Hello I'm Dr. Steve Wyatt and I'm an addiction psychiatrist in Charlotte, North Carolina and I'm going to speak to you today about just the general principles of addiction medicine and I've titled it The Elephant in the Middle of Healthcare in that it is such a strong and important part of the problems actually of healthcare in the United States today. This is part of the Essentials of Addiction Medicine course put on by the American Osteopathic Academy of Addiction Medicine. I don't have any disclosures. I don't speak for any pharmaceutical companies or have any investments. So I'd like to to ultimately give you a better understanding of the impact of substance use problems in the health of our patients and thus the importance of addressing them longitudinally and that's going to be an important part of what I talk about particularly around treatment and then also to understand the neurobiology of addiction. By understanding that I think that we have a better understanding of why treatments have evolved in the ways that they have and that there are effective treatments. Lastly to understand the importance of considering this as this problem of addiction or substance use. It is a chronic disease and therefore should be treated that way. So I like this cartoon in that it depicts the idea that addiction is so much a subconscious mind behavior problem. Our conscious mind has very little capability once the addiction has really taken hold to control the addiction. Now obviously we can use we have to use the conscious mind to to move into a state of recovery but when a person is currently addicted it's just extremely difficult to get a handle on that and turn it around by themselves. I often think about this also in the elephant way in this cartoon that you've probably seen before around perception and how you look at something and someone that is in the middle of of an addiction often has very little comprehension that they're thinking a specific way because of their addiction. They see it as black and white. They see you know young person at a party. He's been drinking. He sees his girlfriend talking to some guy. He believes that they are you know in cahoots or the other guy is coming on to his girlfriend and he's up hitting him. You know it you lose that that understanding that what you think and how you're thinking has been influenced by the alcohol or drug that you may be taking. So in order to get you who I think are mostly clinicians into a state of really being able to have a healthy practice looking at recovery appropriately there's a few things that need to be done. One is the idea of your attitude that empathy for patients that have this disorder and are not seeing it clearly is is extremely important. Respect as you would respect any other patient and then be receptive to the problems that they're experiencing and you know some of that has to do with being open to it be looking for it and that partly comes from skill and behavior planning in your office. So to be able to do some motivational interviewing which isn't covered in this lecture but is covered in subsequent lectures within the essentials course is part of a brief intervention. Once you have identified that there's problem through screening then to use some forms of motivational interviewing to engage the patient. So screening tools, engagement and then having things set up in the office that could could be helpful to patients. So literature that might be available and then obviously being capable of and understanding have the knowledge of using specific medications. Knowledge goes a long way towards certainly reducing our bias or stigma around treating these diseases. So to understand that the origins you know go way back into childhood which I'm going to speak about later that the prevalence is significant in our population. If you start looking for it very closely you're going to see it in overwhelming ways in many in many practices and there are specific mental health and physical indicators of substance use that you need to be knowledgeable and understand what are the treatment options. So how important is this to address these problems? It's considered that around 26% of patients, so it's really 20 to 26% of general medical clinics, clinic patients have alcohol use disorders alone. That is for two things I think there. One is are they at risky drinker and so they're at risk of having problems or are many of the problems that you're already treating associated with the alcohol use problem in the first place. So that that increases the potential that you're going to be treating these problems. When we think of substance use problems in general and particularly if we add tobacco products to this it's really overwhelming how many patients are really presenting with problems in general medical clinics that are associated with substance use problems. Forty percent of all trauma is associated with alcohol that's cut fingers in the kitchens, sprained ankles in the softball field or major motor vehicle accidents, gunshot wounds, lots of traumatic you know accidents and falls and suicide. Forty-two percent of fatal car accidents are associated with non alcohol use drug use disorders and 57% had high blood alcohol levels, 21% had both a drug and alcohol on board. Doctors continue opioids for 91% of patients with history of non-fatal overdoses. 17% of these patients overdosed again within two years because we weren't looking for it. 8.3% of 30-day readmissions to the hospital are associated with substance use problems and higher predicted probability of 30-day mental health readmissions when a person has a substance use disorder. 6% of pregnant women have a substance use disorder and this is a highly vulnerable period for women and very often is associated with an attempt to cut back so if there is an opportunity to engage women that recently pregnant we can have a tremendous impact on reducing and potentially stopping or bringing it in a much better control with identification and treatment. Substance use exists in 40 to 80 percent of families in which children are victims of abuse that's physical, emotional, sexual abuse and neglect so it's highly prevalent in that area and that obviously puts these children at high risk for a whole host of physical and mental health problems including substance use disorders themselves. Up to two-thirds of people in treatment for a drug use disorder report physical, sexual, or emotional abuse during childhood. 6.9% of 12th graders report marijuana daily and 21% smoked within the last month. 35% having drunk once in the last year. Alcohol and drugs are implicated in about 80% of offenses leading to incarceration and given all of this data less than 20% of primary care physicians describe themselves as very prepared to identify alcoholism or illegal drug use. Age-adjusted death rates for four selected mechanisms of injury, these include falls, motor vehicle accidents, firearms, and drug poisonings, are now at the highest rate within drug poisonings. It passed motor vehicle accidents nearly 20 years ago and it's just continued to rise where these others have remained more more stable and I think it's very interesting particularly around motor vehicle accidents that we've done such a nice job since I was a child of establishing that you have to wear a seat belt and now we have airbags and cars that once they have a front-end collision the engine just drops to the to the ground instead of going into the into the driver's area. We've really through understanding a problem we put things in place to fix it and we haven't been able to do that as effectively with with drug use disorders opioids in particular. So addiction has a very clear neurobiology. There are specific areas that are impacted. There are certainly the what are referred to as the unconditioned response that is you take the drug it has a specific effects on the brain those specific effects can be somewhat genetically predisposed to a particular problem but in general they're going to have a similar effect on most people and part of that has to do with the pleasure center the the nucleus accumbens the brain and from there we have memory of that we start to link it to specific places we start having wanting which is associated with the striatum and and this all becomes more conscious so we start looking for specific situations or the the alcoholic drug itself so it affects our motivation which is primarily driven by dopamine and I'm going to show you more on that in a moment it then increases our executive functioning to get the drug secondary to the to that learned memory about the drug and with that we have a reduction in our inhibitory control so craving and that reduction in inhibitory control is what really drives the disease and the inhibitory control just causes so much so many problems for patients here you see PET scans associated with one on the left coronary artery disease and on the right decreased brain metabolism in in addiction and these were brains of individuals that had been taking cocaine on a very regular basis for a period of time and clearly we can identify that this abnormally functioning heart from heart disease is shows up in the in this PET scan when we look at the brain too often we still think that the way in which we think is how is is ingrained it doesn't change we always know you know right from wrong or good or bad behavior on our part the same but we we clearly at the same time know that intoxication changes how people think we know that chronic intoxication results in significant withdrawal symptoms we know that people can have triggers to their use that are now ingrained in their brains they see certain things they hear certain voices they're around certain you know environments and they're going to want to drink more and the idea that they lose some capacity to understand that is is is part of what the brain does so we we we have problems with the brain it's going to it's it's gonna change how we think or how we act or behave or we react to certain things so it's very clear and these changes can improve absolutely but there are certain aspects of it that take much longer to improve than others when we look at dopamine as the primary neurotransmitter involved in motivation you see that on top and two black graphs it's showing two very important aspects of our of our being human our need and our desire and thus our enjoyment of food and similarly our enjoyment of sex which is procreation of our of our species these are tied into this pleasure center in order to motivate us to be doing these specific things on the lower slides you see amphetamines and morphine amphetamines and if you look at the the y-axis you see tremendous increase in dopamine release with amphetamines and and significant increase with morphine also and so what what this is displaying is how it can compete very effectively with food or sex and and does so people stop eating or they stop eating with any with the same habit or desire that they once had and their sexual function goes down very frequently when it's become habitual there can be increased sexual function intermittently but particularly with morphine and opioids in general there can be a significant reduction override of the desire for for opioids over sexual function so in the non addicted brain we see a certain amount of salience driving behavior associated in the nucleus accumbens and we have the ability to remember important ways in which we want to live our lives and and we can we can have a pretty good control of that salience by the nucleus accumbens and consequently be able to continue to have control over our cingulate gyrus and and our our conscious drives within the the frontal cortex to carry out normal you know goal oriented behaviors the addicted brain and the use of drug lets this first this first what I just put up this this idea of what kind of stops that is drugs it overwhelms it with just the way I described it a moment ago with tremendous boosts in dopamine within the nucleus accumbens when that happens repetitively enough so that now there have been these changes that you see in the PET scan then that salience for drug becomes profound the the desire for drug way overwhelms other normal needs that the body and brain and and family and you know all the different things that that are typically very important to us get overwhelmed and we lose that normal control now the drive becomes significant to to get and potentially then recover and keep looking for drug again so the memory of the drug use becomes profound and and this is the habitual part of what's taking place and we continue to use so what is addiction is it a choice then certainly it's a self-destructive choice leading one away from those natural or individual goals that one might have and what motivates our choices is it is an interesting question is it want or is it biologic drives and I think it's important for us all to understand that the majority of what we do on a daily basis however you know you might be watching this sitting in a chair leaning back or wanting to listen but you know really tired or stressed and nodding off you know we can want all kinds of things but it's important to think about the idea of what we if we took all of the things of what we want and really wanted to see what did we as an individual want it's what we've done and too frequently our biologic needs kind of overwhelm our our want so we may want to do certain things we may want to go for a run or get some exercise I'm coming home from work but we walk into our home and we see the couch and we're pretty tired and and all of a sudden we're laying down instead of doing what we had wanted to do the same can certainly be true for all of us with eating or you know relationships all kinds of different things in that in that regard so is it a lack of will is it high impulsivity or poor self-control I think it's important when we think of when we look at it that way to look at what was the person like before using drug and almost invariably when I talked to families you know mothers fathers in particular they'll talk about how you know their young person or their young adult had had significant goals in which they were pursuing and then they got caught up in drug a drug use disorder and it and it took that away so it's not that it's just a lack of will it's takes over that will in some way that's part of the disease the other question is is it a habit you know so some people will talk about you know it's it's no different than any other habit I think it's I think it's interesting and important in that way to consider the difference between a habit like you know you're getting ready for bed and your habit is to go into the into the bathroom and brush your teeth or a habit that you might have about you know positive behavior but you can stop it if you want there's not a biologic drive necessarily to doing those things it's a habit and habits are definitely programmed in the brain they lay down certain tracking takes place we can find ourselves brushing her teeth without thinking about it but at the same time then when you think about thirst you walk into your home you're thirsty you immediately go to the water sink to get a glass of water or to the refrigerator for something to drink and and that was driven by a biologic need so is that a habit you know you always do it it's always it's what you think about right now no I wouldn't call it a habit it's it's satiating a biologic need so addiction falls in between these obviously it's a place of its own it has biologic drives no question, people stop using opioids. They go into withdrawal. They feel agitated and then they know that they can take the drug and feel better. Whereas at the same time, it's certainly a habit. It's certainly driving home from work and they know this particular liquor store that they stop at and they pick up a six pack and drink one or two before they get into the house. So it's more than just a habit. Is it a disease? A disease of the brain resulting in disease thought and behavior that's biologically driven. The definition of a disease is a disorder of structure or function that produces specific signs and symptoms. And I'm going to be making a case for this later in the presentation. But addiction is well established, both genetic, having genetic and environmental causes and objective signs and symptoms that are both behavioral and biologic. So important areas of neurobiology of addiction are that dopamine release leads to a subjective feeling of pleasure and reward and reduction in feelings of stress. That's why people will have a drink or smoke marijuana or take an opioid. That is taking place within the nucleus accumbens. Repeated use over overrides impulse inhibition. It becomes something that's uncontrollable and where we think that we're going to go to a doctor or to a family event, but then we realize there's no drinking or we don't have drug on board, then we may skip the family event, make some excuse. And it was potentially something extremely important to us as something that we wanted, but the override of the drug results in that impulse inhibition, results in the impulse inhibition. Repeated use is also associated with discomfort when stopped, which leads to more use. And that's the biologic effect that takes place. That's taking place within the amygdala, the stress response. And we have both physical and mood dysregulation that takes place that drives using. And many people think that's the only reason I continue to use. And yet we can pull people out of a withdrawal state pretty successfully now with medications. But four or five days after, we can do that within four or five days, but after that's completed, people very frequently fall back into drug use because that's not taking care of the craving part of it. It's not taking care of that impulse inhibition that's taken place. So dysregulation of executive function then is clearly pushing this and that results in this preoccupation and anticipation that takes place in the frontal cortex and the salience for drug. So how is this impacted in our world? We know that it makes all other diseases worse. It causes many diseases. So it can cause acid reflux or asthma or headaches, cardiovascular disease. But even though it can cause them, it also makes the treatment of those diseases worse because adherence is impaired. People don't follow through with the instructions that we may have to help them or to take their medications appropriately. This is particularly true in when we look at the association with, as I said earlier, injuries and overdoses, but also depression and anxiety. It makes them much worse. That's not to say that people, it's not often the driver of those diseases. Excuse me, it wasn't the driver of a substance use problem, but if it's co-current, if we can get the substance use problem under control, we often have a better chance. Well, we'll first of all, see a reduction in symptoms very frequently, but we also have a better chance of actually treating it effectively. We know in PTSD patients that have a substance use problem, we can have a reduction in symptoms if we get the substance use problem under control, and we can then potentially control the PTSD quite well. But if we just get the PTSD under control, it will not necessarily control the substance use problem if it's clearly an addiction, where there have been the types of changes in the brain that have taken place that I've just discussed. So this is a worsening epidemic where we have seen a continued rise in opioid deaths. This has been often talked about as these three waves. One was in the late 1990s and recognizing the rise in opioid use disorders, a result of overuse of opioids for pain in this country and in many other parts of the world. And then as we started to get it under control and there were certain policies, some of which have backfired on us in some ways, but policies that did take place to reduce the amount of opioids on the street, we saw this significant rise in heroin. But then, unfortunately, there was a increase in availability of synthetic drugs and synthetic opioids and fentanyl products in particular, which were highly potent and extremely dangerous. And as that has increased, we saw another considerable rise in overdose deaths from opioids. And certainly COVID has not made this any better. It's actually gotten worse over the last 18 months. There's a considerable overlay between comorbid mental health and substance use problems. Typically thought that nearly half of people with an illicit drug use disorder are gonna have a mental health problem. And on the other side, people with mental health problems, it's in the range of 25%. And so, again, when I teach this to medical students and residents, I often talk about that one should have a low index of suspicion. You find someone has an alcohol use disorder or even smoke cigarettes, to recognize the increased potential that they have a mental health problem is something that should be attended to. And vice versa, people with a mental health problem, we really need to be talking about more frequently screening for substance use problems because it's just so prevalent and it makes treatment, it impairs good treatment. The costs of these are phenomenal. We throw these numbers out, but, and these are older numbers and they've only gotten worse as the costs of healthcare and problems have gotten worse. But it would be a tremendous savings to society and healthcare costs in particular, if we could be more knowledgeable and skilled at identifying these problems and treating them appropriately. So let's talk about it as a chronic disease. Why do we think of this as a chronic disease? And I do think this is one of the important things that I'd like to have you take away from this. They have, comparing it to depression, diabetes, hypertension, asthma, they have similar treatment adherence and relapse rates. I'll show you a slide of that in a moment. It results in, from voluntary behavior. They are doing something contrary to what you've, as a healthcare provider, have advised them to do. And it's difficult to manage behaviorally. It's because these are behaviors that drive the chronicity and the lack of adherence to good care. It's difficult to manage because you can't be inside the person. They often are caused in part, these chronic illnesses by genetic factors and they respond to ongoing treatment. Some will have to engage in lifelong management of their condition and others won't. Others, type two diabetes, they get their blood sugar down from diet exercise and they may not need treatment any longer. Or hypertension, absolutely that can take place. So the criteria of a chronic disease are a patient presents with a problem and there's a biologic basis, identifiable signs and symptoms, predictable course and outcome. And treatment improves the outcome. So if we look at substance use disorders, and they're all defined by the Diagnostic Statistical Manual, Edition 5, the same. So they all carry these same criteria and they are split into four areas, impaired control, social impairment, risky use and pharmacologic, physical problems that are associated with it. And they are very clear and they're reproducible. So we clearly know that once a person has impairment of their use, they have inability to cut back. They're using for larger, longer periods of time. So consequently more time is spent getting, using and recovering and they have craving. They can't stop thinking about it. That begins to result in social impairment where they're not fulfilling certain obligations. I mean, if you're spending more time doing one thing, you're taking away from something else. So the zero sum game gain. And so social and interpersonal problems begin to happen and important social activities are given up. Once it becomes very severe, you're not only doing it and missing some of these other things, you're doing it while involved in more hazardous behavior, driving cars, driving a boat, doing physical activities of sorts that you shouldn't be doing while you're impaired. And yet, even when you have an accident, even when you develop endocarditis from injection drug use, you leave the hospital and start using again. That's severe impairment, severe addiction, significant behavior contrary to what we would typically think as healthy human behavior. Now, pharmacologic involvement in part has to do with what drug it is. If it's opioids that have been prescribed, everyone's gonna have tolerance and withdrawal over time. So that does not meet the criteria. Those two alone for opioids did not meet the criteria. On the other hand, it's an indicator for alcohol. It's an indicator for marijuana. Maybe not so much an indicator for stimulants. People have a binge of stimulants, they're gonna then sleep for a day or two, whether they have been using with regularly and have cravings or not. And so it's variable between drug. The rankings of preventative surgeries are outlined in two different ways. One is clinically preventable burden. That is how much disease, injury and death would be prevented if services were delivered to a targeted individual. And then the cost of effectiveness, the return on investment from doing that, from doing that for screening and delivering healthcare to people with a specific problem. When we look at recent information associated with this, two drugs are on top of this around the world and that is tobacco and alcohol. If more individuals were receiving services nationally, the savings are phenomenal if we were to get that up to 90%. And as you see for alcohol, the number of people receiving services for alcohol use disorders is in the range of about 10%. And so we have huge movement, capabilities of improving this. And it would not be that terribly difficult if in fact it just became part of healthcare services, that this was just how physicians and providers in general worked, how they did their jobs, that they were looking for these problems because they are so prevalent and yet they cause such problems both to the individual and to people around them. So I've gone through the biologic aspects of this in terms of some of the problems that result from drug use disorders. But I wanted to point out also the genetic variation because I think sometimes that can be a hook for people to kind of look at these folks a little differently. 40 to 50% of people with substance use disorders have a genetic predisposition to that problem. You know, one of the ones that some of you may know is around alcohol. You know, people that have high alcohol dehydrogenase will metabolize alcohol quite rapidly. And people that have low levels of alcohol, of acetaldehyde dehydrogenase, don't get rid of that acetaldehyde from the metabolism of alcohol easily. And that's what makes us sick. That's actually the drug that we use for the drug disulfiram. It inhibits that enzyme. So people that have that low level alcohol dehydrogenase, high levels of acetaldehyde, excuse me, high levels of alcohol dehydrogenase, I'm sorry, and low levels of acetaldehyde dehydrogenase, they take a drink, they get sick, and they say, who can drink that stuff? They just don't even understand. On the other hand, someone that has low levels of alcohol dehydrogenase, that is they're metabolizing it slowly, and high levels of acetaldehyde dehydrogenase, they get rid of the acetaldehyde very rapidly, they have natural tolerance. They can drink everyone under the table. They begin to associate with other people that like to drink. They still get intoxicated, but they don't get real sick from it. They can wake up without a hangover sometimes, unless they're really drinking heavily. So this is, you know, this is the difference. Again, that person with the first scenario, they're not gonna become an alcoholic. And in fact, certain nations in the world have low alcoholism because of this, like certain Asian nations. So genome-wide association studies have identified certain SNPs, specific neuropeptides, that are associated with nicotine receptor subunits, and these influence the risk of the disease of nicotine dependence, and others impair inhibitory control so that your ability right off to kind of control that behavior. Now, sometimes that can make a person, you know, very artistic and, you know, doesn't have a lot of inhibitions, but if associated with alcohol and drugs, it can be somewhat of a kiss of death. It can cause or result in the development of an addiction more quickly. There are epigenetic changes that can take place that open certain genetic windows that cause young people, the one that we know most clearly is young people associated with cannabinoids, cannabinoid use that have a predisposition to a psychotic illness. It will open them earlier. And then they lose the understanding of what's happening because of the blossoming psychotic illness, and their ability to inhibit their use is impaired. And then lastly, there's pharmacogenetics involved, and that's one thing that we know in terms of people that will respond more effectively to naltrexone for the treatment of alcohol than others. So again, these are important things to understand. And when we look at it compared to so many other problems that we, you know, that we jump to treating, you know, that are, we feel so terrible about someone that's had a stroke or Parkinson's disease, and yet the potential for it being as a result of genetics, where it was not the person's, you know, lack of will or their, you know, their wanting to, you know, just get high all the time. It was really a genetic predisposition to their illness. And so I think it hopefully will help you understand and kind of stand back and think about, you know, what was their home life like, you know, what was the genetic predisposition to this illness and all the different things that go into it. I've showed you this before, but just to reiterate, the midbrain is where the nucleus accumbens and the amygdala are associated with that increase in the amygdala, that increase in dopamine in particular, tied into that is the basal ganglion. And the ventral striatum compared to the dorsal striatum, where the nucleus accumbens is actually housed, the ventral striatum is where we have some controls and where craving just starts to overwhelm the individual and then the prefrontal cortex. These are the unconditioned responses. I think one of the more interesting things here is that you see alcohol in multiple places on this cartoon that, because alcohol just sort of overwhelms our system. I mean, we take grams of alcohol compared to milligrams of other drugs. And then also that stimulants are working on direct release and disabled reuptake of dopamine. So that's where the release of dopamine secondary to stimulants is just profound. So again, early environment and the effects of adverse childhood events is just so important. It relates to increased mental health problems, physical problems. It's been shown to be associated with employment problems and legal difficulties. More than five ACEs results in seven to 10 times more likely that the individual will develop a drug use disorder. And individuals seeking treatment for alcohol or other drug use disorders show a high prevalence of these ACEs and PTSD. So one of the things there is to just be aware of how frequently trauma is associated with substance use problems. And the reason why so many substance use treatment centers are trauma-informed. They are doing things, setting groups up in a way to make people more comfortable and not re-experience trauma in their life. Age of onset, also hugely important. Young people are naturally prone to risk-taking. This is a developing prefrontal cortex to really think through, is that dangerous to jump off that bridge into the water or should I check out deep the water is first? And how particularly vulnerable that makes them to drug use problems. And exposure to drugs at this critical time may affect the propensity towards a future addiction as shown here where, I take that out, but there is a significant increase in the number of young people that will develop a substance use problem depending on the age of onset. So a 12-year-old that starts using with regularity has a significant increased chance of having a drug use disorder by the age of 25 compared to that young person that starts using at 18. So every year a person gets older, I thought somewhat when my son was growing up, when he went from 12 to 13 to 16 and hadn't been using anything with any regularity and that the chances of the development of a drug use disorder was going down. So again, these problems do have definable biologic signs and symptoms. They are closely associated with increased morbidity and mortality. Particularly the top is tobacco around the world, diet and exercise number two, but alcohol is number three. And I always point out that tobacco and alcohol affect diet and exercise. So, it's just, it's ubiquitous in many ways. The way in which once a person starts using how it affects everything else. And here's just a big list of the problems associated with drinking alone from neurologic problems, numbness, tingling, painful nerves, but some certainly gastrointestinal problems that can result in some vitamin deficiencies, bleeding time and time bleeding within the gastrointestinal system, cancers, premature aging, skin problems, certainly fetal alcohol syndrome from drinking during pregnancy and depression. So the list just, it's phenomenal. The number of physical problems that are associated with chronic use of alcohol. And again, that's partly associated with the fact that you're drinking huge amounts of alcohol, grams at a time. And so it's significant. They do have a predictable course. We know that as people start using, they can have some pleasure and gratification and then may have some regret and guilt over things that they did, but then potentially tension and arousal can result in impulsive use again. And as this goes on more frequently, this starts rolling to the right where it becomes more of a compulsive disorder where if you don't use, you start to get anxious and stressed. That would potentially even be amygdala involvement and some withdrawal symptoms, but that leads to this repetitive behavior that then results in relief of the anxiety and stress because now you've got a little alcohol on board and we're into this obsession. So this is clearly, it's the wanting that happens. It's the wanting that really drives the disease. It's no longer really the liking. You'll hear that frequently where people will say, you know, I don't even like it the way I used to, but I just can't stop. I can't stop. I can't stop thinking about it. I can't stop the behavior. So those are the conditioned responses. Now, opiates on the brain have a certain response. They alter neurotransmission and relaxation, euphoria, stress, buffering, whatever. And that's associated with enteric and interoceptive changes, mood states precipitated and that precipitates use. You know, they get hungry, hungry, lonely, tired, and they use. And then there's the extroceptive conditioning that's from environment and seeing the drug. And we've, you know, there's PET scan and things that have been done where we show them certain cues and their brain lights up very different than a normal brain. So it's the cues after a period of time that really drives the disease. Again, there's this cellular response to neutralizing the effect of the drug. That's alcohol. You put a depressant on the system long enough. It wants to stay alert. It wants to go to work. It wants to drive a car. It wants to take care of its kids. And so it upregulates the, has upregulation mostly of norepinephrine associated with the amygdala. And so they're able to do that if they keep drinking, if they stop drinking. However, now it's dysregulated and this neuroadaptation becomes the symptoms of withdrawal. And the opposite is true with stimulants. They take stimulants regularly. Now they, you know, they just want to go to sleep. They sleep for a couple of days. They start to build back up their dopamine and they're now stimulated and want to go out and use again. So it's really, it's that idea of the system wanting, you know, this allosteric response, wanting to meet that place of homeostasis that results in the counter-adaptation opponent process. So the prefrontal cortex is the big one. And that I say that in that that's where, you know, that's where the term denial came from, you know, that they're in denial, not exactly lying. They just don't see it anymore. It has changed the way in which they view the world. And that's the reason. So it impairs this response to both inhibition and salience. And that's response to the drug and related cues, tremendous response to non-related cues over time, tremendous impaired control that median or orbital prefrontal cortex now can't, can't, you know, stop from doing things. And I've had multiple patients cry in my office, just thinking back on the things that they did that they just never would have dreamed of doing. And that's this impaired control, impaired awareness of the illness is what keeps them from actually getting into treatment early. So the origins of relapse, how does that happen? Some of it happens from a positive effect, that's activation of the condition response, dopamine activation of the mesolimbic system, and negative effect is the other, and that's glutaminergic. So that's the stimulatory aspect where there've been this adaptation so that if they stop, they get agitated, they get depressed, their brain is not functioning normally. And that's why we use some medication sometimes for post-abstinence effect, that early period where they're just not functioning well. And then long-term, there can have been some decrease in dopamine release in the nucleus accumbens reward system that persists. And so this is a protracted abstinence vulnerability. They have a little trouble finding as much reward to sex and good food and watching their children play or things that they may, and it's sort of normal for us, they may not have the dopamine release in a way that stimulates them because of a rather anadonic state. So there's relapse, but there's relapse to all sorts of other problems. People stop their treatment. They stop using their medication or following their diet or putting themselves, keeping themselves away from certain environments. So even though addiction is defined as a relapsing illness, most chronic illnesses are relapsing. You're gonna have periods where you're doing better. And then for one reason or another, things start not working out well and there's a relapse of the illness. So treatment clearly in the last part of this definition improves outcomes. We know that it works, even if the results are measured one year post-treatment. So we're gonna see a reduction and a reduction in use. And this is part of where the harm reduction world has taken some prominence. We know that if a person drinks a case a day and they get down to two or three beers a day, which some people can do, not a lot, but they can, they're gonna have an improvement in their health. If they can reduce their number of cigarettes, they're gonna have an improvement in their health. So the National Institute of Alcohol Abuse and Alcoholism has clearly come around to the idea in the last few years of not necessarily starting off with you've gotta stop drinking, because that just turns people away if that's the first thing out of your mouth. And instead, like, what do you want to try to do? And this is more motivational interviewing, where do you see any problem that you'd like to try to control? How is that maybe associated with alcohol? And then would you like to give me, for me to give you some information? Here's healthy drinking standards. If you can do this, great. And people who have the opportunity to try that, many don't find that they just can't control their drinking, but some do. And so a reduction is a number that we look for. We wanna see that. Well, I've seen significant improvement in people that have occasional relapses of opioids while they're taking buprenorphine. And though that we talk about it, and if you're open and willing to talk about it, they'll freely tell you about it. And they don't typically wanna fall back into it, but they're still improving. So we can see significant improvement with continued treatment. This is a now famous slide, kind of reworked, but slide by Tom McClellan, that I think is very interesting. So in hypertension, they have high blood pressure. We give them a specific medication. Their blood pressure goes down. We take the medication away. Their blood pressure goes up. Boy, that medicine works really very well. In substance use disorders, a patient has a problem. We send them to a 28-day program, or we say, here's an intensive outpatient program. They're in it for a month or three months. They're in a controlled setting. They're getting a lot of support for problems, and they do very well. They're talking beautifully. They're telling family their remorse about things and things they wanna do in their lives. And then they get back into their own environment with no treatment. You take the treatment away, and lo and behold, the problem comes back, and we say, treatment doesn't work. Well, that's because we're not thinking about it as a chronic illness. We're not continuing the therapy and continuing the medication in a way that people can really improve their lives. The current treatment problem so frequently is siloed. It's in different places that primary care is not screening for it. They're not screening for it in the hospital or in the emergency department. And consequently, there's big philosophies differences because of lack of knowledge between these different silos, and it's very fragmented and episodic care. And consequently, there's suboptimal clinical outcomes. So the Institute of Medicine has said, it's not possible to deliver safe and adequate healthcare without simultaneous consideration of general health, mental health, and substance use issues. It's just so important that we understand the clear data on how ongoing substance use problems makes all other chronic illnesses worse, and begin to see that, screen for it, and treat it. The chronic care model of this disease would be addiction pharmacology within the primary care setting. Now, that may be that they went to specialty care for a period of time. They went to that Malibu on the shore and kind of got readjusted, but got started on medication. They return home. They continue medication in a primary care setting. They have a relapse. They might go to an intensive outpatient program or as specialists, just as you would send someone with worsening cardiac disease, that you encourage that they get involved in mutual self-help groups, social support groups. This is developing an environment around them and new contacts that understand the disease, that they can tell someone, I had a thought of using, whereas a spouse or a parent might just freak out the idea that they even thought about using again. And then a self-management plan, cognitive behavioral therapies, relapse prevention, and just thinking about, where am I going? How am I staying healthy? What am I putting in place of that time I spent getting using and recovering from drug and using specialty addiction treatment as needed? So the National Institute of Health and Institute of Medicine encourages encourages organized medicine to make addiction a high priority. It's become very clear in our society, the importance of this. And fortunately, there's more interest in teaching it in medical school. And we're trying to keep that alive because of all that I've just told you. Look at other chronic illnesses. There's a role for both primary care physicians and referral to specialists when their expertise is needed to establish treatment initiatives and maintain ongoing care. So just to bring this to perspective, this was something that maybe a number of you have heard about, but that over the last five years, and it's continued, there's been a drop in the life expectancy. So this was first reported in 2015 out of Princeton that there'd been a drop in mortality in the United States, unlike any other Western nation in the world. And this was associated with poverty, with changes in our economy, that disparities, health disparities, but also significantly alcohol use disorders and the degree of liver disease and other problems associated with alcohol. But the one that really pushed it over the top was opioids. And that was in part because so many of these people that are dying from opioid overdoses are between 18 and 35, which has significant effect in that overall life expectancy. So this is clearly, this is one more indication of the importance of really looking at these problems seriously. And in doing that, I like this plan put forth by Robin Williams at Columbia. And it's like saying, we know the problems there. If we could diagnose it more frequently, we would have at least a jump on then engaging people in care. And if we could increase the ability to engage people in care and engage them in evidence-based care with medications, if appropriate, like medications for opioid use disorders, and then recognize the importance of retaining them in care, then working at sustaining that abstinence, we could have a tremendous impact on the opioid use disorder, the problems. And I would say many other substance use problems also. So those are the goals. And if you can look at your own system, wherever you're practicing, and think about these things, like how are we actually screening for it and diagnosing it? Who's actually engaged in care? And how are we using motivational interviewing or other things to help people get engaged in care? And when that happens, are we using evidence-based care and retaining them in care? So it's just, it would be a wonderful world. Some states are doing a good job at this. They've got ECHO projects, which I would have you look for in your community. These are opportunities to learn more right from your office and prevention projects within communities. Harm reduction, hugely important and associated with reducing stigma and allowing people to at least engage in harm reduction in terms of their use. Developing peer supports, mobile units to get to areas. I know I talk about evidence-based care, but there's a lot of communities that don't have evidence-based care, don't have any specialty services available. Seeing that recovery houses are really recovery houses and that are well-controlled, that there's family engagement. Telehealth has gone a long way to reaching those rural areas that don't have much available. And then medication first. Get them on medication, particularly opioids. We know this. Sometimes alcohol also just gets them to have a fighting chance then to engage in treatment, engage in all the other things that I've talked about. So substance use treatment is evidence-based science that has resulted in public health orientation approach to the effective, practical, and sustainable policies and practices to prevent substance use before it starts, identify it early, and put in place effective treatment. The remission of long-term recovery is improved when it's evidence-based. It's provided for an adequate period of time. I can't reiterate that enough. And delivered by properly trained individuals and augmented by supportive monitoring, recovery support services, and social services. There's more than 23 million people previously diagnosed with a substance use disorder that are now living in long-term recovery. It works, but we need to deliver it appropriately and help people understand that it works if they work it. So that's the ability then to have control over the elephant. That's learning things, having a prefrontal cortex that's healthy and not being bombarded by this other stuff. So you can enjoy your elephant ride. And that's through awareness, through self-efficacy and motivation, behavior changes over time. That's what the individual goes through. A variety of resources available to you. I would, you know, any of you that are interested, the AOAM has all sorts of resources. And the PCSS, the Provider Clinical Support System, has certainly a lot around opioids in general, but more and more in substance use problems also. And the American Society of Addiction Medicine site, the NIAAA site, NIDA, these would all be places to go. Scope of Pain is a project out of Boston University that could help give you some insights into when it's a comorbid problem of pain.

addiction psychiatrist

addiction medicine

chronic nature of addiction

neurobiology of addiction

substance use problems

impact on healthcare system

genetics

effects of drugs on the brain

comprehensive approach

public health issue

evidence-based care