GLP-1 Medications Combined with Buprenorphine Show Promise in Major Opioid Treatment Trial

Dr. T. John Winhusen didn't set out to revolutionize addiction treatment with weight-loss drugs. But when evidence began mounting that GLP-1 medications—the class of drugs that includes Ozempic and Wegovy—could interact with the brain's reward networks, the University of Cincinnati researcher saw an opportunity. Now, he's leading one of the largest clinical trials in the country exploring whether pairing these medications with buprenorphine, a proven treatment for opioid use disorder, can solve one of addiction medicine's most stubborn problems: keeping patients in treatment long enough to benefit from it.

"One of the biggest challenges in treating opioid use disorder is actually keeping people in treatment long enough for them to benefit from it," Winhusen, principal investigator and director of the UC/UC Health Addiction Center, told Rolling Stone in an article published this week. His trial aims to enroll more than 300 patients across 10 sites to test whether GLP-1s can reduce cravings enough to prevent the kind of bad day that leads patients to abandon their recovery entirely.

The stakes couldn't be higher. Research shows that patients who stop medications like buprenorphine are six times more likely to die in the month after discontinuing treatment compared to while they were actively receiving care. With only about half of patients remaining in treatment for more than six months, finding ways to improve retention could save thousands of lives annually.

How GLP-1s Work Beyond Weight Loss

GLP-1 medications were originally developed to treat type 2 diabetes by activating receptors that signal the pancreas to release more insulin. This delays stomach emptying, controls appetite, and leaves users feeling fuller longer—effects that made the drugs wildly popular for weight loss starting in 2021. But researchers discovered something unexpected: GLP-1s also interact with neural reward pathways in the brain, the same structures that influence addiction.

"There's a kind of satiety effect that is generated by these medications that is brain mediated," Dr. Christian Hendershot, director of Clinical Research at the USC Institute for Addiction Science, explained. "Reward-related centers of the brain are what we think leads to reduced cravings."

This mechanism mirrors what weight-loss patients reported as reduced "food noise"—the constant mental preoccupation with eating. For people struggling with substance use disorders, the implications are profound: a medication that could quiet the relentless cravings driving continued drug use, without the stigma attached to traditional addiction treatments.

The Stigma Problem Blocking Access

Despite the availability of FDA-approved medications for opioid use disorder—buprenorphine, methadone, and naltrexone—utilization remains devastatingly low. A 2024 CDC study found that of the estimated 10 million American adults needing treatment for opiate use disorder, only 25 percent were prescribed buprenorphine. The reasons extend beyond simple access barriers; many patients struggle to accept addiction as a medical condition requiring pharmaceutical intervention rather than a moral failing.

"Before 1956, addiction to drugs and alcohol were considered failings in morality or personal will," the Rolling Stone article noted. While medical understanding has evolved, the cultural residue remains. Patients may avoid seeking treatment or refuse medications because of shame, fear of being labeled an "addict," or belief that true recovery means complete abstinence from all substances.

GLP-1s offer a potential workaround to this deeply entrenched stigma. "One of the appealing aspects about GLP-1 therapies is that they're widely accepted," Hendershot said. "They're actually very much in demand, and [an] increasing proportion of physicians and clinicians are familiar with these medications. We think that this will allow us to circumvent some of the barriers related to the uptake of traditional [substance] use disorder treatments."

The medications carry a burnished reputation from their success in diabetes management and weight loss. A patient might be more willing to try a drug associated with health optimization and Hollywood endorsements than one explicitly labeled for addiction treatment, even if both serve the same functional purpose in reducing substance use.

Early Evidence from Treatment Centers

While Winhusen's large-scale trial is ongoing, some treatment facilities have already begun incorporating GLP-1s into their programs with encouraging results. Dr. Adam Scioli, chief medical officer at Caron Treatment Centers in Delray Beach, Florida, started one of the first studies on GLP-1s for addiction in 2023, partnering with Penn State University School of Medicine.

"What we found was a pretty significant reduction in cravings at a much lower dose than the general population tends to be on, particularly for weight loss," Scioli reported. Following the study, Caron began offering GLP-1s as supplemental medication to patients in addiction treatment. Since then, they've treated 150 patients with GLP-1s for substance use disorders, with the large majority reporting significant reductions in cravings.

"This medication gets patients feeling more normal earlier," Scioli explained. Instead of identifying primarily as addicts, patients begin seeing themselves as people managing a medical condition "just like anyone else who is sick—someone who has the potential to get well, contribute in a meaningful way, and be treated as an equal."

For Sydney S., a 27-year-old who spent months at Caron in 2024, the addition of a GLP-1 five months into treatment marked a turning point. Her substance use had escalated from marijuana at age 12 through alcohol, cocaine, Percocet, Xanax, and ketamine by her early twenties, consuming so much daily that she marvels she survived. When she added a GLP-1 to her treatment regimen, "the mental space I had dedicated to drugs and alcohol began to shrink," she said.

The real test came after discharge. Moving out of her Miami home, she encountered enough drugs "for months of relapsing" but didn't touch them. "That was a pretty spiritual moment where I was able to be around drugs and not pick up anything," she told Rolling Stone. Sydney continues taking a GLP-1 and has rebuilt her life, waking at 5 a.m. to paint before her day job. "I've made my best art sober—that's an unmatched feeling that drugs can't give me."

Timing Amid Federal Funding Threats

The University of Cincinnati trial launches at a precarious moment for addiction treatment infrastructure. The opioid epidemic has killed more than 450,000 Americans in the past five years, though recent years have shown modest declines in overdose deaths. Winhusen attributes that progress partly to coordinated harm reduction measures: expanded access to Narcan (naloxone), more doctors authorized to prescribe buprenorphine, and federal funding for treatment programs.

But those gains face significant threats. The Trump administration has implemented $350 million in funding cuts to addiction services and layoffs that gutted nearly half of the Substance Abuse and Mental Health Services Agency (SAMHSA) workforce, according to STAT News reporting. "If people can't access treatment," Winhusen warned, "we're definitely going to see an increase in overdose deaths."

In this context, GLP-1s represent both opportunity and complication. If the medications prove effective and gain FDA approval for substance use disorder treatment, they could offer a new pathway for the millions of Americans who need help but can't or won't access existing options. However, they also introduce new cost and access barriers.

The Off-Label Challenge and Insurance Barriers

The FDA has not approved any GLP-1 medications specifically for substance use disorder treatment, which means doctors must prescribe them "off-label"—legal and fairly common in medicine, particularly psychiatry, where many medications for sleep disorders, anxiety, and depression were originally approved for other conditions. But off-label prescriptions face significantly higher insurance denial rates than approved uses.

This creates a catch-22: researchers like Winhusen and Scioli need to conduct large-scale trials proving GLP-1s work for many patients with opioid use disorders to secure FDA approval, but patients who might benefit from the medications during these years of research often can't access them because insurers won't cover off-label use and out-of-pocket costs are prohibitively expensive. (GLP-1 medications can cost $1,000 or more monthly without insurance coverage.)

For the patients who can't get GLP-1s—either because their doctors won't prescribe off-label or their insurers won't cover it—the wait for formal approval could mean years of continued risk. And time is precisely what people with substance use disorder may not have: every day in active addiction carries risks of overdose, infectious disease, criminal legal involvement, housing loss, and family dissolution.

Caution About Long-Term Effects

Not all researchers share Winhusen and Scioli's enthusiasm. Dr. Carolina Haass-Koffler, an associate professor of Psychiatry and Human Behavior at Brown University, emphasized the need for caution. "I'm a researcher, so I'm excited when there are opportunities for developing new therapies," she said. "But there are only two real clinical trials that show the use of GLP-1s—and the majority of [available] information is anecdotal. We need to be careful."

The FDA notes that common long-term side effects of GLP-1s could include bone density loss and gastrointestinal issues. A 2025 study from researchers at Washington University in St. Louis found links between long-term GLP-1 usage and pancreatitis and kidney conditions. For patients taking these medications specifically for weight loss, such risks might be acceptable trade-offs. But for patients with substance use disorders, the calculation becomes more complex.

If a patient takes a GLP-1 for years to maintain recovery from opioid addiction, then develops serious gastrointestinal problems or kidney disease, was the intervention worth it? The answer likely depends on the severity of their addiction and availability of alternatives. For someone like Sydney, whose substance use had become life-threatening, kidney risks years down the line might seem abstract compared to the immediate risk of overdose. But these are precisely the kinds of long-term outcomes that won't become clear until years of patient data accumulate.

Paradoxically, the only way to truly understand long-term effects is to have patients take GLP-1s for extended periods while being monitored. But without FDA approval, many patients who could benefit from the medications—and who could contribute data to these crucial long-term studies—can't access them.

What Comes Next

Winhusen's trial represents a significant step toward resolving these uncertainties. By enrolling more than 300 patients across multiple sites, the study will generate the kind of robust data needed for FDA consideration. If results show that GLP-1s combined with buprenorphine significantly improve treatment retention compared to buprenorphine alone, it would provide strong evidence supporting formal approval for this use.

Approval would, in turn, pressure insurance companies to cover the medications for substance use disorder treatment, dramatically expanding access. It might also shift the cultural conversation around addiction treatment, making it easier for patients to accept medication-assisted treatment if one of the options is a drug they've heard celebrities and influencers praise rather than one they associate with "junkies" and methadone clinics.

However, approval is neither guaranteed nor imminent. Clinical trials of this scale take years to complete, analyze, and publish. Even after results become available, the FDA review process adds additional time. During these years, the opioid epidemic will continue claiming lives—an estimated 110,000 Americans died annually from opiate overdoses in 2023, though recent years have shown decreases.

Meanwhile, patients and providers face difficult decisions about off-label use. For facilities like Caron that have the resources and expertise to safely incorporate GLP-1s into comprehensive treatment programs, early adoption may save lives and generate valuable practice-based evidence. For individual patients with the means to pay out-of-pocket or insurance willing to cover off-label prescriptions, GLP-1s offer a potentially game-changing addition to their recovery toolkit.

But for the millions of Americans who can't afford expensive medications without insurance coverage, who live in areas with few addiction treatment resources, or whose doctors aren't comfortable prescribing GLP-1s off-label, these developments remain tantalizingly out of reach. The medications might revolutionize addiction treatment in the future, but that future hasn't arrived for most people who need help today.

Sydney S. continues to take her GLP-1 daily, crediting it with helping her maintain the sobriety that has allowed her to rebuild her life and artistic practice. "Knowing how much I can accomplish," she said, "I think I will be on [a GLP-1] for a very long time."

Whether thousands of other Americans struggling with opioid addiction will have the same opportunity depends on whether the promise of these medications, suggested by early evidence and small studies, holds up under the rigorous scrutiny of large clinical trials—and whether the healthcare system can move quickly enough to make proven treatments accessible before more preventable deaths occur.