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GLP-1 Novice
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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.”
These quotes were all collected in a recent study led by Davide Arillotta at the University of Florence, Italy, from Reddit's weight-loss forums. Here, you will find many people rhapsodising about the benefits of drugs like Wegovy and Ozempic. That these treatments are helping people curb their eating should be no surprise: that is exactly what they are meant to do, by mimicking the satiety hormone GLP-1 (see “How they work”, page 32). Among the comments, however, you will frequently find reports of other – wholly unexpected – behavioural changes. According to these accounts, when taking these drugs, the urge to drink alcohol, smoke and even shop compulsively plummets (but not libido, though anecdotal reports on this subject elsewhere online are mixed). Such tales are becoming familiar to prescribing physicians.
How they work
Drugs such as semaglutide (sold as Wegovy for weight loss and Ozempic for diabetes), liraglutide (sold as Saxenda and Victoza) and exenatide (sold as Byetta) mimic the actions of glucagon-like peptide-1 (GLP-1). This hormone promotes the feeling of fullness, or satiety, after eating and stimulates insulin production, lowering blood sugar levels.
Overall, this means that these drugs – technically known as GLP-1 receptor agonists – reduce hunger levels, leading to reduced energy intake from food and significant weight loss for most people when used long term. Recently, a drug called tirzepatide (sold as Mounjaro and Zepbound) has also come on the market, which mimics GLP-1 plus another satiety hormone, GIP.
If this anecdotal data can be supported by controlled clinical trials, it may tell us a lot about how the brain processes anticipation and reward – and could also suggest whole new ways of dealing with addiction. By targeting areas of the brain responsible for reward signals from food, GLP-1 drugs might also reduce the rewards people get from other things, such as addictive substances. But what does the current evidence show about these complex behavioural processes?
First, we need to understand how drugs like Ozempic interact with and influence the brain. In general, GLP-1 and the drugs that mimic it are too large to pass through the blood-brain barrier, but seem to be able to reach a few regions where the membrane is a little more porous. These include a region of the brainstem called the area postrema, which can generate feelings of nausea when activated by GLP-1 hormones, and the hypothalamus, which is involved in controlling our energy intake and expenditure. Another pathway through which GLP-1 drugs may influence our behaviour is via the vagus nerve, which runs between the abdomen and the brain and helps regulate many bodily processes. We know that parts of the vagus nerve are sensitive to GLP-1, and changes to the activity of this nerve could have wide-reaching effects in brain areas like the mesolimbic system, which deals with reward processing.
Research into these mechanisms is still at an early stage, but, by unpicking them, we will better understand the process underlying our cravings and sense of satiety. Animal and human models suggest that the biggest effects of the new medications can be seen in mitigating the anticipation of food, rather than the pleasure derived from 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.”
Whether these drugs can reduce other kinds of compulsion is still an open question. The anecdotal reports of a reduction in desire for alcohol and other substances are backed up by large-scale studies of medical records. For instance, an analysis last year of the records of more than 2 million people with diabetes found that GLP-1 drugs were associated with around a 10 per cent reduction in the risk of substance abuse conditions such as addiction to alcohol and opioids, compared with those taking alternative treatments.
A lot of buzz
However, this evidence comes from observational studies that show correlation rather than causation. Few stringent clinical trials – where the outcomes are compared with participants who received a placebo – have been carried out, and the findings aren't so clear cut. “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.
A small study from researchers at the University of North Carolina, for example, found that semaglutide (sold as Wegovy and Ozempic) reduced the cravings of people with alcohol use disorder and the amount they drank per session compared with a placebo. Another study, however, by Mette Kruse Klausen at the Psychiatric Centre Copenhagen in Denmark and her colleagues, examined the effects of the GLP-1 drug exenatide in 127 participants. They found that the it didn't significantly influence total alcohol intake, except among those participants who were also obese.
Mansur suggests that different mechanisms could underlie cravings in people with obesity and those without. Perhaps obesity and alcohol misuse are rooted in the same problem with reward processing, for instance, which exenatide was helping correct?
This fits with a greater confusion about whether the brain and mental health effects of GLP-1 drugs extend 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
The placebo effect may also play a part in some people's improvements. “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 analyses of patients' reports on Reddit suggests that these positive side effects are very common.
Brain benefits?
Some reported cognitive benefits for those taking GLP-1 drugs – including a reduced risk of dementia – may also be limited to those with serious weight problems and/or type 2 diabetes. Lora Heisler at the University of Aberdeen, UK, points out that obesity is a major contributing factor to conditions like dementia, in which case reducing obesity would, in turn, cut the risk of developing dementia. “My assumption would be that the majority of the effect would be down to their generally improving health,” she says.
The upshot is that we don't yet know whether GLP-1 can act as a general “anti-consumption” medication, or whether the reported effects on unhelpful cravings are mainly the result of better metabolic health. We will get a better idea through trials now under way to see if these medicines can help people quit smoking, alcohol and other drugs.
Heisler is now embarking on a new project to unravel the neural mechanisms of anti-obesity drugs in much greater detail. Such work may help refine the treatments, reducing side effects like nausea, and increase their efficacy – while also expanding our knowledge of the intricate communication between our internal organs and its effects on our behaviour. “These agents are a great opportunity to understand better the brain-body connections,” says Mansur.
That these drugs could be a silver bullet to dampen problematic cravings is a tantalising prospect. 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.”
These quotes were all collected in a recent study led by Davide Arillotta at the University of Florence, Italy, from Reddit's weight-loss forums. Here, you will find many people rhapsodising about the benefits of drugs like Wegovy and Ozempic. That these treatments are helping people curb their eating should be no surprise: that is exactly what they are meant to do, by mimicking the satiety hormone GLP-1 (see “How they work”, page 32). Among the comments, however, you will frequently find reports of other – wholly unexpected – behavioural changes. According to these accounts, when taking these drugs, the urge to drink alcohol, smoke and even shop compulsively plummets (but not libido, though anecdotal reports on this subject elsewhere online are mixed). Such tales are becoming familiar to prescribing physicians.
How they work
Drugs such as semaglutide (sold as Wegovy for weight loss and Ozempic for diabetes), liraglutide (sold as Saxenda and Victoza) and exenatide (sold as Byetta) mimic the actions of glucagon-like peptide-1 (GLP-1). This hormone promotes the feeling of fullness, or satiety, after eating and stimulates insulin production, lowering blood sugar levels.
Overall, this means that these drugs – technically known as GLP-1 receptor agonists – reduce hunger levels, leading to reduced energy intake from food and significant weight loss for most people when used long term. Recently, a drug called tirzepatide (sold as Mounjaro and Zepbound) has also come on the market, which mimics GLP-1 plus another satiety hormone, GIP.
If this anecdotal data can be supported by controlled clinical trials, it may tell us a lot about how the brain processes anticipation and reward – and could also suggest whole new ways of dealing with addiction. By targeting areas of the brain responsible for reward signals from food, GLP-1 drugs might also reduce the rewards people get from other things, such as addictive substances. But what does the current evidence show about these complex behavioural processes?
First, we need to understand how drugs like Ozempic interact with and influence the brain. In general, GLP-1 and the drugs that mimic it are too large to pass through the blood-brain barrier, but seem to be able to reach a few regions where the membrane is a little more porous. These include a region of the brainstem called the area postrema, which can generate feelings of nausea when activated by GLP-1 hormones, and the hypothalamus, which is involved in controlling our energy intake and expenditure. Another pathway through which GLP-1 drugs may influence our behaviour is via the vagus nerve, which runs between the abdomen and the brain and helps regulate many bodily processes. We know that parts of the vagus nerve are sensitive to GLP-1, and changes to the activity of this nerve could have wide-reaching effects in brain areas like the mesolimbic system, which deals with reward processing.
Research into these mechanisms is still at an early stage, but, by unpicking them, we will better understand the process underlying our cravings and sense of satiety. Animal and human models suggest that the biggest effects of the new medications can be seen in mitigating the anticipation of food, rather than the pleasure derived from 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.”
Whether these drugs can reduce other kinds of compulsion is still an open question. The anecdotal reports of a reduction in desire for alcohol and other substances are backed up by large-scale studies of medical records. For instance, an analysis last year of the records of more than 2 million people with diabetes found that GLP-1 drugs were associated with around a 10 per cent reduction in the risk of substance abuse conditions such as addiction to alcohol and opioids, compared with those taking alternative treatments.
A lot of buzz
However, this evidence comes from observational studies that show correlation rather than causation. Few stringent clinical trials – where the outcomes are compared with participants who received a placebo – have been carried out, and the findings aren't so clear cut. “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.
A small study from researchers at the University of North Carolina, for example, found that semaglutide (sold as Wegovy and Ozempic) reduced the cravings of people with alcohol use disorder and the amount they drank per session compared with a placebo. Another study, however, by Mette Kruse Klausen at the Psychiatric Centre Copenhagen in Denmark and her colleagues, examined the effects of the GLP-1 drug exenatide in 127 participants. They found that the it didn't significantly influence total alcohol intake, except among those participants who were also obese.
Mansur suggests that different mechanisms could underlie cravings in people with obesity and those without. Perhaps obesity and alcohol misuse are rooted in the same problem with reward processing, for instance, which exenatide was helping correct?
This fits with a greater confusion about whether the brain and mental health effects of GLP-1 drugs extend 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
The placebo effect may also play a part in some people's improvements. “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 analyses of patients' reports on Reddit suggests that these positive side effects are very common.
Brain benefits?
Some reported cognitive benefits for those taking GLP-1 drugs – including a reduced risk of dementia – may also be limited to those with serious weight problems and/or type 2 diabetes. Lora Heisler at the University of Aberdeen, UK, points out that obesity is a major contributing factor to conditions like dementia, in which case reducing obesity would, in turn, cut the risk of developing dementia. “My assumption would be that the majority of the effect would be down to their generally improving health,” she says.
The upshot is that we don't yet know whether GLP-1 can act as a general “anti-consumption” medication, or whether the reported effects on unhelpful cravings are mainly the result of better metabolic health. We will get a better idea through trials now under way to see if these medicines can help people quit smoking, alcohol and other drugs.
Heisler is now embarking on a new project to unravel the neural mechanisms of anti-obesity drugs in much greater detail. Such work may help refine the treatments, reducing side effects like nausea, and increase their efficacy – while also expanding our knowledge of the intricate communication between our internal organs and its effects on our behaviour. “These agents are a great opportunity to understand better the brain-body connections,” says Mansur.
That these drugs could be a silver bullet to dampen problematic cravings is a tantalising prospect. Whether that is a reality, though, is yet to be proven.
Research suggests the drugs mitigate anticipation of food, not pleasure from eating
