Daniel Ciccarone, MD, MPH.
Justine Miner Professor of Addiction Medicine at the University of California San Francisco.
Dr. Ciccarone is a member of the scientific advisory board for Celero Systems. Relevant financial relationships listed for the author have been mitigated.
CATR: Let’s begin by having you describe your research methodology; it’s a bit unusual.
Dr. Ciccarone: I’m a physician-ethnographer. My methodology springs out of being a clinician. I started as a family doctor decades ago. The work I’m doing now began during the HIV epidemic. I was curious about what people were not able to disclose in a 15-minute office visit, which led me to study under Philippe Bourgois, the renowned urban anthropologist. So my team and I go into the neighborhoods where drugs are being used. We spend time with people who use drugs, building trust and rapport. That’s how to learn what drugs are actually being bought and sold on the streets and how they are getting used.
CATR: Why is it important to combine epidemiological data with narrative?
Dr. Ciccarone: That’s how we’re going to get the most complete picture of what’s going on in the current crisis. Epidemiology gives you the breadth of the problem, answering the questions of “how many” and “where.” Ethnography goes deeper and gets you the mechanism of risk by answering questions that epidemiology struggles with: “why” and “how.” Basic principles tell us that we need to look at two factors when addressing public health issues: outcomes and exposures. The epidemiology gives us outcomes like deaths and overdoses, but that’s only half the picture. To understand exposures more fully, we need to know what’s in the drug supply and how precisely those drugs are being used. Unfortunately, the legal system and law enforcement agencies are not transparent with the supply data, so we get it indirectly through Freedom of Information Act (FOIA) requests.
CATR: Give us a description of the current state of the illicit opioid supply.
Dr. Ciccarone: It has shifted over the last 30 years (Ciccarone D, Int J Drug Policy 2019;71:183–188). It started with excessive prescribing and diversion of opioid analgesic pills, OxyContin and the like, which led to dramatic increases in use and consequences; that’s what we call the first wave of the opioid overdose crisis. When that was partially curtailed, it was replaced with heroin use and rising overdoses; that’s the second wave. Since around 2014, heroin has become increasingly adulterated—I even use the term “poisoned”—with the synthetic opioid fentanyl and its analogues; that’s the third wave (Editor’s note: For more information, see CATR Nov/Dec 2021). Currently, we have an evolving and chaotic situation on American streets, so chaotic in fact that some are referring to it as the fourth wave. Heroin/fentanyl is being used along with stimulants, like cocaine and methamphetamine, in various combinations (Jenkins RA, Prev Med 2021;152(2):106541). You can get heroin both with and without fentanyl. You can buy fentanyl itself. Some cocaine and methamphetamine is contaminated with fentanyl. You can get diverted pharmaceutical products and also counterfeit opioids.
CATR: You are referring to what are sometimes called “pressed pills.”
Dr. Ciccarone: Yes, exactly. These are relatively new and can be very dangerous. They are sophisticated counterfeit pharmaceuticals. By “counterfeit,” I mean that they look just like a legitimate product coming from a pharmacy, with the same size, shape, color, and even ID numbers as pharmaceutical products, but that’s not what they are. There’s no quality control, they don’t have the right filler, and often they don’t even have the right active ingredient. You might be buying what looks like oxycodone or a prescription stimulant, but instead it’s a pill that often contains fentanyl (O’Donnell J et al, MMWR 2021;70(50):1740–1746). And the amount of fentanyl that a given pill contains, or whether a highly potent derivative is included, is highly variable. In other words, some of these pills can be lethal while others are not, and it’s unpredictable. They can be attractive because they are usually less expensive than the real thing, but they can be dangerous.
CATR: Are people typically aware of these counterfeits?
Dr. Ciccarone: Awareness is growing, but it’s not universal (Arya S et al, Subst Use Misuse 2022;57(13):1940–1945). The fact that people are still buying these means that this subterfuge is still happening; people are still being hoodwinked. What’s especially concerning is that prescription pills tend to be favored by recreational users. These are typically students or young adults who do not have the tolerance, or the savviness, to know the difference between a pressed pill and a legitimate pill.
CATR: And drug availability varies geographically as well.
Dr. Ciccarone: Yes, fentanyl has been making its way into heroin for a few years in states east of the Mississippi: the Midwest, down into Appalachia, the mid-Atlantic, up to New England. The degree of fentanyl contamination is not spread evenly either, which adds to the danger. When you buy “heroin,” fentanyl is sometimes there, other times not, maybe replaced by an analogue (Ciccarone D, Int J on Drug Policy 2017;46:107–111). Moreover, fentanyl analogues have a wide range of potencies, from a third of that of fentanyl to a hundred times that of fentanyl. For example, carfentanil is meant to be used for analgesia in large animals and is not for human consumption; a lethal dose is so tiny it is hard to even see unaided (Ringuette AE et al, ACS Chem Neurosci 2020;11(23):3955–3967). People often have no idea what they are buying and consuming. These vicissitudes across space, across purity, across potency, they are what create such a dangerous situation in the northeast quadrant of the US.
CATR: What about other areas of the country?
Dr. Ciccarone: Fentanyl is now coming to the West Coast, both in terms of these counterfeit pills, as we’ve talked about, but also as powders as a substitute for heroin. One difference is that fentanyl is typically being sold as-is on the West Coast. By that I mean it’s not being sold as heroin or stealthily included in a heroin product. Its presence and use are growing in the western US, but it’s not ubiquitous the way it is in the Northeast. The South has lagged a bit, though it is now seeing fentanyl-laced heroin as well. Keep in mind these are general trends. The real message is that the supply is in complete chaos in a way that is unprecedented. It changes on a weekly basis. We’ve compared what is available in New York, New Haven, Philadelphia, Baltimore; there are similarities but also many differences. For example, one of the latest contaminants being found in illicit opioids is xylazine. This is an alpha-agonist that is becoming increasingly prevalent but has its epicenter in Philadelphia (Korn WR et al, Clin Chim Acta 2021;521:151–154). Unfortunately, xylazine is becoming more widespread (www.tinyurl.com/3f4jury4) (Editor’s note: We will cover xylazine in more detail in an upcoming issue).
CATR: What about fentanyl finding its way into non-opioid drugs?
Dr. Ciccarone: It’s a good question. We are seeing increased mortality as a result of opioids and stimulants like cocaine and methamphetamines being taken together. This is what many, me included, have termed the fourth wave. But we don’t know how much of the increased mortality is being driven by intentionally taking mixtures of drugs versus inadvertent opioid exposure (Ciccarone D, Curr Opin Psychiatry 2021;34(4):344–350). As I’ve said, we’re mostly in the dark, so people tend to cling to even the smallest scraps of data. Someone may make a social media post saying, “I smoked cannabis and overdosed,” and suddenly people think all cannabis is full of fentanyl. It is not. It might be true in a tiny minority of cases, but we need to be careful not to overgeneralize.
CATR: Do we have any empiric data?
Dr. Ciccarone: A little; my team was able to acquire Ohio’s drug seizure data through multiple FOIA requests. These data are still unpublished, and it’s too early to know how generalizable the findings are, but it’s at least something. Trace or higher levels of fentanyl were found in approximately 14% of cocaine samples, 3% of methamphetamine samples, and none of the cannabis samples. Now, it could be that cannabis is not being analyzed for fentanyl, and that’s why it’s not detected. Unfortunately, we don’t have a full understanding of how the testing was conducted. We do know that most of the methamphetamine and cocaine is being tested, though, so I have a fair degree of confidence in the 14% and 3% numbers.
CATR: What are the clinical implications of these findings?
Dr. Ciccarone: People who exclusively use stimulants, especially occasional users, should test each and every dose for fentanyl, either with a fentanyl test strip or by other drug-checking means. These people don’t have opioid tolerance, so exposure to fentanyl can be lethal. And they probably don’t want the fentanyl anyway, so it’s an easy selling point. The same thing goes for pills bought on the street (Editor’s note: For more on fentanyl testing, see article in this issue). And just recently, xylazine test strips became available as well (www.tinyurl.com/nt2hmdaz).
CATR: How do you discuss this with patients who haven’t bought opioids illicitly for some time?
Dr. Ciccarone: We know that returning to use after a period of abstinence can be very dangerous. That might be someone leaving incarceration or a residential treatment program. A lot of the danger comes from loss of tolerance, but the unpredictability of what’s available is also a factor. I’m very frank. I don’t like using such dire terms, but unfortunately the truth right now is that using illicit opioids is more dangerous and unpredictable than ever before. I tell patients, “Any single use could be your last.” Sadly, I’ve seen this.
CATR: What can we do to keep our patients safe given this chaotic drug supply?
Dr. Ciccarone: I think of three levels when it comes to promoting patient safety. First, they need to become patients. I think the biggest problem we have is retention. The current excuse is that it’s the disease, the nature of addiction, that keeps people away. But when I talk to people on the street, they say, “I had a falling out with my doctor. Something happened and they gave me some attitude; the next thing I knew, I didn’t feel like showing up. And then I never heard from them again.” Addiction is a brain disease. We shouldn’t be surprised that patient behavior may not be consistent with their stated goals or may not match our expectations. We can’t punish our patients for that. We need to make them feel welcome, supported, even loved—I’m fine using that word.
CATR: What can we do to improve retention?
Dr. Ciccarone: We should recognize that people are intimidated by the health care system and us as providers. We need warm welcoming clinics; that means we check our own attitudes at the door, meet patients where they’re at, use respectful and patient-centered language, address barriers to care to the best of our ability (Editor’s note: See CATR Nov/Dec 2022 for our interview with Lydia Bartholow on trauma-informed care). This is what I hear from people on the street; they don’t want to come in because they are afraid of us, of being judged, of being given the cold shoulder or treated like a half citizen. It’s a matter of improving our services! Peer support and peer navigation is a promising approach with a growing evidence base that needs further implementation (Ramdin C et al, Subst Use Misuse 2022;57(4):581–587).
CATR: And once we get them through the door?
Dr. Ciccarone: Medication treatment is the second level. The single best thing we can do for our patients is get them on medication, which is associated with lower mortality as well as a whole host of other health benefits (Santo T et al, JAMA Psychiatry 2021;78(9):979–993). Often, that’s buprenorphine. We should be having conversations about the benefits of buprenorphine with all our patients and doing everything we can to get people on it. Buprenorphine used occasionally is better than no buprenorphine. Buprenorphine taken with only partial adherence is better than no buprenorphine. Buprenorphine on one month, off another month, on a third month is better than no buprenorphine. Low dose, medium dose, high dose, whatever dose—any buprenorphine is better than no buprenorphine. Clinics may have rules that say, “You messed up your buprenorphine, so you can’t have it anymore.” Rethink those rules!
CATR: And the third level?
Dr. Ciccarone: Harm reduction—doing whatever we can to reduce morbidity and mortality of drug use. And that goes back to step one. Make a clinic that’s inviting; taking buprenorphine is not a requirement, abstinence is not a requirement. You want to come in and talk? Let’s talk. What are we going to talk about? We’re going to talk about how to be safe. I ask: “Do you have naloxone? Do you use with other people?” Then I explain why these are important questions: “It’s safer to consume drugs with other people who can keep eyes on you. It’s safer to have naloxone around in case you go out.” And I make sure people understand that certain practices are safer than others. For example, if you are not sure about a particular product, go slow. Test it with a little inhalation before committing to a larger dose. Partial doses, slower doses, doses in the nose versus the vein first are all good ideas. Drug checking, which we discussed earlier, is a good idea for anyone who wants to avoid fentanyl.
CATR: How can providers keep up with all this?
Dr. Ciccarone: Given how fast everything moves, I recommend online resources because they can be updated regularly. The Center for Substance Abuse Research, from the University of Maryland, posts regular updates (www.cesar.umd.edu). Providers can sign up for weekly updates from the National Drug Early Warning System at University of Florida (www.ndews.org).
CATR: Any final thoughts?
Dr. Ciccarone: I’ve learned a tremendous amount talking with people who use drugs, both my patients and research subjects. A bit of rapport building and a nonjudgmental, curious approach can be invaluable. Remember that they are the experts in the room when it comes to drugs on the street, not us. And I’d like to add that I think addiction medicine is a wonderful field. It’s a young field with a huge and bright future. There’s potential for so much scientific advancement. The best way to make progress is to talk to one another, synthesize approaches, exchange information. We are just getting started; let’s do it together.
CATR: Thank you for your time, Dr. Ciccarone.
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