Why Are People Afraid of the Most Popular Opioid Addiction Treatment?

Dan Gorenstein: The U.S. drug overdose crisis continues to rage. More than 6 million Americans are addicted to opioids. In 2022, 83,000 people died of an overdose. To tackle this epidemic we do have incredible treatments, like buprenorphine.

Ashish Thakrar: It just saves lives and improves outcomes so powerfully.

DG: But illicit use of fentanyl seems to be making treatments like buprenorphine less effective for some people.

Eric Ezzi: I would be willing to die just about rather than feel that way.

DG: Today, how the rise of fentanyl has made it harder to treat opioid addiction, and what clinicians and policymakers are doing to adapt. From the studio at the Leonard Davis Institute at the University of Pennsylvania, I’m Dan Gorenstein. This is Tradeoffs.

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DG: Buprenorphine saved Eric Ezzi’s life.

EE: Without that, I wouldn’t have made it.

DG: Eric is 32. He lives just outside of Philadelphia with his wife and baby daughter. Heroin overran Eric’s life in his early ’20s. He lost jobs, went to jail, burned bridges with his family. But a few years into his addiction he found a solution: buprenorphine.

EE: It was beautiful. I just felt normal and like I was really excited about that.

DG: Buprenorphine, often known by the brand name Suboxone, is itself an opioid. It 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 reduces illegal drug use, improves quality of life and lowers the risk of a person’s premature death by 50%. For Eric and many others, buprenorphine is truly a miracle drug. 

EE: When I wasn’t experiencing the feeling of being on some substance, it felt like I had a bag over my head. And I was like gasping for air. This was the first time where I woke up in the morning, I took my medicine, and I didn’t feel like that.

DG: Eric wanted to leave heroin behind for good. Buprenorphine made that seem possible. 

EE: If I didn’t have that, I wouldn’t have had a day away from heroin.

DG: Eric still used heroin on weekends — recovery is rarely a straight line. But Monday through Friday, Eric took his buprenorphine every morning and slowly rebuilt his life. He landed work as a landscaper. He stayed out of jail. He moved in with his older brother. All thanks to this drug. Eric’s buprenorphine/heroin routine lasted three years, until one Monday in February 2020. Eric still remembers the morning, cool and sunny. He took his buprenorphine, as he always did, on his way to work.

EE: Out of nowhere I got hit with this intensive feeling of cold.

DG: Eric was confused and scared. He’d never had this kind of reaction to buprenorphine.

EE: I was getting the shakes, I was sweating. It felt like the worst parts of withdrawal in this span of five minutes.

DG: When he got to the job site, he says the sunshine felt like a physical assault. Terrified, Eric beelined for the backyard and hid in a pile of mulch. 

EE: I’ve been through withdrawal and I’ve been able to pretend to be normal and fight through it, but I couldn’t tough this out.

DG: See, the heroin Eric had taken over the weekend was mixed with fentanyl. Fentanyl takes longer than heroin to leave the body. And when a person takes buprenorphine while other opioids are still in their system, they can be plunged into sudden and intense withdrawal, often called precipitated withdrawal.

EE: It feels like you’re imploding from within.

DG: Eric had never used fentanyl as far as he knew. But his coworkers had, and they’d seen precipitated withdrawal before. They told Eric his best move was to get more fentanyl.

EE: I feel like at that point, if they would’ve said drinking a liter of cyanide would have fixed it, I would have thought about it. So I gave them $500 of my money to have the drug dealer drive that hour and sell us what was probably realistically $200 worth of fentanyl.

DG: With the fentanyl on board, Eric made it through the day. But the same thing happened the next Monday, and the Monday after that.  Fentanyl now dominated his dealer’s heroin supply, and every Monday, within minutes of taking his buprenorphine, the precipitated withdrawal crashed into Eric.

EE: It just feels so rough, and you were willing to do anything to stop it. Anything to stop that feeling from happening.

DG: Eric was so scared, he quit buprenorphine. He started using fentanyl every day, then meth. He lost his job, started stealing from his family. His brother kicked him out. A handful of weeks without buprenorphine and the stable life Eric spent years building had shattered.

EE: I just felt like a forgotten pile of trash, even to myself, that like, there was no part of me worth loving or worth understanding.

DG: Eric wanted help, but his fear kept him from the one thing that had always helped before: buprenorphine.

What happened to Eric is becoming more common: Some percentage of people who treat their fentanyl addiction with buprenorphine end up with sudden, painful withdrawal symptoms.  Researchers and advocates say fear of buprenorphine is growing on the street and it’s forcing medical providers to scramble for solutions.

Ashish Thakrar: If people start saying no to buprenorphine that means we’re going to be out of options for a lot of these patients.

DG: Ashish Thakrar is a primary care doc and addiction specialist at the University of Pennsylvania. He saw his first case of precipitated withdrawal back in 2019.

AT: The patient, he was a young man, he was in bed dripping in sweat. The hair on his arm was standing up.He was feeling really, really awful and asking really painful questions, like, “Why did you do this to me? Why did you make me feel so much worse?”

DG: Ashish had just started seeing reports in major journals documenting an increase in precipitated withdrawal. Fast-forward to today, Ashish says experts are still trying to answer basic questions including how many people are affected. One of the few rigorous nationwide studies found that just 1% of patients experienced precipitated withdrawal going from fentanyl to buprenorphine.

AT: This is the highest quality study that exists right now. And it surprised me and I think a lot of folks working in the field because that number felt so much lower than what patients were telling us.

DG: Based on other reports and his own experiences, Ashish guesses it’s more like 5 to 15 percent of patients – only a slightly bigger fraction. And yet, horror stories from people like Eric have stoked fear among far more people who use fentanyl, and it’s made buprenorphine a much tougher sell to patients now. When we come back, how clinicians and policymakers are trying to make addiction treatments work better, and how Eric coped with his fear.

MIDROLL

DG: Welcome back. Since it was first approved 20 years ago, buprenorphine — what is sometimes called “bupe” — has been one of the most effective treatments for opioid addiction. And policymakers have continued to make it easier to prescribe the drug. But the rise of illicit fentanyl has made it harder for some people like Eric Ezzi to use buprenorphine to manage their addictions. Here to tell us how clinicians and policymakers are scrambling to respond is Tradeoffs producer Ryan Levi. Hey, Ryan.

Ryan Levi: Hey, Dan.

DG: So you’ve spent the last several months digging into this. What have you learned, Ryan, about the options for helping someone like Eric? 

RL: Well, I’d say these efforts fall into three buckets, Dan: 1) tweaking how buprenorphine is given to people; 2) expanding access to another effective medication: methadone; and 3) adding whole new treatments.

DG: OK, great. Where do you think we should start?

RL: Probably the new treatments, this is a pretty quick one. Right now, there are only 3 FDA-approved medications for opioid use disorder: buprenorphine, methadone and naltrexone … and, Dan, only 20% of people addicted to opioids are getting any of these. Now, most folks are on buprenorphine because naltrexone is considered less effective and methadone — which we’ll get into more later — can be pretty hard to come by.

DG: Right, so lots of people feel like it’s bupe or bust.

RL: Exactly, Dan. And that’s why there’s this big push for more alternatives. There are existing medications used in other countries, like slow-release oral morphine or even medical-grade heroin, which aren’t approved to treat opioid addiction here in the U.S. And there are researchers working on totally new treatments – like vaccines, monoclonal antibodies or even deep brain stimulation — literally electrodes inside your brain, Dan — which could help curb opioid addiction. But all of those potential options are years away at best.

DG: Right, years away. That’s one of the buckets, Ryan. Let’s go to how clinicians are tweaking how they administer buprenorphine to help people like Eric. What’s happening there? And please, don’t lose me in the medical weeds!

RL: I’ll do my best, Dan. For the last 20 years, there’s been a pretty straightforward protocol for starting someone on buprenorphine: First, you wait until they start to feel withdrawal symptoms — this usually takes 6 – 24 hours — and then you give them that first dose. This still works for most patients. But as you mentioned earlier, Dan, fentanyl often takes longer to clear a person’s system than heroin does. So that approach can sometimes plunge a patient into that brutal precipitated withdrawal. In response, clinicians have begun to experiment, and there are two common approaches they’ve come up with: starting people on either a lower or higher dose of bupe — what the doctors like to call low-dose and high-dose initiation.

DG: And what do we know about this high-dose and low-dose initiation. Are they actually working, Ryan?  

RL: They have worked. Docs are using them every day, but experts told me more research is still needed. Low-dose is the more common approach, and the idea here is by starting with less buprenorphine there’s a smaller risk it will throw a person into precipitated withdrawal. But the University of Pennsylvania’s Ashish Thakrar, who you talked with earlier, he told me this can be tricky. To work, that small dose of buprenorphine has to be paired with a steady dose of another opioid like oxycodone.

AT: In the hospital, we can administer a controlled and safe amount at a consistent level. And then while we keep them out of withdrawal with the oxycodone, we slowly introduce buprenorphine.

DG: OK, so this has worked in hospitals, but I know part of buprenorphine’s appeal is that people can get it from their doctor’s office or a clinic. It’s really easy to get. Does this low-dose approach work in those patient settings like that?

RL: It’s a lot harder, Dan. In fact, Ashish told me, it’s illegal.

AT: Yes, I’d be breaking federal law if I prescribed an opioid like oxycodone as short-term treatment of opioid addiction. I can prescribe any opioid I want if it’s to treat pain. But federal law limits what we can prescribe to treat opioid addiction.

RL: In the controlled setting of a hospital, physicians can “administer” opioids like oxycodone to help someone start addiction treatment. But outside of a hospital, there are more rules. And Ashish could be fined or even go to jail if he tried to do a low-dose initiation this way.

DG: So what happens if someone comes to Ashish’s clinic, they want the bupe, but they’re afraid of some bad withdrawal? 

RL: Some clinicians won’t do low-dose outside of a hospital. Full stop. But several doctors including Ashish told me they ask their patients to keep using their street drugs to avoid withdrawal while they do the low dose.

DG: You mean to get off fentanyl — I think this is what you’re saying — to get off fentanyl, doctors tell their patients to keep using fentanyl?

RL: That’s right, for at least a few days.

DG: That sounds pretty wild, Ryan. Does it work?

RL: Ashish has done it, and successful cases have been written up in journals. But obviously it’s riskier. Ashish says he does feel weird about it, but sometimes it’s the only option to try and get someone into treatment.

DG: Wow, that really shows you how precious that moment is when someone wants to deal with their addiction, and how valuable docs see buprenorphine as a tool. OK, so that’s the low-dose process, Ryan. What about high-dose. You’d think giving people more buprenorphine could make precipitated withdrawal more likely. 

RL: A couple recent studies showed this can work, Dan, this high-dose approach, but some docs including Ashish, they’re still skeptical and want more research before they use this method. The idea is that people often end up needing higher doses of buprenorphine to treat fentanyl addictions long-term. So high-dose initiation says let’s jump right to those higher doses. Now, regardless of which approach they favor, every doctor I talked to said taking patients’ fear of buprenorphine seriously is critical to overcoming those fears. 

AT: Almost every patient that I’m seeing has a strong opinion about how they want to start buprenorphine. And most of the time, what they’re suggesting they want to do is plausible. And so I’ll talk them through it and try to support them in that process.

DG: To that point, Ryan, how many clinicians even know about all this? 

RL: It’s really hard to say. There’s no data on this, but based on my reporting, it seems like addiction specialists like Ashish, they’re aware. But that’s really about it. There are only a few thousand addiction specialists in the country, so Ashish told me if these approaches are going to have a real impact, they’ve got to spread.

AT: The scope of the problem is just so huge that we cannot rely on only addiction specialist clinicians to do this. We need to do everything we can to support primary care clinicians and generalists to do it as well.

DG: So that’s how clinicians are trying to make buprenorphine work better in this fentanyl era. But you also have people like Eric Ezzi who are too afraid to go anywhere near buprenorphine. The best option for them, in theory, would be your last bucket: methadone? Tell us about methadone.

RL: Yeah, so methadone has been used to treat opioid addiction in the U.S. since the 1960s, Dan. And again decades of research show it’s just as effective as buprenorphine at reducing illegal drug use, overdoses and death.

DG: Another miracle drug.

RL: Exactly, and it does not cause precipitated withdrawal. But a bunch of regulations make methadone tougher to get your hands on, Dan. Unlike buprenorphine, which can be prescribed in a doctor’s office, you can only get methadone from highly regulated, federally licensed clinics. People often have to go to these clinics every day and be supervised taking the medication. And even though there are more than 2,000 methadone clinics nationwide, 25% of the population — most of them living in rural areas — don’t have one in their county.

DG: So methadone can be pretty hard to get for some people. But here’s the thing that confuses me, Ryan: Why is methadone so much more strictly regulated than buprenorphine? I don’t get that.

RL: Two big reasons. One, it’s a lot easier to overdose on methadone than it is on buprenorphine. And two, methadone hit the scene right at the start of the War on Drugs.

Anti-Drugs Ad: OK last time, this is your brain on drugs, any questions?

RL: Leslie Suen is a researcher, primary care physician and addiction specialist at the University of California San Francisco. She told me that at that time, drug use was seen more as a crime problem than a health issue.

Leslie Suen: The main outcome that people were interested in was not necessarily reducing their death, but really reducing criminal activity because it was assumed that people who were using heroin were criminals.

RL: But over the last 50 years, Dan, methadone overdoses from drug treatment have been pretty rare, including during the pandemic when some of these rules were loosened. And that’s led a growing number of people to say it’s time to rethink these restrictions, especially given the rise of fentanyl.

DG: So what does that look like? What kind of changes are actually being proposed here?

RL: The big one is a bipartisan bill called the Modernizing Opioid Treatment Access Act. Addiction specialists like Leslie and Ashish, they would be able to prescribe methadone outside of a methadone clinic, and patients could pick it up at their local pharmacy. It would be like any other prescription, and it’s how methadone is handled in other countries like Canada, the U.K. and Australia.

DG: Do people see this as a game-changer, Ryan?

RL: One group of researchers estimated this legislation would increase access by nearly 30%. But experts agree methadone would still be hard to get, especially in rural areas. I should add, Dan, the organization that represents methadone clinics, they worry that moving the treatment outside of the clinic system could lead to more overdoses and keep patients from getting the counseling and other services clinics offer. This group thinks it would be better to just open more clinics. But look, at the end of the day, everyone I talked to agreed that more people could benefit from methadone, and given the danger of fentanyl, we need as many options as possible.

DG: Before you go, Ryan, I’m curious: What’s your biggest takeaway from all this reporting you’ve done? 

RL: I’ve been thinking a lot about a couple of things that Ashish Thakrar told me, one that’s optimistic and one that’s a little scarier. The optimistic point is that as hard as it can be to think about all the people who are addicted and dying from overdoses, we do have treatments that work. I really like how Ashish put this. 

AT: I hear about surgeons all the time who take a lot of pride and joy in excising that tumor. There’s actually a really similar joy and satisfaction that I get from helping to care for these patients with addiction. It’s maybe not as immediate as going in the OR and taking out a tumor, but people get better.

RL: The scarier takeaway is that the drug supply on the street is rapidly shifting. We are in this era of easily made designer drugs, any one of which could render the treatments we have right now obsolete.

AT: People who are using opioids can’t access the type of opioids that they’re looking for at the potency they want in a safe way. What that means is that people will go out to a corner, to a friend and buy a white powder. 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.

RL: As bizarre as it sounds, we’ve been somewhat lucky with fentanyl. The treatments we have still work. But they might not work against whatever comes next, and the weaker tools like buprenorphine and methadone become, the more people will die.

DG: You know, Ryan, that raises the question, to me at least, given the unpredictability of the drug supply you’re talking about, whether one day the government — and this does sound far-fetched — but maybe will step in and provide people a regulated “safe” supply of opioids. Obviously that would be incredibly controversial, but I think of Eric Ezzi. His troubles started because he got fentanyl when he wanted heroin. There wasn’t a store though of course he could go to, and maybe that’s what it will take to keep people alive. Tradeoffs producer Ryan Levi, I just want to thank you for your wonderful reporting on this.

RL: You’re welcome, Dan.

DG: By the end of 2020, fentanyl had just about destroyed Eric Ezzi’s life.

EE: I would feel the lowest I ever felt. And then just some time would go by and it would completely get worse.

DG: After months of spiraling and wondering if he was better off dead, Eric’s probation officer gave him an ultimatum: Get treatment or go to jail. Eric went to treatment, but he refused to take buprenorphine. Eric opted to quit cold turkey rather than risk the kind of agony he’d endured through precipitated withdrawal. Today, Eric sees that same fear in the eyes of the patients he treats as a recovery counselor at Penn Medicine.

EE: We just introduce the idea and immediately, “No, no.” Like as if I asked if I could have one of their fingers. 

DG: That’s why Eric tells his story. He wants people who want to quit fentanyl to know that buprenorphine can still work. He wants clinicians to find new and better ways to treat people who are afraid of bupe. And he wants everyone else to remember that people who use drugs are human — they’re suffering and they need help now. I’m Dan Gorenstein. This is Tradeoffs.