<v ->Hello, I'm Dr. Sharon Levy</v> and this talk is on adolescent substance use. I have nothing to disclose. The overarching goal of PCSS MAT is to make available the most effective medication assisted treatments 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 for substance use disorder. This is an older slide that shows brain weight by age. At age 10 to 12 is highlighted, because that is the point at which the brain reaches its adult weight. For for most of human history, until about 150 years ago, people were considered adult when they reached age 13, or thereabouts. We now know that brain development continues until the mid twenties. The pictures on this slide are brain slices taken from individuals at different ages. At birth, there are few cells and few connections between them, then the brain blossoms through tremendous growth into a dense tangle of tissue. The final step involves pruning away unused connections while the ones that remain grow bigger and get wrapped in myelin, which is a fatty, insulating tissue. These last changes increase the speed of electrical signal conduction. So, while young children are great at learning new things like speaking a language or playing an instrument, it's because their brains are perfectly configured for learning. Adults, on the other hand, are more proficient at these tasks, because their brains support faster signaling. These stages always happen in the same order, but they happen in different parts of the brain at different ages. This slide shows immature brain in red and green, and fully myelinated mature brain in blue. The order of maturation is, generally speaking, from the back of the brain to the front. Note that even at age 20, there's still plenty of immature brain. This process is thought to be completed in most people in the mid twenties. Brain maturation correlates with the behaviors of children. We expect to see at different developmental stages. For example, in the first year or two of life, the cerebellum, which controls gross motor movements is developing rapidly. Anyone who's been around the toddler knows that they are completely invested in getting up and walking, creating the practice necessary for the feedback loop that will result in brain development. In the preschool years, the amygdala, which is involved in emotional regulation, is an area area of rapid development. During this stage of life, sometimes referred to as the terrible twos, young children have temper tantrums that seem to be unprovoked, and also, seem to resolve without intervention. These should be coming to an end by the end of this developmental period right as children are entering kindergarten. During the school age years, the nucleus accumbens is undergoing rapid development. This is the time in life when children learn to differentiate between rewards and develop goal directed behavior. The last part of the brain to develop is the prefrontal cortex, which is the seed of executive functions or the things that help us to make good decisions like self-monitoring, error correction, and impulse control. Adolescents can, of course, make good decisions, but during this phase, while their brain is still developing, they don't reliably do so. In this model, we can conceive of adolescents as the period of time after the nucleus accumbens or the gas pedal of behavior is fully developed, but while the prefrontal cortex or the behavioral breaks are still maturing. In other words, adolescents' brains respond differently to rewards compared to both children and adults, as this slide demonstrates. In this study, subjects' brains were scanned as they were receiving either a small or large reward. Young children shown here in blue had significant increases in firing, whether they received a small reward on the left or a large one on the right. Adults shown in green made a response that was proportional to the reward size, as you might predict. Adolescents shown here in black, actually, deactivated their brains below baseline in response to a small reward and made a tremendously large response to a large reward. Adolescents are developmentally wired to seek large neurological rewards. All psychoactive substances feel good when people use them, because they directly or indirectly result in increased firing in the pleasure and reward center in the brain. In a sense, these substances are hijacking the normal reward pathway, and while this is neither natural nor healthy, it does fulfill a developmental drive for adolescents. This is why adolescents are developmentally vulnerable to use substances. If we make them available, we can predict that our adolescents will use them. This is empiric data from SAMHSA. It demonstrates that the peak ages for substance use initiation is between 14 and 20. By age 26, substance use initiation is very rare. People who don't start using a substance in their teens or early adulthood are unlikely ever to start using. Teens are not only susceptible to substance use, they are also vulnerable to developing substance use disorders. Substance use disorders are the result of changes to the brain's pleasure and reward center, resulting from repeated exposure to substances. In adults, the mature prefrontal cortices seem to provide some protection, but in teens, the prefrontal cortices are still developing, and can't offer as much protection. In fact, for every psychoactive substance, the earlier use is initiated, the more likely a person is to develop a substance use disorder. The graft on the left shows that teens who have their first drink before they turn 13 have a 50/50 chance of developing an alcohol use disorder. The risk is fivefold higher compared to those who wait until early adulthood to initiate alcohol use. The graph on the right shows the same pattern and magnitude of effect are about the same for cannabis. This is a drawing of an alcohol molecule. It is chemically similar to a water molecule. It's hydrophilic, which allows it to cross membranes freely, and so, has a lot of other binding sites giving alcohol, overall, a very broad range of effects. The most significant effects of alcohol come from binding at the GABA receptor in the central nervous system. This is a picture of the receptor showing that GABA binds in a different site than alcohol. Benzodiazepines and barbiturates also bind the GABA receptor and each has unique binding sites. All of these molecules are depressants. This picture shows some of alcohol's projections from the nucleus accumbens where binding results in euphoria to the amygdala, which is involved in emotional regulation, and also, to the prefrontal cortex, which is the seat of executive functions. Because adolescents are developmentally driven to seek large neurological reward, their typical drinking pattern is heavy, episodic drinking or binge drinking. In fact, NIAAA estimates that 90% of all alcohol consumed by underage drinkers is part of a binge. Alcohol impacts youth differently from adults. Glycine, highlighted here in yellow, is the major inhibitor neurotransmitter in the brain stem and spinal cord. Adolescents are much less sensitive to the effects of glycine compared to adults. This has been demonstrated in the behavior of adolescent rats where the same phenomenon has been noted. Rats don't like water and will quickly swim to a platform in a water tank. The water maze involves putting rats into a small pool of water with a hidden platform. They have to swim to find it. In this study, researchers divided adolescent and adult rats into two groups, and half of each group got alcohol while the other half got a saline solution. They then put each rat into the water maze, and measured how fast they swam, and how how long it took to find the platform. They found that adult rats that were given alcohol swam more slowly and took longer to find the platform. By comparison, adolescent rats who were given alcohol swam at the same speed, but had more trouble finding the platform, because they were impaired. Adolescents who are impaired from alcohol are less sedated and more motorically active compared to adults. This accounts for the known associations with drinking, including accidents, injuries, and sexual assault. This graph shows that at every blood alcohol level, younger drivers are more likely to have an accident than older drivers. These FMRI pictures were taken from two teens. On the right, a non-drinking individual, and on the left, an individual with a history of alcohol use disorder. The brain images are a top view looking down just above ear level, the warm colors show parts of the brain that were active for the memory task given during the scanning session. Cool colors show parts of the brain that were less active during this task. On the top, at age 16, both teens have a similar pattern of brain response and both perform similarly, but the individual on the right has much more activation. In other words, the individual on the right had to use more brain and work harder to achieve the same performance on the bottom. At age 20, the individual on the right is now 10% impaired on the task, and the brain shows substantially less activation. It's possible that the brain may compensate by working harder and using different brain areas, but if the neurotoxic continues, the brain may not be able to compensate as effectively, and performance diminishes. This is the picture of leaves and stems of the cannabis plant. Delta-9-tetrahydrocannabinol, or THC, is the psychoactive ingredient in marijuana or cannabis. On the left is a picture of anandamide, which is a neurotransmitter made by the human body. On the right is a drawing of THC, which is a chemical made by the cannabis plant, and the active ingredient in cannabis. THC can bind to cannabinoid receptors throughout the central nervous system and mimic anandamide. This is a schematic of the brain showing areas that are rich in cannabinoid receptors. The area in the center that is the brightest is the nucleus accumbens. Binding here results in the euphoria people experience when using cannabis. You can also see that the cerebellum, the hippocampus, which is involved in long-term memory function and the prefrontal cortices are also rich in cannabinoid receptors. You can surmise from this diagram that cannabis use interferes with gross motor control, memory, and learning, and also judgment and executive functions. This cartoon shows what happens when THC or anandamide bind to the receptor. Cannabinoid binding suppresses cell signaling and results in decreased release of neurotransmitters into the synapse. This is important for directing brain development as, normally, cells that are not firing are pruned away as the brain matures. The affinity of anandamide for cannabinoid receptors ranges from about one-fourth to one-half that of THC. The differences depend on the cells or tissue that are tested and the experimental conditions, such as the binding asset used. On average, THC is about twice as potent as anandamide at the receptor. This means that it will outcompete for binding and remain on the receptor longer than anandamide does. This is a slide showing the correlation between hippocampal size on the x-axis and total amount of cannabis used on the y-axis. This is simply a correlation, but given what we know about brain development, it raises significant concern about the impact of cannabis and THC on brain development and ultimately on learning. This study done in New Zealand in the early 2000's looked at just that. Researchers recruited a cohort of more than 1,000 children at age 13, and followed them every three to five years, or so. At each time point, participants were administered an extensive assessment battery, which asked, among other things, whether they were using cannabis currently, and if they were, they had a psychodiagnostic interview to see if they met criteria for a cannabis use disorder. They also had a full IQ test. This slide shows the IQ changes over time. The bottom bar showed the change in IQ over the 25 year study period for participants who never used any cannabis. The mean IQ for this group stayed stable, about 99.8 at baseline, and 100.6 at follow up. The top bar shows the change in IQ for the group that met criteria for a cannabis use disorder at least three times during the 25 year period. The mean IQ for this group fell by about six points from 99.7 to 93.9. While a six point IQ drop would be hard to pick up without a test, it certainly is concerning. Cannabis use during the adolescent years is also strongly associated with psychotic disorders. This slide shows the results of a meta-analysis showing that cannabis use doubles the risk of developing a psychotic disorder. This work is from 2007, and more recent work has continued to strengthen this finding. This slide comes from work at Boston Children's Hospital. My group recruited 500 kids coming in for routine primary care. About 30% of them had used cannabis in the past year, and of that group more than than a quarter had experienced a hallucination, and about a third had experienced paranoia or anxiety while using. Taken together, more than 40% of past year cannabis users had experienced a psychotic symptom related to their cannabis use. None of these adolescents had a psychotic disorder. The experience of psychotic symptoms related to cannabis use by healthy adolescents is concerning. Teen smoking used to be very common, but smoking rates have declined dramatically over the past 20 years, a public health success. Unfortunately, electronic cigarette use or vaping has reintroduced nicotine problems for youth. This graph shows the rates of use of various nicotine products by high school students from 2011 to 2018. The red arrow demonstrates how cigarette smoking had fallen dramatically. While the red circle shows how e-cigarette use has skyrocketed, particularly, since the mid 2010's when newer, pod-based e-cigarettes including JUUL were introduced. On the left side of this slide is a drawing of the chemical structure of acetylcholine, which is a human neurotransmitter, and on the right is a drawing of the chemical structure of nicotine, which is made by the tobacco plant. Nicotine can bind acetylcholine receptors in the central nervous system, and mimics acetylcholine. The central nervous system is very sensitive to having an excess of binding at the acetylcholine receptor. When the brain is exposed to nicotine, cells start to express fewer receptors, making them less receptive to nicotine. This accounts for the tolerance people experience when they start using nicotine, and also, the withdrawal they get when they stop, because the system is out of whack. Nicotine has a very high affinity for the receptor. In these scans, the top is a resting brain, and the bottom is a brain of someone who's smoking a cigarette. The blue areas show receptor binding. By the time one-third of a cigarette has been consumed, after about three puffs, the brain is nearly entirely saturated. This is a schematic of a brain showing the effects of nicotine binding. Nicotine activates dopamine transmission in the nucleus accumbens, the same as all psychoactive substances resulting in a buzz. Though the activation with nicotine is very short, and as a result, it is not as impairing as other substances. Note that there are projections to the prefrontal cortices and this is the part of the brain that is rapidly developing during adolescents. Adolescents typically develop symptoms of nicotine addiction much more quickly than adults, and changes to the prefrontal cortex are thought to make people more susceptible to other substance use disorders. Adolescents also experience nicotine differently, often, oppositely from adults. As with alcohol, adolescents are less impacted by decreases in locomotor activity, more sensitive to the rewarding effects, and less sensitive to aversive effects. Overall, adolescents are more sensitive to the rewarding effects of nicotine, they experience less withdrawal, and they tolerate high doses much better than adults do. This is the schematic of an e-cigarette. Regardless of shape and size, they all contain a battery, metal heating coil, a tank or pod to hold liquid, a wick made of cotton, silica, or ceramic, and a mouthpiece. E-liquids contain a base, an active ingredient, which is either nicotine, cannabis, or in some cases, neither, and flavorings. Formulas are proprietary though chemists have reverse engineered them and found roughly 60 to 70 compounds per liquid, and about 113 chemicals across 50 brands. Beyond that, when the e-liquid is heated into a gas, many chemical reactions result in the formation of many different chemicals. While e-cigarettes generally have low levels of the most toxic, harmful, or potentially harmful chemicals found in combustible cigarettes, they have several other toxic chemicals, many of them in higher concentrations than cigarette tar, and innovation introduced by JUUL Labs is a salt form of nicotine. Initial e-liquids contain nicotine as a free base similar to cigarettes, but those liquids are harsh and cause throat irritation, so they're hard for beginners to get used to. JLI experimented with different nicotine salts and discovered that adding benzoic acid resulted in a less harsh compound with a highly bioactive form of nicotine. The milder formulation made it easier for young and beginning users to tolerate very high nicotine concentration. For many teens, the peak level of nicotine attainable through an e-cigarette is high enough to cause symptoms of toxicity. Commonly reported symptoms include dizziness, nausea, vomiting, headaches, and abdominal pain. Seizures have also been reported in the literature. We don't have definitive answers to the impact of nicotine on the developing brain, but what we do know from animal models is that nicotine interferes with the ability to focus and learn, and this is concerning. This is a quote from a 14 year old boy I saw in the clinic. When he first started describing his experience, I thought he was explaining why he wanted to quit vaping, but then he added, "It felt great," demonstrating how adolescence experience can be very different from that of an adult. He also mentioned that he no longer has the good feelings with nicotine use, demonstrating the development of tolerance. He went on to talk about how vaping ruined his life. He would lose his focus whenever he vaped, to the point he could no longer function in school. He dropped off a sports team, because he would find himself not remembering where he was or what he was was supposed to do, and he worried that he would get hurt. In summary, alcohol, cannabis, and nicotine use are all simultaneously attractive to teens, because of the tendency for thrill seeking and impulsivity typical during this stage of development and also, harmful to the developing brain. Screening, brief intervention, and referral to treatment, or SBIRT, is a clinical framework for asking adolescents about their substance use, identifying those who likely have a substance use disorder, and making an intervention within the context of a healthcare visit. The American Academy of Pediatrics recommends SBIRT for all adolescent patients, and encourages clinicians to give this message. The non-use message should be reinforced by pediatricians through clear and consistent information presented to patients, parents, and other family members. In other words, the AAAP encourages healthcare providers to take every opportunity to recommend non-use as the best strategy for protecting adolescent health and development. Several screens have been developed for identifying substance use disorder in adolescents. The tool on this slide is called screening to brief intervention, or S2B1, and was developed at Boston Children's Hospital. It uses the same STEM question. In the past year, how many times have you used x? And response items for tobacco or nicotine, alcohol, and cannabis. If the adolescent reports any past year use to any of these three substances, the tool continues to ask about four other classes of substances commonly used by teens. This demonstrates how responses to S2BI map onto a pyramid of substance use experience. The next few slides give examples of how the AAAP recommendations can be actualized. For adolescents who report no past year use of any substance, the healthcare provider can deliver positive reinforcement. This is an example of a prevention method for a teen who reports no past year substance use. This slide, together with the next one, are an example of a response to sporadic use. The healthcare provider started by saying, "I see from these questions that you have tried nicotine. Tell me more about that." The teen has responded that someone at school shared an e-cigarette. The physician gives a cessation message. "As a healthcare provider, I can tell you that choosing not to vape is the best decision for your health. The nicotine and THC in vapes are both addictive, and vaping can really damage your lungs." She gives a clear message that not using is best, and she focuses her advice on health consequences. This is an example of a brief intervention with a patient who reports regular alcohol use. When the provider asks the patient to tell her more, for brevity, this is presented as a monologue, though, in actual practice, the provider would most likely need to elicit some of this information with targeted questions. Here the patient says, "I drink at parties with my friends. Last time I was pretty drunk, so a friend drove me home. He was a little buzzed, but he knew he was safe to drive." The provider responds, "I am glad you decided not to drive after drinking. That was smart." Note that she gives him credit for a good decision. She then goes on to give a medical explanation of why getting in the car with a peer who had been drinking is not a good idea. She says, "The truth is, many kids may feel as if they are safe to drive, even when they are not." Next, she gives a clear message encouraging no use. "As a healthcare provider, I can tell you that the best decision for your health would be not to drink at all." Finally, she targets his highest risk behavior and challenges him to come up with a substitute. "If you decide to drink, are there ways you can avoid getting into a car with a driver who's been drinking? How else could you get home?" If an integrated or community behavioral health specialist is available, this patient could benefit from more education and counseling about alcohol. This is an example of an adolescent with heavy cannabis use. When the provider discusses his use with him, he says he uses cannabis daily to relieve stress. He mentions that he has gotten in trouble with his parents and also at school. He then says that he does not see cannabis use as problematic, because he is doing well at school. The provider recognizes that this patient most likely has a cannabis use disorder. She reframes his use saying that he seems to depend on cannabis to manage stress. She also echoes his frustration at getting in trouble. She uses these hooks to invite him to continue the conversation with a behavioral health counselor, emphasizing that a big goal of the conversations would be to help him identify healthier ways of managing stress. She also pushes forward, asking him permission to set up an appointment. The previous examples form the essence of brief intervention, which is just the tip of the iceberg in terms of primary care management of substance use disorders. This slide gives examples of other strategies that we can use in primary care to help address adolescent substance use disorders. The following slides briefly demonstrate treatments for substance use disorders and show the status of evidence-based in youth. Several named brief interventions for adolescents have been shown to reduce alcohol, cannabis, and nicotine use, and an implementation study found that teens seen in clinics that were randomly assigned to provide SBIRT had lower odds of having a substance use disorder three years after initiation of brief interventions compared to teens seen in clinics that did not offer BI. There are also a number of medications used to treat substance use disorder, including three with an indication for treating opioid use disorders. Buprenorphine has an indication for patients age 16 and over. Both naltrexone and acamprosate are effective for treating alcohol use disorders and can be considered in young adults or adolescents with alcohol use disorder. Disulfiram is approved for treating alcohol use disorders in adults, though it is rarely used in adolescents. Two studies have found that adolescents treated with the over the counter supplement N-acetylcysteine have found that it reduces cannabis use among teens with cannabis use disorders. This slide shows the major counseling modalities that have been shown to be effective for treating youth with substance use disorders. These are the modalities behavioral health counselors should be using in their work with adolescents. Typically, counselors will use an individualized combination of strategies depending on the piece of work that they're focusing on and the adolescent's needs. This slide shows the level of evidence for motivational interviewing, cognitive behavioral therapy, dialectical behavioral therapy, and contingency management, all of which are in the moderate range. Group therapy usually mixes together several modalities and includes opportunities for mutual help. It is a developmental preference for many adolescents and newer efforts are exploring the virtual modality for group treatment. Family therapies are among the most effective modalities available for treating adolescent substance use disorders, as demonstrated on this slide. Substance use treatment can be delivered at a variety of levels of care. This slide reviews outpatient levels of care and their health benefits. This slide reviews inpatient and residential levels of care. In summary, adolescents are vulnerable to both substance use and substance use disorders or addiction. The American Academy of Pediatrics recommends that healthcare professionals encourage non-use as the best health advice for adolescents, including screening and counseling or intervention as part of routine medical care for adolescents is recommended. Effective evidence-based treatments for adolescent substance use disorders exist, and can be delivered at various levels of care, including within primary care. These are the references that were used in this presentation. The PCSS Mentoring Program is designed to offer general information to clinicians about evidence-based clinical practices and prescribing medications for opioid use disorder. PCSS mentors are a national network of providers with expertise in addictions, pain, evidence-based treatment, including medications for opioid use disorders, a three-tiered approach allows every mentor-mentee relationship to be unique and cater to specific needs of the mentee. There is no cost for participation in this program. For more information, please visit the website below. If you have a clinical question, please visit the website below. PCSS is a collaborative effort led by the American Academy of Addiction Psychiatry in partnership with many other organizations. Thank you.

adolescent substance use

medication-assisted treatments

adolescent brain development

screening adolescents

evidence-based treatment options

brain maturation

substance use disorders