I'll start off by maybe even before you get started talking about the picture that I have up there. I'm sure a couple people might recognize that. That's Aristotle and Plato. The reason that I put that up here is that whenever I'm talking about controversial issues, I think about Aristotle and Plato. Plato is the one on the left and Aristotle is the one on the right. Their hand gestures can summarize the basis of their philosophies. Plato believes in idealism and Aristotle believes in materialism. Idealism is the idea that thoughts come first and they end up manifesting as form. Materialism is form is the primary source and that ends up resulting in thoughts. They're two of the greatest thinkers of all time. What's amazing is that their opinions are often in opposition. Lots of times in medicine, we have opposing opinions and sometimes I myself can dig in on one side and think that I know the answer. I often remind myself that there's an Aristotle on the other side who's perhaps even smarter than I am. It's just a reminder to me that I have to have some humility about things that I feel certain about. We'll get started. You're already getting some positive feedback on the philosophical intro. I think we're off to a good start. I'll start with welcoming everyone. Good afternoon. I'm Dr. David Stifler and on behalf of the American Academy of Addiction Psychiatry, welcome to today's webinar in our series on Advanced Addiction Psychotherapy, which is a monthly series focused on evidence-based intensive psychotherapy training for addiction psychiatry fellows and faculty. This is hosted in partnership with Oregon Health and Science University and New York University. We're excited you could join us today and to offer you these live trainings that will be held on the second Wednesday of each month from 530 to 7 p.m. Eastern Time. Today's presentation is titled Practical Neurobiology Using Recovery Capital. Our next presentation will be in December when Dr. Richard Hirsch will talk about transference-focused psychotherapy. Please check the AAAP website for updates on other upcoming speakers. And then finally, it's my pleasure to introduce our very own course co-director, Dr. Chris Blazes. He's an associate professor of psychiatry at OHSU. He's triple board certified in psychiatry, addiction psychiatry, and emergency medicine, and he's the director of the OHSU Addiction Psychiatry Fellowship. He's a clinician educator whose practice is based out of Portland VA Medical Center. He lectures widely on topics such as benzos, buprenorphine, and the neurobiology of addiction and recovery. He's currently the principal investigator for a trial studying buprenorphine inductions on patients using fentanyl, and he has recent publications, including an article in JAMA Psychiatry describing a new clinical entity, complex persistent benzodiazepine dependence, as well as reconsidering the usefulness of adding naloxone to buprenorphine. So without further ado, I'll turn it over to you, Dr. Blazes. All right, thank you, David. Welcome, everybody. Thanks for joining today. We seem to be having some issues advancing the slides here, so I'll have to use that. So I start off by talking about a movie called A Beautiful Boy, and first of all, bear with me. I'm feeling a little congested today, so hopefully I'm not coming down with something, so I'm going to do my best. But this is a great movie. It's about a caring father whose young son became addicted to methamphetamine, and he went to see an addiction expert to ask two very simple questions. What is this addiction doing to my son, and what can I do to help him? And I think oftentimes in the modern world, we're stuck in this world of complexity, and sometimes I think it's important to move back towards simplicity in order to come up with more meaningful answers. And so I think by the end of this lecture, I think we'll be able to answer in a simple way those two questions. So what we're talking about today is one theory to understand addiction, and there's many theories that have been talked about in the past. Each of them have value, but none of them are all inclusive. So it'd be great if we had time to talk about all these individually, but what we're talking about today is just one more theory talking about understanding addiction. So the summary of this theory is that neuroplasticity, which as you guys know, is the brain's capacity to change, is what actually ends up creating the reward circuits in the brain. And these neuroplastic changes are also the cause of the addictive process. And then the cool aspect is that similar neuroplastic changes can be used in understanding and helping facilitate the process of recovery. Summary version number two is we're going to kind of combine Eric Nestler's work, who's a neuroscientist out of Mount Sinai, plus Terry Robinson and Kent Barrage from University of Michigan, which is my old stomping ground, and adding in the beginner's mind, and we'll come up with what we're talking about today. Summary version number three, essentially dopamine is an unconscious memory maker. Excessive dopamine in the reward circuits builds neural superhighways, or RUTs, by growing dendritic connections that bypass the frontal cortex, and they end up creating these habit circuitry, which is essentially generating cravings. But remember, this is a theory, and we have to have humility and always have a readiness to reconsider with all the theories that we work with in medicine. So today we're going to use a lot of pictures because I like pictures, they're more fun, and I think that they help with memory. And we're going to start by a review of some terminology, which actually confused me for the longest time. So the important structures in the reward circuit can pretty much be summarized as the limbic system, the nucleus accumbens, the striatum or basal ganglia, and the prefrontal cortex. So for a long time it confused me, but then I realized that much of these structures are just actually smaller portions of the larger structures. For example, the nucleus accumbens is simply a part of the ventral striatum, and the striatum itself is part of the basal ganglia. And so this just kind of helped me kind of categorize and remember this better. So we'll start off by talking about the basal ganglia. This is a part of the brain that's billions of years old. It's a primitive part of the brain. It's associated with voluntary movement and motivation, and it's made up these structures over here, the caudate, protein, and substantia nigra, nucleus accumbens, and subthalamic nuclei. So Morgensen in 1980 described this as the area by which motivation gets translated into action. And this is where it's starting to sound more familiar with understanding addiction. So the nucleus accumbens itself, this is where dopamine is released in the reward circuit, and it's kind of like the Holy Grail, and it's what defines a drug of abuse. All drugs of abuse cause dopamine release in the nucleus accumbens. The ventral tegmental area is simply where the cell bodies of the neurons that release dopamine in nucleus accumbens, they're based in the ventral tegmental area. So the prefrontal cortex, as you guys know, is kind of like the rocket scientist part of the brain. There's innumerable functions, and we certainly can't get into all of them today, but for our purposes in understanding addictions, it's important with impulse control as well as with modulation of uncomfortable emotions, for example, like fear. So the limbic system is a functional system made up of multiple structures. They are spread throughout the brain with a unified function, and it's made up of the structures that are described there. So oversimplified, the functions of the limbic system are the five Fs, feeding, fighting, fleeing, feeling, and sex. I put up a picture of the grizzly bear there because I call it the limbic grizzly. Limbic structures and limbic systems are very powerful, and there's also a strong memory association that's tied into the limbic system. But this limbic grizzly is quite formidable, and in the modern age of psychiatry and psychology, we have become very dependent upon cognitive interventions and cognitive behavioral therapy. These are all very important interventions, but when limbic systems get involved, they may not be enough. We've also determined that in addiction, that the limbic system may be even overactive. So I think part of our intervention is to focus more on limbic interventions in addition to cognitive interventions to help our patients with underlying addiction. So I'm introducing something that I call the conductor. There's something inside us, and there's actually really not a name for it as far as I can understand, that is an unconscious governor of our physiology and psychology. It's like our own personal darling, which is constantly endeavoring to best utilize our mental and physical processes in order to kind of give us a competitive advantage. Some people might call it the ego. I'm not sure I call it the conductor, and it'll help us explain some of the future slides. So how does this all add up, all this esoteric knowledge? So the reward circuit is the part of the brain that encourages us to seek pleasure and to avoid pain. It's important for us to recognize that this is a natural, normal part of the human existence, right? We're hardwired to seek pleasure and to avoid pain because in most circumstances, excuse me, it gives us a competitive advantage for survival. And this is also a reminder that many psychiatric disorders, and maybe even all psychiatric disorders, are simply exaggerated examples of normal psychic functions. And one would argue that addiction might be thought of the same way. So all at once, we can say, what's the main neurotransmitter in the reward circuit? It's dopamine. But what actually happens when dopamine is released into the reward circuit? So it's actually still quite controversial. Back in the 1980s, the neuro-researchers Roy Wise and George Kube described dopamine as the pleasure molecule. And this is what is kind of most commonly accepted and what's most commonly known, even up until now. But this may not be exactly everything of what's going on. So let's look a little bit deeper. There's more research now that's understanding that dopamine is involved with what's called incentive salience. And maybe some of you might recognize that squirrel from the movie The Ice Age. But if you can remember that squirrel, that's the perfect archetype for incentive salience. And what is that? So incentive salience, now we're getting into Kent Berridge and Terry Robinson's research at the University of Michigan. They described this as a cognitive process that confers a desire or want attribute, which includes a motivational component to a rewarding stimulus. So that confused me. So in order to help understand it better, and hopefully to help others understand it better, I simplified things a little bit. I just kind of reversed the words. So if something has salience, that means that something has a quality of being particularly noticeable or important, or it stands out to us. And in the modern world, I mean, we are kind of overstimulated with so many different stimuli coming from all different directions. So a major function of what the brain is supposed to do is to establish salience, what has importance. And incentive, of course, is quite simple. If something motivates us or encourages us to do something or to act, it has incentive. So if something stands out and it motivates us to act, it has incentive salience. So what are the archetypes of incentive salience? This is kind of like the mythical sirens. So as I talked about before, that squirrel from Ice Age, that acorn had incredible incentive salience. All the squirrel could do is focus on that acorn, and it couldn't focus on anything else. And it would put itself in all kinds of dangerous, precarious situations in order to try to get that acorn. Another example is Anthony Bourdain, rest in peace. Exotic foods had incentive salience for him. He would travel around the world seeking exotic foods. And so it stood out to him, and it encouraged him to do many different things in his life. But we all have our own sirens, and incentive salience is normal, and this is important to remember. So I put up a picture of a pelican and a bumblebee there, because for me, these have incredible incentive salience. Every time I go down to San Diego, I need to go find the pelicans so that I can watch them fly and watch these amazing prehistoric creatures kind of glide along the waves. Also at my house, I plant all kinds of shrubberies that will attract the bees, because I really love looking at bees. So incentive salience is a normal thing. And part of what we'll talk about later as part of the treatment plan in our patients would be to help people find their own pelicans and things that have incentive salience for them, because a life in recovery that's better than a life while using is much more likely for the patients to choose their life in recovery. But there's a weird fact associated with incentive salience, right? So the quick version is, unlike the tolerance that we're so used to that happens with drug liking, the compulsion or, you know, towards the behavior actually grows after repetitive drug use. So incentive salience increases. Now this is an important point, so let's go into this a little bit further. So just as a quick review for sensitization versus tolerance. So tolerance is the more times that we use a substance, the less effect that the substance has. But sensitization is the opposite. The more times that we use a substance, the more times we're exposed to something, then there might be increased activity as a result of that. And so this is just a pictorial view of this. On the left-hand side, the more times we use a drug, the less effect it has. And then on the right side, with sensitization, the more time that we use a drug, the more effect that happens. So this is a very interesting study that shows that dopamine actually gets released in a sensitized way. So the hollow circles are rats that were exposed to amphetamine for the first time at the point of the arrow. And you can see that there's, of course, a large dopamine spike as a result of their exposure to amphetamine. But the interesting aspect here is that the dark circles are rats that have been exposed to amphetamine five times in the past. So they've been sensitized to it. But when those rats that have been given amphetamine multiple times in the past are given the same dose of amphetamine, they have a much larger dopamine spike than the rats who were exposed to dopamine for the first time. So this is a little bit atypical and not what we're used to, but it's pretty good proof that dopamine gets released in a sensitized way the more times that people are exposed to the medication. And so, again, this is a pictorial view of that. The more time people are exposed to a drug, the more effect of the more dopamine that gets released. And so this is the genesis of the big paradox that happens with addiction. We're so used to the fact that we hear from patients that drug liking diminishes, right? But that while that's happening, the drug wanting or incentive salience towards the drug continues to increase over time. And this is gaining acceptance. And it really makes more logical sense as to what's really happening with addiction is understanding it from this standpoint. And this is the big trap of addiction. As drug liking goes down, simultaneously drug wanting or incentive salience goes up. Another important conceptual review is, for example, if we eat a cheeseburger and we enjoyed the cheeseburger, there's pleasure in response to that, then dopamine gets released in response to the pleasure in order to create a craving to recreate those circumstances again in the future. But if you eat a cheeseburger and you don't enjoy it, then dopamine does not get released and there's no genesis of a craving. With drugs of abuse, whether there's pleasure or not, there's still going to be the creation of a craving to recreate those circumstances again, because the dopamine gets released regardless of whether or not there's pleasure in the drugs of abuse. So also just remember that most receptors in the brain are actually ligand-gated ion channels, which act more fast, and dopamine receptors are more G-protein-coupled receptors. So they act in a more insidious, slower way. So dopamine is probably not the pleasure molecule as we're describing. It's probably more associated with the slower process of incentive salience. One last piece of the puzzle here is what's even more interesting is that it's commonly known dopamine is, of course, involved with motivating us to seek pleasure, but it's also likely involved with the motivation to avoid pain. And from a teleological standpoint, this makes a lot of sense. But so let's just go a little bit briefly into what's happening in the research here. Dopamine gets released in response to aversive stimuli as well in order to create incentive salience to avoid the situations in the future. Dopamine neurons respond to events that are not intrinsically rewarding and are not cues for future rewards. This is another study by Barrage and Robinson, which showed that both rewarding and aversive events trigger orientation of attention, cognitive processes, and increases in general motivation. So it has long been known that stressful and aversive experiences can cause large changes in dopamine concentrations in downstream brain structures. And the behavioral reactions to these experiences are dramatically altered by dopamine agonists and antagonists. So it's a very interesting part of the future research is to understand that dopamine is involved with not only seeking pleasure, but also with the avoiding pain aspects of things. So the final piece of the puzzle that helps us understand the reward circuit is the frontal cortex. And there's many, many MRI studies showing that there's documentation that addictive drugs will cause volume loss in the frontal cortex. And there's multiple MRI, functional MRIs and PET scans that show decreased activity in the frontal cortex in patients with addiction. So it's relatively incontrovertible evidence. Now, many smart people like the people in this audience are going to say, well, maybe it's just the brain damage that the drugs cause that caused the decreased activity in the frontal cortex. But this was a very interesting study that showed that patients with both chemical and behavioral addictions, including compulsive sexual behaviors and gambling disorders compared with healthy controls actually showed smaller gray matter volumes in the orbital frontal cortex. So it's not just the damage that's caused by the drugs. There's actually something primarily that's happening related to the addiction process that decreases the gray matter. All right. So now let's get into the deep weeds here. Bear with me for a moment to figure out how exactly this is happening. And so one might argue that this is Delta FosB's fault, right? And so what is Delta FosB? So Delta FosB is a transcription factor, which is just a protein that's created within our cells in order to encourage genetic expression. And so how is that important relative to addiction? So essentially what Delta FosB is doing is it's building and pruning dendrites, which is encouraging connections in the brain to happen. So essentially what we, now we're getting into Eric Nessler's work, and what he's learned is that Delta FosB is formed proportional to the amount of dopamine that's released in the reward circuit in order to encourage the growing of these dendrites, encouraging certain pathways, and the shrinkage of other dendrites, discouraging the pathways, for example, going to the frontal cortex. But one thing to be aware of is that this happens only in patients who are genetically predisposed to addiction. This process doesn't happen in everyone. So according to this theory, addiction actually can be seen as an epigenetic process. So for example, much of our genome is actually closed up into these small parts of our DNA, which is called histones, and they're so tightly contained in there that they can't be expressed. But if we're exposed to a certain experience or a certain drug, then this can be unraveled and then it can be expressed. And so exposure to certain drugs can lead to overexpression of Delta FosB, which can lead to the overexpression of these specific neural pathways in the brain. So in some sense, addiction can be considered an epigenetic process. And so what Dr. Nessler says is that overexpression of Delta FosB in the nucleus accumbens is a common necessary factor in essentially all known forms of addiction. Others might argue that Delta FosB might not be the only transcription factor involved and there might be others involved. So we're just probably in our adolescence of understanding of this, but it really is, the research is becoming more compelling and it's really adding up clinically to what we're seeing in the real world. So what's the practicality of what's actually happening here? So the conductor, as we talked about before, wants to find a way to recreate circumstances that were happening at the time of the dopamine release in order to encourage people to find those circumstances again in the future. And the opposite is also true. Dopamine can be used to avoid circumstances that led to aversive experiences in the past. And so what's the purpose of these new dendritic connections that are being created by dopamine and Delta FosB? Well, what's happening is it's actually creating these super highways or weakening connections that go to the prefrontal cortex. And it's creating a type of unconscious memory, which is essentially like a craving or neural ruts. And the key is, is that it's neurobiologically associating the stimulus to the circumstances that are happening at the time of the dopamine surge. So in some sense, in some cases, it's going to increase the dendritic connections. And in other cases, it's going to decrease the dendritic connections. But what's happening at the time, so for example, if someone was polishing their shoes, at the time that they use drugs, well, then that got neurobiologically associated with drug use in the past. So the next time they're polishing their shoes, they're going to have a trigger to use drugs to recreate those same circumstances. So how does this all add up to a better understanding of addictions? So again, some of these dopamine-induced super highways grow so much, and the dendrites become so bushy, and the highways going to the prefrontal cortex shrink so much that people describe that they go directly from stimulus to action. So it's quite common in the world of addiction, we'll hear a story like, I was driving by a liquor store, and the next thing I knew, I had a drink in my hand. And now we have a neurobiological understanding of actually how this can happen. So this is pretty cool in my mind. So it's really, what it's really doing is it's creating these neural ruts. And if you've ever driven a car in like deep ruts in an off-road area, you'll know it's hard to get out of that. So once you get in these ruts, it kind of takes you in a direction, it's hard to break from that direction. So let's look at it from a neuroanatomy lens. So this is just a bad cartoon picture of a primitive brain before we developed a prefrontal cortex. The cheeseburger represents the ventral tegmental area, which is the cell bodies of the neurons releasing dopamine. And there's an impulse there, which causes release of dopamine in the nucleus accumbens here, represented by Anthony Bourdain and the squirrel. Once that gets released, it sets off an impulse towards action, which is represented by the wildly coyote in the green arrows. And that can be turbocharged by the limbic system. So the limbic system can increase that impulse to act as well. And you can have a pretty crazy wildly coyote going there. But then if we look at a normal brain, normal human brain in an adult, you have that same impulse. It causes an impulse to act in the nucleus accumbens, which is the green arrow. But then you have the prefrontal cortex, which can modulate that impulse to act in addition to the inputs from the limbic system. So you can have a much more manageable wildly coyote or a craving. So in the addicted brain, because it cuts off the connections to the prefrontal cortex, that same impulse will cause the same dopamine release. But the end result will be a much larger impulse to act because the prefrontal cortex hasn't had the capacity to modulate that. Another interesting thing to be aware of is if we look at an adolescent brain, the last part of the human brain to mature is the prefrontal cortex. And it actually probably doesn't completely modulate until people are 25 years old. So in some sense, an adolescent brain has structural similarities to an addicted brain. And this fits with what we see in clinical practice, in my experience, because adolescents are already impulsive and have difficulty modulating their impulses. And so if you add in the addictive processes that are happening, this can be why sometimes it can feel refractory to take care of young patients with addiction. And so the addicted brain essentially is creating these shortcut loops that bypass the frontal cortex. So when somebody says, I was driving by a liquor store, and the next thing I knew I had a drink in my hand, it's because of these shortcut loops that work for me. So let's go back and do another brief review of neurophysiology. And this actually does have relevance, so bear with me. Every neuron in your brain has a pulse. So it's not like they're lying there quiescent. So even if you're not using the neurons, they're going to be firing at 8 to 30 times per second. And the way that the conductor encourages a difference in activity in the brain is to send neurotransmitters. And what these neurotransmitters will do is they will increase or decrease the basal firing rate of the neurons. Agonists increase the firing rate of the neurons. Agonists maintain the basal firing rate of the neurons. And reverse agonists decrease the basal firing rate. And so why is this relevant? Well, let's look at this one interesting study that showed that, for example, if you eat a cheeseburger and you enjoy it, that's going to increase the basal firing rate in the reward circuit by 150%. Nicotine has been shown to increase the basal firing rate by 200%. Cocaine has been shown to increase the basal firing rate by 300%. And methamphetamine, I'm sure many have seen this study, has actually shown to increase the basal firing rate by about 1,000%. And so this really helps us understand kind of the telescoping phenomenon. And also what we're seeing in clinical practice is that methamphetamine seems to be fundamentally different and so much more powerful. And that's because it causes exponentially more dopamine release. So now we're going to quote again Eric Nestler. So drugs and abuse act on the reward circuit with a power and persistence that's not seen in the natural world. And so for example, here we go. So some drugs abuse are so powerful that many people with longstanding addictions are no longer able to appreciate subtleties in life. So in the extremes, normal activities don't have enough salience to have psychic energy directed towards them. There's no cathexis. So normal things like food, sex, and social interaction don't have enough salience. So part of what I do in my practice, the brain can recover and slowly over time, if we can encourage people to be able to once again, pay attention to subtleties to get to the point where they can once again, you know, enjoy a walk in the park. This is an important aspect of the process of recovery. And if we encourage this in our patients to know that their brains can recover and use this as part of what our actual treatment plan is, I found this to be quite helpful in the treatment. So as a quick review, in the normal brain, dopamine is released in response to pleasure or pain in order to form associations that will encourage or discourage similar activities in the future. So if you're eating a tuna sandwich and you enjoy the taste, dopamine will be released to place a marker reminding the conductor that you should seek out a tuna sandwich in the future. But if you don't like the tuna sandwich, dopamine does not get released. So this is the genesis of the theory that we're talking about today. So whatever's happening in your world at the time that you're using drugs through neuroplasticity gets bundled together or associated with drug use. And this is how the neural ruts are created. And this is essentially the genesis of a craving. So in other words, dopamine is really like a big matchmaker and it uses delta phosphine, the transcription factor to create these associations and link together what's happening in your world at that time with the drug use. And so this can explain why I was polishing my shoes when I used heroin for the first time and every time I polished my shoes, I wanted to use heroin. And so, you know, it's interesting that there's multiple different understandings and definitions of a craving, but this is the one that makes most sense. And now I think through this theory, it really can describe how cravings happen. And also it can help us understand how we can work backwards and reverse engineer to kind of create more functional cravings in the future. So one last time, I'm just going to kind of go through a cartoon description of what's happening here. So the cartoon arrows in terms of creating these neurologic bundles represent the formation of dendritic connections that form. And each arrow that's formed is kind of a lane in the superhighway and it creates bushier dendritic connections. So the width of the arrow that gets formed is kind of proportional to the amount of dopamine that gets released, but also to the size of the limbic grizzly. So the more hours that get added, the wider the superhighway, the stronger the current, the deeper the rut, the stronger the gravitational pull towards the craving and the bushier are the dendritic connections. And so when drugs are added to the mix, this process can happen very fast. So for example, normal endogenous dopamine release might take hundreds of uses in order to create a significant rut in the brain. But when you add drugs of abuse, which cause really high amounts of dopamine, this process can happen fast. And this explains what we call telescoping. And telescoping is a process that describes the time from which someone uses a drug for the first time until they advance to a significant severe use disorder or a profound addiction. And what we're seeing is with like, for example, methamphetamine, this process can happen within a period of a month or two. Oftentimes with moderate amounts of alcohol, it might take 20 or 30 years for this process to happen. So telescoping, now we understand neurobiologically why this is happening, which is pretty cool. And this slide is just a reminder that anything that people do at the time they're using drugs gets neurobiologically associated and is part of the superhighway. So if someone's driving and they're high at the time that they're driving, well, guess what? Unconsciously, that becomes neurobiologically associated with drug use. So the next time they're driving, there's going to be a craving to use drugs. And the same thing happens with any activity. So normal mundane activities can become cues or triggers towards drug use. And this slide is a reminder just to say that if you add in a limbic component to it, if something has emotional valence to it, in addition to the excess of dopamine from drug use, this process can happen really fast and it can be really, really powerful. And the next slide I'm going to put up is some disturbing pictures of what we see often in everyday life. We see how people with addictions no longer care for their own personal safety or health. They don't have a fear of death. They don't even feel like they need shelter. They don't have a desire for food. They don't seem to care about what's happening with their loved ones. And the reason this is happening is these neurobiological associations that bypass the frontal cortex's capacity, but these changes are profound. So in one way, another way to look at it is that dopamine actually changes what we are interested in or what we care about. And I'd like to think that I could actually control what I care about, but I really can't. So in some sense, dopamine is like the interest maker. So it may be considered like our own personal pop-up generator, that it knows what's going to get your attention and it's going to direct you towards that. And so what we're actually interested in makes up a major part of our personality. And if major parts of our personality get linked to drug use, then it's almost like addiction can be seen as a dominant personality or a dominant persona. So I put up a picture of Inside Out here, because if you've seen that movie, like for example, Anger, the one emotion, is very prone to jumping in front of all the other emotions to take control of the entire person and the whole system. And maybe addiction is kind of like a dominant persona that has, like anger, taking control of the controls of our internal persona. And I like the word persona as opposed to personality, because it makes more sense. And I'm going to talk about Carl Jung for a second, who's my favorite psychiatrist. A persona is a part of our personality that allows us to function in certain circumstances. And normal, healthy, well-rounded people have multiple personas that act at different times. So for example, when I'm at home playing with my dog, I have a different persona than when I'm at work. So normally people can dance back and forth between different personas. And addiction, I would argue, is a dominant persona that ends up running the show all the time. And interestingly, sometimes what I do with patients is I'll encourage them to kind of know what it feels like if their addictive persona is running the show. And sometimes even within the same session, I can notice that this is their addictive persona that I'm interacting with. And then later on in the session, you could notice a subtle change and you're connecting with them in a different way. And that may be kind of a different persona that you're interacting with. And sometimes if we encourage people to have an awareness of that, that can start them understand their addiction better. Because a lot of people would argue, and me being one of them, that addiction itself, the primary issue is not the drugs. The primary issue is a restless, irritable, and discontent state from which people need escape. And then they end up using the drugs. And then those drugs end up building these dysfunctional pathways in the brain. So when somebody uses a lot of drugs, many things get neurobiologically associated with drug use over time. And the end result is kind of like a personality change. So going back to the movie, what he said is like, this is not us. This is not who we are. This is not who my son is. And I've heard this innumerable times coming from patients. And this is as a result of this habit circuitry, which is as a result of the dopamine release. So the bottom line here is that this is actually an epic fail of the conductor. So in late stage addiction, the conductor's messages are false alarms. So the conductor thinks that he's signaling for the person to polish their shoes. But because of these dysfunctional pathways, that same impulse results in drug use. So addiction actually can be seen as drug-induced neuroplasticity. And so if many mundane behaviors become points of entry into a dominant addictive superhighway, once people get into these deep ruts, it's really hard to get out of them. And so it ends up in destination drug use. So that was a lot. Now we're going to regroup and redirect a little bit to what I think is the most exciting aspect of the lecture, which is how do we apply this knowledge to the neurobiology of recovery? And how can we use this knowledge to help people in their process of change? So we certainly can assist the brain in the recovery process. And step one is critical in stabilizing the system from the toxicity of use. And this is where medication management is involved, medically managed detox is involved. And this is critical, but we don't have time to get into that today. And that's discussed in many, many other lectures. But we're going to talk more about step two, which is working on the process of building more functional recovery superhighways. So medications are critically important. MOUD, methadone, buprenorphine, naltrexone, phenobarbital, clonidine. And they are a significant part of the answer. So pharmacology in recovery, the way I look at it, is that can help create stability amongst the chaos. And it can provide space so that someone can actually work on the processes to help build the more functional neural pathways in the brain. I put this slide up just as a reminder to myself and to others who are watching that, yes, we're doing a good job and we're helping people and we're saving lives with, for example, buprenorphine. But we could be doing better. You know, this is consistent with what's been found in many other studies as well, is that after six months, even after a successful initiation of buprenorphine, only 20 to 30% of those people remain on it. And so, although it's an important aspect, I think that we should shoot aim higher and, you know, to do better than 20 to 30%. And so what can we do to start to aim higher? So again, MOUD is necessary, but maybe not sufficient. So let's do more and what else can we do? And so today we're going to give attention to the other aspect of the puzzle, which is certain psychosocial and behavioral interventions, which can help build more functional pathways in the brain. And this is the theory. And this is the theory. So in late-stage addiction, many things have been neurobiologically associated with drug use. And it seems like everything is an on-ramp on to these superhighways. The wind was blowing and they used drugs. Well, the next time they hear the wind blowing, that's been neurobiologically associated. So that's actually a trigger to use drugs. Same thing happens when I feel good, when I don't feel good. If people hear tic-tacs, it can remind them of the way the pills sound when they're using the prescripted opioids and whatnot. That can become a very strong trigger. Also, sometimes people, when they're in the early phases of withdrawal, they can describe themselves as being in a restless, irritable, discontent state in early withdrawal. And so if they use drugs to kind of escape from that early withdrawal phase, well, guess what? That withdrawal phase has now been neurobiologically associated with drug use and the withdrawal phase itself will be a trigger to use drugs in the future. So this really sounds pretty discouraging, right? And I used to give this lecture when I was the medical director at a residential drug and alcohol rehab. I gave a version of this and the patients really, really, this slide resonated with patients. They're describing essentially a hell on earth. It's like, I feel like my entire life is a craving. So what am I supposed to do? And that's what a lot of the patients feel like. It's almost like everything has been neurobiologically associated with drug use. So this is kind of like a hell on earth. So it seems like there's no way out, right? If the patient's entire life seems to be a trigger, well, what can you do? And so this is kind of the genesis of the last part of our theory. If every instinct you have is wrong, then the opposite would have to be right. So dopamine, according to this theory, was involved with the development of our original personalities. And dopamine we've also learned now is involved with the development of our addictive personalities. But the cool part is that dopamine can also be involved in the treatment plan in order to help build a more functional personality or persona because it can actually weaken the dominant persona that's been kind of taking the controls of the system in the past. So now this is the birth of opposite George. So bear with me, I'm going to escape for a second and we're going to play. Every decision I've ever made in my entire life has been wrong. My life is the complete opposite of everything I want it to be. Every instinct I have in every aspect of life, be it something to wear, something to eat, it's all been wrong. Tuna on toast, coleslaw, cup of coffee. Yeah. No, no, wait a minute. I always have tuna on toast. Nothing's ever worked out for me with tuna on toast. I want the complete opposite of tuna on toast. Chicken salad, on rye, on toasted, with a side of potato salad, and a cup of tea. Well, there's no telling what can happen from this. Yeah, chicken salad's not the opposite of tuna. Salmon's the opposite of tuna, because salmon swim against the current, and the tuna swim with it. Good for the tuna. George, you know that woman just looked at you. So what? What am I supposed to do? Go talk to her. Elaine, bald men with no jobs and no money will live with their parents? Don't approach strange women. Well, here's your chance to try the opposite. Instead of tuna salad and being intimidated by women, chicken salad and going right up to them. Yeah, I should do the opposite. I should. If every instinct you have is wrong, then the opposite would have to be right. Yes, I will do the opposite. I used to sit here and do nothing and regret it for the rest of the day. So now, I will do the opposite, and I will do something. Excuse me. I couldn't help but notice that you were looking at my direction. Oh, yes, I was. You just already faintly back mentioned me. My name is George. I'm unemployed, and I live with my parents. I'm Victoria. Hi. So that is obviously hyperbole, but I think you can sense where I'm going with this, right? Give me a second here. Essentially, good things can happen if people change in their process of addiction. So in order to avoid things that have been neurobiologically associated with drug use, which can be everything, folks need to change many different aspects of their life. And so, for example, any physical or behavioral change can be helpful. The creation of new habits, of new hobbies, even simple things like the ergonomics of life. If you're able to move your work desk to a different part of the house, move the bed to a different part of the room, even changing your diet, changing people you associate with. Neurobiologically, now we understand how this can be an important part of the process of creating new, more functional pathways to compete with the dysfunctional pathways in the brain. And this is the birth of, this also helps us bridge the gap. One of the things that I get frustrated with is that it seems like there's this gap between the recovery community and the scientific community, and it doesn't make sense. We can do both and. This is now a scientific theory that may explain how the repetition that's inherent in certain pathways of recovery actually might help like structured residential settings, self-help groups like AA and NA. So if the same old behaviors or activities or cues, just end up reinforcing the addictive superhighways, people have to change all their behaviors. And so I put this up just as a reminder that there was a Cochrane Review, which is pretty much thought of as our highest level of evidence that came out out of Mass General and Stanford, which showed that there's high quality evidence that manualized alcoholics anonymous or 12-step facilitation interventions are more effective than other established treatments, such as CBT for increasing abstinence. And this is just a simple reminder that we are in a situation where I think we should encourage both. And this is not something that works for everyone, but I think it's an important part to have in our toolbox. So how does this all apply to the actual process of helping our patients' recovery? So I summarize this up into kind of like four recovery hacks in a simplistic way that we can help talk to families and patients about the process of change that might be necessary. So I think the first simple way to interact with our patients is to help them understand the importance of deep change. So Robert Downing Jr., who's been sober since 2003, says, job one is to get out of the cave. A lot of people do get out, but they don't change. And so how do we encourage people to change? And one of the ways that we can encourage people to change is to work on the idea of surrender. If people's cup is already full, then there's not space for anything new. So in some sense, they have to let go of old patterns and ideas. And so cognitively, many of our patients can be kind of quite rigid. And so the idea of surrendering that rigidity to the old patterns of behavior in the past are important in order to have the capacity to build more functional pathways. So in the modern world, though, surrender has become kind of a bad word, right? Assertiveness is necessary to function and to get by in this very challenging Western world. So the idea of surrender kind of rubs a lot of people the wrong way. But another way that you might look at it is that having a willingness to surrender or change can be actually the simple most assertive act that you can make. So, but surrender doesn't have to be a bad word. People can surrender to anything. I've had patients who surrendered to their piano teacher. I've had patients who surrendered to their Tai Chi teacher or to their yoga teacher. I had a patient who surrendered to this poem called the Desiderata, which is just a description of a different way of life. As long as people change a significant aspect of their life and surrender to something that's important. Of course, it would be great if they surrendered to kind of our ideas as our clinicians as to how they can move forward. But I think surrender itself for some people with advanced addiction is an important part of the process. So hack number two may sound simple. Chris, let me jump in. There's been some people are kind of commenting on the chat, you know, which is fine. Feel free if you wanna make a little bit more of a clearer question, I'd be happy to ask it. There was one, somebody said, interesting if I'm understanding the overall perspective, right? To encourage AA to target the limbic system. Yeah, I mean, again, AA is just one aspect of things that we can do to, because there are certain aspects of AA which encourage this process of change and this repetitive activity. And I'll get more into that with later slides that might help understand a little bit better. So I'm not specifically singling out AA, it's just that that's something that has some of these things inherent in it, which will help encourage the process of change. But I will get to that in some of the subsequent slides. All right, so recovery hack number two, what can we do to help? So help people understand distress tolerance. It sounds simplistic, but philosophically it's important, right? In the modern era, we've been kind of conditioned to believe that all symptoms require treatment, right? And this applies to us as clinicians. People have a symptom, they need treatment. But many of our emotions are normal, natural experiences that are giving us an impulse towards an action and are telling us that we need to do something. And emotions themselves have a pretty short half-life as long as we don't feed them with other thoughts. So if we can help encourage people to simply tolerate emotions, to tolerate cravings, and to develop distress tolerance, this could be a critical aspect of their success in the future. For many people, their primary mechanism to tolerate distress for many years has been to use drugs. So reminding them simple things as to how to tolerate emotional distress is important. So simple things like psychotherapies like ACT, mindfulness activities, basic like DBT type skills for coping mechanisms to tolerate distress. Simple things like helping people recognize that this too shall pass. I put up a picture of the stallion down there because that's a reminder that what I've found in my practice is that many people with addictions, it's almost like they have powerful emotional engines, powerful emotional stallions. And so they're so powerful that it necessitates escape. So part of what we can help them do is to recognize ways to help tolerate the intensity of their emotions. And an interesting aspect of that is that what I found in my practice is that once they are able to kind of learn how to drive the Ferrari or learn how to ride the stallion, they can do pretty remarkable things after some skills are introduced. All right, hack number three, what else can we do to help? Help them learn how to build new, more functional pathways in the reward circuit. So this sounds really complicated, but it's actually not. So what we've learned about this process is if we could find a way to create endogenous dopamine release in the reward circuit in response to different stimuli, then that can be part of our treatment plan, right? So for example, you know, getting a hug is probably going to cause dopamine release. You know, playing with your dog is going to cause dopamine release. You know, one of the interesting things that a lot of people in the recovery community do is service work. And this is kind of a novel idea. It's something most people don't do, but when they do it, it's a new activity. It makes them feel good about themselves. There's dopamine release, and that's working towards building more functional pathways. And so this is really the most exciting aspect, I think, of the whole lecture. And let's just pause on that for a second and think of how cool that is. When a patient is able to experience organic joy and recovery, that's actually part of the treatment plan. And so what I encourage the fellows that I work with and the trainees that I work with is to follow, you know, recovery capital and to encourage people to find ways to experience joy and recovery and to follow it over time and have that be part of the treatment plan. So if we think about it, contingency management is based on the same principles, right? This involves operant conditioning. And if people are, you know, if they are successful in a certain behavior, then they're rewarded with, you know, drawing from a fishbowl with certain rewards or they're given a certain amount of money. And so there, and it's actually been shown that contingency management works even better if there's like this party environment around their success. And so this is just basically using these same principles under the guise of a psychotherapy. And the more we learn about contingency management, it's really effective. And so in some sense, you're kind of just priming the system by starting to build those new, more functional pathways through contingency management. So for those who are interested and want to geek out more about neuroplasticity, this was a great book. It was written by Dr. Doidge, who's a researcher out of Canada, describing how neuroplasticity actually can be used for healing from multiple other neurologic aspects. All right, recovery hack number four, encourage connection, right? So folks with advanced addiction tend to isolate. So it's something that we've all just kind of noticed. We're not exactly sure why it happens, but it definitely does happen. And we know that connection is an important aspect of addiction. So the rat park experiments by Bruce Alexander were kind of simplistic experiments, but there's wisdom to them. So he placed a rat in a cage with a bottle of cocaine and a bottle of water, and the rat used the cocaine essentially until it died. But he put similar rats in a cage with cocaine water and regular water, with other rats and all kinds of things to do and play and enjoy with. And those rats did not use the cocaine at all. So again, this is a simplistic experiment, but I think that there's some truth in this, that if people are able to experience joy in their lives, they're not going to seek out the drugs. And actually one of our faculty members here at OHSU, Chris Stolfer, has been giving exogenous oxytocin in some of his studies to see if that would encourage people to have more connections in their recovery and have improvement in their recovery process. And he's published some articles on that with positive findings. So we think that connection is an encouraging connection, I think is an important aspect of recovery process. So one thing that I've noticed in my practice is that when patients develop the capacity to enjoy new things, it becomes a positive prognostic factor, new hobbies, new friends, new community. And that we've seen today a scientific mechanism through dopamine activity, how this is true. So essentially we use endogenous dopamine to our advantage by creating new, more functional motivators, new cues and new triggers. So I want to talk about recovery capital for a second. This is something that's been written about. It's been out for 25 years now, but I think it's developing a resurgence and I'm glad that it is. So their definition, Granfield and Cloud said that it's the volume of internal and external assets that can be brought to bear to initiate and sustain recovery. Essentially it's positive things in people's lives that can help them tolerate cravings. So in traditional addiction, research often has used deficit-based forms of assessment, which focus on measuring pathology and harm. So for example, did they not relapse? Did they not get hepatitis C? Did they not die? Did they not use drugs? But recovery capital looks at recovery from the other side with quality of life aspects. So it's following aspects of people's lives that can lead to endogenous dopamine release that can work towards building more functional highways. It follows kind of the degree to which people have learned to derive utility from new behaviors, to develop a sense of purpose, a sense of connection and a sense of joy. So I just put this up as a reference. There are multiple different recovery capital scales that can be used to follow recovery capital. So if you want to geek out about that later, that's in there for your reference. And I left them in here. So I also, I wrote a paper with Jones, who even in Jim Sorensen, thinking about recovery capital scales. And this paper specifically looked at people who were on MOUD. So if they were using buprenorphine or methadone, and sometimes the patients would want to say, oh, it's time for me to stop this medication. And so we created a scale that looked at recovery capital and some of the positive aspects in their lives, which can help kind of stratify if patients might be ready to consider coming off these medications. And so this is just a shout out to Jones Wieben, who is an amazing researcher and clinician at UCSF. She just retired this year after 50 years of service at the VA at UCSF. And Jim Sorensen just died last year, and he was really a bright light in our field, and we all are going to miss him as well. And I put in here actually the recovery capital checklists from that article if you want to geek out on those later. So one thing that I say to patients oftentimes is if your life isn't better in recovery than it was while using drugs, well, a logical person wouldn't want to be in recovery. So we spend some time encouraging them to find a way so that their lives can be better in recovery. So part of what I do in my practice is to encourage people to find their own pelicans. And I remember I put up a picture of the tomato because it reminds me of the patient I had when I was at the University of Michigan, who was in early recovery for a year, and he was just depressed and miserable and couldn't enjoy anything, and he was anhedonic. And we kept trying to find things that he would enjoy. And eventually we landed on gardening, and then he really took to gardening and really enjoyed growing the plants and watching them grow and then harvesting the tomatoes. And he brought me a tomato at the end of the season. And although as a psychiatrist, we're not supposed to accept gifts, I gladly accepted that gift. And it was a distinct sign that he was starting to be able to enjoy things in life and to enjoy subtle things and to enjoy things that have delayed, you know, and people with addictions are used to having immediate responses to cues and impulses. So if people can start to understand that there are delayed rewards, that can be a positive aspect in recovery. So, well, let's remember, right? You know, going back to how powerful methamphetamine is. It might only take a hundred uses of methamphetamine to build a really powerful or really bushy, you know, dendritic connection in a deep rut, but it may take a thousand repetitive chicken salads on rise in order to create a similarly functional pathway in the brain. And so, again, what I've noticed in my practice is that people who do well in the recovery are those who establish new connections and find new ways to feel contented over and over and over and over again. It's the repetition that is important because it's not going to happen quickly like it happened with the drug use. So it requires repetition over and over again. And this is one argument that can explain why certain things like residential treatment facilities or therapeutic communities might be effective. So people with advanced late stage addiction may benefit from being separated from the cues of normal life to give them a jumpstart, to prime the pump, to start building those pathways at the beginning. And this may take months or may even take years for some people. So for those of you who want to geek out about it, you know, there's plenty of old literature that show how when people do engage in therapeutic communities that they have a fair degree of success. So we won't get into the specifics here, but this is just in here for your reference. So this is another article that came out in 2010 that showed despite research showing that living environments supportive of recovery are associated with better outcomes. Sober living houses have been largely overlooked by policymakers and researchers. So sober living houses have been proven to show improvement on addiction scales with improvement in psychiatric severity scales with diminished arrests and diminished alcohol and drug use. So therapeutic communities for addictions, there's been multiple articles also showing that they promote change towards recovery and reinsertion into society with better substance use and legal outcomes. This slide's important though, right? Because there's a lot of bad ones out there as well. And there are people who are just looking to make a lot of money. And I think part of our responsibility as experts is to know which ones are good in our community. Because in some sense we could be sending someone to a sober living environment where people use drugs every day and that's certainly not gonna help them. But if we send somebody to a strong recovery sober living environment, their likelihood of success will go up exponentially. So part of what I do is to try to maintain knowledge of what's going on in my area and which ones are good and which ones are bad. And they can change very quickly. So it does involve a certain amount of effort. But we have to remember that in long-term recovery, right? That relapse lives next, tuna salad on toast lives right next to a chicken salad on rye. So most likely from what we understand is once these super highways are built, that they're not gonna go away completely. So some people say that I had 10 years of recovery and when I relapsed, it felt like that I had not had any time in recovery because they went immediately to kind of like the feeling of late stage addiction. But we also have to remember that the opposite is true. And so if somebody had a couple of good years of recovery, the pathways that they built are still there. And so if they decide to start to recovery again, they don't have to start from scratch. And so that can be a hopeful thing to pass along to a patient. I think it's also important to keep in mind that this doesn't apply to everyone, right? I put up a picture of Keith Richards because he's somebody who probably used drugs on a very frequent basis for many, many years and didn't progress on to dysfunction in his life. And so there's an important aspect of genetics to factor in here. And this is why I actually like to, in my mind, think that there's actually a difference between addiction and substance use disorder. And we'll get more into that in a second. I also put up a picture of Post Malone because he recently came out saying that he had difficulty with drug and alcohol use that led to significant dysfunction in his life. But then he says he's been able to actually drink with moderation from his experience. And so he's like, I'm not... And what I would say from my practice is I am certainly not anti-drug, I'm not anti-drinking, except if somebody has this genetic predisposition towards addiction. So part of what I try to determine, and oftentimes when I'm interacting with patients in my practice, it's like the first time I meet them, I'll say, there's plenty of people who misuse substances, they end up with consequences in their life, but they meet the criteria for a substance use disorder. But many, and maybe most of them might not have this addiction, which is a true compulsion to use that bypasses their will and their capacity to make decisions for themselves. And I say, I'm not sure which one you are, let's figure it out together. Because in my opinion, the treatments are different. If people have a simple substance use disorder, just simply creating stability in their lives, helping them get through the medically managed detox and providing stability with some medications might be enough. But for those with addiction, I think we've learned today that more work might be involved and slowly over time, you might have to pay attention to recovery capital and whatnot. And so this is just a reminder that, what we've learned is that genetics is important here. And it's estimated that 40 to 60% of vulnerability to addiction is actually genetic related. It's probably spread across many different genes. So it's not like we could just localize one and cause a change, but we're starting to understand more about that and that genetics is an important aspect of addiction. So this is something that we talked about on the previous slides. We won't get into that. So just thinking about the future, I think, you know, Eric Nestor starting to look in to another transcription factor called Delta June D. And his theory is that this may have the capacity to limit the effect of Delta FosB. So who knows, maybe it'll be the antidote. So wouldn't it be wonderful if we had a way to help people who had this genetic predisposition to addiction through a pharmacological intervention to turn that off, but we're not there yet. So in summary, addiction changes the brain. It builds new connections. It creates a dominant persona in some sense. And so according to this theory, an important part of the healing process involves abandoning the dysfunctional neural pathways and building more functional new ones. And this is where the recovery hacks come in. How do we build those pathways? Encouraging people to embrace change, to embrace surrender, I think is important. Encouraging people to find new ways to simply tolerate cravings and to tolerate emotional distress. And in many circumstances in the past, their primary coping mechanism has simply been to use drugs. So to learn new skills and also developing connections and recovery is important and experiencing joy. And I use recovery capital as a bullet point for all of my patients at the end of the note to help encourage me to follow these aspects of their lives. So all drugs of abuse cause dopamine release in the nucleus accumbens, regardless of the circumstances, desirable or not. Dopamine is a matchmaker that couples drugs to activities. Too much dopamine or too much Delta FosB creates these super highways or neural ruts or shortcuts that bypass the frontal cortex. And this is the generation of triggers or cravings or cues. For someone with addiction, recovery needs to include mechanisms to build new, more functional super highways, essentially just finding ways to cause endogenous dopamine release. Pharmacological interventions can help create stabilities in people's lives and can maximize the likelihood that all this good stuff can happen. So let's go back to the movie, right? At the beginning, we talked about simplicity. So the two simple questions that he asked the expert was, what is the drug doing to him? And I think now we can answer that in a very simple way. What can I do to help him? I think we can actually answer that in a very simple way. So help them to understand the importance of change, that it's neurobiologically necessary for recovery and that surrender isn't a bad word. Provide help them to tolerate discomfort. Drugs likely became their only coping skill. So mindfulness, ACT, and this too shall pass. Help them find their joy, help them find their pelicans. So, you know, the world of active addiction is scary for patients and their families. And sometimes what makes the most difference is a little bit of added understanding. And so I think in the modern world, many of us often look to science as kind of their form of faith. And I think that there's enough science here to add some understanding and some hope. So I'll end with this slide. And this is NeuroVolkov works, which shows the normal control. And it shows a methamphetamine user after a month of abstinence with decreased activity. And after 14 months, you can see that it nearly returns to normal activity. And so Abraham Lincoln, I'm going to end with this. I believe if we take habitual drunkards as a class, their heads and their hearts will bear an advantageous comparison with those of any other class. And I believe this to be true from my patient interactions. I'm going to end there and stop sharing and then we can open it up for discussion. Thanks, Chris. There's been a lot of positive feedback saying great talk and thank you. A lot of people are hoping to get the slides. Somebody just asked about CME credit. So you'll be sent an email tomorrow from Zoom. So keep an eye out for that. I'm going to start with somebody has their hand up. Let me just go in order, though. Neethu Nandan, I'm going to see if I can unmute him to ask his question. That's OK. Neethu Nandan, if you're there, you're welcome to ask your question. Hello. Hi. I'm a second year psychiatric resident. And I was wondering with this in mind that this is the neurobiology of addiction and that there is already pathways that are circumventing a lot of our prefrontal cortex that is being formed. And also there is this inherent pain pathway that is activated due to abstinence and they have a new one and stuff. Do you recommend harm reduction? Where does harm reduction strategy fit in or do we advocate for absolute abstinence to the patient? So I have to apologize. I missed some of that because my computer was doing freaky things. But what I heard is that at what point do we recommend harm reduction versus abstinence? Um, yes. And also, like, do we at all advocate for harm reduction? Because now there is this unnatural substance that is already to which brain is already desensitized and, you know, or sensitized, whichever way. Um, do we put that option at all in the table? Well, I think it's a great question. And I think harm reduction is a really important thing to have in our toolbox and understanding the nuance as to when to recommend what. And this is why when I meet with a patient for the first time, I'll say, you know, like, if you have a true addiction, then, you know, then moderation may not work for you. But I don't know if you have a true addiction yet. So it kind of gives them the space to say that I'm not telling you what we're going to do, but it plants the seed that, hey, maybe if I do have an addiction, that, you know, abstinence is going to be my best way towards recovery. Um, so I am a strong advocate of harm reduction. Um, and you definitely want to meet people where they're at. Um, and, you know, because sometimes if we come in too hard on any idea, and this goes back to the Plato and the Aristotle, then people's defenses will go up and it will diminish the capacity to develop a therapeutic alliance. And then nothing good can happen from there. So I think that this theory still is very compatible with harm reduction. Um, you know, and you know, I practice harm reduction in my, um, in my clinical practice, absolutely every day. I don't know if that answered the question. Oh, yes. Uh, I, I had another question to follow up. Um, so we know that this, uh, any addicting substance is like a lot of times powerful than the normal stimuli, uh, that can, uh, create dopamine, uh, secretion, um, in the brain. So when we opt for harm reduction in a patient, um, will it work neurobiologically speaking? So again, it's, it's, it's a good question. And, um, one might think that if you're, for example, um, if, if you can encourage them to work towards new behaviors in their lives and you can sort of rewire, um, uh, you can like, for example, even buprenorphine or methadone, which also can cause doping release, um, in the report circuit, if they're doing that in the setting of a recovery pathway that actually might even more strongly encourage that recovery pathway. So, um, you know, I don't, I don't know how to answer this other than this is a very nuanced question and you have to look at each patient individually, um, and meet them where they're at. Okay. Thank you so much. That explains. Thanks so much. Um, I will, Mark Murphy asked two questions. I'll just relay them. The first, uh, Chris was on your specific slide on, uh, retention at six months with buprenorphine. It looks like he's asking, is it based on sublingual bupe alone, uh, or versus subcutaneous bupe? Yeah, that, that was sublingual bupe alone. And again, that was just as a reminder that, um, you know, buprenorphine is a helpful, important, you know, critical aspect of the treatment of addiction, but we could do better. And that's all I really needed me to convey by that slide. Okay. And then he was also asking that you mentioned several times this quote, this theory, but did you give it a specific name? Like maybe neuroplasticity? Yeah, it's, it's not really given a specific name, but it's just the combination of Eric Nestler's work with Terry Robinson and Kent Barrett. So I would say incentive salience is the closest thing to the description of, of the theory. Okay. Um, Karen Turian, she said, what is the overlay of adverse childhood experiences? Yeah. I mean, when you get that figured out, um, please let us all know, you know, it's, uh, what I found is that people are very complex and it's impossible to differentiate what is the absolute, you know, inciting event. Um, in some folks, trauma and adverse childhood experiences can lead to a state from which they need escape. And they started on the pathway of drug use being their, um, you know, the most effective way for them to create a tolerable reality. Um, and so sometimes in those patients who had significant child, like adverse childhood experiences, once they, um, you know, get into therapy and treatment and go through corrective emotional experiences, um, and, uh, and medical management, then many of those don't turn out to even have addictions and they can do great. But also there are those who have had adverse childhood experiences and have a genetic predisposition towards addiction, and those are going to need extra work. Right. And so all that they're going to need treatment for both. They're going to need the management of the trauma, and then they're going to need also management of the addiction. And sometimes patients like to choose one or the other. Like I'd prefer that this is my adverse childhood addiction, adverse childhood experience, and it's really not an addiction. Um, but in, and in some cases that's absolutely correct, but in others, it might need both management of both. And so that's what I would add for that. Okay. Um, we still have some time. So some people have their hand up. So I think this is an order, uh, uh, Casilda, uh, Furia Ciega, if I'm pronouncing it correctly, I'm I've unmuted you so you can speak. Um, looks like maybe the person's not there. Um, okay. I'll, I'll move next to, uh, Suyun Jo. Um, I'm unmuting you. You're welcome to speak. Uh, yes. I'm wondering, yes, it's a little bit related to the harm reduction question. So I I'm also wondering what could be the possible neurobiological mechanism of the effectiveness of harm reduction. Do you have any hypothesis or evidence? Um, so I, I, I, I don't from a neurobiological standpoint. So, you know, and harm reduction means so many different things to so many different people, you know, harm reduction is essentially a philosophy of saying that, um, you know, many people don't want to stop using drugs and they don't want to stop drinking alcohol. And so if they're going to continue to use drugs or alcohol, then let's allow them to do it in a very safe way. So I think it's too big, a, um, a topic to kind of categorize into, into one simple way. So if someone was, you know, practicing harm reduction and using high doses of methamphetamine every day, then I think neurobiologically, we know what's going to happen there. That dopamine is so powerful that they may have diminished effectiveness at other interventions because of the incredible power of that amount of dopamine. And so it might encourage me to manage my expectations, you know, and this is a situation where I also have to, you know, practice the true spirit of motivational interviewing, which is recognizing that the patients themselves are the experts on them. And no matter how good a psychiatrist, I think I am, I'm never going to know truly who they are. So as long as I remain curious to understand what it is that they truly want and where they want to go, then, um, uh, I believe that we'll be going in the right direction. So from a neurobiologic standpoint, I don't think that we have a theory on that and it would be too big, a, too, uh, heterogeneous, a topic to come up with an answer for that. I'm sorry. Yeah. I, I have one more question. Sure. So how would you describe the different, different vulnerability, uh, in to addiction among people in terms of neurobiology or neuroplasticity? Um, can you rephrase that in a different way? Yeah. Yeah. Yeah. How would you describe, so how would you explain the different vulnerability to addiction? So some people are more easily get addicted. I see. Yeah. Well, you know, it's, it's interesting that this would be, um, a really amazing topic for us to learn more about. One thing that, for example, I found in my practice is that patients who use opiates for the first time and it activates them, that their likelihood of developing an addiction to the opiates is vastly increased. And I've seen this over and over and over again. And I think that there's, um, at least one article describing this process out there. Um, you know, there's some theories that people, you know, of course, people who have underlying ADHD, um, have a high likelihood of addiction and there's certain temperamental qualities where people have, um, you know, uh, novelty seeking, uh, temperaments and things like that, that make us more inclined to think that they're going to be predisposed to addictions. So, um, one thing that I will also say is that if I have patients who are young and they have a strong family history of addiction, it's really powerful. And I would very strongly encourage them to try to avoid drugs that cause dopamine release in the nucleus accumbens up until their brain fully myelinated at 25, because we do have data to show that if patients can make it to 25 years old without using drugs, that the likelihood of them developing an addiction, even if they use drugs goes down exponentially. So we're working on it and we have little clues, um, but we're not too advanced, but that's a great question. Uh, thanks. I will switch over to Michelle Alexander. You have your hand up also, and you should be unmuted now. Okay. Thank you very much. Um, your presentation was excellent, and I just wanted to ask you a couple of questions. Um, my, um, practice is occupational health, and I do a lot of, um, medical review, meaning that I review drug tests for positive results for large employers. And I probably, uh, talk to, uh, I would say about eight to 10 people an hour in terms of those positive drug tests. And all of this is over the phone. And I've been doing medical review, um, of drug testing for a very, very long time, but not in the space where I've only talked to them on the phone. And one of the things I've noticed, um, this issue of, uh, addictive persona, persona is that there is a particular, um, persona that we see for almost every single, um, specific analyte that is positive. In other words, when I'm talking to someone who has a positive test for opiates, their, um, personality and the, and the way that they speak to me is very consistent across every single one that has an opiate positive. And the same thing happens for an amphetamine positive, and the same thing happens, you know, there's a different one for amphetamine, a different one for, uh, someone who is using, um, PCP. And it's really become very interesting that I can almost guess, uh, what the drug positive is going to be based upon just my conversation prior to even looking at the drug test result. And I wondered if that's something that you've looked into, and if there's a neuro bio, um, biological reason for what I'm actually experiencing when I'm speaking to, uh, these patients. I absolutely love this question, um, because I know exactly what you're talking about. Like if we really start to pay close attention, there's, there's a different temperament. There's a different type of person that gets primarily addicted to one substance versus another. So anecdotally, yes. And let's connect offline. Cause I'd love to hear exactly what your ideas are. I'm not aware of anything in the literature describing this and, but there should be. Yeah, I think it should be. I mean, it's, to me, it's fascinating. I didn't notice this before when I was doing almost like a face to face, but on the phone, it's almost like I can tell, you know, within a few minutes of talking to them, what the test is going to be possible. And I haven't even opened up the test result yet. It's so great. Yeah. Connect offline. I want to hear more about what you saw. Absolutely. Um, but yeah, to try to get one more. And before we wrap up, um, Angela has asked a couple of questions about, um, treating ADHD within the context of recovery. And, and, um, do you have any suggestions for medication management? I'm in a person in recovery. It's also making me think Chris, that at some point having a talk on working with patients with ADHD, you know, could be good for this seminar. Yeah, no, I think we, we have, we might have one coming up. It's a great point. Um, yeah. And it's, so it's challenging in my practice. I will prescribe stimulants to patients who have underlying addictions if they have a certain degree of abstinence. So I will not prescribe stimulants as a harm reduction, um, process, uh, in patients who have underlying ADHD. So if they're able to stop all substances and then, um, have a period of sobriety, then I prescribe stimulants myself. So also the stimulants I choose, I choose the methylphenidate products for a couple of reasons. Number one, methylphenidate will not show a routine drug screen as positive. So, um, like for example, if they're on Adderall, that'll come back positive for amphetamine on a routine screening test. And so unless we send a confirmatory test, we won't be able to determine whether or not they're using methamphetamine in addition to their Adderall. And also, um, you know, the methylphenidate products, uh, their mechanism is such that they're, they're less abusable. Um, and so I tend to, uh, use methylphenidate products and long acting methylphenidate products like, uh, Concerta. So, um, there are some folks who are, uh, some addiction psychiatrists who are more liberal and will prescribe stimulants to people who are actively using other substances. I tend to be on the more conservative side, but I do do it with close monitoring and very specific medications. It's a great question. Um, I think we're out of time. Uh, thanks everyone for all your comments, Chris, just so you're aware, I was deleting a lot of great talks and thank yous just so I can, um, scan through all these comments. So there was a lot of positive feedback. Um, thanks everyone. I'm really hoping we're seeing a lot of you at triple AP, which is in November of this year. And then our next talk on transference focused therapy in December. And as Chris usually ends this talk, I'll end it, um, quoting him. I think we're all a lot smarter after having attended and listened to this. So thank you very much. Thanks everybody.

Addiction

Neurobiology

Recovery Capital

Neuroplasticity

Dopamine

Epigenetic Process

Brain Changes

Impulse Control

Contingency Management

Recovery Hacks

Genetics

Treatment Outcomes