here so bright and early. Whoa. And then the lights were on. All right, well, it is morning here now. Thank you guys for coming on this lovely Sunday morning, enjoying your breakfast with us. I am going to get the slides loaded here. Let's see, there we go. Oh, nope, wrong one. You guys are very early for the symposium. So while we're loading the slides up, I'll go ahead and make some introductions. Again, welcome. Thank you for your being here for your last day of this awesome conference. I think it's been a really great conference. We hope to make this an engaging and enjoyable way to spend your Sunday morning. My name's Carla Marienfeld. I'm a professor of psychiatry at the University of California in San Diego, where I'm also the program director for the Center for Psychiatry and Psychiatry in San Diego, where I'm also the program director for our Addiction Psychiatry Fellowship. We have two other co-presenters here with us, and then two discussants. So our co-presenters are Dr. Joshua Lee, who is a professor of medicine at NYU and the program director for the Addiction Medicine Fellowship there, and the originator of the concept for this symposium. Then we have Dr. Brian Hurley, who works for the Department of Public Health in Los Angeles County and is the current president for the American Society of Addiction Medicine. To my left, we have Dr. Larissa Mooney, who is a professor of clinical psychiatry at UCLA and the immediate past president of the AAAP, and Daryl Shorter, who is an associate professor of psychiatry at Baylor College of Medicine and the medical director of addictions at the Menninger Clinic there. So welcome to our great panelists for agreeing to do this with us. And I think we're waiting for another couple moments on our slides. So I guess I can talk just a little bit about our process. We'll go through the methodology a little bit more in depth in just a moment. Or I don't know if, Josh, you want to speak extemporaneously. There we go. Never mind. No extemporaneous speaking needed. All right. So welcome, everyone. So we're going to be talking about what we call the High Impact Publications, right? So these are publications that are ranked using a certain metric that we thought were interesting and relevant to discuss. This is our disclosure slide, so we do have some disclosures for you to be aware of. The educational objectives for this session. So at the end, we hope you have some increased awareness of some of these key studies that got media attention. So this is specifically focused on studies that got some media attention in our field that you have an increased working knowledge of some of the key findings in these studies that are being picked up by the media, and that you're going to be able to discuss the clinical utility and methods for applying some of the knowledge, right? So our discussants really are going to focus on some of the clinical implications of what these studies are saying from these key findings. All right, and with that, Josh. Josh. All right, thanks again. It's always wonderful to be a triple AP as a non-psychiatrist, to infiltrate your meeting and find out what you do. But we have been doing this at ASAM for a couple of years with Sarah Wakeman, who's at Mass General, another general internist like I am, and in addiction medicine. And we were kind of invited by the ASAM committee to put together a new greatest hits the year that was review presentation. And we kind of rethought the usual way of doing that, which is what Brian, Carla, and I think were the biggest articles. Let's just say what we think. We try and do a systematic scan of the literature. If you type in addiction medicine, quote unquote, into PubMed, you get about a million plus results. And then if you narrow it down to the last calendar year, you'll get about 50,000 to 60,000 results. And then that's kind of our starting point. We narrow it down using the biggest journals. We don't want to miss anything that was in New England journals, so we'll search that kind of specifically as a journal. We will review key search terms. And then we'll get to addiction specialty journals. So all our favorite smaller journals in our field from addiction on down, which is, by the way, the highest impact factor specialty journal, addiction, the journal, but all the way down to AAAP's journal, ASAM's journal, JSAT, all the rest. Those you can search kind of by table of content. So you look at essentially every article published in the last year. And we do this using an altmetric score. Altmetric is a proprietary, I think they're even a for-profit company, but they've generated a score that your article gets. If you get tweets, if you get likes, if you get citations, if you get media mentions. And so it was kind of half and half driven by media and Twitter over the years. Twitter's obviously changed a lot for many of us in the medical field. It's probably not used nearly as much as it was, say, pre-COVID and pre-Elon Musk. So the altmetric score more and more reflects media attention. What gets picked up and what wire article gets rebroadcast across 20 other outlets, and that's going to drive the score of your article up. So there's some caveats there. That's not necessarily the most important thing to our patients. It's not necessarily the most important thing to my practice. It's not necessarily biologically the next breakthrough. Those may not rate very highly or be kind of recognized in the moment as important articles. But we have no other way of kind of ranking what's the hot article. And this is the way we've gone. OK, so we wound up with a list, literally a spreadsheet of 117 papers. Again, that's kind of boiling down for around 60,000, which would have been kind of eligible for this list. And then we're going to show you the top 10. And then we're also going to talk about some of the other ones we found really interesting within certain themes in the longer list. A lot of what shapes the news, and therefore what of our articles are picked up, reported, and kind of given attention to is what else is happening. So cannabis legalization has been a huge news story, really, for over a decade now. Any kind of thing about cannabis or older people use cannabis from a latest survey or from somebody's relatively small study, if you can get kind of the right keywords into your article, that can really zoom up the charts in terms of what the media does with it and then what your resulting altmetric score is. So a lot of what the hits are from the last year reflects what's been covered in the news, from kind of general population interest stories to Matthew Perry to what happened kind of politically. So here it is. Drumroll, please. The top 10. The biggest paper we saw, yeah, was from Chris Jones. And if you know that name, it's really like a new Beyonce album every time Chris comes out with a paper. He works for the government. I believe he is currently at SAMHSA, or the FDA. Is it SAMHSA? Anyone know? Yeah, and he gets great government data, and then he puts out important articles, along with many other esteemed co-authors, usually from NIDA and all the other agencies. But this was an estimated number of children who lost their parent to drug overdose in the US in 2011 and 2021 in JAMA Psychiatry, and Brian's going to cover that article. You might also note how the JAMA journals are looking on this list. They're looking great. It was a big JAMA year from big JAMA, but especially JAMA Psychiatry. And JAMA Network Open will show up in this list with a ton of articles. So good for JAMA. And then you see down at number three, just to jump there, addiction. This is the highest ranking article in addiction. You could say it's the highest ranking article in an addiction specialty journal in the last year, and that is looking at problematic opiate use in chronic pain patients with non-cancer pain. And I believe we covered that. And look who the author is, Tom Costin, I think. I think I wrote that name wrong. All right, and number two, this got a ton of attention in and out of the organ policy changes, and that was an observational and kind of modeling study about the organ drug law changes, Oregon and Washington, which for different reasons over the last three years had drug decriminalization, and then of course, Oregon has swung back to kind of recriminalizing drug possession and open drug use. But the point of that article was that it probably wasn't this change in drug laws, which was essentially a more liberal policy that had to do with rising overdose rates in Oregon, but that was a political mess for that policy. Overdose rates went up, and they tried to change the policy. They have changed the policy since back to criminalization. Number four, looking at kind of how we've been prescribing meds through COVID. Number five, looking at Delta H THC, which is of course not Delta 9, but it's hemp-derived psychoactive kind of gas station version of cannabis, and that's become very, very popular looking at adolescent use. To the kind of bottom of the top 10, there's number five again. And then we'll get to an e-cigarette article in JAMA Network Open. Overdose crisis in US adolescents. Number eight, a semiglutitude, semaglutide, I can never pronounce it, but looking at GLP-1s. This is the first time a target trial emulation or a kind of synthetic trial on observational data has made our top 10 list, so interesting kind of methodologic moment for this presentation. And then looking at alcohol consumption in older adults, and finally risk of incident psychosis and mania with prescription amphetamines, and we're going to cover that one. So that's your top 10, and now I'm going to hand it to Brian. Thank you, and good morning. So with those top 10, we were faced with, how do we present this in a way that's cohesive, coherent, educational, and compelling for 8 AM on a Sunday morning? And so these were the themes that we came up with. We were sort of looking through the top 10. We said, well, there's kind of an overdose theme, looking at both opioids but other drugs both opioids but other fourth wave opioid combination with stimulants. There's a cannabis theme. There's electronic nicotine delivery systems. There's rapid high dose or novel buprenorphine starts. There's the semi-glutides, and there's stimulants. And then we also noticed that there was articles on older adults and adolescents. Some of that we're covering in overdose, but we're not sort of covering that as a separate topic. What we're going to do this morning is each of the three of us are going to each take two of these themes and present articles that were published within the last year that we thought were important to the theme, which means two things. The first thing is we're going to be covering articles that weren't in the top 10, but which we liked. This is a curated list of articles. We're not stuck to top 10. Second thing is there were, we were covering almost every article in the top 10, but not every article in the top 10. So in other words, this is a curated, our favorites presentation, not just strictly methodologically the top 10 altmetric articles. So our favorites, an in-depth review of 2024. I'll go ahead and kick us off with the topic of overdose. We've been in the worst overdose crisis in American history. That is not new information. What is new is that overdose deaths have sort of fallen for the first time since 2020 between 2023 and 2024. This article, this is a not great resolution screenshot, as it turns out, from NPR showing a 10% decrease. And I think the last I looked after these slides were due, but before I, anyway, was like 14% decrease as we went from 2023 into 2024. So it looks like there are now shifts in the overdose crisis. And the literature actually sort of speaks to what do we know about the impact of the overdose crisis. So this is actually two, this is one slide with two studies on it. The first study was the number one article, the Jones-Jama psychiatry study that looked at the count of children who lost a parent to overdose in the United States in the decade between 2011 and 2021. It was 321,566 children. One of the reasons this is important is we sort of think about addiction as an individual illness, a family illness, a community illness. And clearly, this is going to have impact on adverse childhood experiences. There were significant disparities across racial and ethnic groups, though. So there were certainly disproportionate impacts of which children were impacted. The second article is a Friedman New England Journal of Medicine article that shows something that we've actually known for a while, but this was a pretty big trial, showing the adolescent overdose rates are going up, but adolescent substance use is going down. So if you look, so one of the drivers of adolescent substance use, from my vantage point, is not that more adolescents are using, it's what people are using. It's the composition of the drug supply, not the prevalence of drug use. Moving forward, there was the Joshi-Jama Psychiatry Cohort Study that did this sort of synthetic control analysis. Are laws that decriminalize drug possession, do they impact fatal overdose rates? And the answer is this was a negative trial that showed that the overdose rate did not shift one way or the other in Oregon and Washington with laws decriminalizing drug possession. Moving forward to the HEAL trial, some of you probably heard this was one of the largest funded NIDA initiatives, actually, in history. And it was a 12-month multimodal intervention that involved community coalitions deploying overdose education and naloxone distribution, medication for opioid use disorder, and prescription opioid safety, all of which were hypothesized. If you do each of these things, it will lower overdose rates in the community. That was the idea. And as it turns out, it was a negative trial. The HEAL study was a negative trial. Coalition implemented OAND, MOUD, and prescription opioid safety did not seem to impact the death rates between the intervention groups and the control groups. Of note, the HEAL study launched, and then we had a pandemic. Less than 40% of the evidence-based practices associated in the protocol was initiated. And then this was a trial out of Connecticut looking at what do we know about the death rates associated with different treatments. So for opioid use disorder, for opioid use disorder, no treatment, had an overdose death rate of just under 10 per 1,000 individuals. What do we know about the overdose rate during the trial period? Methadone and buprenorphine lowered that. Short-term and long-term psychosocial treatment without medication for opioid use disorder seemed to increase the death rate compared to no treatment. And one of the other things around overdose, New York City is the only city that openly operates overdose prevention centers in the United States. This was a cohort study of administrative data asking the question, if you open up an overdose prevention center, what impact does it make on crime? 911 calls for crime, drug possession, criminal court proceedings. So it sort of looked at the impact on crime, and the author said, and disorder in New York City. And the answer is there was no significant increase in crime, 911 calls for crime, medical incidents or unsanitary conditions reported in New York City neighborhoods where the two overdose prevention centers were located, and there was a decline in arrests for drug possession and criminal court. That is what we had to present on overdose. I'm now moving to the cannabis thing. If you've never seen a cannabis plant, behold. This is what it looks like. All right, so cannabis. Again, this is one slide with two studies on it. The Monitoring the Future survey, which is a survey of high schoolers, found that 11.5% of 12th graders, according to the survey, reported delta-8 THC use. And it seems to be highest in states without cannabis legalization, or without regulating delta-8 THC. In a separate study, a cross-sectional analysis of adults, and so this is the AmeriSpeak survey, they asked about self-reported emerging cannabinoid use. So there's cannabidiol, which many of us are familiar with, but delta-8 THC, which is, again, a minor component of THC that you can extract it or manufacture it using other cannabinoids. There's actually cannibarol, and then cannabinol, which are other kind of emerging cannabinoids that were found on this AmeriSpeak survey. Edible cannabis. In a cross-sectional study in Ontario, this study looked at emergency department visits for older adults in the pre-legalization period versus sort of the legalization of cannabis flowers versus the legalization of edible cannabis. So there's sort of phases in the evolving legal landscape of cannabis in Canada, and found that essentially ED visits related to cannabis poisoning went up during this period of time between pre-legalization and legalization of the cannabis flower. But there were some things, particularly around edible cannabis, that seemed to spike the ED visit rate. And what do we know about cannabis tobacco use and COVID-19 outcomes? This was a cohort electronic health record study that asked the question, is cannabis use associated with COVID-19 related outcomes? If you get infected with COVID, are you hospitalized, in the ICU, and do you survive? And there was an association between people that used cannabis that when they were infected with COVID-19 seemed to have a higher rate of hospitalization and ICU admission. There was no difference in death rate. There's a couple prenatal cannabis studies that came out that I thought were worth discussing. One was a retrospective cohort study looking at pregnancies in Northern California. So they looked, again, retrospectively. And they found that cannabis use was associated with a higher risk of gestational hypertension, preeclampsia, a weight greater than guidelines, and percentile abruption, and a reduced risk of gestational diabetes. And cannabis exposure and adverse pregnancy outcomes, this was a multi-center observational cohort. They found that adverse pregnancy outcomes, so what they were particularly looking at was small for gestational age birth, medically indicated preterm birth, stillbirth, hypertensive disorders like preeclampsia, found that people who used cannabis, and this was assessed by urine assay, had a greater risk of these adverse pregnancy outcomes. And so I think we move forward to our, oh, ah, oh, yeah, thank you. OK, cool, yeah. So we now move forward to our discussants. So Dr. Moody, we just presented on the cannabis topic. Any reflections? Thank you. Can you hear me? Perfectly. Great, and it stays on. Yes, I will make a few comments about the cannabis papers that you discussed and their clinical implications. I was interested in these papers that are starting to describe prevalence of these emerging cannabinoids. These are cannabinoids derived from hemp plants. They're manufactured from hemp plants, so they're federally legal. They are available online, in stores, often without age verification. Some states are moving to ban some of these at the state level. So the findings were interesting around adolescent use, and I think that's particularly important, because delta-8-THC, for example, has intoxicating effects, and knowing that it's being used more commonly in states in which adult cannabis use is illegal makes sense. These are going to be perhaps more available, but there are particular risks to the adolescent developing brain and potential for psychiatric reactions, effects, and neurodevelopmental changes and also addiction. So I think we have to pay particular attention to perhaps screening more. I was also surprised by the rates in the other study of knowledge of these emerging cannabinoids by name. The percentage of people who had heard of Delta ATHC and the others, people are becoming aware. They're seeking them out for pain or sleep or other same conditions for which some people seek cannabis. And so for myself, I thought I should be screening more for these, asking patients specifically about them, and paying particular attention, though I'm an adult psychiatrist. For adolescent use, I think it's particularly important. I think it's also interesting you mentioned the fact that they know what these are, but we don't. Right. We know so little about THC because of all the limitations in trying to study it, and we know even less about what Delta A might be. And so I think that's a really important clinical kind of thing. How do we really try to prevent harm from something that we really don't even know what the harms are? We need to learn more for sure. And then the second group of studies I'll comment on are the emerging evidence for risk during pregnancy. And I think this is particularly timely because we're learning that more women are using cannabis during pregnancy, and this is also related to perceptions of safety being a natural substance. And these studies really support the idea that these are risky in pregnancy. And the one study in which they used validation of samples, urine, that was unique because many other studies have relied on self-report, and there was even a dose effect of greater concentrations, quantitative THC being associated with worse pregnancy outcomes. So again, screening and education more definitively about the risks of cannabis use in pregnancy. And I have patients who come in and tell me that the dispensaries are recommending cannabis for nausea and pregnancy-related insomnia and things like that as healthy alternatives for managing these things and all natural, et cetera, et cetera. And so I think your point about this being actually dose-confirmed is really critical. We published a paper a few years ago using the California registry that did not get picked up by Altmetric, but there's a number of papers showing these sort of adverse associations with cannabis, and I'm glad it is kind of finally getting picked up by the lay press because that message needs to get out there. One other thing that I would add is that when I was reviewing the articles, I thought a lot about collaboration with other specialties and the amount of communication that we have within the silo versus outside of the silo. So to what extent are we speaking with the OB-GYN folks, the internal medicine folks about these very same issues that impact all of our patients? It's great that we're talking about this here, but I would love for this to be presented at the American College of Obstetrics and Gynecology as well. Yeah. That's a really good point. One final point from one of the studies was there was greater harms if cannabis was used throughout the pregnancy than just in the first trimester. So not just the dose, the quantity in the samples, but the duration of use throughout pregnancy. Yeah. I think that's an important point because we often are so focused on the first trimester and the developmental tasks going on at that particular time, and then we sort of think that things are safer once the nascent brain is a little bit more developed, and that's not actually the case, but I just want to highlight your point. I think our role when we're talking about how do we want to make these articles relevant for people? Well, we want you guys to be aware clinically in how this might affect your populations, but I think, Daryl, your role of us in so few numbers is really as a liaison as well to educate our colleagues, and so we need to be kind of aware of our own data in order to then help disseminate it more broadly. So there was another topic that we touched on, the topic of overdose. Just a small little topic for us to discuss, and of course, I got the number one article. So I tried to group these articles into subcategories, one about overdose and children and adolescents, and then the other in terms of interventions that have an impact on overdose, and so if we look specifically at the articles related to overdose and children and adolescents, it's not terribly surprising that these articles ended up in our top ten list. What I think is interesting about these articles, however, at least number one especially, is how it highlights the disparities in terms of race and ethnicity, and really looking at how American Indian and Alaskan Natives have been quite disproportionately impacted by the overdose, children have been impacted by the overdose epidemic, as well as black African Americans. This sort of mirrors what it is that we've been seeing in terms of opioid overdose deaths in these very same communities, and so it's not terribly surprising that we would see the children from these communities disproportionately impacted. So when we zoom out from that, thinking about clinical implications, I thought about those from a couple of different standpoints. One, how do we prevent opioid overdose deaths among racially minoritized individuals with children, specifically? So to what extent are we building programs that are focused on pregnant and parenting persons with opioid use disorder? How inviting and welcoming are our clinical environments for those particular populations? Do we have places that provide childcare while people are actually receiving treatment? What about residential treatment? Can people bring their children with them while they are also receiving substance use disorder care? And again, I think it speaks to that collaboration and partnership piece where we have a responsibility to go to other specialties and other fields to make sure that we're building programs that are much more inviting and can help retain patients that are pregnant and parenting. The other piece is to, of course, try to reduce opioid use among minoritized individuals so that we don't get to the point where we have over 300,000 children who have lost a parent. And so again, these opportunities for collaboration and partnership with community organizations, with Department of Children and Family Services, even sometimes with the jail or the court system really provide opportunities for us to incentivize people in very different ways perhaps to engage in recovery. The utilization of peers, matching caregivers with peers, both before the development of the substance use disorder as well as perhaps if someone is parenting someone that has lost a biological parent to an overdose, what are we doing for that kid in that case? What are we doing for that family in that case? And then thinking about school-based care and home-based care. So those two articles gave me a lot to think about in terms of the way that we set up our systems in taking care of folks. So then after that, we switched to the interventions. And just thinking about them more broadly, either it was helpful, it was harmful, or there was no effect. It seemed like there's no effect in terms of the drug decriminalization. It's not that opioid overdose went up. It also did not go down. I think for opioid communities, the takeaway for that wasn't necessarily that there was no effect. I think the takeaway from that one is that they were able to successfully mobilize communities to interact, community partners to interact with each other in a way that provided for an opportunity to implement evidence-based practices. So I've actually thought that that was a positive from this particular study, and again, gives us hopefully some energy and some fire in the gut to get out of our silos and communicate with community partners. And then the final bit that I'll offer is that I end up having lots of conversations with people about the importance of using medications for opioid use disorder. And depending on what field of specialty they may be in or what discipline they're in, certainly if they may have lived experience, it can be very difficult and very challenging to convince people that medications for opioid use disorder actually save lives. I live in a state where we preach a lot of abstinence. We don't support a lot of harm reduction. And so amplifying this message can be critically important to save lives. Not only that, we need to be able to tell people that to not give them those medications is actually worse for them. And so that is the takeaway from my article. Thanks. Thank you guys very much. Great discussion for that. And I'm just going to take an opportunity at this transition point for all the trainees in the room. The Friedman article was written by a medical student and published in the New England Journal of Medicine. He's currently a PGY-1 psychiatry resident in our program, but there are opportunities to engage with people and end up having really high impact publications. You could be featured on Sunday morning. You could be featured at the AAAP. I mean, that's what more could you ask for? All right. So we're going to switch gears and talk about GLP-1 agonists and GYPS, which are all the rage in all the news. And what the heck are these things? What do I keep hearing about them? So they're both incretin hormones. So they all play a crucial role in regulating blood sugar levels and appetite. And so they come in kind of two forms. One are the GLP-1 agonists, which stands for a glucagon-like peptide 1 agonist. So these stimulate insulin release when you have high blood sugar, they suppress glucagon, which is the hormone that raises your blood sugar, they slow gastric emptying, which helps to regulate appetite and food intake, and they promote a feeling of fullness. So the examples of the GLP-1s are the dulaglutide, semaglutide, and liraglutide. So GYP is glucose-dependent insulinotropic polypeptide. And this has a synergistic effect. It's not as effective kind of by itself, but there is a medication that has both of these things called terzepatide that is probably the most impactful for weight loss. So weight loss, insulin, hormones, endocrine, blah, blah, blah, what does this have to do with us? So the idea is that they promote this sort of sense of satiety and satisfaction. And in a lot of anecdotal reports, and now some emerging evidence, there's evidence for these being helpful for that same sense of satiety, that lack of desire to use substances across a number of different substances at this point. And there's even been some reports about well-being and depression and other things with these medications. And so I think my simplistic understanding, I think about them as promoting satiety, but then my other simplistic understanding is I think about them as that gut-brain access, something's going on there with our digestion and our gut and all the rest of us. So on that top 10 list, the number eight article was this one, which was looking at semaglutide for tobacco use disorder. So both of the articles that I'm going to talk about here are relating to people who have type 2 diabetes and so who are prescribed these for that indication. These meds are FDA-indicated specifically for type 2 diabetes. And so all of this data that we're using, these are off-label when we're talking about using them for substance use disorders. So there was anecdotal reports about reduced smoking desire. So again, this was like an emulation trial where they're sort of mimicking this using real-world EHR data. And they were looking specifically at tobacco use disorder-related healthcare measures. And so semaglutide was associated with significantly lower risk for tobacco use disorder-related healthcare measures, particularly within 30 days, right? So not only is it associated, but it's associated pretty quickly with a response. And we all know how behavior works in humans. If you don't pair the behavior with the effect of that behavior quickly, we don't learn that quite so well. So there's limitations to this study, documentation bias. They're using EHR data, confounding, missing data, et cetera. But overall, this got a lot of press and excitement. This is another study that wasn't in the top 10 but got a fair amount of press coverage as well. And this is looking specifically at semaglutide and opioid overdose risk as well as opioid use disorder. And I think this study is directly leading to, there's going to be a clinical trial now looking at trizepatide in buprenorphine-maintained patients and looking at OUD outcomes. But this study was a cohort study, and they used, again, electronic health records using this Trinet X analytics platform over a six-year period. And they were comparing semaglutide specifically to a kind of pseudo-control of other anti-diabetic medications. And the results are that semaglutide was associated with a significantly lower overdose risk compared to the other anti-diabetes myth. Not shocking. We're not really thinking that insulin helps reduce overdose, but it's good to confirm it. The hazard ratios went from 0.32 to 0.58. And so, again, more compelling evidence across a very different substance, you know, going from tobacco to opioids, that, you know, these medications might have a role to play in our field, and there's a lot of excitement about it. This study also had some limitations, unmeasured, uncontrolled confounders and biases. It's also an EHR study. So we really do need to move into the, you know, the controlled, randomized, double-blind, placebo-controlled trials kind of world for these things. Switching gears to start talking about stimulants. So what's new in stimulants, right? What's new in prescribing stimulants and using stimulants for treatment? So the number four study that came up on our top 10 list was this one, trends in incident prescriptions, right? So new prescriptions for behavioral health medications. And this study looked at a bunch of different new prescriptions for all kinds of different psychiatric meds, including antidepressants, benzos, category two controlled substance stimulants, non-stimulant ADHD meds, and buprenorphine as their sort of broad categories. And what they noticed across all meds was that there was an initial drop at the onset of the pandemic for prescribing psychiatric meds. This was probably due to difficulties with accessing care and all kinds of things like that. But then as the pandemic progressed, the new incident prescriptions for ADHD meds, especially the stimulants, the schedule two stimulants, significantly increased during the pandemic. This was most notable in young adults and women. And then again, once after that initial drop, there was no change in rates of prescription for other psychiatric meds, despite well-documented increased rates of loneliness, a loneliness pandemic, increased rates of anxiety, depression. We really didn't see that move the needle on prescriptions outside of the stimulants. So there's, and then cynically I noted that nurse practitioners had the largest increase in prescribing across all drug classes. So strengths, this is comprehensive national level data, limitations, any sort of association study, we don't have causal relationships. We don't have any other clinical information about whether this is appropriate increase in prescribing or inappropriate increase prescribing. I think there's still some controversy, is this an unmet need where there are a lot of people who are just not being prescribed medications because people are afraid of controlled substances? Or is this a signal for over-prescribing of ADHD meds? And this study doesn't answer that question, but it's an important question. The number 10 study in our top 10 list was this one. And this is looking at incident or new psychosis and mania with prescription amphetamines. I personally think this is one of the most clinically relevant studies that made the sort of lay press. So previous research has shown this association between prescription amphetamines and psychosis risk. So this was a really interestingly designed study, a case control study using electronic health records from McLean, and they had case subjects who were patients who were hospitalized in their behavioral health hospital, McLean, for an incident, a new psychosis or mania episode, and the control subjects were the patients who were also hospitalized there for any other sort of psychiatric reason. And the odds of psychosis and mania increased with past month prescription amphetamine use. So, what did they find? And I think this is, again, really interesting. A dose response relationship was observed. So for people who had a high dose of amphetamine, which was defined as greater than 30 milligrams of dextroamphetamine equivalents, had a 5.28 fold increased odds of a new incident episode of psychosis or mania. Very, very interestingly, past month methylphenidate use was not associated with this at all. So clinically, if I've got, I was talking about I had a patient in my clinic, cannabis induced psychosis, question about whether or not there was an underlying psychotic disorder who was coming in to get his ADHD meds refilled, and so I was like, why don't we have a conversation about methylphenidate? So again, there's a dose dependent thing, so lower doses of amphetamines did not show this risk. So this is specifically the high dose group and specifically amphetamine. So there were a couple of other stimulant related studies. So this one was looking at when we treat ADHD with stimulants, what's the risk for subsequent substance use and risk for substance use disorder. So this was a study in Canada that was looking at six sites, one in the US, sorry, six in the US, one in Canada. And it was a 14 month trial, so they took kids who were ages seven to nine who had ADHD in the 90s, repeatedly assessed them over 16 years until they were about 25 years old. They looked at a bunch of different substance use outcomes, they adjusted it for all kinds of things that you could think about, age, demographic information, clinical factors, familial factors. They even adjusted it for what they called opposing age related trends in stimulant treatment and substance use. So really looking at sort of broadly we're seeing increased rates. And even with all of that, there was no evidence that current or prior stimulant treatment were associated with either subsequent substance use or substance use disorder greater than age controlled matches. That more years of treatment for your ADHD with a stimulant were associated with development of adult substance use or substance use disorder up until age 25. And that continuous uninterrupted stimulant treatment was associated with any of those outcomes, right? So there's this theory that maybe we take breaks on the weekends, maybe that's better at reducing risk, et cetera. There was no evidence for any of those things. So I think the take home message here is somebody's not psychotic, treating their ADHD is not associated with harms. And one more study on stimulants. So ADAPT2 trial, very pivotal in our field, presented I think yesterday or two days ago. So Trivedi had this very important study looking at a new sort of approach using combined therapies to treat methamphetamine use disorder. The trial had positive outcomes, a lot of buzz about it despite the controversies. However, the overall rate of abstinence reduction was about 11% in that trial, which has a question, you know, is that clinically meaningful? So this study looked over 12 weeks of the entire trial and they actually showed some more nuanced findings that the naltrexone, the Vivitrol once monthly long acting injectable naltrexone with a high dose bupropion had a significant 27% versus 11% in the placebo group increase in probability of testing negative for methamphetamine across the course of the study, whereas once the study ended and the medications were stopped, there was no further difference, right? So people who were on the meds were finding benefit and the meds were stopped went back to the rate of methamphetamine-positive urines that they had prior to the study. And so I think this is kind of giving you some nuance that there are some beneficial effects despite the relatively high abstinence ratio needed for that. So with that, thank you, Daryl. Thank you, Carla. So again, two buckets, prescribing and medications for stimulant use disorder. When we think about prescribing, the first study was interesting because it highlighted a few things. One about the nurse practitioner involvement in prescribing medications, both non-stimulant and stimulant medications for ADHD. In that article, they found that a nurse practitioner prescribing increased by 78% for non-stimulant ADHD medications and by 53% for stimulant ADHD medications. So what I began to think about is, what about the folks that were started on a non-stimulant who will fail that medication for whatever reason and then end up transitioning to a stimulant medication down the line? And how can we sort of look at that overall trajectory? I think that that's an important question that's still sort of hanging out there. And if anybody has any thoughts about that during the Q&A, I'd love to hear them. The amphetamine-associated psychosis article was really critically important as well. One of the reasons that I liked it is because of the dose response aspect of it. So dextroamphetamine, 30 milligrams a day, is equivalent to, and write this down, Adderall, 40 milligrams a day, and Vyvanse, 100 milligrams per day. So why is that important for us? This becomes an opportunity for our practice improvement project from a maintenance of certification standpoint. So we can all go back to our patient rosters and our cases and take a look and see, well, am I actually prescribing high doses of these medications to patients with ADHD? And can I talk to them in a different way about their risk for developing mania or psychosis? What kind of changes can I make from a PIP standpoint? The other piece of it is that what was not mentioned is that we really need to think about other vulnerability risks that people have present. And that includes their family history, as well as cannabis use, which was mentioned. And also in that group, the people that develop psychosis and mania were also more likely to smoke or have past-month hallucinogen use. So how are we talking to these folks about their use of other substances? And how aggressive are we being with smoking cessation? It's also important to note that black and Hispanic folks were overrepresented in that particular study. The other piece that I thought was particularly interesting about the overall trend and the impact of treating someone with a stimulant medication and whether or not that they were more likely to go on to develop a substance use disorder is we've spent a lot of time, I think, trying to help people understand that untreated ADHD represents a risk for going on to develop a substance use disorder. By extension, I think people began to assume, oh, well, then stimulants prevent substance use disorder. Well, what this does, what this study does is it actually says, well, there's really no, it doesn't increase it, it doesn't decrease it. And at the same time, we still need to treat ADHD to reduce that risk. So there is a little bit of nuance with that clinical recommendation that we give both to our colleagues, as well as to patients, families, and communities. Okay, so switching gears, again, the use of medications for a stimulant use disorder is something that I hope we are all doing. Even if it is off-label, the use of these medications can become critically important and can become a way of helping to retain patients in care. You know, I love it when somebody comes back to me and they say, Shorter, you started me on this stupid medicine. It didn't work. I'm like, great. At least you came back. Thank you for coming back. Let's try another one, and then let's try another one, and then let's try another one. So setting abstinence as the only acceptable bar for the use of these medications, I think, is at this point just not helpful. It's just like not even helpful at this point. So let's focus and center things like treatment retention and engagement as a valid and worthwhile goal when taking care of folks, especially if they are dealing with conditions as tough as methamphetamine use disorder. So I wanted to amplify the AAAP-ASAM Stimulant Use Disorder Practice Guideline and talk a little bit about some of the non-stimulant medications that can be prescribed or that are recommended for treating meth use disorder. That's bupropion, topiramate, mirtazapine, and of course the combination of bupropion with extended release naltrexone. That is given every three weeks. Now, when we were talking yesterday, one of the things that became painfully obvious is that some states have a really easy ability to provide extended release naltrexone or Vivitrol to their patients, even if it's every three weeks. That is not necessarily the case across all healthcare systems and certainly not across all states. And so thinking about how patients might be able to access this medication is going to be a barrier, a potential barrier to overcome when we think about how to prescribe and implement the recommendations from this study. Awesome. Well said. Thank you. Larissa? Yeah. Thank you so much for those comments. I'll just add one more that even from a patient-centered approach, some patients don't want an injectable or even if it's available, they don't want to come every three weeks or it's some burden associated with the regimen as the design was in that study. And so that was the study design, but in the real world, we're making some adaptations and it doesn't mean that other PO naltrexone or other doses of bupropion won't be effective for some people. We just, we haven't, you know, that was the study design. So thank you so much. And I think we were remiss in mentioning that the first study, the first ADAPT study lead author was Dr. Larissa Mooney. So if you have questions about this topic, we should ask her. That was the other pilot trial. So I'll just say a few things about the GLP-1 studies. This is really, and I think an exciting and emerging area of research. We're going to see more and more on this. In my clinical experience, I'm hearing from patients anecdotes about they happen to be on a GLP-1 agonist and they're experiencing reductions in urge to drink alcohol or use substances. I think this is a shared experience among other colleagues. And we are seeing, you know, signals in early studies for tobacco use disorder, alcohol use disorder. And then these studies were interesting because they were, you know, big data, EHR based, looking at outcomes, comparing people on these medications versus others, and noting reductions in opioid overdose. And actually it was some interesting outcomes related to tobacco use, like prescription of tobacco cessation medications or behavioral treatment for tobacco cessation, which suggests that there could be less need for those treatments, use reduction, though that's not necessarily what's happening either. But it's giving us some signals for future research. And I'll mention the NIDA Clinical Trials Network is starting a study using its terzepatide to augment MOUD in individuals with OUD. It's going to be a multi-site trial. So already, you know, larger scale clinical trials will be underway soon. I just want to add one more thing. So diabetes is disproportionately impacting communities of color, black folks, Native Americans, Alaskan Natives, and they are also the folks that are disproportionately impacted by overdose, death, as we just discussed. They are also not getting access to GLP-1 agonists. And so there is a health equity component to this that must be considered as well as we move forward. That's so important. I did have a comment. The increase in amphetamines for ADHD, that was also, as talked about in that article, almost certainly related to telehealth, like cerebral, which has obviously been a big story. And they no longer prescribe it because they're essentially facing severe criminal legal consequences. We haven't really seen that in the Bupe telehealth world, though, interestingly enough. So Bupe good, amphetamines over the internet bad. All right, we're in the home stretch. We're going to talk about nicotine e-cigarettes. These make a lot of noise when they come out. And for good reason. E-cigarettes I find fascinating because they could be a great, great way for adult smokers to not smoke cigarettes anymore, which is the whole point of smoking cessation, yet from a kind of total tobacco control standpoint, they obviously have a lot of risks, a lot of appeal to youth, and if it gets, for instance, teenagers addicted to nicotine for the rest of their life, that is potentially a public health disaster. And then, of course, we've had stuff like e-valley and kind of side effect related crises that don't seem to really relate to commercially available e-nicotine cigarettes, but that's still kind of in the water. Just to laser point you, that's what your kids are doing right now. They're puffing on a Elf bar, which is a whole kind of world of flavored e-cigarettes. And you thought the FDA and your state got rid of those, but they are now made primarily with synthetic nicotine, all of which is manufactured, packaged, and shipped from China. And the FDA can't regulate, yet, synthetic nicotine, so not an actual tobacco product. And then, I'm going to mention in a couple studies, you can come on laser, Cystazine, which is a herbal-derived product used for many years for smoking cessation, not in the U.S., not labeled and really kind of pharmaceutically available. I think you can get it as a supplement, but in other countries has been not as well studied as other medications, but has been now well studied enough that it's starting to rise up like the Cochrane rankings for tobacco control. The biggest article we saw was actually pretty simple. It's like public opinion surveys in the U.K. about e-cigarettes. Green is favorable opinion, red is bad, and basically showing a decline in favorable opinion about the safety of e-cigarettes in the U.K. and the general population. And essentially, the trend is down. That's the green line going down, and unfavorability is going up. And that's about it. And they link it to, if you want to watch, this is Vapors. People who actually use these cigarettes, they also have a declining kind of favorability rating for what they're doing. And that, they related to, essentially, two new cycles. One was the e-valley crisis, right before COVID, when, of course, there was severe lung injury and death, probably related to illicitly manufactured cannabis products in the United States, but kind of gave all vaping a bad name. And then increasing news reports in the U.K. of teen vaping, kind of a U.K. version of the teen vaping crisis, also drove worse stuff. And this was a hugely popular, high-ranked article, so demonstrating that if you want to get noticed, people, you've got to have colorful lines and drafts and visuals. Don't give us a bunch of tables. You've got to go full color, and it looks great, and it was fun to make a slide out of it. All right. This is a kind of round-the-horn. I really apologize for all the text. You won't really be able to read it. But this is kind of showing you a bunch of other e-cigarette and cistazine tobacco control papers from the year. So we just went through the first one, from Jackson et al. The second one is secondhand nicotine absorption from e-cigarette vapors versus tobacco smoke in children. And this is an NHANES study. NHANES is our national kind of go-around with a big mobile health trailer and take people's blood and measure their weight and ask them all the questions. So a real in-depth population-based health survey that's a wonderful source of all sorts of epidemiologic data. And so they looked at cotinine levels in kids and then compared it to household rates, self-reported of actual smoking, vaping, and then none of the above. And the e-cigarette households, the kids come in kind of in the middle. So they look a lot lower in cotinine than a smoking household, but they still have substantially higher levels than a non-smoking household. So you can get, and children can get, exposed to nicotine, essentially, through secondhand vaping. The third one I'm highlighting is electronic nicotine delivery systems for smoking cessation. This was a pretty standard RCT from Switzerland. The comparison was really just encouragement to quit smoking and a voucher that you could use for NRT, so some counseling and kind of financial support, but they weren't handing you NRT. And it was not versus Orenaclean, Bupropion, or other smoking interventions. And then the intervention arm got e-cigarettes for free, an encouragement to use them and stop smoking. And they look better over the course of the trial. This has been done repeatedly now. If you use e-cigarettes versus NRT for adult smokers, e-cigarettes win, and their kind of Cochrane strength, if you will, in systematic reviews now is going up, up, up. So e-cigarettes really do look like a successful, effective, replicable, practical way to get your adult smokers to stop smoking. What happens then and what happened in this trial is they keep vaping. So it's not necessarily a pathway to nicotine abstinence, which was the classic goal of smoking cessation, so no cigarettes, but that also means no nicotine. That's not what seems to happen with adults who switch or try to stop using e-cigarettes. They keep using e-cigarettes, and then we have to deal with whether or not that long term is still positive or gets negative, and do they switch back and forth for the rest of their life? We don't know. Evaluation, the effectiveness of cistazine, here it is again for the treatment of smoking cessation, a systematic review. That's from authors in Argentina, and it looks good. Cistazine looks kind of like bupropion. So it's not going to blow your mind in terms of treatment effect, but it looks like another med we could be using more often. I don't know if someone's going to try and get it labeled and approved in the United States. That can be a struggle if it's otherwise kind of available through other sources or as a generic. But it can be used increasingly once we figure out that pathway for smoking cessation. Cancer risk following smoking cessation in Korea, it stops smoking and your cancer rate goes down. It's a huge study from Korea. We kind of know that stuff, but it's repeating that message that we all learned in med school. Vaping cessation text messaging for adolescents. So they took adolescents who vape and started texting them, hey, stop vaping and other helpful messages. And they did better by self-report. It was kind of an entirely national but internet driven study. And it looked like just a lot of texting to the vaping team was effective in terms of what the team reported back in terms of stopping. And finally, cistazine for vaping. So this is now looking at, okay, you're addicted to vapes and we want to get you off it. Not cigarette, but vaping cessation and cistazine there from Nancy Rigotti's group in Boston looked pretty good in a pilot study. And then finally, last bunch of studies, highlights from the bupe world. There was a lot of innovation going on as we struggled to get fentanyl using folks onto buprenorphine. Induction has become more and more complicated. Do I microinduce? Do I macroinduce? What about the injectables? And then how do kind of AAAP, ASAM and the like deal with this kind of changing world? So highlighting some of those emergency department use of bupe, this was kind of low barrier, just start prescribing a lot more bupe in a bunch of demonstrations, EDs, mostly I think in California, maybe exclusively in California. No, they've got some others. It was all over. And it looked great. They got, just start prescribing more bupe from the ED, which means inducing people or you're going to get a prescription and take it later. Just being more liberal with bupe prescriptions for OUD in the emergency department seemed to drive a lot higher rates of treatment downstream. ASAM coming in to kind of take stock and give kind of high level guidance on the changing world of bupe induction. I won't highlight anything they said because it's kind of a guideline that says you got to be individualistic. It's not dogmatic and you got to be creative now, but it kind of endorses doing anything you can to get people onto treatment and taking some liberties with drug labels as we do in Actually, let me highlight the final one. So just start putting people on a brixade in this case in the ED and don't necessarily have to give them a test dose of buprenorphine. So they come in post-overdose, they're in withdrawal, they're there for any other reason, but the primary problem now is their opioid use disorder and you want to treat it with buprenorphine. It started with a weekly brixade and it worked great in the emergency room setting. Okay, I'm going to stop there. Thank you. Thanks. So I'll start with some comments about the novel bupe induction strategies. I think the field is really hungry for this. We really are struggling with some of the challenges inducting our patients who are using fentanyl primarily onto buprenorphine or at least learning that there are different challenges with induction and more variable responses. And so starting to see some of these papers come out that tend to both synthesize this information, the existing literature, the ASIM clinical consideration paper is a really useful one, I think, that just synthesizes and pulls together clinical consensus together with the literature with some experts in the field. And in some, they support, and this is consistent with my clinical experience in clinics across the VA and UCLA, that higher dose rapid inductions onto bupe are, we are finding more effective or less variable than the low dose initiations, let alone it can be problematic in an outpatient setting to say, you know, continue to use fentanyl while we attempt this very low dose induction. They mention in that paper that inpatient settings where patients are on full agonist opioids for pain, those low dose initiations can be very effective. Or in OTPs, transitioning patients from methadone to bupe, those low dose initiations can be very effective. And we certainly use them frequently in our OTP at the VA. So this paper and emerging literature is supporting the idea of actually just getting them on bupe more quickly. And the same would be true for the, I was really excited by the Mariani paper, one of our own, our president, looking at the rapid induction onto extended release bupe as sublocate using just a single test dose. And this was a paper looking specifically at the subgroup who tested positive for fentanyl and finding that it is effective, feasible, tolerated in that population. And I have colleagues who are doing this. The package insert says, you know, seven days of stabilization on sublingual bupe. So this would be an off-label use. But I have even heard of colleagues who are going straight to the 300 milligram injection in individuals who are, they're carefully selected patients who are using fentanyl daily or at higher doses. So there's a lot of room for clinical flexibility and adapting our approach based on individual needs of our patients and getting creative. So everything you wanted to know about nicotine delivery systems in three minutes or less. No pressure. No pressure. Thanks. Yeah. So again, kind of broadly thinking about these, I liked looking at the article about harm and perception of harm and how it really has a perception of harm of e-cigarettes and how that's gone up alongside the information about the article about secondhand vapor versus secondhand smoke. That was really a nice juxtaposition. Whoever did that one, that was great. So how do we amplify this message for patients, families, and communities? I think that that's really where we need to go with this because the misinformation is really doing us in. And so the challenge for us is to think about, well, how am I going to counteract this message to put this information out on social media, to talk about this in the broader media so that we can begin to have some impact there? The other information about the intersection of smoking and medical consequences I don't think will necessarily come as a surprise that sustained smoking cessation resulting in a reduced risk of cancer is necessarily groundbreaking, but I think it's helpful and good for us to know that information so that we can talk about that with patients. On to the interventions now, this I thought was pretty interesting. So when we think about electronic nicotine delivery systems, do we think of them as pharmacotherapy? Should we begin to think of them as pharmacotherapy and to what extent might we begin to have conversations with patients about making that switch from cigarettes to, so they all kind of work together. If we are talking about the, if we are counteracting this message about how e-cigarettes are more harmful, we're amplifying how they may be less harmful, then perhaps we can begin to talk to patients about how to switch from tobacco product from cigarettes to e-cigarettes. It is important to note that in that study that roughly 40% of the folks that made the switch continued to use nicotine, but they used nicotine as e-cigarettes. And so it's not necessarily that tobacco abstinence entirely, but nicotine abstinence entirely, but really tobacco abstinence. I kind of think of that clinically as like when we have conversations with patients about supplements, right? Yeah. Like we don't have the same level of data to talk to patients around supplements. You know, there's data on SAMe or these kinds of things, but you have to kind of educate yourself to know that patients are taking these kinds of things. And we have to be able to have a conversation even if we're not prescribing them. Absolutely agree. There is a conversation to be had because oftentimes patients are not necessarily interested in taking our medications. And so working with what they are using or what they may be more open to using can be a first step in terms of engaging them and saying, well, all right, we weren't as successful with the taper as we might have liked by using the e-cigarette. Can we also, can we now begin to think about using something that is FDA approved? So then from there we switch to the cytosineclin. There are many confusing names. I mean, just come on. And it's not cysteine or inositolcysteine. That's the other confusing word. Yeah, so we all had a fun time trying to learn how to pronounce this one. So this comes from the legume pea or bean family. And it's been in existence for decades actually, being used in Europe since the 1960s. Now, the nice thing about this medication for some people is that there's a shorter treatment duration. So instead of having to take it like Chantix, like you might for 12 weeks, this is 12 or more, you would take this for really only 25 days. It's also significantly cheaper. And so I think that there could potentially be a place for this medication here in the States. We'll just have to see what happens. And it's also kind of interesting and important to note that it does outperform placebo. It's a little bit better than nicotine replacement therapy and seems to have sort of no real benefit over varenicline. And we need more medications, frankly. We need more options available to us. The final thing is, I love a great behavioral intervention. And I've noticed that lots of you all are already on your phone probably texting during this panel. And so imagine if you were to have received a text message telling you to put your phone down. Pay attention. Pay attention. Show some respect. So there is something I think that can be said for the use of these types of interventions with people when they are trying to make changes to their behaviors, which are almost automatic. You know, the number of times we pick up our phone at this point is kind of automatic in many ways. The same thing is true for people when they are reaching for their vape or reaching for a cigarette. So prompting someone with a text message could be powerfully, powerfully helpful in helping them to curtail that behavior. Thank you. All right, well thank you guys for those excellent discussion points. We have this panel who has done their homework and read through all these articles. I'm sure there are questions from the audience. And we are very excited to try to engage in a little bit more of a conversation. You know, how might we use this? What are some questions that came up for you guys? So I think you were walking first. Those very interesting articles about cannabis and potential fetal maternal harms. Does anybody know whether those studies were controlled for other substance use? Yes, both of them, when they did the regressions, they were controlling for other substances. That's what I wanted to get at. Other known substance. So that data is often missing from those data sets, but what is known is controlled for. So EHR data is famously incomplete, right? So they control for what they got is probably the best way of putting it. Good signal, yeah, thanks. David. Regarding the nurse practitioner stimulant prescribing, do we know any more data about that? So for instance, there's also a faster increase in the number of nurse practitioners licensed than other prescribing professionals. Were there any controls like that? Was it like prescriptions per nurse practitioner, or was it just an overall lump sum that might not really indicate anything unusual? I appreciate your nuance to not, you know, labeling nurse practitioners as terrible and trying to think about those important considerations. Yeah, I don't actually recall that specific detail. They did speak specifically to the rate of prescriptions that were written every month, and they did find that that went up, but they didn't necessarily, to my recollection, correlate it to the increasing number of nurse practitioners being licensed. Yeah, good point. Nita. I wanna thank you all for being here, and once again, an amazing job. This is actually, to me personally, the highest impact presentation. I have several questions, but I'm gonna limit it to one which is very important to me, because I have several patients who use cannabis. They use cannabis all day long, and they don't wanna discuss it. I'm thinking of one particular case who was referred to me for alcohol use disorder. And then eventually we learned that he was using cannabis. What I have noticed is that at least nine emergency room visits within the last six months, and three ICU admissions every time he was discharged. The last one, at least I was able to confirm that it was for ischemia and eventual diagnosis of MI. We also know that cannabis can increase the oxygen demand, and there are several articles. However, no indication. He was told by the ICU within three days of discharge that you have anxiety, and you need to go back and tell your psychiatrist to help you. So now he's stuck on getting benzodiazepine. So I wonder how we can get the primary care, our colleagues to be on board. Taking advantage of these opportunities, right? There's so many lost opportunities. And again, this gets to our role as liaisons with our colleagues to make sure that they're aware of these kinds of things. But aware of one, the risk of cannabis, potentially for increasing oxygen demand. The literature previously has been sort of all over the place. Cannabis and cancer risk, maybe not. Cannabis with stroke risk, yeah, that signal looks good. So us really being knowledgeable about where the literature stands on what cannabis risk is so we can educate our patients and other providers. But then also, in terms of system level interventions, making sure that when somebody's in the ICU, that's a really prime opportunity to educate and make interventions. The other point I think I hear there is a lost opportunity for treating cannabis withdrawal. So somebody who's smoking cannabis all day, every day, and goes to the ICU has probably likely pretty significant anxiety, insomnia, some of the physiologic parts of cannabis withdrawal going on at the same time that nobody's treating, nobody's taking care of. And so of course, the second they get out of the hospital, the best way to resolve that cannabis withdrawal is to use cannabis again. And so that not being attended to also, I think is really important. Other thoughts on? Yeah, that's precisely the lost opportunity and we all can do better. Thank you. The role of consult liaison. Yeah, right, absolutely important. Hi there. Thanks so much, great presentation. I've been in nicotine policy for a long time and it's always amusing watching every pharmaceutical nicotine preparation being pure as the driven snow and every non-pharmaceutical nicotine preparation being conflated with all the others. It drives epidemiologists nuts. And in the process, I'd like to know if the studies on cannabis and pregnancy outcome were able to look for any signal with respect to mode of cannabis delivery. Thank you. They weren't. It was sort of cannabinoid exposure. It wasn't looking more specifically than that. Yeah, that study was just black and white, yeah. Hey, first of all, I just wanna echo amazing presentation. I saw you guys give it at the ACM in April and so I was like, time number two, just as good. My question is more around the kind of like the diagnosing and prescribing for ADHD lack of guidelines. And kind of context, I supervise a fair number of PMH and P's, multi-state. Most of them are very well-intentioned. They're really, quite frankly, I think scared of kind of the fallout that's come from Cerebral and Dunn, which we now call the Dunn debacle. But interestingly, I can't point to, here's the APA page that has guidelines on the diagnosing and prescribing for ADHD, which is kind of weird because we have it on the APA for schizophrenia, there's a new one for borderline, there's major depression. And so when I'm guiding them, it's kind of like me, Dr. Grower, saying, okay, you should take a comprehensive history. It needs to match DSM-5. You could get a neuropsych eval. You could get testing. But I bet if all of us in the room talked about it, people would have, we wouldn't have a consensus on it. But yet, it's probably the most highly-scrutinized diagnosis and treatment. So just thoughts on like. I can comment on that across the hall here. Yeah, go for it. Okay, I'm sorry to interrupt, but. No, go ahead. Last year's discussion. I'm the co-chair of the American Professional Society for Adult ADHD Guidelines that are being developed right now. We have the leaders in the field on that committee. Tim Willens and I are both on that. I'm the co-chair. He's one of these on the medications committee. So we're working on just what you said because one of the questions that you have with the nurse practitioners, I mean, they may be feeling a need because I can tell you that trying to find a psychiatrist, a child psychiatrist, to treat is extremely, frankly, expensive. And people are turning to nurse practitioners more and more, and I think these guidelines are gonna be critically important for adult ADHD. So I'm just sorry to interrupt, but I just, you were gonna look to the panel. I'm not sure the panel knew that that's under development right now. Amazing, and do you have a timeline? Because I read that y'all's are supposed to come out maybe the end of 2024. It's probably, the timeline, it's not gonna be at that point, but we're currently vetting a lot of what we're working on right now. So soon, I'll just tell you soon. And this is part of our dream team from our initial symposium last year. So Dr. Levin, thank you for reprising your discussant role for us. Much appreciated. Okay, I did have a couple of things to say. I mean, I think, first of all, wonderful job. I mean, you took a tremendous amount of literature and distilled it, and I was taking screenshots and everything else. So thank you to all of you on the panel. The one thing I will say is that a lot of the studies were epidemiologic studies or target emulation trials, and that's still not sort of the gold standard. And you mentioned the glutamide study, the studies that are gonna be done in the CTN. Those are super expensive, super intensive, and so it is becoming easier to look at these large epidemiologic studies and coming away with conclusions that I think there has to be sort of large caveats. So for example, I'll just give you an example. With the Molina study, it was based on the MTA study, and the MTA study had a lot of limitations, including the fact that kids with conduct disorder were excluded from that study, as well as how they define treatment and how they define protection. In that study, all you needed for treatment was 10 milligrams of the medication for at least 50% of the time. So was that adequate treatment to be protective or negative on a patient? Now, gratefully, there's no shown negative effect of it, but the question comes up is was the dosing and was the effectiveness of it enough to produce something that would be considered protective? One is the protective nature of putting people on a stimulant early. The other thing is just at the same time as that study came out, there's another one by McCabe in which they found that early treatment was protective, but later treatment actually was problematic, and there were a whole bunch of reasons why. So a lot of the data is showing that early treatment, continuous, long-term treatment may be protective. Treatment that's intermittent, we don't really have a good handle of. So I would just have that caveat there. And that nuance is really, really important. And the nuance is really important. People don't read, I mean, you guys do, but the nuances are not oftenly presented, and so people come away with a conclusion, and you have to dig into the methods to see how they define things. The other thing with the high-dose treatment, at least in treatment settings, substance use treatment settings, higher-dose treatment seems to be protective of keeping people in treatment, and that, so the one question is is that you need to know your sample. A sample of adults with long-term substance use disorders may require higher dosing. It doesn't, you know, throw out or make, it's not inconsistent with what you're showing with the other study, but again, you have to know the population you're looking at. And I think, unfortunately, what I tell fellows all the time is don't go just by the headlines. You've got to read the body of the paper to see what assumptions were made, and then, you know, modify what you think based on the assumptions. So, but otherwise, great. No, I mean, excellent, excellent points. I mean, these are all metric scores, right? So this is what's being picked up by the sort of lay press, and this was what's kind of getting out there, but I think understanding that level of nuance in how to interpret things that are going out into the world is really, really important. And I think, I don't know, just reflecting clinically, it's really interesting trying to sort through these pieces about high-dose stimulants being helpful for methamphetamine use disorder, but also having a lot of methamphetamine use disorder induce psychosis, and trying to sort of put those two things together. There's a lot of different things there. And the other thing I would add is that there's so much switching between medications when it comes to treatment for ADHD that oftentimes people are really confounded with what to do next, and so our real-world application of a lot of this can be complicated by the amount of switching that takes place and adding on and taking things off. Well, it was an interesting sort of real-world experiment with all the stimulant shortages because I had patients who were stable on one med for 20 years, and then they tried like 10 new meds in a one-year period because that's what the pharmacy had available at this dose or this formulation or whatever. So it was really interesting hearing their feedback, you know, like, oh, I switched to Vyvanse, and I love it. I switched to Vyvanse, and I hate it. I switched to this, and I switched to that, and like, it was an interesting real-world experience there. I would add real quick, that's a great point. We're not presenting a hierarchy of evidence. We're presenting kind of what hit, and to your point about investment in large, important trials, the biggest news of the year was the HEAL Community Study. You know what the budget for the HEAL Community Study was? I don't know specifically, but it was like $300 million? Yeah, we've never spent more on a single trial, if that's what you want to call it. Of course, it was a very complex, kind of clustered four-state effort to really just change people's lives on the massive scale, and that was an Altmetric 300, you know, which doesn't get you in the top 10. So we've tried to make that point when we presented the HEAL Study, but just to be clear, if you just follow kind of news ratings like Altmetric, you do not get to necessarily what's the most important thing for mankind. Popularity and scientific, you know, strength of the evidence are not always the same. That's another good example of the nuance, because that study theoretically is a negative trial, but I think that there's a lot of positivity and really understanding the context of the timing of how that all happened with the pandemic and other things. I mean, there's a lot of nuance in things that are ultimately beneficial and we should still keep doing that resulted in a negative trial. I work for a health department working on a lot of those things, and I'll just say, like, it's really hard to do with fidelity, and it sounds, you know, if you're, say, working at a medical center that, you know, with a team that's, like, all up to date with protocols, you can execute something in, like, a week, and I'll tell you, like, working for a health department, it could take me a year to do something with fidelity, but you can do it at scale, and I really appreciated the point made earlier that the health study is not a negative study. It's a positive study. Look at who you can get in the room to work together. That's a huge step forward, but really disseminating our treatments out into the community and our approaches out into the community, it's just, it's a lot of work. Yeah, the 38% uptake rate there was not super high for $300 billion or whatever it was, a million. Hi. Hi, Karen Drexler, Emory University, Atlanta. Thank you again for a really wonderful presentation. Thanks for the deep dive into the articles, and my comment actually segues nicely from this discussion. The e-cigarette companies and other folks who are trying to sell potentially addicting drugs have huge marketing budgets, and they know sophisticated ways to get their articles that are favorable to their product to the top of the altmetric list, as well as the popular press and social media, so I appreciate your skepticism about them, and I just wanted to offer a counterpoint. I just read a really interesting review as part of my maintenance of certification for the ABPN, and it's Review of Health Consequences of Electronic Cigarettes and the Outbreak of Electronic Cigarettes, Vaping, Product Use Associated Lung Injury. It's in the Journal of Medical Toxicology. We probably wouldn't read it otherwise, but it points out that a lot of the constituents that are in e-cigarettes, like propylene glycol, once you heat it, it turns into carcinogens, and the heating coils have heavy metals that are potentially toxic as well, so these things have not gone through, as another commenter said, through the FDA approval process to say the way we're delivering this thing is actually safe for the user, and we may not see the downstream consequences in a big enough population way for another decade, so part of what you were saying earlier about cautioning around supplements, we don't have the data one way or the other, but here's some things that we're concerned about as maybe a better way to counsel. And here's what we do know. I mean, I think on par, there's still that concern that it's less than the 400 or so chemicals in smoking, but it does not harm less, and I think we learned that with the vitamin E acetate debacle, with the illicitly prepared ones with THC in it, about these risks of these sort of new things that as we're learning, but we still need to balance that with kind of the known risks of other things, but it's an important point. I think it's a great point for tobacco-naive populations, but for adult smokers, we know all we need to know, like vaping is better for you, period, and it doesn't- It's not as harmful for you. Not as harmful. What? Better for you. Not as harmful. Well, it is if you're not smoking. It is relative to adult smoking, it's better for you. That's a true statement. So you don't need decades worth of is enjoy versus views gonna give you bronchitis. You know your pack a day of smoking is gonna kill you, and this is a pretty effective way to not do that. So that's why we are positive about it. We'll end on some controversy. Totally acknowledging all the other questions. And continued discussion. Thank you. So they're gonna take us off the stage. We'll stick around for any other questions. Sorry, Dr. Mariani, you didn't get to make your comment. Thank you guys so much for everything. Thank you to the discussants and the co-presenters. Thank you.

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