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What do weight-loss drugs tell us about the brain?
David Robson for New Scientist Volume 265, Issue 3536, 29 March 2025, Pages 31-33
“I just cannot believe how I don't crave alcohol anymore!” writes one person. Others declare: “Took my first shot… have not had a drink or cigarette since,” and “I love coffee but I've noticed that I cannot finish a cup anymore.”
Davide Arillotta, at the University of Florence in Italy, ran the recent study that harvested these quotes from Reddit's weight-loss forums, where rhapsodising about Wegovy and Ozempic is everywhere. Nobody should be startled that the drugs help people curb their eating: imitating the satiety hormone GLP-1 is precisely what they are for (see “How they work”, page 32). What is less expected is how often those same threads describe behavioural changes of a wholly different kind. On this telling, alcohol, cigarettes and even compulsive shopping lose their pull while a person is on these drugs (libido does not, though anecdotal reports on that elsewhere online contradict one another). Prescribers are hearing such stories with growing familiarity.
How they work
Semaglutide, sold as Wegovy for weight loss and Ozempic for diabetes, is one of several drugs in this family, alongside liraglutide (Saxenda and Victoza) and exenatide (Byetta). All of them imitate glucagon-like peptide-1, or GLP-1, the hormone that after a meal produces the feeling of fullness, known as satiety, and stimulates insulin production, bringing blood sugar levels down.
The net effect is less hunger: people take in less energy from food and, used long term, most of them shed a significant amount of weight. That is what a GLP-1 receptor agonist does, to give these drugs their technical name. A newer arrival, tirzepatide (Mounjaro and Zepbound), is now on the market too, imitating GLP-1 alongside another satiety hormone, GIP.
Were controlled trials to bear these anecdotes out, they would teach us a great deal about how the brain handles anticipation and reward, and might open whole new routes into treating addiction. If GLP-1 drugs act on the brain areas that generate reward signals from food, the rewards people get from other things, such as addictive substances, could shrink too. So what does the evidence collected so far actually show about processes this tangled?
The starting point is how a drug like Ozempic engages and shapes the brain. As a rule, GLP-1 and its mimics are too big to pass through the blood-brain barrier, yet they appear able to reach a handful of places where that membrane is a little more porous. Among them are the area postrema, a brainstem region whose activation by GLP-1 hormones can bring on nausea, and the hypothalamus, which governs how much energy we take in and expend. A second route by which GLP-1 drugs may influence behaviour runs through the vagus nerve, the line between abdomen and brain that helps regulate a great many bodily processes. Parts of that nerve respond to GLP-1, so shifts in its activity could ripple outward into brain regions such as the mesolimbic system, which handles reward processing.
Work on these pathways is still at an early stage, but unpicking them will sharpen our picture of the process that underlies craving and satiety. Animal and human models point to the largest effect of the new medicines falling on the anticipation of food, rather than on the pleasure of eating itself. “I'd say that's fairly well established,” says Rodrigo Mansur at the University of Toronto. “And it's something we hear often from patients – that they are just thinking less about the next meal.”
It is still an open question whether these drugs dull other compulsions as well. Large-scale work on medical records does sit behind the anecdotes about alcohol and other substances. Last year, for instance, an analysis of records for more than 2 million people with diabetes found that those on GLP-1 drugs carried roughly a 10 per cent lower risk of substance abuse conditions such as addiction to alcohol and opioids than people on alternative treatments.
A lot of buzz
That evidence, though, is observational: it demonstrates correlation rather than causation. Stringent clinical trials, the kind that compare outcomes against participants given a placebo, remain scarce, and their findings are muddier. “Regarding the potential of these medications to treat substance abuse disorders, however, there's a lot of buzz, but very little high-quality clinical data,” says Mansur.
One small study, out of the University of North Carolina, found that semaglutide (sold as Wegovy and Ozempic) cut both the cravings of people with alcohol use disorder and the amount they drank per session, relative to a placebo. A separate trial, led by Mette Kruse Klausen at the Psychiatric Centre Copenhagen in Denmark with her colleagues, looked at the GLP-1 drug exenatide in 127 participants and found no significant effect on total alcohol intake - except among those participants who were also obese.
Mansur's suggestion is that craving may work through different mechanisms depending on whether or not a person has obesity. Maybe obesity and alcohol misuse are rooted in the same fault in reward processing, for instance, which exenatide was helping correct?
This sits inside a broader uncertainty about whether the brain and mental health effects of GLP-1 drugs reach beyond the widespread benefits of weight loss. “Weight management and metabolism may indirectly impact mental health and behavioral patterns,” says Arillotta. “For example, some studies showed that the reduction of systemic inflammation associated with obesity may have a range of positive effects on mood and cognitive function.”
12 per cent Proportion of US adults who have used Ozempic or related drugs
For some people the placebo effect may be at work as well. “Experiencing one major positive change (such as significant weight loss) can boost overall self-confidence levels, thus making individuals feel more in control of other aspects of their lives, including addictive behaviors,” says Arillotta, whose reading of patient reports on Reddit points to these positive side effects being very common.
Brain benefits?
Some of the cognitive gains reported by GLP-1 users, a lower dementia risk among them, may likewise be confined to people with serious weight problems and/or type 2 diabetes. Lora Heisler at the University of Aberdeen, UK, notes that obesity contributes heavily to conditions such as dementia, in which case shedding the obesity would itself lower the chance of developing it. “My assumption would be that the majority of the effect would be down to their generally improving health,” she says.
Nobody can yet say whether GLP-1 works as a general “anti-consumption” medication, or whether the reported effects on unhelpful cravings mostly reflect better metabolic health. Trials now under way, testing whether these medicines help people quit smoking, alcohol and other drugs, should give us a better idea.
Heisler has begun a new project aimed at unravelling the neural mechanisms of anti-obesity drugs at far greater resolution. Work of that kind could sharpen the treatments, cutting side effects such as nausea and raising efficacy, while widening our understanding of the intricate communication between our internal organs and what it does to our behaviour. “These agents are a great opportunity to understand better the brain-body connections,” says Mansur.
The notion that these drugs might prove a silver bullet for problematic cravings is tantalising. Whether that is a reality, though, is yet to be proven.
Research suggests the drugs mitigate anticipation of food, not pleasure from eating
David Robson for New Scientist Volume 265, Issue 3536, 29 March 2025, Pages 31-33
“I just cannot believe how I don't crave alcohol anymore!” writes one person. Others declare: “Took my first shot… have not had a drink or cigarette since,” and “I love coffee but I've noticed that I cannot finish a cup anymore.”
Davide Arillotta, at the University of Florence in Italy, ran the recent study that harvested these quotes from Reddit's weight-loss forums, where rhapsodising about Wegovy and Ozempic is everywhere. Nobody should be startled that the drugs help people curb their eating: imitating the satiety hormone GLP-1 is precisely what they are for (see “How they work”, page 32). What is less expected is how often those same threads describe behavioural changes of a wholly different kind. On this telling, alcohol, cigarettes and even compulsive shopping lose their pull while a person is on these drugs (libido does not, though anecdotal reports on that elsewhere online contradict one another). Prescribers are hearing such stories with growing familiarity.
How they work
Semaglutide, sold as Wegovy for weight loss and Ozempic for diabetes, is one of several drugs in this family, alongside liraglutide (Saxenda and Victoza) and exenatide (Byetta). All of them imitate glucagon-like peptide-1, or GLP-1, the hormone that after a meal produces the feeling of fullness, known as satiety, and stimulates insulin production, bringing blood sugar levels down.
The net effect is less hunger: people take in less energy from food and, used long term, most of them shed a significant amount of weight. That is what a GLP-1 receptor agonist does, to give these drugs their technical name. A newer arrival, tirzepatide (Mounjaro and Zepbound), is now on the market too, imitating GLP-1 alongside another satiety hormone, GIP.
Were controlled trials to bear these anecdotes out, they would teach us a great deal about how the brain handles anticipation and reward, and might open whole new routes into treating addiction. If GLP-1 drugs act on the brain areas that generate reward signals from food, the rewards people get from other things, such as addictive substances, could shrink too. So what does the evidence collected so far actually show about processes this tangled?
The starting point is how a drug like Ozempic engages and shapes the brain. As a rule, GLP-1 and its mimics are too big to pass through the blood-brain barrier, yet they appear able to reach a handful of places where that membrane is a little more porous. Among them are the area postrema, a brainstem region whose activation by GLP-1 hormones can bring on nausea, and the hypothalamus, which governs how much energy we take in and expend. A second route by which GLP-1 drugs may influence behaviour runs through the vagus nerve, the line between abdomen and brain that helps regulate a great many bodily processes. Parts of that nerve respond to GLP-1, so shifts in its activity could ripple outward into brain regions such as the mesolimbic system, which handles reward processing.
Work on these pathways is still at an early stage, but unpicking them will sharpen our picture of the process that underlies craving and satiety. Animal and human models point to the largest effect of the new medicines falling on the anticipation of food, rather than on the pleasure of eating itself. “I'd say that's fairly well established,” says Rodrigo Mansur at the University of Toronto. “And it's something we hear often from patients – that they are just thinking less about the next meal.”
It is still an open question whether these drugs dull other compulsions as well. Large-scale work on medical records does sit behind the anecdotes about alcohol and other substances. Last year, for instance, an analysis of records for more than 2 million people with diabetes found that those on GLP-1 drugs carried roughly a 10 per cent lower risk of substance abuse conditions such as addiction to alcohol and opioids than people on alternative treatments.
A lot of buzz
That evidence, though, is observational: it demonstrates correlation rather than causation. Stringent clinical trials, the kind that compare outcomes against participants given a placebo, remain scarce, and their findings are muddier. “Regarding the potential of these medications to treat substance abuse disorders, however, there's a lot of buzz, but very little high-quality clinical data,” says Mansur.
One small study, out of the University of North Carolina, found that semaglutide (sold as Wegovy and Ozempic) cut both the cravings of people with alcohol use disorder and the amount they drank per session, relative to a placebo. A separate trial, led by Mette Kruse Klausen at the Psychiatric Centre Copenhagen in Denmark with her colleagues, looked at the GLP-1 drug exenatide in 127 participants and found no significant effect on total alcohol intake - except among those participants who were also obese.
Mansur's suggestion is that craving may work through different mechanisms depending on whether or not a person has obesity. Maybe obesity and alcohol misuse are rooted in the same fault in reward processing, for instance, which exenatide was helping correct?
This sits inside a broader uncertainty about whether the brain and mental health effects of GLP-1 drugs reach beyond the widespread benefits of weight loss. “Weight management and metabolism may indirectly impact mental health and behavioral patterns,” says Arillotta. “For example, some studies showed that the reduction of systemic inflammation associated with obesity may have a range of positive effects on mood and cognitive function.”
12 per cent Proportion of US adults who have used Ozempic or related drugs
For some people the placebo effect may be at work as well. “Experiencing one major positive change (such as significant weight loss) can boost overall self-confidence levels, thus making individuals feel more in control of other aspects of their lives, including addictive behaviors,” says Arillotta, whose reading of patient reports on Reddit points to these positive side effects being very common.
Brain benefits?
Some of the cognitive gains reported by GLP-1 users, a lower dementia risk among them, may likewise be confined to people with serious weight problems and/or type 2 diabetes. Lora Heisler at the University of Aberdeen, UK, notes that obesity contributes heavily to conditions such as dementia, in which case shedding the obesity would itself lower the chance of developing it. “My assumption would be that the majority of the effect would be down to their generally improving health,” she says.
Nobody can yet say whether GLP-1 works as a general “anti-consumption” medication, or whether the reported effects on unhelpful cravings mostly reflect better metabolic health. Trials now under way, testing whether these medicines help people quit smoking, alcohol and other drugs, should give us a better idea.
Heisler has begun a new project aimed at unravelling the neural mechanisms of anti-obesity drugs at far greater resolution. Work of that kind could sharpen the treatments, cutting side effects such as nausea and raising efficacy, while widening our understanding of the intricate communication between our internal organs and what it does to our behaviour. “These agents are a great opportunity to understand better the brain-body connections,” says Mansur.
The notion that these drugs might prove a silver bullet for problematic cravings is tantalising. Whether that is a reality, though, is yet to be proven.
Research suggests the drugs mitigate anticipation of food, not pleasure from eating
