Welcome to the PCSS training module on adolescent substance use. My name is Sharon Levy, and I'm the director of the Adolescent Substance Use and Addiction Program at Boston Children's Hospital and an associate professor of pediatrics at Harvard Medical School. I have no financial relationships to disclose. The overarching goal of PCSS-MAT is to make available the most effective medication-assisted treatment to serve patients in a variety of settings, including primary care, psychiatric care and pain management settings. At the conclusion of this activity, participants should be able to explain how adolescent brain development poses unique risks associated with substance use. Identify tools for screening adolescents for substance use in clinical settings and appropriate steps to take based on response. Describe evidence-based treatment options for adolescents with moderate to high risk substance use. This is a graph from a publication of 1978. It's showing us brain weight on the y-axis versus age on the x-axis. You can see that we've highlighted age 10 to 12. At this age, by growth measures, the brain has reached full size. But this is a slide of pictures taken from Google Images using the command adolescents. By looking at these young people who are roughly 14 to 18 years old, we get the sense that even though their brains might be full size compared to adults, they're not exactly the same as adults. And this is an important principle in Developmental Pediatrics. This is a slide that shows sections of brain under a microscope at different ages. On the left, we have a slide that was taken at birth and we can see that there are few neurons and few connections between them. The first couple of years of life is devoted to brain growth. The middle picture is the brain of a six-year-old and here we can see that there are many more neurons and many, many more connections between them. On the right, we see the brain of a 14 year old and we see that there are actually fewer neurons and fewer connections at this age. So what's really going on here? The slide in the middle of a six-year-old, we're seeing a brain that's perfectly configured for learning. We know that younger children are able to pick up new knowledge and skills much more quickly than adults. That's why people will say if you want to learn a language should learn it when you're young and indeed learning a language generally before puberty allows people to speak as native speakers too whereas after that, people will usually retain an accent from their native tongue. On the contrary, the 14 year old slide is a brain that's more configured for proficiency. So what happens between 6 and 14 years is that there are pruning of connections that are no longer used and growth of connections, of cells that are used, they become bigger and ultimately they become insulated with myelin to make signal transduction much faster. The learning a language might be best at age six, but giving a very proficient speech would be much better at adolescents or beyond. So brain development has an orderly progression to it, but it doesn't happen in every part of the brain at exactly the same time. This slide shows us brain development with the blue parts on these pictures being relatively more developed and the green part still being immature brain. We can see that there's a pattern that roughly goes from the back of the brain to the front and also of note, even at age 20, you can see that there's still some significant areas of still immature or still maturing brain. Now, it turns out that brain development, skill acquisition and child's behavior are actually very well coordinated and we can actually see in their behavior the parts of the brain that are developing. For example, in the first couple of years of life, one of the most active areas of brain development is the cerebellum. This is the part of the brain that's responsible for gross motor coordination. And of course during the first couple of years of life, children are very focused on learning how to walk. In fact we even call this period toddlerhood. In the preschool year, an area of the brain that's developing rapidly is the amygdala which is in part responsible for emotional control. This is just the time in life where we see the terrible twos both come and go. Children in the preschool years will develop tantrums, which are emotional outbursts that seem to have no real trigger that rage for a little while and then self resolve. This is a function of brain development. And typically, these tantrums will go away by the school age years. In fact, in Developmental Pediatrics, we become concerned that there's a sign of abnormal brain development if tantrums persist beyond this age period. In the school age years, one part of the brain that's developing very quickly is called the nucleus accumbens which houses what's known as the brain's pleasure and reward center. It's during this time in life that children develop motivation and they begin to distinguish between unimportant rewards and important rewards. Finally, the last part of the brain to develop is called the prefrontal cortex. And this is the seat of executive functioning, which is so critical for good decision making. That's not highly reliable in adolescence and even young adults. So, We can define the period of adolescence as the period between the full development of the nucleus accumbens while the prefrontal cortex is still developing and this drives behavior. So adolescents are neurodevelopmentally wired to seek highly stimulating activities while they're only partially deterred by risk and harm. This is a problem because one of the most effective ways to stimulate nucleus accumbens or the brain's pleasure and reward center is by drug use. So this line shows that regardless of which substance you're using, all of them have the same final common pathway, which is direct or indirect stimulation of the nucleus accumbens. This makes drug use one of the most effective ways to achieve that highly rewarding stimulation that adolescents seek. As a result, adolescents are developmentally primed to use substances and if we make them available, this will be an easy way for adolescents to achieve highly stimulating experiences. In fact, most substance use begins in adolescence. This graph shows us the percentage of past year initiates, people who've used substances for the very first time in their lives, by each category. You can see that there's very little uptake of drugs in the before age 14. The first blip in drug use happens around age 14 to 15 when children typically enter high school. The peak ages of initiation are between 16 and 20, and you can see by age 21, rates of initiation have fallen off rather substantially and almost to zero after age 26. Now, I want to speak specifically about alcohol. So for those of you who remember your biochemistry, this is a drawing of the ethyl alcohol molecule. It's a small molecule that's a homologous to water, which means that it has good capacity to travel throughout the body. It can bind intracellular as well as extracellular receptors. And if we look at the parts of the brain affected by alcohol, it's essentially all of them. Well, most of the effects, the prominent effects of alcohol are actually receptor-mediated. And alcohol has many many smaller effects throughout the brain and the central nervous system. The National Institute of Alcoholism and Alcohol Abuse estimates that 90% of all alcohol consumed by underage drinkers occurs in the context of binge. Adolescent who are seeking neurologic pleasure and firing at the nucleus accumbens typically will drink much much larger volume than adult drinkers. So the most common pattern is heavy episodic drinking for this age group. And adolescents also respond differently to intoxication. This experiment that I will take you through is involved putting rats into a water maze and allowing them to swim to a platform where they can get out of the water. What the investigators found is that if they gave an adult rats alcohol, their swimming speed decreased and their time to find the platform increased. Both of these were expected as the rest became sleepy and slow down by the alcohol. Not only did they move slower, but it took them a longer time to figure out where they were going. In contrast, Adolescent aged rats, when impaired by alcohol, swam at the same speed of before they were given alcohol. So they were moving quickly and briskly through the water, but they were still having trouble finding the platform. Same is true with adults, adults with higher blood alcohol concentrations tend to become very sleepy and less active, where adolescents maintain or even increase their activity. This makes them more likely to do dangerous things like drive a car or go swimming, even when they're substantially impaired. And this graph shows us that for every blood alcohol concentration, younger drivers are much more likely to be involved in a car crash than older drivers. Chronic, alcohol exposure also has significant impacts on brain development. So in this study by Susan Tapert, investigators looked at 16-year-olds and compared heavy drinkers on the right to non-drinkers under a scan where they could see the parts of their brain that were recruited to complete a simple task. What we see is that both non-drinkers and heavy drinkers were both successful in completing the task. But under scanning, we can see that the non-drinkers used a lot less brain while the heavy drinkers had to recruit more areas of brain to accomplish the same task. Now, this is at age 16, relatively early in the course of heavy drinking. This slide is a few years later, by this point, heavy drinkers were no longer as successful in recruiting brain tissue to complete tasks. And compared to non-drinkers, by this point, performance has declined. want to take a moment to talk about college alcohol use which is heavily reported on in the news. This is a graph that shows the prevalence of heavy drinking amongst high school students. In black, we have those who are intending to go to college and invite those who are not intending to go to college. We follow that graph out and look at these same groups several years later. What we see is those who actually gone to college has now higher rates of heavy drinking than peers. This is an environmental factor causing these, causing these two lines to cross. And this is a graph that showing the alcohol density in a 2-mile radius of the university campus shown in the circle. As you can see, there is a very high concentration of these outlets around the college campus, even though the majority of undergraduate students would not be old enough to legally purchase alcohol. Not only do many college campuses have very high density of alcohol outlets around them, but 75% of campus bars also offer special on the weekends. This is a marketing strategy that offers the availability of large volumes of alcohol, low sales price, and frequent promotions. And these tactics are indeed associated with higher binge drinking rates positively associated with consumption. This slide shows us that students who are exposed to this kind of alcohol marketing have higher binge-drinking rates, higher past 30-day drinking rates, and higher annual drinking rates compared to students who are not exposed. This slide is from an advertisement from a label of a beer that was pitching itself as the perfect beer from removing "no" from your vocabulary for the night. This campaign was short-lived, it was quickly taken off the market due to complaints from all kinds of groups, but it makes a very serious point. This is a serious issue because up to 74% of sexual assaults on campus are committed by men who have been drinking. I'd like now to move on to discuss marijuana. This slide shows on the left a molecule called anandamide, which is a natural protein, a natural compound made by the human body. On the right is a picture of Delta-9-tetrahydrocannabinol, which is the active ingredient in marijuana. The two are similar enough so that THC can actually mimic anandamide and bind to the human receptors that were meant to bind anandamide. We call these the cannabinoid receptors, and they can be found throughout the central nervous system as well as other places in the body. This slide shows us areas of the brain that are particularly dense in cannabinoid receptors. We can see that the cerebellum responsible for gross motor coordination has a high density of cannabinoid receptors as do the prefrontal cortex, the hippocampus and also the limbic system including the nucleus accumbens. This slide shows off the effect of binding at the cannabinoid receptor regardless of whether the receptor is bound by an endocannabinoid anandamide or exogenous cannabinoid such as THC. The impact of the same, the binding causes a decrease in activity of the cell by inhibiting release of neurotransmitters from the presynaptic cell into the. Basically, cannabinoid binding tell cells to be quiet and stop firing. But there is an important difference between THC and anandamide, and that is the endoreceptor. So THC has a relative potency of almost twice that of anandamide. What that means is that, it binds more voraciously to the receptor and stays on the receptor longer than anandamide, the human compound would. We know that the cannabinoid receptor is very important for pruning the brain and when the brain is exposed to exogenous cannabinoid like THC, it can interfere with that process. Pruning should be happening with a scalpel with high precision. Do not want it to occur with a sledgehammer. It's possible that some of the very well described effects of marijuana use during adolescence are due in part to impaired pruning. So for example, we know that the hippocampus is very densely populated with cannabinoid receptors. And we know that the hippocampus is also responsible for learning and memory. And that individual who use marijuana heavily during their adolescence tend to have smaller hippocampal volumes as adults. This is a study done in New Zealand, a number of years ago that recruited a cohort of more than 1,000 kids at age 13. And follow them prospectively every couple of years of their lives with interviews that included questions about whether and how much marijuana they were using. And also, questions about how they were functioning as well as formal IQ tests. What the researchers found is compared to individuals who never used marijuana, those who were using heavily at three or more of the time points had significant false in their IQ. Marijuana impacts on brain pruning may also play a role in the association. We see between early marijuana use and risk of psychotic disorders. This is a slide that shows that's highlighting the corpus callosum. On the left, we see a healthy participant with no history of marijuana use compared to on the right, participant with daily marijuana used to have a much thinner corpus callosum. Corpus callosum thinning is also known to be associated with development of psychotic disorder. So in this slide, we can see reductions in the thickness of the corpus callosum from prepsychotic to first episode to establish illness space. Epidemiologic studies have found an increased risk of psychotic outcomes among individuals who use marijuana compared to those who did not use cannabis. This meta-analysis which involves six studies, 5 of which had significant increases in rates of psychotic disorders. The meta-analysis combined more than two folds increase in psychotic disorders amongst the marijuana smokers. The evidence speaking as a whole has been enough for the British medical journal to conclude that cannabis use is a risk factor for the development of incident psychotic symptoms. In other words, marijuana use itself is not just an association with the development of psychotic disorders, but an actual risk factor and that continued cannabis use might increase the risk for psychotic disorders by impacting the persistence of symptoms. The chronic risks of marijuana, perhaps the most prominent that is similar to the risks of tobacco smoking which are well-known. So, tobacco is known to be one of the leading causes of excess mortality in the population because of its close association and causal impact on heart disease, cancer, stroke, emphysema and chronic bronchitis. The long-term impacts of cannabis are actually much more subtle and can be more difficult to attack. They involve things like cognitive decline, mental health disorder and suicidality. All of which are challenging to detect and to, And to follow because they don't always present for medical care. Almost all of the problems associated with tobacco use will ultimately result in patients presenting to medical care where they can be carefully and objectively counted. But problems related to marijuana use are much more challenging to identify. This is a graph that shows drug-related school suspensions in Colorado between 2002 and 2014. You can see that we've marked 2009. This was the year that some changes in the legal status Allowed Colorado to open up dispensaries and vastly increase the marketing of marijuana. You can see that that right around that time drug-related school suspensions increased enormously. You can also see there was a small increase in drug related explosions, but because this is a much more drastic intervention, it's much less frequently used. This is an article called Building a Learning Marijuana Surveillance System that discusses the challenges of modern effects of marijuana use. and so just thoughts about big data and other strategies to create a more comprehensive surveillance system that goes beyond the typical surveys that we currently use to track marijuana use. A report from the SAMHSA issued in September of 2016 showed that while national reports your left underage drinking and smoking overall substance use and mental illness levels remain constant. One of the reasons for this is that while we have fewer adolescents initiating alcohol and tobacco use and a stable number of individuals initiating marijuana use. There has been a constant revolving door of substances and the substances that are available to adolescents high school students these days are typically more potent than what was available generations ago. The American Academy of Pediatrics recommends that health professionals conduct substance abuse screening brief intervention and referral to treatment. And specifically that health professionals deliver the nonuse message should be reinforced by pediatricians through clear and consistent information presented to patients parents and other family members. In other words the message that the AAP promotes is that nonuse is best for health. This slide shows a screening tool that is called the S2BI that has been developed for identifying substance use and risk of the substance use disorder among adolescent patient. The tool asks a question about past your tobacco alcohol and marijuana use and adolescents are given category response option that include never once or twice monthly or weekly. These response items map very well on to the pyramid on the right and which we see different levels of substance use and different with each with its own recommended brief intervention. From new substance use to substance use disorder mild to moderate used and severe abuse on the top. This is an algorithm that suggests the recommended intervention for every level of substance use. So for example for no use, the recommended intervention is a prevention message such as you've made a really good decision and deciding not to drink. For use without a disorder the American Academy of Pediatrics recommends a cessation message such as as your doctor recommend you don't smoke marijuana at all. For mild to moderate substance use disorder the American Academy of Pediatrics recommends an intervention or counseling to stop or reduce use. For example here the pediatrician is having a conversation with the adolescent and it sounds like you enjoy drinking and it is getting you into trouble. How can you protect yourself better? This is meant to be the start of a conversation regarding behavior change. Finally, for severe substance use disorder the recommendation is referral to ongoing counseling. So here is a pediatrician and thing it sounds like your marijuana use helps you manage stress and you're tired of getting into trouble with your parents at school. A counselor can help you both with your stress and with your marijuana use. For individuals in the severe substance use category, this is a decision tree that helps clinicians determine what level of intervention is recommended. This figure is available through the Massachusetts Department of Public Health toolkit. I'd like to take a moment to review evidence-based treatment for adolescent substance use disorders. The most common form of substance use interventions are brief interventions, which can be done in primary care subspecialty care or other health setting. A number of brief intervention models have been looked at in the literature and this slide summarizes the findings. Perhaps the most common brief intervention if something called the brief negotiated interview, which is heavily based on motivational interviewing. This has been looked at for both alcohol and marijuana and the results have been promising although not definitive. Second model for brief intervention is the 5 A's which has been well described for tobacco. A number of studies have been done in school-based setting which again have shown promising interventions, although not definitive. Project CHAT has been looked at to identify and reduce alcohol and marijuana use among high-risk teens. Early studies found that CHAT which is based on motivational interviewing and cognitive behavioral therapy has shown decreased perception of pure alcohol and marijuana use. Finally, on this line U-Connect is a electronic or in-person intervention that has been looked at for both alcohol and marijuana. And early studies found significant changes in attitudes towards alcohol and marijuana regardless of whether the intervention was administered on in person or online. When it comes to treating adolescents with Opioid use disorders, medications are the number one recommendation. And the American Academy of Pediatrics and other organizations recommend that medications be offered to all adolescents who have been identified as having an Opioid use disorder. These are the three medications that are currently available, although the level of evidence for methadone is an effective treatment for Opioid use disorder is very high. Although it can only be prescribed in a license Methadone Program. Most of which cannot accept patients under age 18. Buprenorphine indicated for patients greater than or equal to 16 years of age. Can be prescribed in medical office if the prescriber had undergone additional hours of training and apply for an FDA waiver. The level of evidence is high-end similar to methadone, although as with methadone the effect on the developing brain are not entirely known. Finally extended-release naltrexone now has moderate-high level of evidence associated with it as atreatment for opioid use disorder. This can be used in primary care settings and no special waivering requirements are needed for use of naltrexone. Regarding medications for alcohol use disorder, both naltrexone and acamprostate have been approved by the FDA. Neither one of them has a clear indication for use in adolescence, although they can be used off-label. Evidence for naltrexone is moderate for decreasing alcohol consumption and preventing heavy drinking. It's considered a good option for adolescents with concurrent opioid use disorder and alcohol use disorder as well as for adolescents strong family history of alcohol use disorder. Acamprosate also has a moderate level of evidence for decreasing alcohol consumption though it is rarely used in adolescent due to limited evidence. One medication, n-acetylcysteine has been tried for treating cannabis use disorder. One study, a small study done in adolescence showed improvements in treatment the treatment group as compared to control. This binding was not substantiated in adult populations. N-acetylcysteine is not FDA approved for the treatment of cannabis use disorder, but it is available as an over-the-counter supplement. This slide shows the different counseling modalities that have been used for adolescent substance use disorder and for which there is a substantial evidence base. The level of evidence for motivation, the level of evidence for all four of these, motivational interviewing, cognitive behavioral therapy, dialectical behavioral therapy and contingency management is moderate and in general was found to be most important. It's not so much the therapy that is chosen but how well patients can be engaged in the therapy. Group therapy tends to be a developmental preference for adolescence. It can be very cost effective and allow for peers to support one another. But there are some precautions, availability is limited in many areas, group therapy has not been well studied. And there is at least a theoretical risk of contagion if some of the group members are using and not committed to behavior change while others are. Perhaps the greatest level of evidence exists for family therapy. This is a page that shows five different types of family therapy. Which range in level of evidence from moderate high on the bottom are a number of references which gives more detail on each of these therapeutic modalities. This slide shows us levels of outpatient care that are available specifically for substance use disorder patients. There is a substantial variance, everything from outpatient therapy. Which has the benefit of treating kids while they're in communities and attending schools and doing their other activities through intensive outpatient programs. Which typically meet three to four days a week for three to four days and are appropriate for patients who need more than standard outpatient treatment for a period of time. But without pulling them out of school work or other activities. Partial hospital programs are slightly more intense, they typically meet every day for six to eight a day for one to six weeks. They are appropriate for patients who need more intensive care but are still able to sleep at home. And maybe an opportunity for patients to practice new skills in the evenings after coming home from their program. Recovery high schools are are also available. There are therapeutic setting where kids can get their schooling in conjunction often with a variety of different therapeutic modalities, including group therapy and individual therapy. And in this setting academics and treatment resources are combined under one roof. Patients who need a higher level of care that can be supported in outpatient care, there are several levels of inpatient treatment as well. Acute residential treatment typically lasts these two weeks. It's usually best suited for individuals with co-occurring mental health and substance use disorders. And is used primarily for stabilization at time of mental health crisis or during a need for medical monitoring of withdrawal. Residential programs typically lasts 30 to 90 days and are best for patients who are unable to maintain abstinence within their community. Particularly kids who are unstable at home and need that level of support. Finally, therapeutic boarding schools are long-term policeman's that offer typically mental health and behavioral supports and are for kids who can no longer be managed at home. They are settings where adolescents can get constant supervision, small specialized classes in both social and emotional support. So, in summary, adolescents are vulnerable to both substance use and addiction. The American Academy of Pediatrics recommends abstinence or non-use as best health advice for adolescents. The AAP also recommends including screening and counseling, brief intervention as part of routine medical care for adolescence. Finally, effective evidence-based treatments for adolescent substance use disorders do exist and can be delivered at various levels of care. On the next few slides are the references that support the content that was viewed in this webinar. The PCSS Mentor program is designed to offer general information to clinicians about evidence-based clinical practices of prescribing medications for opioid addiction. PCSS mentors are a national network of providers with expertise in addiction, pain, evidence-based treatment, including medication assisted treatment. There's a 3-tiered approach allows every relationship to be unique and cater to the specific needs of the mentee and there is never a cost for participating in this program. For more information, please visit the website at the bottom of this page. PCSS also has a discussion forum where you can post clinical questions and ask colleagues. It's a simple and direct way to receive an answer related to medication assisted treatment. And finally, this slide acknowledges the PCSS-MAT partnership with the American Academy of Addiction Psychiatry and many partners which are listed on this slide. For contact information, please see the URL at the bottom of this page.