Xylazine - The "Zombie Drug"

We're talking about Xylazine again. We haven't covered it on the podcast since 2022, and since it's becoming more common in the drug supply, it was time to discuss it again. 

Unlock the secrets to understanding one of today's most alarming substances misused in addiction – Xylazine, infamously dubbed the "Zombie Drug." Join me, Dr. Casey Grover, as I dive into the world of Xylazine, a veterinary medication with unintended and dangerous consequences when misused by humans. Discover the pharmacological effects of this alpha-2 agonist, closely related to medications like clonidine, and learn how it disrupts normal physiological functions, leading to slowed heart rate, low blood pressure, and sedation.

In this episode, I unravel the complexities of Xylazine use, highlighting the dire risks of overdose and the challenges faced due to the absence of a human reversal agent. By sharing my 14 years of experience in the emergency department and my current role as a medical director in addiction treatment, I aim to provide crucial insights into how healthcare professionals can respond to Xylazine-related emergencies. This episode offers a comprehensive guide for anyone involved in the realm of addiction medicine, from healthcare providers to individuals battling addiction and their loved ones, emphasizing the importance of informed and compassionate care.

To contact Dr. Grover: ammadeeasy@fastmail.com

Transcript

Speaker 1: 0:00

Welcome to the Addiction Medicine Made Easy Podcast. Hey there, I'm Dr Casey Grover, an addiction medicine doctor based on California's Central Coast. For 14 years I worked in the emergency department, seeing countless patients struggling with addiction. Now I'm on the other side of the fight, helping people rebuild their lives when drugs and alcohol take control. This podcast is my way of cutting through the confusion and making addiction treatment easier to understand. My goal to leave you with real knowledge you can use, whether it's to help your patients, your loved ones or even yourself. Thanks for tuning in. Let's get started.

Speaker 1: 0:54

Today we are going to be talking about the drug xylosine. If you think, you might have heard of it before, it's also known as Trank Trank Dope and the Zombie Drug. I work as the medical director for a residential drug and alcohol treatment program and I do education for my colleagues every month, and this is what they wanted to talk about this month. I referenced some photos of wounds during this episode and obviously this is an audio-only podcast, so if you want to see what I was talking about, just do an internet search for xylosine wounds and you will have plenty to look at. So, as was requested last month, we're going to be talking about xylosine. Xylosine is not a human medication, it's a veterinary medication and it's used around procedures specifically for anesthesia and to also sedate the animals during procedures. And the way it works it's an alpha-2 agonist and the way to think of it is it's in the same class of medication as clonidine.

Speaker 1: 2:03

And the way clonidine and these other medicines in this class work is they reduce the output of stress hormones from the brain. There's a small nucleus in the back of the brain called the locus coeruleus. It's a little cluster of nerves and it generates our stress hormones, like adrenaline, for example. And it's interesting for opiates. What happens is opiates actually suppress this area of the brain and so opiate withdrawal is an overstressed state of the body because this area of the brain releases more stress hormones now that it's no longer being suppressed. So each of these meds there's a couple of them People recognize the name clonidine. So each of these meds there's a couple of them, people recognize the name clonidine. There's a muscle relaxant called tizanidine, and then at the hospital we use a sedative called dexmedetomidine. And all of these are in this group of meds called alpha-2 agonists. So they blunt withdrawal and they can cause sedation. And that's because, again, they reduce the stress hormones leaving the brain that contribute to arousal and then stimulation. And so xylosine is an alpha-2 agonist and that's how it works in veterinary medicine, as you can imagine, by reducing the stress hormones leaving the brain, it's going to basically reduce anything that speeds us up. So clonidine can also be used to treat high blood pressure as a side effect. Clonidine can also be used to treat high blood pressure as a side effect. Clonidine can lower the heart rate, and then a lot of these meds cause sedation, like some patients get really sleepy on clonidine, and that's what xylosine looks like in humans. Again, you can think of xylosine and clonidine as cousins. So you can see here on the screen the clinical effects in humans from xylosine are a slow heart rate, low blood pressure, and then it causes sedation. Now where most people are worried about xylosine is in the case of overdose. You can imagine if the clinical effects are as it drops your heart rate and your blood pressure, makes you sedated. Overdose is just going to be that amplified. So patients are going to be lethargic, unable to be woken up. They may be very hypotensive or having low blood pressure and then their heart rate may be low. There is a reversal agent in the world of veterinary medicine, but it's never crossed over into human medicine. I'm not quite sure why that is, and treatment for a xylosine overdose is essentially supportive, meaning that if a person has low blood pressure, we give them IV fluids to bring their blood pressure up, or we use medicines to support the blood pressure. If people are so sedated they can't breathe, we'll give them oxygen and or put them on a ventilator. Essentially, we just wait for the xylosine to wear off and we support the organs in the meantime. So that's kind of what xylosine is in terms of the pharmacology, but let's talk about how it fits into more of what we're doing around testing to see when and how it's in the drug supply. So the first thing is you can see in the lower right corner of the screen they do make xylosine test strips and people are very familiar with fentanyl test strips. This is the exact same thing, it's just for xylosine. So this is just a screenshot from Amazon. It is $11.50 for 10 test strips. Now, in terms of urine drug testing, xylosine does not show up on standard urine drug screens. So if you go on Amazon and buy a little kit the little kit with the bars that shows you. Yes, no, if a person has it in their system, xylosine is really not able to be detected by that, and none of the local hospitals as a result of that are testing for it. You can actually get xylosine testing kits to see if it's in someone's urine online as well, but we actually asked our lab to add it to our standard drug testing panel. So here's two screenshots of patients that I've seen in the last three weeks. One of them, you can see the threshold to detect the xylazine is 10 nanograms per milliliter, and this person tested at a level of 572, so that's a pretty significant exposure. And then this is one of the patients I actually just saw earlier today. This person's xylosine was so high that they couldn't actually give us an exact number. So in our office we're routinely testing all of our patients for it. Most of them have a fairly low level exposure because it's laced in rather than getting pure xylosine, and we'll talk about that in just a little bit. Now people have heard of xylosine because of what it does to the skin, so chronic exposure of xylosine leads to a lot of wounds and we'll look at some photos in just a little bit and these wounds are most commonly on the arms and legs. Wounds can be elsewhere on the body, but most commonly on the arms and legs. We don't exactly know why this happens yet, but it's thought to be that xylosine changes the blood flow to the arms and legs because, as you saw, it affects the blood pressure and the heart rate. And the way it does that is, the stress hormones in the body change how much the arteries, how much they squeeze down, and arteries are blood vessels that actually have the ability to dilate and constrict and so, like cocaine for example, causes the blood vessels to constrict, which decreases the blood supply, which is why people will get nose damage from cocaine. So there's some thought that xylosine must be affecting blood flow in some way, but normally we think of clonidine as causing the blood pressure to drop and the heart rate to drop and the blood vessels to dilate, so it's almost like it's an opposite effect. So we don't know exactly why, but we think it's something related to how it affects the blood vessels and xylosine wounds can be necrotizing, meaning that they start to get flesh-eating bacteria, and they can also be gangrenous, meaning that the tissue actually starts to die. Now there are different ways that this can happen. So when people actually inject xylosine, they can get a wound at the site of injection. But we also see some of these wounds in people who smoke and snort xylosine as well. Again, we still need to work out the full mechanism and, in addition to these specific wounds, we've also seen some patients develop rashes after exposure to xylosine as well, and we'll take a look here. So this is a picture from the internet of somebody who has a xylosine wound and you can see it. Basically, the top layer of skin is just missing and there's quite a bit of scar tissue around it. This individual also has a bandage on the right forearm, so there's likely something else there as well. And essentially, if you look at this picture, what you can see is you can see the scar tissue around the wound, which would suggest that this wound happened and is now in the process of healing, or it's come and gone several times before. You can also look and you don't see a lot of infection around it. It's not red, it's not weeping, it's just the wound won't heal. Here's another example. This is a picture of someone showing off a wound on their leg, and I zoomed in so you can see it and it's the same thing. It's basically the top layer of skin looks like it's missing and it looks like a shallow crater and that's called an ulcer, and that's a particular type of skin wound. For context, when people have problems with the arteries in their arms and legs, they actually get these sort of wounds on their feet and legs. So it probably again means that there's some sort of issue that xylosine is impairing the blood flow to their legs. Here's another photo, and this is a person who has scar tissue from previous wounds. They look like craters, they look like divots and essentially what happens is some of the tissue dies and then the skin tries to grow over it, but it leaves a defect because some of the tissue died in the process. Now, this is a picture from one of my patients. I saw her earlier today. Now, this is a picture from one of my patients. I saw her earlier today. This is her right thigh and her family sent me this and we couldn't figure out what was going on, and then I saw her in the office and she was the one who had the xylosine level that was too high to actually give a specific value. Now, in terms of how we treat these wounds from xylosine. The first answer is you stop xylosine and then just like, if it's a burn, we do wound care. So CHOMP, our hospital locally, actually has a wound care clinic and they can use various bandages and various dressings and various medicines and then obviously, if anyone's got infection in the wound we're going to treat with antibiotics. Now you may be wondering why is xylosine in the drug supply and people who use it say it gives fentanyl legs. What does that mean? Well, as we all know, fentanyl is very short-acting and people withdraw multiple times throughout the day. Short-acting and people withdraw multiple times throughout the day. So one of the ways that people remember heroin is that you only had to dose it a few times a day and you weren't constantly in withdrawal. But with fentanyl it's very different. In fact, one of my colleagues has a patient who can't sleep through the night because they wake up in withdrawal every few hours. So, if you can imagine, we use clonidine to treat opiate withdrawal. So xylosine probably also helps with opiate withdrawal because it acts like clonidine and so essentially, adding in xylosine to the fentanyl allows the fentanyl to feel like it lasts longer, so people can actually go longer between doses of fentanyl. In terms of how common it is. I had to research this, but it turns out it was first detected as an agent in the drug supply in 2001 in Puerto Rico and we didn't see a lot of it, probably because the market was mostly prescription opioids and heroin, which we talked about. You only have to use a few times a day, but it started to become a regular occurrence in the drug supply on the East Coast beginning in 2019, and that probably reflects the transition to fentanyl. And, just for context, between 2015 and 2022, the number of overdose deaths that involved xylazine increased by 20 times, not by 20%, but it increased 20-fold. So it has really jumped in how common it is in the drug supply. Now it also turns out, like all drugs, that the supply is very regional, and xylosine is no exception. I'll never forget we just hired a doc in the ER about two years ago and he had come from Chicago and it was really funny. After about six months he goes Grover, why is there no one here who uses PCP? And I said, well, we just don't have a lot of PCP here and he was not familiar with methamphetamine to the extent that we see it in California. So again, the drug supply is going to be regional. So in Monterey County we probably detected it first in the last 12 to 18 months, and maybe six months ago I was getting a few positives a week in our office. Now I'm probably getting one positive a week, so we're seeing more of it Again. For context, I looked at one 2022 study looking at how common xylosine is in the drug supply and in Philadelphia as many as 26% of overdose deaths involved xylosine, whereas in other cities they didn't detect any, and Philadelphia really seems to be the epicenter of xylosine. That's where we're hearing the most about people who are using it and we were getting the most information from healthcare providers who are treating people using xylosine. Now, in terms of the patient experience, some patients don't recognize the name xylosine, but they recognize it as trank or trank dope, and then in the media it's often called the zombie drug, because it causes these horrible flesh wounds and it's been described to look a little bit like Crocodile. I don't know if anyone remembers that. That probably was about maybe 15 years ago. That was mostly in Eastern Europe, but if you look up the zombie drug, you'll see some news stories about xylosine. One of the research papers that I found actually interviewed people who stories about xylosine. One of the research papers that I found actually interviewed people who were using xylosine to get their perspectives and one person says it gives the dope more of a heroin-like effect. And again, that speaks to the fact that it makes fentanyl last longer, more like maybe four plus hours rather than the one to two that some of our patients experience. Interestingly, one patient reported that it hasn't had a very specific taste. Well, you know, a bag got drank in it because you'll shoot it and your mouth goes dry right away. And you know it, you taste it. I actually not ask my patients if they have had the same experience, but mostly because my patients are intermittently exposed to it as opposed to any with any regularity, and the drug supply varies so much that it's hard to know. I mean, I saw one of my patients this week who talked about how strong the drug supply was and you know she's tested positive for xylosine, she's tested positive for paraflorafentanyl, she's tested positive for acetylfentanyl. So it's a little bit hard to piece out exactly what's causing what in terms of how it's sold and used. In the vast majority of cases it's mixed in with fentanyl to make fentanyl last longer. The same study that I looked at in terms of drug overdose in 2022, it found that 99% of deaths that involved xylazine also involved fentanyl. So again, the vast majority of the time it's xylaosine or whatever else mixed in with fentanyl. It can be sold on its own. There are some users who do seek out xylosine on its own and they're usually looking for the sedating effect of it. It can be sold by itself. It's usually sold by the dealer as fentanyl and then it's maybe, or maybe not, later found to be xylosine. Here are some pictures. So in the upper left that's from the California Department of Public Health that's just a white powder. You know, it could look like cocaine, it could look like anything. It's just a nonspecific white powder and that is one form that xylosine is in. In the upper right, this is an Asian pharmaceutical company that's offering to sell it and it is again a white powder. In the center, you will see some fragments of a blue pill that is in my hand. So we had one young man check into the emergency department at our hospital and said help, help, I'm in fentanyl withdrawal. It's horrible, I need to quit. And we tested him and we couldn't figure out what he was on. We have a handheld laser spectrometer that we can use to analyze drugs in our ER. I kept scanning it. We couldn't figure out what it was. We sent off his specimens to the lab that we use that does more comprehensive testing, and this is actually pure xylosine. It's basically a chalky blue pill. It actually, according to him, was pressed to look like an M30. And on the lower left you can see just a standard medical vial of a clear liquid and that's xylosine to be used for injection in veterinary medicine. Now the last thing I wanted to mention well, not quite the last thing, almost the last thing I wanted to mention was does it have a withdrawal syndrome? There's not a lot of research on this so it's not been very well studied. I will tell you that Clonidine, its cousin, has a withdrawal syndrome, so there probably is some signal here. I found some information from drug and alcohol treatment programs that talked about high blood pressure, anxiety, irritability and rapid heart rate, and that makes sense, right? We know xylosine is a downer. We know it affects the heart and when people are on clonidine and they stop, they can get some anxiety and they definitely get high blood pressure. So this really makes sense In terms of the treatment, I really couldn't find anything. But anecdotally I have used clonidine, and that makes sense, right? Xylosine and clonidine are cousins, so it probably makes sense that you could use clonidine to treat xylosine withdrawal. But there's really not a lot of research on this. In terms of an overdose, it's really not that different from an overdose on anything else. They clearly need medical attention if they're unresponsive, so we're going to call 911, and then you're going to use naloxone. Naloxone, as you probably know, will not reverse the xylosine, but it definitely will reverse the fentanyl, so it may be enough to get them at least breathing again until the 911 responders arrive. Before we wrap up, a huge thank you to the Montage Health Foundation for backing my mission to create fun, engaging education on addiction, and a shout out to the nonprofit Central Coast Overdose Prevention for teaming up with me on this podcast. Our partnership helps me get the word out about how to treat addiction and prevent overdoses To those healthcare providers out there treating patients with addiction. You're doing life-saving work and thank you for what you do For everyone else tuning in. Thank you for taking the time to learn about addiction. It's a fight we cannot win without awareness and action. There's still so much we can do to improve how addiction is treated. Together we can make it happen. Thanks for listening and remember treating addiction saves lives Bye.