<v ->Hi, I'm Nicholas Chadi.</v> I'm a Pediatrician Specialized in Adolescent and Addiction Medicine. I work at the University of Montreal. Today's webinar is going to be about nicotine and stimulant use in adolescents. I have no financial relationships to disclose. Just as a reminder, the overarching goal of PCSS is to train healthcare professionals in evidence-based practices for the prevention and treatment of opioid use disorders, particularly in prescribing medications, as well as for the prevention and treatment of substance use disorders. Our educational objectives for today will be to discuss recent trends in nicotine and stimulant use among adolescents. We will also describe the health risks of nicotine and stimulant drugs. And finally, we'll apply evidence based treatment for youth with tobacco and nicotine use and stimulant misuse. And if we look at our outline, we will start by some definitions and trends in nicotine products. We'll then dive into the neurobiology and health impacts of nicotine use. We will also talk about nicotine prevention and cessation, specifically in adolescents. We'll then shift gears and talk about illicit stimulants, trends, risks, and treatments. Then prescription stimulants, trends, risks, and treatment. I will say a few words about caffeine trends and health risks and conclude with some take home points. Let's get started. If we look at the landscape of nicotine and tobacco products, it's definitely changed quite a bit in the past few decades, and I've tried to represent this schematically in terms of what young people are using nowadays. As you can see, aside from the nicotine and tobacco bubble in the middle, the largest one is the e-cigarette bubble. Definitely today, the most common way of using nicotine among young people, adolescent, is in the form of e-cigarettes or vapes. You can see that the cigars and cigarillos box is similar size to the cigarettes one, in that the hookah and water pipe and chewable dissolvable tobacco boxes are still around, meaning that these are also forms that young people use. And I've also included nicotine replacement treatment here, although in a different shape because of the different purpose. If we talk just a little bit more about smoke tobacco products, and this may be a bit of a reminder, but the main forms are obviously cigarettes, cigars, and cigarillos, but then Kretek, bidi and hookah. A table here is showing some alternate names as well as a quick description. Basically, cigars are large, tightly rolled bundles of tobacco wrapped in tobacco leaf. Hookah is a pipe that includes lit tobacco bubbles through water inhaled through a shared mouthpiece. You can also use hookah that does not contain tobacco or nicotine, but in all cases, there are emissions that are potentially harmful and toxic. Even though this goes through water, there are toxic emissions. Bidis are hand rolled leaf wrapped cigarettes, often with flavors. And Kretek are rolled mixtures of tobacco, cloves, and additives. If we talk now about smokeless tobacco products, we can include in this category chewing tobacco, dissolvable tobacco. And you see different forms here. Orb sticks and strips. Other forms, snuff and snus. I say here at the title tobacco products, but we are seeing more non tobacco nicotine containing products that look very similar to those, and those are rapidly increasing in popularity among young people, so we will need to keep an eye on those. But essentially, they contain nicotine and can be consumed in similar ways, whether they are derived from tobacco or synthetic nicotine. Again, a quick table here with a few alternate names and some descriptions. Chewing tobacco, which is typically consumed by holding the chewing tobacco between the gums in the cheek. Snuff is finely ground tobacco, either dry or moist, that is either inhaled or held in mouth. And as I mentioned earlier, you could find a variation that is made out of synthetic nicotine and doesn't necessarily contain tobacco. Snus is a form of moist snuff dispensed in packets and usually held in mouth without spitting. Dissolvable tobacco in different forms. And we could also add emerging forms here like gummies or other forms of edible nicotine that we'll need to keep an eye on and see how they involve in terms of popularity and use among young people, given that they are on the newer end of the spectrum. The missing one of all the different forms I've just discussed, obviously e-cigarettes and vaping devices. And as a quick history of these devices. Around the turn of the century, beginning of the years 2000, we first started seeing e-cigarettes that looked a lot like traditional cigarettes. They were yellow and white, although made of plastic and were disposable, and they would dispense nicotine in a rather inefficient way compared to the more advanced third, fourth, and you will, see fifth generation devices. And with time we started seeing larger devices that were shaped like pens and had a reservoir that could be refilled. Third generation, which you can still see around nowadays, larger, more complex devices with adjustable features, and definitely large refillable tanks, usually for nicotine containing liquids. The real change in landscape, for young people at least, came with the fourth generation towards the middle of the years, 2000s. 2010s actually. These smaller slicker pod mod type devices have replaceable cartridges or prefilled pods, which contain nicotine salts dissolved in liquid. Those e-cigarette products are quite efficient in delivering nicotine in almost a similar pattern or way that traditional cigarettes. More recently, there was a surge in popularity of fifth generation of devices, disposable e-cigarettes, which look a lot like the fourth generation pod mods, though they're only one time use. Probably part of a reason why they became so popular, in the US at least, as you can see, the surge use between 2019 and 2020 was a national ban on flavorings contained in pod mod based devices, but that didn't include disposables, so young people, being very attracted to flavors in general, there was a shift towards those devices, which remains quite high, even today. When we talk about what comes out of an e-cigarette or vaping device, the proper term is aerosol. And the aerosol contains a mixture of water vapor and fine particles. This mixture is inhaled and can absolutely have certain medical effects on the human body. A typical pod or disposable will contain anywhere between 0.7 and 2.0 milliliters of e-liquid. Obviously, there are larger devices. Most will contain nicotine. I placed 1.5 to 5% as a range here. Some devices do not contain nicotine, but most young people will use nicotine containing vaping products. You could find, if you do the math, about 15mg to 100mg of nicotine salts in a small pod or disposable, which more or less is the equivalent of 1/3 to 2 packs of cigarettes, in terms of nicotine. Obviously, a lot of factors come into play here, including inhalation technique, device type, and the actual liquid itself, which could affect the amount of nicotine that is actually absorbed. But in this schematic, I show here in the bottom of the slide. You can see that definitely e-cigarettes or vaping aerosols can contain several different things including nicotine, but volatile organic compounds, ultra fine particles, cancer chem causing chemicals, traces of heavy metals and flavoring such as diacetyl, which can be linked to serious lung disease. Definitely not harmless, especially if consumed in large amounts. And although the risks of long-term e-cigarette or vaping use are just starting to be uncovered, we would expect any harms to be greater with a longer period of use. Looking at some numbers from the US in the National Youth Tobacco Survey, so we can see from the years early 2010s to the end of that decade that e-cigarettes went from being not very common among young people, middle and high school students here, to the main form of nicotine use in youth, overtaking cigarettes, cigars and other forms of tobacco use. If we look at more recent numbers from 2021, we can see that definitely even after the onset of the COVID 19 pandemic, e-cigarettes remain much more used to than other forms with cigars in second, cigarettes close after, and other forms of tobacco still present, but to a much lesser extent. If we think of the type of e-cigarette device that is most popular among young people, I mentioned disposable e-cigarettes as the top type of device in the US. After that, pre-filled or refillable pod or cartridges. The tank and mod systems, those larger devices, are used by a smaller proportion of middle and high school students. And in this slide, we're showing past 30 day use in the US from the 2021 National Youth Tobacco Survey. If we look at flavors, and I mentioned flavor is definitely a draw towards e-cigarette and vaping products, young people tend to use fruit and mint flavors nowadays as their top, but also candy, dessert, and other mint, menthol, alcoholic drinks, chocolates, and other flavors that are used in pretty much all types of e-cigarettes. Even though there's been quite a large shift in patterns of nicotine use and different forms of nicotine use among youth in the past few decades, one thing has remained quite steady, and that is of those young people who were smoking or using tobacco, there's always a significant proportion who is interested in quitting in a somewhat nearby future. And on this slide you can see about a third of young people say that they're seriously considering quitting in the next 30 days and a little over half in the next six months. Definitely as health providers, there's a role that we can play here trying to leverage that intent to quit or reduce, at least, in use of nicotine or tobacco products. Before we talk more about cessation and reduction, let's just talk a little bit more about the neurobiology and the known health impacts of nicotine use in young people. As per DSM-5 criteria tobacco use disorder can be defined according to 11 different criteria which I won't go over today, but are similar to other substance use disorders, are actually the same. And what we know of nicotine is that it is a highly addictive substance, possibly more so than cannabis and alcohol and comparably to other stimulants like cocaine. A part of this is that nicotine is a rapid acting substance that will produce a rapid peak and intense reward sensation through the release of dopamine. That will lead to potential cravings emerging in young people and adults after a short period of regular use. In some, only three to four months after the first cigarette or e-cigarette use, sometimes less. We also know that a year and a half after the first cigarette, a quarter of young smokers will lose their confidence in their ability to quit, showing that even though they may want to or feel inclined to do so, the pattern of use and dependence may be quite strong. It's been reported that youth tend to have less severe withdrawal symptoms, which may be in part due to a shorter period of use, but these symptoms can appear only after a few cigarettes or sessions of e-cigarette use. And it's also said that some youth may be more sensitive to these effects, potentially due to some immaturity in their brain development, which will altogether represent an obstacle for early cessation. And I did mention tobacco use disorder is part of the DSM-5. When we talk specifically about nicotine and its impact on the adolescent brain, what we know in primarily from animal studies in animal models that exposure to nicotine during adolescent years can lead to persistent changes in the development of neuronal connectivity and specifically dendritic formation. So, these connections between our neurons can be impacted by exposure to nicotine. The specific brain areas that are affected are, unsurprisingly, the nucleus accumbens, the reward and pleasure center of the brain, which I like to call grand central processing in terms of exposure to different substances. But also the medial prefrontal cortex. The center of executive functioning in the amygdala the center of emotional regulation. In addition to actual cortical changes, nicotine has been shown to bring epigenetic changes and an increased sensitivity to other drugs. The way I like to explain this is if you expose a young brain to the effects of nicotine, you may strengthen some connections between neurons that are involved in reward processing and sensitivity to some psychoactive substances. Because of the common pathway that leads most of these substance use receptors to the common nucleus accumbens and other reward and pleasure processing areas of the brain, this young brain will be fine tuned and primed to seek these sensations and potentially go towards patterns of use that are more intense and more problematic. Again, mostly in animal studies, we've shown that long term exposure to nicotine can lead to increased impulsivity, decreased attention and performance, and overall impact positive brain development. To represent this schematically, we can see that there's a high concentration of these acetylcholine nicotinic receptors in the ventral tegmental area in this subcortical area represented in the middle of the slide. In these areas is directly related to or connected with the nucleus accumbens. As I mentioned, a lot of the dopamine firing from the stimulus of nicotine entering the system will go through there and then later on affecting other areas of the brain, notably the prefrontal cortex and the amygdala that is very nearby, where we process our emotions. One key take home message from today's presentation is that all forms of tobacco and nicotine products carry important health risks for youth, and we've just gone over some potential effects of nicotine on the youth brain, and we should be keeping in mind that tobacco and vaping are not safe in any amount or form due to nicotine that they may contain, but also the other chemicals that are contained in the smoke and in aerosols of these products. And even if the health risks may seem somewhat smaller for some tobacco products when compared with others, all tobacco and almost all vaping products contain nicotine, which can lead to increased use of nicotine tobacco products and addiction to those products and other substances. We've also seen more recently that youth who use e-cigarette or vaping devices can be at risk of acute and severe lung injuries. And a good example of this would be the outbreak that we saw in the US of e-cigarette and vaping associated lung injuries, or EVALI, which were primarily recorded in the years 2019, early 2020, just before the onset of the COVID 19 pandemic actually. We reported just over 2,800 cases of hospitalized episodes, young adults, adolescents, primarily in the range of 13 to 85 years old, but with a concentration among younger people. These people presented with acute and severe respiratory symptoms that looked quite heterogeneous. A few chemicals were identified as potential causal agent, one of those being vitamin E acetate, which tends to be found primarily in some cannabis vaping products. Vitamin E acetate no longer is allowed in circulation in those products. We've also had cases of EVALI from people primarily vaping nicotine based e-cigarettes, suggesting that there probably are several different chemicals found in the aerosols that could lead to acute and potentially severe presentations, so definitely we need more study, more monitoring about this and certainly some control over what is contained in those e-liquids and e-cigarette products. Let's shift gears and talk a little bit about smoking and vaping prevention and cessation, specifically in adolescence. Some of you may be familiar with this Screening to Brief Intervention screening tool. Really, this for me represents the simplest evidence based single question tool to have an idea of a young person's risk related to the use of nicotine in tobacco vaping products, but also alcohol and marijuana which tend to be the most common psychoactive substances, potentially leading to substance use disorders used among youth. According to this tool, if you have an adolescent who will report weekly or more use of nicotine tobacco products or other of these three substances, there is a correlation with risk of substance use disorder. And clearly, the more intense the use, the more frequent the use, the higher the risk. But, according to some studies that have been done in this population, even reporting weekly or more, which may not seem like that much, will be tightly correlated with the risk of having a severe substance use disorder with this substance. Once you've asked the initial three questions, which all have the same stem in the past year, how many times have you used so and so, you may certainly continue and ask about other substances such as prescription drugs, or other legal drugs and inhalants, or other herbs and synthetic drugs, which will give you a more complete picture of the level of risks here for the young person. And this falls nicely in expert framework. The American Academy of Pediatrics suggests using a three-step process to screen, discuss and then act on substance use among adolescents. SBIRT stands for screening, brief intervention, and referral to treatment, which is represented here in this slide. After using a validated screening tool such as the S2BI, a very short one, there are other ones like the CRAFFT, for example, that have a larger number of questions, then it's possible to have an idea of the level of risk. And if there's low no risk or low risk, then positive reinforcement is totally appropriate. And if there is substance use without a disorder, then we may want to go into some brief health advice or brief intervention plus or minus referral to treatment with ourselves or other resources. And so what does brief counseling look like with young people who report using tobacco or vaping? Well, we do know that there is certainly a potential for health providers to help young people reduce either the risk of initiation or use of tobacco and vaping. Counseling should definitely be seen as something that can be done in an interdisciplinary way. Can be provided by pretty much any healthcare or behavioral health provider, or even a trusted adult, just to get a feel of what young people are getting from their use, what are their perceptions, and certainly how that ties into their everyday life. And there are opportunities for intersectoral collaborations to do some forms of brief counseling in different settings like healthcare, school and community. Different counseling modalities have been studied and tried. Face-to-face encounters remain common and those can be associated with motivational interviewing techniques or more standard cognitive behavioral therapy. Counseling can also be done in the form of providing print or online materials, plus or minus discussion with a health provider or trusted adults. They're more and more text messages or online app programs that are starting to emerge and give some interesting options for youth who may be living further away or not necessarily have access or be willing to connect with someone in person. And brief counseling can also include involving parents and families because definitely they can play a role in supporting young people and it's very important to make the content age and context specific. The idea with brief counseling is not to lecture young people. It's to create this trusted relation so that young people can feel more comfortable discussing their pattern of use and potentially identifying some goals. Adolescents tend to need more short term and concrete elements versus long term elements related to vaping or tobacco use, for example, if we want to try to motivate them to make a change. There's several factors that do impact teen smoking and vaping. Initiation and cessation and certainly peer influence and family tobacco vaping product use are big ones. Age and sex. We know that male sex and older teens tend to be more likely to quit. Educational and cultural context can be important in the context of a more in-depth discussion. Psychological conditions in comorbid untreated mental health issues and use of other substances should also come into play when we're counseling. It's hard to counsel about one substance and forget about others. Excess weight and weight preoccupations could also be a factor and it's known and it circulates that nicotine can cut appetite and then nicotine cessation can increase appetite and potentially have young people gain weight. That's something that could be interesting to explore. Also, physical health conditions and chronic illness can be tied in some way tobacco use. Could increase the risk of medical complications, and so important to keep in mind. Without going into too much detail. We have people who are slower versus more rapid metabolizers of nicotine. If we have a person who is a slow metabolizer of nicotine, then this tends to be associated with increased likelihood to quit. I haven't used this in my practice specifically, but this may be where we might be going with more personalized medicine if we start doing more genetic testing for people with substance use. Access to tobacco product is a big thing. And trying to identify these sources and try to understand how they come into play. Time availability. Knowledge about the substances and beliefs about tobacco and nicotine products can also be important. It can be interesting and try to address those and deconstruct some myths if they come up. Having good behavioral skills, being able to say no or to do other things and not get pulled into what the social circle may be doing with tobacco nicotine is important. And clearly pregnancy or parenthood can be important motivators for cessation in adolescents if it happens, or young adults. So again, some important considerations. As part of normal teen development, pushing boundaries, exploring and experimenting, is normal, but it isn't all teens who use cigarettes or nicotine tobacco products. A proportion of them, certainly, but normalizing the fact that more and more teens now. And it's been shown through the years, are actually not using tobacco, and even e-cigarettes in their high school and adolescent years. Dealing with anxiety or stress and the perception that using nicotine or vaping may help with that is something that could be addressed. I mentioned fear of gaining weight and also fear of peer rejection. Fitting in can be important to address. Are there other ways to fit in the peer group without using these substances? Hand in hand with adolescent development, and brain development, and the formation of one's identity, their need to control something or feel independence may be tied to the use of these these products and can be interesting to explore. The need for privacy. Some young people may just not be ready to discuss why and how they do it and how they use these products. We know also that LGBTQ+ youth tend to have higher rates of tobacco product use. Also vaping products, but perhaps not as high. This definitely needs to be studied still. Same with racial ethnic disparities, which are extremely important to address, but will go a little bit outside the scope of this presentation and certainly could deserve the time for an entire presentation in itself, as we do see some disparities and inequalities between racial ethnic groups and sexual minority groups. When we talk about assisting young people with cessation, we can definitely think about pharmaceuticals. Counseling is definitely something that I tend to see for as the gold standard first step for all youth who report use of nicotine tobacco products. But more and more professional societies, including the American and Canadian Academies of Pediatrics, will endorse the use or the potential use of nicotine replacement at therapy for young people who are regular users of e-cigarettes or smoke on a regular basis, and that's based on an acceptable safety profile and potentially low side effects that usually are limited to mouth and/or skin irritation depending on form. Perhaps an increase in heart rate and blood pressure, but not out of line of what we would see with the use of these tobacco and nicotine products themselves. What's recommended is that it's best to combine both long and short acting NRT to prevent withdrawal and reduce cravings. The forms that are recommended in young people are gums, lozenges, and patches. Nicotine sprays and inhalers are not recommended as much because of the way they can be similar to e-cigarettes or cigarettes and potentially lead to increased nicotine use through those products, which isn't the goal. Really, the goal should be to try to help young people taper down with their use. There are some contraindications for nicotine treatment, but I would argue that if young people are using the nicotine products themselves, then it's potentially safer for them to use a nicotine replacement than the tobacco or vaping products. And yes, prescriptions are important and often needed for reimbursement in the US for youth under 18. So, good thing to keep in mind. A few practical tips when it comes to energy and dosing. Dosage for NRT in adolescents should be considered in a similar way to recommendations in adults, though we may want to start with somewhat lower doses for youth who are under 45 kilos. How to convert use of cigarettes or e-cigarettes, into amounts of nicotine replacement therapy. What's been known for a long time is a pack of cigarettes is pretty much the equivalent of a full strength 21 milligram patch. With nicotine salts, which is how most people will vape nicotine, it depends really on the type of device, on technique, but if you look at different sources, and definitely based on my clinical experience and some professional guidelines that are out there, we could probably convert one milligram of nicotine salt in the form of vaping to 0.5 to 1.0 milligram of NRT. That definitely needs to be adjusted and tapered according to clinical response. Young people should not feel buzzed from their NRT. NRT should really prevent cravings and young people shouldn't feel much. They could feel a little something with the shorter acting ones, but they are, even though quicker acting than the patch, they're shorter acting or they take more time to actually deliver the nicotine than the inhalation of the e-cigarette or cigarette. That's one important thing to mention to young people. Giving or prescribing nicotine replacement will not give the similar experience or feeling than the actual smoking or vaping devices will. What would be a reasonable starting dose for nicotine replacement? If young people are using 50 plus milligrams of nicotine salts a day, which could be the equivalent of a one to two ML pod with full strength nicotine 5%, then yes, the full strength patch plus gums and lozenges. Those come in different strains. Two to four milligrams for the gums and one to two for the lozenges. we go down the scale, if we have smaller use and fewer milligrams a day of nicotine. It is a good thing to try to calculate with the young person. How many pods are you using? How many milliliters? What's the concentration? Let's try to figure out how much nicotine you're actually using in a day or in a week and then try to figure out a reasonable regimen. And we could definitely think of a three month total decreasing regimen of nicotine replacement therapy to assist young people over a gradual process. And that life can be adjusted and ideally would be combined with behavioral support such as counseling or therapy. There are other medications that are potentially recommended for smoking and vaping cessation. Really, I need to say that the evidence base remains to this day quite limited. Very small number of trials for Bupropion as an anti-craving medication. It could be combined in some cases, but usually best if combined with nicotine replacement and with behavioral means. Varenicline. Also small number of trials. only recommended in some cases for youth over the age of 16. That's based on no demonstrated effectiveness. Potential side effects for youth under the age of 16 or 16 and under. Some other avenues that are being studied in adults, including tricyclics, clonidine, cytisine, have really not been studied either for smoking or vaping in young people. And I have to say that we can endorse a strong recommendation at this time. All together, one question that I get asked a lot is can we still consider e-cigarettes a harm reduction tool or something that is less harmful than cigarettes or other forms of tobacco? And there was this report in 2018 from the National Academies of Sciences Engineering and Medicine trying to summarize the public health consequences of e-cigarette use. At that point, there was conclusive evidence that definitely nicotine exposure and emissions from e-cigarettes and other forms of vaping devices were highly variable, and that potentially completely substituting cigarettes for e-cigarettes would reduce the number of toxicants and carcinogens. However, if there is dual use, then the potential benefits are reduced. However, and that's the really important caveat, there is substantial evidence that e-cigarette use in adolescence is associated with current and subsequent tobacco product use, and also potentially increased risk of alcohol, cannabis, and other substances. Evidence that came out since 2018 really emphasizes the fact that there are strong associations between e-cigarette use and subsequent use of tobacco products, cannabis and potentially other substances. And there really is no convincing evidence to date that e-cigarettes would be an effective tool for smoking cessation. Anecdotally and definitely in my clinical practice, some young people will tell me that they have replaced tobacco cigarettes with e-cigarettes, but potentially using e-cigarettes on a long-term basis, and even in higher amounts with more nicotine, and potentially with exposure to higher amounts of chemicals tied to this intensity of use. There's the association with other substances. Really, we shouldn't be considering e-cigarettes as a first line or a prime smoking cessation tool in adolescence and even considering it at all as a smoking cessation tool would be risky. I would really be cautious to use that as a potential avenue. Given the potential risks for long term use of e-cigarettes, dual use with other tobacco products, and risk of using other substances, either concurrently or subsequently. I'm just sharing a few resources here, a page from the American Academy of Pediatrics, with lots of interesting resources for providers and different tools that can be distributed to patients and families, so constantly updated. I definitely encourage you if you have an interest to go and take a look. This is just one example of the quit start app, which is an example of a cessation app that can be used for smoking and/or vaping among young people and can definitely be an interesting avenue for those tech savvy young people. All right, let's now change directions and talk about other stimulants. I'll share some numbers to get us started. If we're looking at different trends in stimulant use among US middle and high school students over the last 45 years, which coincides with the period of existence of the Monitoring the Future survey, an annual national survey of young people's substance use patterns, behaviors, and mental health, we can see that here on one side of the slide, cocaine has been decreasing in the past years and is reaching historical lows in terms of use in 8th, 10th, and 12th grade students. Similar pattern with MDMA or ecstasy. Looking at amphetamines and methamphetamine, again, we are seeing decreasing trends in use of these substances, which I guess should be considered as some good news in the adolescent population. To try to sum up the different categories of illicit stimulants, I've put here the street names or more common name, the commercial names, if they apply, the different forms and the common ways that they are taken. If we talk about cocaine, several synonyms here or common terms that are used to describe cocaine. And there are definitely topical solutions that can be used but are rarely used as anesthetics. Cocaine looks like a white powder or whitish rock crystal if it's in a crack form. Cocaine can be sniffed, smoked or injected. Ecstasy or Molly another commonly used term. It doesn't have any known commercial uses. Will often come in in colorful tablets, potentially with some imprinted logos. Could also come in capsules, powder and liquid. Could be swallowed or sniffed. Amphetamines, methamphetamines. Again, several street terms that we hear are listed here. The commercial name for amphetamine would be Desoxyn. Common forms would be either as a white powder or pill, crystal meth, which falls in that category, will look like a piece of glass or shiny blue white rocks of different sizes. And these substances can be either swallowed, sniffed, smoked or injected. Let's zoom in to the different subcategories. Cocaine, as I mentioned. Use and accessibility have been steadily decreasing in adolescents since 1999 and reaching historic lows. Acute effects of cocaine. Definitely is stimulant. In the psychological realm, euphoria, increased energy, restlessness, anxiety, paranoia and potentially psychosis, depending on the dosage, depending on the person's response. Physiologically, vasoconstriction, mydriasis, hyperthermia, tachycardia, hypertension, potentially nausea. Definitely some acute hazards with cocaine use. Many of them are in the cardiovascular categories. Arrhythmia, stroke, seizures and potentially coma with high dosage. Long-term effects, depending on the pattern of use and mode of use, anosmia if intranasal use, nose bleeds, nasal damage, trouble swallowing. Bowel ischemia also with potential vasoconstriction happening on a chronic basis, poor nutrition and weight loss, depending on the intensity of use. Definitely, cocaine can bring several different negative health effects. If we think about MDMA or ecstasy, there has been a somewhat recent increase in popularity among young adults, not seen in adolescents or high school aged young people. Ecstasy is both a stimulant and a hallucinogen to some extent. The short term effects on the psychological realm would include a decreased inhibition like social inhibition, increased sensory perception, and potentially why this tends to be used in dance parties and in raves to increase, or enhance if you want, sensory perceptions tied to those activities. Physiological effects. Again, in the stimulant realm, tachycardia, hypertension, hypothermia. Muscle tension, nausea and faintness can also happen. One thing to look out for would be hypothermia and dehydration, especially if in the context of intense physical activity or dancing. Those can lead to kidney failure. Some long-term effects to look for would be long-lasting confusion, depression, problems with attention, memory and sleep, increased anxiety, impulsiveness and potentially decreased libido. Methamphetamine. We've seen use decreasing in both adolescents and young adults since the turn of the century. Rates remain somewhat low. Under 1% of 12 graders will report using methamphetamine. The perception of risk is quite high. Methamphetamine is structurally similar to amphetamine and produces similar effects, but some important differences. Onset is quicker, effects can be stronger. Users will often use repeatedly and go on binges. Some short-term effects that we can see. Increased wakefulness and physical activity. But then, decreased appetite, tachycardia, hypertension, hypothermia, and arrhythmia. Some long-term effects. Could lead to anxiety, confusion, insomnia, mood problems, violent behavior, paranoia, hallucinations, delusions, weight loss, severe dental problems, also sometimes referred as "meth mouth" intense itching leading to skin sores from scratching. Some additional considerations with stimulant use. All illicit stimulants are frequently laced with substances including opioids and high potency opioids like fentanyl. There definitely is a risk of overdose from the stimulant, but also from some senses that are potentially laced with it with one single pill or use. Stimulant use can lead to increased sexual arousal. Definitely important to think about SDI screening and contraception counseling. Doing all the necessary sampling and blood work, especially with youth who are sexually active. So, how to treat stimulant use disorder? There are today, to date, is no FDA-approved medication to treat a stimulant use disorder. There are several experimental trials for cocaine use disorder such as using amphetamine salts, or baclofen, or disulfiram, methylphenidate, modafinil, N-acetylcysteine, topiramate, topiramate and amphetamine salts. I mentioned experimental because trials, especially in young people, are either small or results aren't quite clear. For methamphetamine, bupropion, methylphenidate, naltrexone, naltrexone plus bupropion, have been studied and I've listed the more salient substances that have been studied to date. Behavioral therapies thus will represent first line treatment and in that category we could think about cognitive behavioral therapy, we could talk about contingency management using motivational incentives including vouchers and gift cards. And that obviously will require a set up and a setting in clinic a to make that happen. The reSET app is an app that was cleared by the FDA that could be used to help with the treatment of stimulant use disorder and it combines education, cognitive behavioral therapy and contingency management. And also in the community we can think about a 12 step program such as Narcotics Anonymous that can support people or young people with stimulant use disorder. Definitely important to think about harm reduction when we are thinking about illicit stimulant use. Trying to counsel young people if they're going to continue to use, to use with others. Never alone due to the risk of overdose and pretesting a dose. Starting with a very small dose to see if there is a strong or unusual response with that dose. Naloxone rescue kits would be very important to think about and to prescribe or recommend if young people are telling you that they're using illicit stimulants because of the risk of being laced with opioids and others. Definitely that should be very present in our minds if injecting stimulants, thinking about sterile needles, no needle sharing and no reusing. If smoking, trying to use clean glass pipes. Using mouthpiece to avoid burns. Again, no sharing if possible. Test strips for fentanyl and derivatives could also be interesting. They can have high sensitivity and specificity if they are used properly. That requires to dissolve the substance in water. If tablets need to be crushed, that also could be something that could be recommended. Let's talk now about prescription stimulants. Just some numbers here. Another story here. The national survey on drug use and health. 2020 edition. What we can see is misuse of prescription stimulants among young people. In 12 to 17 range in gray, quite stable. In older people, young adults, seems to be a bit of a decreasing trend here in the past few years. But altogether, this is something that remains present and needs to be considered. In that category, we can include amphetamine based and methylphenidate based prescription stimulants. I've listed, again, some straight or common terms. And then some commercial and brand names. In the amphetamine category, amphetamine salts, dextroamphetamine, and lisdexamfetamine, also known here with the commercial names. In the methylphenidate based categories, some examples. Dexmethylphenidate and methylphenidate, often with different commercial names. Commonly in tablet and tablet chewable, either swallowable and capsule form, sometimes in liquid form. Common ways to take them would be swallowed, sniff, smoked, injected, or chewed. Use has been decreasing among young adults, but as we could see in two slides back, use has remained relatively stable among adolescents since 2015. Some short term effects, definitely psychological effects. The main indication why they would be used in the medical setting would be to increase alertness, attention and energy. And physiological effects would be potentially hypertension, tachycardia, vasoconstriction, and hyperglycemia, especially at higher doses. Yes, again, hyperthermia, arrhythmia and seizures can be seen in higher doses. One thing to keep in mind is that these substances can prolong QT and increase the risk for arrhythmia. Obviously with higher doses and especially if of underlying medical conditions or use of other medications that could also prolong QT. In some cases with high dose or high administration, we could see anger, psychosis, and paranoia. A few words about substance use in ADHD. Children and youth with ADHD are, at baseline, 2.5 times more likely than their peers to develop substance use disorders. And when we think about what ADHD is and the increased impulsivity, this makes sense. And we know that ADHD is also associated with an earlier onset of substance use and higher likelihood of using multiple substances. What is also known and becoming increasingly clear is that treating ADHD with stimulants at the right dose with adequate follow up may reduce the risk of substance use disorders. There's certainly no evidence of harm and potential benefit if done the right way. There could be some interesting screening questions to ask in the context of young people coming in and requesting treatment for ADHD with or without previous prescription of ADHD medication or substance use. And those could help get a sense of risk of misuse of ADHD or psychostimulant medication. Those could be, have you ever shared or sold your medication? Have you ever taken a larger dose than prescribed? And have you ever taken your medication more often than prescribed? And if yes to any of those questions, this should definitely raise some questions about having a thorough discussion about how to reduce the risk of misuse and best accompany young people who may received a prescription for these medications. So, different strategies to reduce the risk would be to optimize behavioral and non-pharmacological management of ADHD. Medications are one way of addressing it, but definitely school accommodations, potentially work with special educators or people at school that can help find calmer spaces and definitely find ways of learning or being in class that would optimize learning would be helpful. Safe prescription and documentation practices are definitely recommended for any physician who would prescribe psycho stimulants with or without evidence of prior misuse. And one important thing to do would be regularly checking any drug monitoring database for controlled substances to make sure that there's only one prescriber and see if there are other controlled substances being prescribed at the same time. Single prescriber, regular follow up every one to three months could be a way of decreasing risks of misuse. Shorter medication supplies, if indicated, to make sure that there's a regular contact with the pharmacy. And avoiding early refills. Using formulations with lower misuse potential could also be an interesting avenue. Privileging longer acting versus shorter acting substances that tend to give less of a euphoric feeling when they are taken and tend to be less trafficked and misused. Prescribing prodrugs can also be an alternative. Looking into non stimulant medications, although the evidence shows that they can often be a little bit less effective for ADHD symptoms, could still be considered if there's a high suspicion of potential misuse. Direct observation treatment could be an avenue for parents who are present at home. Keeping the medication locked in the home setting. Urine drug screening could also be done to help ensure patient safety, but should always be done with patient consent. Avoiding surprise testing is definitely a good way to privilege therapeutic alliance and disclosure of health information and behaviors. What would be an approach to actually prescribing psychostimulants in the case of ADHD? A first step would be to try to get an accurate diagnosis of ADHD and this often will become clearer on history and with the necessary workout, which may include questionnaires to parents and teachers and getting a good developmental history. Clarifying the nature and onset of symptoms is important. Looking at previous diagnoses, if there have been previous psychological assessments or neuropsychological assessments for things like learning disabilities or ADHD in the past. And then, yes, if it hasn't been done, considering referrals to neuropsychological testing because there can be overacting symptoms between ADHD and substance use disorders themselves, because capacity to pay attention and being more impulsive can happen with substance use, or be at the basis, or a risk factor for it if we have undiagnosed ADHD. This often is a challenge, especially if we have young people who are already on substances and come up, and have symptoms of ADHD have never been diagnosed. It may be tricky to actually get a reliable neuropsychological assessment. And definitely, it could be possible to prudently and slowly, with adequate follow up, to consider treating ADHD, even on the basis of a somewhat imperfect assessment or history. There are no FDA approved medications to treat prescription stimulant use disorder, per se. Behavioral therapies used for listed stimulants may be useful, including cognitive behavioral therapy, contingency management, and again, mobile medical applications. Treating and addressing comorbidities, including use of other substances and mental health comorbidities is important. But I would say that if there is misuse of a prescription medication, then trying to find the right dosage and keeping tight follow up over those things would be definitely a recommendation. Let's talk a little bit about caffeine in its different forms. Caffeine is the most wildly used psychoactive substance in the world. Not necessarily considered in the DSM-5 as a proper substance use disorder, but definitely there is some talk and discussion about the potential harms and addictive nature of caffeine. And what we have seen is that use of caffeine in adolescents in the US has really increased since 1980. Doubled, we say. Now about 75% of adolescents consume caffeine each day. Caffeine has different effects on males and females after puberty. Before puberty, it's more similar. And what's reported is that there seems to be stronger cardiovascular reinforcing and subjective responses in boys versus girls. Not to say that girls are immune to any of the effect of caffeine. Some health risks with caffeine. Caffeine use will produce greater tolerance in teens versus adults. And in according to animal studies, caffeine use during adolesce can really be associated with greater sensitivity to cocaine and other illicit stimulants, and other drugs in adulthood. Effects are not really seen if caffeine exposure starts in adulthood. Early exposure to caffeine may actually be a risk factor for substance use in adolescents. Something to keep in mind. Caffeine consumption is associated with increased risk taking, impulsivity, and sensation seeking in teens. The association is stronger in boys, who also consume greater quantities of caffeine than girls. It's somewhat unclear if caffeine is a cause or if youth who are more prone to risk taking are also more prone to caffeine use. But there's definitely an association. The American Academy of Pediatrics recommends a maximum of 100 milligrams of caffeine per day for adolescents, which is more or less the equivalent of one standard eight ounce cup of coffee or two sodas, and really not uncommonly will you see young people far exceeding this amount. If you look at FDA recommendations in comparison, the recommendation would be to stay under 400 milligrams per day in adults. Just as a general guideline, I've indicated some approximate caffeine contents of different beverages and those can obviously vary. We see that the decaf beverages here contain little to no caffeine. Depending on the technique used to decaffeinate coffee, this may vary. And we can see that teas can also contain significant amounts of caffeine, especially black tea. Energy drinks can certainly contain high amounts of caffeine and definitely over the recommended daily amount, and also can contain some "hidden sources" of caffeine, so other supplements or substances that can mimic the effects of caffeine and enhance those effects. Again, talking about energy drinks, typically they'll contain approximately 50 to 80 milligrams of caffeine, which is a little bit less than a standard cup of coffee. College students who regularly consume energy drinks are at greater risk for future use of alcohol use disorder, cocaine use and misuse of prescription stimulants. Should be considered as definitely a risk factor for substance use. Again, we're talking about associations and not causal relations. One thing to note is that there have been anecdotal reports of overdose related to caffeine use. For example, the death of a 16 year old teenager a few years ago, secondary to caffeine induced cardiac arrhythmia. And in that specific case, there was the combination of coffee, and soft drink and energy drinks. In all cases, caution is advised. Caffeine can also be available in the form of powder. Over the counter caffeine pills can be used by young people for increased awareness and attention, but also can have misuse potential. One thing to keep in mind is a teaspoon of pure caffeine powder is equivalent to approximately 25 cups of coffee and 2,700 milligrams of caffeine. Definitely that could be a lethal dose even for a healthy adults or adolescent and can lead to all sorts of acute effects including tachycardia palpitations, arrhythmia, seizures, diarrhea, vomiting and disorientation. Again, another anecdotal report to the high school student secondary to caffeine powder use has prompted awareness on this issue. In 2018, the FDA provided a statement recommending for the industry to avoid highly concentrated caffeine and dietary supplements just because of this risk, and just to know about this potential avenue. In conclusion, we've covered a lot today. Just a few take home messages about tobacco use disorder and tobacco and nicotine use in adolescents. We've seen that nicotine has important deleterious effects on the developing adolescent brain if used regularly and intensively during that period. Cigarettes and e-cigarettes are never safe for children and adolescents and e-cigarettes are associated with increased use of tobacco product and other substances and therefore should not be considered a smoking cessation tool or strategy in young people. Screening and brief intervention by health providers can delay the onset of smoking and vaping and should be included in all teenage health encounters. Nicotine replacement therapy should be considered in adolescents who are daily users alongside with behavioral support and in other means. If we talk about stimulant use disorders, rates of illicit stimulant use has decreased among adolescents over the past two decades, but prescription stimulant use has remained fairly stable. Untreated ADHD, as we mentioned, is a risk factor for substance use. And caution is needed when treating youth with stimulants, which also have a potential for misuse and potential diversion of the medication. There is no approved pharmacological treatment for stimulant use disorder, but behavioral interventions including CBT and contingency management should be considered first line of treatment. Finally, caffeinated beverages and caffeine powders and pills can be dangerous and even lethal if if misused. Here are some of my references shown on this slide and in the second slide. Just very quickly, a few reminders about the mentoring program. The PCSS Mentoring Program is designed to offer general information to clinicians about evidence-based clinical practices in 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 disorder. There's a 3-tiered approach, which allows every mentor mentee relationship to be unique and catered to the specific needs of the mentee. And there's no cost. More information can be found online. If you have a clinical question, don't hesitate to use the PCSS discussion forum, which is a simple and direct way to receive an answer to medications for opioid use disorder. Again, more information online. Just some acknowledgements here. This does bring us to the end of our session today. Thank you for your attention and I really hope this was helpful for you.

Dr. Nicholas Chadi

adolescent

addiction medicine

nicotine use

stimulant use

health risks

e-cigarettes

illicit stimulants

prescription stimulants