 So, I will get started. I'm happy to be here. My name is Libby Stout. I am an addiction psychiatrist from Colorado, and Catherine invited me to come here and talk. I've actually been here a couple... well, virtually a couple of times and then in person, like once, to help with the marijuana issue. So, I do a lot of talking about marijuana, but I want to start. I'm going to talk about... this is my disclosure slide, and I'm happy to share these slides with anybody that wants them. And if you get them, then you can look at these websites because these actually are excellent websites for more information about marijuana. These are the things that I'd really like to cover. So, I'm going to talk about addiction really, kind of from my perspective, but I think it explains it, where most people can understand it, how it happens, and then talk about how I believe the worst drugs for the developing brain are nicotine and THC, and those are the two drugs that we kind of say, oh, that's not that bad. But I'll talk about why that is, and then talking about the components that are necessary for treatment. I have been working in this field for the last 90 years, okay, 90 years, 30 years, 30 years, and for the last 20 years, I was running a program in Colorado, which is phenomenal. It doesn't exist any more sadly, but it was a 90-day inpatient treatment program for people who have failed everything else. So, something funded by the state of Colorado, I didn't really have to have money to get treatment. 80% of the people that I treated were there as an addition of probation, so mostly had legal problems related to their substance use. And it was a very intense cognitive behavioral program for people with dual diagnosis, and we had really excellent outcomes. And I thought it being closed for the 20 years, and then finally they succeeded in including it because they think it's a very expensive program. It's a program that didn't exist anywhere else in the country, but it's like the ideal program, and I really wish that other places would take on the novel. So then I'm going to talk about all these things that I think should be a component for treatment. So to start with, I'm talking about addiction, and addiction happens in the part of your brain responsible for learning and memory. So this is a very important part of your brain because this is where we learn to do everything. That's important. And dopamine is the drug that's responsible for this, and it's the salient factor. So dopamine is the thing that says, this is really important, you should remember this. And so drugs have abused work in this pathway, and then they can hijack this pathway, which is the problem. Because this is a pathway that we have on purpose, it's to help us survive. And so if you think about the first time you ate something really good, and I have juicy hamburger, but I don't know if you don't like them, that might not fit you. But whenever you remember eating something really good for the first time, you get a dopamine release, it says this is really good, we should do this again. You do it over and over again, and it gets hardwired into your brain, and you don't ever forget to eat it. And so the next time I think about it, you drive past the place where you can get it, you get hungry, and you go get one. Then if you remember when you learned how to ride a bicycle, you don't probably remember exactly the whole day, you know, the whole incident, but you remember it was a really powerful experience, you were successful in riding it without turning wheels, and it's hardwired into your brain. And even if you don't ride a bicycle again for years, you can get on a bicycle and ride it because it's hardwired into your brain. So this is a pathway we have on purpose, it's to help us learn to remember to eat. So when you eat something, you get a release of dopamine in the nucleosacanopens, it says that was really good, you should do it again. And you do it over and over again, it's kind of hardwired into your brain. It's also for appropriation of the species. So the first time you have intercourse, you have a release of dopamine in the nucleosacanopens, it says, that was good, we should do this again. You do it over and over again, it's kind of hardwired in there, and you don't ever forget. You'll notice that with food, there's a one and a half fold increase with dopamine, with sex there's a two fold increase in dopamine. However, the drugs of abuse that work in this pathway are more powerful. So nicotine is more powerful than sex. So it's a two and a half fold increase. Opiates are similar to nicotine. However, what that slide shows is that the more potent the dose, the higher the release of dopamine. Cocaine is not on there, but it's a four fold increase. Methamphetamine is an 11 fold increase in dopamine. That's why that drug is so powerfully reinforcing. So somebody just uses that one time and they're like, oh my gosh, this is really something. I need to do this again. Marijuana, this was back then in 1997. That is when the highest potency of THC was around 5%. And that slide is showing that even though it's like food, one and a half fold increase, if you use the more potent variety, so it's higher dose of THC, you get a higher dose release of dopamine. And so this is what we're seeing now with the high potency THC. The high potency THC is more like methamphetamine. You guys in Vermont have done a really good job and you're the first state ever to put a potency cap. So your plant potency is 30% and your concentrated potency is 60%. In Colorado, our average potency of the concentrates is 69% and we have concentrates that are up to 99.9% THC, which we really do not want. But that's what we have. So this is the reward pathway and all of these parts of the brain communicate via glutamate. Glutamate is the major neuro excitatory chemical and it's balanced by GABA. And so the normal situation is that they are balanced. So if your brain increases glutamate, it increases GABA. And so it's always wanting to be balanced. I'm going to walk you through a scenario about using drugs. So say you used a drug for the very first time. You're going to release a dopamine in the nucleus that sends a message to all these different parts of the brain via glutamate. So it sends a message to the amygdala, which is your warning system or your scout that's kind of scanning the environment all the time, warning you about stuff. It says to the amygdala. Next time you see that guy that gave us that stuff, warn us, because he's got some good stuff. Then sends a message to your hippocampus via glutamate, which is your place where you put all your new memory and learning. Next time the amygdala sees that guy, remember what he's good for because he's got some good stuff. Then sends a message to the orbital frontal cortex, that green part of your brain, your motivational drive. Next time the amygdala sees that guy, go get him because he's got some good stuff. You just need to do that a few times and it's hardwired into your brain and you don't ever forget. Now, if you're doing this as an adolescent, that dark blue part, the prefrontal motor cortex is not working very well. And that's why you can't say, wait a minute, maybe that's not such a good idea. The other thing that shuts that off is using any addictive substance chronically. So if you're heavily using alcohol, that thing's not working. So you get this in this vicious cycle and I use this because I got this from a guy who's a trial and analysis psychiatrist and single, I think it's his name, this hand model for your brain. It kind of looks like your brain. And this is your reward pathway. This is your amygdala. This is your hippocampus. This is your cortex. You have your sensory cortex, your motor cortex, and your prefrontal most cortex. And this part of your brain, the prefrontal motor cortex, is the last thing to come online. It's the last thing to develop as an adolescent. It's not fully developed until mid-20s. And this has got protective factors because most of your inhibitory neurons, like serotonin or GABA, are located in this part of your brain. And so they're supposed to protect your amygdala. So my example of this is, you're walking through the forest and you see a stick on the ground. Your amygdala is going, oh my God, there's a snake, there's a snake. Oh, we need to run away. If you've got an intact prefrontal motor cortex, it's saying, oh, calm down. It's just a stick. Or if it's a snake, this is what we need to do. We need to back up, walk away. If this isn't working, then you're just freaking. You have to keep freaking. And you have to run away or fight or something. And so this is what happens during development. It takes a long time for this to come online. But if you're using substances, this is not online. And that's why people that are afflicted with things can't control their amygdala. And so I use this when I'm talking to patients and they come up to me and say, I think I'm right back here. Because when you start using substances, it's when you stop developing. And so I have worked with many, many people in treatment who are 35 and they're acting like they're 13. Because they're really back to where they started when they started using substances. The good thing is when they stop using substances, then development happens a lot faster. You don't have to wait years. But anyway, that's how that happens. And it's all by glue to make. And this is measurable. And so there's a single long-term potentiation. And what that is is, and it was in the learning literature for a very long time before it got into the addiction literature. And what that means is, when you do something for the very first time, you get a release of dopamine. The next time you do it, you get an even more powerful release of dopamine that really reinforces the learning. And that is because of the increased glutamate. And you can measure that by glutamate receptor ratios. And so this is AMPA versus NMDA. One of the other things that causes increased long-term potentiation is stress or trauma. So they've done experiments with animals that just stress one time can increase long-term potentiation. This is really good support for why children who have been abused or neglected or traumatized growing up are more susceptible to addiction. This is why you do the ASIS score. The adverse childhood experience score and treatment programs should be doing that any time you admit somebody for treatment. You should get an ASIS score to find out where they are, what happened to them, because they got long-term potentiation from that trauma. And you wonder, well, why would that be helpful? Well, it's supposed to help you. When you have a bad experience, you're supposed to learn from that so that you can avoid it in the future. The reason why people don't, though, is because of the effect of these drugs on the hippocampus. So I'm going to talk about that in a minute. But anyway, these kids, the first time they use a substance, they get a really powerful dopamine release because they already have long-term potentiation from the trauma or stress. This is a really great study. I really think it's fascinating. You have to use animals because you have to chew up their brain to extract the receptors or the glutamate. But what we're seeing on the left are the saline. Saline is salt water. That's the control. So that's the normal glutamate receptor ratio. All drugs of abuse cause long-term potentiation and they all do it in the exact same way. So the brain doesn't really see them differently. Drugs that are not abused do not work in this pathway. So what we have here are fluoxetine or prozac, or amazapine is tigrotol. These are psychiatric drugs. They don't cause long-term potentiation. That's why psychiatric patients have difficulty remembering to take their medication because there's no salience associated with them. You don't take a prozac and go, oh, that was really important, I should do that again. You just have to remember to take your medication. And then stress or trauma causes the most long-term potentiation. Then what happens with the dopamine is we all have mood swings. We all have ups and downs. You use an addictive substance. You get this really high, great release of dopamine and you feel really, really good. But then there's this crash and burn that comes down after it wears off. And then the more you do it, the more you deplete your own central stores of dopamine. And so you get to the point where you have to use just to feel normal because you've done that to your brain. The answer, though, is that recovery is completely possible. What we're looking at here, the most important part of this slide is the red. So the red are the dopamine, two receptors, and your reward pathway. If you look at the person on the left, this is somebody who's never used methamphetamine. They have a lot of red. So they have a lot of dopamine. The middle person is somebody who is a metabuser, one month absent in it. They have hardly any red at all. This is why these people have crash and burn depression. And we cannot really help them, psychiatrically, because antidepressants are dependent on your own natural stores of chemicals. And so if you don't have the chemicals, the antidepressants can't really help. But what does help is time. So people have to have time away from the drug. They have to be doing things healthy like eating healthy, exercising. And then that same person 14 months later, their red is back, meaning the dopamine has returned. That's a really positive statement for people because that means that recovery is possible. And the other thing is the hippocampus. So the hippocampus is where you put all your new memory and learning. And it is what we now know is an area that has neurogenesis, meaning there are new cells being born and differentiating every day in your hippocampus. It makes sense because you're learning something new every day. And you need to have new cells to put that into. However, if you're using any addictive drug chronically, you can suppress neurogenesis in your hippocampus and it actually can shrink, meaning it makes it difficult to learn new things. So the things that affect this are all these drugs, and it includes nicotine and it includes THC. And the other thing that affects the hippocampus is stress or trauma. And that can also shrink the hippocampus and decrease neurogenesis. And this is why people who have been traumatized then tend to not learn from their experience because they can't learn new things or it's more difficult. This is why I have been an advocate my entire career for treatment programs being tobacco-free. And so I go around the country trying to teach programs how to do that because very few programs actually are. But I think that especially inpatient and residential programs, they have no excuse. And I think they're stealing people's money because if you're sitting there in treatment doing this the whole time, you have a really difficult time learning anything new because it's shrink-shared hippocampus. And of course this is studied in animals as well. And so this is a fascinating study that they do to test all drugs. So all drugs have been tested in this way. This is how you know you have a smart animal. So you have this big, better water in the middle of the room and somewhere under the surface is a little block of wood. And you put the animal in there like a rat or a mouse and you calculate how long does it take until it swims and swims and swims and bumps into the block of wood and then can get on it. I'm not going to drown now. You know that's animal smart but you put pictures all around the room. And when it's sitting on that block of wood it can triangulate where it is in the vat so that the next time you put it in there it goes right to the block of wood and you say, boy that is a really smart animal. They've taken animals like this and studied all drugs. So they drug them up. And this is true for nicotine. This is true for THC. This is true for any other drug that's addictive. And they can now find that block of wood in their life. They have to keep swimming around until they bump into it because they cannot learn something new. And so this is just an example of a study like this where this is control where this is the normal amount of time that takes them to find the block of wood after they've learned. This is a sham which means they gave them like salt water or something so they find the block of wood. And this is morphine nicotine opium. Morphine plus nicotine opium plus nicotine. They have to keep swimming around until they bump into it. That's really sad. However, recovery is possible because they found that if they take the drugs away and put them in a rat park where they have all their friends and they can eat healthy and they can run to their heart's content on these little wheels within a short period of time they can find the block of wood. Because one of the things we now know is the best thing to improve neurogenesis in your hippocampus is voluntary exercise. That's why treatment programs should offer exercise every single day because that's the best way to start healing your brain so that you can start learning something new. So you need to get rid of all the drugs including tobacco and then exercise. This is a thing that sets people up for addiction is exposure. So if the developing brain is exposed to the drug it can actually prime the brain. And a lot of the priming happens because of smoke. Because a kid can't control that their parents are smoking. And this is smoking anything. So if it's in the air and you're breathing it, it is in your brain. This is actually how they got smoking out of airlines. If you remember the olden days where you could smoke in an airline it was all the back of the plane. They actually did this study that was a three hour flight where they took people in the front of the plane who were non smokers and they peed in a cup at the beginning of the flight and at the end of the flight they had enough nicotine in their urine as if they had smoked three cigarettes. And they weren't smoking but it's in a closed environment so it was in their body which means it's in their brain. So this is something that happens the other way that people are exposed is poorly like somebody who's been prescribed opiates or an acute injury so that primes their brain. It doesn't make them an addict but it makes them potentially prime them especially if they're doing it as adolescents. So this is also studied in animals. So this is a study just showing that if you give an adolescent rat nicotine they're more likely to press the lever for nicotine than if they're given as an adult. And this mirrors what we know in adults for smoking cessation because what we've learned from research on that is that if you start smoking before the age of 19 it's very difficult to quit. If you start smoking after the age of 19 it's easier to quit. And the brain is cross-tolerant it doesn't see these drugs differently and so this is a study showing that if you give an adolescent rat nicotine they're more likely to press the lever for cocaine. This also happens in adults when it's not as powerful as in adolescents and then this is showing that if you give an adolescent rat riddling they're more likely to press the lever for cocaine as an adult than if they were given saltwater. And this is why when I talk to prescribers I caution people when you're prescribing stimulants to young people for ADHD you should get a really thorough history because if these kids have trauma abuse, neglect, bad things happening they already have longer potentiation from that and so then you give them this addictive drug then they are more potential to then use it addictively. I mean there are lots of people my colleagues who believe that if you treat ADHD aggressively as an adolescent you protect them from getting substance abuse which I don't agree with at all but it's the population I work with because pretty much everybody I treated who was methamphetamine as their primary drug used riddling or Adderall as a kid but they also had really high ASA scores and so I think that that's one of the things you have to really pay attention to. So we're starting to see the same thing with marijuana so this is exposure data this is pregnant women using marijuana during their pregnancy and the effect on the offspring and so this is just comparing women who smoke marijuana while they're pregnant to women that don't and the kids that were exposed in utero to cannabis had significantly impaired intellectual functioning compared to the ones who were not exposed and then this is the ABCD study which is a very big prospective study that is ongoing now in this country looking at kids in their development and this was published back in 2020 looking at the kids were exposed to marijuana prenatally have a greater incidence of psychopathology as middle school children so they have a greater incidence of like psychotic symptoms or behavioral problems and then this was just came out this year just very recently and this is following them to adolescence showing that that continues to be the goal of what's happening is that the kids are exposed prenatally to marijuana they have a higher risk of psychiatric disorders and problematic behavior compared to the kids that are not exposed on intra-utero and the ones that are showing the biggest exposure to are having increased conduct disorder and aggressive behavior rule-breaking behavior now that exposure can prime the brain but it does not make the person an addict what makes the person an addict is they have to engage their prefrontal motor cortex to make a decision to use the drug whether it's you know like inappropriately or you know use it so that the drug can actually hijack the brain that's how the drug hijacks it and I learned this by having tobacco-free programs because I would you know talk to people about their tobacco abuse and get that history and so I'd ask when did you start using tobacco and it was usually around 13 and I said well why did you start using it and I invariably got this story from many many people and they would say things like I don't know why I ever started smoking I hated the fact my parents smoked they smoked all the time the car that smoked in the house I was stealing their cigarettes I was flushing them down the toilet I said well then why did you start smoking well I don't know my friend gave me a cigarette when I was 13 and I was hooked like that and there is research out there demonstrating that that can happen so basically that kid was exposed his entire life to tobacco smoke but never made the decision to use until that other friend gave him a cigarette and that allowed the drug to hijack the burning and so anyway that is what causes the addiction problem and so that's like somebody who has been using opiates for pain and they've been using them appropriately and then makes the decision to snort them or take more than they are supposed to that's when the addiction hits you and so there's actually this psychiatrist in Florida who's been using this data to try and explain why anesthesiologists have the highest risk of addiction in the medical world and he actually is showing that he thinks it's fentanyl exposure because that's the number one drug that puts people to sleep in the operating room so it's injected into the body and then it goes to the body and it's breathed out by the patient and so the person sitting next to the head closest to the head longest in the room is the one most exposed that doesn't make the person an addict but I can absolutely see this happening where somebody goes I wonder why people like this so much and so they have a little bit of fentanyl left over and they take some and put it under their mask on their gum it can be addicted like that and that's really scary