Hi, everyone. Thanks for joining us today. I'd like to welcome you all to today's webinar, Substances and Their Effects on Our Brains. The webinar is brought to you on behalf of Bennington Rescue Squad and sponsored by the New England Region Opioid Response Network. Next slide, please. I'm Kathy Whalen, Technology Transfer Specialist working for the New England Region of the ORN. The ORN is funded through a grant by the Substance Abuse and Mental Health Services Administration and our grant prime is the American Academy of Addiction Psychiatry. We provide technical assistance to individuals, groups, and organizations in the form of education and training regarding opioid and stimulant use disorders and we cover the areas of prevention, treatment, recovery, and harm reduction. Next slide, please. This is provided at no cost as it's covered through the SAMHSA grant. And next slide. If you wish to submit another request in the future, our contact information can be found in this slide. We're fortunate to have Dr. John Brooklyn as our presenter. Dr. Brooklyn is board certified in family medicine and addiction medicine and is clinical associate professor of family medicine and psychiatry at the UVM Larna College of Medicine. He is on the UVM Center for Rural Addictions faculty as a clinical expert. Dr. Brooklyn has a 30-year career as a practicing physician at the federally qualified community health centers of Burlington and continues as the medical director of the Howard Center Chittenden Clinic Hub and the St. Albans Bar Hub. In 2000, he collectively started the nationally recognized CHARM group to coordinate the care of pregnant opioid users and their babies to promote intact families. Dr. Brooklyn helped open five of Vermont's eight opioid treatment hubs and was one of the first physicians nationwide to prescribe buprenorphine. He created the internationally recognized Vermont Hub and Spoke model to integrate opioid treatment into primary care, helped establish opioid treatment in Vermont prisons, works on technology solutions to expand access, and has mentored many in the field. Before I turn the webinar over to him, I wanted to review a few of the Zoom controls that you'll be using. I enabled the live transcript feature if you wish to use it. Please drop your name in the chat and you can also use the chat if you need any technical assistance or for any topic related comments. The webinar will be recorded during the didactic portion and you'll be muted and your cameras will be turned off. Please use the Q&A box for any questions that you have during that time. When the presentation is finished, I'll turn the recording off and we'll open up to the Q&A session. We'll address the questions in the Q&A box and if you wish to speak with Dr. Brooklyn directly to ask a question, you can use the raise hand feature. I'll promote you to a panelist and you'll be able to unmute and turn your camera on. The last slide in the presentation will include the ORN evaluation survey. You can access it with either the link or the QR code. Please take a few minutes to complete it as your feedback is very important to us. We'll be sending you a certificate of completion and copy of the slides in about one to two weeks. And I'll now hand this over to Dr. Brooklyn. Thank you, Kathy. I appreciate it. Good afternoon, everybody. Thanks for joining. I just want to express my appreciation for all the work that you do in the trenches day in and day out because I do recognize that people who have substance use disorder can be extremely challenging on a day-to-day basis and somewhat frustrating. And I include myself in that category. What I'm hoping to do today is share with you some things about the way the human brain works when it's exposed to drugs, specifically opioids and alcohol. The common treatments that we use so that you'll have a better understanding of what actually happens when people go to treatment. And then hopefully answer some questions that you may have about some of the details I'm going to describe. I have 90 slides. Most of them don't have words on them. They're more for illustrative purposes and I hope to leave about 20 minutes for questions. So without further ado, I'd like to begin. So I think one of the most important concepts I try to get people to understand is that our brains, as many of you probably know, are hardwired for novelty. We actually have in a system built in for a reward network. So when we go to work, we get paid. When we buy food in the store and we eat it, we feel sated. And generally the currency in the brain that's used is a chemical called dopamine. When something pleasurable happens, we release dopamine. And drugs can hijack that system by increasing the amount of dopamine that normally would be released. We also do think that there are some people, some individuals, who don't make a lot of dopamine and they tend to choose substances that will increase the level of dopamine that they get released. This is an example, for instance, of when we're eating food, we release a little bit of dopamine. But when people use cocaine, they release a lot of dopamine. So in many ways, it's a hijack. But all humans and most mammals actually use dopamine as a currency. So these are some of the activities that are non-drug related that people engage in. Gambling, eating, especially fatty foods, sugary sodas, shopping, skydiving, all of these things will release dopamine and can become quite compulsive in individuals, even though they're not particularly drug related. We have a variety of substances that people use. Up in the upper left corner, we have different cannabinoids, which are in the form of gummies. We have K2 spice. We have crystals. We have powders. We have things that are made in a lab. And all of these things are unfortunately or fortunately used by individuals to get some kind of a psychoactive effect. A key thing to understand is that in the beginning, when most of us do something pleasurable, and that includes drug taking, we get a positive reinforcement. We like it. Some of you out there may have had alcohol or a substance at one point and didn't like it. You had a negative reinforcement. And so in many ways, you would not have continued to use it. But for many people, if they get a positive reinforcement, they like it, they repeat the behavior, and they continue to do it until they reach a certain saturation point where doing it doesn't any longer provide the same amount of pleasure or enjoyment. For some individuals who become physically dependent on a substance, and we'll talk about that in a minute, they can't stop using because if they do, they actually become physically ill through withdrawal. And that provides a negative reinforcer so that they almost have to do something in order to feel well. In this case, we see in blue the lines that relate to the positive reinforcement and the red relating to where the negative reinforcement in the brain is. And that part of the brain where the red is, is the part which is fear-based. So we also have individuals who've had traumatic events happen to them, and they have a negative reinforcer all the time. And so they might take alcohol or opiates or cocaine to try to reduce the amount of fear that they feel on a regular basis, even though it provides a negative level of reinforcement. So drugs can provide both a positive and a negative reinforcement in the brain. This is just another depiction of the same process. These processes are deep in the brain, they're kind of below the level of consciousness, but once people start to like something and they do it over and over again, they become volitional. They go out of their way to make the same process happen over and over again. Now there's a distinction I think we need to make between people, between drugs and substances that people like and ones that people can become physically dependent. The word physical dependence means that there's a receptor in the brain, and we have receptors in the brain for opiates, for cannabis, for alcohol, for nicotine. So these are drugs that when people take them, they can become physically dependent on them. But being physically dependent doesn't mean you necessarily have a use disorder. So if your doctor puts you on painkillers for a period of time and you're not misusing them and you're taking them as needed, you will become physically dependent to the point where if you're taken off of them, you will actually be physically ill. So physical dependence merely means you're binding to a receptor, which causes tolerance, meaning you need more and more for the same effect, or withdrawal. You get sick if you don't have that substance. So these drugs, as I mentioned, nicotine, alcohol, opioids, and cannabis all have receptors in the human brain. However, cocaine and amphetamines, while there is some theoretical aspect to people being physically ill when they don't get them, don't actually bind to a receptor. They cause the release of dopamine, but they typically don't have a withdrawal syndrome associated with that. And I think that's critical in our understanding when it comes to people who are using opiates and using alcohol, is they are sick when they don't continue to use that substance. In many individuals, people can use a substance and not use too much of it. In other individuals, they continue to use despite having enough. And the question is, what distinguishes each person when is enough enough? And so we get to this point of this compulsive use, and some people would call this addiction, where you continue to use despite all the consequences, the social, the physical, the legal aspects of it, people continue to use despite the consequences. And many of us who don't do that scratch our heads and say, how come this person keeps doing this over and over again? Don't they know better? Don't they know that this kind of behavior is getting them in trouble or they're overdosing over and over again? And in many cases, their brains have been damaged through years of substance use where it's hard for them to actually stop. So there are certain conditions that predispose an individual to substance use. There's a strong family history, a strong genetic component to this. We have, you see, and probably in your work, families where there's generations of alcohol use or substance use, and there's a certain way that drugs are metabolized. Some people metabolize them quickly, some slowly. That all plays a role. Certainly the history of trauma, victimization, adverse childhood events, and then the social aspects where people just feel pressured to use. All of these things can contribute as risk factors for why people choose to use substances. And then we have some psychological factors that go into it. We know that people with these conditions listed here are more likely to use substances than people without them. Certainly there are different personality types that lend themselves more to using substances such as antisocial, sociopathic, borderline. But that doesn't mean that everybody with these conditions uses, it's just, it's a comorbid situation where people perhaps also have this situation and use substances, which makes treatment sometimes more complicated. So then we're left with this situation of craving. And craving is an interesting concept because cravings seem to come on from the part of the brain I showed you early, the amygdala, and they come on kind of out of nowhere. Someone could be, in fact, many of us could be sitting here right now saying, boy, I'm really craving a pizza. I'm already getting tired of listening to this lecture. And you're thinking, where did that come from? And it comes from the part of the brain that's a little bored, a little tired, and wants a little novelty or a little pickup. And so people who are in long-term treatment with alcohol or opiate treatment can also still have cravings at times, especially in response to psychological stress. And so for a lot of people who are doing well for a while, they may encounter a bump in the road and they suddenly can't do anything but think about using substances. And so we recognize that even though people are in treatment, they're still at risk for relapse often because of cravings. There's also an interesting thing about the probability of using. So we know that the less craving a person has, the less likely they are to use, and the more cravings they have, the more likely they are to use. So we often work with people to try to deflect or divert their attention from the craving to do something else to take their mind off it. And oftentimes, that feeling will go away. We also know that stress and anxiety lead to cravings, which lead to use. So we also work with people to try to reduce their anxiety and their stress so they're less likely to have a craving. OK, so let's talk. That's sort of a brief overview of the biochemistry of the brain and what leads to use. So let's talk now specifically about opioids, and the word opioid refers to any substance that is derived from the opium poppy. This is a poppy from Afghanistan. In the fields, people will go and make a slice on the side of the poppy, the sap will run out, it's dried, it's removed, and then it's made into a variety of compounds. This is morphine, which is 10 times stronger than opium. This was first discovered in the mid-1800s, first actually opioid designed to treat pain. It was valuable in the Civil War and the Crimean War when it first came into widespread use. Codeine is a weaker form of morphine, also derived from opium, used often in cough syrup. In Canada, you can buy it over the counter. Some countries think lowly of codeine, but it still is an opioid. Heroin, believe it or not, was marketed by the Bayer Corporation, who makes aspirin, somewhere in the 1880s, 1890s, as a cure for people who were addicted to morphine from the Civil War. Because after the Civil War, so many soldiers in the Crimean War in Europe, so many soldiers were exposed to morphine on a regular basis because of horrific wounds, they become physically dependent on it. It was a problem in the United States to the point where the Bayer Corporation thought if they gave people heroin, at the time was an oral form to take, it would relieve them of their morphine dependence, but in fact, it did not because people found that they could inject the heroin and it was 10 times or 50 times more potent than if they took it by mouth. Heroin suddenly became a drug of abuse in the turn of the century into the 20th century, but it was originally marketed for pain and for treatment of addiction. Fast forward to the 1960s, where we have oxycodone, which designed as a more powerful medicine than morphine. You could take it in smaller doses. Oxycontin, as we all know, was formulated in the 1990s by the Purdue Corporation and marketed as no abuse potential. We know that that was completely false at this point. Then we see that in anybody who is exposed to painkillers, this is a study from 2020, that the likelihood of getting a prescription for pain from your doctor and the likelihood of one year later, you actually having a opiate use, continued opiate use, goes up with every day that you've been prescribed. You can see that even at day 10, if you got 10 days worth of medication, that at one year there's a 25% likelihood you would still be on it and have a problem with this. We now know that there's probably no duration of time which opioid painkillers were relatively safe. In Vermont, as many of you know, we have these laws now or regulations around prescribing where we have to be very careful of how we prescribe and why we prescribe so we could try to avoid the problems that we encountered at the turn of the 20th century. And then we move to heroin. Heroin is unfortunately very easy to make. It's a white powder, as many of you probably know, it's packaged in these little baggies and branded and sold throughout the world. Unfortunately in the United States and Canada, we are the only two countries in the world currently that are suffering from fentanyl because as you can see here, if I go back a slide, the amount of powder in this bag is typically about 100 milligrams of powder and the dose of fentanyl that one uses is right here in terms of the amount of fentanyl that one would need for the similar amount of heroin. It's about 100 times as potent as heroin. Now fentanyl that we get in the hospital is manufactured through a very complex regulated process. The fentanyl that's brought into the United States and Canada from Mexico is made usually in the jungle in one pot. The precursor chemical comes from India or China. It's made by the cartels. It's stirred with baking soda and made into fentanyl with potency anywhere from 0.5 to 30%. When this stuff comes up into the United States, no one really knows the potency or the purity of it. You'll see here is bags or little bits. It's pressed into pills. The trouble is that, as many of you know in your work, is that when someone's using fentanyl, at least with heroin, you had a relatively good idea about the potency of it. Even though it might be cut with fentanyl, no one knows. It's really difficult to determine how much fentanyl someone has used, which is why it is so deadly and so difficult to deal with because it's just an unknown quantity oftentimes. Also, as many of you probably know, you can buy counterfeit prescriptions over the internet. These things are advertised. You have some of the more common drugs that actually don't contain this. You have Xanax, Adderall, Klonopin, OxyContin, Ativan. All of these pills have actually been found, even though they look like this, to have fentanyl in them. It's a really Russian roulette when someone's buying some of these things to know if the drug is actually in it because these are all counterfeit pills manufactured by cartels and advertised. Someone might think they're buying the Xanax when actually they're getting a pressed fentanyl pill. Opiates in the brain have an interesting effect. We make adrenaline in the brain. We have receptors on these cells for a chemical called an endorphin to bind to the cell to stop the production of adrenaline. Let's say for the sake of argument, you're in pain or you're really stressed out, you're making a lot of adrenaline. We release an endorphin. It's a relatively weak opioid that we make. This is something that we create. We have a receptor for it. When people hijack this system by taking opioid pills, you begin to change the way that the cells operate. It prevents the cell from making adrenaline. Over time, the cells make more and more of these receptors because they want to make more adrenaline and you need more and more binding of the endorphins to actually prevent that from happening. Let's say you replace this with morphine or oxycodone or heroin and you begin to take it. Over time, this cell becomes oversensitized and you need more and more of the drug to stop the production of adrenaline. If for some reason you don't get the drug that day and the receptors are not occupied by the drug, you begin to increase the amount of adrenaline that you make. Most people who are going through opioid withdrawal are actually going through an intense adrenaline rush that doesn't stop and can go on for days on end. When they use, they rebind the opioid at this receptor and it stops the production of adrenaline. For most people, this becomes a chronic condition, especially if they use heroin and probably fentanyl because those drugs have a very fast action. They don't last very long and then they wear off and people use over and over again. That stimulation of the cell on and off with heroin or fentanyl creates a situation whereby we know that for many, many people, once they reach a threshold of using on a regular daily basis may have permanently altered the way that these cells work so that they don't have something binding to that receptor, whether it be methadone or suboxone or naltrexone or an opioid, they're going to feel ill. For many of us in the field of opioid use, we know that people need long-term treatment. It's not like you're going to go to rehab for a couple of days or a week or a month. You've actually changed the way your brain works, which makes it challenging because it means that there's going to be a long-term commitment to people being on methadone or buprenorphine in order to stop using. This again is a picture of pressed pills and the danger that we all know. There's also some newer opiates on the market. We haven't seen much of this in Vermont, the pinkie or the iso, but this is also added to some of this opioid mixture, as is this one, xylosine, which you're probably all familiar with. Just to recap, xylosine is an animal tranquilizer. It's in some ways similar to clonidine, which is a blood pressure medication. I think since 2022, it's been seen in the drug supply in Vermont. It took a little while to get up here. It was in Massachusetts for a while, but by adding xylosine, you're actually complicating the situation whereby people are now getting an opiate and a sedative, and Narcan has no reversal capability of this because this is not an opioid. As many of you know, you try to reverse somebody who's overdosed, and if they have fentanyl on board, it will help with that, but the xylosine just causes people to be continuously sedated. I heard reports this past fall, especially in the Burlington area where there was sales of only xylosine. There was actually no fentanyl in some of this stuff, and people were actually seeking it out because they got very, very sedated, and they couldn't be reversed with Narcan. In addition, as many of you know, this drug, when it's injected into humans, and it's typically only when injected, not when it's sniffed or smoked, causes these wounds, and the wounds don't often appear on the site of which they injected. So someone could inject in the arm and develop a wound on the leg that takes a long time to heal. So we really struggled, I think, for a while. It seems like the supply of xylosine has dropped off with a lot of people also dealing with wounds in addition to dealing with their opiate use. So the effects of opioids, as many of you know, it's an analgesic. It can make you drowsy. It can cloud your thinking. It can also cause constipation. It can make your pupils small, and it can affect your respiration. So oftentimes, people who are intoxicated from opiates will have some of these symptoms. Obviously, the worst case scenario is reduced respiration and even cessation of breathing because of the effects of the opioid. And then when people are going through withdrawal, it's really looking like somebody who has the flu. They've got runny nose. They've got runny eyes. They're often vomiting. They have diarrhea. They're tremulous. They're sweating. And this mostly is because of the uncoupling of the opioid from the different receptors in the brain, the gut, and the spinal cord. And so people just feel terribly. And then when they take opiates again, most of these things tend to resolve. So we're often dealing with people who want to avoid this situation. All right. So let's talk about the three FDA-approved medications for opiate use disorder. In this picture here, you can see the little pink spots are areas where there's predominance of these opioid receptors. And the opioid receptors are attached, as I mentioned, cells that make adrenaline. So we have methadone. Methadone is a pure opioid agonist. It was developed in the 1930s as an alternative to morphine by the Germans who couldn't get opium from Turkey at the time. It was studied in the 1940s and in the 1960s, really codified to show that if you gave a heroin user methadone on a daily basis, they would stop using heroin altogether. And in about six months, their brains would stabilize to the point where their cravings went away. Their using stopped. And there are people who've been on methadone for 40 years now. I've met a number of these folks around the country in my different travels who've been on methadone for a long time. And it's really just kind of a replacement situation for them where without this drug, they wouldn't do well. And with the drug, they're completely functional. Buprenorphine is an alternative to methadone. It was developed. We did a lot of research here at UVM in the 90s, a couple other places around the country. The FDA approved it in 2000. 2002, we first started prescribing it in Vermont in the United States. Buprenorphine also fits into that receptor a little bit differently. People can still use on top of methadone and feel the effects of opioids until they reach a point where they're not using anymore. Buprenorphine in the pre-fentanyl era did a very good job of blocking heroin users from feeling euphoria. It prevented oxycodone users from feeling euphoria. But in the fentanyl era, people have discovered that fentanyl can actually overcome the effects of buprenorphine. And so one of the things to know is that people who are taking buprenorphine on a regular basis, if they use fentanyl, they may not feel the effects or they may feel the effects. And if they stop using buprenorphine and start using fentanyl, it's difficult for them to get back on to buprenorphine because buprenorphine will displace all the opioids at the receptor. So we see a lot of times people who are previously doing well on buprenorphine, no longer doing well and actually needing to go on to methadone to make that transition so that they can continue to remain in treatment. Naltrexone is the third one here. It's actually not very effective against opioid users. You all use Narcan in your work. Naltrexone is the long-acting form of Narcan. However, you need to be in an opioid-free state for Naltrexone to work. And Naltrexone actually works quite well for alcohol use. We'll talk about that later, but not very effective. In Vermont, we have about 10,000 people currently in treatment for opioid use disorder with methadone and buprenorphine. And I think out of that number, maybe 20 people are on Naltrexone. It's just not an effective treatment for a lot of people. So we tend to shy away from it. The other thing is that if you go on to Naltrexone, let's say you're in jail and you decide to use Naltrexone, you're in an opioid-free state and you come out. Because you're in an opioid-free state, you're much more likely to overdose and die on Naltrexone because you've lost your tolerance. And if you use, if you stop going for your injection, your monthly injection, and you use, the likelihood of dying is much higher. So there's a lot of studies pointing to the fact that people on Naltrexone are higher risk of overdose than people on methadone or buprenorphine. This slide basically shows that methadone is a full agonist. The more you take, the more effect you have. Buprenorphine is a partial agonist. It works up to a certain level, and then it just stays in your body and is a blocker. And then Naltrexone doesn't give you any effect, but it's a complete blocker for opiates. So anybody who's on methadone in Vermont in the United States, essentially for opiate use disorder, tends to get liquid methadone. People who get treated with methadone for pain tend to get pills. We do have some studies going on here in Vermont where we're using the pills in a wheel that dispenses medication through the hub with a video app, but we're really not going to talk about that. Essentially, people need to go to the clinic to get methadone in a liquid form. Once they're stable, we begin to get in a liquid form. Once they're stable, we begin to give them take-homes. But for the most part, it's liquid methadone for opiate use disorder and pills for pain. People are constrained. So down in the Bennington area, your closest clinic is either Brattleboro, Rutland, or perhaps North Adams. Maybe even people go to Albany. The hours are somewhat restricted. They're not open all day. The clinics are sometimes far away. And you need to have a clinic available to do that. I think there's talk of a clinic of an opioid treatment program opening up in Bennington, but until that happens, Vermonters do have to travel a bit of time. I have patients who travel hour and a half each day to get treatment. So in many ways, you're competing with the, as I call it, the Amazon drone delivery of fentanyl to your doorstep. Some dealer can drive up to you and bring you your fentanyl. No one's going to do that with methadone. So the commitment to going onto methadone is higher than it would be to continuously use, especially in a rural state. And there are restrictions, but we're doing the best we can to make methadone more available with less restrictions in the U.S. Buprenorphine comes in typically tablets or film. Brand name Suboxone, one we typically use in Vermont, is now a generic form. The Suboxone here and here have Narcan added so that people can be less likely to inject. This Mono only has Buprenorphine without the Narcan. It's thought to be more divertible, but there are people who have intolerance to Narcan and they have to go on the Mono product. There's also an injection now for Buprenorphine called Sublicate. It's a monthly injection. You start with a 300 milligram dose for a couple months and then move to a 100 milligram dose. It can be very effective. People don't have to travel. They don't have to go to the pharmacy. They don't have to take the dose every day. There's actually another brand that's come out called Brixadi that's weekly and monthly shots. So for a lot of people, we really like this. And one could envision just parenthetically, if you're in the field and we're going to initiate Buprenorphine, there are some places around the U.S. where after you've been reversed with Naloxone, if you're interested in treatment, they can actually start you on the injectable form of Buprenorphine. Now, typically what happens is that people are supposed to be on the oral formulation, a sublingual formulation for a number of days to make sure they tolerate it. But I've read case reports of people starting Buprenorphine in the field and then the person has like a month long injection already in place. So that's something perhaps down the road we'll be talking about more. So in terms of starting people on Methadone and Buprenorphine, I like to use the analogy of a swimming pool, an empty swimming pool. Let's say you're going to start somebody on Methadone. We have two ways to fill a swimming pool, right? You have the garden hose and you have the tanker truck. So for me, Methadone is more like filling the swimming pool with the garden hose. We have to kind of bring you up to a certain level. You can't end up on the level you're going to end up the first day. But when it comes to Buprenorphine, we theoretically could dump the water into the pool and you could be swimming later in the day. There are cases where people end up on 16 or 24 milligrams of Buprenorphine the very first day. A comparable dose of Methadone would be 120 milligrams. And in the best circumstances, it would probably take you a couple of weeks to get to that dose. However, it's becoming more available to be started at different places. So now we have emergency departments starting people on Methadone. We have inpatient admissions to hospitals where they're starting people on Methadone. We will always start people on Methadone at the hub. That's what we do. And also in prisons, people are being initiated on to Methadone. So there's many more ways on to Methadone now than once were. As far as I know, Valley Vista, which used to have a Methadone program is not inducting people. They will take people on Methadone and Serenity House is not currently inducting people, but perhaps someday those places will also become places that Methadone can be initiated. All right. And so Narcan, you're probably relatively familiar with Narcan. Having used it in the field, it reverses opioid overdose. It says here with one dose. We know now that's not the case. Sometimes people need four or five and six doses because of the varying purity of Fentanyl. It's also added to Buprenorphine to make Suboxone. It was added so that people wouldn't inject Buprenorphine, although Naloxone won't reverse Buprenorphine. It was more designed to prevent heroin users from injecting Buprenorphine as an alternative. It kicks all the opioids in the brain and precipitates withdrawal. I can imagine what it's like if you're in a rural environment and you find somebody who's down and you give them Narcan and then you got them in the back of the squad and you got to drive them all the way into the hospital. They're probably madder as a wet hen and there's probably no way to really, or maybe you do, regulate the amount of Narcan you give somebody to just kind of lift them a little bit but not make them completely agitated because you all know that it precipitates withdrawal and people don't feel well. I believe the availability is much greater in Vermont than it once was. It's almost as though it ought to be everywhere given the preponderance of overdoses in our state right now. As I mentioned, we have levels of treatment here in the state. We have the hubs which are, there are eight of them. There is methadone and Buprenorphine dispensed for both of those places. People have to go daily until they get take-homes. There are spoke programs called Super Spokes. There's a Civita. There's Better Life Partners. These are somewhat virtual online programs but they're also programs that do provide Suboxone as a singular entity. The Phoenix House used to do that. The Howard Center has some Super Spoke programs where they just prescribe Buprenorphine but typically a spoke is a community health center or an internal medicine or an OBGYN practice that also provides Buprenorphine and is linked to the hub in that county. We have the needle exchange programs where in some cases Buprenorphine is dispensed and then we have people who are buying it and inducting themselves on the street. The idea is that there's probably no wrong door even though we're not fans of street inductions. We know that a lot of people will share their medication, their methadone or Buprenorphine with somebody, keep them from using fentanyl that day. They'll start taking it, they'll like it, and they'll seek treatment. That's really the goal is that if you've been exposed to it, you like it, let's get you into formal treatment so you can get it properly. One thing I want to point out is this whole concept of harm reduction. Harm reduction does not mean poor care. It means you're working with somebody to reduce the harm from their use. These are often practical strategies to reduce negative consequences for you. For instance, if you're going to use opiates, are you using with somebody else? Do you have Narcan available? Are you using clean needles? We're using evidence-based intervention. Abstinence is a great idea, but it's not necessarily where everybody is at. Some people enjoy using once a week, using with friends. We might think of having a beer with friends as an enjoyable thing. Some people like the idea of using opiates with friends, but the idea is we're reducing the harm and the damage that occurs. If someone has gone from using six times a day, seven days a week for 42 times a week, and they're down to one time, they've reduced from 42 to one. That's a significant victory, but they haven't decided to stop. It also provides low-threshold access to service. It's not anything goes. It's not ignoring or minimizing the harms. It's really just trying to make it so that there's a common understanding of what we're working towards, and not like an all-or-none approach. Let's talk about the most common drug misused in the state of Vermont, which is ethanol. For many of you, you may not actually think about how alcohol works in the body, but once we start to drink alcohol, it immediately gets into the bloodstream through the mouth. It goes to the brain within a matter of minutes, and then it goes to the stomach where some alcohol gets into the bloodstream, small intestines. It then passes into the heart where it gets pumped through the body. It doesn't reach the liver until later in the game. Really, liver metabolism doesn't happen right away. Alcohol is actually metabolized initially in the stomach and then in the liver. The thing is that alcohol, once you reach a blood alcohol level, is metabolized by the liver at a fixed rate. Your BAC, whatever it is, is the rate at which you have to break it down. There's nothing that you can really do to break it down faster. We convert alcohol into water, carbon dioxide, and energy. We're just going to take you through the pathway of how alcohol actually works in the brain. This is an image of different size glasses of what equals what in Vermont now, which has become homebrew capital, microbrew capital. You have beers that are 8% and 9%. When you have here this 12 ounces of a beer or a cooler, that's typically a 4%, 4.5%. Then when you have the higher potency alcohols, you're really talking about 8 ounces of an 8% IPA would be equal to 12 ounces of a 4% IPA, something of that sort. These are the chemicals that are released. We actually release opiates in our brain when we drink. Initially, when you drink alcohol, you feel euphoric, you feel giddy, you feel relaxed. That's because you're activating both the endorphin, the opioid system, and you're also activating the dopamine system. You've got two things happening at once. Alcohol works very similar to opioids initially in the brain, but over time, if you continue to drink, that fades in about 30 minutes. Then you begin to have a sedating effect from the alcohol, where it reduces your cognition, your coordination, then you have emotional swinging. Usually, by the time you're onto your second alcoholic drink, you're beginning to have some of the negative effects of the alcohol. In fact, I often say to people, if you really want to have the full effect of alcohol, take a few sips and savor it and close your eyes. You'll feel that warm, giddy, euphoric feeling, because after that, it's all going to be a negative effect from that point forward. The problem is that when people like that initial effect, they keep drinking because they think more and more is going to give them the same, and then they run into a situation where their blood alcohol level goes up. We're also then faced with these two chemicals in the brain called GABA and glutamate. GABA is an inhibitory neurotransmitter, which prevents the transmission of adrenaline and dopamine. Glutamate counteracts that. It's an excitatory chemical, where when that gets released, people get really anxious and uptight. These two chemicals, once you pass the endorphin, dopamine, are the ones that are getting activated. As I mentioned earlier, alcohol is metabolized in the liver, and the rate of alcohol clearance is a constant. It's this number, 0.015% per hour. For the sake of argument, for those of you who aren't super strong in math, say you've got somebody with a BAC of 0.1, above the legal limit. It's going to take them seven hours to get to 0%, because seven times 0.015 is essentially 0.105. There's nothing that someone can do to, once they reach that blood alcohol level, make that metabolism work any faster. Yes, you can drink some coffee to be a little bit more alert, but it's not going to help you metabolize the alcohol any faster. It takes two hours to fully eliminate one standard drink. There are people who have genetic variations, who don't have the first enzyme that breaks alcohol down, and so they get a flushing response. All humans, when we drink alcohol, we break it down to acetaldehyde, which is similar to formaldehyde or embalming fluid. If I said to anybody in this room, would you like to drink this glass of formaldehyde? You look at me like I'm crazy, but when you consume alcohol, you convert it to a compound like formaldehyde, which we then have to process. That formaldehyde buildup, or that acetaldehyde buildup, is actually what leads to hangovers. People who wake up the next morning fairly poorly, it's because they've accumulated all that acetaldehyde. Men who have alcohol use disorder have less of this enzyme, so they're not able to metabolize it as quickly. They get higher blood alcohol levels because they're not breaking it down, and they're much more susceptible to being intoxicated. This is a chart showing you, as I'm sure you all know, what happens with your BAC in terms of coordination and intoxication. Just to point out, at 0.04, 15% of drivers are still too intoxicated to drive. The legal limit in Vermont is 0.08, but you certainly have people who are driving under that limit who are too intoxicated to drive. In some ways, it almost doesn't matter what ... I mean, it does from a legal perspective, the BAC, but there are people who are impaired even at lower BACs. We need to pay attention to those individuals also. The recommendation for alcohol use, you've probably all seen this, for healthy men up to 65 is no more than four drinks in a day, no more than 14 in a week. This has been a little bit disputed by Canadian studies, but we'll let it stand for the moment. Healthy women and healthy men over 65, no more than three in a day, no more than seven in a week, something we should pay attention to. People that have alcohol use disorder, they start drinking young, they start developing problems young, and they tend to die young. We need to know that in people that start drinking at a young age, it's not a great idea and it usually doesn't turn out well for them. There are two questions I like to ask when I'm interviewing somebody with their alcohol use because I'm trying to make a connection. I usually say, when was the last time you had a drink of alcohol? The reason I ask that is it normalizes the fact that people do drink. When was the last time you had a drink? Then I like to know how much does it take for you to get a buzz? How much do you need to get an effect? Those two questions can really help you identify who has a problem and what the extent of the problem is. The reason for that is that we have people who we have to think about the negative consequences of their alcohol use, the risk of seizures, the risk of severe withdrawal. When you're seeing somebody determine, do I need to take this person to the hospital or not? Are they at risk for seizure and withdrawal? If you've ever had a seizure before, you're likely to have one again. Most people experience mild withdrawal. So should I take him to the hospital or not? That's a determining question. These are the conditions in which it's more likely that people will need to go to the hospital. We have a lot of people in treatment who have these histories also need to go to the hospital. But for the most part, we can treat people with medications. And I'm just going to spend a few minutes and then we'll be done and take some questions. So we have different kinds of therapies. We have aversive therapy, which is called anabuse or desulfiram. People take it. If they drink, they get sick. We have our friend naltrexone, which is an opioid antagonist. When people take it orally or a monthly shot, it can really cut down on the amount of alcohol that they drink and the frequency with which they drink. And I think this is probably the most effective of the three FDA approved medicines we have for alcohol use is naltrexone. So getting people on monthly shots of Vivitrol, as it called, would be very helpful. We have acamprosate, which also is an oral medication that reduces that amount of glutamate, reduces the cravings that we talked about earlier. And then we have these other drugs that we'll also use to parimate and gabapentin. Lastly, we know that people who do some kind of talk therapy can be very helpful. We know that AA can be very helpful for some people. Rational recovery can be helpful, smart recovery. And it's usually this helper therapy principle. When you begin to work with somebody, begin to help them, it kind of helps yourself. And one study actually showed here that if people actually volunteer and give back to the community, it's this dotted line here, they're the most likely years later to be abstinent from alcohol. And so we really try to get people to do things for others, which will make a big difference. I mentioned those two things. Okay. So I am done. Hopefully that was an overview that was not too fast and understandable, and I'm happy to take any questions.

substances

brain effects

opioids

alcohol

receptors

neurotransmitters

addiction

dependence