What We Don’t Know Can Kill Us

[Jaunty Guitar Music]

Mike: Welcome, everybody. This is Avoiding the Addiction Affliction, brought to you by Westwords Consulting and the Kenosha County Substance Use Disorder Coalition. I'm Mike McGowan.

Mike: Today, we're going to have yet another conversation about opiates and fentanyl in particular. We're going to discuss the reasons fentanyl continues to be a tremendous problem.

Mike: Our guest today is Dr. Philip Randy... Oh, Randy, I just spaced it! Say your last name.

Randy: Torralva.

Mike: Torralva. You know, you learn this stuff and then you mess it up, but that's all right. Dr. Torralva is a board certified anesthesiologist and specialist in addiction medicine with over 30 years in clinical medicine. He has extensive expertise in pharmacology, invasive monitoring, and central nervous system drug delivery of potent opioids and anesthetic agents, specifically fentanyl and its analogs.

Mike: In 2018, seeing the need for new treatments for fentanyl and fentanyl analog overdose treatment, he started, say it again?

Randy: Torralva.

Mike: Torralva Medical Therapeutics. We're going to call it TMT from now on and began self funded contract research. with the Portland Veterans Administration to investigate the underlying molecular mechanisms of fentanyl toxicity.

Mike: Well, welcome, Randy. I'm so thankful you prefer to be called Randy, so.

Randy: It's a lot easier for all of us, Mike.

Mike: Torralva. Just so you all know I can get it right.

Mike: All right. First, I want to start with some basic, you were an anesthesiologist for about 20 years, long before the opioid crisis hit, right?

Randy: That's right. So, you know, I actually I was in practice for about 20 years in a small central coast California town and was pretty happily ensconced in my practice there. And what happened was we had an interesting, well, sad, tragic series of events. We had three fentanyl overdose deaths that happened in a very close timeframe in 2015.

Mike: Wow!

Randy: And yeah, that immediately it's a small town. And so it really brought. all of our attention to fentanyl and to the opioid crisis. And suddenly that was my first awareness that fentanyl had actually taken over the opioid crisis.

Mike: Well, you know, we're going to talk about that, but you know, I just had surgery again.

Mike: I say again I feel like anesthesiologists are my best friends sometimes. When you go in, like most people, they ask you all sorts of questions, right? Height, weight. a sensitivity, done this before, et cetera, et cetera. Why?

Randy: Yeah. Great question, Mike. And, you know, that's the interesting thing about anesthesia and what makes it so complicated is that everyone is slightly different in how they respond to the anesthetic drugs that we use.

Randy: And we, you know, anesthesiologists in general, we're experts in pharmacology and physiology. And what we need to know about a person before we actually provide the anesthetic for them is, you know, height, weight, their baseline medical issues or medical problems, any allergies that they've had or, or negative reactions to anesthetics or different medications in the past.

Randy: And that all kind of comes into our assessment of what we can use for that patient and how careful we have to be in administering different agents that we use. And so we've kind of learned, we have an arsenal of medications that we use in the operating room. We essentially learn to master those and then understand how an individual's physiology and their baseline medical issues may actually change their interaction with those drugs and so everybody's a little different.

Randy: And so that's what makes anesthesia challenging and quite complicated in some cases.

Mike: I can't be alone in this but I understand it's not the norm. I snap out of that stuff like, really easy. And I tolerate it very well. I understand some people get nauseous or sick. I just want a chocolate shake when I come out of surgery.

Mike: But do you know ahead of time which chemical combination you're likely to use?

Randy: You know yeah, great question. So a lot of the medications that we use are fairly standard that we use across a large grouping of patients, but some patients are so ill that we have to really tailor and change up some of the anesthetics that we use.

Randy: We definitely have to evaluate each person. And you're very fortunate in that some patients, when I give an anesthetic, no matter what I give them, no matter what I try to, what preventive you know, methods I use to prevent them from getting nauseous or ill, they just have a negative reaction to anesthesia.

Randy: And it's one of those things. It's certainly again, one of the challenges that we face with administering anesthetics to patients.

Mike: Well, let's get into the meat of the matter now. Among other drugs, you use fentanyl occasionally. What's the difference between fentanyl used in anesthesia and the other chemical compounds?

Randy: So fentanyl is actually one of the most common drugs we use in anesthesia and in the operating room environment. And in the hands of anesthesiologists, we're trained to use fentanyl. We're experts with fentanyl. In fact, I've given it to probably 20,000 people in my career. Or more. And so we're, so what separates Fentanyl from other anesthetics and other opiates is that fentanyl is a fully synthetic, highly potent Opiate, opioid I should say because it's fully synthetic So it's an analgesic, so it's a pain medication. It's about a hundred times more potent than morphine and it actually is unique in that and it's very different from morphine in that it's very it's very, what we say about fentanyl is that it's very hemodynamically stable.

Randy: So we can give fairly large doses to individuals, to patients in that operating room environment. And it doesn't change their blood pressure or heart rate. And it's a very safe drug to administer in that environment. So fentanyl is interesting also in that it can actually cause unconsciousness. It can actually be used as a complete anesthetic agent.

Randy: So not only does it provide profound pain management and analgesia. That's the R word for it for pain management, but it also can at a certain dose, it actually causes unconsciousness. This is different than morphine. Morphine is actually a kind of an unstable opiate in the sense that when we give high doses of morphine it actually causes the blood pressure to drop so profoundly it can actually harm the patient and so fentanyl when it was first introduced in the 1960s completely revolutionized surgical anesthesia and medicine because it changed the level, changed the types of procedures that we could safely do for patients.

Randy: It dramatically enhanced that safety compared to morphine. We were, we were actually limited by morphine. And some of the other anesthetic agents we use that folks are probably familiar with are Propofol. That's the most, you know, very common medication that we use to have a patient go off to sleep.

Randy: So it's a, we call an induction agent and anesthesia. So it causes sedation. It provides sedation. And then we usually use fentanyl in combination with propofol to blunt some of the the fight or flight responses the body tends to go through whenever we provide whenever someone goes through a surgery.

Randy: And so that's one of the reasons why we use fentanyl and it's, again, it's a life saving drug in the operating room.

Mike: Okay, I feel a big butt coming. But...

Randy: But, so this is where we run into problems with fentanyl. Now fentanyl, and this is what I can tell you as an anesthesiologist in the beginning of my career, I was trained to do cardiac anesthesia.

Randy: And so those are individuals who are coming in, they're coming in for bypass surgery. They're very ill, you know, they have heart and vascular disease. These are very very challenging patients to work with because they are so ill. And so what anesthesiologists noted when we first started to use high dose fentanyls for this type of surgery for cardiac surgery was that, you know, at low doses fentanyl acts like any other opiate, it causes, you know, it gives you pain management, and it also causes respiratory depression so it can slow the breathing down.

Randy: When you get into higher doses of fentanyl, literally what happens is it, it freezes the chest wall muscles and it can close the vocal cords. And we call that laryngospasm, but it can close the vocal cords and that vocal cord closure is sustained. Now, the reason that that's dangerous is that it's, basically, once those vocal cords closed, nowhere comes in, nowhere goes out, right?

Randy: And so we're there, we're trained to deal with that, and we can give a muscle relaxant through the IV that relaxes all the muscles, including the vocal cords, and we can actually put in a breathing tube, and then there's no problem. So it's very safe. We expect to deal with this in the operating room. But, you know, that's the difference between fentanyl and morphine and morphine derived drugs.

Randy: Morphine itself and morphine derived drugs actually don't have this, this effect. And we call it wooden chest syndrome. And so, morphine and morphine drugs, derived drugs, do not cause wooden chest syndrome.

Mike: So, alright, we're gonna walk me through this again, right? So, if I take too much, if too much fentanyl enters my system, it, you said it freezes up the chest wall.

Randy: That's right.

Mike: And then closes the vocal cords.

Randy: That's right.

Mike: But you're standing right there.

Randy: Right. And so I'm standing right there. So that patient is going to be safe. I know to expect this. I'm actually monitoring their breathing because I'm actually helping them. At this point, the patient's usually asleep.

Randy: They're usually unconscious and I'm assisting their breathing. With, you know, with like you see in the movies with, you know, the mask and the bag, you know, I'm, I'm helping them breathe. Now I can actually feel when their chest wall gets tight. I can feel when it's, it becomes harder to mechanically ventilate that person.

Randy: And so once I start to sense that that's happening, I know fentanyl is causing that. I started to administer the muscle relaxant through the IV. And within seconds, all of those things reverse, and I'm able to control the person's breathing again. And then ultimately, then I'll put in a breathing airway for them so that that way they're safe.

Randy: So that's what we noticed. And that's what we see with, with fentanyl. And now obviously the thing about that is that, you know, if I were to step away from that patient, you know, and that is occurring, it's lethal. It's actually a lethal effect because the vocal cord closure is sustained.

Randy: And within usually about, you know, 60 to 90 seconds, the blood oxygen level really goes down by about 60 to 70%. And at that point, that's when the body becomes depleted of oxygen, that's when the heart starts to malfunction, the electrical system in the heart starts to malfunction, starts to miss beats, and then that can lead to the heart stopping [inaudible].

Mike: So you've got a minute to a minute and a half to counteract the effects of well, if it's okay to say this fentanyl overdose.

Randy: Sure.

Mike: But you're not on the street.

Randy: Right. That's right. That's right. And the other thing too, you know, to just to, you know, without getting too complicated or too technical here, Mike, I can, I can talk about this all day long, but the bottom line is this, is that, you know, we also take other precautions when somebody comes in for surgery.

Randy: We actually, we provide you know, a hundred percent oxygen for them. We pre oxygenate them. So they actually have an exceedingly high level of oxygen in their blood, in their bloodstream. And so even if I were to step away or things got complicated, we bought about three to five minutes of safety margin for that patient by providing that oxygen ahead of time. So this is all really well thought out to make sure we optimize safety for patients. And again, I just really want to emphasize fentanyl is one of the safest drugs that exists in medicine in the operating room in that controlled setting. It is exceedingly safe.

Randy: But going out to the street people are obviously not pre oxygenated and when someone's vocal cords close, it's essentially however long they can hold their breath. That's about as long as they're going to survive.

Mike: Wow!

Randy: And it's very, I know, it's like lightning. Now, the other thing to remember too is that, you know, there's the thing with fentanyl is that it has a very narrow range where this effect occurs. So if somebody takes, you know, literally like the equivalent of one grain of salt of fentanyl, that's enough to probably cause respiratory depression, but it's not going to kill them. You go to two to three grains of salt, then that person is probably going to start to have chest wall rigidity, and they're probably going to have problems with their breathing.

Randy: You go to four to five grains of salt, right. Then you're in the actual target range of fentanyl induced vocal cord closure and wooden chest syndrome. And so it's such a narrow margin and that's why this drug is so dangerous because it is so potent. And how can somebody, you know, discern, you know, one grain of sand or grain of salt from five grains of salt in, you know, in a powder or in a pill.

Mike: How do you do it? How do you do it as a, or how do the pharmaceutical people do it? I'm assuming that the dealers aren't doing it this way.

Randy: No, no, they're not. They're not. I mean, what I can tell you is, you know, when I get fentanyl in the operating room, it comes from, you know, it's manufactured by a pharmaceutical company.

Randy: It comes through the pharmacy and the hospital, and it comes in a vial that has a specific concentration, right? So in most cases, it's, you know, one CC or one mil of fluid has X number of micrograms of fentanyl in it. And so I know exactly how much fentanyl I'm drawing up in a syringe. I know exactly how much fentanyl I'm administering to a patient every single time I administer it.

Randy: There is no guesswork at all. Whereas in, you know, street drugs, you have no idea what's in there. And, you know, at this point, you know, I should tell you, you know, I started off. I, you had, you had some really good questions here for me that I wanted to address and one of them is that, you know, the reason I will, we'll probably get into this a little bit here, but I've actually transitioned from anesthesia after 20 years into addiction medicine.

Randy: And I actually did an addiction medicine fellowship at OHSU here in Portland, Oregon, at the Health Science Center, and I've spent the last seven years actually treating folks for opioid addiction, so I've talked with many, many, many folks who have used fentanyl, have survived fentanyl overdose, have witnessed fentanyl overdose and death, and what I can tell you is that, you know, what these individuals tell me is that, you know, when they use fentanyl, it varies so much, even from if it's the same dealer from batch to batch.

Randy: And so, many times, they really don't even know what they're getting.

Mike: Well, it makes sense, right? I mean, they're not getting it from, I trust that the drugs on the street aren't coming from your hospital pharmacy.

Randy: Right, they're not. They're not. I mean they're probably some places where drugs can be diverted, but the most of what is actually out there in the world in the community setting is, you know, illicitly manufactured fentanyl.

Randy: You know, it's, it's, it's made some other place and it's not made by pharmaceutical company so I or diverted from a hospital I can tell you that.

Mike: Yeah, we had an agent on a while back, Randy, that was talking about one of the things no matter, you know, what you read in the paper, the political deals are, we have not slowed down the analog.

Mike: And various chemicals that go into it. So while we may slow down, you know, fentanyl itself, the analogs that go to making it haven't been slowed at all.

Randy: That's really true, Mike, you know, and the thing is that, you know, the gosh, I have so much information I want to share with you. (laugh) Oh, you know I mean, the bottom line is that, you know, these precursors essentially, this is what makes fentanyl.

Randy: Fentanyl is probably going to be with us for a long time, unfortunately, because the precursors, it takes two to three precursors. You put them together. You provide heat and suddenly four hours later, you've got fentanyl.

Randy: And this is very different than, you know, plant based opiates, because you don't have to grow anything.

Randy: You don't have to process anything. It's really just putting these precursors together. And it's so concentrated that one kilo, you know, 2.2 pounds of fentanyl is roughly about a million doses, and not just a million doses, it's a million lethal doses if it's used, I mean, if it's used inappropriately.

Mike: Yeah, well, if I'm using it on the street, thank goodness we have naloxone out there.

Randy: Yes, yes I will say this.

Mike: But...

Randy: Yeah. Let me, so I guess that kind of segues into what brought me into this field, into this field. And so, you know, once, so as I mentioned to you, we had in this small town that I lived in and we had the series of fentanyl overdose deaths and one of, you know, we all know each other in the medical community.

Randy: And I can't remember if it was a paramedic or one of the medical examiners who asked me. You know, several weeks later, after these deaths had occurred. He said, Hey, Randy, come here. you're an anesthesiologist, you get fentanyl, right? I'm like, yeah, I get fentanyl all the time. Well, hey, you know, I just wanted to ask you a question.

Randy: You know, this is the first time we've all seen heroin overdoses and opiate overdoses. We've never seen fentanyl overdoses before. And this is the first time we've seen three in a row. And I just want to ask you, does fentanyl cause seizures? And I said, no, fentanyl does not cause seizures. Why would you ask that?

Randy: And so what that person described was they said, well, we found each of the bodies that were in these really weird contorted positions, like they had had a seizure. And so I walked away from them thinking, well, fentanyl doesn't cause seizures. I know that for a fact, but then I was later on that day, I was on a run or something.

Randy: And I, I was, my mind was just wandering all of a sudden, like a lightning bolt. I thought, Oh my God, wooden chest syndrome, folks are having in the community setting that they're having that this is going to be a catastrophe. This is going to be so awful. So then the first thing I thought like you might is like, Hey, Hey, we've gotten Naloxone.

Randy: This should work. It'll be okay. So immediately I came back from my run. I got onto PubMed, you know, and which is you, I don't know if you're familiar with it. It's a worldwide database that has all the medical and scientific literature in the world. It's all right there in PubMed. It's an incredible resource.

Randy: And so, and it's free. It's available to anyone. And so anyway, so I went on PubMed and I'm looking for Naloxone, Naloxone fentanyl, you know, wooden chest syndrome. I'm looking, I'm looking at them. I'm not seeing anything. I'm not seeing any good studies where somebody has shown very clearly that naloxone antagonizes wooden chest syndrome.

Randy: So I'm looking in the clinical literature, the human literature, not seeing much. Then I look in the actual, the animal research, and I see that yes, someone has actually looked at wooden chest syndrome. No one looked at this vocal cord closure phenomenon. It had been completely just, not even touched in research.

Randy: And so I thought, Oh my God. We don't really know if Naloxone works. We don't really, no one knows the mechanism of fentanyl induced vocal cord closure. What's going on. And so I thought, well, before I, you know, before I get too crazy here and making plans of what I'm going to do, I'm going to call some folks that I know in addiction medicine.

Randy: And I'm going to ask them, I mean, obviously they have to know about wooden chest syndrome. They, you know, this is a common phenomenon with fentanyl, right? So I'm calling up there like. Randy, what are you talking about?

Randy: Wooden boat, wooden shoe? What? You know, and we all know that respiratory depression is how people die from opiate overdose.

Randy: Randy, what, what are you talking about? And so then I realized that they didn't know about it. And I knew if they didn't know about it, their patients definitely didn't know about it. Right. And so then that kind of pushed me to shift gears to think about, well, okay, all right, I'm a logical person.

Randy: I'm gonna I have to prove my hypothesis one step further. And I need to talk with people who are actually using fentanyl. Now, if I talk with them and I ask them if they've overdosed on fentanyl or witnessed a fentanyl overdose and they describe wooden chest syndrome to me without knowing about it, then I know that I need to be doing this.

Randy: And so the place that I ended up landing was I came to Portland, Oregon. And Portland already had a significant opiate issue, an opiate problem. But it was most commonly heroin. And so I came to Portland in 2017 and I just started talking to folks. And I went downtown, I started just talking with people, and what I learned from some of the folks that were using fentanyl that had either overdosed or witnessed an overdose, they started describing Wooden Chest Syndrome to me almost just textbook, without me providing any information to them.

Randy: And I said, Well, you know, is it is it different than with heroin? Oh, yeah, it's really different. My buddy, he overdosed. I mean, it was like immediate, was like lightning. And all of a sudden, he looked like he was having a seizure. And he just fell out on the ground. And he was unconscious. And I've never seen that before.

Randy: And so then I knew, and that's what wooden chest syndrome actually looks like when when fentanyl overdose occurs. And so so at that point, I thought, well, okay, You know I'm going to get some additional training. There was an addiction medicine program fellowship at OHSU, Oregon Health Science University.

Randy: So I, I joined the program. It's just 12 months. So I did the program and knowing that I would need to find a research team that I could work with. And so pretty shortly after getting there, I met up with Dr. Aaron Janowski, who was the head of, he's a neuropharmacologist there. And he was the former head of the methamphetamine research center.

Randy: And Aaron was like, Hey, Randy, this is fascinating. I've never heard of this wooden chest thing, you know, and this is crazy that we all know that it's respiratory depression, but you're saying it's something different. Okay. How can we help you? How can we figure this out? You're not an NIH researcher, you're just a clinician walking off the street.

Randy: What are we going to do? And how do you propose that, you know, we, these are the experiments we can do, but how do you propose to do this? So Mike, I bootstrapped it. I just, I, I started, I you know, begged my wife to lend me some money. (laugh)

Mike: (laugh)

Randy: She made me sell a couple of guitars and I'm a musician. So she made me sell a couple of, a couple of instruments and, you know that funded, that became the beginning of TMT.

Randy: So we started doing some of the just the binding assay studies where we look at what fentanyl actually binds to and with human receptors that we grow up in petri dishes. And we were able to show that fentanyl not only binds opioid receptors, just opiate receptors, just like we all know, but it also binds these off target receptors and adrenergic receptors, adrenaline receptors.

Randy: And so anyway, so we said, okay, well, this is interesting. And so then Aaron said, well, Randy, this is interesting, but where do we go with this? So he said, Hey, you know, we have to develop an animal model. So how are we going to do this? So I developed with my team there, we developed a translational animal model.

Randy: Where we can actually that replicates the symptoms that we see that the effects that we see in humans of wooden chest syndrome and vocal cord closure. We're able to replicate that in an animal model, and then we've used that as a platform to identify the targets in the brain that control this vocal cord phenomenon that fentanyl causes, and we've also been able to find several molecules that can reverse this this effect of fentanyl.

Randy: And so right now we're in the middle of seeking out more funding from what now we're funded by NIDA with the National Institute on Drug Abuse, we basically that first set of data that that I was able to get with Aaron's lab, we use that to to apply for grants through the NIH and NIDA, and they have been exceedingly supportive of this project now moving forward.

Randy: And so, we're basically in the middle of drug development and drug discovery. We're still in the preclinical stages. So in the animal stage, but we hope that here over the next couple of years, we will and really over the next 12 months, we're about to turbo charge our program here.

Randy: But we're hoping that we'll be able to move forward with some of these molecules through the FDA and hopefully be able to get more effective therapeutic agents out into the world. And one of the things that we didn't talk about, and you know is that in developing this animal model, the first thing that we wanted to do is we wanted to say we wanted to see whether or not Naloxone was effective for reversing this vocal cord closure phenomenon.

Randy: And what I can tell you is that at low doses of fentanyl. This is really important for your listeners and for your audience. I'm not saying that Naloxone doesn't work. What I'm saying is it has, it has limits. So for low doses of fentanyl, Naloxone works great. It reverses all of the fentanyl effects, but at higher doses.

Randy: Fentanyl, the higher dose effects of fentanyl with the airway with the upper airway, with vocal cord closure, those are actually resistant to Naloxone. And so if you give Naloxone immediately after somebody suffers from a fentanyl overdose, it may, it's probably going to work. It may work, but you're going to need higher doses than normal of Naloxone.

Mike: Well, I hear that from EMTs and law enforcement. I mean, every time I'm talking to people in law enforcement, they're like, it's everywhere. And now people are going straight to fentanyl now. And, you know, used to be, I've been present when somebody was having an overdose on an opiate and one puff.

Mike: Boom, boom, and they're talking to you. So it clearly, but that's not been the case with law enforcement in the last several years, right? It's like we're having to give multiple doses, and even then it may not be successful. So what you're looking for, Randy, if I'm right, is a partner to Narcan that might be more effective fentanyl since it's ever present.

Mike: And as you said, not going away?

Randy: Right. And so, yeah, so that's exactly what we're looking at because fentanyl has two separate effects Mike. One is it causes respiratory depression. You heard me on this, just like any other opiate, but it also causes this mechanical failure of respiration from airway obstruction and from chest wall rigidity. And so that is a completely separate phenomenon, physiologic phenomenon. And it's controlled by a completely different set of receptors in the brain, not opioid receptors. And so we're still trying to isolate the, unfortunately, the molecules that we're using hit multiple targets.

Randy: So we're still trying to isolate the exact targets involved. And that's what's taking the time here, but there are two separate targets. And so ultimately the ideal, you know, the ideal drug for reversing fentanyl effects at all levels will be a combination therapy of some kind. And so so yeah, it, you know, that's the thing is that.

Randy: Naloxone again. Naloxone is very effective for low doses of fentanyl, but once you get into those higher dose ranges and once you, you extend time, you know, in our animal model at 45. So if you give it immediately after somebody overdoses with high dose fentanyl it can reverse these effects of fentanyl, all the effects of fentanyl. You wait 30 seconds, that response rate goes down by about 60%.

Randy: 45 seconds. Yeah. 45 seconds, you're at 10 percent. At 60 seconds, it's zero. So, yeah.

Mike: That's a minute.

Randy: Yeah, it's a minute. It's a minute. So it's like lightning and that's, you know, so ultimately our goal is to develop new therapeutics that are safe enough for individuals to carry around just like Naloxone or nasal Narcan, and they'll be able to use it in conjunction with nasal Narcan or separately from nasal Narcan.

Mike: Wow.

Randy: And they'll be able to use it for any type of opioid, you know, overdose. Whether it's fentanyl or heroin or any other morphine derived alkaloid. So.

Mike: I hope you'll consider coming back and talking to us as your research continues.

Randy: I would love to, Mike. And I realized, you know, you said 30 minutes will go really fast.

Randy: Sure did.

Mike: I know. The hardest thing, Randy, for me with these is when I have somebody I really like talking to is going, Ah, looking at the clock and sometimes they go over 30 minutes, but we know that there's a listener fatigue, right?

Randy: Right.

Mike: People are listening in their cars, they have to go somewhere. But I'll let you go with this though. And it's something that you said, or that I read that you, you said, this information is important to share. What you just shared is important to share. Now we have a number of therapists that are listening.

Mike: We have a number of treatment professionals, as well as lay people who have and are using and recovering folks. How optimistic are you that the crisis we're currently going through can turn around with research and education?

Randy: You know, I'm so glad you asked me that question. You know, I don't mean to paint a picture of doom and gloom here.

Randy: This is the only way that we are going to find the effective treatment and therapeutic solution for fentanyl is by understanding its mechanism. And we've reached that point. So at this point, I can tell you, I'm very optimistic that we will be able to move past this fentanyl crisis. We'll be able to save lives.

Randy: And that 100,000 year, you know, 100,000 patient per year death mark will go away at some point in the near future. But it begins with education to like, like today, you know, sharing this information with your audience and with other therapists and other physicians who are out there and medical providers that can share this information with their patients.

Randy: The other thing too, is just to really point out that fentanyl is a highly addictive substance. And it is unique in that it has it's highly addictive because it has a very short half life. So it's very fast on, very fast off. It also causes something called hyperalgesia, which is just as bad as it sounds.

Randy: It dramatically increases the pain that someone can have. It lowers the threshold for physiologic pain. And so when someone goes through withdrawal on fentanyl, it's particularly horrific. And so it's those feeling that the physiologic symptoms of withdrawal are significantly elevated with fentanyl. And the other thing, too, is that fentanyl stays on board in the body in the muscle and fat compartments in the body for up to 30 days. So it stays a really long, long time. And so it makes it challenging for us to treat folks who come in who are actively using fentanyl.

Randy: What I would say is that you know, it's important to know that there is medically assisted treatment like methadone and suboxone, which are can be very effective and helping someone to pull themselves off the harmful path of using fentanyl on a daily basis. And then, you know, and then over time. As the brain heals, that's the other thing too.

Randy: At some point, you know, I would love to talk to you, to your, to you and to your audience more about what the nature of addiction is actually, the neurogenetic process of addiction. But the bottom line is that when that, that person comes in and makes the choice to, to shift off of fentanyl, they're saving their life.

Randy: That first step is saving their life. So if anyone you know is, is actively using any kind of drug at this point, because it's basically in everything.

Mike: Yup.

Randy: And I can say that for a fact because our lab actually, Aaron's lab is contracted with the DEA. They send us samples from hotspots all around the country.

Randy: Everything has fentanyl in it, some form of fentanyl. And so if anybody's using drugs that you know, they're at risk for being exposed to fentanyl and all it takes. Again, it's just that two to three grains of salt, of fentanyl, and anything that they're using, and it's lethal. Whether they smoke it and inject it, or take it orally, it becomes lethal.

Randy: So get into treatment. There is good treatment available. Don't, you know, know that, know that help is there, there in Portland, Oregon, we have CODA, we have Central City Concern, which are incredible facilities and help thousands of people who are here suffering from opioid use disorder and other addictive substance use disorders.

Randy: But bottom line is I would love to come back and talk with you more. and provide more information to you. Bottom line, if you see somebody have an atypical response to an opiate, they're probably using fentanyl. If they look like they're having a seizure, if it's immediate and onset, that they become unconscious, call 911.

Randy: You got to get backup. You got to get the cavalry there. And then you give Naloxone and you do the supportive therapy that you need to do for helping with their breathing and trying to get that Naloxone on board. And it's going to probably take multiple doses. So just be aware of that. Carry multiple doses of Naloxone with you.

Randy: And so anyway, with that, thank you so much for having me today.

Mike: Thank you, Randy. And instead of doom and gloom, I found that you're the opposite. This is innovation and initiative. So thank you for your work. Thank you for the research and thanks for taking the time. You all know this we're going to put links to TMT RX at the bottom of the podcast.

Mike: Thanks for being with us today. And for those of you listening, we always invite you to listen in next time. And until next time, stay safe and stay informed.