The opioid crisis: From pill mills to the rise of fentanyl, and current glimmers of hope

Tiny Matters

In 2021, 80,411 people in the United States died of an overdose involving opioids, making up 75% of all drug overdose deaths that year. That’s also 10 times as many opioid overdose deaths as in 1999. How did we get here?

In this episode, Sam and Deboki trace the origins of opioids, from opium and morphine to fentanyl, and scrutinize the significant role pharmaceutical companies played in kick starting the opioid crisis in the 1990s. Today, the highly potent opioid fentanyl has become the street supply of opioids, which has led to a steep incline in overdose deaths. On top of that, it can be adulterated with dangerous substances like xylazine or "tranq." Now more than ever, facilities focused on harm reduction are crucial. These facilities allow for safe needle exchange, which reduces the risk of transmitting diseases like HIV and hepatitis C, and also provide opioid users with treatment and access to other healthcare testing.

Although the opioid crisis is a tragic reality in this country, harm reduction, increased opioid research funding, and hefty pharmaceutical company payouts are providing glimmers of hope.

Transcript of this Episode

Sam Jones: In 2021, 80,411 people in the United States died of an overdose involving opioids, making up 75% of all drug overdose deaths that year. That’s also 10 times as many opioid overdose deaths as in 1999. So how did we get here?

Welcome to Tiny Matters, I’m Sam Jones and I’m joined by my co-host Deboki Chakravarti.

Deboki Chakravarti: In today’s episode, Sam and I are taking on an intense, misunderstood, often controversial topic: opioids, which includes drugs like oxycodone, heroin, and fentanyl. We’re asking, “What are opioids? What makes them so dangerous? Why have the number of overdose deaths skyrocketed over the last few years? And what’s being done to help pull us out of the current opioid epidemic?”

We’ll start with opioids themselves. Maybe you’ve heard both the term opiate and opioid. They’re often used interchangeably, but “opiates” technically refers to natural opioids like morphine. “Opioids” is an all encompassing term that refers to all natural, semisynthetic, and synthetic opioids, including drugs like fentanyl. 

Although opioids vary in terms of potency and method of delivery — for example, a pill versus an injection — they all work the same way. 

Sam: Opioids mimic endorphins, which are pain-relieving chemicals that your body naturally produces. I feel like we’ve all heard about, and probably experienced, that “endorphin high” after exercise. When you take an opioid, it gets into your bloodstream and heads to your nervous system, binding to opioid receptors on cells in your brain, spinal cord, and other parts of your body. This blocks the release of chemicals called neurotransmitters that would normally alert your brain to the fact that you’re in pain. 

I think we can all agree that being in pain is terrible, and opioids are incredible at relieving pain. But here’s the thing: they also make you feel happy, even euphoric. This is where things get dangerous. So opioids cause your brain to release dopamine, which is a neurotransmitter produced when we expect or experience a reward. Like when we eat food we love or get some amazing news. Typically, dopamine levels are kept in check by another neurotransmitter called gamma aminobutyric acid or GABA. But opioids block GABA   release. So dopamine levels go unregulated and we get hooked on that feeling of euphoria. In other words, we become addicted to it.

Deboki: And opioid tolerance can increase fast, so a person will need to take more and more of the drug to feel the same effects. In the case of an opioid overdose, a person will experience intense drowsiness, have trouble speaking, and their breathing and heart rate will become dangerously slow or even stop.  

So, how did opioids become so pervasive? Well, they’ve actually been around for thousands of years — since the beginnings of human civilization. It all started with opium, which is a mix of chemicals in the milky fluid of the opium poppy, which some historians say may have been used as anesthesia during surgery in ancient Greece and Egypt.

And the power of opium went far beyond surgery. In the 18th century, British traders began importing opium to China from its colonies in India, which led to a rapid rise in addiction. In 1796, China completely banned opium, but British traders continued smuggling it into the country. We’re condensing a lot of complex history here, but these tensions led to the First and Second Opium Wars, which resulted in the British colonization of Hong Kong in the 19th century.

So opium was a big deal, and it was an object of scientific curiosity as well. In 1803, a German Chemist named Frederich Sertürner discovered a chemical in opium that was more powerful on its own than as part of that opium mixture. He called it morpheum, but we know it now as morphine.

Sam: When he first made his discovery, Serturner thought that morphine would actually lower the risk for addiction because its strength meant that you’d need less of it to get the same effects as opium. But that turned out to not be the case, and Serturner actually became addicted to morphine in the process of doing his research. He sounded the alarm, but people didn’t listen.

And within a couple of decades, morphine was being mass-produced by a major German pharmaceutical company as an opium replacement, and it quickly became clear that people could absolutely get addicted to morphine. Following the Civil War for example, thousands of veterans became addicted to morphine and opium, which had been used to treat their horrible injuries. 

So scientists began looking for a different opioid that might not cause the same problem. They settled on heroin, which is actually made from morphine but is more potent so, again, scientists reasoned that not needing to use as much of it would make it less addictive. We all know this didn’t work.

Fast forward about a century later, and we have a whole host of other drugs available and are on the brink of the modern opioid crisis.

Amy Bohnert: I think we started in the US calling it an opiate crisis around 2010, but the seeds of the problem really started in the late 1990s, so a good 10 to 15 years before that. What was happening at that time was that pain, and particularly the treatment of chronic pain, was not getting nearly enough attention in medical settings, which created an opportunity for pharmaceutical companies to exploit that gap in what we were offering as care for profit.

Deboki: That’s Amy Bohnert, who is the co-director of the Opioid Research Institute and a professor of anesthesiology at the University of Michigan.

These pharmaceutical companies began creating extended release opioids. Before, the opioids available were immediate release, and would typically only last a few hours. 

Amy Bohnert: These companies were getting approval for eight to twelve hour medication formulations under the idea that they could be used for chronic pain, but used a pretty questionable study design where you start people on the opiates, the people who don't tolerate it well drop out of the trial. So you're kind of biasing it towards people who can tolerate opiates to begin with, and then you randomize people to stopping them or not, and seeing if they feel worse. And of course, if you've become physiologically dependent on the medication, you're going to feel worse when it stops.

Deboki: So these studies weren’t actually showing how well extended release opioids were treating pain. They were showing that, among people who could tolerate taking opioids, those who became dependent felt worse when they stopped. 

Amy Bohnert: Which was kind of something we already knew inherently about what it means to be physically dependent on anything — that you feel worse when you stop. Think about when you drink coffee every day. When you don't do it, you get headaches and you feel bad. It's the same concept. And one of the things you will feel when you are physically dependent, and you remove that thing that you're physically dependent on, is pain.

So then they advertised these medications widely to physicians and in particular had a pretty strong influence on the content of physician education. Again, downplaying the risks of potential long-term exposure to opioids and overstating the effectiveness. And really, there was a sea change among physicians for a while where their confidence that this was an appropriate treatment for chronic pain for the average primary care physician was quite high because that was the education they were receiving.

Deboki: In the late 90s, going into the 2000s, the rate of prescription opioid use began to rise, as did the number of overdose deaths related to prescription opioids.

Hansel Tookes: There were a lot of pill mills, a lot of unscrupulous physicians prescribing buckets full of oxycodone. There used to be the I-95, the “Oxy Express,” so people all along the East coast of the United States would come to Florida and access these pill mills.

Deboki: That’s Hansel Tookes, who is an Associate Professor of Medicine at the University of Miami Miller School of Medicine. He grew up in Florida — one of the places where, for many years, it was quite easy to get an opioid prescription.

Hansel Tookes: So basically we have these pain management clinics giving people access to just excessive amounts of opioids. And it was very well known that it was that easy to access opioids in Florida. 

But the legislature shut those down to try to combat the epidemic. But their well-intentions did not turn out so well because they had no solution for all of these people who were already dependent on opioids. And the cartels are very adept at responding to demand.

Sam: Hansel told us that the cartels started with counterfeit pills. Then they moved to heroin because it was cheaper and more potent. And then heroin was replaced by fentanyl because fentanyl is far more potent than heroin. There’s an incentive to have high potency drugs because it means being able to transport smaller volumes of that drug into a country where they’re illegal, like the US.

And that transition from prescription opioids like oxycodone to heroin and fentanyl led to a steep rise in opioid overdose deaths. The CDC lays out this trajectory in three waves. So the rise in prescription opioid overdose deaths in the 1990s is the first wave, followed by the rise in heroin overdose deaths in 2010, followed by the rise in synthetic opioid overdose deaths in 2013, which includes illicitly manufactured fentanyl. And over the last few years there has been an astonishing rise in the number of synthetic opioid overdose deaths, mainly attributed to fentanyl.

Part of what makes fentanyl use so challenging to treat is that fentanyl accumulates in fat cells. 

Hansel Tookes: So even though it has a very short half-life, it lingers for days, which complicates starting Suboxone, which complicates starting life-saving medications for opioid use disorder because the fentanyl is still on board. And you can cause something called precipitated withdrawal or, as my patients call it, “precip,” where you basically start the Suboxone too early and put yourself into opioid withdrawal.

Deboki: Suboxone is one of a few medications that are effective for treating opioid use disorder. Others include methadone and naltrexone. Suboxone contains the drugs buprenorphine and naloxone, which work by binding to opioid receptors, which then blocks opioids like fentanyl from binding. So suboxone still relieves pain and gives people a sense of euphoria, but the effect is weaker, which helps slowly wean people off of opioids. 

Hansel also just mentioned fentanyl’s short half-life. The half-life of a drug is a measurement of how quickly it breaks down. Fentanyl breaks down fast — much faster than heroin. So many people with opioid use disorder might go from injecting heroin a few times a day to injecting fentanyl a dozen times a day. Injecting so frequently requires a lot of needles, which has led to needle sharing and HIV outbreaks.

Hansel Tookes: We've had multiple HIV outbreaks in this country since fentanyl occurred. The first was Scott County, Indiana. That's when vice president, then Governor, Mike Pence authorized needle exchange in Indiana. 

Sam: Needle exchange programs, often also referred to as syringe exchange programs, provide drug users access to sterile needles and syringes and facilitate safe disposal of them as well. Hansel’s the founder of the first legal syringe services program in the state of Florida, called the IDEA Exchange. The work he does centers around harm reduction, which syringe exchange programs are a part of.

Hansel Tookes: Harm reduction is a philosophy of meeting people who use drugs where they are, both physically — meeting people where they’re at — as well as mentally. So respecting their autonomy and their right to self-determination. It has been around for decades. One of the fundamental tools of harm reduction is syringe services programs, otherwise known as needle exchange. And those are locations where people can access new injection equipment to combat the spread of infectious diseases. But in the modern overdose crisis, they have expanded to naloxone distribution. So people who inject drugs are the first responders there to revive their loved ones if they have an accidental overdose. And now harm reduction programs do a lot of medical care as well, including HIV and hepatitis C testing, treatment and prevention. 

Deboki: You’ve probably heard of naloxone before, but maybe by one of its brand names: Narcan. Narcan is a simple nasal spray that reverses an opioid overdose. It does this by knocking the opioids out of opioid receptors and then blocking any remaining, circulating opioids from binding. The reversal is incredibly fast but temporary. Narcan only works in the body for 30 to 90 minutes, so whoever is on the scene should still immediately call 911 in case further medical attention is needed.

Anyone is able to carry Narcan, and that has already saved so many lives. And Hansel also reminded us that most states have Good Samaritan laws, which protects you from arrest, charge, or prosecution for drug possession or paraphernalia when individuals who are experiencing or witnessing an overdose summon emergency services.

Sam with Hansel Tookes: Just to play devil's advocate for people who might be listening and thinking, well, but we're in an opioid overdose epidemic, an opioid crisis, why would we be doing things that could help people continue to take opioids? What would you say?

Hansel Tookes: Yeah, so I spent 10 years advocating for the legalization of harm reduction programs in Florida. And I think initially I was asked the question of whether or not providing syringes was facilitating substance use. And what I would say is that people are going to use substances regardless of whether or not they have a safe syringe to use. So we have to meet people where they are and take that opportunity for engagement, take that opportunity for love, because, above all, harm reduction is love. 

So in syringe exchange programs, we're able to meet people, give them syringes if they are interested in testing, we're able to get people into HIV care, hepatitis C care. It just opens up an array of possibilities in terms of all of the services that we can provide for people who are struggling with substance use disorder and if they choose to go into recovery, how amazing is it that so many syringe services programs now have telehealth and a provider such as myself can hop on the screen and provide that access to lifesaving treatment? It's really just opening the door for a community that has had every single door closed on them, because we know that the stigmatization of people who inject drugs is profound in society amongst other people who use substances, amongst other communities that have HIV. 

I mean my patients, my folks, the people that I take care of have really complicated challenging lives. And I believe that the IDEA exchange where they're able to access syringes is the one place in this city where they are not judged. They do not feel stigmatized and, I mean, we have people who work at the IDEA Exchange, which is part of the University of Miami, who were once unhoused and used our program. And to have them with their University of Miami badges now is probably, other than the decrease in the number of preventable overdose deaths in Miami-Dade County, which we have seen, having those peers, those people with lived experience who have used our program now working at our program, sharing their recovery journey is just such a testament to the power of harm reduction programs.

Sam with Hansel Tookes: You just touched on this, but I'm wondering if we could talk a little bit more about what harm reduction for opiate use looks like.

Hansel Tookes: Harm reduction for opioid use is very complicated in this country right now. Of course, we have a drug supply that is unstable and is mostly fentanyl, which is an extraordinarily potent opioid, which is why we have the soaring rates of preventable overdose deaths in our country. We have new complications such as the adulteration with xylazine or tranq, which increases the risk for overdose and causes horrific wounds. 

Deboki: Xylazine, also known as “tranq,” is a powerful sedative that the U.S. Food and Drug Administration has only approved for veterinary use and has been known to cause awful skin ulcers in people who inject it. In 2022, the US Drug Enforcement Administration reported that approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine. And because xylazine is not an opioid, Narcan does not reverse its effects. 

Harm reduction facilities like the IDEA exchange make xylazine test strips available so that people know if the fentanyl they’re using has xylazine in it. 

Fentanyl test strips are also available but Hansel told us they’re less relevant to opioid users because, at this point, the street drug supply of opioids is fentanyl. But for people primarily using stimulants like methamphetamine and cocaine, testing for fentanyl could be life saving. 

Sam: Because this is such a polarizing issue, Hansel told us that making these services available nation-wide is and will continue to be a massive challenge, but he said he and his colleagues’ successes in Florida — a state with a very complex political climate — should provide inspiration for other communities hoping to introduce harm reduction. 

Hansel Tookes: So a major opportunity for education was the Florida Sheriff's Association. They did not fully grasp harm reduction, and were definitely making it challenging for us to pass the legislation at the capitol, but we had our Miami Police Department speak to the Florida Sheriff's Association and say how life saving these programs are, the impact that it's had. Our bicycle and street police officers were responding to overdoses and people were already revived. I mean, it was a transformational implementation in our community. And the Miami Police Department really supports our program. So I think law enforcement's probably the largest barrier, but our police Chief Chief, Chief Collina, said something that really resonates with me. He says, whereas substance use is a law enforcement problem, there's not a law enforcement solution, but there is a medical solution. So in those words, he's really expressed his support for our program.

I just got back from West Virginia — I'm on the Presidential Advisory Council for HIV/AIDS — and the largest outbreak, amongst people who inject drugs, of HIV right now is in West Virginia. There are about 200 infections in this outbreak, and they're closing syringe service programs in that state. And it's just, unfortunately, it's a political hot button issue. And in the face of the largest outbreak in the country, they can't see the value of harm reduction and preventing new infections. I think it's really important for people to know that the exchange of syringes is just such a small part of what syringe services programs or needle exchanges do. It's really about comprehensive healthcare, a one-stop shop, a home base for people who inject drugs.

Sam: Opioids have had, and continue to have, a devastating effect on so many lives in this country. I asked Amy what she was anticipating for the future and some of the things she thinks need to happen to begin moving out of this crisis.  

Sam with Amy Bohnert: When I think about the opioid crisis, I put it in a similar category in some ways to things like climate change where it just feels so overwhelming to kind of think of how to even approach it. So I’m wondering, what are some of the initial steps or things, maybe things that are already happening, that are going to help this country and other places around the world where this is the case, pull itself out of the opioid epidemic?

Amy Bohnert: I think an encouraging thing about working in this area is we actually have a lot of tools that we know can help reduce the opioid crisis problem. So primary prevention, really, there's two key aspects of that. There's increased youth prevention, and a nice thing is that for doing, say, prevention programs in schools, there's a lot of evidence that there's pretty general effects. So what you do to prevent smoking also helps to prevent opiate misuse, helps prevent depression and so on. The other thing is continuing to improve opiate prescribing, to try and make it safer, and also to develop more pain treatments and to improve access to pain treatments that work.

So for example, we know that physical therapy can be a really useful treatment for pain, but a lot of people have trouble accessing it, and if we could improve access to that, it makes it easier to get someone the pain treatment they need in a way that isn't just pulling out a prescription pad. The next thing is medications for opiate use disorder. So for people who have developed an addiction to opioids, medications are quite effective, and this involves methadone treatment, which in the US you have to go to an opiate treatment program daily. So that has some limits to how much it can probably be accessed, especially in rural areas because they don't have the population density to have a large number of people to sustain a business of people who can come there daily.

Deboki: Amy told us that, unfortunately, medications like suboxone and methadone are also underused in the US for reasons that go beyond access. There are so many stigmas surrounding opioid addiction and there’s a not only inaccurate but damaging belief that opioid addiction is a choice that can just be overcome by willpower, and that using a medication like suboxone to treat it is a crutch and just the replacement of one drug for another. Those stigmas can make it really difficult to get people on board for treatment. 

At the University of Michigan Opioid Research Institute they’re exploring how to increase engagement so that more people are taking these medications. 

Amy Bohnert: We do what are called implementation studies to better understand how you can get people to use treatments that we know work more often in practice. And then we also do policy studies to understand what has worked and hasn't worked in terms of policy change at a population level.

Sam: There are no quick fixes to solve the opioid crisis, but over the last decade, there have been some bright spots. Many of the pharma companies who played a large role in kick starting this crisis in the 90s are now paying out a lot of money that will go to states to support opioid crisis response. There’s also increased government funding for research on the managing and treatment of pain and improving prevention and treatment for opioid addiction. The last decade also saw highly successful programs like the IDEA Exchange and, just this year, the establishment of the Opioid Research Institute.

Amy Bohnert: I feel cautious hope. I think the hope comes from the fact that I know we do have tools that work, like medications for opiate use disorders and like naloxone for overdose reversal, and for a lot of problems we don't even have that, right? So that definitely makes me feel some hope. I also have seen the stigma around opiate addiction really be chipped away at over the past 10 years, and particularly among clinicians who are an important part of this. So I went from having colleagues who would be like, “why would I want to treat opioid use disorders? I'm going to have all the problem patients coming to me,” to embracing it, and seeing treating those patients as one of the most rewarding parts of their practice.

Hansel Tookes: Don’t be discouraged, it took us 10 years to bring these programs to Florida, but now they're part of the culture here in Miami. We'll have our seventh anniversary, this World AIDS Day, which is December 1st, and IDEA Exchange is a part of Miami, both in our social services safety net as well as in our medical education and innovation. So my word of advice would be just go for it, because with tenacity, you will succeed.

Sam: If you’re a listener in the United States, the Substance Abuse and Mental Health Services Administration has a National Helpline for individuals and family members facing mental and/or substance use disorders. And it can be reached at 1-800-662-HELP. That’s 1-800-662-4357. It is confidential, free, in both English and Spanish, and open 24/7, 365 days a year. The helpline provides referrals to local treatment facilities, support groups, and community-based organizations. We’ll leave that info in the episode description. 

Alright so let's close things out with a tiny show and tell. Today I am going to tell you about a really cool new study that came out. It's actually a pre-print, which means it has not undergone peer review yet and been published in a journal, but it's near that stage. I think it's undergoing review right now.

Deboki: And the data's available online for people to look at.

Sam: Yes, and the data's available online. Normally, I would wait until the study is officially out, but I thought it was really interesting, so I'm sharing it. So this study has shown that marathon runners during races to get energy actually use myelin, which is the fatty tissue that's bundled around your nerve fibers, and it acts as an insulator, it allows electrical messages to quickly travel from one nerve cell to the next. So myelin is essential for nervous system function, including brain function. Very, very important. And so what these researchers saw was that in the day or two post marathon, the brain scans of marathon runners showed less myelin. But then just a couple of weeks after that, so two weeks post-race, it was back to almost pre-race levels. So I knew that we dip into fat and muscle stores for energy when we've run through all the sugar, the glucose, in our bodies. But I didn't actually think about the fact that we might tap into these fatty stores surrounding our nerves.

I thought this was really just interesting in itself, but there is a greater impact here than just my interest. Because it could offer clues for treatment for people who have lost myelin, which is very common in neurodegenerative diseases. So for instance, in many cases of Alzheimer's, the loss of myelin appears to be this initiating step in early stages of the disease. So I don't know anything about myelin truly, and I didn't even think about its regenerative capacity, but how amazing is it that we can somehow, if we're in this intense exercise environment, use it as an energy source and then produce more of it? And so that feels very relevant when thinking about treatment for certain neurodegenerative conditions that lead to degradation of the myelin sheath.

Deboki: So I didn't know this. Apparently there are these blobs in our planet. There's probably a more technical name, but the article that I was reading, they call them blobs. They're somewhere between the core and the mantle, and they're huge. There's two of them that we know of, and they're very mysterious. There's one under West Africa and another one under the Pacific Ocean. They're like the size of a large continent. And we first found them like 50 or something years ago because we just saw seismic waves that we were using to study things just slow down in those areas. We don't really know that much about what those blobs are or how they got there. There are various theories, maybe they were part of some magma ocean that got crystallized, like weird geology things.

But some scientists came up with an explanation that I find fascinating, which is that they're actually bits of the moon. Not like somehow the moon fell here. But really this is related to another mystery, which is how did we even get the moon?

And so one of the theories about how we got the moon is that there was this protoplanet, which we call Theia, that hit Earth, and then a bunch of the debris went around, did stuff, and part of it, part of that debris became the Moon. But the question is, what happened to the rest of the debris? And so there's this theory now that maybe those blobs are bits of that protoplanet, which I think would be so cool if it's true. The scientists in this paper, they wrote this simulation to see if that could be theoretically possible. And it does seem to bear out, I guess, mathematically and physically. But they also are reminding us that this is not proof. This is not evidence that this has happened. I think it would be really cool just to think about how we would prove that. But also I just think it would be so fascinating if it's like, oh, we have a little bit of the moon inside our planet.

Sam: Yeah, that's crazy. So they just know that these blobs exist and that they're a different consistency than what's between the ... You said they're between the mantle and the crust?

Deboki: And the core.

Sam: Okay. So they know. Right. And we can't get there.

Deboki: Yeah, it's hard. So we just got to use those waves to be able to study it. That's how we learn what things are down there.

Sam: That's really cool. That'd be kind of fun.

Deboki: Yeah.

Sam: Awesome. Thanks Deboki.

Deboki: Thanks for tuning in to this week’s episode of Tiny Matters, a production of the American Chemical Society. This week’s script was written by Sam, who is also our executive producer, and was edited by me and by Michael David. It was fact-checked by Michelle Boucher. The Tiny Matters theme and episode sound design are by Michael Simonelli and the Charts & Leisure team. 

Sam: Thanks so much to Amy Bohnert and Hansel Tookes. If you have not rated and reviewed Tiny Matters, please do! We’re trying to grow and that really helps us. If you want another way to support the show and look really cool drinking your morning cup of coffee, tea, juice, or water, whatever, we have left a link to our Tiny Matters coffee mug. You can find me on social at samjscience.

Deboki: And you can find me at okidokiboki. See you next time.