To our first symposium panel, they will be talking to us on cannabis policy. Is it misaligned with science? The chair for this symposium is Dr. Hill. So let me begin with a brief introduction. Dr. Kevin Hill is Director of Addiction Psychiatry at Beth Israel Deaconess Medical Center and also an Associate Professor of Psychiatry at Harvard Medical School. He has a very extensive bio. I will just highlight some of his very impressive work. He has authored and published a lot on cannabis. Cannabis use disorder, cannabis policy, and also have authored a Hazleton publication on marijuana and medical cannabis and evidence-based guide with Walter Kluwer in 2020. He also serves on the editorial board of Cannabis and Cannabinoid Research as well as American Journal on Addictions. He has been named one of the Boston Magazine's top doctors for the last four years. He also treats professional athletes and consults to NFL as well as co-chairs, NFL providers, Players Association, Pain Management Committee. So with that, Dr. Hill, welcome. Thank you. Thanks. Thanks, Nita. All right. Welcome. Thanks for coming this morning. So it's a great honor, obviously, to lead this panel. Thank you. this off with a symposium. And I'd like to thank the speakers for joining me as well. I know that they're constantly being asked to volunteer their time. So I appreciate them being willing to put in the effort to develop slides. One of our speakers, Dr. Pakula, who I'm going to introduce in a minute, she was unable to join us. She fell ill recently. So Dr. Williams has graciously agreed to step up and introduce her slides. Just one quick announcement that I want to make in terms of other opportunities to talk about cannabis throughout the meeting. Right after this, actually, we're going to have a meeting for the Cannabis Special Interest Group in a KCF4. So that's at 12.15. And then, as they mentioned earlier tonight, there's these committee tables. And I'll be at a table there. So a lot of opportunities. If we don't cover all the ground that you want to cover today, we can talk later. So just to introduce our speakers for today's symposium. So first of all, I want to introduce Dr. Das, Smita Das, board certified in addiction psychiatry and addiction medicine. She's a clinical associate professor of medicine at Stanford and chair of the APA Council on Addiction Psychiatry. In addition, she's the senior medical director at Lyra Health, which is a telehealth company. Dr. Pakula, who we're going to present her slides in the second portion of the symposium. Rosalie Pakula is the Elizabeth Garrett Chair in Health Policy, Economics, and Law at the Sol Price School of Public Policy at USC. And she's a senior fellow with the Leonard D. Schaeffer Center for Health Policy and Economics. She spent 21 years at RAND prior to that, serving for 15 years as co-director of RAND's Drug Policy Research Center, working on drug policy studies for the US Office of National Drug Control Policy, US Centers for Disease Control and Prevention, the European Commission, and the UK Home Office. Arthur Robin Williams is an assistant professor of psychiatry at Columbia with a decade of experience analyzing observational data, including electronic health records, insurance claims, and epidemiological reports. His work is funded by NIDA, SAMHSA, and the CDC in response to the opioid crisis. Robin is the former recipient of a NIDA R21 to investigate outcomes among medical cannabis patients. He also serves as the director of AAAP Area 2 in New York. And so with that, we'll have Dr. Das begin. Thanks. Great. Well, it's wonderful to see everybody this morning. Thank you for getting up bright and early to be with us. And I also wanted to take a moment to thank my co-presenters and our leader here, as well as the AAAP planning committee for putting together such a fabulous event that has been something we've all been looking forward to. So in terms of the topic of cannabis misaligned with policy, I'll go on in just a moment. For disclosures, I do have options at Lira Health, which Dr. Hill mentioned is a telemedicine company. And at the end of this part of the presentation, and we're fortunate to have several pieces of the presentation, I wanted to just talk about the changes in policy and how to approach cannabis in practice and give a broad overview of cannabis before we go into deeper dives by my colleagues on cannabis as it pertains to treating SUDs and psychiatric conditions. All right. So legalization. This is a slide that I tend to present when I'm talking about cannabis. And every time I present it, I have to say different numbers from what's available on the slide. So 37 states have laws that permit the use and sale of cannabis for medical reasons. And I put medical in quotes. I'll go into that in just a moment. 19 states have approved cannabis for non-medical use. So that's the recreational use that we see. That's actually gone up to 21 states at this point since we first submitted the slides. At the same time, so there's these state policies and state legislation. On a federal level, cannabis is still a Schedule I controlled substance under the Controlled Substances Act. And the FDA has not approved cannabis as a safe medication for any indication. And so there's this disconnect between what we have in state policy and federal policy, and finally, in practice, because we know as addiction psychiatrists that many of our patients are coming in using cannabis. And we'll look at the numbers in a moment, especially when it comes to other substances that are being used. Before we continue, I want to make sure that we're all on the same page about the different terminology because cannabis is a widely confusing topic, not just in the field, but also for our patients and their families. So cannabis is a plant that has many, many compounds in it. The thing that we often think about when it comes to cannabis is the psychoactive compound, the THC. And so the delta-9 tetrahydrocannabinol is the main psychoactive component. This is the thing that causes the high and also causes the most addictive potential out of the cannabis plant. In addition to that, there's other cannabinoid compounds. For example, CBD is one that we'll talk about briefly because it's probably the one that we've heard about most often in addition to THC. Traditionally, cannabis has been consumed by smoking it, right? So over the last 50 years, it's kind of common knowledge and using terms that our patients might use that a joint is a piece of paper where cannabis leaves are, dried cannabis leaves are rolled up and that is smoked. This has changed a whole lot. And there's an entire industry now associated with cannabis, as we know. So instead of just having smokable cannabis, there are edibles. Edibles are interesting because somebody may, well, first, they're interesting because they're often in forms that are appealing not just to adults, but things like candies, gummies, so on. And they have a delayed effect because it requires absorption. And so somebody may use an edible, not experience that euphoria, that high, and then use more of an edible. And so edibles have been associated with overuse because that time delay that happens. And then there's more concentrated forms of cannabis. And I have an image of one up there, but there's things like hash oil and butter and shatter. These are all very concentrated forms of cannabis. So it used to be that decades ago, top shelf cannabis was about 20% THC. And now we're looking at some of these products having 40% to 80% THC. So when we're thinking about what makes a substance have more potential to develop a substance use disorder, potency is important. And we see cannabis is off the charts now in terms of THC. We'll look at a chart in just a moment. I wanted to spend just a minute here about on CBD because CBD is growing in popularity and we see it everywhere, right? You go to the drug store, you go to the grocery store and there's CBD gummies and CBD lotions and CBD oils. And these things are being marketed out there, right? They're being, people are being told that they treat anxiety, they treat pain, they treat many, many things. At the same time, they haven't been approved for these purposes. And so the FDA has issued several warnings to companies that are heavily marketing CBD and they're especially being marketed for psychiatric indications, which is of interest to all of us. And so it is something to be aware of. And then when it comes to the concept of hemp, which there are laws in agriculture that allow CBD to be sold so freely. Essentially hemp needs to be less than 0.3% in THC. And so that's how a lot of these products are out there. At the same time, when laboratory studies are done on some of these products, it's found that the THC levels don't match what is listed or what they're supposed to be in there. And while this is supposed to be this non-harmful in your lotion sort of substance, it is pharmacologically active. So through cytochrome P450 also affects levels of other medications. So on one hand, it's this inert substance that we can have that is in lotions and candies and ice cream and drinks. And on the other hand, it has pharmacologic effects. It also is being marketed as intensely powerful for and helpful for sleep, anxiety, depression, so on. So it's an interesting place where we're at and the industry with CBD in addition to cannabis in general is also exploding. So I mentioned there, I would flash a chart here of cannabis samples that have been obtained by the DEA. And we see that now, whereas 20% THC was considered top grade cannabis for, now it's hard to find things that are less than 20% THC. So this inverse relationship between THC and CBD in the last several years. This slide has to do with driving. And it also, I included it in this section because it's a question that I get asked often when it comes to policy. So where do states stand when it comes to driving and cannabis use? So there's states that don't have policies around this. There's states that have per se policies where if you're found to be driving and above a certain level of cannabis in your system, then that's considered illegal. And then there is permissible inference laws. So that's where somebody can make an argument that they, even if they have above a certain level, that they are not impaired for one reason or another. It's interesting though to look at some trends that are available in insurance data. So for example, 17% of all DUI arrests by Colorado State Police involved cannabis. And also that there has been an increase in the number of crashes in Washington State since cannabis was, associated with cannabis since cannabis was legalized in 2012. So we're still getting more data about this. It's not as clear cut as say alcohol use and driving, but there certainly are impacts on the brain that would impair somebody's ability to drive and coordination of course. So moving from what the policies are and what cannabis is, we're now gonna talk about the impacts on use and then furthermore use disorders. So cannabis is the most federally illicit, I put illicit in quotes because federally illicit, of course we just talked about how states have legalized it, sub drug with almost one in five people 12 and older using it in the last year. The age where it's most common is in people who are young, so 18 to 25 year olds understandably. And if we look at all of the substances, so we're here at the Addiction Psychiatry Conference and we're interested in substance use disorders and so the most used substance is alcohol followed by tobacco and nicotine and then cannabis is a close third. And so these are the things that are really important to ask about with our patients. I'll give a plug for nicotine as well because that's my area of specific interest. We often may not ask about cannabis and nicotine because we're focused on alcohol use disorder, opioid use disorder and so if nothing else, I hope that we start to integrate cannabis into our conversations with all of our patients regularly moving forward. Young people, this is especially interesting and I will discuss briefly about the developing brain and the impacts on earlier use when it comes to cannabis use disorder and substance use disorders. So one out of three high school seniors is using cannabis in the last year and one out of 20 using daily. What's interesting is in the chart on the right, we see that the number of daily users in the lower grades has been increasing and this is impactful because again, this means that we're having a higher dose or higher influence of cannabis on the brain at earlier ages as time goes on. And so while there has been some encouraging news about stabilization of cannabis use in young people within those numbers, we see earlier use and a higher concentration of use at these younger ages. One study that has been very consistent and quoted a lot in the literature is the Monitoring the Future study out of Michigan. And essentially, if we look at risk perception and use of cannabis in young people, they are very inversely related. So the more something seems to be risky, the less the uses and the more something seems to be safe and normalized, the more the uses. And this is really important as we're talking about policy because as we legalize for recreational use or non-medical use, and then we also medicalize cannabis as in state legislation, that sending a signal and a message about the risks associated with this substance. And so when the policy discussions are happening, it's important to also think about not just the people that these laws are intended for, which are usually 18 or 21 plus, but also the messaging and the risk perception for younger people. Because we see, for example, in this study that was done in the last few years by NIDA, that people who use cannabis at a younger age, so when adolescents initiate cannabis use versus young adults, the risk of developing a cannabis use disorder in the next one year or three years is almost double that compared to if they had waited when to be 18 and above. So the earlier the use and the earlier the exposure, the increased risk of developing a cannabis use disorder. And so as an adult psychiatrist, obviously I think it's very important to screen for cannabis use and cannabis use disorders in our adult patients, but I would ask, and I know that all of my child adolescent colleagues that are doing the very important work of addiction psychiatry in that age range, that this is something to always have in mind. Use disorder rates. I'll talk in detail about the DSM criteria for cannabis use disorder, but as we know, it is a uniform DSM criteria now that we have for all of the substance use disorders. And so really, how much does cannabis use impact somebody's functioning? And then also, of course, is there withdrawal and is there tolerance? And what we see is that in people who have, in people that are 12 and older, about 5% of the population has a cannabis use disorder. And oftentimes when I'm talking to groups about cannabis, whether it be patients or professional colleagues or people who are not in medicine but interested in the topic, there's this kind of surprise of, oh, but cannabis was this thing that I'm not supposed to get addicted to, right? It's something that you can use recreationally and there's not an addiction. But what we're seeing is that there is an increase in the rates of cannabis use disorder over time. So we have alcohol use disorder and illicit drug use disorder, which has kind of many things underneath it. But then marijuana use disorder or cannabis use disorder is the bulk of that illicit drug use disorder. So why is there this rise in cannabis use disorder? So I've talked about several of these things in the last many slides, but there's a decreased risk perception and an increased acceptability. This has to do directly with the policy. And the risk in developing cannabis use disorder is about one in 11 in general. However, for daily users, that risk can go to one in three. So in people who are using cannabis on a daily basis, we have also discussed how cannabis potency is increasing that influences the risk of developing the cannabis use disorder. And then I think it's also important to talk about how cannabis is the most commonly reported drug in treatment admissions. And this doesn't mean that people are coming to treatment for cannabis use disorder. They may be coming to us for, again, alcohol use disorder, opioid use disorder, stimulant use disorder. And when they're admitted, they also have cannabis in their systems. And so cannabis is something that's there in the background. And when we're thinking about, say, an inpatient or residential admission, we may, again, kind of putting on my nicotine hat, we often screen for nicotine use disorder because we know the withdrawal from that is so uncomfortable. Well, if cannabis is the most commonly reported drug in treatment admissions, then it makes sense for also to us to screen for that, even if that's not the substance that we're necessarily working on with the patient because we need to be aware of it. And we'll talk about withdrawal in just a moment here. But before we go to withdrawal, we'll talk about the opposite, the intoxication. So cannabis intoxication. This is kind of what we think cannabis intoxication is. It's all of the components of feeling the euphoria or that high that people are seeking when they use cannabis. Feeling relaxed, difference in sensory perception, kind of these, quote unquote, good feels that people have when they use marijuana. At the same time, for some people, depending on, especially if they are newer to using cannabis and also if they're using a highly potent form, they may have uncomfortable experiences like paranoia, feeling delusional, feeling uncomfortable, and rarely having some suicidal ideation. So these are the effects of intoxication. On the flip side, when somebody is withdrawing from cannabis, we see all of these things which are uncomfortable. They're also symptoms that patients come to us for, right? As psychiatrists, patients are coming to us for depressed mood. They're coming to us for irritability, difficulty with concentration. And so we may be treating something, say we're treating depression, anxiety, ADHD, and underlying that, there's also this cannabis withdrawal. And so it's really important to be able to, again, if nothing else, that we ask about cannabis and we document it in our charts because it has so much impact on the other things that we're treating. And so again, often under-detected in inpatient settings, and it may be why somebody's not feeling better over time because they're using cannabis, they're stopping cannabis, they're using cannabis, they're stopping cannabis, and these symptoms keep coming and going over time for them. So I already mentioned a substance use disorder is defined by how much something impacts somebody's functioning and tolerance and withdrawal. And I'll use this as a way to start talking about how to address cannabis in our practice. So approaching cannabis use from an MI lens. Not every patient we see that uses cannabis wants to talk about it or wants to treat it. They're like, no, I'm actually here for my alcohol. I'm actually here for something else. And this is where having this MI approach to cannabis use in that discussion is really helpful. So tell me more about what, you know, first screening for cannabis, and I'll talk about that in a moment, but once we've established that somebody's using cannabis, how does it impact your life? How has it ever brought up anything for you? How does it, does it impact your relationships? Do other people use cannabis with you? Things like that, things to start opening a conversation non-judgmentally. And then the very concrete pieces of withdrawal and tolerance are kind of easier to approach. Do you feel like you, when you stop using cannabis, that you experience any symptoms? Does it feel uncomfortable for you in any way? And over time, have you needed more to get the same effect? So in terms of how to approach step-by-step, so include it in a regular screen. So I've said that three times now, because I think it's very important, because it is under addressed in clinical visits. So including cannabis as use in a regular screen. When we ask about, do you use any drugs? That's a very unfortunate way of asking about substance use disorder. Folks may not, or do you use any illicit drugs? Folks may say, well, cannabis is not illicit in my state. And so just kind of breaking it down as you're asking about each substance, making sure to include cannabis because it isn't always volunteered, finding out about what form they use as well. And if positive, if there is a positive screen, there is use, then continue with the assessment. Do they meet any DSM criteria for cannabis use disorder? Are they interested in talking about this? What are their goals? And even just planting that seed at that visit, even if it's not part of your plan moving forward, it's in the assessment, and it's also something that the patient will then continue to think about. And that's why I said, keep it in the assessment. And next time, even if you're not doing your whole screen, you remind yourself, oh, fill me in on where your cannabis use has gone since we last met each other. There are a number of screening and assessment tools. I'll talk about those, but I want to just make it easier to integrate cannabis use into practice. I'm going to generalize some of these tools into what we do for every other substance use disorder generally. So here's a cut it, and it's like the cannabis analog of the audit, and it looks at cannabis use and severity of use and impacts. So again, looking at cannabis-specific tools over here on your left and on your right are general approaches in practice. I'm going to focus on general approaches in practice, but cannabis-specific tools are listed for reference. And so when it comes to use patterns, just again, asking about use, asking in a non-judgmental way, normalizing that many of your patients use cannabis because they do, and so you want to have a conversation about it, and that it's important to you. When we, as physicians, as psychiatrists, bring up these topics, they, their importance and their value is increased for our patients. Then continuing on to the, is there a cannabis use disorder? Asking about the impact on their life and using the DSM criteria, which we're very familiar with, to guide that conversation. Looking at difficulty with stopping when it comes to cravings and withdrawal. And where do they want to go from here? So what stage of change are they in? Are they completely in pre-contemplation and they have no desire to quit, and it's going to be annoying for them if you continue to have the conversation? Or are they contemplative? Are they open to this discussion? And you can continue to discuss this over time. And looking at their goals. It may be that stopping cannabis, like many of the other substances, is not something that somebody wants to do entirely. They are using cannabis, let's say you have a patient, they're using cannabis daily, and they only want to use it once a month when they go and hang out with such and such person. Well, that's a goal. And even though that's not an entirely stopping cannabis goal, it's a goal that's, you know, in the step, step in the right direction for their health. And it may be a lot of hard work to stop using cannabis every day. So a very reasonable goal in harm reduction. And how, how confident do they feel? Again, coming back to the MI approach to cannabis, how confident do they feel about these goals and using that at every visit? So cannabis use disorder treatment, it doesn't need to be scary or this unknown or this, I don't know how to do that because, you know, when I was in training, we didn't focus on that sort of discussion. It is using the same principles as treating other substance use disorders. We can use those same things to treat cannabis use disorders. Treating co-occurring both other substance use disorders and other DSM diagnoses is important because you want to try to provide relief overall. And I think this is important. When someone seeks treatment, they've used nearly every day for more than 10 years and have attempted to quit more than six times. It is really validating when a patient who has been struggling with cannabis comes to treatment and feels like this is worthy because goodness, how in the world did, you know, for that patient, how in the world did I get addicted to cannabis? People don't get addicted to marijuana is something I hear often. And reminding them that among daily users, one in three people can develop a cannabis use disorder. And so we're seeing this more and we have ways to help them. Unfortunately, when it comes to medications, we're limited. I will go over that in just a moment, but behavioral approaches, in addition to starting the conversation with MI include other proven approaches, which are CBT and relapse prevention, contingency management, as well as MET, the four session version of MI. And then consider reducing and setting a quit date. So making goals and goalposts is important and having those in the plan and agreed upon by the patient. And then of course, like we would do with any other substance, removing triggers, suppliers, strategize on relapse prevention. Most importantly, ask about it and listen. And we know that doing this in a nonjudgmental way will encourage the patient to be able to meet their goals. And finally on medications, there are no FDA approved medications. I took this from a slide from Dr. Williams in a presentation we had done before. And this is from one of their shared publications, but, and I added a couple of words in there that were added to the slide as well, but we can look at anti-craving. Let me just say again, there are no FDA approved options for treating cannabis use disorder or cannabis withdrawal. So all of these are considered off label, but anti-craving medications are listed there, managing the withdrawal, the symptoms associated with the withdrawal, particularly anxiety and difficulty sleeping. And then finally, we do have FDA approved medications for psychiatric comorbidities that often go hand in hand with cannabis use disorder. And at the base of all of this, again, are those psychosocial approaches that we would use for any other substance use disorder. I'm gonna close with a couple of resources and advocacy pieces for you to just take away as things that you can look up later. So as noted, I am the chair of the American Psychiatric Association Council on Addiction Psychiatry. We have several position statements that we've developed on cannabis. So if you're involved in advocacy in your state or locally, then know that we have these resources available on the American Psychiatric Association website. This is a triple AP proposed legislation. Again, contributions from co-presenters here on model legislation for cannabis when it comes to what you might be seeing in your state or localities. The AMA, I'll point out, has this statement, which is they continue to maintain opposition to so-called medical marijuana and full legalization. Another good resource is the National Academies of Science and Medicine. They have a very comprehensive review of cannabis and very easy to digest summaries that are useful to us as clinicians, but also to refer our patients to. And then finally, I'll close with some of these websites, but I'll show this APA, the American Psychiatric Association. We were getting so many questions about cannabis from patients, from family members, from psychiatrists that we wanted to have a place, instead of each of us sending out resources to people, we wanted to put it all in one place. And so we developed a cannabis toolkit, which is available on the American Psychiatric Association website. And in addition, I'll also give a plug, we have a nicotine toolkit too. So a lot of good resources there, again, for multiple audiences. Wonderful. So with that, I will pass it on to Dr. Williams. Thank you. I'm standing in for a senior colleague, Rosalie Picoula in California, who unfortunately couldn't join us today. So I'll try to do justice to her slide deck. Our research overlaps a bit in the policy and public health world. This will build on what Dr. Das just presented. I think there are several really rich examples in here, explaining sort of how did we get to where we are. And I think that a lot of clinicians, unfortunately, haven't been involved in the state level and federal level policies. It's really been industry-led, and that's going to be the recurring theme throughout this deck, the impact of cannabis legalization on cannabis markets. This will bridge the illicit market and the legal markets, and the legal markets being medical in most of the states and increasingly recreational almost in most of the states. And when we say legalization, I think one of the conclusions that will come out of her slides is that legalization in the U.S. more or less is synonymous with commercialization, the same way that we've commercialized the sale of alcohol or processed foods or sugar cereals for children, and that this has had major ramifications throughout the cannabis and cannabinoid-based products that people in the U.S. have access to. These are her disclosures. So we want to focus on how cannabis markets have changed. They've really changed over the last 20 years, but especially in the last five to 10 years that we'll talk through point by point, and then in particular, how these industry-led policies have not been in the interest of moderation and have, if anything, really been in the direction of facilitating not just access, but heavy use of high-potency, high-strength products. When we think about the cannabis market in the United States, if you're not aware, this is a huge market and rivals many of our Fortune 500 companies. If you look at the revenue, and this is not about illicit sales. This is about the legal market for medical and adult-use recreational cannabis and cannabinoid products in the U.S. It's approaching $30 billion a year. So this is how much McDonald's makes in the U.S. This is how much Starbucks makes. I think a better example is that this is about the amount of revenue that Uber brings in every year in the U.S. What this means is that these companies have a huge amount of political clout and influence at every level of government by design. And so they've been very, very heavy-handed. The reason I say Uber is, you know, I'm sure McDonald's lobbies for all sorts of things. But especially for those of you in cities, you use airports, hotels, Uber is completely up into the transportation industry in the U.S. And they barreled their way in, often doing illegal things and then working on the backside with state legislatures or Congress, lobbying to be allowed to do whatever they wanted. And I would say that that model is more or less what would translate to the cannabis market in the United States. It's not just about tax revenue from sales. I didn't know until I saw her slide yesterday. We have almost half a million people in the U.S. employed by cannabis companies. It's just a ton of jobs. And so all in all, this leads to about $4 billion a year in taxes going to state and federal governments. So this is a huge part, a growing part of the economy. And there's really been a major push for unfettered access in ways that go way beyond, that transcend any of the allowances that we would have for other intoxicants. Certainly way more liberal access or sort of unregulated, unfettered access to high-strength products that would never be allowed with tobacco or nicotine products or alcohol products in the United States. This is showing, there may also be a bit of a COVID effect here in 2020. But clearly there have been important associations between legalization or decriminalization status, and those are two different things that I'll dive into in the next slide, and arrest rates. And you can see the slide begins in the 60s, so this goes back a bit. But you can see in the early 90s is when cannabis arrest rates really started going through the roof. This, of course, is in parallel with when, in general, drug arrest rates and over-incarceration, especially of minority communities, began in the 80s and 90s. And the arrest rate for cannabis dropped precipitously, especially after 2020. And this is inarguably related to the status of cannabis and its legality across states and regions. What this slide is emphasizing is that if we start on the right and you look at states where they didn't change the legal status of cannabis, you don't see significant changes in the arrest rate of adults in orange or youth in blue. When you look at, on the left, at legalization, you see a significant difference. And sorry, the axis is small. Focus on the zero. So zero is when the change goes into effect. It's a time-varying variable across different areas. And so when you look at the zero in the left graph for legalization of cannabis, your arrest rate for adults plummets. But it doesn't change for youth. And then if you look at the middle graph, what that's showing is in the areas where states may have decriminalized cannabis but not legalized it, you actually see declines in arrest rates for people of all age. So when a state legalizes cannabis, it's going to be for people 21 and above. But the legal status doesn't change for youth or young adults below age of 21. So I think this is pretty convincing. It's empiric study. It's showing that we actually have more benefits from decriminalization with this one example of arrest rates, more benefits from decriminalization than from legalization. This is where we'll pivot into really thinking about what's the difference between legalization in the US context and commercialization and decriminalization. And I think our patients talk about these things all the time, about decriminalization, have questions about it. Our colleagues, I think, are a bit confused. We're often confused by these distinctions. And the point is that in the US, companies, and I think there's a notorious Supreme Court decision from just five or 10 years ago. Companies are largely treated like individuals under the Constitution and Bill of Rights, which means that companies, just like people, have freedom of speech. So in the US, a company that's selling a legal product typically can't be disallowed from saying whatever it wants, from advertising the products however they want. And so in the US, unlike many other Western countries, legalization has been equated with full-scale commercialization of products. And the products, the market, there's just so much money in this market that there's been a proliferation and explosion of the kinds of cannabis products that people now have access to. One of the ways that this is most commonly tracked is by the number of stores or the outlet density, whether medical or adult use recreational outlets. And Dr. Kula's point is that that's a useful proxy, but there are other, perhaps, more important metrics in terms of understanding the penetration of cannabis into our communities that I'll get into in subsequent slides. This is the same graph that Dr. Das had up a moment ago. And I just want to emphasize what we're looking at here. This is the potency of cannabis that's seized on the black market. So this is more or less the seizures of cannabis by law enforcement. So this is not about what's being sold in medical or recreational dispensaries. Part of what this reflects, there's several things embedded in this. One, the red line is THC, and you can see the strength as Dr. Das was emphasizing, has just gone up tremendously for THC. If you're not aware, in the cannabis plant, Cannabis Sativa, there are over 140 cannabinoids. We think about THC and CBD the most. THC and CBD have a common precursor that's related to CBG that then breaks down into either THC or CBD. So in general, as growers preferentially increase the strength of THC in a given plant, that also means they're breeding out the CBD, because the precursor's being channeled into the THC direction. So not only is THC going up, but CBD, and in my slide deck next, I'll talk much more about CBD's pharmacology in particular. As THC goes up, CBD goes out, the ratio really balloons between the two, meaning that the cannabis product, the cannabis, the distillates, cannabinoid derivatives, really can have very different effects for individuals. They're much stronger. I think part of what's also embedded in this graph, though, is that if you look at this really noticeable bump around 2015, 16, 17, and the strength of THC, again, this is among black market drug seizures of cannabis in the US. That's coinciding with when the recreational adult use shops opened in the first two states that legalized cannabis for adult use, so Colorado and Washington states. So I think one implication here is that as adults started to have access to high strength, high potency products in legal channels, that also had a driving force on black market cannabis that was available for purchase outside of legal channels. So overall, whether legal or illegal, medical or recreational, the strength of these products has grown considerably. This is a bit busy in the graph. What she's showing here is that if you look at just the legal stores in Washington state, which again was one of the first two states, so past the legislation 2012, the shops opened up 2014. This is showing in the orange boxes, the box and whisker plots, that about 20% of whole plant was THC, so 20% THC. On the right, these are so-called balanced THC products that would intentionally contain CBD. So in the legal store, when Washington first opened, the average THC potency was 20%. So this is about quintuple what would have been on the black market through the 90s. Okay, this is now showing not just whole plant or flower. So Dr. Das was pointing out, it used to be for a long time, until about 10 years ago, if someone was using cannabis, they were smoking it, maybe 10, 20 years ago they were vaping it. Now we have this whole proliferation of products, so it's not just the whole plant or flower marijuana, but there are drinks, gummies, chocolate bars, any kind of food, anything really can be infused. This in part reflects, it used to be that people had to cook up cannabis in a lipophilic, like a butter, and then use that to make brownies. So this is why there were weed brownies in the 80s and 90s. Everything's changed because now we have these distillates or concentrates, and the cannabinoids can really be added to any sort of product. You've probably seen, you can go into $300 tasting menus, 10-course tasting menus in Brooklyn, they have a restaurant, and the chef, every single dish for the 10 courses has cannabis baked into the food. So it's just a very different world, and I don't think the media's fully caught up to this. I don't think clinicians and patients are fully, probably if anything, users are much more aware than the professionals. So what this is showing is that when you look at these concentrates, not just the shacks or the shatter or wax that people may dab recreationally that they obtain illicitly, but there are all sorts of other edibles and concentrates that are upwards of 70 plus percent THC positive. Those are the fastest growing segment of the market. So the dark blue is showing between the two states that first legalized adult use recreational access. The dark blue is whole plant or sort of traditional flower. Cannabis, the light blue, is what's growing the fastest in terms of market share, and that would include, I know it's hard to read, but the edibles and concentrates and things like that. Okay, so this slide, what we're looking at is, this is rate per 100,000 people, and we're looking at hospitalizations for youth cannabis poisonings, and the youth here are ages zero to nine, so it's really child poisonings. And what we're looking at are the provinces around Canada, and orange is Ontario, green is Alberta and British Columbia, and then blue is Quebec. And the significance of what this is showing is that adult access to whole plant cannabis was allowed in earlier years, and there was an upward trend, but not a huge difference across the provinces. What happened in late 2019 was that the national government allowed the provinces to choose whether or not to allow edibles, basically, for adult consumption, and Quebec declined to do this. And so the childhood poisoning rates really exponentially increased immediately in Alberta and British Columbia and in Ontario, whereas they did not in Quebec. Just for reference, this rate of nine per 100,000, it can be hard to interpret these rates sometimes, in the U.S. with the opioid crisis, when the media really, Congress, the White House, because of political pressure from the affected families, that really got traction, I would say around 2012, 2014, this led to all sorts of major pieces of legislation, the HEAL Initiative, funded by the NIH. The average rate of overdose deaths in the U.S. was 25 per 100,000. So when we think about all of the alarm five or six years ago that finally got national media attention around the opioid crisis, the national overdose death rate was about 25 per 100,000 people, and this is a third of that rate of children being poisoned by cannabinoids. And the reason this is happening is because they're gummy bears, and they're pieces of chocolate, and they're things that kids are drawn to and put in their mouths. If a kid's not going to be drawn to putting a leaf in their mouth, they do it, but it's not going to poison them the way that the products do. So it's just a different world, and again, I don't think we really have the guidance in PsychoEd to help patients think through this. Here we're looking at cannabis hyperemesis syndrome, which used to be called cyclical vomiting syndrome, and the rate of, here we're looking at the rate of ED visits for cannabis hyperemesis syndrome, and the point is that it's not decriminalization that's driving these rates, and it's not even necessarily legalization, it's specifically commercialization. So it's allowing these companies to flood the market with all sorts of products, to have all sorts of claims that are not evidence-based, that are probably technically we know are running afoul of the law, but the federal agencies largely haven't kept up with them or haven't had the political pressure to really keep up with cease and desist letters to the extent that, and enforcement that they should be. Sorry, the button's a little bit slow sometimes. There are endless slides showing just how many products there are. Dr. Das mentioned ice cream, there really is ice cream, anything you can think of. Okay, so the point here is that commercialization has led to not just wider access to stronger products, but that it's also driven down the price, and her point in the notes, I'll tell you, is that, so the solid lines are for adult use, recreational, the dotted line, same color as for medical, it's a little bit hard to read on the bottom. The point is that you can get, a medical patient can get a dose, like a 10 milligram equivalent dose of an edible, a medical patient can get it for 50 cents now, and recreationally you can get a 10 milligram THC for under $2. So they're just incredibly low cost sort of intoxication units these days that are available in the U.S. So there's a rising potency, proliferation of products, and so the price per unit has declined by over 80% on average. Clearly you think about behavioral economics, the cheaper something is, the more of it people are going to consume. Basically intoxicants are elastic, meaning that their users are more sensitive to price changes. You have an 80% reduction in the price, use is going to go way up, which is part of what Dr. Das was showing, is that among active users, past month, past year, users disproportionately now, both adults and teenagers, are much more likely to be daily users of cannabis. Here we're looking at states, it says NL, that might be hard to read, but if it's not a number, it says NL, which basically means that there's no regulation, there's no limit. Part of what she's emphasizing is that all of these states have limits on the total amount, like the volume that can be sold. I think this is a relic of our enforcement state, where law enforcement, DEA, all of our criminal charges, if you're not aware, whether we're talking about crack rocks or crystal meth or bags of heroin, number of cannabis plants, it's all by volume and has nothing to do with strength or potency. The states that have legalized recreational access have limits on the number of grams, for instance, that people can take home, but they're totally agnostic toward the strength of the products that people are actually getting. I'm going to jump ahead here. A keg has 165 standardized drink units. In most states, you have to sign a form. In a lot of states, if you buy more than six-fifths of vodka or something, you have to sign a form or it's just not allowed. Here what she's showing, Michigan's the most extreme, that people can go in and in a single purchase, purchase up to 1,000, 2,000 plus units. This would be like buying eight cases of wine when you go into the dispensary. You can think about exceptions where this is a reasonable thing. You're throwing a wedding. Why not buy eight cases of wine? At the same time, on a regular basis, the idea that in all of our states, on average, patients can purchase more than 500 drink equivalents in cannabis is pretty wild. I don't think we fully appreciate this and that the states are fully aware of what's going on. The point here is that we often think about drink equivalents, I think, in counseling our patients. It's much harder to do that with cannabinoids. What are the implications for the body? I'll talk more about this in the next deck. Her point here is that cannabinoids are active throughout the central nervous system and the periphery. We really don't know what happens when people are exposed to these extra physiologic doses of cannabinoids, especially over decades of heavy use. To summarize, due to really the widespread allowance of commercialization of cannabis markets, the markets have had big impacts both on legal and illegal cannabis trade with higher potency, flower and derivatives, proliferation of new kinds of products, which have led to all sorts of externalities, and there's really been a collapse in terms of the average price of procuring cannabis, especially THC-based cannabinoids. The industry has really been leading this, and so I do think there's a big opportunity for AAAP to be much more vocal, both at the federal level and at the state level, in terms of getting good information out. I think the media, something I talked to Dr. Levin about a lot, I think the media has been very uninterested in the risks, and now that our rates of adult cannabis use disorder, cannabis addiction in the U.S. have doubled in the last 10 years, hopefully there will be more attention to safeguards that could be put into place to help people make better decisions. So thank you very much. I will keep going here. So I'm going to give a talk on cannabis and cannabinoids for substance use disorders and where the evidence is, because there's a lot of hype around this. And then after my talk, Dr. Hill will be giving a presentation on cannabinoids, especially for psychiatric conditions and where the evidence is there. And then we're going to open this up and hopefully have a good 20-30 minutes for a Q&A from everyone. I will hit on these. This is a little bit of an exploratory presentation to touch on different aspects of where the evidence does or doesn't exist and where the hype does and doesn't exist for using cannabis and cannabinoids for the treatment of substance use disorders. I am going to focus on opioid use disorder in particular. So why is this even a possibility? I think it's being trained at and being on faculty at Columbia in Dr. Kleber's division, one of the things he would always talk about in the early opioid epidemics was how we had the opium wars. A lot of people were addicted to opium at the end of the 1800s, early 1900s. And then morphine was thought to be this great cure for the addiction to opium. Didn't work out so well. A lot of people were addicted to morphine. The doctors started going to prison for prescribing morphine maintenance. And then heroin came out as this great cure for morphine addiction that also didn't work too well. A lot of people were addicted to heroin. And then cocaine was touted as this great cure for it. So I think there's always been this kind of hope for substitution of one intoxicant for another that may be less dangerous. And there may be ways, and I'll go through this evidence, where the use of cannabis may help people moderate or cease the use of more dangerous substances or routes of use of more dangerous substances. But there are reasons to be skeptical. So why would we think that potentially cannabis could be helpful? And I don't want to belabor this. So cannabis is going to be the term really for marijuana, the plant. And cannabinoids typically is going to be specific to a THC or CBD or a ratio of these or other less well-known cannabinoids that are typically in products that are derived from cannabis. But how could these potentially be helpful? And when you look at all sorts of different settings, there really are a lot of interactions between the endogenous opioid system and the endocannabinoid system. So the endocannabinoid system, or the ECS, this is going to refer to the more familiar cannabinoid 1 receptor in the central nervous system, the cannabinoid 2 receptor in the periphery that's more in the periphery than CB1. It's going to refer to the endogenous ligands. So in the 80s, we discovered anandamide and 2AGs. So there are two ligands that agonize the cannabinoid receptors. And then there are enzymes in the body that degrade or boost the production of these endogenous ligands. So that's the endocannabinoid system. The endocannabinoid system is deeply intertwined with many of our other neurotransmitter systems in the CNS, and in particular, with the endogenous opioid system. So there's a lot of overlap when you look at the basic science between cannabinoids and opioids in the CNS. In real-world settings, what do we see? So we know there are very high rates of cannabis use among MOUD patients. So if you look at methadone programs, if you look at multi-site OBOT clinics with buprenorphine patients, typically 30%, 40% plus of patients are using cannabis on a regular basis. I, with my NIDA-funded research, have access to two multi-state databases of patients on buprenorphine. And in both cases, across different states and dozens, maybe 100-plus clinics, it's pretty consistent. And when people come into care addicted to opioids and they're going on a buprenorphine, about 30% to 40% are cannabis positive. And that will persist throughout their care journey for out to 12, 24-plus months. So cannabis use is incredibly high among patients in treatment for opioid use disorder. We know from all sorts of different studies, including medication development trials, RCTs, that patients who are using cannabis typically have lower opioid withdrawal as they're trying to induct onto buprenorphine or start extended release naltrexone. We know that when you look at medical cannabis participants, if you were to interview them, there's all sorts of anecdotal and qualitative survey-based studies that have been published that patients going to medical cannabis dispensaries report that they're seeking medical cannabinoids in order to reduce opioids. There are also some population-level studies that question whether this is really what's happening. Some states have now proposed access to medical cannabis, for instance, that opioid use disorder or reducing opioid use might be a qualifying condition at the state level for having access to medical cannabis. There are also studies that have shown that even low-dose or sort of subpressural dosing of opioids in conjunction with THC can actually have superior analgesia than other full dose of either of those alone. In terms of CBD, and I'll get into more detail about this in future slides, CBD generally is anti-inflammatory. The strongest evidence base, and this is where Dr. Hill can talk in more detail, the strongest evidence base for the medical use of cannabinoids is really for pain, maybe spasticity. CBD in particular is anti-inflammatory. That's both true in the CNS and in the periphery. CBD is a negative allosteric modulator of THC. What that means is in the presence of CBD, when THC is agonizing a CB1 receptor, CBD decreases the agonism of THC. THC is actually a partial agonist at CB1, which a lot of people don't. You sort of think of it as a full agonist. I think that's more intuitive. It's a part of why the synthetic cannabinoids like K2 and Spice have been more dysregulated, lead to more dysregulation because those are full agonists. THC is a partial agonist. But the point is that CBD basically lowers the THC tone or activity at the CB1 receptor in particular. It's actually true. It's not necessarily a negative allosteric modulator, but CBD generally acts as an allosteric modulator of other neurotransmitters in the CNS, so serotonin, glutamate. It also works at acetylcholine receptors. So the endocannabinoid system really does have implications for all sorts of different aspects of physiology related to substance use and the conversion from heavy substance use to a substance use disorder in terms of reward and memory pathways. The CB1 is actually the most prevalent G-coupled protein receptor in the CNS. So there's all sorts of reasons to think about how potentially cannabinoids could be used for all sorts of things, and yet we're very early. My main conclusion is that we're very early in the research in terms of actually getting medications to people in a therapeutic manner that will be helpful. CBD has been shown to decrease cravings, and there are probably a few mechanisms for this. One, it's anti-inflammatory. Two, it may be treating withdrawal. Three, in particular, and I'll go into a few examples of these in future slides, in particular, CBD can disrupt aberrant memory formulation that contributes to the condition-place preference for drug-related cues. And so one take-home, I'll jump ahead, is that potentially, CBD may be more helpful not for initiating abstinence as much as for patients who have become abstinent from their drug of choice, like cocaine, maybe opioids, or methamphetamine, it may actually help maintain abstinence because it decreases the drug-related cues or response to those. So there are all sorts of studies, and I'll show a systematic review next that goes through dozens and dozens of studies with CBD and THC, mostly in animal studies, but also preclinical human studies. So there are actually lots of studies and lines of investigation that can lead to all sorts of interesting ideas. But ultimately, I'll show some population-level studies that raise questions about how likely this is, with our current cannabinoid on the market, how likely they are to be actually helpful. Okay. So here, I won't belabor this, but the red dots are just to draw your attention. Make sure you pay attention to the column headings. So here in the sample, we're looking at humans versus animals. Then there's the substance for the exposure, and then the treatment. And hopefully you can read this. In general, we're looking at CBD that's about 10 to 40 milligrams per kilogram. I was talking about dose units in Dr. Bakula's slides earlier, and we typically think about a THC dose, a single dose, as being about 10 milligrams. And CBD is very different. It's not one-to-one. So in general, people are gonna be dosed CBD in medication studies closer to 600 or 800 milligrams. Just like two orders of magnitude different, almost. So for sensitization, you can see on the far right is the effect. And you can see there's mixed effects across these studies. So half of them, more or less, on this slide are negative, and then about half of them show potentially a therapeutic benefit in terms of decreasing. Sensitization is measured by locomotor activity. So remember, these are mice and rat studies. In terms of reward facilitation, that it can decrease euphoria, decrease the pleasantness ratings among humans. Probably what matters most in terms of self-administration, it's a little bit more mixed. Again, this is a mix of human and animal studies. Withdrawal, again, not always true, but often has been found to decrease withdrawal. And this is spanning nicotine, morphine, and cannabis on this slide. And then reinstatement, and not to over-interpret this, but if anything, a greater percent of studies looking at reinstatement are actually finding that CBD may have beneficial effects. This is a study from a former colleague at Columbia's Eva Cooper's lab, looked at combining opioids with sub-therapeutic doses of cannabinoids and found it was actually superior analgesia. So several lines of evidence, different kinds of study settings. And this, I thought, was a bit alarming a few years ago. So this was pre-COVID, around probably 2017 or 18. The state of New York, which traditionally had one of the more regulated medical cannabis programs in the U.S., added opioid use disorder. They kind of tweaked this and went back and forth, changed it to addiction and general substance use disorders, landed on reducing opioid use. But basically included opioid use or opioid use disorder as a qualifying condition for access to medical cannabis. This was about five years ago, so it was before the recreational market had been approved. However, when you look at patients, whether they're in medical-only states or also have access to recreational, the great, great majority of the time, patients are gonna, if you interview them, they're gonna say that they're using cannabinoids for chronic pain. This doesn't, you know, you can only generalize so much from a given study. We know that a lot of patients are seeking CBD, in particular, for anxiety and sleep. And if you haven't driven on the highway, in particular in places like California, you're gonna see billboards advertising cannabinoids for any indication you could possibly imagine, and it's more or less just, you know, made up or hype. So it's a very small percentage of people who are reporting that they're seeking cannabinoids to reduce the use of addictive substances. So there are a few, and you have access to our slides from the references list. This is the CARINI study where they're looking at CBD, in particular, for the whole array of substance use disorders. Main conclusion, that more preclinical and clinical studies are needed. Always a safe conclusion. To dig into CBD a little bit more, this is a busy figure, but it, I think, is really helpful to see. I mentioned a moment ago that CBD is not just a negative allosteric modulator at the CB1 receptor for THC, but it also directly works on dopamine receptors, serotonin receptors, FA, and anandamide, or the enzymes and the endogenous ligands that work on CB1. And then there's a whole host of other receptors throughout the CNS where CBD is active. So clearly, there's a lot of therapeutic potential, but obviously, at this point, we don't really have the products or know how to use them at what point of the treatment cycle, in a way. It can be FDA approved. So how could CBD be helpful for stimulant use disorders, for instance? So CBD, this gets into a lot of detail here, but it can lead to the normalization of drug-induced alterations in the dopamine mesolimbic system, so our whole process in the brain of moving from heavy use to addiction can disrupt that. Also, modifications of cannabinoid systems, other neurotransmitters systems, as I mentioned, and signal transduction pathways. So there's really a lot in reducing neuroinflammation, as I mentioned. I'm gonna wrap up, but just hit a couple more notes here before handing it over to Dr. Hill. So there is interest in cannabinoids, specifically for psychostimulant use disorders. I didn't have the, the study wasn't out yet for me to put into the slide deck, but the first, in the clinical trials registry, the first prospect of RCT looked at eight, it was a double-blind, two-arm study of 800 milligrams of CBD versus placebo for patients with cocaine use disorder, and it was a negative study. The only significant difference between the groups was higher rates of diarrhea for the patients randomized to CBD. So unfortunately, that didn't work out in a human treatment setting. But there are, on the right in the blue, examples similar to the last slide of how potentially CBD could be protective or helpful for patients with psychostimulant use disorders. I'll touch on Delta-8-THC. This was coming up a lot in the spring. I haven't heard as much, as many questions about this. Dr. Das mentioned hemp. So the 2018 Farm Bill legalized hemp, more or less, and the idea with hemp is that it's like, it's a cousin to cannabis sativa, but the THC content needs to be extremely low. So CBD can be harvested. Sorry, Delta-8-THC can be harvested from hemp, but the concentrations are so low that when patients are talking about using Delta-8-THC, compared to Delta-9-THC, they're typically using products that are converted from CBD, which is not from hemp. So there's this whole gray zone in the market, sort of similar to CBD itself, where people often have, can buy, just buy the stuff online and use it, and it's a little bit unclear where it came from and whether it's really legal. The point here, this is an industry report that many users of Delta-8-THC are just curious about it and think about it like a light Delta-9-THC, that if you haven't had them, you will have patients who say they're using CBD marijuana or using Delta-8 in order to try to reduce their cannabis use because of their high levels of tolerance and addiction to cannabinoids. Okay, so just to wrap up, there was this promise in 2014, a big study came out showing that states with medical marijuana laws had, even though they had higher rates of opioid analgesic involved overdose death rates, that the rate was plateauing at the far right. This was picked up by all the major media news outlets. And then a follow-up study five years later showed that if we continued following populations in these states, that actually the rate of opioid-involved overdose mortality really increased tremendously, even in the states with medical access to cannabinoids. So it really threw cold water on the hope that just simply expanding medical cannabis programs would help us respond to the opioid crisis. I'll go a step further and suggest that there are actually, you know, some studies that would suggest that there may actually be additive risks. So this is a study, actually my mentor published this using NSARC data, so this is a national survey, it's panel data, so they had the respondents from 2001, 2002, they followed them up again three years later in 2004, five. And what this is showing is that based on the heaviness of cannabis use in the first wave of the study, the patients were actually in this sort of dose-response relationship, much more likely to have an opioid use disorder when they were followed up three years later. Doesn't mean by any means that the cannabis was causing this, but if the cannabis was protective and heavier rates of cannabis use was protective, you would think that this would not be the direction of the association. Keith Humphreys had an article in JAMA recently where looking at medical cannabis use, that there was really no substitution. Cannabis, they concluded, was simply added to the mix of addictive substances taken by patients with pain. We know that THC in general can have a priming effect for reward for other intoxicating substances. And then here, Dr. Hill recently had a review in the American Journal of Psychiatry in the conclusion, which I think he'll talk about in much more detail in his deck coming up, that there is currently no psychiatric indication, whether a substance use disorder or otherwise, for the use of any of the FDA-approved cannabinoids or cannabis. So it was a little bit of a whirlwind. Thank you for sticking with me for two slide decks back-to-back, and I'll hand it over to Dr. Hill. Thank you. and for stepping up on short notice to present Rosalie's slides. Oop, let's go back. So yes, we're gonna talk about cannabis and cannabinoids for psychiatric conditions over the next 20 minutes or so. Then we're gonna have hopefully a spirited Q&A in terms of my disclosures, a couple of books on cannabis. And as Dr. Desai mentioned, I consult to the NFL and did consult to Greenwich Biosciences. So what are we gonna do in this segment? We're gonna talk about discrepancies between the current laws and the science. Has there been progress at all? Are they becoming more aligned over the years as we would hope, right? People usually revise protocols and algorithms as you use them. Has that happened with medical cannabis? And then we're gonna talk about the state of the evidence. What does the science say at this stage when it comes to medical cannabis? So what do we have available? So three FDA approved cannabinoids right now, Dronabinol, of course, oral THC, Nabolone, which is a cannabinoid one receptor agonist. They're FDA approved for one or two things. So nausea and vomiting associated with cancer chemotherapy and appetite stimulation for wasting conditions like HIV. So Dronabinol is approved for both of those and then Nabolone is approved for the first one. And then CBD, cannabidiol, was approved in 2018 for three seizure disorders. So Lennox-Gastaut, Dravet syndrome, and then seizures associated with tuberous sclerosis. However, it's very important to point out that I noticed I was looking at the spa offerings at the hotel here and you can get a CBD massage, you can get CBD mani-pedi, and the CBD that you're getting is not Epidiolex. So that's critical. I think that when we talk to our patients about CBD products that they're using, over 99% of what they're getting is not the FDA approved version. So there's a host of issues that come with that. Purity and potency, so a couple of really great papers over the last few years, 2017, Marcel von Miller showed that only 30% of the commercially available CBD products were accurately labeled. And then he collaborated with some folks in 2022, primary author of a spindle, and they looked at the topical products and they showed that, so that number is becoming lower. So 24% of the topical CBD products were accurately labeled and importantly, 35% of those products had THC in them. So this becomes an issue over and over again for our patients who are going to be drug tested, whether that be when they're taking a job or if they have safety sensitive positions that require them to be tested. So you're responsible for what you put in your body at the end of the day. So I wanted to talk a little bit about a paper that we published earlier this year, a couple of my colleagues at University of Maryland, so Marleek Burnett and David Gorelick, who you probably know. We wanted to look at, again, this issue that we've had medical cannabis now for over 25 years. Have the laws been more tightly aligned with the science over the years? As we would hope, right? You would hope that there would be some progress. So Smita mentioned this earlier. We have these policies in most states. So I've been doing this for 10 years now in this area and so more and more states have had these policies. We're up to 38 now, plus DC, plus territories that have medical cannabis policies. I think Smita mentioned we're over 20 now that have legalized recreational cannabis policies. So trains left the station, this is where we're going. So the question becomes, as states do this, what are the policies like? Are they getting better? Are they learning from the early states? And that's really the point of the paper that we published in Psychiatric Clinics. So in those states, there's a group of core conditions. 42 conditions overall, but I'd say there's around, you know, anywhere from 12 to 20 conditions that are in most of these states. So five to 29 overall in these states, but a core group. So what we did was, again, we've referenced a few times today, and I'm gonna also mention it again one more time after this, the NASM report, which is outstanding, came out in January of 2017. So it's a bit dated at this point, but we wanted to follow their procedure, really, and so we graded the evidence in 2022, or early part of 2022, in terms of the studies. And what we found was that there were five of the 42 qualifying conditions, only 12% of those conditions have conclusive or substantial evidence of efficacy. And there's also, you know, they're commonly listed in these jurisdictions. Half of these qualifying conditions have no evidence at all. So that's worrisome, of course, or insufficient evidence. And then 9% have some evidence of harm, only a limited amount, but again, it shows the variability in the levels of evidence available for conditions. And Robin just mentioned a minute ago, right, people are talking about things like opioid use disorder. So, you know, these are very, very serious conditions for which medical cannabis is being stipulated as a potential treatment. So overall, in that psychiatric clinic study, we saw that the mean number of qualifying conditions per jurisdiction and proportion, with or without evidence, has really not changed at all since 1996, when California first had medical cannabis. So over the years, we're really not seeing a more tight alignment, unfortunately. And I think that's really a problem, right? We would expect that people would improve, right? I mean, that's really the nature of the work that we do, whether it's a scientific protocol or a clinical algorithm, right? You look at it, you say, how's this going? What are the strengths and weaknesses of what we're doing? How can we do it better? And that has not happened here, unfortunately. So we have a lot of people who are interested in these topics, and we've heard about the number of people working in these industries, the money that's involved, but the policies really have not gotten better. And that's frustrating, I think, for anybody that does this kind of work. I believe that we should be trailblazers in this area, recognizing that, again, this is where things are heading. We should have better policies that give people what they vote for, usually, while limiting the risk. And that just hasn't happened. Why is that? Well, I've said over and over again, the rate and scale of the research has not kept pace with the level of interest. And why is that? I think part of that has to do with responsibilities that stakeholders have. So companies that are making a lot of money, and states that are generating a lot of tax revenue, really, and I'm not saying that none of these companies or none of these states, but most of them really have not been involved, frankly, with advancing the science in a meaningful way. And you can understand why, right? If you're a company, and your company's doing very well selling CBD products, or Delta Aid, or if you're a dispensary, you would not want research, really, to run afoul of the sales that you're engaging in. So, and I'd say, there are groups that are trying to do this. I think one of the things that we've been able to do in the NFL, I mean, we funded four studies in the last year, so about $2 million worth of smaller studies. But again, looking at these questions that we're gonna talk about today, can cannabis treat pain? Can CBD treat pain? There's very little science there. So there are some groups that are actually trying to do this work. But I would also point out that when legislators are making these policies, they're just really busy, and it's easy for them just to look at what other states have done, right? So we would encourage you, and we'll talk about it, I'm sure, at the special interest group, how can you have more of a voice in these policies? It's hard, frankly, but you definitely can do better, and we've, of course, crafted some model legislation that people can use. So thinking about where the evidence stands now, what's the best evidence when you think about this from a clinical perspective? So I have patients who come in, 60 years old, have chronic back pain, they've tried multiple medications, multiple injections, and they're interested in cannabinoids, and they get sent to me for that reason. We have a cannabinoid clinic that we deal in one hour with patients with CUD, the next hour with a patient that I'm describing now. So we deal with these folks, and I wanna have a sensible conversation with them. So I think it's important to talk about where the evidence is. And from my end, I think that the best evidence as it stands right now, and Robin alluded to this, chronic pain, neuropathic pain, spasticity associated with multiple sclerosis. So that really hasn't changed. My JAMA paper came out quite a long time ago now, and we haven't seen a lot of movement, frankly. And then CBD, of course. And I point to CBD, certainly it's easy to point at the problems associated with CBD, but we also can use that as an example for rigorous science. So the company that got the FDA approval did great studies looking at those indications, as I mentioned, the seizure disorders, and those studies were published in the best journals, New England Journal and Lansing. So you can do this. People will say, oh, you know, it's really hard to do the research, we can't do the research. Well, you can do it, there are barriers to it, but if you really want to put the resources towards it, if it's that important to you, you absolutely can do it. And it's been done, it's been done before. So the NASM report, like I said, January 2017, outstanding job that they did, very important. A lot of people have looked at it, does need to be updated, but what did they say? Quote, conclusive or substantial evidence that cannabis or cannabinoids are effective for chronic pain in adults, chemotherapy-induced nausea and vomiting. We kind of knew that already because of the FDA approval. And then patient-reported MS spasticity symptoms. And then Penny Whiting had an excellent meta-analysis in JAMA in 2015 that said moderate quality for chronic pain and spasticity. So to me, take-home point there, important for folks to do the work that you do, and really for all physicians. I think that a lot of people have been trained to feel like there's no benefit from cannabinoids. And I don't think you can really say that, right? It certainly can point to the problems associated with formulations and how people are using them, the levels of evidence, certainly, but to say no evidence, I think it's hard to do that. So I think to me, the take-home point, while there are minor differences between what I wrote and what Dr. Whiting wrote in the NASM report, but I think that, again, the take-home message there is some evidence. We could have much better evidence, but when a patient comes in, they're not coming completely out of left field to wonder about whether they should get a medical cannabis card to treat their back pain if they've done all the right things, first-line, second-line treatment. And that's something that I've also said many times, too. We're not thinking about CBD or medical cannabis as a first-line treatment, or a second-line treatment, really, but in some cases, when someone has really done, they've collaborated with their doctor and done everything right, I think you can have a discussion. And for those cases, I mean, I certainly would prefer an FDA-approved cannabinoid if we can do that, and I've done that with Dronabinol, for example. So this paper came out over a year ago now. It's hard to believe, time flies, but I think that we also covered some of the things that we covered in the psych clinics paper, talking about specific psychiatric conditions and where the levels of evidence is. And also, put in a plug, although Robin had a great figure earlier with CBD, but that's one of the other things that we covered in this paper, the idea that CBD is far more complex than most people believe. It interacts, as Robin said, multiple neurotransmitters, and the concentrations necessary to interact with those receptors varies quite a bit. So when you're thinking about a desired effect of CBD, the dose is gonna have to be usually considerable and perhaps different, depending on what the desired effect is. And so that's also another important piece when people are talking about going to Harvard Square and getting 10 milligrams of CBD in their coffee. That's not what we're talking about. That's probably not gonna do much. But if you're taking hundreds of milligrams of CBD, then there are issues that we could talk about, certainly in the Q&A, if you want to. So anxiety, various psychiatric conditions for anxiety in the psych clinics using the NASM grading system, we found moderate evidence of efficacy based upon 31 published studies and 17 RCTs. However, important to point out that these studies are not looking at anxiety as a primary outcome. And importantly, we're looking at a heterogeneous group of cannabinoids. So these studies might look at the FDA-approved cannabinoids. They might look at various, cannabis flower, depending on where they're done. There's nabixamols, which is not approved in the United States. So we're just looking at the studies that have been done, although we're not saying that they're as uniform as they could be. But these are studies that have looked at anxiety as a secondary outcome, looking at other disorders. And then again, none of them are evaluating medical cannabis specifically. So that's something that you hear, right? People who are advocates for this say, yeah, the studies haven't been done. Well, why haven't the studies been done? Or the other flip side of it is, yeah, there really haven't been studies here. So in cases like anxiety, when I'm having a conversation with a patient, I have treatments that work here. Whether it's a behavioral intervention or medications, have we thoroughly exhausted those options before we start talking about this in a serious way? So again, as I've said many times, I think that if you have that conversation in a sensible way, you may be able to get patients to entertain a trial of an SSRI, perhaps where they wouldn't have before. If you're not discarding what they say, their interest in CBD for anxiety, for example, but if you have that conversation, they might be willing to try something that they weren't willing to try before. The story for depression is more bleak, certainly. So limited evidence of harm in 40 studies, 22 RCTs that have looked at depression as a secondary outcome. So none of these studies looking at as a primary outcome, none of them showed benefit at all. So while it is, I'd say, a nuanced conversation to talk to patients about cannabis and anxiety, it's really not for depression. There's no evidence there. And in fact, some of these studies with high THC content, THC-predominant products, flower products, usually showed worse mood. So for that, I think we feel very, very confident to say, look, if you feel like cannabis is going to treat your depression, you're probably looking in a place that's not gonna lead you where you wanna go. In terms of OUD, definitely a limited evidence of efficacy. If you're using the grading scales, three small RCTs, dronabinol, CBD, and then Yasmin Hurd has done excellent work at Mount Sinai, significant reduction in opioid craving and withdrawal symptoms. But importantly here, these studies haven't looked at opioid use. And I would say that this is one area where I get alarmed, frankly. In Massachusetts, we have certain cannabis clinicians, people who really write certifications for the bulk of their day. And for those folks, they do sometimes use cannabis as a monotherapy. And I think that's really dangerous, frankly. So will we get to a point where CBD might be an adjunct for OUD? Maybe, I mean, we're not there yet. But particularly when we're talking about the people that are dying with the opioid crisis, over 2,000 deaths every year in our state for the past several years. I think this is a place where you really have to be careful. So really try to pump the brakes on cannabinoids when you're talking about using them for OUD. I think that people want to believe that you can avoid the FDA-approved medicines for OUD, but they work really well. And so when people are interested in talking about cannabinoids for that, and I think that, again, such a dangerous predicament that we're in. Post-traumatic stress disorder, moderate level of evidence, not many studies, though. So 12, one RCT. So the JETLI study looked at Nabilone in 10, so a sample size of 10 Canadian military officers. And for that study, it was pretty positive. Again, small sample size, increased overall well-being, reduced disturbed dreaming. I think that, and again, Eden Evans and Meg Haney published a nice review quite a few years ago now looking at the idea that CBD, not whole plant cannabis, probably has better potential for PTSD, but the studies are mixed here. So we've heard a lot about, from the VA and other places, people interested in using cannabis for PTSD, but data is not very good there. So overall, the policy is out ahead of the science. I mean, I hate to keep saying this over the years, but it remains the case, unfortunately. And again, you would hope that people would look at what's been done in other states and see what has worked well, what has not worked well, but overall, as our study in psych clinics showed, really not seeing a closer alignment of those policies with the science. And I will also say that some states have better policies, probably, than others, but overall, the strength of the policies is not one that inspires confidence. And really, very few people are happy with them. People who want more access can tell you they don't have the access they want, et cetera. Those of us who treat these patients recognize the problems with follow-up and the idea that there's poor communication. A lot of times, patients are taking these products, nobody knows it. Should they be connected to the prescription drug monitoring program? That doesn't happen in most states. So there are a lot of steps that need to be taken here. So we are in a critical period. I would say there is some evidence. It's not the best evidence. We'd like to have better evidence, but the use far outpaces that evidence if you agree that some evidence exists, especially for psychiatric conditions. And again, as Robin alluded to, this idea that you need more research, definitely, but I think that really what we're looking for here is informed consent. People are using these products constantly. So I have a wife and two daughters, and there's an endless parade of Amazon packages that show up at my house. Just the other day, I happened to pluck one from the pile, and it said hemp on it, and then my wife actually ordered some CBD, and I said, look, do you have any idea what the problems are here? I mean, there are papers on drug-drug interactions. I published one last year. So again, I think that we have to do a better job of educating people about these things. When we talk about using hundreds of milligrams of CBD, I mentioned purity and potency, but you've got questions of liver function tests. You've got the idea, like I said, drug-drug interactions, which are prominent, as you can imagine, at those doses. And then, of course, when people are using CBD in lieu of treatments that have better evidence, there's a host of problems there. So I agree with the promise. I mean, we're excited about that, but we really need to push the science forward. All I want are people to be making informed choices about these things, and really not there, unfortunately. So with that, I also wanna thank my crew at Beth Israel. These are the folks that kind of free me up and are covering the division while I'm here today, so I wanna thank them, too. And then we'll take Q&A, so I'll moderate. When you come up to the microphone, just say who you are, where you're from, and then we'll hopefully have some good discussion. Thanks. Thank you. Hi, I'm Brian Adanoff. I'm president of Doctors for Cannabis Regulation. Thank you so much for an excellent symposium. Very comprehensive, a lot of information covered. I appreciate the disconnect between policy and science and the need for physician input. I'm worried that our policy, for instance, at AAAP and throughout much of, if not most, of organized medicine our policy is that medical marijuana, we shouldn't have it. And it is so out of touch. 91% of the population now approves medical marijuana. For, Kevin, exactly the reason you saw in your own home. Your wife got it. Everybody hears from someone's mother or father or sister or best friend that it changed their life. So that's where we are. And there are so many important things for us to be weighing in on. Things brought up. Appropriate drug labeling. Should we have gummy bears? What is the potency? Should we have a potency cap? So there are very important things we should be weighing on as a medical profession, particularly AAAP. Yet this blanket, oh, it's a bad idea and we shouldn't do it. I'm worried about that that approach does not seem successful or helpful. I appreciate your comments, obviously. So Dr. Adanoff, for those of you who don't know, has been in this area for quite some time and leads a prominent organization. I mean, I would say having available on our website model legislation, I don't think we're not being involved. But it's hard to do this, really, and be measured about how to do it. So our group, the Cannabis Special Interest Group, we're certainly interested in helping those who want to be involved in their states and their communities to try to educate and affect policy where you can. But it's hard to do. Can we do more? Yeah, I mean, I think that's what we're going to be talking about probably at 12.15. Anybody want to add? I'll add. So I think what Dr. Hill said at the end of his talk that we are excited about the potential. And at the same time, we need to recognize where the science is. It's very important. When we're thinking about these position statements, and I'll speak more for the APA, American Psychiatric Association, there's a desire, especially district branches, are asking for what is the state, what is the official state of things right now. And while there is a hope that we will get to a place where we have therapeutics from this field of drugs, we're not there. And I think if we were to position statement that there's hope and there's promise, that would get carried away in how this is communicated on a legislative level. And so that's why it's important to be very clear and crisp in our position statements. And while they're not rosy and exciting and optimistic, there's so much room for interpretation that that's why, unfortunately, they end up becoming, this is not where we're going, where we're at right now with the science. I can add also. Is this working? Yeah. So Brian, thanks for the question. I think you're absolutely right that our organization could be much more involved in terms of getting useful information out to lawmakers. From a couple of years ago, it was pre-COVID, but Kevin and I had worked between our Canada Special Interest Group and the Public Policy Committee at AAAP that modeled tenets that Dr. Das had put up. We really focused, as addiction psychiatrists, on having a short list of recommendations that really spoke to trying to contain the harm for mental health or addiction related to the use of cannabis or cannabinoids. And I think we were able to rally everyone around that in a way that I think is a bit more difficult for broader aspects of cannabis access, because there's a lot of variation among our membership and the board in terms of what they would support. So we started with where we thought was the most narrow and focused for AAAP, specifically as addiction psychiatrists. But I do think it would be great if we could be more involved in these conversations. Hi. I'm Jim Halicus. In clinical practice here in Naples, a difficult posting, but someone has to do it. First, a general preclinical question or comment. It seems to me that the receptors evolved for a reason. There's something going on that we share with other creatures. And I think we ought to be looking not at psychiatric unique conditions of humans, but rather at systems like the muscular system or sleep system, things that we have in common with animals for utility of the CBD system. And then a comment to Dr. Das. I think the horse has left the barn. I don't think you find anyone who's coming in saying I have a cannabinoid problem, that I'm abusing marijuana, I'm dependent on it. I write marijuana here because it's a medical state, medical marijuana state. And just yesterday, I had a woman in her early 30s who uses it just by the vape cartridge. And it takes care of her four or five-year-old. But she'll step outside to take a toke during the day. Now, we don't have anything like that for alcohol, nor do we have any insight into the behavior. The patient just doesn't appreciate their dependence. I don't think treating it or even identifying it is doing us much good at this point. I'll comment that I think you're right. The horse has left the barn. It's just so common. And I think it's become so commonplace that oftentimes it is not addressed. We just assume everybody is using cannabis, they're not interested in quitting, or they're not interested in changing that use. And so opening the conversation is still important. It's still important to have that as part of the things that we assess, just like we assess for alcohol use and nicotine use, other use. Thanks. Thank you for the excellent presentation. My name is Meher Kazman. I'm a practicing child psychiatrist in Ontario, California. And I just want to ask about, there's no mention of the cognitive effects of cannabis versus CBT, especially for teens and really in the developing brain. And if you can comment on that, considering that even CBD available is kind of like 30% of it kind of like meets FDA kind of like percentages. I mean, has cannabis, I'm sorry, has cannabis in it. So I think it's important really, as we think about policies, is to see how it will impact our adolescents, especially with teens coming, promoting the use of medical cannabis. Is there a question? Sorry. Well, asking a comment. I'll respond a little bit. So I think part of the question was about adolescent exposure to cannabinoids and CBD, but to cannabis, especially the higher strength and daily use of higher strength cannabis for adolescents. And I think a couple of years ago, I gave a talk at MUSC. It was actually a debate on the gateway hypothesis, so a very loaded topic. But through that process, I think one of the things that became more apparent to me is that when we think about the adolescent brain, so through roughly age 24, but certainly in the teen years, a lot of the pruning and the processes of brain maturation, THC is directly impactful for pruning and plasticity of the brain. And I think that has both implications potentially for patients who are at risk for having schizophrenia or primary psychotic disorders, and also implications for patients who are also predisposed to substance use disorders, that especially early life exposure to cannabinoids, especially THC, could have a meaningful impact on throwing them further off course than they would be otherwise. In the spirit of getting people a chance, we'll move on to the next question. Thank you. Karen Drexler, Atlanta, Georgia, Emory University. And I just want to thank all three of you and your absent presenter for just a really wonderful symposium. And I love this idea that you introduced, Dr. Hill, at the end about really the importance is informed consent. So am I drawing an appropriate conclusion that someone who's using cannabis daily has a 30% risk of developing a cannabis use disorder? So as we're talking about cannabis for medical conditions, that's one of the risks we ought to be talking about. How about the other risks that you all touched on, but suicide and psychosis? Can you say a little bit about how you might counsel patients that are thinking about using cannabis for whatever condition about their risk of suicide and psychosis? Sure. So there are a number of studies now that are looking at the risks of, and I'll focus in on psychosis because there's been a lot more interesting work in that area recently. But that, especially with earlier use of cannabis, as well as there was a great study out of Europe that looked at the strength of cannabis and where they have better data about this and found that there was earlier onset of young people experiencing psychosis. And so these studies don't go as far as saying that cannabis causes psychosis, but within people who may have a predisposition to a psychotic illness, it can make that come on sooner and with more intensity. And so definitely a risk there. And there's a dose response, right? Yes. I would totally agree with that. I think one thing that, when I'm speaking to high schools and that type of thing, you definitely can debate some of these questions, cognitive decline, the IQ decrements, things of that sort. But psychosis, you really cannot. So if you do, as Smita said, if you have a family history of a psychotic disorder of any kind, I mean, you're really up to five times more likely to trigger that. Again, we're not saying causal. But I think that, especially when you're talking to young people, they need to be aware of that. So the levels of risk, if you have these predisposing conditions, is really important. And I think, as many of us have seen, once you trigger that, you're not going to walk it back. There are some transient cases of psychosis. But a lot of times, people with a family history will use cannabis, and it will trigger that psychosis. And now you're on this really horrible trajectory where you're battling with people that take medicine that they don't want to take. They might take it, do better for a while. But there's this downward drift that occurs. And so again, I think it's just so important to take time to educate groups where you can so that people are more aware of the risks of what they're choosing to do. Thanks, Karen. Yes, my name is Linda Lundblad. I'm a nurse practitioner from Boston. I have numerous patients who have problems with sleep. And cannabis constantly, or gummies, are constantly being proposed to me. What do I think? And I would like to know what you think. Yeah, I'm happy to take that. So both cannabis and alcohol really have been shown to not be effective to treat sleep. So you're decreasing the amount of time in REM. So I think it's worth having the conversation with a patient saying, look, I understand that you feel like it helps you get to sleep, but the quality of sleep that you get. And CBD as well. I think that if you talk to the real experts in CBD, a lot of people will say that the ability of CBD to help sleep, if it does, has more to do with the other compounds that that particular formulation is constructed with. So I'm always open to evidence, if there was going to be better evidence to come out. But there really isn't evidence for either THC or CBD at this point. But very, very popular, certainly, that people continue to use these products. Good, now I can repeat that to them again. Yeah. Thank you. Yep. Thank you for the presentation. My name is Justin Kunkun. I'm a psychiatry resident from Calgary, Alberta, Canada. Welcome. Where, as you mentioned, cannabis has been legalized for some time. One of the arguments proposed while this was being debated in Canada was that legalizing it and regulating it would actually lower access to youth, because it was, you know, you need an ID, et cetera. I'm just curious, has there been any data on this in states or countries that have legalized cannabis about youth rates of use? That's a great question. Thanks. Asking about youth versus adult changes in access and use after legalization, the joke through the 80s, 90s, until states started legalizing, was that you'd have an adult go to the local middle school or high school, because those were the people who had the marijuana. And they'd trade them a six pack of beer to get the marijuana. And then as there was interest in medical cannabis in the late 90s and aughts, the joke was that the grandmother would go to the teenage grandson and ask for some of the marijuana from the friends to help with her cancer pain, chemo-induced pain. So the children have always been the ones who've had really easy access, for the most part, to cannabis. What's really changed with legalization is that now adults, and older adults, not just 20s, 30s, but throughout the lifespan, are using cannabis at much higher rates, because they have access to legal products. As I was talking about, very commercialized, consumer-friendly packaging and products and sales pitches and all these things. So in general, when you look at legalization, especially for recreational access, you see in response, and we had some of these studies out maybe five or six years ago in addiction, you see that adult rates of use and heavy use do change after recreational legalization. But that doesn't really change among youth. At the same time, I think there's this secular trend where because our cannabis and cannabinoid products are so much stronger, that that's probably in part contributing to among active users, they're using on a daily or near-daily basis. And so when you look at, I think Dr. Dodd said this from the Monitoring the Future, when you look at school-age populations who are using cannabis, it's just incredibly, it's something like 20% of the users may be using on a daily basis. Thanks for the question. I'm gonna actually, sorry, I just wanna add one quick thing. You mentioned regulation too. I think that that's just so difficult because of just how this cannabis and nicotine, like vaping juices are supposed to be regulated. There's so much variability and there's so much variety, I think even though, to your question, when there is regulation, it'll take a long time to figure out how to actually, one, enact it and enact it well. Thank you. Great, thank you. Hi, I'm Leslie Dixon from Las Vegas, Nevada. And my, where of course it's been legalized for several years and now we are in the process of licensing cannabis lounges so that our tourists have a place to use. Anyway, my question is really about the horse that's not out of the barn and that is with the feds. And our problem right now is that we legalized marijuana several years ago by initiative. The voters all voted for it. So now everyone thinks it's in our constitution is legal. And so the ACLU stepped in and they said, we can't keep, our Board of Pharmacy can't keep marijuana as products on the Schedule 1 because it's in our constitution. And yet, and actually a judge agreed with the ACLU on that. So now we're in conflict with the feds and the DEA. And so I'm wondering where you think the federal government's going to be on this issue? I don't think the federal government's going anywhere on this issue right now. I mean, I think that they're making very small, but in terms of legalizing cannabis, if it didn't happen in the last few administrations or prior to Trump, I mean, nothing happened there. I don't see it happening imminently now. There's so much flux going on. But I don't know if you guys think any differently. I don't have any specific information. Clearly, it's preposterous that it's Schedule 1. Our National Academies has this 200-page-plus report on medical applications, and there is substantial evidence for certain medical uses. And so the whole justification for Schedule 1 is that there's no medical application. So we know that that's not true. So it's just so outdated. I do think we've gotten a little bit of traction, and maybe it's just because I'm closer to it. But I know that in the research community, there's been a big push to get THC not unscheduled, but rescheduled at 2, 3, 4, anything that would allow for access to actually conduct studies the way we can for other substances. So it's long overdue, but I don't know of anything that suggests it's really going to change anytime soon. Thanks. Hi, my name's Jesse Gerber. I'm a psychiatry fellow from Portland, Oregon. And you touched on most of the things I was going to ask in the last two questions, but I just wanted to build on that last question and just ask, in terms of this kind of discrepancy where the policy is way ahead on the state level of the science and way behind on the federal level, could that discrepancy in and of itself be responsible for a lot of the issues we're seeing, where we're lacking the regulation and the federal oversight, which could potentially be more protective for people? And at the same time, we're increasing access on a state level, so maybe it's this kind of discrepancy that's problematic. Definitely. I think that people are on the same page on an issue that has very significant risks. So think about it. On other issues like that, like how you prescribe benzodiazepines in a practice, if everybody is not on the same page, people are getting different messages from different people. You're going to have all kinds of different behaviors that are very risky. And that's really what we've seen. Like you said, it's hard to regulate something when there isn't a uniform policy in place. Thanks for the question. Thank you. Dr. Reese? Hi, Rick Reese from Seattle. A couple of things. One is looking at effects of marijuana or components of marijuana. One of the big problems we made with opiates in opiate prescribing that skyrocketed in the 90s was focusing on people's feeling about how they were taking their opiates. And so patients were getting more and more opiates on doses because they were telling doctors it was helping with pain. And it wasn't until you started evaluating function that things started becoming apparent, like people falling asleep with their face in their spaghetti at night or other kinds of things like that that were more dramatic, shall we say, like death. So I hope then the research around cannabis that we start focusing more on function. Now, the people I know who've been heavily into marijuana, and I talk to them about their life trajectory, it seems to kind of level out and stop. It doesn't keep sort of going up. They kind of get stuck in a certain place, daily marijuana users. Whether they get in trouble, whether they get an autorex, that's a different thing. But I think if we start looking at function, we'll get some insight. That's number one. Number two, when we think about opiate users and how many smoke marijuana too, we wonder, well, why is that? Same reason they use meth, too. They can still get high on something that they can't really get high on anymore with their opiate use. I talk to people about, I do a lot of 12-step facilitation with my people that are on buprenorphine and methadone, for that matter. Kathy Carroll did an interesting study 10 years ago. Kathy Carroll was probably the most productive addiction researcher that has ever existed at Yale. She passed away recently, unfortunately. But she did a study where people were randomized to an abuse or to 12-step facilitation that were in methadone treatment. And the people that are on 12-step facilitation decreased their cocaine use by 50%. Nobody ever pays attention to that study, but that was an interesting study. The problem with still using marijuana is, and you start trying to get people into 12-step meetings, is they run into this issue, and actually, if they do stick into 12-step meetings, they actually decrease their marijuana use because they start understanding, it's that issue of needing to be intoxicated that is the challenge in their life and that keeps them using not only marijuana, but methamphetamine and other drugs. So that may be one of the issues with focusing more on marijuana in people that are on opiate-stabilizing medicines that we need to talk about. And the last thing I'm gonna raise is, if we look at the craziness of our society with mass shootings and mass anger and mass craziness, it goes right along with your trajectory of the amount of marijuana use we're using in society. So that might be an interesting societal association. I wouldn't say a cause, but who knows? Thanks. Hi, my name's Mike Susco. I'm in private practice and a medical director of Substance Use Clinic and Program in the Finger Lakes, New York. And I always get asked this question, so now that marijuana's essentially legal, so what do you think about it? My common response is, well, if I drank and I drank every day, several times a day, do you think I have a problem? Usually I get some traction with that one, but it's very difficult because we're against a tide of legalization. I can't help but think the parallels between alcohol use disorder, because alcohol was legal, then it was illegal, then it was legal again. And there's such a financial push now because a lot of practitioners got lulled into this $250 for very little work. And if you ever have gone to a doctor or seen a doctor or a prescriber for medical marijuana, that's gotta be the shortest evaluation I've ever seen. The most informal evaluation I've ever seen. I'll never forget, someone was online, he was in bed, you know, with his phone like this, making a judgment. That was a, it was predetermined that someone was going to get this. So it's very difficult, and I'm in a position that I know an attorney who's left law and now is going into medical marijuana, not prescribing, but growing. So it is a tough situation right now. In addition, I had a father of a young man suffering from bipolar disorder, who asked me, well, should I give my son marijuana? What do you do with that? So it's a tough situation right now, but thank you for really balancing this thing out. Thank you. I don't know if there's a question there. Okay, yeah, no, I do want to say, though, I mean, you know, we've said some things about the cannabis clinicians. I mean, there are people that are trying to do this in a rigorous way. I mean, there are, even in our city, you know, there are people who do, I think, a thoughtful evaluation, but overall, the quality, as I think you were alluding to, it's not great, it's not what it should be. Thank you. Mike Dawes, VA Boston and Boston Medical Center. My one, it's a question of clinical approach and how it informs clinical research. I was just looking at the slides in terms of the one-third frequent users often going on to cannabis use disorder and thinking in terms of, in my own practice, where have I seen that? And oftentimes, the ones that are heavy users are also users of not just marijuana, but tobacco. So I'm just thinking of maybe a way of informing policy is to promote more clinical research, looking at the co-occurrence and the decline when you're treating nicotine use disorders and looking also concurrently at the cannabis use. But I just thought, the panel, what are your thoughts of kind of informing, you know, the funding agencies of specific RFAs and how we would approach that? Because I think that's, we need evidence in order to change policy and we don't really have a ton of evidence, but where would you recommend research guidelines if we, that have any interest in this, moving that forward? We do have a nicotine expert, so. I would say, so thank you for bringing this up, first of all and anytime I can do a plug for nicotine, I will. The, cannabis probably suffers from the same issues of, if you cut this down, this is the case with nicotine, if I don't have my nicotine, then my other substance use disorders are gonna get worse, my other diagnoses are going to get worse. And what we see with nicotine is kind of, the opposite of what you just said, or the flip of what you just said, not opposite, that when people are able to cut down and quit nicotine use, then there is an impact on other substance use disorders, including cannabis use disorder. So kind of in the other direction, there's less around cutting down on cannabis to lead to reducing things like nicotine, but certainly, nicotine is still the leading preventable cause of death in this country, accounting for more morbidity, mortality than alcohol and all other drugs combined. So if that is not a reason to do research in the area of the relationship, I don't know what is. There is evidence though, that stopping nicotine does decrease the prediction of relapse, a couple of years out, there's data, longitudinal data on that. So I'm just thinking that maybe we're talking about, there's not a lot of data, but just looking at the data and asking more questions of terms of treatment. So how would you address that for a patient that we're seeing that's smoking marijuana and tobacco in terms of clinical practice and clinical guidelines? I often discuss the common pathways in the brain. So when we're talking and pull out a picture of the brain and talk about how we know that there's these common pathways. That's why, for example, when I'm treating somebody with OUD and AUD, there's a common medication because of these common pathways. And so pulling on that research and that kind of easier to digest understanding has been how I approach it with patients, be it nicotine and cannabis or nicotine and anything else or cannabis and anything else. Let's try to reduce the strength of these circuits that are, that lead or are associated with a use disorders in general. Okay, thank you. So we're out of time. I'm happy to, we're happy to take your questions if you guys want to come up here, but you guys are heading to lunch. I appreciate you hanging in to the very end. Thanks. Thank you.

cannabis policy

scientific evidence

public health

cannabis use disorder

cannabis commercialization

substance use disorders

endocannabinoid system

opioid use disorder

CBD

withdrawal symptoms

therapeutic applications

cannabis legalization

rigorous research

brain development impact

addiction

informed decision-making