Overview of substance-use disorders. I'm Richard Saitz. I'm Chair of the Department of Community Health Sciences and professor of Community Health Sciences and Medicine at Boston University School of Public Health and Boston University School of Medicine. I'm an addiction specialist and a primary care physician. First disclosures, alkermes is provided medication for an NIH supported study that is ongoing here at Boston University. The target audience for this presentation is really those who are interested in this overarching goal of the PCSS-MAT which is to make available the most effective medication treatments to serve patients in a variety of settings, including primary care, psychiatric care, and pain management settings. The educational objectives are to identify the spectrum of substance-use, described neurobiological responses to substances, assess existing theories regarding substance use disorders, use accurate clinical terminology, describe the basic epidemiology and public health impact of the disorder, list Common comorbidities in people with substance use disorder, and to describe how chronic disease treatment applies to addiction. We'll cover those as follows. I'll spend a little time on the spectrum of unhealthy use. Talk about societal impact, neurobiology, theories of addiction, accurate terminology, epidemiology, comorbidity and then end by discussing chronic disease treatment or integrated care. So first, the spectrum of substance-use. This figure describes the whole spectrum of substance use and you can see at the bottom of the figure that there is no use and no consequences since there's no use. The triangle as you go from the bottom to the top, increases both consumption as well as consequences and that's the severity of those consequences and heavy consumption as you go up that triangle from abstinence or no use all the way up to a severe substance use disorder. Now the triangle that in sort of an orange greenish color is meant to depict unhealthy use. Unhealthy use is the whole spectrum from use that increases the risk for consequences, risky use, at-risk use or hazardous use. Those terms can be used interchangeably all the way up to use that lead to recurrent consequences. The disorder or the disease, substance-use disorder can be characterized as mild, moderate, or severe. The reason harmful use appears on this triangle is because that's a diagnosis in the international classification of diseases that still uses the term harmful use and dependence as a diagnosis and those could be thought of as interchangeable with substance use disorder. Again, that's the greenish part of the triangle at the top. There's also a category on the triangle I didn't mention yet, lower-risk use or low risk use and that's really an epidemiological definition or a public health definition that at some point we begin to pay attention to the risk of substance use. That is that there are high enough to slip into that category of risky or hazardous use. This is more commonly thought of and more easily defined when we talk about alcohol because there are certain amounts above which the risks increase substantially. But it could also be thought of for other drugs. For example, it's likely that there's low-risk infrequent cannabis use and that at a point where it becomes more frequent and greater amount, it may trip into a threshold where we really are concerned about unhealthy use. These are the DSM 5, or the diagnostic and statistical manual of mental disorders, fifth edition criteria for substance use disorders for the diagnosis. There are 11 criteria and at two or three criteria, it's a mild disorder, 4-5 moderate, 6-7 severe. Then you specify the substance. So for example, opioid use disorder severe. On this slide, you can see four of the 11 criteria. Taking the substance in larger amounts and for longer than intended, wanting to cut down or quit but not being able to do it, spending a lot of time obtaining the substance, craving or a strong desire to use the substance. Craving is really as I said a strong urge to use the substance such that you can't think of anything else. Spending a lot of time thinking about use and having difficulty resisting that use. More criteria, repeatedly unable to carry out major obligations at work, school, or home due to substance-use, continued use despite persistent or recurring social or interpersonal problems caused or made worse by substance use. Stopping or reducing important social, occupational, or recreational activities due to substance use, recurrent use of the substance in physically hazardous situations, consistent use of the substance despite acknowledgment of persistent or recurrent physical or psychological difficulties from using substances. The last two are tolerance and withdrawal. Tolerance is a need for more increased amounts to achieve intoxication or the desired effects or markedly diminished effect with continued use of the same amount and in older adults use of less but achieving the same effect is a measure of tolerance. Withdrawal is development of a characteristic syndrome due to cessation or reduction in heavy and prolonged use of a substance and then use of the substance to avoid that withdrawal. Now, these two criteria don't apply when there's a substance that's used appropriately under medical supervision. This largely applies to some prescription stimulants and an opioids, prescription opioids. One other thing to note about the criteria is that there's no criteria that addresses the amount of use. That's not a criteria for substance use disorder. So let's move to societal impact. First of all, a few comments on employment. Most people who use drugs are actually employed. As a result, actually impressively I take 10-20 percent of workplace stuff involves drug use. There are effects on productivity, absenteeism, and injuries at work. A few other observations on societal impact, two-thirds of people who experience partner violence report that the perpetrator was drinking. Forty percent of traffic fatalities involve alcohol and marijuana is the most common other drug that's detected in auto crash fatalities. Regarding state and federal prisons, 80 percent report substance use, 70 percent report weekly substance use, and about half have a substance use disorder. A third report using at the time of their offense and this is the crimes that are related to their behavior being affected by their drug use, crime to fund the drug purchase, and crime-related to manufacture and sale. These are estimates, some of which need to be updated, but they're the latest estimates from the National Institute on Drug Abuse showing the cost of various substances or attributable to these substances. Although the numbers may change as numbers are updated over the years, the relative costs remain the same across substances. What I mean by that is tobacco continues to be the most costly substance. Alcohol is next, followed by illicit drugs, as you can see on the slide. Now move to neurobiology. These key brain structures and their functions are affected by addiction. As you can see, these functions are critical to survival and successful living. They involve reward, motivation, learning, memory, and executive function, then inhibitory control. Now these graphs are from rat studies and they provide significant lessons for humans. The horizontal axis display time and the vertical axis dopamine output as a measure of reward experience in the brain. Food boosts dopamine by about 50 percent, sex doubles dopamine output. Now one explanation for the existence of the reward center and the rewarding value of food and sex is survival of the species. Drugs act at the same center and their rewarding effects often exceed those of other stimuli. For example, opioids can more than double dopamine, you can see on the bottom right with morphine and amphetamine can increase dopamine output by 10 fold so much more than normal stimuli in life. Repeated drug use changes the brain. Here in the top images of a person that doesn't use cocaine. You can see red where there's a concentration of dopamine D2 receptors and on the right, normal metabolism in the orbital frontal cortex, where behaviors are controlled based on likely consequences. The bottom two images are from a person who repeatedly used cocaine. There are lower levels of D2 receptors and less activity in the orbital frontal cortex. This slide displays brain activity as signal intensity on functional imaging in three parts of the brain involved in the reward pathway. What's most important here are the differences between people who do not and people who do use cocaine regularly. In this experiment, people watched an erotic film and they watched a film about cocaine. The white bars on the left indicate that people who do not use cocaine do not have a response to watching a cocaine film, but their reward pathway becomes active when watching an erotic film. For people who use cocaine regularly however, we see the opposite. The reward pathway lights up for the cocaine film just as you might expect. But a side effect of that regular cocaine use is that normal stimulus, the erotic film, no longer stimulates the reward pathway as it did in those not using cocaine. Now this experiment suggests that biology interacts with social circumstances. This is done in monkeys, and subordinate monkeys, graph on the top-right, use more cocaine than the dominant monkeys. Social or group housing increases dopamine receptor binding, but only for dominant monkeys, not the subordinate ones whose stress remains. So there's an interaction between stress and being subordinate dominant, essentially showing the effect of social circumstances and how they interact with drug use. Now one last rat experiments before we get back to people. This experiment is also informative. This is where laboratory rats generally live. It's called the Skinner box and they're isolated in there. Sometimes in some experiments they get foot shocks by those wires on the bottom. When living in that circumstance, and this is a foreshadowing of the experiment, I'll tell you about it in a second, rats given access to drugs essentially use them to death. It's when they're living in these circumstances. A psychologist, Bruce Alexander, did a study that's now famously called Rat Park. It's not a perfect study and there are a number of methodological limitations, but the study has some lessons for consideration in humans. This is a picture of Rat Park. It looked nicer than that Skinner box that I showed you, with drawings of trees and rats have the freedom to wander around, and exercise, and hang out with other rats socially. What was observed was that when rats were caged, in example of that Skinner box that I showed you, they use more drugs. When they were housed in a nicer place like Rat Park, they had less drug use, and that's what we see on the slide here on the left. Now, this is a study now moving to people. This was done in the 1970s around the Vietnam War. It was a study of men who were in Vietnam who developed addiction, generally, addiction to heroin and other opioids when they were in Vietnam. The thing to focus on here is that 60-70 percent of men, and this is really the graph that looks like curved lines on the right here, 60-70 percent of men who have opioid addiction while in Vietnam were not using opioids 8-10 months after their return. So they went to Vietnam under extremely stressful and awful circumstances, developed addiction there. When they came back, most of them were no longer using drugs just under a year later. Conversely, only about 10 percent of men who did not go to Vietnam but developed their addiction in the United States, and even had inpatient treatment, were not using opioids six months later. So very few of that sample stopped using opioids. So these results reinforced the idea that social circumstances have great influence on both the risk for and recovery from addiction. So those observations are a good setup for discussing theories to explain addiction. There are key components that drive compulsive use that can come under a neurobiological theory. Dopamine release as we talked about before leads to subjective feelings of pleasure and reward, reduction in feelings of stress, and repeated use of drugs override impulse inhibition. There are places in the brain where you can study this. Repeated use is often associated with discomfort when it stopped, which leads to more use. That's withdrawal and mood dysregulation, and then there's that dysregulation of executive function or control over behavior. There are some conceptual models to understand addiction. Although addiction isn't a simple choice, it may well be a disordered choice because those parts in the brain that I showed you that are affected earlier, that affect motivation and impulse control, et cetera. Those could relate to choices that aren't so good, and we might think of that as disordered choice related to drug use. There are problems with impulse and self-control. Some people look at addiction as a disorder of learning, that is learning how to use drugs or when to use drugs, or consequences on our learning from using drugs, and whether something becomes more automatic behavior or habits. Some have tried to synthesize these areas as follows; That maybe addiction is a chronic condition that affects our motivational systems, and it gives abnormally high priority to a particular activity, that is drug use or behavior for the behavioral addictions. The system is abnormal due to that drug use, and we can describe some of the features by these terms; sensitization, tolerance, withdrawal, their mood and social effects. Then drug use can also be affected by concomitant, either exposures or conditions like anxiety, depression, low self-esteem, and trouble with impulse control. These are all affected by the environment. On a normal system, the environment can affect one's use by stress, and you could imagine if there are particularly distressing circumstances or fame or social relationships, that can also contribute to drug use. So this is a way of trying to put some of these conceptual models together. Although I'm not sure how useful it is to really have arguments about whether addiction is a disease, it's very much seems to be one, and it has lots of characteristics of disease. So just a definition, the commonly used definition of disease is a disorder of structure or function that produces specific signs or symptoms. Addiction certainly has defined causes, genetic causes, environmental causes, and observable consequences that are behavioral and biological. So it pretty much looks like a disease, and I think it's useful to think about it in that way. There is something that may be different that's worth admitting I think about addiction that's a bit different, at least in degree from some other diseases. That is that there are high negative externalities. Keith Humphreys pointed this out in a editorial written in 2017. We do have to observe that sometimes people with addiction perpetrate violence, commit crimes often related to drugs, and exhibit some harmful behavior to others. Now not all people with addiction are committing crimes and doing these harmful behaviors, but we do associate it with some, and it is a fact that often drug use and purchase and sale is an illegal behavior, and that can have such consequences. We might think of it like a chronic infectious disease, where sometimes infections do affect others. So it doesn't take away the idea that addiction is a disease, but I think it's worth recognizing that, that disease can affect other people. Then what about addiction as a chronic disease? So one can compare it to chronic conditions like depression, type two diabetes, hypertension and asthma. These all have with addiction in common, similar treatment adherence and relapse rates. Some voluntary behavior is involved. They can be difficult to manage behaviorally. They may be caused in part by genetic factors. They all respond to ongoing treatment, and sometimes lifelong management of the condition is necessary. So these are features where addiction is similar to these other chronic conditions. It's interesting to think about that way because I think sometimes the way we think about this disorder colors are thinking of the effect of treatment. This is an example I've borrowed here from Tom McClellan, who published on this conceptual thinking that if we think about something like high blood pressure or hypertension and look at treatment on the left-hand side here, you have somebody with high blood pressure start the treatment, start the medication treatment, and during that treatment, their blood pressure is lower. Then when the treatment is stopped, then you see the blood pressure go back up. Usually the conclusion that we would draw from something like that is that the treatment was effective for this chronic condition. When we stopped the treatment, the effect of the treatment goes away naturally. So what we would do in that case is we would treat hypertension for a long time, perhaps forever to get that treatment efficacy. Often what happens with addiction treatment though is, as you might hear, "We sent the patients to treatment. They went to treatment, and then now they still look like they're just as sick as before." What we ignore there is the idea that that person is no longer getting the treatment, and so in a way, we shouldn't be surprised that if this is a chronic condition, that if they're no longer getting the treatment that their symptoms might reappear. So this is just a way of framing how we look at this and why it might be important to look at addiction as a chronic condition. That's a good setup for talking about accurate clinical terminology. We've talked about some of this already earlier in the presentation. But I just want to mention all of the terms that might be relevant here on this slide. So remember in the triangle at the beginning of the presentation, we talked about unhealthy use, which includes risky use but also includes harmful and then use that ends up being characterized as a disorder if people meet those criteria by having recurrent consequences and inability to quit. Binge use can be a term that at least should be defined better than just binge. Usually, what we mean for alcohol is that it's a heavy drinking episode that sometimes the term is used to mean multiple days of use, like with cocaine, cocaine binge, meaning several days in a row of use. So it's just worth defining beyond just the term binge. Disorder is what is characterized by DSM5 or also DSM-4 in prior editions. Dependence can be a confusing term. It was a diagnosis in DSM-4, and it still is a diagnosis in the International Classification of Diseases or ICD. But it can also mean simply physical dependence. Physical dependence which can happen on medications that even aren't addictive like high blood pressure medications. The body becomes physically dependent too, and that's not addiction. Addiction is a term that's used, let's say, by the American Society of Addiction Medicine, and some other groups worldwide. It doesn't have the same diagnostic criteria as the DSM, but it generally refers to the same disorder and is often used that way. The term misuse, again, should probably be defined if it's used. The best way to use this term or the place where this term is most useful is around misuse of a medication, like a prescription medication, meaning using more than prescribed or using without a prescription. But sometimes the term misuse is used to refer to the whole spectrum of unhealthy use. Sometimes it's used to refer to risky use. So if you're going to use that term, I'd suggest being clear about its definition. I think I'd not use it to talk about people with a disorder because misuse really doesn't represent a chronic disease or disorder very well. Return to use is a good descriptive term. It seems very clear. Some people use the word remission or recurrence in opposite ways, recurrence of going back to using. But you have to be clear about what you mean with people with a substance use disorder when you use the term relapse. Just does it mean going back to use, or does it mean going back to having the symptoms or criteria or the disorder? So although the term is used widely, it at least should have some definition if used. Some people don't like the term relapse because it really implies that it's a simple dichotomy that one is either relapsed or not. It's probably best described as a process. So being descriptive about whether somebody's returned to use or whether they've had a recurrence of their substance use disorder symptoms is probably the best way to go. Then around medication treatment, which is pretty central to the reason why we're giving this talk, I would avoid substitution because medication treatment of addiction doesn't directly substitute for any illicit substance. It's is not a good substitute in the sense that if you were to use a medication for addiction treatment, it doesn't produce the symptoms of substance use disorder. What it does is it reduces substance, illicit substance use and hopefully help somebody into recovery. I would not use the term assisted as in medication-assisted treatment because it's a misnomer. Medication doesn't assist something. Medication is in fact a treatment. Just like I wouldn't use the term substitution, I'd avoid the term replacement. So instead, it's just medication treatment for addiction, or treatment, or medication, or if you want to use the moniker MAG, you could say medication for addiction treatment. Then the last term to make a comment about, although it's not the focus of this presentation, is neonatal withdrawal. In the press, sometimes we see addicted babies described. Babies cannot be addictive because they can't try to stop use, and they can't meet the criteria for addiction. They can simply be physically dependent. Sometimes this is referred to as neonatal abstinence syndrome, which seems a fine term as well, although some now prefer neonatal withdrawal. Okay. Epidemiology. This slide displays the numbers of people age 12 or older who have a past year substance use disorder. These are recent data from just a few years ago. About eight percent of people in the general public aged 12 and older have a substance use disorder. For most, the substances is alcohol. Half as common as alcohol are all other drugs combined. Then the most common drug use disorder is cannabis use disorder. Now this fight is a little bit different because it's adults only starting at 18 and over. Drug use disorder, so all addictive drugs is about four percent. In the population, alcohol use disorder is at about 14 percent. This is a substantial increase over the past decade. Opioid use disorder is at about 0.8 percent of the population of adults. Non-medical prescription opioid use disorder is at 0.7 percent. Misuse of non-medical prescription opioids or of prescription opioids is about four percent, and heroin use disorder is about 0.3 percent of the general population. Here, this is just to show that the prevalence of drug use disorder varies by socio-economic status. You can look down the column on the right-hand side. More common in men, there is some racial and ethnic variability. Probably the biggest risk factor on this slide is youth with much higher prevalence in 18 to 29-year-olds. Never being married is associated with a higher prevalence of drug use disorder. A few more on this slide with relationships between education, income, not much of a difference between urban and rural, and some regional variation. This slide is more specifically focused on opioid use disorder, or OUD. So men younger than 45 have higher rates than women. Women 45 and older have higher rates than men. Race, ethnicity, there's more in whites than African-Americans. It looks like the opioid use disorder is increasing in Hispanic Americans. There are higher rates of OUD for lower-income. The data for employment are what I showed before, it's really for substance use disorder in general. There are higher rates in people who are unemployed and uninsured, but over half with substance use disorder are employed full time. Some more discussion of risk and protective factors. I mean, age really is a very strong risk factor with substance use disorder, in this case, drug use disorder. This label is from DSM-4. Abuse and dependence is much higher in the younger age groups, as you can see on the graph. The environment though, does play a significant role in addiction. Even though genetics account for at least half of addiction, risk and protective factors are from observational studies. So causality and mediation moderation always remain issues with these, but they do still help to identify populations in which use and disorders are higher. One example is that the age of onset of use is a powerful risk factor for addiction. In this case on the graph on the right. But the younger you are when you have your first drinking episode, it's much more likely that you'd develop a alcohol use disorder in adulthood. Nine out of 10 people with addiction started using substances before they turned 18, 97 percent started using before age 21. One in four Americans who began using any addictive substance before age 18 developed addiction. Now, there are some developmental risks for those focused on youth, and adolescents, and younger. So early in life, risk factors can be related to temperament of the child, attachment with parents or someone else in the home, parenting warmth, and stability. In middle school, issues that relate to risk for substance use and disorder include self-control, aggression, permissive parenting, low parental aspirations for the child, parental use attitudes, peers and peer use, and school failure. In adolescents, academic mastery is a protective factor. School engagement too, parental supervision is as well, and peers who don't use. In young adulthood, taking on the adult role, leaving home, and college, and peers at that stage of life can also have effects on substance use and disorder. There are biological risks. Genetic factors as I mentioned before, that comes from twin studies as well as studies of specific genes. These are just two examples of nicotine, Some people are fast metabolizers, and they end up smoking more cigarettes, and therefore end up progressing to addiction, have more severe withdrawal, and find it harder to quit. An example for alcohol that most people would be familiar with is the genetic risk or flushing as a response to drinking, which makes it less likely somebody's going to drink so much or develop an alcohol use disorder. There's also a genetically associated biological low response to alcohol, and when you have a lower response to alcohol, just like in the nicotine example, you may drink more, and that puts you at higher risk for alcohol use disorder. There are psychological risks as well. Depression, anxiety, and psychotic disorders, conduct disorder, and ADHD, stress, trauma, abuse, and PTSD are risk factors. Risk-taking or impulsive personality traits, and low self-esteem are associated with use and then positive expectancies, that is you expect to have a good experience when you take a substance, it's also associated with use and disorder. Then there are the environmental risks. When I mentioned the environmental component earlier, it's referring to these things. So access to addictive substances, how easy is it to go and buy a substance? This is now becoming an issue with legal marijuana, which will be much more easily accessible in communities. Is there a liquor cabinet at home that's easily accessible to an adolescent? Let's say, where are sales outlets, and prescription opioids became more available through more liberal prescribing, and accesses a feature. Access isn't the only cause of addiction, but it's certainly a contributor. Substance use in the family, and even involvement of a youth in the home with that use, even if they're not being encouraged to use, some things like having them involved in the purchase or preparation of alcohol, let's say, can increase risk. Parental anti use messages and expectations can affect risk. Peer influence, use and approval of use, community tolerance, and thinking of substance use as a rite of passage. Lax enforcement, glamorous advertising, media, or direct to consumer advertising for prescription drugs can contribute to greater likelihood of use, and high levels of parent-child conflict, poor communication, and weak family bonds. I'm going to briefly mention the association of substance use disorder with other conditions. Simply said, addiction is associated with other chronic and co-occurring conditions, other mental health conditions, and medical conditions. The next few slides show great detail on that, and you can see on this list, these are medical and psychiatric conditions that are associated with addiction from acid related disorders even to arthritis and asthma, liver disease is of course, there's symptoms like headache, hypertension, or high blood pressure, and the list goes down to some cancers, and then injuries, overdoses, depression, anxiety disorder, or major psychosis, and of course liver cirrhosis. These are odds ratios of lifetime DSM-4 drug use disorder diagnosis and other psychiatric disorders, and you can just scan across the bolded numbers, and these are associations between the disorder that's on the left. So alcohol use disorder, nicotine, any mood disorder, anxiety disorder, and some personality disorders with drug use disorder which is across the top, and really, the first column is probably where your attention should be focused so that you can see that alcohol use disorders is associated with drug use disorder as is nicotine dependence, mood disorders, anxiety disorders, and personality disorders in general. In particular, probably driven by antisocial personality disorder at the bottom of the list. Alcohol and drug use are associated. Sorry, drug use disorders are associated with each other, and both are associated with mood disorders, anxiety disorders, personality disorders, both with an array of medical conditions and symptoms, and this basically summarizes the last slides that I just showed you. Now, there are a lot of ways that drugs affect health even beyond developing addiction, and so people who suffer from addiction may have these health consequences in addition to the criteria that we see in substance use, disorder diagnosis. So there are direct effects that are really due to just taking the substance, like intoxication or overdose and withdrawal. There are direct effects that are really not due to taking more but just due to taking the substance itself like lung cancer, cirrhosis, talc lung, medication interactions. Some of these are from contaminants. There are indirect effects that are really due to the method of administration, not the drug itself. Like injection drug use can reach infection of the heart endocarditis using a needle near in the neck can lead to a collapsed lung or pneumothorax and of course, transmission of infectious diseases like HIV. Then there's indirect health consequences or harmful effects of drugs due to associated behavior like sexually transmitted diseases, assault and injury, motor vehicle crashes that might injure others in the vehicle or on the street and again HIV infection. Injection can lead to damaged veins or here said bad veins. As I said before endocarditis and other infectious complications which are really listed in the next three bullets. Hepatitis, HIV, and other sexually transmitted diseases, and then skin, bone, nervous system, infections as well as malaria, and even tetanus. Then there are other non-infectious complications like pulmonary hypertension from injection, talc granulomatosis, pulmonary emboli, and as I mentioned before, collapsed lung and then kidney failure and amyloidosis have been associated with injection drug use. Hepatitis C and HIV deserves special mention because a third of young people who inject drugs have HCV, Hepatitis C infection and among older people with the history of injection drug use at 70-90 percent, about 11 percent of people who inject drugs have HIV infection and nine percent of cases of HIV in 2016 were attributable to injection drug use. So let's move to chronic disease treatment. This chronic disease we're talking about is substance use disorder. Addiction can be treated and brain function. I showed you some effects on the brain earlier in the talk. Some of those functions can recover and this slide really displays partial recovery of the brain as it's really displayed as dopamine transporter in people who use methamphetamine and what you see is a control on the left and then there's someone who was using methamphetamine regularly who was drug-free for just a month and you can still see that it doesn't look like the one on the left. It's green without the red dots in the middle of intense dopamine transport. On the right-hand side far right, it's 14 months of abstinence, so it may take some time. I don't think we know exactly for each drug and how long it takes, but this is a demonstration that the brain effects of recurrent drug use can recover. Then for people with more severe addiction, the course of substance use disorder and achievement of that stable recovery can take a long time. This isn't about any individual person, but for many, it may take years of suffering symptoms of substance-use disorder before they seek help. Maybe in the health care system we could do something about that if we try to detect it or if we encourage people to seek help earlier, but it can take years for that. Then once people begin to get treatment, the first treatment episode, especially if it's delivered only episodically, may not solve the issue and it may take either multiple treatment episodes or better, some sort of continued care over time. But it may take years to achieve some remission or recovery. Remission on this slide is defined as one year of abstinence and it takes a while, another several years before the risk of returning to substance use and substance use disorder symptoms here labeled as relapsed risk drops below 15 percent, but about half of people with addiction will achieve full sustained remission overtime. This slide really talks about how 10 percent of people with a documented substance-use disorder in the medical record get any treatment at all. About 10 percent of substance use disorder people in the general population gets any treatments. Half of those who withdraw in a detoxification setting, go on to any treatment beyond those few days of detoxification, and half of those who do go on complete that initial treatments, and that's not to say anything about ongoing continuing care for this chronic condition. So circumstances are not good out there and we can really do better. One possible way to help is by integrating care rather than having separate disjointed care across the health system or not even in the health system for some specialty addiction treatment programs that are out there and not so well integrated into the care system where patients with drug use disorder may be. There's some evidence for integrated care. These are older studies. Mark Willenbring had studied treating medically ill than in the VA, in Veterans Affairs hospitals, in a specialty care clinic for those who had alcohol related medical illnesses, and even found reduced mortality with that kind of integrated treatment. At Kaiser in California, Connie Weisner, the second citation here, found greater absence for those with substance use disorder related medical conditions, if they got medical care integrated into their addictions care. But then the question is really not so much integrating medical care into specialty addictions, treatment care as most people aren't in a specialty addiction treatment settings. So the question became, can we integrate addictions care into medical and primary care settings? We took a look at that in a trial that I'll just refer to briefly here where we brought chronic care management into primary care setting for people with addiction. In this randomized trial, we randomly assigned people to that versus usual care, which was simply asking them to go and get primary care without specifically arranging addiction treatment. In that study, we actually did not find any benefit of this chronic care management. All people in the study, well, I shouldn't say all, but overall there was improvement in both groups. So here you can see the outcomes that we looked at on the left-hand side; abstinence, addiction severity, both alcohol and drugs, mental and physical health-related quality of life, and health care utilization, hospital and emergency department. If you look at the baseline numbers compared to the 12 months numbers, you can see, for example, that while none were abstinent at baseline, about 30-40 percent were abstinent at 12 months follow up. Similarly, you see improvement in addiction severity, and the other variables that I just listed, but none of it was attributable to climate care management. This may have been because these were folks who weren't necessarily at a stage when they were ready for addiction treatment. Other studies have begun to look at this question, I'll mention a few. Mentioning some null studies here, because later I'm going to contrast this with ones that I think have had more effect, and they're informing our ability to integrate care. So this is just another example of a study for alcohol use disorder. Actually, a list for people with high-risk unhealthy use or alcohol use disorder. It was nurse care management in a primary care setting in the context of a large health system. They did find in this study that nurse care management increase the chance that people with alcohol use disorder would receive medications, but they didn't find any differences in the use of specialty treatment or mutual help, or in heavy drinking days, or good drinking outcome, which was defined as tricking lower risk amounts or not at all, and not having consequences. But these studies, the ones listed on this slide, do show some effects. There are different designs from the previous two examples that I showed you, and that's why I think this is informative. So the first one done by Stephanie O'Malley, sometime ago now, compared specialty cognitive behavioral treatment to primary care management with Naltrexone and found that, if you treated people with Naltrexone in primary care, this is for alcohol use disorder, that they had similar outcomes, as if you referred them to a specialty treatment setting. They got their care in that specialty treatment setting. David Oslin, in the Veterans Affairs System, more recently published a study looking at medical management with Naltrexone in primary care, versus referrals to specialty care. It turned out that those in primary care actually did better. They were more likely to engage with treatment and had better drinking outcomes, less heavy drinking in the primary care group. David Oslin and the New England Journal, now over a decade ago, it compared three different intensities of counseling for primary care office-based opioid treatment, that's buprenorphine, and found no differences between these three levels of intensity of counseling, suggesting that in primary care when treating with buprenorphine, it was feasible and just as efficacious to give the relatively minimal type of counseling that can be delivered in a primary care setting by a nurse practitioner or primary care physician. The last one on the list here is a randomized trial of HIV clinic versus referral, and that means specialty addiction treatment referral base treatment. There is a more opioid agonist treatment and less drug use, and more primary care use when the care was delivered in an integrated fashion in the HIV clinic. The most recent one of these studies was just published last year, and it's collaborative care for both opioid and alcohol use disorders. Some people had both. Some had one or the other. People in this study got collaborative care by their clinicians that were trained to do so and care coordinators. The long and the short of it is that any opioid use disorder, alcohol use disorder treatment that was more common in the group that got exposed to this collaborative care integrated approach in a federally qualified community health center, 39 percent versus 17 percent. They were using buprenorphine and injectable naltrexone, and a brief evidence-based therapy. Not everybody got all of those, but they could get some or all of those. Abstinence from opioids or alcohol at six months was significantly greater. What about initiating care? This is a study that really a landmark study that I think had tremendous impact and really should. There's a study that compared buprenorphine prescribed from the emergency department, versus referral, versus a brief intervention. The referral was to specialty care. Engagement in addiction treatment was much higher if you simply prescribed the medication right out of the emergency department when the condition was recognized. Then if what was what is essentially usual care across most of the countries still today, which is to give somebody a referral to an addiction specialty treatment program, or to give them some brief advice, which might include that referral as well. The next line on the right-hand side at the bottom is just the number of days of opioid use, five days decreased to one in the buprenorphine group; in the referral group, it decreased to two; in the brief intervention group, it decreased to two. This is common in many studies like this where overall the population gets better. But what we're looking at is which group did better overall, and the greater decrease, and the greater increase in engagement in addiction treatment were both in the buprenorphine group prescribed from the emergency departments. So to conclude about substance use disorders in general, substance use various individuals can have low-risk use, risky or hazardous use, or harmful use that can meet DSM-5 criteria for a disorder. So there's that spectrum of unhealthy use. Substances work on many areas of the brain, pretty important areas of the brain, including the reward and pain pathways and dopamine systems. There are many theories to explain addiction. Most likely, I think the most successful theories are ones that combine etiologies across an abnormal motivational system, neurobiology, and environmental factors. Accurate language is important to use for a variety of reasons. Substance use disorders are associated with a range of mental health disorders and medical conditions. More evidence is needed on the benefits of chronic care management for substance use disorders, but it looks like integrated care is likely advantageous. The distinction between studies in which it was not effective and studies in which it was, was that the studies in which there was an effect of integrated care, they focused on specific substance use disorders like opioid use disorder or alcohol use disorder, and they did so in patients who were interested in starting that care. These are references for your review that support much of what I said during this talk. Other slide of references, one last slide of references. I lied. There's one more, and there's even one more after this. With that, I just want to make a few comments, make you aware of to resources that are offered through the PCSS that you might be interested in. The first is on this slide, the PCSS mentor program, which is designed to offer mentoring assistance to those who would like one-on-one interactions with colleagues, to address clinical questions as they come up. The mentor program is designed to offer general information to clinicians about evidence-based clinical practices prescribing medications for opioid addiction. You have the option of requesting a mentor from the mentor directory, or you can ask to be paired with one. You can find out more information by taking a look at that website. The link is on the slide. The PCSS mentors are a national network of providers with expertise in addictions and evidence-based treatments, including medication treatment for addiction. Second, the PCSS offers a discussion forum that's comprised of PCSS mentors and other experts in the field who can help provide a quick response to clinical cases and questions. There's also a mentor on call each month who's available to address any submitted questions through the forum. You can get a login and account by clicking on the image on the slide to get to that registration page. Lastly, this slide notes the consortium of organizations that are part of the PCSS project, as well as contact information, the website, the Twitter handle, and Facebook link to find out more about what the PCSS offers. Thank you very much.