agonists, digestive rhythm decreased, so it was common for patients to have less interest in eating and drinking. But in light of the latest studies, Dr. Morales explained to Toi that what was happening was a side effect of the drug. Over time, its effect on the central nervous system and pleasure center became clear, showing that it affects alcohol and even other addictive substances and behaviors.
The flood of anecdotes from patients like Toi has paved the way for a handful of studies that confirm a scientific basis. Some show that the drugs cause rats to get less dopamine from alcohol. Others have stopped feeling attracted to cocaine. A kind of African monkey with a tendency to drink has stopped doing it.
Experiments on 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 alcohol consumption in patients who were using a GLP-1 agonist called exenatide. We saw that there was a dramatic decrease in the amount of alcohol they drank, he confirms in a video call. But this was only in some of the participants, and since 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 sift the analysis against certain criteria. She looked at what happened to patients with a BMI over 30, which is considered obese. There we saw a significant decrease in alcohol consumption, he explains. Fink-Jensen now believes that drugs may have an effect on alcohol consumption, but not in all patients. The study results are promising, but not enough to say the drug can end alcohol addiction, says the psychiatrist. We need more studies to confirm that. These studies are already underway.
Fink-Jensen points out that three trials have started in the United States, and it has just started one of its own, this time focusing on obese patients and on semaglutide, a more modern version of the drug. The new studies received funding from the Novo Nordisk Foundation, an employee of the pharmaceutical company that makes the drugs Ozempic and Wegovy.
End addiction without diminishing pleasure
Mara Ins Lpez-Ibor, a professor of psychiatry specializing in anxiety and substance use disorders, has been closely following the effects of GLP-1 agonists. Many of her patients started taking them after antidepressants made them gain weight. In a telephone conversation, she explains that the drug acts at the brain level and can cause a modulation of various 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’s a doughnut, a glass of wine, or a line of cocaine. Semaglutide would control pleasure and eliminate anxiety. This could help us understand why it might have an effect on addictions, Lpez-Ibor says.
The idea that, given one injection a week, a drug promises not only to facilitate weight loss but also to help patients quit smoking, reduce alcohol consumption and eliminate other addictions could spark a revolution in the field of medicine. It would forever change the way we relate to addiction. So far they have been treated more specifically, for example with methadone for opioids and bupropion for tobacco. But GLP-1 agonists could change all that by attacking the root problem, by altering the brain’s reward circuitry.
The pleasures associated with food, alcohol and drugs are different, but the brain uses the same circuits to process the emotions they elicit. These drugs could modify them, radically changing the focus of the problem. Who would like to consume drugs that have had no effect? Why choose a burger over a salad if they offer the same amount of pleasure?
Playing with dopamine and pleasure could have side effects which in the case of GLP-1 agonists have been totally ruled out. In three clinical trials on obesity, we gave patients suicide questionnaires due to the possibility of anhedonia, explains Juan Jos Gorgojo, head of nutrition at the University Hospital of the Alcorcón Foundation in Madrid. Anhedonia is the general decrease in the ability to experience pleasure. And those questionnaires have been routine in psychiatric offices since a drug called Acomplia caused a surge in severe psychiatric disorders in 2006.
GLP-1 agonists do not have this effect. The injection doesn’t diminish the pleasure, Dr. Gorgojo says. It just makes you not go too far. The specialist believes that the effects referred to by patients make scientific sense. But he cautions against caution, pointing out that one of the other possible side effects of GLP-1 agonists is reduced fluid intake. That patients drink less alcohol may be because patients drink less, in general.
After a year, Toi has an occasional beer or two. But she doesn’t feel like drinking like she did before. That doesn’t mean she doesn’t go out or have fun. On the contrary, she says, when I was on a diet I tried not to go out to avoid temptation. Now I go out and enjoy myself, because I know 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 insights into the nature of pleasure and addictions. They could save millions of lives every year, through the treatment of obesity and the use of drugs and alcohol. They could even end the social stigma of those struggling with addiction: if a drug can change 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 results, but it wouldn’t be the first surprise to come out of this drug.
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