all. It's great to be back with you. Today we are doing our second session in our series of three sessions with our partner Boston Children's Hospital. Today we have a different fellow with us, Dr. Aishwarya Thakkar, and she will introduce herself in a moment. I did just want to note, again, this session is being recorded. And we also, I have the recording almost ready to go from the last session. I apologize for the delay and getting that out, but I will get it out very soon, as well as the slide decks. And if you have questions, please feel free to put them in the chat as they come up, or you can raise your hand if you feel comfortable doing that, or unmuting, we would love to have your questions throughout, but we will also have time at the end. All right, I think that's everything I needed to say. So I will go ahead and pass it over to you, Dr. Thakkar. Okay, amazing. Thanks, everyone for being here today. So yes, I am a fellow, which means I'm getting more additional training in addiction medicine, specifically in adolescence. And then I did my pediatrics residency. So I'm a pediatrician. And I'm excited to be chatting with you all about this. I, you know, know that you got a little bit of an overview in terms of just substance use in general. Today, I'm hoping to talk a little bit more about just adolescence and how substance doesn't affect their brain specifically. And I'm also just curious, like, what your guys's role is and what you're curious about. So feel free to put it in the chat as I kind of began talking and I'll and I'll look at it. I'm just want to be able to tailor some of what I'm talking about to like your specific needs and questions. And, again, like Emily mentioned, at any time, please interrupt, ask questions. And I hope this is not like too in the weeds. I tried to keep it general and relevant to y'all. But please let me know what questions you have as we go along. Let me share my slides here. Okay, so um, let me make sure I can see you guys and the chat in case anything comes up. Okay, perfect. We are all set up here. Um, so like I said, we'll be talking about addiction in the brain. And specifically for adolescence. Why is substance use? Why does it happen in adolescence? Well, how do how do substances affect the adolescent brain? And so, you know, oftentimes, a lot of addiction medicine or a lot of addiction work that's been going on right now as an adult. And I think we are just now in the last couple years, we're starting to realize that a lot of substance use often starts in adolescence. And we can do a lot of prevention and early treatment work. And adolescence brains are specifically developmentally primed to seek thrill, and they find substances appealing. And this is some recent data from 2023, as to when people initiated using substances. And so the blue is first use before 21. And the gray is first use at 21 and older. And you can see in alcohol, which is the second bar and cannabis, which is a third bar, over half started use before the age of 21. Nicotine vaping, which is the first one and cigars, which is the fourth one is about 40% there. So still a significant group of people who are initiating use before the age of 21. And so what makes adolescence primed to use substances, and these are actually images that I show adolescents I work with, because I think it's helpful to give them education and information about their how their own own brain works. And so this is a graph or an image of the brain from age five to age 20. And the green parts of the brain are immature and the blue are mature parts of the brain. So you can see that, you know, at age 20, there are still some immature parts of the brain. And so brain development continues to happen until we know about like age 25. And hence why anything that disrupts brain development early on is can impact, like your brain going forward, since since these neural connections and pathways are still forming. And so different parts of the brain develop rapidly at different times. And the cerebellum, which is the part of the brain that is involved in motor movement, this part of the brain develops when when kids are learning to walk. And then the amygdala, which is the part of the brain that develops rapidly when kids are learning how to control their emotions, you can think of temper tantrums, terrible twos, threes, they're just figuring out how to navigate all the emotions that they're feeling. The nucleus accumbens is the part of the brain that is developing kind of in like school age slash early adolescence. And this is the part of the brain that responds to rewards. And so, you know, kids are learning about their boundaries, they're learning about positive rewards, negative rewards. And then comes the prefrontal cortex, which I'm sure you know, you've heard about and know that that part of the brain is developing as teenagers are going into young adulthood. And this is the part of the brain that's responsible for that executive functioning for being able to decipher what's wrong or right or, you know, what is okay to do what is not okay, what's safe, all of those things. And that part of the brain is is what is what continues to really develop until the mid 20s. So adolescence is this like, really fun and interesting time where the nucleus accumbens has developed super rapidly, because that's, again, happening in that school age years, but the prefrontal cortex is is lagging behind a little bit. And so what happens is that adolescents, you know, want to explore their boundaries want to try new things. And so, you know, adolescents are always on the, the they know what's up and coming, like they know what's the next big new thing, and they're willing to explore it and try it out. And what happens then is you have all the gas, but no brakes is kind of what I how I like to think about it. And so we're, you know, waiting for that prefrontal cortex to kind of kick in and help adolescents decide, like, is this a safe activity to participate in? Or is this not? And then this is interesting, where, sorry, Emily, I'm just noting, did you see the chat? Yes. Okay, perfect. And so another another way in which adolescent brain is specifically different from the brain of a child, the brain of adult. So you can see in let me start with children first, and that's this blue line right here. And so you can see that with a small reward, children are equally excited as they are by a large word that that blue line kind of hits that that same point on both of these graphs, which means that you know, if you give a child a sticker, they're equally excited by it as if you give them a new bike. Adults, on the other hand, is this green line, and you can see that they have a small response to a small reward, and you know, a decent response to a large reward. Teenagers, on the other hand, have a negative response to a small reward and a more positive response to a large reward than even adults do. So you know, you give a child if you give a teenager a sticker, and they're gonna laugh in your face. Although, you know, there are some some cool ones out there. But a large reward, they are even more motivated by than, say, an adult would be, hence, you know, substances, they provide this large reward to the brain. And hence, they're even more susceptible to that reward. So the reward pathway is really what substances and addictive substances act upon. And they release a neurotransmitter called dopamine, which kind of activates this reward pathway. So it's it's kind of like, and different things in life get released dopamine, and I'll talk about that in a second. But substances do that at a higher level. So your brain is just primed to, in like a very simplistic way, you know, uses something gets a high reward, obviously, you want to use it again. And so what they found in in research is that people who have developed a substance use disorder, have fewer dopamine receptors. So again, that dopamine is that neurotransmitter, it's that signaling molecule, that's that signals the brain that oh, this is a reward. And so what happens is over time, as people are using substances, they have a lot of that dopamine that they're getting from outside the body. And so what the body does is get rid of some of those receptors, because it does it recognizes that there's a lot of dopamine out there. And so there's actually then fewer receptors that people have over time. And what this does is, if you look on the left, so you know, having good food that you like, friends that you like hanging out with family time activities, those all give you a level of dopamine. However, on the right, you can see that big graph with substances, that it gives you a much higher level of dopamine. And so your brain has this like sensitivity level. And you know, as you kind of hit that level, you have to like trigger that that level to get the response to get the like pleasure and happiness and reward from that experience. And because substances have raised that normal level to much higher, having your favorite meal, hanging out with your friends, family activities, don't hit that level that it needs to have you feel that response. And so people over time, who are who have a substance use disorder can't really find that pleasure and happiness in experiencing some of those like daily activities that do give us dopamine. And this is one of the hardest things about when people are trying to cut down or stop using substances is that things don't feel enjoyable, like they're, they're bored a lot today, they don't find that pleasure from kind of, you know, everyday normal activities that they should. And I like to tell my patients that this, this is not a forever thing, right? Your brain is not forever changed by this, like you can, especially with young people, because their brain is still growing and is still changing, that they can they can reverse this and it in it. From research, we've seen that it takes about like, two to three months for that dopamine sensitivity level to come back down. And so that three month mark is like, is the hardest part. And so after that, hopefully, you know, they can utilize their other coping strategies and have it have a much better effect because it's actually able to hit that dopamine sensitivity level. And we know that, you know, substance use is experienced differently by people of sexual and gender diversity, as well as racial diversity. And this is a whole host of factors, but I just want to put up these numbers so, you know, we can be aware that this affects people differently. This is from a study, I'm seeing a question, I'll stop here for a sec. Is there any research with dopamine desensitization and social media? That is a great question. I will admit that that is not my area of expertise. And so I won't spread any misinformation. So I will, you know, get back to you. I know the person who's speaking next time. And so if I have any information with that, I will pass it along to next week's person and hopefully they can get back to you. But thank you for asking. You can imagine that I think that there's, you know, a lot of similarities there. So this is a study that was done and looked at folks who were transgender, folks who felt gender differently, meaning that they asked them, how much do you feel like a boy? And so it was trying to figure out their congruence between their gender identity and their assigned sex. Gender non-contendedness. So the question that they were asked was, how much have you had the wish to be a girl? And then gender expression. So how, you know, their expression of their gender and in terms of gender norms. So like, for example, how much have you dressed or acted as a girl during play? Just some examples of questions that they were asked to assess some of these questions. And so they found that, so this is like a ratio. So this means that people who identified as transgender were twice or 2.13, twice as likely to ever in their lifetime use alcohol. Twice as likely and nearly three times as likely to use nicotine. Six times as likely to use cannabis. And you can see some of this other stuff is less significant, but definitely the bolded is what is, you know, statistically significant. So there is an increase in terms of gender diversity and substance use. This slide is, here we go, is past your use. And so again, we're seeing high numbers in terms of cannabis use, nicotine use, less so with alcohol in terms of transgender use, but definitely across the board in terms of gender diversity, an increase in substance use, lifetime use, as well as substance use, you know, more recent past your use. And then this is some data on adolescents who report symptoms of anxiety or depression in the past two weeks. And so you can see that adolescents who experienced anxiety is about 21%, depression is about 17%. Female identifying sex experience anxiety and depression more. And then people who identify as LGBT plus experience more anxiety and depression. And I bring this up because we know that adolescents experiencing a past year major depressive episode, and this is data from 2022, were more likely to have used an illicit substance, more likely to use cannabis, misuse opioids, and binge drinking. And so just to highlight some of the data on this, and so also we know that Black and Hispanic adolescents drug overdose death rates have increased faster amongst them, even though, you know, overall substance use overall has been declining, rates of that have been declining, but drug overdose death rates have increased. And so recognizing that there are various stressors to people from diverse backgrounds, including violence, victimization, harassment, stigma, and obviously a lot of like systemic issues in terms of race and gender and sexual diversity. And, you know, all of these stressors add on to each other and adolescents are finding, you know, a need to cope and substances in the way that they impact the brain and the way that they impact those dopamine receptors and those reward pathways and giving that really high level of dopamine, you know, that's why it's so appealing. So obviously we're kind of focusing on, you know, the goal is to help adolescents find other healthy ways in which to cope and, you know, obviously always working on some of these bigger stressors that are present in our society. So I wanna dive into a couple of substances in particular. So I'll hit the nicotine, cannabis, alcohol, and we'll talk about opioids a little bit as well. So how does the brain, or how does nicotine affect the brain? Again, this is the dopamine reward pathway and the nucleus accumbens is that area from where dopamine is released. And something that people don't always recognize that nicotine is that it does affect this prefrontal cortex. So it does affect part of the brain that is, you know, executive functioning, decision-making, things like that. And this is a slide showing the brain and how it responds to cigarette use. And so the blue area are parts of the brain that can bind onto nicotine. And 0.1 is one puff of a cigarette, 0.3 is three puffs, one is one cigarette. And so you can see that, you know, even by three puffs of a cigarette, a lot of your brain has receptors for nicotine. And so it affects a lot of different parts of your brain. And nicotine is interesting in that it releases a lot of other neurotransmitters as well. Apart from dopamine, it can release something called acetylcholine. And, you know, you may have heard of serotonin, which is the neurotransmitter that makes you feel happy. And so different people use nicotine for different things based off of how it affects them. And so, you know, sometimes teens will often tell me that, you know, nicotine, it helps them focus or they, you know, it's like there's a lot on social media about, you know, using nicotine before you go to the gym because it helps you focus or before you do any homework. And, you know, so part of it is that, yes, it releases some of these neurotransmitters and it does that in the immediate. However, what happens over time is that, again, the same thing that I talked about in terms of the dopamine receptors, your brain sees all this external acetylcholine and serotonin and, you know, all the other neurotransmitters. And so it down-regulates or it shuts off the receptors that are, that shuts off your body's inner ability or like on its own ability to produce some of this. And so people actually have a worse time after a period of using nicotine in terms of focusing or in terms of regulating their emotions or end up feeling more anxiety, more depressive symptoms. And so I, you know, I like to inform them of that effect as well. And adolescents in particular. So I'm gonna point you to this nicotine withdrawal, or sorry, the sensitivity right here, which, you know, we've talked about that, how adolescents are more receptive to rewarding behaviors and they have that high response to high rewards. So they're more sensitive to nicotine rewarding effects than adults are. And nicotine withdrawal, they actually don't have as much withdrawal symptoms as adults do, but they're able to tolerate higher doses of nicotine. And so they're able to use much higher doses of nicotine. And I will show you this slide here, where, you know, Juul, if you compare it to the early, early e-cigarettes, which is the Ciga-like ECs and there's refillable e-cigarettes and stuff like that, but this is kind of an old slide, but Juul and you can see it's like that, the straight black line, the amount of nicotine that Juul can hold is so much higher than what other products like it before. And, you know, we've come a long way from Juul where there's even more innovative products on the market. And so I don't even know what this graph will look like now, I bet it's much higher than Juul. And the way in which that the formulation of vape products is the nicotine is in a nicotine salt form, which means that it is more palatable. So it doesn't taste as bad or, you know, have a negative effect like cigarettes do. And it is more rapidly absorbed than cigarettes ever were, which means also that, you know, because of those things, you know, disregarding all the issues with the flavors and all of that, but that adolescents can actually tolerate higher nicotine concentration levels. And so what we started seeing, and some of you may have heard this, but NIC-sick, so like getting sick from having too much nicotine, which, you know, can look like a headache, dizziness, nausea, vomiting, that's actually nicotine poisoning. And that's like, that's when, you know, you've had a very high concentration of nicotine in your body, which we weren't seeing before with cigarettes. That is like a new phenomenon that we're seeing with vaping because it can give such a high level of nicotine. Thank you. I will stop there for a sec and see if there's any questions so far or thoughts. Love this, this is a great link. Thank you, Melissa. I will, I didn't know about that either, but I will check that out. Yeah, great. Okay, I will talk about cannabis now. And again, please feel free to keep typing away. So cannabis use, so, you know, this is, we're kind of at an interesting point with cannabis because it's being legalized more. I think the social commentary on it is permissive and it's hard to be an adolescent and feel like, oh, this is okay for other people to do why is it not okay for me to do? And so I've done a lot of education in terms of how cannabis can affect the adolescent brain, which adolescents are often surprised by. So younger, so the earlier people start using substances, the more risk they have of a use disorder. And this is with alcohol, with other substances and also with cannabis. These are parts of the brain where THC can impact the brain. You can see it's like the prefrontal cortex. It is this middle part right here is the hippocampus, which we'll talk about, it's involved in memory. This back part right here is the cerebellum, which is again involved in motor movements and reflexes and things like that. So we will talk about that. So you can see it's a lot of different parts of your brain. Again, same idea here where your body has, the reason THC can affect the human brain is because we have receptors in the brain that THC can bind to. And we have natural neurotransmitter signaling molecules in the body that bind to these receptors and they're involved in regulating emotion and pain and in a lot of different things. And so THC when it, again, the same idea when you have an external molecule that's coming in, your body then says like, oh, there's a lot of this. I'm going to turn down the volume on having the receptors available for this because there's a lot of this molecule out in the open. So that's kind of like a similar idea that we've been talking about for all these substances. And so anandamide is the endogenous or the neurotransmitter that's already in our body naturally occurring that binds the same receptors that THC does. And so I think of this and this is how I explain it to adolescents too is that you can think of anandamide, down-regulating or up-regulating parts of your brain with a scalpel. So it's very fine, it's very precise. THC is twice as strong as anandamide is. And so you can think of it as a hammer that's just kind of like going off in different directions. So it's not that precise and it can, you know, sometimes take away for, you know, to keep it simplistic parts of the brain that you don't really want it to. And so this is studies that we've done on adolescents, not we, but other researchers have done on adolescents who have been using cannabis heavily. And you can see that over time, the more cannabis that they're using, the size of their hippocampus, which again is that part of the brain that holds memories and is responsible for memories decreases. And so this is a structural change of the brain that's happening. And, you know, we see often that kids over time after using substances, there's more brain fog, there's more memory issues. So it's, this is not like something that you see years later we see it, you know, as teens or still teens. And this is a study that was done with folks who were followed from the age of 13 to their mid thirties. And they were categorized into never having used cannabis, used occasionally, or who were dependent, which is kind of an old term for a use disorder and the number of years that they were. And those who never used cannabis, their IQ was 99.8 to 100.6. Those who use cannabis for over three plus years consistently, their IQ was a little bit lower. And so, you know, we have data on how cannabis can impact some of these like neuropsychological effects from childhood to midlife. And then this is, you know, one of the more concerning parts of it. This is looking at schizoaffective disorder, which part of schizoaffective disorder is a component of psychosis. And so you may have heard or seen that there are more episodes now of psychosis with cannabis use. The THC in cannabis now is much higher than it used to be and like much, much higher. And obviously, you know, people are, well, I shouldn't say obviously people are using it more cause I think it was always present, but the THC content being higher is what we're kind of gathering or attributing this to. So again, this is like that ratio that I was talking about. So 7.4 is like seven times is what you can think of it as. So those who use cannabis over 50 times in their life had a seven times more likelihood to develop a schizoaffective disorder. And what is 50 times? I mean, if you used it once a week, that's a year. If someone used it once a month, that's their entire high school career. If they use it every day, that's two months, right? Approximately, and so you can see that it puts people at by not a lot as in like, you don't have to use it a lot. It's not like you have to use it for 10 years. It's really 50 times where you have this, such a higher risk of developing a schizoaffective disorder, seven times higher likelihood. And so I like to inform kids of this and, you know, not, and I think the important thing is you guys work with kids and you know this, but scare tactics are not helpful. I don't present this in a way that's scary, but I give them just the information that we have. And so that they can be empowered to make those decisions and know what's out there. Cause there is a lot of, you know, misinformation on social media and the internet and, you know, newspapers and everything really, especially around cannabis and its effect for young people specifically. And then this one is, I'm sorry if this is a little small, but this is about cannabis and driving. And so people ask me a lot, like, is it safe to drive, you know, using cannabis and parents often ask this and it's, this is not, you know, driving while high that is, you know, obviously not okay. This is actually just how cannabis affects your ability to drive even when you're not high. So in this study, people were asked to not use any cannabis for 12 hours and they separated people into people who had started using cannabis early in life. So before the age of 16 versus later. So after the age of 16 and the bars with the asterisk at the top is what's significant. And then the, on the left side, there's two bars that say HC and CU. HC is healthy controls. So people who never use cannabis. CU is cannabis users, people who were used to cannabis. Again, they did, they were not high during this. They had not used for 12 hours. And so you can see here that those who were chronically using cannabis were more likely to hit pedestrians. Those who started using cannabis early in life were more likely than those who started using cannabis later in life to have collisions. Those who started using early and those in general who are chronic users of cannabis had more stop signs that they missed and more, this is number E where they were caught for speeding more. And then G at the very end of the right there had more crossings of the center line. So this is data that I show them. And I, it's show them that it's risky to be behind the wheel even after using cannabis. And even if you're not high at that moment, cause it can affect like that picture that I showed you at the very beginning of the THC molecules and how it affects the cerebellum because it's causing long-term changes to parts of your brain. And so it's affecting people's ability to do some of those like motor functions and reflexes and things like that. Okay, any thoughts, concerns, questions there before I talk about alcohol? Okay, I don't see anything in the chat, but let me know. Okay, so alcohol and the brain. So this is a graph of folks of a 16 year old who had a two year history of heavy drinking and compared to someone who had it drink before. And so the red is parts of the brain that are activated. And so the 16 year old who was drinking heavily was able to complete this like spatial working memory task just as well. However, needed higher levels of brain activation. And then comparing this with 20 year old who had a five year history of heavy drinking, they had a 10% impairment on spatial working memory task. So they weren't able to complete the task as well. And you can see that parts of their brain, that they had less activations, like less of those like red orange spots, less activation of their brain. And so it's this idea that like with drinking, the brain can work harder to compensate for the effect in the early stages. But after continued use, the alcohol has neurotoxic effects on the brain and it can affect brain function over time. And so how does alcohol affect rats differently? So adult rats, when they when they have alcohol, they sleep and we found that adolescents, adolescent rats dance. And so and this is after the same dose of alcohol. So they did this study where adolescents, or sorry, adolescent rats, not adolescents, were placed in a pool with a small platform hidden just under the water surface and the rat had to swim around the pool, find the platform, and escape the water. And they measured the swim speed and the time it took to find the platform. And so an intoxicated adult rat had decreased swimming speed. And time to platform was increased compared to a non intoxicated rat. And intoxicated adolescent rat, the swim speed was unchanged. So they were still able to swim as fast. And then the time to platform was increased. And so just highlighting the differences between when adolescents have used alcohol versus adults. And, you know, often we talk about how blackouts affect the adolescent brain. So blacking out, not remembering anything. So blacking out is actually parts of your brain, you know, to put it in simplistic words, parts of your brain shutting down. Because it's it's just trying to keep other important functions of the body alive, because the level of alcohol in the body is so high. And so and so long term effects of that are, this is a long term study that was done to and it looked at parts of the brain. So this is particularly the fusiform gyrus, which essentially is parts of the brain that involve visual recall. So like remembering visual things that you've seen, and then the hippocampus, again, part of the brain that holds memory. And so those two parts of the brain, that's this is the the red line here. And so that that volume decreased. So the brain's ability, so the more blackouts that someone had the ability for them to remember just things in general, as well as recall visual memory, in general, not not during the blackout, decreased. And again, this is a structural brain change that has happened. And so we don't really know what that means. So, you know, what we do know is that there's reduced hippocampus volume, again, the memory reduced activity during memory tasks. And so we don't know if this effect is permanent or not. And so something to just, you know, know and talk about with with adolescents in terms of, you know, even if we're approaching it from a harm reduction perspective, just, you know, giving them the the information and knowledge about what what does it mean to blackout and why that is concerning. Yeah. Okay, I'm going to talk about opioids. So the distinguishing factor here that you know, I want to start off with is opiates versus opioids. So, opi- opioid is like kind of the general term. And so if you're not not sure what to use, opioid is the correct term to use. Opiates are from the like naturally occurring plant. And so morphine and codeine are from like naturally occurring plant. And so hence they're opiates. And then other there's derived compounds, natural synthetic analogs, like buprenorphine, heroin, oxycodone, those are synthetic. Benton methadone, those are fully synthetic. So those are opioids. So that's just a if you just if you see that, that's what that is. So how do opioids affect the brain? Essentially, there are three different types of opioid receptors in humans. And they're located in the sexual nervous system, so the brain, the spinal cord, and your peripheral nerves and your gut, and also in the immune system. And endogenous opioids, so opioids in the body respond to this new receptor, which is one of the three receptors. And clinically prescribed or illicit opioids also bind to this new receptor. And it's a part of this. So in terms of endogenous, so so ones that are in your body, they're the normal response, they normally are released during injury, pain, stress. And they affect prefrontal cortex, the limbic system, brainstem and spinal cord. So the prefrontal cortex, again, is that executive functioning, the limbic system is the pleasure and reward. The brainstem is what we worry about that that affects your cough and respiratory drives, your breathing, and the spinal cord is affected, affects your your pain. And so what happens during like pain, so immediately after tissue injury, the spinal cord receptors, which are responsible for that pain aspect, they become available. And those who are injured or in pain, they're able to tolerate large opioid doses without having that euphoria or high or, or risk of overdose. So the same dose that someone is using, when they're in pain, when they're not in pain, because those spinal cord receptors have closed, other other receptors are open. And so they could affect, you know, euphoria or overdose. And so people who are in pain, when they're receiving appropriate treatment should not really experience that euphoric effect. And hence, you know, reduces the risk of developing an addiction, though, we know that, you know, these substances have a high, high risk for for addiction, because a whole host of reasons, but people are often, you know, hopefully not as much anymore, but people are prescribed a lot more than they needed. And it was more widely available. And we didn't really understand how opioids worked. And not all of that that I won't really dive into. But you may, you may know about, and see. So what does opioid intoxication look like? So bradycardia has decreased heart rate, decreased respiratory rate, shallow breathing, pinpoint pupils, slurred speech, and people may experience a sense of euphoria or lack of pain, calmness, sleepiness. And then what does withdrawal look like? So kind of the opposite of those signs and symptoms. So increased heart rate, more insomnia, dilated pupils, sweating, muscle spasms, cramps, nausea, vomiting, diarrhea, anxiety. And the timing of the withdrawal symptoms. So it depends with how much was being used or how long they were being used. But just as a rough, like there's short acting opioids, and there's long acting opioids. So things like heroin, oxycodone, and fentanyl are very short acting opioids. So the onset of withdrawal can happen when someone stops using them within six to 12 hours, gets worse between 36 to 72 hours, and withdrawal lasts about five days. And then methadone, which is a long acting opioid, withdrawal takes about 36 to 48 hours, symptoms peak in 72 hours, and the withdrawal can last up to three weeks. And the way these substances work is, so a full opioid agonist essentially is like a lock and key with the mu opioid receptors. It's the perfect fit. And these include things like morphine, codeine, methadone, oxycodone, fentanyl, basically most narcotic pain medications. And they're highly reinforcing. And they have the greatest potential for non-medical use. I know methadone is on this list, but methadone is on this list because it's a full opioid agonist, but because it's a long acting medicine, and then we know it doesn't create, it doesn't give the same euphoria effects as some of the other short acting medicines or drugs do. Hence we use it for opioid, for treatment for opioid use disorders. Partial agonists essentially are an imperfect fit, but they still have some partial stimulation of the receptor. So the big thing in this category is buprenorphine. And Dr. Lam will chat with you folks more about this next time, but just to give you a sense of how this works. So buprenorphine is a partial agonist. And so it's less reinforcing. It's less commonly used in terms of non-medically, but hence why we use it a lot for opioid use disorder treatment. And because it has that partial agonist effect, there is a ceiling effect essentially of buprenorphine where while in methadone you can take a lot of it and overdose, and there is a risk for respiratory depression. And that's why people go to methadone clinics every day to assess for that and get methadone. And so buprenorphine, there's less of that concern because there is a ceiling effect where after a certain point, while there is still a risk for respiratory depression, especially if used with other medications that decrease your respiratory drive, commonly benzodiazepines, but there is less of that risk because basically all your receptors get bound to, and then it doesn't keep stacking up like some other full opioid agonists do. And then antagonists, they occupy the receptor, but they don't stimulate it. So things like naloxone, so Narcan, and then naltrexone, which is in the injection form, it's called Vivitrol. And so both of those bind to the receptor. Naloxone or Narcan does it very quickly, hence why it quickly pushes off all of the opioids that are on the receptor, and that's why we use it in emergency situations. And so naltrexone can be used as a treatment for opioid use disorder because it doesn't do it as quickly. You can still, if you use opioids and you take naltrexone, you can definitely have withdrawal because naltrexone does push all the opioids off. But we can use it as long-term treatment in the sense that naltrexone can decrease some of the effect in the dopamine pathway and so can decrease some of that reward effect from opioids, and we also use it in alcohol use. So I'm leaving it there because, so that's kind of like a push-off point for Dr. Lem next time to chat about more in depth with opioids and treatment and things like that. But those were the end of my slides. There's no link on here, and I think Emily will share one with you guys, but I'll stop sharing for now, and I'm happy to take any questions, thoughts. Yeah. I don't necessarily think the pressure is one of the thank you for talking to us today. It was very informative. Okay, good, good, no problem. I know we ended quite early, so I'm happy to give you guys your time back, but if there's any other thoughts, I'm sure you guys know how to get in touch with folks for that, but if there's anything, I'm just putting my email in here, too, if there's anything that you want to ask, personally, and it's a long name. Yeah, you're welcome, you're welcome. All right, thanks, everyone.

adolescent substance use

brain development

prefrontal cortex

nicotine

cannabis

alcohol

opioids

diverse populations

prevention education