How does one become addicted to opioids? Why are so many people dying during America’s current opioid crisis? Is the current epidemic part of a larger trend? Addiction expert Dr. Thomas Kosten explains.
Thomas Kosten, M.D., is a professor of psychiatry, neuroscience, pharmacology, immunology and rheumatology and director of the Division of Alcohol and Addiction Psychiatry at Baylor College of Medicine. His professional interests include developing medications and vaccines for addictions and pharmacology.
See more about Baylor College of Medicine’s Department of Psychiatry and Behavioral Sciences.
See below for some of the research studies mentioned in the episode:
- Current status and future prospects for the development of substance abuse vaccines
- Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment
- Psychopharmacology: neuroimmune signaling in psychiatric disease-developing vaccines against abused drugs using toll-like receptor agonists.
Hooked: America’s Opioid Crisis | Transcript
Erin: Welcome to Body of Work, an exploration of health topics in the news and important issues facing science with experts from Baylor College of Medicine. I'm Erin Blair, and my guest today is psychiatrist and addiction expert Dr. Thomas Kosten.
For the last several years, America has been embroiled in an opioid crisis. Why are opioids so addictive?
Dr. Kosten: Why are opioids so addictive is probably a bit of a misunderstanding in the sense that a very large portion of the population gets opioids one time or another in their life, for various kinds of pain or surgery that they get. Yet, the percentage of people who become dependent, and who abuse opioids, it's actually rather small. It's about 2% of the population or less. So if you look at that sense, you would say they're not very addictive in the least. However, if you do like them, you like them a lot. And they don't have their sustained effect unless you use them at higher and higher dosages over time. Particularly that euphoric effect, but even the analgesic effect does develop tolerance, and as you get more and more tolerant, and take more and more of the drug, the withdrawal syndrome that will occur when you stop the drug is more and more severe.
Erin: What is involved with withdrawal?
Dr. Kosten: Opioid withdrawal is unlike alcohol withdrawal, or some other types of withdrawal, which can have an actual mortality associated with them. But, it is very unpleasant. It's like having a very bad case of the flu, lasts anywhere of seven to ten days, and then the acute syndrome is over. But, there is a protracted period of withdrawal that can last as long as six months, where people don't sleep well, where they feel uneasy, where they're certainly having a lot of craving to use the drug again. And it is that sustained period that often leads to relapse. Even when someone has a successful medical withdrawal, or detoxification, as it's often called.
Erin: What does the progression look like once someone is addicted? What are the effects of long term use?
Dr. Kosten: When people begin using opiates that occurs in different contexts. The most common one in the recent epidemic has been people being treated for chronic pain of various sorts. These are usually benign pains, meaning that it's low back pain, it’s headaches, it's peripheral neuropathies, it's sometimes things that seem a little odd, like being treated for gastrointestinal symptoms, when mostly opiates would make them worse. But a lot of different pains, and they are treated for months, or years with the opiates and they then become quite tolerant and dependent on them. Now for most people, they will eventually, if their doctor wants to do that, and often should do that, discontinue the opiates, they do not go on to become abusers. But, there's a percentage of them that do and that percentage is quite variable, so that in some primary care clinics and that are high-end ones, that the rates can be as low as only three or four percent of the patients that become opiate dependent and abusers of the drug. In other settings, such as in AIDS clinics, where people often have variety of pains that are reduced by the AIDS, or the medications are being treated, the rates of going on to develop opiate abuse and dependence are as high as 50%. So the setting varies a great deal. Then, there are also adolescents who will begin by using opiates that they usually snort, and that they'll just use them on weekends, and they use them to get high. As they keep doing that, they will usually move on to more frequent use and typically you have to be using the opiates daily in order to get to the point that you'll get tolerance and dependence. So, those adolescents can, in fact, become like the chronic pain patient where they are in fact quite dependent on the opiate. And when they discontinue its use, will get fairly sick. That’s the usual course that leads to people becoming, what we usually think of as addicts, that is they have to get the opiate, or they don't feel normal.
Erin: What's the difference between an opioid that's prescribed by a doctor, like OxyContin, and opioids that are obtained illegally, like heroin?
Dr. Kosten: They are fundamentally very similar drugs. Heroin is a version of morphine that has been modified chemically so that it gets into the brain faster than morphine does. So that makes it more euphoria-producing, more addictive you might say, in that way. What is on the street now increasingly are what's called pharmaceutical opioids which may, in fact, be made by a reputable manufacturer and get diverted. Or they can be made in factories that are located in various parts of the world, China and Mexico being two of the largest. They are usually made by growing poppies, and then taking those poppies and extracting the morphine from them. Then the morphine can be converted into a wide range of other drugs.
Erin: If this is just an addiction problem, why are so many people dying in this current epidemic? We’re not just hearing about increased use, but about deaths?
Dr. Kosten: One of the unfortunate characteristics of opiates is that overdose from opiates will suppress your respiration. And suppressing your respiration, if it's sustained, leads to death. And so just taking an overdose of an opiate can, in fact, kill you. And one of the ways that that happens is that when people buy opiates on the street, they don't know exactly what they're getting. They don't know the potency of it. They don't know how much they should take to just get a high, as opposed to how much they should take if they want to avoid dying from it. And because of that, they're titrating it in a way that is fairly dangerous. Now if that titration is occurring when you're smoking opiates, it's relatively easy to do. You, once you stop getting high you just put the cigarette out. On the other hand, if you're injecting, that injection is usually got a fixed amount of drug in it, and the method of doing it is to push the whole bolus in all at once so that bolus may, in fact, contain a lethal amount of it. The other way that lethal amounts are increasingly occurring is that fentanyl is anywhere from a thousand to ten thousand times more potent, depending upon what type of fentanyl it is, than are the usual opiates that are taken. So when people are buying heroin, the heroin often has fentanyl in it now, or a fentanyl derivative. And so while they may think that they're taking the usual amount that they're tolerant to and that they would get a from, they may, in fact, be taking a thousand times that dose, which would certainly be lethal to them.
Erin: How potent is fentanyl compared to OxyContin?
Dr. Kosten: Fentanyl is much more potent. In some of the formulations of it, it's merely a hundred times more potent than OxyContin on a milligram per milligram basis. Other formulations such as carfentanil can be 10,000 times more potent. Carfentanil is, of course, the one that's now been made illegal for any use, except for sedating elephants.
Erin: And is fentanyl a substance that you have to smoke or inject?
Dr. Kosten: You can certainly get fentanyl through a variety of means. You can smoke it, you can snort it, you can eat it, but unfortunately you also absorb it through your skin. And the absorption through your skin is one of the ways that it has been nearly fatal with the criminal justice people who have been cleaning up after opiate overdoses that have occurred in a person. And if they're not wearing gloves, and they touch surfaces where the drug has been, even though they might not be able to see it, they will absorb it through their skin and it will lead to an overdose. So those overdoses usually are recognized right on the spot, and they get the EMT people in there, and revive them. Usually, with large dosages of naloxone or Narcan, but it is quite a potent drug and absorbed through every way you could imagine.
Erin: Since fentanyl is so potent, is it ever used to mix in with any other kinds of street drugs?
Dr. Kosten: Certainly, that is one of the problems particularly in Texas, where the heroine often is a black tar heroin, and fentanyl is a white powder. So that black tar and white powder makes it fairly obvious that something's been mixed in with the heroin, which may not be a good thing. So the white China heroin, which it's often called, is what it's usually mixed with. However, in Texas, the fentanyl has been mixed increasingly with cocaine and with methamphetamine. With methamphetamine, some of the low-grade versions of methamphetamine, so that they're not actually 100% methamphetamine. But maybe as little as 20 to 30 percent methamphetamine. Or 20 to 30 percent cocaine, if it's cocaine shipment. Putting in a very small amount of fentanyl into that gives the user the experience as if they're taking a drug that's very potent, and they're not very good at telling opiates from stimulants. The problem with that is that when they then are treated for an overdose, either in the emergency rooms or by the EMT people, they will have cocaine or methamphetamine around, or the people around them they say that's what we were using. And if the medical professional, or EMT, is not very careful, and by very careful I mean looking at the pupils of the person who just had the overdose, they may mistreat them. That is, if you have a stimulant overdose, you have very broad pupils, and you can hardly see the colored part of your eye. On the other hand, an overdose with opiates gives you pinpoint pupils. So in that sense the distinction is very easy to make, unless you don't look for it. And if you don't look for it, and you treat the stimulant overdose, there's a very limited amount of time between when you take fentanyl and you overdose, and you can, in fact, revive them. That is if they don't breathe for several minutes, they'll be dead, and so even if you gave them naloxone at that point, or Narcan, it would not reverse the fentanyl overdose because the patient I s dead already. So, there is a very high importance in making the correct diagnosis as soon as possible, and when it is a mixture of a stimulant with fentanyl, it can be quite confusing as to what exactly you're treating, and you have to get to the treatment of the opiate first, and quickly.
Erin: Who is to blame for our current addiction epidemic?
Dr. Kosten: Depends who you want to talk to and who you want to read about, but certainly the New York Times has quoted more than once how the general public blames the doctors who have prescribed chronic opiates as much as they blame the people who take the chronic opiates and then go on to abuse them. There was certainly a period in the beginning of what would be 2000 through 2006 or 2007 where there were a number of manufacturers of opiates that were encouraging doctors to treat every patient who has pain with opiates, and treat them with escalating dosages as need be. Some of those manufacturers have in fact now faced federal lawsuits for that, and they're increasingly facing lawsuits yet again, because they didn't discontinue some of those practices. And that led to fairly massive overprescribing of opiates for people who had these chronic low-grade pain syndromes that, the data are now very clear, opiates make those syndromes worse rather than better. The way they make them worse is with the withdrawal and dependence that occurs, but they also induce a condition called hyperalgesia, where small pains get greatly magnified. And so it's not advantageous to use opiates chronically, and that was an advertising ploy that worked in such a way to sell a lot more opiates, but did not benefit the patients who got them.
Erin: What are some possible long solutions? is it greater regulation of pharmaceuticals? Is it education? Is there a cure?
Dr. Kosten: Well certainly regulation and greater education are very helpful in this particular case. I think regulation of the marketing that the pharmaceutical companies can do, since an unfortunate part of continuing medical education is that it comes from the drug company representatives as much as it comes from people attending continuing medical education. Hopefully, that trend is changing. Then, there is the other mandatory education that's increasingly being required for recertification, either in specialty boards or to just get your medical license renewed. And that I think are good advantages so that the doctors who are prescribing these medications prescribed less of them. And that approach has had a very significant effect, it’s certainly true in Texas, where the amount of opiates that are prescribed have gone down considerably. And the number of opiate prescriptions that are given for more than three months have also declined quite a bit. Finally, within that same kind of regulatory framework is the dose of opiates that people are given, that there are recommendations from both the CDC and from HHS, that have specified a highest level dose which is considerably less than what the pain medications were given out before as opiates. So those have been regulatory things that have been quite helpful. I think the lawsuits against the companies have certainly motivated people to not want to take so many opiates, and have had an effect on the pharmaceutical company's practices in terms of how they advertise their wares and push this forward with doctors or hospitals. One of the interesting things was that a fifth vital sign was invented by the hospital accrediting board, which was pain, and the way that that went is that patients are supposed to be relatively pain-free as a good mark for the hospital, and if you had patients who were complaining about pain that was a mark against hospitals further accreditation. That was not a good idea, and led to a fair amount of over-prescribing of opiates and led to, I think, part of the current epidemic that we have.
Erin: What are the other four vital signs?
Dr. Kosten: More usual things, such as your blood pressure, your pulse, your respiration, your temperature. Things that really are vital. If they stopped functioning you stopped functioning. But with pain management, in general, you're not looking for stopping all the pain, what you're looking for is improvement in function. And 80% of what your baseline function is, is usually thought of as cure.
Erin: So why don't you tell us a little about your own research into addiction?
Dr. Kosten: Yeah, I've certainly been involved with the treatment of opiate dependence for quite a long time. Initially, when I was a medical student was working with methadone when that just first came out. Obviously dates me a little bit. And then, later on, did the initial studies with buprenorphine as a maintenance agent here in the United States when I was back at Yale and did the initial studies, for naltrexone as a maintenance agent. And then most recently have been interested in vaccines for treating opiate dependence, in particular for treating fentanyl. The reason is that the fentanyl derivatives are not blocked by buprenorphine, naltrexone, or methadone. so that even if you're in treatment with those drugs, you could still overdose with fentanyl. You could also get high from the fentanyl, and that can be a significant problem with the overdoses because the fentanyl is increasingly mixed in with all the other drugs of abuse.
Erin: How would a doctor and a patient use a vaccine, like a fentanyl blocker?
Dr. Kosten: The vaccines are made in such a way that you have to give usually two or three boosters after the initial vaccination, and that occurs over about a two-month period. And then you develop sufficient antibody levels to block the fentanyl. Those antibodies will remain relatively high for two to three months, and then over the normal course of time, those antibody levels drop. Unfortunately, just using fentanyl during that time will not increase the level of the antibody, so it's not like an infectious disease where every time you get infected, that stimulates the b-cells to make more antibody. You have to give the vaccine itself to stimulate that production because it is the coupling of the drug of abuse to the carrier protein that produces the antibodies. So one would need to get a booster vaccination about every, probably three months. And we did some of that work with the cocaine vaccine and found that it worked very effectively, that a single booster would push the levels of antibody back up to what were in the therapeutic range. So the expectation would be perhaps every three months, you would need a vaccination for as long as the drug of abuse is an issue. And in general what we found if people can stop using the drugs of abuse, whatever it happens to be, for about a two-year period, and at the same time engage in some various types of behavioral therapies, that they can then, you know, get on with their life and not be burdened with abusing those drugs anymore. So that would be the ideal. We could of course though conceivably vaccinate you every three months for the rest of your life.
Erin: Do you see the vaccines being used preventatively with people who are not addicted? Or would they only be for people who are already addicts?
Dr. Kosten: All of these vaccines, they’re really designed for people who have a problem. Could you use it in a preventative way? Well, many vaccines are in fact used that way, but we don't have good enough predictors who this is going to be a problem for. And to just use a small example, there was a book that I wrote with the National Academy of Sciences about 15 years ago now, about the ethical issues of if we started vaccinating people. And with nicotine, if you vaccinated say all the teenagers against nicotine so they wouldn't smoke cigarettes, it's not clear that they would stop smoking cigarettes. They may, in fact, want to smoke enough cigarettes to override your vaccine, your blocker. And what would effectively be doing is teenagers capable of sticking, you know, 10 cigarettes in their mouth all at the same time lighting them up. and they would get, you know, some effect from the nicotine at that point. But, the amount of carcinogens they would be getting would be ten times more than what is in one cigarette. So, that would be an unintended consequence that's not at all positive.
Erin: How does the current epidemic affect the future of healthcare?
Dr. Kosten: Well, I'm hoping that it leads to more educated doctors who will use opiates more sensibly, and understand something more about what the effects are, considering opiates are probably our second or third most commonly prescribed medication and the amount of medical school education that's devoted to their use, abuse and complications is vanishingly small. So that first we’ll provide more education to students as they go through medical school, and anybody else you might prescribe opiates. And then beyond that, the continuing medical education will be importantly used by all doctors and required so that they'll learn more and more about these medications, the opiate-related medications. The other is that there's still hopes for finding opiate-like compounds that would be analgesics, but would not produce the same level of tolerance and dependence, and that's a hope that has been worked on, for oh, about a hundred and fifty years at least, so one can't get overly optimistic.
Erin: Are we seeing a bigger government response to this current epidemic because of who it affects?
Dr. Kosten: Well certainly I think the political response to opiates as a problem is very much driven by who has the problem. And so, if there's a greater proportion of the voting population that is affected by opiates, either directly themselves or through their children, or relatives, then you can expect a much bigger political response to it. When opiates were a problem through the 80s, 90s, and were often more of a problem within inner cities, and areas where people didn't vote, in areas where a number of the people sometimes were in fact illegal aliens - although ironically, illegal aliens are some of the lowest rates of addiction problems - when it was confined there, then you didn't see a lot of motivation for politicians to do much. On the other hand once the voting population, the middle-class America, the out in the suburbs, or even wealthy families begin to see this as a problem that's happening in their families and people close to them, then you get political action. Now you might ask, well, “How effective is that political action?” And I think that that's been quite variable. And the current political action seems to be kind of muted in comparison to what it's been with other administrations in terms of doing something. The HEAL Initiative is a very big initiative for doing something about opiates, and has very ambitious goals. For example, the latest HEAL Initiative, which I'm involved as one of their senior scientists, is to reduce opiate overdoses by 40 percent in the next four years. Now that's a tall old order to do that, and we're doing it in four states around the country. So, we'll be looking at Ohio, Kentucky, Massachusetts, and New York. But those are the places where you have some of the highest rates of fentanyl overdoses, so that is part of the rationale. Whereas on the west coast and across the south there's less of a fentanyl overdose issue for opiates. As I said, in Texas, there’s quite a fentanyl overdose issue with stimulants, which is the next thing that's coming. So I think that, yeah, who gets affected and who votes, that makes all the difference.
Erin: Addiction has been called the American disease. Why is that?
Dr. Kosten: It's an interesting expression that I think was coined by David Musto quite a number of years ago when he wrote his book about The American Disease. And it got that name because America has always been in the vanguard of abusing drugs during, at least, the 19th and 20th centuries, and of course going into the 21st. While there was much abuse of drugs before that that were in many parts of the world, America seems to be the leader, and has been the one that has also been the most forward going, I suppose you'd think, in terms of legislation, but also thinking about how you might develop new treatments for it, because of the National Institute of Health which had a subinstitute for alcohol, and another one for drugs of abuse.
Erin: Is this current issue part of a larger story?
Dr. Kosten: Well, the current epidemic that's happening with opioids can certainly be seen in that cyclic boom-and-bust where opiates have come back three times. The initial time was during the Civil War when the hypodermic needle was invented, and people were then injecting opiates. There then was another one that came at the turn of the century, that is the 19th to the 20th century. And then there was the one that came through in the 1970s during the Vietnam War era. And now there's the one that we're facing now, which has been highlighted by fentanyl and some of these synthetic drugs. So, with the opioids, there is a constant in and out, up and down.
Erin: Are we doomed to keep repeating this cycle of abuse, and addiction, and potential solutions, and then another cycle of the same?
Dr. Kosten: Well the creativity of the human mind in coming up with things that are potentially abusable and lead to a chemical high, and as some people have said, you know better living through chemistry, is almost endless. I think that the way it seems to go is, it's a little bit longer than generational, so it's a little bit longer than 20 years, but over that period of time if we've had an opiate epidemic, 20 or 25 years after it ends, you will see then another one because people don't seem to remember or translate things or transmit them across the generations. And the stimulant epidemics have pretty much looked like that - about every 25 years we have another stimulant epidemic.
Erin: Because see I'm 50, and I've seen over the years these cycles, and it is, 20-25 years. Yeah, I hadn't thought of it that way, but it's every generation.
Dr. Kosten: Well, David Musto deserves credit for it, he wrote the book. That's the way he thought of it. It's sad that we have no memory.
Erin: Or that we just don't transmit it down the generations.
Dr. Kosten: Yes, yeah exactly. The news cycle I guess is just way too short for that to happen. And so I don't think that my field will ever be put out of business, and that there'll always be some other new development in what people can abuse, and perhaps maybe even put them to therapeutic use. As you’re probably aware of the hallucinogens such as MDMA and psilocybin are now being tested in FDA approval studies for the treatment of post-traumatic stress disorder and the treatment of depression. Clever ideas doesn't mean that those clever ideas can't be turned into something abusable, or that something abusable can't be turned back into something that becomes a clever idea again.
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