So, hi, everybody. Thank you for the invitation. My name is Fernando Montero. I'm a medical anthropologist. I have been doing research on drug supply chains in the United States and the public health implications of those transformations for the past 16 years. Most of my work has been in Philadelphia, in the predominantly Puerto Rican neighborhood of Kensington. I lived in Kensington between 2008 and 2012. I moved to New York City for graduate school in 2012, but luckily Philadelphia is just an hour away, so I have been going back very often since then, and I have stayed in touch with all my former neighbors, and I continue collaborating with people who use drugs and with people who sell drugs. And my work in general tries to bridge the worlds of drug supply and drug use to better understand transformations to drug supply chains and the public health implications of those transformations. So it's based on that research that I am going to present this material on xylosine to you today. And please do feel free to interrupt me with any questions. I wanted to first give a shout out to the Opioid Response Network, a very generous organization that makes possible trainings like this one for organizations that are interested in hosting them. If you are a part of any other organizations or are interested in bringing this training there, please get in touch with Courtney and she will very kindly assist you. So I always start this presentation, which is ultimately about xylosine. It's going to be a prelude to your much more useful trainings on xylosine wound care. I always start this presentation by talking about the history of the drug supply in the United States. The reason I do that is because I insist that it is very important to understand what happened before xylosine to understand how xylosine emerged, why it emerged, in the places where it emerged and how it emerged. The same thing can be said about fentanyl. You need to understand the state of things before fentanyl to understand fentanyl. So I started in 1991 because that is the year when something really important happened in the drug supply of the United States. Starting 1991, two monopolies developed on either side of the country. East of the Mississippi, heroin markets were controlled and were monopolized, actually, by a Colombian form of heroin that was known as China White, even though it was Colombian, which was an off-white powder that would turn brown when mixed with water prior to injection. This is what we have always had in the East since 1991. This is what you had in Vermont for about 22 years. And west of the Mississippi, the United States had exclusively a Mexican form of heroin that was known as black tar. This form of heroin was very different from powder heroin. It was a gooey, waxy substance that did not easily dissolve in water the way that powder heroin does. Again, it came from Mexico and it was even chemically a very different substance. People would refer to black tar as being a kind of cocktail that contained many substances in addition to the ones that characterize powder heroin. And now epidemiologists and anthropologists studied people who use drugs on either side of the country and they realized that these differences in the material characteristics of the heroin that was available in different parts of the country had huge public health implications. So people who injected drugs during the heroin era on the West Coast had lower rates of HIV and hepatitis C than people who injected drugs on the East Coast. And anthropologists found that the reason for this is that the black tar heroin that was available in the West was a very kind of difficult substance to deal with on an everyday basis. I've got to listen to this, honey. It's a live webinar. I mean, otherwise, it was a very difficult substance to deal with as a person who uses drugs. If you needed to say, reuse a syringe to inject black tar heroin. And this was very common in the 90s when syringe service programs were even more scarce than they are today. You had by force to flush the syringe with water repeatedly, very thoroughly to prevent the syringe from clogging. Because again, black tar was this gooey substance, right, that would clog the syringe. Also, if you wanted to dissolve it in water to inject it, you had to heat it. You couldn't just dissolve it the way that people dissolve heroin in the East Coast in Philadelphia. I have never seen people use heat, which is very interesting, right? This would have been impossible in California through the 1990s and 2000s. And the act of flushing the syringe with water, especially, even more than the heat, eliminated the HIV and the hepatitis C virus from the heroin solution and the cooker that people who inject drugs would use on the West Coast. So these details about the material characteristics and these differences in the material characteristics of the heroin that was available in different parts of the country had huge public health implications, right? And this is why I insist that it's very important to pay attention to the details, to pay attention to the material characteristics of the substance that people are actually using, right? And it's not enough to say that somebody's using heroin. That doesn't mean anything. Black tar heroin is a very different substance than powder heroin. And those differences make all the difference. Let's put it that way. So starting in 2013, fentanyl begins to emerge, right? Sometimes fentanyl is described as a new phenomenon. It is not new at all. It's now 11 years old. And it's very interesting in that the geographic distribution of fentanyl's emergence was conditioned by that preexisting division in the heroin market in the country. Fentanyl emerged as a powder, and it could only be easily mixed into the powdered forms of heroin that we already had east of the Mississippi. It took a very long time for fentanyl to finally make an impact on the West Coast. And the reason for that is that the West Coast was controlled by black tar, and black tar was this waxy, gooey substance that was very difficult to adulterate with a powder like fentanyl. In fact, black tar was almost never found with fentanyl. It took a completely different transformation of the open market on the West Coast for fentanyl to finally make an impact there. And it took about six years for fentanyl to finally spread to the West Coast. Again, this is why we need to pay attention to these details in the material characteristics of these substances. Silazine followed a very similar story as fentanyl. Silazine emerges as a powder. Silazine is bought on the wholesale market in vials as a liquid, but it's placed on a plate in the microwave and evaporated into a powder. And it's that powder that's mixed into the opiate supply. So because it was a powder, it emerged, not surprisingly, on the East Coast, right? To this day, silazine is not yet very highly prevalent on the West Coast. By 2020, the opiate supply on the East Coast had become increasingly a mix of fentanyl and silazine. Heroin had essentially disappeared. You can still find heroin here and there in parts of the country, but overall heroin has disappeared. I myself, I'm now running a small drug checking project in Philadelphia. Out of the hundreds of samples we have tested, we have found heroin in two samples. And the coroners that offered heroin one week offered fentanyl and silazine the next week. So nobody has a consistent access to heroin. If you hear that somebody does, I would question it very strongly. Interestingly, the West Coast, I'm not going to spend a lot of time on the West Coast because that's not the focus of this presentation, right? And we're clearly not in that region ourselves. But the West Coast has completely transformed into a pill-oriented market. Black tar itself has also disappeared. Some people can find it in their pockets here and there where you can find it. But overall, if you go to places like Seattle, what you will find is people buying pressed pills that contain fentanyl. They crush these pills on aluminum foil. They light the aluminum foil on fire and then they draw up the smoke using a pipe or an emptied out big pen, right? So it took that transformation of the opioid market from a black tar market to a pill market for fentanyl to finally make an impact on the West Coast. So in this slide, I just wanted to spell it out. Fentanyl spread unevenly and that unevenness was shaped by the pre-existing heroin market, right? By the differences in the types of heroin that were available in different parts of the country. One point that I feel does not receive enough attention, this is the second bullet point here, is that when law enforcement confiscates fentanyl at the southwest border when it comes into the United States, the data from the DEA and Customs and Border Protection show that fentanyl is already heavily diluted. So even at the international wholesale level, fentanyl is such a potent substance that it's already heavily diluted and it appears generally in concentrations ranging from 1.5 to 10 percent. I think that that has not received as much attention as it deserves and we're going to come back to this in a little bit. Something that's very important about fentanyl that helps to understand xylosine is again related to its details. The details of fentanyl consumption and how fentanyl consumption is different from heroin consumption. Most of the time when you hear about fentanyl, you simply hear that fentanyl is more potent than heroin. That's kind of as far as people tend to go when it comes to a description of what fentanyl is. I insist that that is a very poor way of understanding fentanyl. That doesn't tell us much about what fentanyl does to a human being when they consume it and in fact in most ways that matter to the people who consume opioids on an everyday basis, fentanyl can be considered a worse drug than heroin, an inferior drug to heroin. When you hear about a substance being more potent, you assume that the substance is better but it's not. It's an inferior drug. The most important way in which it is inferior to heroin is that it lasts less. I'm sure you all know this better than me. This is pretty generalized common knowledge by now. Fentanyl has a shorter metabolic half-life than heroin. It's metabolized by the body much more quickly than heroin and that means that people get dope sick faster. People develop opioid withdrawal faster. This is a huge problem for people who have opioid use disorder who need opioids on an everyday basis and consume opioids on an everyday basis. They're experiencing a torturous experience, experience of dope sickness much more quickly with fentanyl than with heroin. This also has huge implications because that means that a person has to buy more drugs, more dope. If they are injectors, they have to inject more frequently. That sometimes means that a person will have to reuse syringes more frequently or share syringes more frequently. You can begin to imagine the public health implications that fentanyl has had because it is worse than heroin, not better. Another way in which fentanyl is worse than heroin, and this was clearer in the earlier period of the fentanyl era, there is more confusion now because the kind of time, temporal boundary between the heroin era and the fentanyl era has become somewhat confused. The temporality is not very clear in people's minds, right? Again, a lot of people think that fentanyl is a phenomenon that started, what, after COVID or in 2018 and then started in 2013, so a lot of people don't even remember what a pure heroin high feels like. A lot of people initiate, became initiated to opioids after 2013 and don't even know what a pure heroin high is, right? It's not as easy to capture this difference anymore, but in the early fentanyl years, people who use drugs were very clear that fentanyl provided an inferior high to heroin. Heroin was always described as a holistic full-body embrace that was very satisfying, whereas fentanyl in the early years was described as a more localized high, concentrated in the neck and the face. Some people described it as a flushing feeling in the face that was nowhere near as satisfying as the full-body embrace of heroin. And it's important to understand these ways that fentanyl is worse than heroin because one reason for xylosine's success, for xylosine's staying power, is that it compensates for all these ways that fentanyl is worse than heroin. It makes up for fentanyl's deficiencies. We're going to come back to that point. So firstly, I think you probably all know this by now, but I very briefly wanted to review xylosine's pharmacology. Xylosine is an alpha 2 adrenergic agonist. It's not a traditional mu-opioid. There is a new clinical literature, mostly based on experiments with rats, that is showing that xylosine is a different kind of opioid, not a traditional mu-opioid like heroin or fentanyl. It instead attaches to kappa opioid receptors. It's a different opioid receptor in the body. The substances that adhere to that other kappa opioid receptor do not produce the same type of effect on the body or the same type of experience as mu-opioid agonists like heroin or fentanyl. It's a very different type of high, nowhere near as pleasurable as the opioid experience. In fact, it is often described as a more dysphoric high, an experience of deep discomfort in addition to deep sedation. In any case, the implications of the fact that xylosine is a kappa opioid as opposed to a mu-opioid are still being investigated. I actually don't think that it's going to be a very productive avenue of investigation. I think we should focus on the differences at this point between xylosine and opioids and move on from that. Concerning its history, again, I'm pretty sure you'll know this, but the first place where it was found in the opioid supply was in rural Puerto Rico in the early 2000s. A lot of the most important investigations and research into xylosine and its effect on humans was done by Puerto Rican public health researchers in those years. They were the first to document these new types of skin wounds that are different from the traditional heroin abscess. They were the first to document and write about the fact that people were falling into periods of deep sleep after consuming xylosine. I always cite this literature because it's very good, and I always encourage people to go back and read it. They were also doing things that a lot of people are not doing now, like going back to the Eastern European literature from the 70s and 80s on xylosine experimentation on rats to try to understand why it was that xylosine was creating these new types of wounds, why it was producing deep sleep among humans, this kind of thing. I find this literature very good, and I always encourage people to look into it. Let me skip this. Philadelphia, which is where I work, has a very good drug checking program, and they have very good statistics on the composition of the local opioid supply. They test dope samples very frequently, and they have found that the average dope sample in the city contains between 2 to 10 percent fentanyl and 30 to 40 percent xylosine, virtually no heroin, as I was saying earlier. Xylosine is the bulk of the substance that people are consuming when they consume dope. In fact, people are increasingly complaining that there's not enough opioids in their opioids, there's not enough opioids in their dope, and that's causing all kinds of transformations in people's drug preferences and drug using behaviors. For example, a lot of people complain that because there's so little opioids in their opioids, they're not even feeling a rush consistently from the dope anymore, so they're turning to substances like cocaine or crack or methamphetamine, which are the only substances, stimulants, that reliably give them a rush, those euphoric 20 to 30 seconds after you consume a substance, that are very important for people who use drugs. They're not getting it from dope, so they're turning increasingly to stimulants to complement their drug experience, their drug using experience, in order to be able to feel something. As I was saying, xylosine's spread throughout the United States has been very uneven. It is not a universal phenomenon spreading everywhere without distinction, just like fentanyl was not a universal phenomenon spreading everywhere without distinction. It spread unevenly, right, because of the reasons that we explained earlier. Data from Millennium Health, which is a lab that tests urine samples submitted by doctors throughout the country for all kinds of reasons, confirms this uneven spread. Urine samples in the mid-Atlantic are very frequently positive for xylosine, and you can see that xylosine prevalence decreases as you move west. Y'all very helpfully provided me some up-to-date data on Vermont, and I see there's a question, actually. Stephanie? Yeah, sorry. I was curious, why is that distribution so different? Like, obviously it's kind of marching West for lack of a better term, but is it kind of because of how, like some of the supply chains work? I know Vermont, which you might, I can't remember if I actually mentioned this in the email I sent to you guys or not, like Vermont has kind of like five source cities. So Philly is definitely one of them, but I'm curious briefly if you can just, why are those differences so much? Yeah, that question still needs to be investigated. It's a really good question, by the way, and a really good research question. You know, the fentanyl's uneven spread was a little easier to explain, because again, because fentanyl was a powder, right? As I was saying earlier, so you could only mix it into powdered forms of heroin and those were only present in the East. So that explained fentanyl's higher prevalence in the East Coast very well. With xylosine though, logistically, the substances that are available on the East Coast are easier to adulterate with xylosine. Basically, for the most part, it's pressed pills. Whoever is producing those pressed pills, I actually don't know who it is. I don't know as much about the West Coast as I know about the East, unfortunately, but whoever is producing those pressed pills could easily include xylosine in the pill that they're producing. Why they are not doing so is not, yeah, would need to be investigated. One of the interesting things about xylosine that have to do with its supply is that it's different from fentanyl in that xylosine is always introduced, well, in my experience, in the places that I've studied, like Philadelphia and Puerto Rico, I'm actually in Puerto Rico right now, xylosine is introduced locally. For xylosine to spread, what needs to spread is the idea of xylosine adulteration. People get xylosine from a vet usually, whereas for fentanyl, you actually had to have a connect in the criminal- International flow of drugs versus diversion. Lie, yeah, you had to get it from the criminalized black market. And so fentanyl was hard to get, basically, much harder to get than xylosine. So there's no reason really, there's not as many logistical obstacles for xylosine to make its way West. So the fact that it hasn't made it there is actually really interesting. It does have to do, as you suggest, Stephanie, with the fact that it's clearly a different supply chain, because otherwise, they would have the same supply. But much more research would need to be done on supply chains in the US to really properly explain that question. Thank you. So y'all, I think it was, it's Stephanie who sent us this material. This is very good, very complete, very thorough. You actually have better data than New York State right now on the prevalence of xylosine and other drugs in the state as evidenced in data from fatal overdose deaths, right? So these were substances that were present, not necessarily in a causal way, right? They were just present in a dead person at the moment of death. And it's very interesting to see that xylosine's prevalence indeed increases substantially every, it has increased substantially every year, starting in 2020, going from 3% to 13% to 28 to 32, right? I was noticing that there's some actually pretty interesting other substances. Can you see my cursor moving? Yeah. See, look at methamphetamine, for example. It experienced a rise here until 2021, got to 10% and then began to decline. This is actually very consistent with what I've seen in Philadelphia. Meth in Philadelphia had its kind of heyday of popularity around 2021, and then it began to decline. And cocaine became increasingly popular and prevalent. Cocaine is becoming, you might've even seen the New York Times article about this, cocaine is becoming much cheaper and much more prevalent everywhere in the hemisphere. Actually, there's an overproduction of cocaine in Colombia right now, and you can find it in very pure forms for very cheap almost everywhere in the hemisphere. I have a drug checking program in Puerto Rico right now. We're finding cocaine in concentrations approaching 87% purity, which is like almost ridiculous. And you can see that cocaine also rose in prevalence in Vermont in the last four years. There went from 36% to 61%. Small point of clarification, we could totally have an offline nerd conversation about this, specifically within Vermont, missed the like early 80s, late 90s, early 2000s meth that a lot of the West Coast saw. Cocaine's always been kind of the, has historically been the predominant stimulant that's used. This specifically, the increase that you're seeing is specifically deaths that involve cocaine, which is something that's weird and is likely, or what we think is an adulteration of the cocaine with fentanyl. So people who are opiate naive and are not intentionally seeking out, but we can have a conversation. Interesting, yeah, yeah. Yeah, the way that we draw kind of relations between medical examiner data and prevalence of substances is always very complicated, right? And we do need to be very careful about, drawing conclusions too quickly from medical examiner data like this, right? I mean, I do want to just repeat though that it tracks with my experience in Philadelphia where cocaine is becoming more popular, right? As an opiate. Like back when I lived in Philly between 2008 and 2012, people used cocaine, but it wasn't like an everyday thing. They used it whenever they had like a little extra money or when they wanted to feel a new experience, or it was kind of like a treat. That's what I mean. It's not like, a new experience. It was kind of like a treat. Now in Philly, everybody's using it every day, right? And one of the reasons people offer for doing that is that it's like the only substance that's consistently reliably giving them a rush as opposed to the opioids, which are kind of bad right now. Actually people complain about the opioids just being bad. Yeah, Kimberly. Hey there. So my question is in, so I've worked in the Bennington, Vermont community for about 15 years, but what I've been seeing in the agency I'm working in now, which I've only been there a few months, but I've worked with them for multiple years is we have a multitude of people that are coming in with xylosine wounds. And I think we're seeing more people with heroin and meth addictions and overdoses than we are cocaine at this point. But I guess my concern is, xylosine is relatively new on the scene in the Southern Vermont area, maybe the last couple of years and based on anecdotal experience, not necessarily actual qualitative data. So I guess my question is, to support my staff is like, how, I mean, like, I guess I'm just worried about how can we combat this and make, for example, this one, this was a month ago, we had a gentleman come in who's in our medically assisted treatment program who's seeing a blueprint nurse regular basis. He comes in, he's septic, he's got an open wound down to his bone, he ended up being sent to Albany Medical Center for a week. He literally, if he hadn't come in when he did, he would have lost his hand. But we're not, I'm really struggling to help my staff find ways not only to reduce harm, but because these people aren't getting, like you say, like the high they're thinking or the result they're seeking, they're just using more and more and more and more and more because they cannot afford the other stuff. So I don't know, I don't even really know if there's a question there, I guess it's more frustration. And we have a whole new outreach program, we are fully accessible, we're expanding our services, but we're very rural. And I guess, I guess personally and professionally, xylosine is fairly terrifying. Where I think I had gotten to a place where, I mean, meth use and heroin use was scary, yes, because I knew, because in my former position, I worked with people, trying to get them into treatment, but now they, with the additions and the increase of fentanyl and xylosine, where I'm at a loss, basically, professionally and practically, about how to, oh, what's the word I want? Underscore, the deadliness, this. Yeah, yeah, I completely understand the frustration. We are gonna go a little bit into kind of the public health implications of xylosine in a little bit with a focus on the wounds. Okay. The focus of the rest of the training, but I completely understand the frustration, especially because it's just such a different harm reduction landscape. Yeah. One of the things in the later slides is, how would you, much more than me, right, are dealing with challenges that you haven't seen before. The wounds, the deep sedation, people passing out on the street in public, you know, questioning for long periods of time. I mean, I've seen some scary stuff, but this one particular guy, I don't think I'll ever get those pictures out of my brain. Like, I was literally dumbfounded. I, I, I don't know. It's just the addiction to the high, but yet seeing this physical manifestation in his own body. I'm trying to understand that mindset, I guess. And I'm hoping this clarifies some answers, I guess. Yeah. You know, one thing that I always end with, and we're gonna get to this in a later slide too, is just, you know, this really highlights the need for safe consumption sites, places where people consume safely without the fear of overdosing or the risk of falling asleep and getting assaulted without the risk of developing the wounds, increasing healthcare access, right? The need to provide safe supply to people who have a dependence on substances so that they don't have to turn to these very toxic substances available on the criminalized market, right? Right. And that tends to be my focus when I think about these things, right? Right. Right. And maybe that's more of a statement than a question, but it just concerns me because I feel like the more I know, the less I know sometimes. So hopefully this series helps me quell some of that. So I appreciate it. Thank you. Oh, no, thanks to you. So as far as not the best transition to this slide, because I wanted to go back to the point Sorry. No, it's okay. No, I mean, we're going to go back to the challenges, right? But I did want to go back to the point of why xylosine has had staying power and how it is that it makes up for some of fentanyl's deficiencies, right? So one of the reasons for the success of xylosine is that it complements fentanyl in ways that it can sometimes be thought of as welcome among people who use drugs on an everyday basis, people who have a dependency on substances. So back in early 2021, I spoke to a lot of on-house people who use drugs in Kensington and Philly, and it was really impressive. And I'm sure you all as frontline service providers already had encountered this kind of stuff even earlier. But in early 2021, people had a very, very sophisticated understanding in Philly of the differences between say a heroin high and a fentanyl high and a xylosine high and the various combinations between these substances and what was good about some of the combinations and what was bad about them, right? And I wanted to share with you this one statement because I thought it was particularly, I think it's particularly insightful and clarifying of these differences, right? So I was talking to this person about those questions and this is what he said. Fentanyl is such a short-lived high. First thing he did was complain about fentanyl, right? Because of how short-lived it is. It's a short-lived high that the high, it's a good high, but it's so short that the nod is over real quick and you get sicker faster. See, the tranq extends the high. It gives the dope more of a heroin effect. It's a good rush with a heroin like legs, but they straight put bags out there that are just all tranq. You shoot it, you feel no rush. Tranq fent is like, you shoot it, you get the rush of the fentanyl, then the tranquilizer comes in, you nod and you fall asleep. A straight tranq bag is like, you shoot it, you get no rush. You're sitting there for a second talking and then you're waking up two to three hours later in a weird position. Like one case, I did a Newport. I shot a bag with a Newport. I woke up with a whole Newport burnt into my stomach. You could literally drown in a half inch of water if you did a tranq bag and you fell out, right? A lot of these things have now become pretty commonsensical. I think most people in harm reduction know them, but at the time it was kind of a huge realization for me talking with Tom, right? I didn't know that tranq staved off withdrawal symptoms. It's actually still unclear to me, and maybe you all have a better understanding of this, whether tranq xylosine is extending the sedative high, the opioid high, or just staving off withdrawal symptoms and letting people maintain for a little, stay well for a little longer. I think that point actually has not been clarified. But that's generally seen as a welcome effect of xylosine, the fact that it's staving off withdrawal symptoms. But then look, notice also that Tom is aware of all the downsides of tranq, right? Tranq gives you no rush, right? This is another reason why people complain that dope bags are bad these days. Tranq doesn't offer you those 20 to 30 seconds of euphoria that heroin used to give you, and that fentanyl can give you if it's present in high enough concentrations. And then he's realizing all these new challenges, right? You pass out in public in awkward positions. So you can burn, cigarette burn into your stomach. You can drown in a half inch of water, right? Women complain of a heightened risk of sexual assault and robbery. And it really shows that it's a new harm reduction landscape, right? We're not concerned with the traditional harms that you all had to deal with in the time of heroin. These are new public health complications. Yeah, so I already kind of explained this. Yeah, so just wanted to emphasize that, right? The idea that xylosine makes up for some fentanyl deficiencies. One very interesting piece of data coming from Philadelphia is that xylosine seems to be replacing benzodiazepines as an opioid adulterant in Philly. Benzodiazepine detections at the medical examiner's offices in cases of fatal overdose began to decrease exactly at the same time as xylosine detections began to increase. It suggests that there was a period between 2016 and 2017 when suppliers were experimenting, trying to tell which adulterant, benzos or tranq would be more profitable and successful. And xylosine appears to have won that battle. And it's very interesting that in that drug checking program I've been doing for the last four or five months in Philly and in Puerto Rico, I found very little benzos in the dope. Benzos and other things, but not really in dope. Okay, so we spoke about ways that xylosine may be considered by some people a welcome phenomenon, especially when it's present in low concentrations. One thing that I insist on that's not in this slide, I'm sorry, is that it's very important to begin to talk to people and study the differences between using xylosine in places where it is present in low concentrations versus those where it's present in high concentration. So in Philadelphia, xylosine is present in very high concentrations. We saw that the average dope sample contains 30 to 40% xylosine, right? And you can find bags that are 70% xylosine or 60% xylosine. But there are other parts of the country. Vermont might be one of them, I don't know. Maybe if you all have experience with drug checking, you can tell me. But there are places in the country where xylosine is just as prevalent, just as common, but present in very low concentrations. If dope bags only contain 5% xylosine or 3% xylosine or 10% xylosine, it's likely that people might even find the experience of consumption more pleasurable. It's possible that wounds wouldn't be as bad. It's possible that sedation wouldn't be as prolonged or deep. And I'm still a little surprised that there's no, now it's been already like five years. I'm surprised that there is not a lot of research on the difference between high concentration xylosine and low concentration xylosine. Because if we look at low concentration xylosine, the news might not all be bad. But anyway, thinking about the public health challenges of xylosine, let me begin with the second one, because that's really the focus of the training. The problem of skin wounds is really the biggest public health challenge of the xylosine era, as I was saying. And as you know, the deep sedation that xylosine produces has increased the risk of sexual assault and muggings, especially for people who are unhoused, who don't have access to many services. And also, it's very important to keep in mind that xylosine has complicated the treatment and the experience of withdrawal and detox for people with opioid use disorder. In Philadelphia, most of the unhoused folks that I work with are scared of going to the hospital for the treatment of a wound because they're scared that they're gonna be taken into the hospital and they're gonna be given buprenorphine to treat their fentanyl withdrawal, but their xylosine withdrawal is going to go unrecognized and untreated, and people insist that xylosine withdrawal is its own phenomenon that's torturous, and they will literally avoid the hospital because they know that in the hospital, their xylosine withdrawal is going to go untreated. Now, there's pioneering hospitals and clinics that are beginning to try to address this problem, but xylosine withdrawal has not been officially recognized as a medical condition by the medical profession, and so most emergency departments in the country, most hospitals do not even attempt to treat it, right? And this is a significant problem, right, because it aggravates the problems of access to healthcare that were already pretty bad in the first place for people with opioid use disorder. So going to the wounds, which of course are gonna be the focus of the rest of the trainings, it's important to keep in mind that the biological mechanisms that cause them have not been fully clarified. We know more and more every year that passes, but there is no definitive explanation for why the wounds are appearing. But the reigning theories actually come from the Puerto Rican public health literature from the 2000s, right, that the reigning theory is that xylosine is a very severe vasoconstrictor, so it restricts the blood vessels and impedes the flow of blood and oxygen to the skin, and that affects and kills skin tissue, right? In addition to that behavioral mechanism, vasoconstriction, a whole host of behavioral things happen as a consequence of vasoconstriction. So for example, because xylosine is such a severe vasoconstrictor, people's veins get shot, as they say, right, on the street very, very quickly. They lose access to their veins, their peripheral veins in their arms and their legs very, very quickly, and people respond in two ways. They lose access to their veins, right? So they begin to shoot into central veins, their neck or their femur, and they begin to skin pop or muscle, they're injected directly into skin or muscle much more frequently, right? In Philly, back when I lived there 2008 and 2012 in the Heron era, people had really good veins. It was very easy for them to inject. Now you increasingly see people skin popping, people injecting into their neck. I had never seen that in Philly, and this is a consequence of xylosines, vasoconstrictive properties. Skin popping, injecting directly into the skin, you can imagine, will increase the risk of developing skin wounds, right? So it's important to keep in mind that there's a combination of biological and behavioral mechanisms, right, that are causing and then aggravating the skin wounds. Now there's another phenomenon that's behavioral that's also very common is that people inject directly into the wound, and initially I assumed that people were injecting into the wound because xylosine might be like a local anesthetic, so it would be providing pain relief, but the majority of people that I ask in Philly if Trank is a local anesthetic say, no, it's not. It's actually not relieving my pain, and so then I asked them, why are you injecting into the wound, and the most frequent answer is that people are kind of doubling down and cutting their losses, so when they see that a wound is developing in their right arm, for example, they identify and they know that they're putting their right arm at risk, so they're not gonna inject into the left arm and put that limb at risk as well, right? They're kind of just cutting their losses and doubling down on the wound they already have, right, which actually makes a lot of sense. That is the most common response. Now, y'all might have a different experience. I'd be interested in hearing if it's different in Vermont, but the people who exclusively smoke that I speak to in Philadelphia don't develop the gruesome wounds. They develop small wounds that look like the beginning of a typical xylosine wound, but that small wound doesn't develop into the gruesome wounds that you have all seen and that we're gonna see a few photos of in a little bit. So smoking does appear to be protective in relation to wound development. Now, another factor to keep in mind is what we were just talking about, right, that increased popularity of cocaine and methamphetamine. Stimulant use has long been associated to skin picking. People develop the compulsion of picking their skin when they use stimulants, and we need to think of that as a potential additional contributor to the formation and aggravation of the wounds. And of course, this is all really a structural phenomenon, right, that a lot of this has to do with people not having access to showers, people not having access to a safe supply, right, and that's where their focus should be, right? All these behavioral things that I'm talking about are kind of the details of how the phenomenon ends up playing out on the street, right? We should not use these explanations as ways to blame people who use drugs for their problems or to think of people as crazy and undisciplined and producing the problems that they have to contend with. The problem really, the culprit really is prohibitionism, criminalization, lack of access to healthcare, lack of access to housing, those things, right? Okay, so I did want to show you a photo of the wounds. I'm sure you've all seen them in person or in pictures, but I just wanted to show one of the photos that I took a few months ago in Philly. If you're squeamish, you might want to look away. But I wanted to say a couple of things about this, really both in Philly, that the slang term for these wounds is tranq burn, right? The wounds look and feel so much like burn wounds that this is the slang term that has emerged among folks to describe them, tranq burn. And these are wounds that appear in places, again, where xylosine is present in high concentrations. I'm still interested in seeing whether, I'm talking to folks with experience in places where xylosine is only present in low concentrations to see if wounds that are this bad develop that frequently among participants and our folks. Wanted to come back also to the point about xylosine withdrawal not being recognized as a medical condition yet. It's very important for that to happen. There are hospitals and clinics developing protocols for the treatment of combined xylosine and fentanyl withdrawal. I think maybe at this point, you'll know about this literature, but I'd be very happy to share with you the best article that I've seen on the subject that offers like an 18-day protocol for the treatment of combined fentanyl xylosine withdrawal. The doctors and providers I know and collaborate with in Camden and Philadelphia swear by this protocol. So in these presentations, I tend to insist on how good this article is. And it's in the bibliography here, and I'd be very happy to share with you the PDF after the presentation if you're interested. I did want to say a couple of words about metatomidine. This is the new thing, right? It's being found all over the East Coast. My own little drug checking project in Philly has been finding it since late August. You might know that metatomidine is in the same family of drugs as xylosine. It is more potent, though it binds more potently to the same receptors and produces even deeper sedation. The folks on the supply side of things that I talk to in Philly say that metatomidine's rise is very similar to the rise of fentanyl in that it has to do with the criminalization of the less potent substance, right? So xylosine, because of its criminalization and increased punitive control has become more expensive and difficult to get. Right, so suppliers are switching to a substance that is not yet regulated that happens to also be more potent and therefore cheaper to introduce into the supply because you need less of it. So metatomidine is cheaper, but also more potent and possibly more problematic for public health. In the drug checking program that I have in Philly, the metatomidine appears in concentrations ranging from two to 25%. Usually between two and 10%, which is again interesting because this more potent substance is not showing up at the same concentration as xylosine. It is as those suppliers know that it's actually more potent and they need to use less of it, but that would need to be studied. It's also important to keep in mind that metatomidine is a different substance. It's in the same family of substances, but it's not the same substances, right? The relationship to skin wounds is not necessarily the same. It is possible that metatomidine might be less harmful to the skin. That would need to be investigated, right? I just insist on the fact that it's always important to look at each individual substance in its details and in its differences as much as in its similarities to all the others, right? Because otherwise we're just gonna be left always spectacularizing or saying things that are not true, right? These days we wanna leave lies to MAGA and Trump, not to the world of public health and harm reduction. I don't wanna say too much about meth because I realized that, you know, we know now from the data that meth use is actually not that prevalent in Vermont. It's also even decreasing in popularity throughout the East Coast, even though it had its little moment of popularity in 2022, 2020, 2021. But one thing I wanted to say is that the increase in meth consumption in the East Coast, you know, if you compare 2020 to the 2000s, in some ways is similar to xylosines increasing and increased popularity. One way that folks who use drugs in Philly explain the appeal of meth is also in relation to fentanyl's deficiencies, right? So these are two quotes where people, I'm not gonna have enough time to read them out, but quotes where people describe that meth became popular to them or became appealing to them when they started to get dope sick faster, right? Meth was helping them maintain for a few hours and those hours were crucial to make more money, to be able to buy more opiates, right? So even though a stimulant is very different from a sedative, there can be some similarities in the appeal of these substances. And in this case, that similarity has to do with the ways that fentanyl is worse than heroin, right? Because it's so short-lived. So I think that's a good point. Because it's so short-lived. Thinking in general about the broader public health implications of all these transformations, it's interesting that we still don't have enough data to see, let's say, what the impact of xylazine and fentanyl is on long-term HIV rates and hepatitis C rates among people who use drugs. But speculating based on the ways that people's drug use behaviors are changing, it's interesting that we could actually see this era as a very complicated one that's gonna be very, that's gonna be harder to explain and understand than the heroin era where you're technically just thinking about one or two substances, maybe one opioid that was used consistently and one stimulant that was really used sporadically. Now you're thinking about a lot of substances at the same time, and each substance has a different relationship to the risk of contracting an infectious disease. So one interesting thing, for example, is that xylazine, in extending the sedative high or in staving off withdrawal symptoms, is leading people to use less dope than they used to. So you're not getting dopesick as fast as with fentanyl alone. So you don't have to buy again as often. You don't have to inject as often. And in the last few months, I've been trying to really ask people about this and quantify the difference. And in average, people are using a fourth to a fifth of what they used in dope in the heroin era or before TREC. And the drug corners are actually finding that xylazine is not very profitable because even though it's cheaper at that wholesale level, they end up selling less of it at the retail level. And the impact of that on the drug supply will be very interesting in the long term. It's not inevitable that xylazine will stay around forever because it's just not profitable. People are clearly buying less than they used to. Dope, right? They're now buying more stimulants. So that makes up for some of the economic loss. And now because people are using less times throughout the day, they're also injecting fewer times, right? So counterintuitively, some of the news around xylazine might be good. It is a possibility that people have a lower risk of contracting hepatitis C or HIV through injection. And now the rising use of stimulants is a countervailing force. It's a contradictory force. Stimulants have long been associated to increased risk of contracting infectious disease, right? But I think it's important to be mindful of the good news and the bad, let's say, right? Like all the ways that a substance can transform behaviors in ways that have implications for public health. It's not, I think we tend to over-scandalize and over-spectacularize and over-emphasize the bad. And sometimes we don't see all the other changes that might be instigated by a new substance. So looking ahead, what are some of the things that could be done to address the problems that Stephanie was identifying, right? So I am a big supporter of overdose prevention centers or safe consumption sites. It's very important to keep in mind that in the era of xylazine, overdose prevention centers would not only prevent overdoses, they would also prevent sexual assault or robberies that take place when people are heavily sedated, right? I'm a big proponent of community-based gas chromatography, mass spectrometry, drug checking, where the democratization of sophisticated drug checking, we need to move from the 1960s computer to the MacBook Air very, very quickly. And the technology needs to become cheap and available at the local level so that service providers and people who use drugs know the composition of their supply on a real-time basis, right? Not a month later, which is what most of the best drug checking programs in the country are doing right now, right? They're giving us data a month after the fact. My point, that's not very useful. We need real-time data. I'm a big advocate of safe supply, the provision of substances to people who are dependent on them so that they do not have to turn to the unregulated street market. And this is probably my most controversial position because I am also a strong advocate of the need to engage with people who sell drugs and not only the people who use them, right? We need the voice and the experience and the lived experience of people who sell, not only of the other people who use. I think we vilify people who sell too much and too quickly. We assume that people who sell are completely uninterested in anything related to public health. We assume that they're profit-obsessed, evil characters. In my experience in Philadelphia, that is absolutely not the case. And I think it's a failure, a historical failure of harm reduction not to engage systematically with supply. And I'd like to end with that because I really think that that is the future. That is where one of the important components of the future, of course. I think that's where harm reduction needs to go to take over interaction with supply. Right now, police, law enforcement have a monopoly over interacting with supply. Nobody else interacts with supply and that makes absolutely no sense. Public health needs to have a prominent role there. There should be a public health commissioner in every city whose role is to engage with, negotiate with suppliers. There's other parts of the world where that happens, even if that market should not be criminalized, but even if it is, you can still negotiate and sit at the table with the stakeholders of those markets in order to regulate them and make them safer and less violent. It's a dream right now, given the political environment in the United States, but I really think that if we are invested in harm reduction and in prioritizing public health over criminalization, that's what the United States needs to do. Well, thank you very much. I'm excited to hear your questions.

Fernando Montero

medical anthropology

XYLAZINE

opioid market

public health

drug supply chains

harm reduction

overdose prevention

stimulants

healthcare challenges