ourselves quickly and then we're going to sort of run through this this presentation. Just to get a feel for who's in the room, how many West Coasters do we have here? All right. Is xylosine a big thing out here yet? Not really, right? Not according to the data. Just want to make sure that people on the street. So the one theme about this presentation is that sometimes the grassroots efforts on the streets actually know more than the medical community does. Can everybody accept that maybe? I know it's hard. All right, because that's the flavor of this. We don't know a lot medically. We don't know a lot of through the science yet, but we do know a lot about what's happening on the streets. So we're really really interested in that. That's a lot of the information that we're promoting. How many people are from sort of the middle sliver of the country? Xylosine, Midwest. I'm going with the whole does the South Southwest count? I mean, you know, I don't know. Yeah. And then the East Coast, I don't really have to. I'm from the East Coast. If folks are from Philly, then that's I know why you're here. You probably know more than I do. So we're going to talk about this a little bit today and a lot of myths about xylosine. A lot of misinformation about xylosine. A lot of complications emerging because of the the onset of xylosine as an adulterant in the supply. So we're going to really try to work through that as much as we possibly can in the hour and a half that we have. I can tell you we do this and have been doing this for a full six hour training and can hardly get through it because we get so many questions. So an hour and a half, we're pretty much, we got no shot. But we're going to do the best that we can. So I'm Mike Chappell. My name is bolded up here because apparently I'm a narcissist. I did not do that. I will be talking to someone from AAAP when this meeting's over. I'm an assistant professor at Columbia University. We're here in our capacity with the Opioid Response Network. I'm going to talk a little bit about the project that led to sort of much of this work once I get started with my part. But I'm an assistant professor of clinical medical psychology, which is a really fancy title for an assistant professor. I'm not a psychologist. I'm not a clinician. I am none of that. I am a criminologist. So how did I get here? I'm not really sure. I have a long sordid history that, you know, as you can imagine, working with criminal justice populations, you're then working with people with high rates of addiction and mental health disorders, which then means you're working with everything that's tangential to that. I got a call while I was on vacation two years ago to team up with the School of Nursing and my colleague Kelly, who I never met, and I said, I don't know anything about nurses. Like, okay, fine. Why me? I was new to Columbia, so it was hazing, I think. And here we are, and it's been this amazing project that will tell you a little bit about and get a sense of where we've come from. But that's my background. Good afternoon, everyone. Thank you for being here after lunch. I know that's a little tough. Sorry. So I am Kelly Bryant, and I also am not a psychiatrist. I'm not in addiction medicine. I am actually a nurse. I'm a nurse practitioner, and my background is actually OBGYN. So you may ask, how the hell did I get here also? And I was pulled into this project. I happen to be the medical program director of an opioid overdose prevention program, and Mike will give you the history of how we all came together, and we were pulled into this project. But it's been a long journey. We went from one project. We're probably on our third or fourth now, and I'm looking forward to sharing some of the work that we've been doing and the work that we continue to do. And my role is I am assistant dean at Columbia University School of Nursing. That's my role, and I'm going to pass it to Fernando. Hi, my name is Fernando Montero. I'm a medical anthropologist. I'm a postdoctoral researcher at Columbia University. Should we get started with the slides? Yeah, you'll get a really good idea of who Fernando is when he gets into his slides. So we're just going to kind of pop into this quick. We have no financial relationships to disclose. Catherine, we already plugged orange, just so you know. But empirical assessments of drug-related wounds and people who use drugs. So several years ago, we got a call. Kelly had been working with some folks in the South Bronx, in New York City. They were doing outreach in the context of, you know, everyday outreach for various reasons with people who use drugs, and they were coming across a lot of wounds. And this was probably in what, early 2021? Late 2020. And eventually we put in for a project. We were going to do it, but we needed some support. We put in for a project through the Chosen Center at Columbia University, and we got a very small demonstration project to go out into the community, accompany these outworkers, and our interest was in documenting the prevalence of wounds. We looked in the literature. If you look in the literature around wounds among people who use drugs, there's really not a lot of information out there. Obviously it's a higher risk associated with injection use and whatnot, but there really isn't a lot of routinized information. So we're really looking to do a simple demonstration study, assess prevalence, but then also really start to think about basic intervention around what could outreach workers do to provide first aid, and then possibly make an referral to address some of these wounds. So really it was very simple. Again, we had $25,000 to do this, so don't ask me any scientific questions. There are no scientific answers. It was a $25,000 study. That's all you need to know. All right? It's consisted of, basically we're looking for people who had self-reported illicit substance use in the last 30 days, right? We want to know they were an active user. If we were going to document the prevalence of wounds, it was the prevalence of wounds among active users. So that was the criteria, a quick screen of like a drug inventory for the past 30 days. If they were, they would be accepted into the demonstration study, and then we would do a wound assessment. And really what we were doing, we had a little protocol around that to document various aspects of the wound, but of course we had to first observe, did we see a wound? If we didn't see a wound, we asked about whether or not they had a wound. It was, a lot of it was done in the winter, right? A good portion of it was done in the winter in New York City, so people were clothed. People didn't have any trouble taking off their clothes in the middle of the park in January to show us what they had, but they were closed. So we really did have to ask a lot of questions and gain their trust. We did a wound assessment that talked, that asked a lot of questions. Where is it? Look at it. Observe it. What's the color? Is it infected? Is all these sorts of characteristics of the severity of the wound. We distributed gift cards, and then we distributed wound care kits that had first aid supplies, and we taught them how to provide basic first aid for their wound, and then encourage them to to go get medical care. Using sort of like an S screening brief intervention, right, like a brief negotiated interview, five to ten minute interaction, motivational interviewing skills, to develop their intrinsic motivation and make a referral. So we did it for about six months, roughly on Mondays, for about five, four or five hours a day. Set up a table. Kelly could tell you more about this in front of a Burger King. Over the course of that six months, one day a week, we saw almost 600 people that we assessed and intervened with, and at that particular time, 23% had one wound or more, at least one wound. So 23% of the 600 people we saw that had self-reported drug use had a wound. Most commonly used substances, you can imagine, this is heroin, stimulants, and alcohol. And these are some maps out of the location of where these wounds were. It's a little bit blurry probably for you, or it's just that I need glasses. No, it's small. So we have these slides to give out, but mostly on the hands, arms, feet, pretty common in terms of where wounds will develop. And then we had other data on the severity of the wound that we didn't put up here because we didn't want to overwhelm folks who were working on a publication. But what's really interesting, so first of all, key lessons that we learned. Participants were open to sharing and disclosing wounds, to receiving wound care education, but none of them wanted to go to the hospital. That probably doesn't come as a surprise to many people in this room, but nobody wanted to go to the hospital. This is highly stigmatized as substance users to begin with, and then some of these wounds that they had were further stigmatizing, and they had not had good experiences. So we were giving out the wound care kits, and anecdotally people were very receptive to taking them. They were using them, and as we'd see them from week to week, they were using the supplies, and they were getting better, and they were coming back for more supplies. Probably the craziest part about this whole study was that when we started it, and by the time we finished it, we had not really had xylosine on our radar. You heard me say everything I just said, and you probably thought that this study was inspired by the presence of xylosine, and wanting to know what was going on. No, we actually were looking at wounds among people who use drugs absent of any real understanding of what xylosine was at the time. It wasn't in New York City. It wasn't there yet. It wasn't prevalent yet. It wasn't being talked about yet, despite the fact that it was in Philadelphia, probably 90 miles down the road, right? So xylosine was only really starting to creep up when we had our results in, and we started to go around and present on this stuff. Everyone was coming up to us from other places around the East Coast going, have you heard of this? Hey, check out this picture of this really gnarly wound that I had on a patient, and like all this stuff started kind of percolating. And so we didn't really observe, and we don't know because we weren't looking for them at the time, what was or was not a xylosine wound, and really set out to kind of expand the work on this, and knowing that participants were open to getting help, but not to getting medical support, we started thinking about, well how much can we get out there and train? We started talking with harm reduction organizations in New York City and elsewhere, and folks wanted to learn how to do wound care. It's been mainly harm reduction organizations that have been interested in this, but they want to learn how to, they were already doing it, a lot of them, just with whatever information they had, and so we've been doing that for months and months and months, developed a curriculum around that, and what we do is we talk about xylosine, we talk about basic wound care, we talk about motivational interviewing, we talk about all kinds of different tools that they can use while doing outreach. So a lot of the work we've been doing was not really developed by the medical community, for the medical community necessarily, right? It was a lot of outreach context. So we developed this module. What I will say, I'll just put in a plug through the Opioid Response Network, if you folks are from a place and there's anything you hear today that you find interesting, and you want an expanded sort of approach, whether it be a training, whether it be more information in your regions, you can put in a request through the Opioid Response Network, you can come to me after the presentation, I can tell you how to do that, and you can get any of this information in your respective regions. The ORN covers all 10 regions, all 50 states, U.S. territories, so wherever you are, as long as you're from this country, you can get some of this information in a more expanded format if it's useful to you, or you want your colleagues to have it, or whatever. It's free. You got to pay me sometimes, but that's why my name's bolded. If you know Catherine, she'll pay you to take the training. So yeah, this is, it's free, and these resources are out there in the network. So what I'm gonna do at this point, I'm gonna pass it over to Fernando, who's got a little bit of background, some really important background, to put xylosine, provide the kind of context that I think we feel it's important that everyone has around xylosine. Why is it here? What is it? Why is it here? Why is it here now? And what does it mean? Hi everybody, great to see everybody here, great to see some of our harm reduction heroes in the audience. So Rivera, a little shout out. Oh yeah, so for the past 15 years, I've been doing research on drug economies in the United States. I lived in Philadelphia in the neighborhood of Kensington between 2008 and 2012. This is a predominantly Puerto Rican and black neighborhood that has become somewhat famous in the last couple years because of the impact of xylosine on people who use drugs there. And so I left Philadelphia for New York City for graduate school in 2012, but I have continued visiting my neighbors. I have maintained my relationships with all the people that I've worked with, starting when I was a very young man, 15 years ago. And as soon as the COVID moratorium ended in 2020, I went back to Philadelphia to visit my neighbors again, see what COVID was doing to the neighborhood, the impact that COVID was having in the neighborhood. And that was the first time that people started telling me about this new thing called Trank. And people were starting to show me their very severe skin wounds. People were starting to tell me about the fact that they were passing out right after consuming opioids and falling asleep in very awkward positions for extended periods of time. And that was the moment. Also thanks to conversations with harm reduction service providers who were already aware of Trank and were already passing out flyers trying to alert their participants about the presence of xylosine, also known as Trank or anesthesia in Spanish, in the supplier. So it was thanks to those conversations that I began getting interested in this and began doing research specifically about xylosine in Philadelphia. And so I'm going to tell you a little bit about the pharmacology of xylosine and the reasons why it emerged at this moment in time in the US opioid supply and give you some sense of why it is that it has emerged as a successful adulterant with staying power at this moment in time. So as many of you probably already know, xylosine is predominantly an alpha-2 adrenergic agonist that has long been used as a veterinary analgesic, sedative and muscle relaxant for large animals. It was first documented as a heroin adulterant in Puerto Rico in the mid-2000s by harm reduction service providers and public health researchers there. I was actually in Puerto Rico 2010 and some of her friends in the harm reduction community took me to the small little mountain towns in Puerto Rico where people were starting to use xylosine along with their heroin. And it was very interesting because those towns were towns where horses were bred for the racehorse market in the mainland United States. And so xylosine has long been used for the treatment of those animals as well as to facilitate the transportation of those horses to the US mainland from the island of Puerto Rico. So the colonial relationship between the United States and Puerto Rico is kind of all over the emergence of xylosine as a component of the opioid supply in the US. And to this day we are all basically still kind of just citing the Puerto Rican public health literature that emerged in those years, documenting the public health impact of xylosine. They were the first to document the emergence of these special skin wounds that are different from traditional heroin abscesses. They were the first to document the the long periods of xylosine-induced sleep and all the public health complications that emerged along with that when on house people are using xylosine passing out on the concrete for extended periods of time in awkward positions. That leads to a whole new host of public health and safety complications. And so I'm gonna tell you a little bit more about this this literature and the public health concerns that they first identified in this presentation. I wanted to start though by reviewing very quickly the history of the US opiate supply since the 1990s because I think it is very important to understand the emergence of new adulterants like xylosine. It's crucial to know what came before, right? Only by knowing the transformations that happened before xylosine can we understand why xylosine emerged in the places where it did and why and how, right? And so very interestingly for 22 years between 1991 and 2013 the United States had a very consistent opiate supply. What it had was basically two monopolies. The West Coast had a Mexican form of heroin that was known as black tar, a waxy gooey substance. The East Coast had a Colombian form of heroin that was a an off-white brownish powder that turned brown when mixed with water prior to injection. Those two monopolies held for 22 years with very little interpenetration or interrelation. Interestingly places in the Midwest like Chicago had both supplies. Those were the only places where you could find both black tar and powder heroin but these differences in the consistencies and the textures of heroin that were available in different parts of the country had huge public health implications and I apologize to those of you who are familiar with this literature that has looked at this. But for example epidemiologists documented that HCV, hepatitis C rates in the West Coast were much lower among injection people who injected drugs again in the West Coast than among people who injected drugs in the East because in the West Coast people had to heat black tar heroin in water prior to injection whereas the powder heroin that was available in the East didn't need to be heated and in fact in Philadelphia I have never ever seen anybody use heat to dissolve the heroin in water. It dissolves very easily. You just mix it in water then inject. In the West Coast you needed heat by force and that clearly had an impact on hepatitis C rates among people who inject the drugs. So this is why you need to understand the details of the textures of the substances that are available at different moments in time in different parts of the country. You can't just say that a person does heroin. That means nothing. You need to know specifically what kind of heroin, what the exact composition of that heroin is, what texture it is because that conditions or almost even determines the preferred modes of administration, the frequency of consumption, how many times a day a person uses, how much, the size of their habit as people say on the street, right? All these things are largely determined by the specific material characteristics of the substance that people are consuming, right? Starting in 2013 is when fentanyl starts coming into the picture. Fentanyl emerged as a powder. Guess what part of the country fentanyl came in first? The East Coast. Why do you think that is? Why wasn't it present in the West first? Because you could only mix a powder into a powder not into a solid. So fentanyl made a huge impact in the East Coast and not in the West Coast for a very long time. It took a very long time for fentanyl to finally emerge in the West Coast and it only did so when something else completely different happened to enable fentanyl to enter West Coast drug markets. Do you know what that is? What's that? Well what really happened in the West Coast is that the market completely changed from a black tar market to a pill-oriented market. The West Coast is now predominantly a pill market where people crush pills and smoke them as a matter of fact. And the pills are mostly a fentanyl combination these days. So it was only when the pill form emerged kind of as a dominant form of opioid in the West Coast that fentanyl was able to enter the supply. Back when the supply was black tar, fentanyl couldn't be incorporated into the substance. Yeah very interesting yeah but interestingly in the West Coast when that happens when there's a fentanyl powder and available in the street people know it's fentanyl right it was never advertised as though it were heroin because people know that it's just a completely different substance it's not the black tar that they that was always available there where whereas fentanyl was able to camouflage itself as heroin in the East Coast for a very long time right it took us it took about six years for people people four years really for people to really begin to find figure out that this was a different thing. Silazine begins to make a significant presence in Philadelphia around 2017. Again it took a few years for people to really realize that harm reduction is sought before anybody else. Philadelphia was the first city to raise the alarm when they began documenting an uptick in fatal overdose data. Medical examiner's office began to see xylosine in the bodies of people who had died of a fatal overdose, and they began documenting the increasing presence of xylosine in the local drug supply. By 2020, heroin had disappeared from the East Coast. It's now basically impossible to find heroin in the East Coast. You can still find a little bit of black tar here and there in parts of LA, parts of Arizona, but overall, heroin is gone. In the East Coast, the supply is increasingly a mix of fentanyl and xylosine. In the West Coast, as I mentioned, you mostly have a pill market. It's mostly fentanyl. Xylosine still hasn't made a significant impact here. Interestingly, Mexican methamphetamine, which I never saw in Philadelphia when I was there between 2008 and 2012, all of a sudden is beginning to increase in popularity in the East Coast. About a third of the drug corners in Philadelphia that used to sell only heroin and cocaine are now selling methamphetamine as well. There's been more fluctuation in the story of methamphetamine's rise, actually. I was just in Philadelphia a month ago, and I'm sorry if I'm boring you with these details, but I think it's very interesting how, actually, in 2021, when I first did research on xylosine, methamphetamine was rising in popularity significantly. I thought it was just going to take off and become as popular as heroin used to be. But I was just in Philadelphia for a week last month, and everybody was complaining that the quality of meth had decreased, and everybody had switched to cocaine. Everybody's doing speedballs all of a sudden, mixing fentanyl xylosine, which is known as dope and cocaine, and meth is kind of not going away, but it's not rising in popularity anymore. Sorry, because I'm a little worried that I'm going a little too slow now, no? In order to understand all these changes and transformations in the U.S. opiate supply, I think it's always very important to pay attention to each particular substance, its particular characteristics, right? Just as we spoke about the differences between black tar and powder heroin, it's also very important to understand fentanyl. And I always insist that it's very important to think about fentanyl beyond the question of potency. When people describe fentanyl, they usually just go, what's the usual line that you hear? A hundred times more potent than heroin. That's basically all you get. That's the only description that you get, and it is true that fentanyl is a more potent respiratory depressant. This is what causes an opiate overdose, right? You stop breathing and you die, very different from a stimulant overdose that causes a heart attack or a stroke or a seizure. Fentanyl is indeed a more potent respiratory depressant, so it's more likely that a person will die from a fentanyl overdose than a heroin overdose. True. So in that sense, fentanyl is more potent than heroin. But in almost every other way, from the perspective of people who use drugs on a daily basis, fentanyl is an inferior drug. It's worse than heroin. And this is very important to keep in mind, right? At this point, I'm sure many of you, if not most, know that fentanyl has a shorter metabolic half-life than heroin. That means that it lasts less, significantly less. That means that people get dopesick faster, right? Opiate withdrawal comes on much quicker. This is hugely significant for a person, especially the in-house people that I work with who use drugs on a daily basis, who all of a sudden are buying the same substance, but it lasts a fraction of the time than it used to, right? That means they have to buy more. That means that they have to use more. They have to reuse syringes more, share syringes more, right? So it unleashes a whole host of public health problems that weren't necessarily there for heroin. The other way in which fentanyl was long described as being inferior to heroin has to do with the very quality of the high. Heroin, back when it was very pure in Philadelphia, back when I lived there, it was always described as this holistic, full-body embrace that lasted for a very long time. Fentanyl instead was described as a much more local high, concentrated in the neck or the face. So most people described it as a flushing feeling in the face, not the kind of holistic, full-body embrace of heroin. And that is also another way in which fentanyl is basically worse than heroin. And these are very important differences to keep in mind because it is these deficiencies of fentanyl that open a space for the emergence of new adulterants or even new substances. The rise of xylosine and even the temporary rise of meth can be largely explained in relation to those deficiencies of fentanyl. Not the fact that it's more potent, the fact that it's a worse drug. So this is one of the first conversations that I had with a person who uses opioids in Philadelphia that kind of began to help me realize what the specific characteristics of tranq were as opposed to fentanyl and heroin. And as you see, the first thing that this person talks about, Tom is his pseudonym, is fentanyl's deficiencies. That's the first thing that he talks about when he begins to describe tranq. So he said to me, fentanyl is such a short-lived high that the high, it's a good high, but it's so short that the knot 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 the heroin-like legs. They straight put bags out there that are just all tranq. You shoot it, you feel no rush. Tranq fent, there was already a slang term for the combination of xylazine and fentanyl, right? Tranq fent. It's 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 lit a Newport, ran a Newport cigarette. 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? This is such a complex description already in early 2021 of the differences between tranq and fentanyl and heroin that it's mind-boggling how smart and how quick people are at arriving at these kind of complex explanations. So he's already recognizing, okay, so tranq staves off withdrawal symptoms. We can appreciate that, but tranq also makes you feel no rush. That's important, right? If you only consume xylosine, you lose that rush, you lose those first 10 to 20 seconds of euphoria, so you still want a little bit of opioids, you still want a little bit of fentanyl in there to feel a rush, right? So you tranq fent, as you shoot it, you get the rush of the fentanyl, then the tranquilizer comes in, you nod and you fall asleep. And then he goes into a description of this new, basically public health hazard of falling asleep in an awkward position, you can burn a hole with a Newport into your stomach, you can drown in a half-inch of water, women are increasingly concerned about the uptick in sexual assault, men are complaining about getting mugged or robbed when they're passed out on the concrete for extended periods of time. These are the new public health complications and safety complications of the xylosine error. So this slide is just kind of to spell it out, right? So xylosine kind of emerges as a successful adulterant in the face of all these deficiencies of fentanyl, right? It kind of compensates for the problems of fentanyl's short duration of action. It also brings, as people say in Philly, it brought back the nod, it brought back more of that kind of full body embrace that many people had lost with the emergence of fentanyl. Because again, remember, fentanyl was a more local high, right? And for suppliers, of course, xylosine also fulfills important purposes. I mean, I also work with people who sell drugs in Philadelphia, and they tell me that, you know, at the wholesale level, you can get a vial of xylosine for $150 from a vet, basically. This is how most people are getting it. From that vial, you put it in a microwave to evaporate it, you get 14 grams of powder. That's a ton of powder. A gram normally makes two bundles in Philadelphia, that's 28 bags. So multiply 28 times 14, which is the number of bags in every bundle, and that's how many bags of dope you can get from a single vial of xylosine. That's a ton and much cheaper than fentanyl. The problem, though, is that this is actually, and this is kind of like, at this point anecdotal, because I still haven't talked to enough people to confirm it, but xylosine, I think, is ultimately an economic miscalculation on the part of suppliers. It seems as though it's more profitable because it's cheaper at the outset. But people, because it lasts longer, people are doing less of it. Much less of it. When I talk in Philadelphia to people who used to do three or four bundles a day, four times 14 bags a day, they're now doing 10 bags a day. And there's clearly an economic crisis emerging in drug corners in Philadelphia as a result of this economic miscalculation, really. So back in 2021, after this month-long visit to Philadelphia, I went back to the public health literature to see what had been published. There hadn't been that much out there. Again, harm reduction service providers knew about it. They were spreading flyers out. But there were only two very small, very short public health articles in the U.S. mainland about xylosine published by the Philadelphia Department of Health. So my research team and I began to call jurisdictions across the country to try to get as much data as possible on xylosine and to get the word out as soon as possible. And we were able to get data from 10 jurisdictions across the country, from medical examiners' offices basically. And even though the data was very rough, again, our concern was kind of just to get the word out, right? So sometimes we were able to get data from local jurisdictions, sometimes from a state jurisdiction. If xylosine testing is a mess now, imagine what it was like in 2021. A lot of jurisdictions were not testing for xylosine. They still aren't. The protocols for testing vary significantly from jurisdiction to jurisdiction. So take this data with a grain of salt. But it was clear, even in that data, that xylosine prevalence had risen significantly in the country. 0.36% of accidental overdoses in the U.S. involved xylosine. Doesn't mean that xylosine cost it, right? We're going to get to that in a second. But xylosine was involved in 0.36% of deaths in 2015. By 2020, it had been present in 6.7% of them. Already Philadelphia observed the highest prevalence, witnessed the highest prevalence of xylosine in the country. And very importantly, in 2020, Philly's data showed that fentanyl was present in 98.4% of xylosine-involved overdose deaths, right? And this was a very important kind of piece of information at that moment in time because that told us that xylosine and fentanyl go hand in hand, right? You can't go out to a corner to buy xylosine or to buy tranq. What you're buying is dope. And that dope is increasingly a mix of fentanyl and xylosine, right? Xylosine by itself is not available in the drug market. Philadelphia has a really good drug-checking program, and they're finding that the average dope sample in the city is comprised of 2-10% fentanyl and 30-40% xylosine, right? So xylosine is the bulk of the substance that people are using when they use dope in the East Coast now, right? And in fact, just this week, there was an update of this data from the lab that is producing this, and the level of xylosine is actually going up. Fentanyl is remaining steady, but xylosine concentration is going up. What's the bulk agent that they use other than fentanyl and xylosine? Yeah, stuff that they've used forever, vitamin D, mannitol, inositol, this kind of thing. There's more data. I think there's a slide on... I'm not sure if this one has that slide, but there's a slide from the medical examiner's office in Philadelphia that shows that benzodiazepine adulteration falls exactly at the same time as xylosine adulteration goes up. So xylosine basically directly replaces benzodiazepines as an opioid adulterant, as a fentanyl adulterant. This is the most recent data from the DEA. I think it confirms what you all know now from the beginning of Mike's first question. Again, this data has to be taken with a huge grain of salt because of the inconsistency in testing protocols. But in terms of magnitude, in terms of relative magnitude, documenting what regions of the country are most affected by the emergence of xylosine, I think it's generally accurate. It is the Northeast and the South of the country that have seen the greatest prevalence of xylosine. The Midwest is catching up quickly. I think it's going to take a while for the West to catch up, if it ever does. I mentioned all these reasons why xylosine is successful as an adulterant, but there's no question that it has also produced a whole host of new public health challenges and problems. This is now also out of date. This literature is coming out so quickly that every week there seems to be a new kind of discovery related to xylosine. There's now a study out saying that in rats, not humans, in rats, xylosine is actually a kappa opioid, so not a traditional mu opioid like heroin and fentanyl, but a different kind of opioid that generally in humans produces feelings of dysphoria. So actually very different from a mu opioid agonist like heroin or fentanyl. But the public health implications of that, including the relationship between Narcan and xylosine, is now a huge question for public health, for clinical research, right? But xylosine's most prominent characteristic in humans seems to be its alpha-2 adrenergic agonistic properties, and in those cases where xylosine overdose does occur, which seems to be quite rare as a matter of fact, we will need to invent a new reversal agent to complement Narcan, right? Not to replace it, but to complement it. We're going to talk a little bit more about overdose and xylosine. Then the real crisis of the xylosine era is going to be the skin-wound crisis. This is why the work of Michael and Kelly is so important. Not just because people are getting these very gruesome wounds that are very smelly, people are losing limbs as a result of these wounds that go untreated for long periods of time. It's also that the wounds are aggravating the problems of access to healthcare that were already significant before xylosine's emergence. People are increasingly ashamed to go to the hospital or to a clinic because of these wounds. They face increasing stigma in hospitals or in clinics because of the wounds, and this is aggravating, again, problems of healthcare access that go far beyond the realm of just wound care, right? Yeah, we'll get to that too also in a second, and I think that will also be some of what Kelly will have to say. I mentioned the problem with the risk of sexual assault and muggings that goes along with xylosine-induced sleep. Then the problem of xylosine withdrawal and the treatment of xylosine withdrawal is also very significant. Another reason why people are scared to go to the hospital in Philly these days is because they feel like if they go to the hospital to treat a wound, their wound will get treated, their opioid withdrawal will be treated, but their xylosine withdrawal will go untreated, and that is a terrible experience that many doctors are not even aware of, right? I was just talking to doctors at the emergency department at Columbia University. A concept of xylosine withdrawal has not even begun to enter their register, right? And so this is also kind of aggravating problems of healthcare access, the problem of the treatment of xylosine withdrawal. There's really good literature coming out of New Jersey and Philadelphia on the treatment of combined fentanyl xylosine withdrawal. I would be happy to refer you to that literature after this presentation. Yeah, so xylosine and overdose. This is very important actually because when xylosine first emerged, the hysteria revolved around kind of basically conflating xylosine and fentanyl, analyzing xylosine the way that fentanyl had always been analyzed, which is kind of worrying about the increased likelihood of an overdose. Slowly the clinical literature is showing that there doesn't seem to be a strong correlation between xylosine and fatal overdoses. There's a relatively recent study led by Jennifer Love that showed, it used data from nine emergency departments across the country, and it shows that when you look at patients who come in after a non-fatal overdose, who are taken into the hospital, they test their urine. Those who show a positive for xylosine have lower odds of falling into cardiac arrest or going into a coma than those who show a positive for fentanyl alone. Very interesting. Nine emergency departments across the country, tons of data, tons of patients, and so the hypothesis there is not that xylosine has any protective characteristics. It doesn't, right? This is very important. Xylosine is not making things better, right? The hypothesis is that suppliers who are using xylosine are using less fentanyl. So what's going down is actually, or what's becoming less likely, is fentanyl overdoses. I have a question. Are there regular screens for xylosine in the emergency room? Do they do that routinely, or do they just take it? Yeah, there's huge variation. Yeah, there's huge variation. This study is good in that there was some consistency between the emergency departments that were a part of the study, but no. I mean, the fight around testing is still being fought. Not all medical examiner's offices, not all emergency departments are testing for xylosine routinely. Many of the tests themselves are relatively new. This has an impact on the street, though, because, you know, and we had an interesting debate with folks, harm reduction service providers in Trenton about this a couple weeks ago, because the way forward is not necessarily clear. Like, let me tell you by just telling you about my experience in Philadelphia. On-house people in Philadelphia who use drugs are today scared of paramedics, because they consider that they are being too trigger-happy with a Narcan. Narcan sends them into precipitative withdrawal, right? So when you give Narcan to somebody who's not actually having an overdose, you're basically torturing them, right? And paramedics have a sort of tough choice, because they're kind of, the dilemma is whether to potentially save a person or to accidentally just unnecessarily torture them, right? When this happens, when you accidentally torture people, enough times you begin to antagonize the population that you're trying to serve, and that is the situation in Philadelphia right now. People are scared of paramedics. That means that the standard of care needs to change. Most of the time what the paramedics are witnessing is xylosine induced sleep. The first time I saw people passed out on the concrete because of xylosine, I thought I was witnessing an overdose. I had to get out of the train. It was just the train platform. Notice that the person was moving. Realize that her face wasn't blue and that her lips were an or more color before I finally went like okay that's not an overdose. But most paramedics are instructed to just administer these overkill doses of Narcan that are currently the standard of care in cases of suspected overdose and the result is that paramedics have antagonized the population of unhoused folks who use drugs. And so service providers in Philadelphia are now carrying pulse oximeters which is a very quick and effective way in which you can determine if a person is breathing normally that usually in two seconds you already have a proper reading of whether a person is actually having an overdose or not. Kelly here will have a few nuances to add to that because yes there's some complications around the technology of pulse oximetry. It's not it's not foolproof, right? Are we almost running out of time? But so like to veteran service providers I say you have to work on becoming more adept at distinguishing between silazine induced sleep and an actually potentially fatal overdose because if you are to trigger happy with a Narcan you are going to antagonize the populations that you serve, right? Again it's a very difficult kind of advice to give because the other option is that you know you're gonna mistakenly allow somebody to die by not administering their Narcan, right? But but there's no question that public health has to at least consider changing the standard of care to a more diluted dose of Narcan so these overkill doses aren't being administered left and right when they're unnecessary, right? A far more diluted dose of Narcan is usually enough to reverse the fentanyl overdoses that occur now, right? Okay so I don't know if we're gonna have time to go through all the mechanisms. Okay okay so you asked about the wounds, right? Yeah so the dominant hypotheses today are still actually from the Puerto Rican public health literature from the mid 2000s. They were the first to have to to point out that silazine is a vasoconstrictor, restricts the flow of oxygen to the skin, this kill stitch tissue and is usually the way that the wounds initially appear. Once the wounds begin to become aggravated people go into a vicious cycle especially those who are unhoused and don't have access to showers. People begin to inject directly into the wound. Because silazine is a vasoconstrictor, it impedes vein access, right? It kind of has a very destructive effect on people's veins. They begin to, they become unable to inject into a vein and they begin to inject into the wound partly for pain relief, partly because of the vascular sensitivity of the wound, partly because they don't want to develop wounds in another place. This is another thing that people started telling me a month ago when I was in Philly, like if I inject into another part of the body then I'll get another wound there and I want to kind of just cut my losses I suppose, right? So they keep injecting directly into the wound and then people are passing out for extended periods of time in awkward positions, right? The development of bed sores or concrete bruises is another significant factor behind the wound care crisis. I'm gonna have to skip through some of these, I'm sorry. Just bear in mind that the question of silazine withdrawal and the need for the development of protocols to treat combined fentanyl silazine withdrawal is crucial today. Hospitals and clinics are going to lose a lot of patients, are going to antagonize the populations if they do not begin to treat silazine withdrawal and to identify that as a significant problem. Then I have a section on methamphetamine that I think I'm not gonna have time to address but we already kind of talked about that methamphetamine is interesting because its popularity in 2021 also had to do with the fact that it's helped to stave off opiate withdrawal that had become, you know, that have become increasingly a concern in the fentanyl era because of the short duration of fentanyl. People in 2021 told me that meth, like silazine, gave them an extra four or five hours so that they could make more money to buy opioids. It didn't have, of course it wasn't the same kind of mechanism, right, did not have the same physiological effect as silazine. Apparently it was only the first use of meth that allowed you to stay well for an extended period of time. After those four or five hours you needed to do opioids, right. But so the reason I have this slide here is because it's then also crucial to see that the rising popularity of meth is also linked to the deficiencies of fentanyl, right, to all the ways that fentanyl is worse and not better than heroin. Thinking in general about kind of like the public health impact of all these transformations that are happening in the US drug supply, I think it's going to be a complicated story, right. It's not going to be a story where basically every infectious disease is going to become more likely or transmitted more quickly. I think there's going, there's there are a lot of countervailing forces. We do not have enough data to know what the actual impact is or will be, but we can speculate based on the fact, for example, that xylosine lengthens the opioid high, staves off withdrawal symptoms. People are injecting fewer times throughout the day, using syringes less, sharing syringes less, right. That's actually going to have a counterintuitively protective impact on HIV and HCV rates among people who inject drugs. On the other hand, the increasing use of stimulants like methamphetamine, cocaine, and cocaine in places like Philadelphia is likely to have a negative impact, right. It's likely to increase rates of HIV and HCV among on house people who use drugs especially. Then I do like to end with some proposals for the coming era of synthetic drugs. Looking ahead, I am a big proponent of overdose prevention centers. It's very important to keep in mind that in this era, overdose prevention centers are not only going to help prevent overdoses, they are also going to help prevent sexual assault in the context of xylosine, or robbery or mugging in the context of xylosine, because of xylosine-induced sleep, right. I am a big proponent of democratizing mass spectrometry technology. Drug checking programs need to become more generous. There's too many territorial drug checking programs in the country right now that are hoarding their data and not publishing the data quickly and widely so that people know on a real-time basis what the composition of the local drug supply is, right. We need generous drug checking programs. I'm a big proponent of safe supply. People who are dependent on opioids need to be prescribed them. This is a particularly good era for this to happen, I think, because for once the street supply is almost universally described as terrible. People don't like the combination of fentanyl and xylosine. Safe supply would have more appeal now than it would have ever have had, say, in the era of heroin. When I lived in Philadelphia, heroin was incredibly pure. People were really happy with a very cheap, pure heroin that they could get on the street. Safe supply back then wouldn't have been that appealing. Now it really would be, right. So this is, I mean, it's something important to keep in mind. I'm also a big proponent of the need to engage people who sell drugs and not only people who use drugs. We need to talk to people who sell and establish and develop the field of supply-side harm reduction in the United States. I lived among people who sold drugs for four years. I was always surprised that Prevention Point, the big harm reduction organization in Philly, was doing such a heroic, good job working and doing outreach among people who used, but they never once approached my neighbors who were selling. And when I would ask my neighbors, would you be okay, like, having Narcan in your house two doors down from the drug corner, they were always like, yeah, of course. They would have been thrilled to do that, but they never approached. People are just, even in public health, people just assume that that people who sell drugs are evil and sort of profit-obsessed, and this is not the case in my experience. So it is important to find ways to engage people who sell productively and bring them into public health research and intervention. That's it. Thank you very much. All right, so we're gonna switch gears a little bit, and I'm just gonna show you part of module two, which I'm responsible for, which is the wound care. So this is probably some of the more important slides that we show during this training. It's usually a 90-minute training, and it is a basic first-aid training, and most of the people that attend this training are our outreach workers, are the people from our overdose prevention centers, and this, again, has been very popular, particularly in our region, because of the increase in xylosine wounds that we're seeing. So, I went backwards, and in the beginning, we do start with just basic, what is skin? What's the purpose of skin? And then we go into what happens when we have an injury to the skin, and how does the skin normally heal? What are those signs and symptoms of infection we go over? What are those factors that can delay skin healing? Those are all slides we go into before we start talking about xylosine wounds. So we give them a nice foundation, and then we get into talking specifically about xylosine wounds. So, again, as Colleen Fernando explained, it is vasoconstriction. We're cutting off the blood supply. That's what's causing these cells to die, and that's what's causing these, what early xylosine wounds, they actually look like bruises, which people can mistake and think they're bruises. I've heard people refer to them, they think they were spider bites, and so they ignore them. But the problem is, when you ignore them, within a few hours, a few days, they can actually turn into what we're seeing on the right-hand side. And then when we have these wounds, even though they're not initially infected, it leaves room for infection, which we know infection can lead to cellulitis, to abscess, and ultimately what we're trying to prevent is sepsis. So when I got the call in November to say, Kelly, we need some help with these wounds, it's because during the outreach, they were finding people getting their limbs amputated. They lost some individuals due to sepsis. So that was the dire need and why they wanted us to come out and actually do this kind of wound care education. So again, back to the tranq wounds, the best thing that we can do for these tranq wounds is simply putting some petroleum jelly or A&D ointment when we see that early stage. If we can keep wounds moist, that is the best condition for wounds. So simple, cheap A&D ointment, petroleum, a piece of gauze, and keeping it covered can prevent it to going into that stage. So that simple is the most important part of the education. Oh, Michael gave a warning. Warning, we're going to show some xylosine wounds that are pretty graphic. And so again, they start out early. They start to what looks like scabs. Sometimes these actually will pop out and leave scars, but over time you can see if the person continues to inject that these wounds can not only just appear at the injection site, they also can appear in other places. So even if I inject here, I can get wounds on my leg or the other arm, okay? And again, they can become very extensive and the more we have that open skin area, the more chances that that wound can get infected. So what else do we cover in these wound care education classes? We just talk about the basics. Again, we're not telling people to do anything that's out of the scope of their practice. This is anything we would teach the community. Just simply just washing your hands, you know. We take that for granted. Here we are doing wound care and we're introducing bacteria because the hands are dirty. Using hand sanitizers, washing with soap and water. We go over how frequently to change the dressings. If there's more drainage, you're going to change it more frequently. How to dispose of the drainage, the dressings, rinsing the wound, keeping the wound moist, which we'll get into a little bit later about how do we keep those wounds moist. Making sure we're doing proper wound care. If we're putting the dressing on too tight, we can actually cut off the blood supply and cause more harm. If we're using the wrong products on the wound, it can cause more harm. And then just reviewing. Most importantly, I tell the individuals, because we're usually educating outreach workers, but it's important that they also give the same information to the individuals they're coming across during their outreach. Let them know the signs and symptoms of infection. Let them know. Teach them how to do their wound care themselves because you're not going to see them all the time. So when we give them these kits, they'll know how to use those kits properly. And I can tell you it is working. And this is just what we developed as part of the wound care kit. In our study, we had two different kits. We had a prevention kit, which is ideal. We want to prevent the wounds from occurring to begin with. But we also had a separate, more detailed kit in case they already had a wound. So simple things we put in prevention kits. Just the soap and put soap. If we didn't have soap, we had these hand sanitizer wipes because we know that everybody doesn't have access to running water. We had gauze, normal saline bullets, or they can be sterile water so they can rinse out the wounds. Sanitizing wipes, alcohol pads that were used to wipe before they inject. And then band-aids. And we put it in a Ziploc. At first we had these paper bags, but we realized when people were in-house, they got wet, they got destroyed. So we just bought simple Ziploc bags. Classic Ziploc. Now if the person had a wound, then we had, again, a little bit more supplies including some gauze, something to keep the gauze in place, which is called Coban or, where is it, Zero Form Dressing was another one. And then we'll talk a little bit about honey. That was the strongest thing we had in our kit, was medicinal honey, Manuka honey. Manuka honey works very well at getting rid of necrotic tissue, especially because we can't give them anything that requires a prescription. However, there are some caveats to the honey. My colleague who is in a warm region, honey does attract bugs. Okay, so although it's great at destroying that kind of dead tissue, it does have its caveat that it does cause, in some situations, you don't want to use it because the wounds can get infected with ants and different bugs. And then this is the key to the wound care that we basically teach. We teach it as just three different steps, or I should say four. The first is obviously washing your hands, cleaning the wound. But then it's just putting, what's that contact layer? What's that first thing that you're gonna put on the wound? And that depends on the type of wound. And we do go over different types of wounds. We go over healthy wounds, which means we want to continue it, it's healing fine. And then we go over the unhealthy wounds, which is what we call the sloth or necrotic tissue, which impedes healing. That is when those wounds get stuck in an inflammatory stage and they won't heal. So our goal with those wounds is to put the honey on those wounds or put the Zero Form, which is just a thin dressing that has petroleum jelly and another substance which helps it to heal. If the wound is healing fine, good old petroleum jelly or A&D ointment. That's our first layer. Then we need to keep that ointment in place. So we tell them just put a piece of gauze on it. Simple piece of gauze to keep that dressing in place. And if there's a lot of discharge, we tell them to use a little thicker pad. It's called an ABD pad, which absorbs a lot more discharge. And then lastly, that'll fall off. So you got to wrap it to make sure that all stays in place. So we tell them, individuals, you can use this co-band, which is a wrap that wraps on itself. You can use this Curlex. And if people don't have supplies, cut a sock. Put a clean sock on the arm. Put anything that'll secure it that people have that is clean. And that's the basics to the wound care that we teach all the individuals. And then other, we talk about other situations when it comes to wounds. If it's dry, the last thing you want to do, if somebody leaves their dressing on too long, what's gonna happen if they rip that off? Oh, I see people cringing. They're gonna rip it off. They're gonna rip off all that nice new tissue that's growing over there and cause more damage. It's gonna bleed. So we say, if you're going to do wound care and that dressings dry, just wet it. Take that same saline bullet or the sterile water, wet it, and then take it off. Okay. So it needs more moisture. If the wound is dry, also add a little bit of ABD ointment or petroleum jelly. If the wound is too wet, meaning there's a lot of drainage, we teach them, you're gonna have to change the dressing more often. Make sure you use a thicker pad that's gonna absorb that drainage. Use a baby diaper. Use a maxi pad. Anything that is really good at absorbing. If the wound is infected, you got to get rid of the bacteria, plain and simple. So what's the way to get rid of the bacteria? Huh? Antibiotics, right. So this is someone we really want them to seek medical care, because they're really gonna need antibiotics. And then if they have that dead tissue we were talking about, we tell them, if it's the right situation, to use that manatee honey, which causes a body to kind of autolyse and get rid of that dead tissue. Or preferably, go and get that removed by a medical provider, which they can cut out or they can put enzymes to dissolve that necrotic tissue. And then lastly, we go over just the do's and don'ts of wound care, because inevitably, somebody's gonna say, well, can you just wash it out with hydrogen peroxide? That's like the number one thing people always want to say, because growing up, that's what we did. We saw the bubbles, you thought it was doing something. It's actually causing more harm. So I would say that's probably the one thing that I have to kind of tell them that, no, we don't do that anymore. Or they say, use iodine or use alcohol. So that's one that I would say is probably the most common one that we want to make sure people know, because it can actually destroy the new tissue. And we talked about moistening when it's wet, being careful when you remove the dressing. Obviously, these are people in harm reduction are really good at establishing rapport with individuals, providing privacy, and then just, again, knowing that you're taking care of a person and not a wound, just tips that we include in our training. And then the wound care does work. This is actually my colleague who was doing wound care in the Maryland area, and this was a woman that all he used was the Xeroform, and that was a simple dressing that has petroleum jelly in it. And it took a long, long time, but over time, you can see, even though all the books and wound care specialists say it should not work, it actually does work, and this proves that it does work. So over time, that wound was able to heal, because as we know, a lot of these individuals are not going to seek medical care because of the stigmatized care that they receive. No, still continue to use. Unfortunately, she did die from an overdose, and she actually lost her other hand. But this is to show that, you know, treatment does help. It does take time, but it can work. All right, and I think that's all I have. So I guess it's time for question and answer. Thank you. So we could take questions on anything and everything related to xylosine, wound care, overdose. There's increasing use of smoking as opposed to injection, especially on the West Coast. In the East, it hasn't taken on as much. I mean, I will let some folks in the East Coast, definitely going up. I saw some of it in Philly. Interestingly, in Philly, it's kind of racialized. It's Latinx and black folks who are smoking before the white folks turn to injection. I'm talking about the on-house people that I work. I mean, I know it sounds silly to put it like that, but a lot of people are saying that they switched back to smoking because it helps prevent wounds. In fact, the people who smoke that I spoke to in Philly didn't have significant wounds. They did talk about their regular wounds taking longer to heal, and maybe our friends here have some explanation for that. But they didn't have the kind of very gruesome wounds that the folks who were still injecting did. I can face the crowd. I'm Sue Pinch in FEMA, and I do homeless outreach in Boston. And I was saying that amongst unhoused folks, the smoking is becoming much more popular. And at a needle exchange where we have pipes for smoking, that the pipes are a lot more popular. And people are not complaining about lack of effect or significantly different effect between the smoking and the injecting. But I haven't kept an eye out for a difference in wound prevalence. And people who inhale are also complaining about respiratory problems and wounds in their respiratory tract. So I'm from Baltimore, and we started to see quite a bit of these cases in the emergency room. It initially was a surprise to the people in DD that they did not know what they were coming up with. And one of the things that I want to address or ask you is about the vital signs instability. Because some people were having hypotension, bradycardia, the opposite. They wanted to use clonidine, for example, as a substituting withdrawal. And I don't understand much about the withdrawal from salicine, but they wanted to use clonidine. But some people were hypertensive and bradycardic. So I was seeing this combination of crazy vital signs with these guys. Yeah, yeah, absolutely. This is one area where I would refer you to the emerging literature. There's an article by Rachel Herman Dupre that details very carefully various symptoms related to xylosine withdrawal, the rebound effect after xylosine discontinuation, and protocols that are used to treat those symptoms. They usually involve some kind of substitution therapy using clonidine, using dextromed. I'm not a clinician, so that's why I'm saying I'm going to refer you to the literature without giving you the details. Because, again, that's not my realm of expertise. I don't treat. Yeah, there you go. Withdrawal. So yeah, we don't have a lot on, as everyone knows, on xylosine withdrawal. I mean, the science just isn't anywhere near that yet. NIDA did a panel in June, I think. It's on YouTube. I have a link to it, where they had various presentations from preliminary research that had been done. And one of the topics was on withdrawal. They were observing it in a hospital setting. And I think they ended up with a sample of 73, where they had people who had xylosine positive and were going into withdrawal. And they were trying to describe the symptoms, the common symptoms. And the primary conclusion of it was that they varied significantly. So I built that up, all to say that we don't know. A lot of it is case studies. There was another physician who did a case study on someone that they had managed through xylosine withdrawal. And it was an 18-day stay in the hospital with a litany of medications. A lot of people think that the best that we have is to borrow from what we know about Klonidin, because it's part of the same drug class. But the research on withdrawal from Klonidin is from probably the 1970s. And people didn't really directly research withdrawal from Klonidin. They really just, it was a byproduct observation of other research. They weren't setting out to design studies that were doing that. So we don't have a lot of information on withdrawal. I don't know, folks, anyone in here who's managed it themselves probably is on the cutting edge just as much as the science is at this point. I mean, that's the truth, which makes our jobs a lot easier up here. What's the reference you used? Was that a case of Aaron Dupre? Oh, OK. It's a case report in Journal of Addiction Medicine. Dupre, D-U-P-R-E. Yeah. Yeah, it's a case study. I think it's one patient, 18 days, and a litany of medication, and how they sort of introduce titrated and move through. Yeah, and I'm sure that's not a protocol. There's like three different outlets where they get that. It's like buprenorphine, they do phenobarbital for a while. Yep. They've got dexmedetomidine for a good part of it. They do ketamine for the pain control, as well as galapentin. With cozannidine, you got the cozannidine. Yeah, and cozannidine. It's very multimodal in the wound care approach, especially. And then I think afterwards, they still have to ask questions on, well, can they really engage with their addiction psychiatry and their recovery afterwards, because of the complications from the wound care. It's pretty involved, especially 18 days and that many different medications and papers they had to manage. Right. So we can't imagine that becoming a protocol, because it would just be so inefficient. But they were sort of building the plane or flying it and figuring things out. Treating symptoms, basically, is what you're doing. You're treating symptoms that are coming up. So yes. So the question I had was, there's a lot of talk about fentanyl is very lipophilic, and when people have this chronic use of high doses. Can you use the microphone? We can't hear him, is that all right? It's all right. Oh. Yeah. This is a question that probably other people will have, too. So the talk is that we know that fentanyl is very lipophilic. And in folks that have a lot of chronic use, they're developing enough in their tissue so that it almost is starting to act like a long-acting. It's almost appearing to extend its half-life. So you're saying that it's very short-acting. We know fentanyl is very short-acting. But how do you make sense of that? So folks are, for example, there's a lot of incidents of folks not going into withdrawal as soon as you would expect. Even taking days sometimes to go into withdrawal after their last use. I don't know if that's true. I haven't seen that myself. But is it because of the lipophilicity? Or is it because the xylosine is there, which is extending that withdrawal-free period? You know what I'm saying? Have you seen this? Have you teased that apart yet? I guess that's what I'm wondering. Yeah. Yeah, no, that question about fentanyl being lipophilic and staying in the organism in different ways, I think is very interesting. And right now, for me, it's a research question. I definitely don't have any answers to them. In Philadelphia, it seems pretty universal that people say, yeah, I need three days before I can really start taking buprenorphine. I can only use a microinduction. There's a panel tomorrow on microinductions. And I'm really looking forward to it. I think it's very important. But it's going down. Yeah. I mean, a lot of things are happening at the same time. One of the reasons why people are switching to cocaine, no stimulants were popular, really, in Philadelphia when I lived there. It is only with these recent transformations that meth really became a thing and that even cocaine really became a thing of daily use. Back when I lived in Philly, it was kind of like a thing you did on a weekend when you had extra money to do it. Now people are doing it because they say that there's so little fentanyl, even in the dope, that they're not getting a rush at all, even from the fentanyl. And so they're doing cocaine because it's the only thing that gives you a rush. It's the only way to get some of that euphoria back. And so at the same time that you consider the question concerning fentanyl's lipophilic characteristics and its relation to withdrawal or detox, you would also have to consider the fact that the amount of fentanyl people are using is going down, right? So I guess it's a complex research question, and I'm sorry that I don't have any answers right now. Some of the folks who are actually clinicians might have a better response. I'm a non-clinician that has a response. How are you doing? Yeah, so we have, and I run only two OPCs in the country. So we have 4,200 participants, 107,000 utilizations in two years. So there's your answer for me, right? There is a very quick turnaround. I just had a conversation with Jonathan Mermin Jano from the CDC who visited us yesterday. We were talking to a participant in the OPC who said in the 80s, he would use dope, euphoric. I'm sitting here just like, I feel like I'm back at work. This euphoric experience that lasts for hours. Back then, people had to eat to use heroin because their bodies needed food to sort of feel good and process, which is why they look different, too. So he was talking about how different it was back then. It would last for hours. It was longer. And of course, they used a lot less. And with fentanyl, it's hours. It's on. It's on for a little while, and they have to come back. So just think, 4,200 participants in just two sites utilizing our sites. We're only open. We just started opening till 11.30 PM. We were closing at 8 PM, opening at 9 AM. And we saw basically 50,000 utilizations a year. I mean, that's a lot. The impact then on the community is 100,000 times, people didn't use in the community. They used inside with us. And the other thing I just wanted to say, because you guys covered some of this, is around the overdose. And you talked about Narcan. So of about 1,200 overdose interventions we've had in our sites, we're only using naloxone, 0.4 milligrams, not 4 milligrams, 0.4 intermuscular injectable. We're only using it 18% of the time for over 1,000 overdoses. So that's the other thing, right? Oxygen protocol. There are so many other protocols that people need to learn and learn how to use them. So even on our outreach teams, which you've worked with, and I appreciate you for that, we have oxygen on our outreach teams. And everybody wears a pulse. Everybody, everywhere, and our staff. So the approach is very different. And that's the biggest thing, I think, in our model, is what we're teaching people across the country, is how to respond to an overdose very differently. Unfortunately, EMS doesn't want to pay us to teach them how to do it correctly. So our staff are trained to respond to an overdose at the level of an RN. Something, I don't want to share this as being too proud, because I think as Overdose Prevention Centers, we put ourselves up against this number. But in two years, we've had zero deaths in our sites. And thank you. So I promised my team we wouldn't talk about it so much, because if we have one, then we're like 99.99% great. But it's terrible, right? But it's still something we're proud of. And what we know is no one ever has to die of an overdose. So thank you. I had a question about, I thought conventional wisdom was that fentanyl was cheap. It was readily available. So why is it that you're seeing these dosings that people are getting with a very low concentration of fentanyl? Has something changed? Going back to COVID, you know. The xylosine is much, much cheaper now. Whole cell up is cheaper. OK. So it's just simply that xylosine is cheaper. But has the cost of fentanyl gone up? In Philly, it varies a lot. But yes, generally it has gone up. For the people who sell that I know, it has gone up at the wholesale level, yeah. And I don't know what the explanation for that would be. Yeah. Hi there. I'm Michelle. I live in Iowa. And what I really appreciated about this talk is you talked a lot about things that we can't find on a PubMed search. Like, this is how we got here. This is why we're seeing what we're seeing. This is why people say they use. And we learn a lot from our patients. Do you have a good resource for us that's in the public domain on how we can best understand what's in our community's drug supply and where are the trends really going? I can make guesses based on what patients are telling me. But is there any place that we can go to do a kind of search like that that's not on the dark web? I mean, I am happy to send you some articles if you email me or we can, when we share the slides, do we share the slides to the audience after this? Yeah. Yeah. And I think this is a lot of variation in jurisdiction. Some places like Philadelphia have really good drug checking programs. Others have drug checking programs that are not publishing the data. You know, so it depends on where do you live. But I do encourage people, like I think everybody's next grant should be to set up a really generous drug checking program using full mass spectrometry. If you are managed to get, like I, you know, I know chemist friends, obviously IRB is always a problem, but mass spectrometry is the most basic thing for a chemist. It takes a few hours. That's the toughest of substances. It shouldn't take a month to get the results back. You could potentially contact a crime lab in your particular state. I mean, I'm from Wisconsin and I happen to be in the control substance board of Wisconsin. So I am well aware of what some of these, like, drug use trends are based on reports we get from the crime lab. I'm sure each state probably has their own. So that would be a place to start. I don't know if you've ever checked Arrowhead out, but that's another kind of, that's sort of a nonjudgmental forum kind of place where people can talk about their drug use. And a lot of times people will openly discuss what they're using, where they got it from. And so it gives you kind of a real time discussion for your particular area. But it's interesting because it's not, there's a lot of really well informed people, but it's not people who are really critical of their drug use. It's more just kind of an open discussion. So a lot of times when you look at Arrowhead stuff, it's a whole different, the tone of it is completely different and it's people that are just openly talking about their experiences with whatever drug. And so you get a lot of, you get a lot of real time information on Arrowhead, at least from my experience. And to piggyback that, I have a question. I'm Liz. I'm from Atlanta. And so the question is how, and for clinicians in the room, everyone in the room, how are y'all testing for xylosine? Are you testing, our send out doesn't have xylosine in it. Have you asked your send out companies to include it? Are you, are you using that as a resource clinically and then for patients? So I've heard varying degrees of xylosine test strips being effective and, and obviously in some states they're paraphernalia. So we can't give them to patients because of stigma and other issues. So how are we testing for this? Anyone want to share? How are you testing for xylosine? Xylosine test strips? How effective is the xylosine test strip? So Brandeis, which is a local university in Boston, is actually going around and testing the local drug supply and they have independent funding. And they said it's like, it's pretty close, the test strip sensitivity to what they send out. They did a little bit of research really quick. They found fentanyl, cocaine, para, fluoro, fentanyl, xylosine, caffeine, gabapentin, acetaminophen, methamphetamine, levamisol, some ibuprofen, all kinds of other things. There's a test done out of Philadelphia, out of Philadelphia, Philadelphia. There's a test on a Philadelphia lab on the xylosine test strips. I think the final results, I can send you a link to it. Final results like 91% accurate. There's really, the whole point of it was basically that all the, the, the rumors sort of in the beginning that they weren't that effective, weren't that accurate or not true. It was an independent lab. It wasn't the BTNX who does the strips. So that's pretty good. Where I am in New York, we can use them in New Jersey. They're paraphernalia. I know you mentioned that. That's one of the things that I think has to change real soon because that's kind of ridiculous. But I mean, and they're no different than fentanyl test strips in the general operating principle. Hi, thanks. Ayanna Jordan from the best place on earth, Harlem, New York City, stand up. That's really just so, I just, I really love this talk and you brought it home. So thank you so much. I am just sitting here just infuriated because one of the themes that went throughout the talk was, and I get it, but like we have folks that need help and for all of the reasons they will not interface with the traditional healthcare system. And I think we have to do better. Like what are we doing here? Sam is doing amazing work and yet I can't, as an addiction psychiatrist, use resources to train my folks to go work with them because we can't use our dollars for a harm reduction, right? So what do we do? And so yes, I'm with you, safe supply, I think it's ridiculous in this country, we don't have safe supply. I think it has a lot to do with the identity of people who use drugs being minoritized, all those things. If you're black and brown, we really don't care about you. But like what I need to hear from you all, help me think together. What is the advocacy points? What should we be doing as physicians to work alongside community who's already doing the work? Like I was, I need to take your wound class, right? I'm a whole doctor and I'm still over here putting on hydrogen peroxide. Like what do we, like the bubbles are not working, right? So I own that fully. So it's like how can we help in the medical profession to really put more pressure on our research colleagues, NIH specifically, because we all, for those who pay taxes, you know, they get money to do the funding. But also what a type of, what does advocacy look like for institutions, for medical centers? Do we need like zylozine teams? Like I'm really trying to think about projects that we can employ for our young people to do because ain't nobody coming to save you Otis. Like these institutions are not going to help us, right? Our community. So what can we do to advocate in a real way? You have so many addiction docs here. Okay. I'm done. Wow. I think you've made some wonderful points. I'm Virad Deshmukh. I'm from New Orleans and I know there are some hospitals, especially in the East that are starting to actually have protocols put in. So there's one in Philly, I can't remember which one off the top of my head, but they've talked about, you know, having immediate access to ICUs so that they can debride these wounds, that they can have treatment under anesthesia, that they can have burn specialists look at these wounds. I think that appropriate wound care at all levels is going to be paramount because ultimately wounds are often, just as much as we talked about the stigmatization, there's a good component of that becomes a massive barrier to care. Especially with our homeless population, untreated wounds can often become the hurdle for them to get into a place to live. Just as well, I actually had this question for y'all, but did you guys notice anything about patient attitudes towards the wound care vans? You mentioned like going into the hospital, you mentioned EMS, but I know a lot of communities are rolling out these wound care vans. I'd imagine those attitudes are a lot different, but that was just one thing that I was thinking of when you were talking. I don't know if Fernando, but I can tell you we have wound care vans, we call them show vans in New York City. And let me tell you, they're amazing. And you know why they're amazing? Because they provide sensitive care to this population. And that word spreads, so these individuals are very willing to go to those vans. They get excellent care in those vans. We just need more of them. There's not enough of them. It's from health and hospital system. Yeah. Hi, I'm Lou Treveson, and I'm an addiction psychiatrist at Yale and at Creighton in Omaha. And I just want to say that, and to answer your question, I think I have an answer for you, is we need more presentations like this in the medical community. We need to hear from people who are out in the street and working with patients. I mean, obviously, we're supposed to work with patients, and we do. But when you're in the emergency room, and I shouldn't really name this, but when you're in the emergency room, you're an ED doc, and you've got 20 minutes to see somebody and to get them going, you don't deal with this stuff. And I'm running into that these days in what I'm doing. And it also goes back to the concept of what's cheaper. Is it cheaper to do this than not? All the way down from whether it's fentanyl and xylosine versus heroin versus just fentanyl, back up to whether it's a private equity group that owns the staffing people that run the ED and the place that you work. So it's the profit motive and the fact that doctors need to listen more to people who are out in the street, as well as the patients. One second. Thank you. Yeah, I just wanted to add very quickly to what you just said. The wounds and the responses to the wounds reminds me of late 80s, early 90s, carpose sarcoma for people living with HIV. I was only like seven or eight, so I wasn't working then. I heard about this. But really, right, there's that stigma attached to what shows up and how much are you willing to show people. And there's a reason in my head, and I have a theory I want to share with you guys first. Why we don't have xylosine in New York City like we have in other places. It's a very good reason. And my history and involvement in organized crime is what feeds me that theory. You want to hear it? Yeah. Okay. Why not? And you touched on it a little bit earlier. If you look at the impact of xylosine throughout the, let's say the East Coast is the best place to look at it. So Maryland, right, the DMV, South Jersey, a little bit more about Jersey. Let's forsake, my team yells at me when I say this, but kind of skips New York City, goes to Connecticut, right, and then gets large again going up. So my theory around why not New York City is because when you talk about the drug dealers is that New York City still has an organized crime. And xylosine is bad for business. So it's not as organized as it once was. But to me it's that simple. Why would I allow this to enter my supply? So it tells you that all these other cities don't have any organization. And so should we publish that or something? How do we make this happen? But to note that I think it's interesting that I only learned recently is that xylosine disappeared largely from Puerto Rico, which is a huge historical transformation. And the theory there is that our harm reduction service providers did supply-side harm reduction, spoke to suppliers, and managed to get them to stop using xylosine. There could also be some- Very quickly, as a person from what he thinks known as Puerto Rico, when this was in Puerto Rico, we didn't discuss it at all. Remember that. Remember that. People in Puerto Rico were having wounds all over their body. There wasn't one conversation about it. Typical response to black and brown and poor white people in this country. I'll say it one more time, because I'll be dying later for this. And I know we can go on and on with this conversation, but we just want to say thank you.

Xylazine

heroin adulterant

drug users

fentanyl substitute

health challenges

skin wounds

sexual assault

muggings

sedative effects

accessing healthcare

wound care

overdose prevention

public health