Adam Scioli gets excited when he speaks about GLP-1 medications.
Not because they’re known globally for revolutionizing weight-loss management, but because he thinks this class of drugs is the next frontier of addictions treatment.
Dr. Scioli helped to transform care at Caron Treatment Centers in the United States during his recent tenure at the elite non-profit as an addictions psychiatrist and chief medical officer. Caron is believed to be the first of very few rehabilitation facilities in the world that prescribe GLP-1s off-label to treat substance-use disorders.
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Adam Scioli has studied whether GLP-1s can be used to treat addictions, and was encouraged by what he saw in several patients at Caron Treatment Centers in the United States.Joe Lamberti/The Globe and Mail
Caron added GLP-1s to its arsenal of addiction medications in 2024 and has since prescribed them to more than 500 residential clients. Dr. Scioli said researchers warned him and his colleagues that they were “putting the cart before the horse,” but it’s a decision they stand by.
“It’s no doubt groundbreaking. It’s no doubt transformative,” he said.
GLP-1 medications, such as Ozempic, Wegovy and Mounjaro, are only approved by the U.S. Federal Drug Administration and Health Canada for diabetes and chronic weight management. Early research, however, has shown that this class of drugs may help dampen drug cravings, similarly to how they quiet intrusive thoughts about food.
GLP-1s, developed initially for blood glucose and weight control, work by mimicking natural hormones that bind to receptors in the brain that process hunger and satiety. They also alter the brain’s dopamine pathway – the circuit for reward, motivation and desire – which helps to mute the mental preoccupation with eating.
That pathway is also central to addiction. The use of addictive substances triggers massive dopamine surges. So, a natural question has emerged: Could GLP-1s be the next big treatment for substance-use disorders? Dr. Scioli said he has seen evidence to support this idea. “What we’ve observed is that these GLP-1 receptor agonists seem to provide a cognitive buffer,” he said. “They allow our patients to recognize their triggers without being compelled to act on them.”
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Ozempic belongs to the GLP-1 family, which has dramatically reshaped diabetes and weight-loss care.Alison Boulier/The Globe and Mail
Canadian researchers are part of a growing network of scientists who are putting such early findings to the test. Results have varied, but studies so far have shown that GLP-1s have the potential to lower the risk of developing a substance-use disorder and reduce negative outcomes and cravings associated with drug use, including for nicotine, alcohol and opioids.
Experts who spoke to The Globe and Mail are optimistic about the prospects of GLP-1s, especially as opioid deaths continue to mount across the country. But, above all else, they are urging prudence. These drugs are not yet an established treatment and robust trials are still needed to confirm their safety and efficacy with greater certainty. Such trials would need to look, for example, at the longer-term effects, dosing and who stands to benefit the most.
“There is a sense that these may be miracle drugs,” said James MacKillop, director of the Peter Boris Centre for Addictions Research at McMaster University. “But there always has to be quite a lot of caution when something doesn’t have the gold-standard evidence that we look for.”
GLP-1s have shown tremendous success in treating weight loss and diabetes and have been praised for their potential to address a slew of other medical issues, such as heart disease and neurodegenerative disorders.
There is also an undeniable excitement about the prospect of GLP-1s being able to blunt cravings broadly. Researchers are even looking at their potential for behavioural addictions including sports betting, compulsive shopping and pornography.
To date, addiction-related research has largely focused on the relationship between GLP-1s and alcohol use disorder, but it is increasing for other substances. Most studies have been performed on rats and mice rather than on humans.
The gold standard, as Dr. MacKillop put it, requires randomized control trials where people are split into two groups. One cluster receives the new treatment while the other does not, removing bias and reliably proving true cause-and-effect results. So far, these are limited, especially for opioid addiction.
But on the horizon in Canada is a randomized trial run by Eli Lilly, a leader in the GLP-1 medication market, which makes Mounjaro and Zepbound. This trial, expected to end in 2028, aims to investigate whether brenipatide, an experimental GLP-1 drug, enhances the recovery of people with opioid use disorder who are already taking a proven treatment called buprenorphine. Eli Lilly is looking to enroll 465 participants, ages 18 to 75, across Canada, the U.S. and Britain. The Canadian trial sites are located in Alberta, British Columbia and Ontario.
Alberta-based addiction physician Monty Ghosh, Calgary’s site investigator, said this is the first study of its kind in Canada. If brenipatide proves successful, he said it could lead to the expansion of treatment options for opioid use disorder. “This is hugely exciting as we have such limited options. This would provide us with a whole new class of medications to manage this severe disorder,” he said.
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This discarded bottle in Oshawa, Ont., once held a drinkable concentrate of methadone, a synthetic opioid to wean people off more harmful drugs.Galit Rodan/The Globe and Mail
The most common treatments for opioid use disorder in Canada are buprenorphine and methadone, long-acting prescribed medications used to manage drug withdrawal and cravings.
Other options include naltrexone, slow-release oral morphine or an injectable opioid agonist treatment, which is typically reserved for cases where oral treatments have not been successful.
There is no single medication currently available that can blunt cravings across all drug classes, which could make GLP-1s a novel solution.
The first randomized controlled trial to test GLP-1s against opioid addiction was conducted by researchers at Pennsylvania State University at a Caron treatment centre.
The trial involved 20 participants and found that those who received the GLP-1 drug liraglutide had a 40-per-cent reduction in opioid cravings compared with those who received the placebo.
Those findings, released in 2024, set the foundation for a larger clinical trial currently in progress with an anticipated 200 participants across four U.S. sites. It will test whether patients who receive semaglutide, the active ingredient in Ozempic, reduce their illicit opioid use over 12 weeks.
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This is a molecular model of semaglutide, Ozempic’s active ingredient.Ali Withers/Reuters
One of the principal investigators, Jennifer Nyland, an associate professor of neuroscience and experimental therapeutics at Penn State, said the study is targeting patients who are struggling with illicit opioid use despite being on standard medications.
She said they are using a subtherapeutic dose, meaning it is lower than what is needed to produce weight loss. This has so far proved effective for silencing drug appetite in animal studies. But Dr. Nyland added that researchers are still determining what the baseline dose should be for humans.
Her team will evaluate whether the GLP-1 is reducing urges by examining urine tests and participant-logged data. Dosing can be increased depending on how a participant responds.
“That’s why it’s important that we are testing a variety of different GLP-1 agonists for reducing the use of various drugs in both clinical trials and animal models – to give people options,” she said.
Observational studies have also been crucial to understanding GLP-1 potential. Take, for example, research published in March that analyzed the medical records of more than 600,000 U.S. veterans who were prescribed either a GLP-1 or SGLT2 inhibitor, which is a common treatment for Type 2 diabetes.
Senior author Ziyad Al-Aly, a Washington University clinical epidemiologist, said they sought to answer two questions: Can GLP-1s prevent addiction? And can they reduce harm for those already struggling with it? The answer to both was yes.
Among veterans living with addiction who were taking a GLP-1, the study found there were 50 per cent fewer substance-related deaths and 39 per cent fewer drug overdoses compared with those taking an inhibitor. Additionally, the group taking GLP-1s had a significantly lower risk of developing a new addiction to a number of substances the researchers tested for, including nicotine, alcohol, cocaine and opioids.
“I’m excited about this because finally we have a drug that seems to be working on addiction,” said Dr. Al-Aly, adding he’s never seen anything like it before. “At the same time, I see the uncertainties that need to be resolved, the side effects that people don’t talk about enough.”
GLP-1 drug makers have been busy converting their wares into new, more easily administered forms, like these Wegovy tablets at Novo Nordisk’s production line in Malov, Denmark. Canada is reviewing several generic GLP-1 drugs for use here.
Tom Little/Reuters
The most common side effects of GLP-1s are gastrointestinal, including nausea, vomiting and diarrhea. There are also less common but more serious side effects, such as inflammation of the pancreas, bowel obstruction and gallbladder disease.
Much less is known about the effects on those with addiction.
Alexander Caudarella, chief executive of the Canadian Centre on Substance Use and Addiction, has a list of questions he said need to be answered before this treatment method should be widely prescribed.
He wants to know how long the medication stays active in the body, what happens to individuals when they stop using it and whether discontinuation will heighten the risk of relapse or overdose.
“We don’t want to deprive people of having access to something that could be a game changer, but you want to make sure that we’re doing all the research that’s necessary,” said Dr. Caudarella, who is worried that off-label prescriptions will take off before there are conclusive answers.
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‘There is a sense that these may be miracle drugs,’ McMaster’s Dr. MacKillop says, ‘but there always has to be quite a lot of caution when something doesn’t have the gold-standard evidence that we look for.’Nick Iwanyshyn/The Globe and Mail
Researchers in this field also want to know whether the body will adapt to GLP-1s and respond less over time, if efficacy will be comparable across drug classes and how the use of multiple substances could interact with the medication.
It is also still unclear who the best candidates are for the proposed treatment. The illicit-drug-using population is vulnerable, and many have concurrent mental illnesses. Additionally, there could be a risk of malnourishment.
In the long term, Dr. MacKillop, from McMaster, said he is concerned about the possibility of anhedonia, which is the reduced or total inability to feel pleasure. Such symptoms have been anecdotally reported by some GLP-1 users.
“If these drugs effectively abolish our capacity for pleasure, are we giving up that core part of who we are as people?” he said. “They may be lifesavers in some cases … but they may be more selectively relevant for really severe cases as opposed to a very large proportion of the population.”
Although Canada is likely years away from designating GLP-1s for addiction treatment, there are also concerns about who will be able to access this class of drugs. Coverage gaps related to the cost of the treatment already exist across the country.
Last year’s installation of the Blue Hat Memorial Project in Campbell River, B.C., underscored the human cost of addiction. Its 50,000 flags – blue for men and boys, purple for women and girls – each represented a life lost to overdoses. Nationally, that toll has kept growing, though annual rates have been declining.
Chad Hipolito/The Globe and Mail
There is also a broader ethical question to ponder, said Dr. Al-Aly, the Washington researcher.
In Canada, more than 56,000 people have died from opioid-related poisonings since 2016, driven by the rise of illicit fentanyl. In the U.S., that figure stretches beyond 400,000. Add in other substances, such as cocaine and alcohol, and the numbers in both countries increase substantially.
So, Dr. Al-Aly asks: Is it fair to withhold a possible treatment option when studies, like his, have demonstrated that GLP-1s can reduce the risk of harm?
He concedes that the answer isn’t so simple. Though GLP-1s could help people with addiction, he said, they may also lead to harms not yet fully investigated or understood.
“I would hate to see someone start on a GLP-1 and, for one reason or the other, stop it and experience a roar of addiction coming back again where all of a sudden they’re feeling the magnetic pull to cocaine or opioids,” he said.
This, too, is a road that could lead to overdose and, potentially, death.
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GLP-1s are ‘not a magic bullet’ in addiction care, Dr. Scioli says.Joe Lamberti/The Globe and Mail
At Caron, patients must undergo a comprehensive medical evaluation by the non-profit’s addictions medicine team to determine if they are a suitable candidate for GLP-1 therapy. Patients prescribed the medication off-label are then carefully monitored.
Dr. Scioli, who recently left Caron and is stepping into the role of president of the American Osteopathic Academy of Addiction Medicine, said his former patients have so far not reported any negative outcomes.
He said GLP-1s helped bring a spark back to many of their lives, allowing patients to reconnect with themselves and their loved ones.
But he stressed that GLP-1s are not a stand-alone treatment option and must be coupled with other supports, such as psychiatric services and other substance-use disorder medications.
“It certainly sets patients up for long-term success, but it’s not a magic bullet,” Dr. Scioli said. “I’d reserve the word miracle for a cure.”
GLP-1s in focus: More from The Globe and Mail
Skinny Inc.
To get ready for generic Ozempic’s debut in Canada, The Globe’ limited-series podcast Skinny Inc. took a deeper look at the GLP-1 revolution. Learn more about the science and big business behind the drugs, and the effect they’ve had on the body positivity movement and mental health.
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