Hi, everyone, we'll get started in just a few minutes, but as we wait, feel free to let us know who you are and where you're joining us from in the chat. All right, good afternoon, everyone, and welcome to today's webinar titled What Now? of Zylozine in the Age of Opioid Use Disorder, Guidance for OUD Treatment Providers hosted by the Providers Clinical Support System Medication for Opioid Use Disorder Project in the National Council for Mental Well-Being. My name is Rachel Palikde and I am a project coordinator here at the National Council, and I will be moderating today's event. So, before we dive in, just a few housekeeping items to cover. Today's webinar is being recorded and all participants will be kept in listen-only mode. We will have an opportunity to ask questions toward the end of the webinar, so we encourage you to submit any that you have via the Q&A box located at the bottom of our screen. The recording and slides will be made available on the PCSS MOUD website within two weeks. And within 24 hours of today's session, you'll also receive an email from the address on your screen with evaluation and certificate claiming information. This is a note that this presentation is prohibited from promoting or selling products or services, and rather the goal of PCSS MOUD is to increase healthcare professionals' knowledge, skills, and confidence to provide evidence-based practices. All right, and I'm pleased to introduce today's presenter, Daniel Rosa. Daniel is a senior medical director at Acacia Network, as well as an ER physician at Philadelphia VA Medical Center. Please see the chat to reference Dr. Rosa's full bio. Dr. Rosa, we are so thrilled to have you with us today. You can see here on the screen a disclosure to our learners regarding AAAP's commitment to unbiased and evidence-based education. And today our educational objectives are as follows. We'll discuss the prevalence of xylosine and its relevance to opioid use disorder, describe medical issues associated with xylosine use and effective strategies to address them, and we'll also examine treatment options for xylosine use. At this time, I'll hand it over to Dr. Rosa. Thank you, Rachel. What a kind introduction. I appreciate it, and I also appreciate, of course, that you're going to manage everything from your end because my ideals are zero. Thank you for that. I just want to reiterate that I was born broke, I grew up broke, and I'm slightly less broke now, but I have no financial disclosures to make at this time. And basically, greetings from the South Bronx, the home of the New York Yankees' Aaron Judge, and also the Bronx Zoo, Fordham University, and the birthplace of hip-hop and breakdancing, which is an Olympic sport now. That last part, I was forced to mention by my kid. Necessarily proud of that aspect, but I was honored, actually, to present on this particular topic about a year ago to the Addiction Committee of the National Mental Health League, and this past year, I just did a brief presentation also at NACCON 24 in St. Louis. So I started out the presentation, I started out with a question to the audience that if anyone had ever personally or been witness to a naloxone rescue in a suspected drug overdose, almost the entire audience, if not the entire audience, raised their hands, yes, they had either personally, and then I followed up that question with, was it successful? And the entire audience joyfully put up their hands, and I said, okay, wonderful, it was great to see so much happiness in the room. I said, but what if the naloxone rescue wasn't successful? And again, a look of curiosity from the audience, and just keep that in mind as we go along with this presentation. Next slide, please. This is me, and this is my setting. I work at the Acacia Network here in the middle of the South Front, which is just a mile or two away from where I was born and raised. And I'm always kind of like at a loss to describe what it is that we do here and what services that we actually offer. It's so much easier for us to just describe what we don't offer for the community. We have SAMHSA-certified methadone OTPs along the Northeast, here in the Bronx and points, Brooklyn, Albany. We have mobile units. We have outreach, harm reduction, and just so much, HIV services, residential services, everything that we can possibly imagine to actually put in place to help the community. The communities that we serve are usually marginalized, low-income populations with a heavy emphasis on substance use disorders, mental health, behavioral health, and harm reduction along the Northeast. Next slide, please. On the weekends, I still…you have to…of interest is that I suspect that the organizers of this particular event probably were scouring the nation trying to find someone who was necessarily very, very expert in the human use of xylosine. And they couldn't find anybody, so they settled on me. I've been an emergency physician for over 25 years in academic emergency practice for 20 years in New York City, and currently I practice out of here. And the reason that they settled on me is because, again, this is such a broad topic, but very little is known about xylosine. So, I see what, you know, these things frontline in the emergency department, and then I follow them up here in the office here in the Bronx. So, I'm not an expert, but the fact is that I don't think that anyone is. And that brings us to the first poll. How familiar are you who are tuning in with xylosine? A. I haven't heard the term before. B. I've heard the term before, but don't really know anything about it. C. I know some things about it. And D. I know a lot about it. I'll give you a second to kind of like go through that. All right. And if, here we go. And now, the folks that I, okay, I'm glad to say I know some things about it, seems to be. That's the one that I would choose. I know some things about it. I know a lot about it. I would imagine that you're either a veterinary anesthesiologist or toxicologist, because the only, it's not a human drug, or it was first created as a human drug, but it was far too sedated, found to be far too sedated to be used in humans by the German. So, they, about 10 years later, then it's solely used to sedate and their procedures of cats and dogs and horses and what have you. And one other reason that I think that they probably chose me also, like I said, emergency physician, primary care, you know, I'm also a certified provider, expert for the past 15 years, is I'm Puerto Rican. I know, I know, since when is being Puerto Rican a credential? But it probably isn't. The fact is that it might be relevant as we come to this particular presentation. My introduction to xylosine was, I was visiting Puerto Rico in 1998. And as, towards the tail end of my trip, I heard that one of my cousins, unfortunately, had been incarcerated in a prison there called El Paso Blanco. And he had a known history of intravenous drug abuse. And I asked him whether he was still using while he was on the inside. And he says, no, not really, because all they have here is Anastasia de Caballo. And I go, Anastasia de Caballo, which roughly translated is horse tranquilizer. I didn't, I didn't pursue it. But about 10 years later, when I first started here at Acacia, I started seeing these young men who were basically presenting, they were, they had one thing in common, which is that they were native, just recently arrived from Puerto Rico. And they had these strange, some of them had these strange ulcerated lesions. And one of these lesions looked very familiar to me, because I had seen it in my cousin from 10 years before, in 1998. Next slide, please. So the curiosity got the best of me, because the patients that I was seeing here kept saying, oh, this is, these, these came from me using Anastasia, Anastasia. And again, I remembered that my cousin said that he wasn't using stuff, because the Anastasia. So it sent me on this kind of like, just trying to figure out what's going on with this. I did a little bit of research. And I found that there was very little written about it, except for a couple of articles, you know, from Puerto Rico. This particular article drew my attention, simply because one of the authors was Vargas Vidal, Jose Vargas Vidal, which is, he's relatively a hero out of Puerto Rico, and in harm reduction, local politics, as far as advocacy was concerned. And they did a study, next slide, please, of going from place to place, different municipalities in Puerto Rico, collecting needles. It was a needle exchange, but they were testing them for all sorts of different drugs. And they found that from 2005, 2008, when they were actually examining these needles, that 37, almost 40% of the 37.8% of samples were positive for xylosine. 90% of the samples were from people that were speedballing, which is, of course, the cocaine heroin, but that were testing positive for xylosine. And these lesions, they made specific mention of these lesions, that there was a great, much greater, what I say, visual lesions in these particular individuals than people that were non-users. Next slide. So, now we really are fast forwarding, but the fact is that it really was something to see, as I kept, you know, basically seeing patients in my office here that were presenting, and the folks that were recently arrived from Puerto Rico. And from as early as 2006, in certain communities in Philadelphia, xylosine was actually being detected. It wasn't broadly being tested for what I understand, but there was some kind of studies and observances, especially wound care individuals that were testing for xylosine. And they saw that there was an increase of population that were actually testing positive for it. And from 2019 to 2022, xylosine detection in drug samples more than doubled in 30 states. Of course, the Northeast was necessarily the highest incidence. Let's go on. For Maryland and Connecticut also. Next slide. Now, no one knows exactly what the prevalence and the incidence of xylosine really is. We certainly know that in Philadelphia in 2021, a nice study detected that 91% of the samples, almost 100% of purported heroin and fentanyl also contains xylosine, making it the most common adult in the drug trade. And, you know, as far as research is concerned, they're having an enormous problem even trying to do research on this particular drug, simply because there is no ICD-10 or whatever, as far as a code for xylosine use. They basically, xylosine is actually merged into, as far as code is concerned, with anti-seizure medications and sedative, hypnotic. So as far as research is concerned, they're having a heck of a time trying to track and, you know, basically doing retrospectives on this, as far as xylosine-related drug tests and xylosine use is concerned, simply because it's hard to track down. There's no ICD-10. So it's very, very difficult for them to track how xylosine contributes to the overall deaths, overall overdose deaths across America. However, in Philadelphia, we certainly know that there is a high incidence of the adulteration there. Next slide, please. Well, obviously, it is a national issue because Dr. Rahul Gupta, who is the director of the White House National Control Policy, and basically all drugs are, he actually made mention, okay, and actually had a press conference and put out something making it xylosine as an emerging national threat. Now, how was this so important? It really was because it's the first time that a drug or a drug combination, fentanyl and xylosine, had been designated as such. And about a month later or so, he actually did an op-ed in the New England Journal of Medicine, describing the dangers of xylosine use in the United States. And this basically came after a careful review of xylosine on the opioid crisis, and basically letting us know that it may contribute to a growing role in overdose deaths in every region of the United States, not just the Northeast. Next slide. And in that article in the New England Journal of Medicine, this is basically something that we saw, which is a remarkable uptick in drug poisonings as far as in which xylosine seems to be related. It's the first time ever, like, more than an illicit drug designation. Next slide, please. And you wonder, why is it that the traffickers, the people, the traffickers are actually putting xylosine into fentanyl, which is deadly enough, as we know. But the fact is that it appears, well, first of all, it's cost-effective. I mean, it's profitable. And you take a small amount of fentanyl, and you add xylosine to it, which is not a controlled FEA or DEA medication, because it's a veterinary medication. Once you add it to fentanyl, you can expand now the amount of fentanyl that you consume. And this is the next slide, of course, fentanyl. So if you look at the trajectory of that last slide of the xylosine, and you look at this particular trajectory, it leads to two things, obviously, okay, that fentanyl and synthetic opioids and their analog, they have the same trend. But the fact is that it's very rare to find xylosine that's not actually mixed with fentanyl. And that is something that we've been deliberately trying to keep track on. So if we can't track the xylosine, at least we can track fentanyl, because there are multiple ICD-10 codes for fentanyl-related deaths. Next slide. And just to go through this very, very quickly, and I really want to make mention, okay, that why is xylosine relevant to opioid use disorder? Because we're beginning to detect it more and more across the country, first of all. 48 of the 52 states that I know that weren't included, that actually had xylosine fentanyl mixtures were Wyoming and Hawaii. And I believe that is probably because of positive testing that's being done up until recently. This was released by the DEA in 2023. It's not an opioid. So xylosine does not respond to opiate reversals via naloxone. So if you're going to rescue somebody and they actually respond, it makes you wonder what else is that they're responding to. And again, going back to that little question that I made before. So in 20 states and in DC, xylosine combined was involved in 11% of the drug use in DC. Next slide, please. Now, very, very quickly, how does it work? How does xylosine work? Well, it works by the alpha-2 receptor. Basically, once the alpha-2 receptor is stimulated, it reduces the amount of catecholamines that go into the neurosynapse. And what that is, norepinephrine and dopamine and several of the other catecholamines are what we call the awake drugs. If you prevent those neurotransmitters, if you decrease the amount of norepinephrine and the other catecholamines into the neuroreceptor, you go from awake to sleep. Pretty much the way clonidine, as many, many of you know in the patient here and in the audience, clonidine is used actually as anti-hypertensive and also as someone to calm them down when they're withdrawing from opiate withdrawal. But tonadine and dexamethylaminodine and the other medications like tanzanidine, which is a muscular muscle relaxant, are imidazolines drugs. They, in addition to being alpha-2, they also have another receptor that they're active on, which causes hypotension, bradycardia, which is for depression. Xylosine is not an imidazoline drug, so it doesn't have as much of an effect on respiratory depression, bradycardia, and hypotension. Next slide. But it definitely causes sedation and analgesia and amnesia. The others, in very, very high doses, I would imagine that xylosine causes some respiratory depression and bradycardia and hypotension, but not as much as the other medications like tonadine. And even, believe it or not, the thiazine, I've heard of some reports of people who have overdosed on the thiazine, which is tetrahydro. But it doesn't have the same effect. Go on, please. Unfortunately, simply because of the fact that it causes, what xylosine does is that it causes an anonymous knot. It basically causes sedation, and that particular knot, plus the fact that these individuals sometimes have very smelly, malodorous lesions on their skin, which are basically necrotizing lesions, dead skin. The drug, unfortunately, has got, and even users consider it by the name either anesthesia, not anesthesia, anesthesia. So if you say the anesthesia, you'll sound very Spanish in the way it was heard at first. And one thing about that particular article that I mentioned earlier was that it made me wonder whether it was mostly in Puerto Rico seen in ranching communities that 37% that I've discussed before. I think that Adesivo in Puerto Rico, which is close to where my family was from, might have been area zero where some of this xylosine first got started. But we certainly know that it's the stigma at this time because it is called a zombie drug, or a tranche is the colloquial term or label that has been put on this particular drug. The next slide, please. And now I want you to take a very quick look at the title of this particular slide, and then forget. It makes the drug deadlier. Now, I want you to concentrate a little bit more on potentially because xylosine makes the unregulated drug supply maybe even potentially deadlier than it already is. We don't have absolute concrete 100% evidence at this point to say that it does because we don't know exactly how xylosine in humans basically works. We certainly know that fentanyl does. Fentanyl, there's just no doubt about how deadly fentanyl is. It does cause respiratory depression. Xylosine in the amounts that are usually in the particular drug are available on the street may or may not actually potentiate it. And it is projected, and I can say that this is true. It is projected that the current drug overdose death toll will increase as xylosine prevalence continues to rise. That remains to be seen as well, but it would be reasonable to conclude that that might be the case. Next slide, please. So how do we treat xylosine and its effect? First and foremost, since fentanyl and xylosine run hand in hand, if we're discussing xylosine, we are also discussing fentanyl as well. So MOUD, which is Medications for Opioid Abuse Disorders, either methadone, buprenorphine, are strongly to be encouraged and considered as first line to treat people who have xylosine-related issues because fentanyl is the opiate. It definitely causes withdrawal as an opiate when it's used long-term, and most of the people who are injecting are using it. And then afterwards, naloxone. Naloxone is important, widespread distribution and use of naloxone to residue. Constellating, needle exchange, addressing the social determinants of health, peer support, mental health, primary care, absolutely. But the first and foremost is to treat the substance use disorder. People ask me all the time, you treat patients who are HIV, have hypertension, cardiovascular disorders, And how do you know? If I see a person here today and they die tomorrow, more likely than not, they didn't die of cardiovascular, and they didn't die of anything other than the overdose. Is I concentrate on the overdose, I concentrate on the Medicaid, the MOU, the MATs, and naloxone distribution. Keep them alive until the next day, until the next week, that as long as they're alive, I can address the other. Next slide, please. And of hope, a 40-year-old white man would have known history of anxiety. He's on Xanax, one milligram three times daily, and opiate use disorder is found unresponsive and barely breathing in the bathroom of your facility. The pulse ox is 82%. He has administered Narcan nasally, and his breathing normalizes. Now he has a pulse ox of 99%, has a good pulse rate of 50. He is responsive to painful stimuli, but still overly sedated. What do you do next? Next slide. Do you start CPR? A, do you continue? Continue to give additional doses of nasal Narcan until he wakes up? B, do you give Maxicon, which is Flumazid now, to reverse the likely benzo overdose? Do you immediately call 911 and apply oxygen if available, and monitor his breathing until help arrives? Or four, do nothing, as this is probably a xylosine overdose, and he will probably eventually wake up. Give you a second. Let's see how we do. All right, absolutely. Don't start CPR on someone who has a pulse in his breathe. Nobody will appreciate it, especially if you break a rib or two. It's not a good idea. Do you give additional doses of nasal Narcan until he wakes up? Well, if you remember, maybe if you consider this, that maybe it's someone who actually has a xylosine and a fentanyl overdose, and he responded, then you pretty much know that there must have been something that responds to Narcan, and most likely that would have been fentanyl, heroin, or some type of opiate, because all the other, like cocaine, and 30 xylosine, even benzos, would not respond to Narcan. Do you give Maxicon to reverse the likely benzo overdose? Well, it was mentioned that the person was already on Xanax one, three times daily. If you give Maxicon to somebody who is chronically on benzos, you may precipitate a withdrawal that you may not ever get that person out of. I've seen it in the emergency department. That's the reason that we, I don't even know if we stock it. I'm pretty sure we do, but no, you would not give Maxicon. Do you do nothing, as this is probably a xylosine overdose, and he will eventually wake up? Well, no, you have to do something, because unless you really work in an emergency department and you have several hours to watch this patient, and there's a possibility that he could, again, if it was fentanyl, that he could again become apnea, not breathing anymore. So D, immediately call 911 and apply oxygen if available, and monitor his breathing until help arrives. That is probably the best of the five available choices here. So the reasoning behind it is, again, as I mentioned before, even if naloxone reverses the overdose, there may be other health problems. People who survive any type of overdose are at risk of experiencing other health complications, and when you give naloxone to someone and continue to give naloxone to someone who is still sedated, you risk the possibility that they can actually vomit and maybe even aspirate, and that would make a bad situation even worse. Next slide, please. All right, so do not give more than two doses, if possible, and I kind of mentioned that already. And let's go to the next one. Yeah, so look for any signs of head or physical trauma, and like I mentioned before, it's possible that there's something else going on, and if possible, check the fingers they go, and turn them over to the side just in case they actually do vomit on you and avoid aspirating, and that would be a much worse scenario. And let's just go to the next one. So monitor and support the acute intoxication, discuss chemical dependency, and that's one thing that we're just not doing enough of after a person is, you have to remember that the best time to actually incorporate buprenorphine induction, even to the high dose buprenorphine induction, okay, is when somebody is in active withdrawal. If you give benzoyl to, I mean, buprenorphine to somebody who's already in withdrawal, there's little chance that you're actually precipitating withdrawal. They're already in withdrawal. So this is a perfect time to actually approach them about doing so, and I've had remarkable success in folks who come here who actually have had a precipitated withdrawal from inadvertently starting buprenorphine on the street, and they happen to be a methadone or some kind of, and you can actually just really flood them. I mean, really give them a very nice, robust doses of buprenorphine, because remember that buprenorphine also is not something that really causes that much in the way of respiratory depression. So anyway, examine the skin for any kind of lesions, if possible, because then again, this is one of the things that go hand in hand with the xylosine use paradigm at this point, that you can almost say, or at least the overall few patients who people are very highly aware that patients may actually be on board. So, and next slide. As a knee or a back, I rely very heavily on epithelial blood clots and alcohol. So xylosine toxicity has kind of really redefined what it is that we do, and it's very, very challenging because at this point, like I said, very little is known about even xylosine withdrawal. We certainly know that fentanyl has a withdrawal, but what about xylosine? How much does it contribute to it? Most authorities, myself included, I think that it probably does worse in the severity of the withdrawal. And certainly it appears like it may actually prolong the time of withdrawal as well. So you have a certain amount of opiate withdrawal, and then you can add the severity actually seems to be increased, and also the prolongation, although we don't have concrete evidence of either one of them. Next slide, please. So, though not evidence-based, my common sense approach is to target the receptors that share the similar neurochemistry. You remember that I said that it was an alpha-2 agonist. There are other drugs that actually share this quantity, and I mentioned this, and we'll go on to the next slide. So as far as xylosine withdrawal, it mirrors the same as opiate withdrawal, irritability and sleep, tremors, depression, the euphoria, the dysphoria, sweating, restlessness, all of these, and then some, according to folks who actually have lived experiences with the known use of xylosine. So, next slide. So, clonidine, 0.1 every six to eight hours to, and titrated to with effect. I usually start a little bit on the higher side if the blood pressure allows me to do so. Most people who are in withdrawal are somewhat tachycardic, meaning very high heart rates because of discomfort, the anxiety, and also their blood pressures are increased, which is interesting because how do you know part of the Cal score, which is the clinical withdrawal scale, involves, okay, taking, you know, just measuring the vital sites. If a person is truly withdrawn, they usually are somewhat tachycardic. They usually do have a blood pressure. Their respiratory rate increases. They look anxiety, they're sweating. They're uncomfortable. It's very, very uncomfortable. So when I start the alpha-2 agonist, like clonidine or tizanidine, tizanidine is mostly used as a muscle relaxant, but those particular medications, tizanidine, again, is a relatively safe medication. Two to four milligrams every six to eight hours has less of an effect than clonidine on the blood pressure. And all of these drugs, the alpha-2 agonist, as I mentioned before, in very high doses can cause hemodynamic instability. So it's something to keep your eye on. If a person, next slide, if the person is having trouble, and most of them are anxiety, just add Avistaril, 25 to 50 milligrams every eight hours. I usually go a little bit on the high side. If they're very agitated or having some symptoms of mild psychosis, you can consider some of the atypical antibiotics, such as Lexapro, Cyprex, Olanzapine, and Quetiapine, which is there. And lastly, you may actually need to use Sub-N in the end. Again, no evidence-based for any of these at this point. It's just common sense. And you use it at your discretion and try to target the worst of the symptoms of the withdrawal. Now, the last thing that I'm going to discuss, next slide, please, is actually the central focus of my practice, which is xylosine wounds. Most authorities, so-called authorities at this point, that deal with this are very, very tuned into the fact that xylosine seems to have a direct effect on patients. So the next is, have you ever seen a xylosine-related practice? One, you've never seen these wounds. Two, B, I've seen the wounds in my practice, but didn't recognize them at the time, but there may have been xylosine present. C, I've seen this wound a few times in my practice. And D, I've seen these wounds several times. All right. And the results are. Oh, interesting. Very few people have seen these wounds in my practice, and that's nice, because I'm going to get to another, another one now. Do we have another poll? Oh yeah, here's another one. Xylosine-related lesions are only seen in people who use intravenous drugs. B, I have seen these only occur at the sites of injection. C, are present in all people using or exposed to xylosine. D, will always require surgical intervention. E, all of the above. Or F, none of the above. Xylosine-related wounds are seen in people who use intravenous drugs. Only occur at sites of injection, are present in all people, or will always require surgical intervention. All of the above, none of the above. And the results. All right, the majority of us got it right, okay. Cool. Actually, as it turns out, are seen in people who are using. Next slide, please. And the reason that we're only going to touch on the xylosine-related lesions and the wounds is because it's a very, very large topic. Certainly, you can fill an hour, half a pill, an hour or two, but it can occur in anyone, xylosine, via any route of operation. It could be inhalation, people who are using intramuscular, snorting, or oral, or using the medications, using xylosine orally. And again, the xylosine that came with a lot of different ways of administration at this point. There are pills, there are intravenous, there are intramuscular, and it could be actually, can occur anywhere on the body, not just at the injection sites, are not present in all people. As a matter of fact, if you remember that study from Puerto Rico, even with high use in those particular areas, only 20 to 40% of people have, and do not always require surgical intervention. So, next slide. As an ER doc, I use a lot of sonography in my practice, and I decided, well, I could use it here in my office as well. So, I bought myself one of these portable sonogram machines that I could get to my phone or tablet. And next slide. And I've been scanning people coming with wounds. And this is what the normal, I'm not gonna make you, but this is what normal skin would look like, upper layer of dermis and then higher. Nice and smooth and actually nice linear patterns there. And you see a biopsy on the knee that shows you what you're looking at above. The next slide. Now when you see at the top of the left hand, a caption there, a subcutaneous edema. This is somebody who already has, doesn't have an ulceration, but actually has the beginnings of a wound that may be infected, certainly causes edema, which is swelling of the upper portion. But the swelling is, and you see that little copper stoning there, basically shows that there's some involvement and some irregularity, okay, that may lead to necrosis or an ulceration. But it's very superficial. So and basically on the right side, you see a little black hole there. That particular black hole is an abscess, but it's very superficial. And if you see that there is a separation between the abscess and the muscular, the deeper layers with muscular, this is something that's so superficial that I could just put a little knife in there, a little, do a little IND, drain it, pack it a little bit in my office and avoid with careful wound care, this particular patient will probably do fine and doesn't need surgery per se, I mean, besides a little bit of an IND that I do in the office. So the sonogram for me has proven to be quite, quite, quite effective and very, very, because I'm noticing that these superficial ulcerations can be approached with just simple wound care and superficial abscesses with just simple IND, maybe some antibiotics for a short period of time, and they seem to do relatively well. The next slide, please. Okay, so I'll do a little case study. Oh, we'll go back to the final knowledge check. And next slide, please. So we'll return back to my 40-year-old white male. And I got to mention that everything that I've discussed here, about an hour ago, we had an overdose here in my clinic. And he was certainly somebody who had been under the silencing because he responded to the Narcan, started breathing again, wasn't breathing well at first, and then, but he remained completely sedated, basically. But we got him off to the hospital, which is actually kind of helpful. So the 40-year-old white male with his own history of anxiety, our response is barely breathing. You give him the Narcan, and his breathing normalizes. He is responsible to painful stimuli, still overly sedated. What do we do? Start CPR, continue to give Narcan until he wakes up, give Flumazenil to reverse the benzo, immediately call 911 and apply oxygen and monitor his breathing. So help arrives, or do nothing, that this is probably just a zalazine overdose, and he will eventually wake up. And what's the, there we go. That's cool. I'm not the only one. Now, finally, very, very quickly, you get really queasy looking at the, you know, images of skin lesions, and then please turn away. We're just going to show you very, very quickly what some of the lesions may look like. And this is a superficial ulcerations. But this is actually, these were given to me by the organizers. And you can see some lesions here that some are actually in different stages of healing. You see some ulcerations there, but you see nice pink, kind of reddish granulation tissue overlying some well-marginated scar, and the rest of the arm seems scarred. So you can see that it was, that the lesions were much, much, much larger, because you see those hypertrophic areas surrounding the ulcerations. So this is somebody that's in the process of healing and doing relatively well. Looks almost like a, like when it's completely healed. Next, next slide. Looks almost like somebody who recovered from a burn injury. And indeed, the majority of the real experts at wound care that have to usually, now, I don't want to make it seem that these particular wounds are always going to be superficial. They could get, they can get super infected and become very, very deep, necrotizing lesions that actually go down almost to the bone. And amputations have been seen. We've repeated, what causes these lesions, we think is a direct effect or systemic effect from the xylosine, and it's causing what we call basal constrictive, which is narrowing of the small arteries in the skin superficially. And it causes dead tissue to, the ulcerations and eventually the tissues. And if they keep injecting into it, but sometimes it actually occurs in areas, okay, distant from where they inject. So it doesn't always necessarily have to be at injection sites. It could be somewhere else. But anyway, that's enough about lesions because we just don't have time. That's beyond the scope of my presentation today. Even though I consider it to be one of the more aspects of their intoxications. So one last poll, are lesions only seen, here we go. Are lesions only seen in people using intravenous drugs? B, only at sites of injection. C, are present in all people using or exposed to xylosine. Will always require surgical intervention. All of the above or none of the above. And I'll keep my fingers crossed. There we go. All I can say is thanks for listening. And now in summary, okay, a xylosine adulteration in the unregulated blood supply appears to be expanding eventually. The best response to treatment of an unresponsive user's drugs is still naloxone. Okay, and I saw somebody in the chat who asked whether just use enough naloxone to get the person breathing. Yes! Treatment options for xylosine use disorder include MOUD and adjuncts that help with prolonged effects of with xylosine. And xylosine related lesions in many, many cases can be effectively treated with known techniques. Okay, and you would know, believe me, not when you see it, but I've even seen some people who have gone to the operating room with xylosine related, very related, horrible wounds that actually didn't require amputation. So, I think that at that point, these are a couple, next slide, a few of my references. And I thank you for your kind attention. I hope this was somewhat helpful. Of note, it's interesting because I went to a conference in California, a three-day conference on addiction medicine. And despite the fact that it was three days and just intensive addiction medicine, not a word, this was in California, not a word, not a mention, xylosine was made. But there is plenty of evidence and suspicions that xylosine is very much across all people. And I think that if you tuned into this particular talk that now you're ahead of the curve. All right, well, Dr. Rosa, thank you for a wonderful presentation. And we have a number of questions in the chat, I mean, in the Q&A box. Unfortunately, we won't be able to get to all of them, but I'll try to run through some of the more pertinent ones. We had a couple questions related to detox or detoxing from xylosine. Do you want to talk a little bit more about that, about what might be most effective? How do you think about that? Yes, absolutely. When you're detoxing from xylosine, you're detoxing from something else usually. So we certainly know that it could be that xylosine is being adulterated in multiple vectors at this point, and vehicles of drug use. So if you're detoxing from psychostimulants, there's one process. And then majority of people are basically requiring a detox and rehab or a treatment for the fentanyl aspect. And again, like I mentioned before, it does make it a little bit daunting when xylosine is involved simply because of the fact that the xylosine can worsen the severity of symptoms of withdrawal and also prolong the process. And that's the reason that I suggested that some consideration is made for some of the adjuncts that I mentioned in the talk. And I'm sorry that I have to go so quickly through them, but they're in there. And this entire thing was recorded so that we can go back and look at a couple of others. And I even included the doses that we use non-normally. You certainly are not required to stay within those particular limitations, but those are the ones that I use. Okay. Okay. That makes sense. We had another question here, and talk about how xylosine is different from something, say, like ketamine. Ketamine is very, very different. It's an NMDA drug and it uses a different pathway altogether. Ketamine has a lot of different... Boy, that's a great question because ketamine is even being used now in the mental health field for treatments of resistant depression and psychosis. But it has a completely different mechanism of action. And the effect and the side effects are also different. We certainly don't see much in the way of people who are abusing ketamine who have these particular lesions that I mentioned are sometimes related to the xylosine use. So that's... And it doesn't necessarily prolong, and it's much less adulterated drug supply. So our focus, if they're abusing ketamine, it doesn't necessarily mean that they're anything else other than ketamine. So there's a lot of... And there's a lot about the difference. Thank you. That's a great question. Exactly. I have two questions that are kind of related. I'll try to combine these. One is, what are your thoughts about xylosine test strips? Is that an effective tool at all? And the other question related is, can xylosine be detected under your analysis? Yes, on both. And the xylosine test strips, let's say, for instance, where you are. And if I'm practicing here in the Northeast or in Philadelphia, it's probably less useful to me to know, to use the test strip, because anyone who is using illicit fentanyl, or heroin, is becoming much, much less prevalent at this point. But anyone who's actually using fentanyl, intravenous drugs, are probably also either deliberately or inadvertently using xylosine. So how much more information am I getting from those high-density areas, as opposed to, boy, would that be so helpful in Oregon and in California and San Diego, who are not testing as much right now to actually make the public aware. I just mentioned, okay, that I went to a three-day conference, three-day conference in addiction medicine in California, and not a single mention of xylosine. It's out there. It has to be. So I think that depending on where you are, I think that it's an important one. Fentanyl test strips, again, I'm not sure, because if you're using any bag of anything, you're probably using fentanyl. And again, it depends on where you are, as far as xylosine is concerned. Okay, good. Thank you for that. Another question here, which I thought was interesting, is what do you think, in your view, veterinarians should know about human use of xylosine? Well, they know about it, first of all. They certainly do know about it. But I think that the question should be turned around. What should we know that the veterinarians know? Now, don't get me wrong. I mean, again, veterinarians are not necessarily very knowledgeable about the misuse of xylosine in animals, because you don't see that many cats and dogs who are actually trying to score, well, in this neighborhood, but the cats and dogs who are trying to score xylosine on the street, or heroin. But the fact is that I think that we should try to judge, to use the information that the veterinarians have, okay, as well as whatever it is. But I'm not sure that, at this point, collaborating with them on almost anything. Plus, again, I presented on the misuse of xylosine as opposed to the proper use, which they use in small dogs and men. Okay, all right. And so another question here was, any thoughts about what someone like outreach workers and those who are charged with helping people who are in high-risk areas, such as the folks who are unhoused, when they see wounds, or they see people that may have some effects of xylosine, contamination of xylosine use? Yeah, I think that those particular individuals who are individuals who work with the homeless population, and I felt to them that it's our obligation to try to get them whatever is necessary for them to begin the process of wound care. Because in many, many cases, and to educate, and many of these individuals who actually have these particular wounds don't seek care immediately simply because of the fact that they're embarrassed. And these are horrible wounds. They sometimes come to terms with the fact that this is so horrible that I don't even want to seek attention to it. I'm just embarrassed to go there. So these particular individuals who go to those particular sites, if we can give them the supplies necessary to begin the process of the healing and educate them and convince them, no, this is not embarrassing. Let's take you to the hospital. Let's get you to the doctor so-and-so or PA so-and-so or whatever it is. Let's get you to an emergency department even, okay? And get the process started. And there, the ball gets started. And then we start the treatment for the fentanyl and the MAT, MOVD that I'm talking about. They're so important in the process of getting these people treated. These are family members, neighbors. These are people that we care about, somebody cares about. And we have to reach out to them as much as possible. Thank you for that question, Dustin. Thank you. Yeah, exactly. All right, we have a slightly technical question but I want to make sure we cover it a little bit because I know we have some other folks who may be dealing with this as well. What about Lucemira instead of Clonidine? Lucemira? I'm not sure I'm familiar with that. I'll spell it out. I may not have said it quite correctly. It is L-U-C-E-M-Y-R-A, about use of that instead of Clonidine. Yeah, I haven't used that one. Okay, okay. And there's another one, a question related to the potential use of Guanfacine. Guanfacine? Yeah, yeah, Guanfacine might be something that might be. I think that Guanfacine, if nothing else is available, of the other medications that I kind of like alluded to, like Hydroxazine for the anxiety and a consideration for the atypicals and of course Clonidine and Clonidine. And I think that you should use whatever you feel comfortable with, including the ones that I'm not so familiar with. I probably wouldn't use Guanfacine because I'm not as familiar with its use. Okay. If it utilizes the same, Guanfacine does, it utilizes the same pathway. I think that that would be helpful. I think that we're, time is up. Yeah, so we're at the end now and I'll turn it back over to my colleague. Here's Dr. Rosa's email if you have any questions or comments, but I do want to thank all of you for your questions. Apologies, we couldn't get to all of them, but there were so many of them. And I'll turn it over to my colleague here for some closing thoughts and move us forward. All right. Well, thank you so much. As Aaron shared, that is all the time that we have for questions. But Dr. Rosa, we just appreciate you also providing your email address for further questions or follow-up if we do have those, which looks like we do have a lot of questions. So thank you for that. You can access his email on the screen. We'll also drop it in the chat. But again, just thank you so much, Dr. Rosa, for your presentation today. And I did want to share a reminder that in two weeks from today, the slides as well as our recording will be live on the PCSS MOUD website. And if you're able to stick around, we have just a couple of logistical slides here. So this is regarding our PCSS MOUD mentoring program, which is designed to offer general information to clinicians about evidence-based practices. So you can learn more about this mentoring program at the website listed on the screen. And then if you've got a clinical question, you're welcome to ask a colleague through the link below. This is also provided by PCSS MOUD, and it is a great way to directly receive and answer any questions related to medications for opioid use disorder. Here, we've got a quick shout out to all of our collaborative partners at PCSS MOUD and a continuation of our partners. And that is the end of our presentations. Thank you so, so much everyone for joining us. We will share also just all the ways that you can access PCSS MOUD on the screen as well as in the chat for you. But thank you again, Dr. Rosa, and I hope everyone has a lovely day.

MOUD

recovery housing

holistic care

collaboration

12-step programs

smart recovery

medication-assisted treatments

open-mindedness

supportive environment

Xylozine

Opioid Use Disorder

OUD treatment

fentanyl

overdose deaths

naloxone

wound care

detoxing

evidence-based practices