When Sarah Bennett started taking semaglutide for weight loss last year, she noticed other unexpected changes in behaviour – that longstanding habits fell away without her consciously intending them to.
Semaglutide is commonly known as Ozempic, the brand name for the drug when prescribed as a treatment for type 2 diabetes. Ozempic has been widely used off-label for weight loss; the same drug, branded as Wegovy, is now approved for weight management in Australia, but is not currently available.
Prior to starting on semaglutide, the Queensland mother smoked at least 10 cigarettes daily. “Whilst on Ozempic, it dropped down to one to three per day,” Bennett says. She noticed that she was not enjoying smoking any more. “The smell and taste of it repulsed me and whenever I’d have one cigarette, halfway through I would feel I had had enough.”
Turning to an online support group, Bennett realised others had also noticed changes in their smoking and drinking habits. Some had given up smoking entirely; others found they had gone from having alcohol nightly to monthly, or even not at all.
A few people, like Bennett, also reported that they had stopped biting their nails – a habit that had plagued her for more than 40 years. It wasn’t until Bennett’s daughter remarked that she was growing her nails out that she realised the urge to chew had disappeared.
“This was a big deal for me as I tried so many times to stop,” Bennett says. “I had been biting my nails since what seems [like] for ever.”
Semaglutide’s rapid and controversial rise in popularity has brought increasing reports from patients and doctors about the drug’s coincidental dampening of addictive or compulsive behaviours.
Though not everyone on the drug experiences these effects, the anecdotes square with research in animals finding outcomes that extend beyond appetite reduction – and scientists are now investigating whether semaglutide and related drugs could be used to treat addiction in humans.
The evidence
Semaglutide belongs to the latest generation of a class of drugs known as glucagon-like peptide 1 (GLP-1) receptor agonists. Exenatide, the first of these drugs, was approved in the US for diabetes treatment in 2005. There’s also dulaglutide, sold under the brand name Trulicity; liraglutide, sold as Victoza and Saxenda; and more recently tirzepatide, marketed as the brand name Mounjaro.
GLP-1 is produced in the gut when we eat, but also in the brain. “One of the actions of GLP-1 in our bodies is to prevent blood sugar from increasing too much after meals, but [it] also acts in our brain to reduce our appetite,” says Dr Priya Sumithran, an obesity researcher at Monash University.
The natural form of GLP-1 only lasts minutes in the body before being broken down; GLP-1 medications mimic the natural peptide’s effects but persist for far longer. “They help people feel less hungry and full more quickly after small meals,” Sumithran says.
GLP-1 receptors are also found in an area of the hindbrain known as the nucleus tractus solitarius. “That area is of interest for addiction because it projects to other brain structures that are important for regulating addictive behaviours and responses to drugs,” says Christian Hendershot, an associate professor in the department of psychiatry at the University of North Carolina. GLP-1 medications also act on the mesolimbic pathway, a dopamine-based system that regulates responses to rewarding stimuli like drugs and food.
Sumithran, also an endocrinologist at Alfred Health, has heard anecdotal reports of reductions in drinking and smoking in people on semaglutide, but has not encountered this in her own patients.
“There is some data showing that the GLP-1-based drugs do reduce intake of alcohol and certain drugs, but those are almost entirely studies conducted in rats and mice,” she says. “We certainly don’t have high-quality data in humans, but it’s plausible.”
A study published in May found that semaglutide seems to reduce binge drinking in rodents. Previous research in rodents found that earlier generations of GLP-1 drugs are associated with reduced consumption of nicotine, cocaine and opioids such as fentanyl; and liraglutide and exenatide appear to reduce alcohol consumption in vervet monkeys. In humans, exenatide has been found to be more effective than nicotine replacement therapy alone in helping people quit smoking.
A 2021 review led by Prof Anders Fink-Jensen at the University of Copenhagen suggests that the “effects of GLP-1 in alcohol and substance use disorders [are] mediated centrally, at least partly through dopamine signalling, but precise mechanisms are still to be uncovered”.
“The preclinical data on GLP-1 receptor medications suggest potentially widespread effects across alcohol, stimulants, nicotine and opioids, which is a relatively unique set of findings,” Hendershot says.
He is now running clinical trials to determine whether semaglutide can help smokers and people with alcohol use disorder reduce their intake. “It’s an exciting area,” he says, but data is not yet available. “The anecdotal reports that are coming in certainly suggest that there is a signal there that we should follow up on.”
Lasting results?
For weight loss, evidence suggests semaglutide is more effective than earlier generations of GLP-1 drugs. One study found people taking semaglutide lost 15% of their body weight on average over 68 weeks – a figure two to three times that of earlier GLP-1 drugs, according to Sumithran.
Researchers are still unsure why that is. “It is possible that semaglutide is more effective for weight loss because it has a prolonged action compared with some of the older GLP-1 medications,” Sumithran says. “It may also be better at getting into the brain areas where these medications work than the older GLP-1 medications, but this isn’t proven.”
Whether Ozempic also has stronger anti-addiction effects remains to be seen. “There are some early indications that perhaps semaglutide might show stronger effects in reducing alcohol motivation relative to others in this class. That has yet to be examined in human studies,” Hendershot says.
Anecdotally, Bennett found that her smoking and nail-biting habits returned to their previous state when she went off semaglutide. After several months without the drug, she was then prescribed liraglutide (branded as Saxenda), but found that it did not give her the same “wanted side-effects”.
“It’s weird that I don’t get the same effect,” she says.
People taking semaglutide for weight management typically regain weight after coming off it. If the drug is shown to have anti-addiction properties in humans, whether these effects can be maintained after someone stops taking it is also an open question.
“Some preclinical studies … show that when rodents, or in one case nonhuman primates, discontinue exposure to semaglutide, the reductions in alcohol intake that were observed tend to rebound. I think we would expect that to happen [in humans],” Hendershot says.
It raises the possibility semaglutide would have to be used for long periods of time for sustained effects. That is consistent, Hendershot says, “with our view of addiction as a long-term health condition that needs to be managed on a long-term basis”.
