Buprenorphine saved Eric Ezzi.
Heroin had overrun the Philadelphia-area native’s life in his early 20s. He lost jobs, went to jail and burned bridges with his family. A few years into his addiction, Ezzi found what he hoped would be the ultimate solution: buprenorphine.
Often known by the brand name Suboxone, buprenorphine is a medication that blocks a person's cravings for stronger opioids without offering much of a high and prevents symptoms of painful withdrawal. Decades of research have found that buprenorphine helps people reduce their illegal drug use, improve their quality of life and lower their risk of premature death by 50%.
"If I didn't have [buprenorphine], I wouldn't have had a day away from heroin,” Ezzi said. “I would have been continuously using day in and day out.”
But the rise of the deadly synthetic opioid fentanyl has made it harder to use this highly effective treatment. With 83,000 people dying from opioid overdoses in 2022 — 75,000 involving fentanyl — clinicians, researchers and policymakers are scrambling to adapt.
Fentanyl can trigger a sudden crash
If someone takes buprenorphine while other opioids are still in their system, they can be plunged into sudden and intense withdrawal known as precipitated withdrawal. Over the last five years, clinicians and people using fentanyl have reported an uptick in this painful reaction, likely because when used over long periods of time, fentanyl takes longer to leave the body than heroin or other prescription opioids.
One morning in February 2020, Eric Ezzi experienced precipitated withdrawal on his way to his landscaping job.
For three years, Ezzi had used buprenorphine during the week and heroin on the weekends. It was a step, Ezzi hoped, to leaving heroin behind for good. This approach had allowed him to find steady work, stay out of jail and rebuild relationships.
But the previous weekend, his dealer had mixed Ezzi’s heroin with fentanyl.
“Out of nowhere, I got hit with this intense feeling of cold,” Ezzi said. “I was shivering. I was getting the shakes. I was sweating. It felt like the worst parts of withdrawal in this span of five minutes.”
By the time Ezzi got to work, he said it felt like his skin was crawling and sunshine felt like a physical assault. He beelined for the backyard to hide in a pile of mulch. His co-workers had seen precipitated withdrawal before and recommended Ezzi take more fentanyl to end his agony. Ezzi paid a drug dealer $500 to deliver to his job site.
“At that point, if [someone] would’ve said drinking a liter of cyanide would have fixed it, I would have thought about it,” Ezzi said. “It feels like you're imploding from within.”
Ezzi said he made it through the day thanks to the fentanyl. Ezzi experienced the same shaking, shivering, skin crawling symptoms several weeks in a row. Fentanyl now dominated his dealer's heroin supply and on Monday mornings, within minutes of taking buprenorphine, the precipitated withdrawal shut him down.
Ezzi quit buprenorphine. He started using fentanyl every day of the week, then meth. Eventually, he lost his job, stole from his family and got kicked out of the house he shared with his brother. Ezzi wanted to stop using, but his fear kept him from reaching for the one sure thing that had helped: buprenorphine.
Buprenorphine still works for most patients
The true size of this problem is unknown. One of the few rigorous studies suggests just 1% of fentanyl users experience precipitated withdrawal.
“Buprenorphine still works well for opioid use disorder in people who use fentanyl,” said Ashish Thakrar, an addiction specialist at the University of Pennsylvania. “Most people who start buprenorphine will feel better even if they were using fentanyl.”
Based on his own experiences and other reports, Thakrar guesses precipitated withdrawal affects somewhere from 5% to 15% of people. What experts do agree on is that fear of the treatment on the street is growing, now some clinicians and policymakers are racing to adapt as the nation's overdose epidemic worsens.
“If people start saying no to buprenorphine, that means we’re going to be out of options for a lot of these patients,” Thakrar said. “People are going to die.”
New approaches to buprenorphine seek to overcome fear
Right now, buprenorphine is the most widely used of just three FDA-approved medications to treat opioid use disorder. (The other two are the less effective naltrexone and less available methadone.) Policymakers have actually expanded access to buprenorphine in recent years. In 2016, Congress started allowing nurse practitioners and physician assistants to prescribe the medicine, and at the end of 2022, lawmakers removed the so-called “X-waiver,” which had required providers to get special training and registration before they could prescribe buprenorphine.
But with only 22% of people with opioid use disorder getting any medication for their addiction — and fear of buprenorphine growing — the call for new approaches has gotten louder.
Some experts have urged health officials to allow treatments available in other countries, like using slow-release oral morphine or medical-grade heroin. Other researchers are testing wholly new treatments, such as vaccines, monoclonal antibodies or deep brain stimulation. But none of these alternatives are likely to come into use in the U.S. soon.
The most immediate work is focused on tweaking existing treatments.
Clinicians are experimenting with ways to start patients on buprenorphine that are less likely to cause precipitated withdrawal. The most common approaches involve starting patients on lower or higher doses of buprenorphine. Both techniques have been shown to work and are used every day, though experts say more research is needed.
These alternatives can help patients overcome their fears, Thakrar said, but too few doctors are aware of these approaches right now.
“The scope of the problem is just so huge that we cannot rely on only addiction specialist clinicians to do this,” Thakrar said. “We need to do everything we can to support primary care clinicians and generalists to do it as well.”
Congress could make methadone easier to get
Many addiction experts believe easier access to methadone could also help. Methadone is just as effective as buprenorphine and does not cause precipitated withdrawal. But unlike buprenorphine, which can be prescribed in a doctor’s office, methadone is only available in the U.S. in highly regulated federally licensed clinics.
Patients often have to go to these clinics every day and be supervised while swallowing the liquid medication, and about one-quarter of Americans — most of them living in rural areas — don’t have a clinic in their county.
Methadone restrictions date back to the 1970s, said Leslie Suen, a researcher and addiction specialist at the University of California, San Francisco, when drug use was viewed as a crime problem instead of a health issue.
“The main outcome that people were interested in was not necessarily reducing [a patient’s] death, but really reducing criminal activity,” Suen said. “It was assumed that people who were using heroin were criminals.”
Expanding access to methadone carries some risk. It's easier to overdose on methadone than buprenorphine. But decades of data, including during the pandemic when restrictions on the drug were loosened, show that overdoses from drug treatment are rare. A growing number of addiction specialists and federal lawmakers are using that evidence and the ongoing overdose crisis to argue that methadone rules should be eased.
The bipartisan Modernizing Opioid Treatment Access Act, approved by a key Senate committee in December, would allow addiction specialists to prescribe methadone outside of a methadone clinic. Patients could pick the medication up at their local pharmacy like people do in other countries including Canada, the United Kingdom and Australia.
A group of researchers estimate the legislation, if passed, would increase access to methadone by nearly 30%. But experts agree methadone would still be hard to get, especially in rural areas.
The American Association for the Treatment of Opioid Dependence, the organization that represents methadone clinics, opposes the legislation. Mark Parrino, the group’s president, said he worries moving the treatment outside of the clinic system could lead to more overdoses and deprive patients of the counseling and additional services clinics offer.
Challenges Loom Beyond Fentanyl
It’s important to remember, Thakrar said, that even as fentanyl makes treating opioid addiction more difficult, buprenorphine and methadone remain incredibly effective treatments. The situation is likely to get more difficult, he warned, as new designer drugs could hit the street and threaten the usefulness of those treatments.
“People will [continue to] go out to a corner, to a friend or somewhere else and buy a white powder,” Thakrar said. “That white powder maybe was heroin at one point. Right now, it's probably fentanyl mixed with xylazine. In 5 to 10 years, it's probably going to be a different synthetic opioid.”
He said the ease of synthesizing cheaper, even more dangerous variations of illicit drugs makes the purity of what’s sold on the street unpredictable. To stay ahead of the next wave of overdoses, some doctors have suggested policymakers provide people who have opioid use disorder a “safe supply” of opioids. Thankrar said such a move would be extremely controversial in the U.S. and a political longshot.
Both Thakrar and Eric Ezzi agree maximizing the effectiveness of current treatments is a step in the right direction.
In 2020, fentanyl nearly destroyed Ezzi’s life in just a few months. It took an ultimatum from his probation officer — get treatment or go to jail — to finally get Ezzi to seek help. Even then, he refused to take buprenorphine and risk precipitated withdrawal. Instead, he chose to quit fentanyl and other drugs cold turkey — another sort of agony he does not recommend.
Today, Ezzi sees that same fear in the eyes of some of the patients he advises as a recovery counselor at Penn Medicine. He tells his story hoping to dispel those fears.
He wants his patients to know that buprenorphine can still work. He wants clinicians to find new and better ways to treat people who are afraid. And he wants everyone else to remember that people who use drugs are human. They’re suffering and they need help now.
This story comes from the health policy podcast Tradeoffs. Dan Gorenstein is Tradeoffs' executive editor, and Ryan Levi is a senior reporter/producer for the show, where a version of this story first appeared.
Side Effects Public Media is a health reporting collaboration based at WFYI in Indianapolis. We partner with NPR stations across the Midwest and surrounding areas — including KBIA and KCUR in Missouri, Iowa Public Radio, Ideastream in Ohio and WFPL in Kentucky.