My name is Michael. I am a addiction psychiatrist at the Greater Los Angeles VA Medical Center. And I'm joined here by esteemed colleagues, Dr. Robin Williams, an assistant professor and addiction psychiatrist at the Columbia University School of Medicine, and Dr. Kevin Hill, an associate professor and head of the addiction division at Beth Israel Deaconess Medical Center and Harvard Medical School. And we're doing a workshop on diagnosis and management of cannabis use disorder and other cannabis-related problems. So here are some of our disclosures. So I think it goes without saying that cannabis is a really hot topic of today and is a constantly evolving landscape. As we're learning more and more about the potential medicinal properties of cannabis, and as more and more people are adopting use of cannabis all across the country and the world, we're also finding out a lot about the challenges of cannabis use, ranging from risky behaviors to problematic use with comorbid medical conditions to even dependency. And so it's becoming increasingly more important for us as clinicians to be able to engage with our patients and discuss the benefits in a nice, non-judgmental way, but also the risks that it might bring to them in a way that will improve their overall well-being and outcomes. So that's really the purpose of this workshop today is to equip us with being able to identify some of these challenges that our patients might be going through, from dependency to other related problems, being able to provide some empathic-driven psychoeducation and practical inventions, and also looking into the evidence behind psychopharmacologic interventions and psychotherapeutic interventions as well. And I hope you all can stick around until the end, as we will have a nice case discussion, as well as a Q&A session, where I'm hoping that we can really have an enriching talk about this topic. So without further ado, I'm going to invite Dr. Williams onto the stage to talk about the overview of cannabis. All right, so great to see you all, and thanks for coming out. You know, I think this is an important topic. It's constantly changing. The landscape in the US is constantly changing. And so I think it's helpful to get a straw poll, because people have come from all over the country. So a couple of questions, just by a show of hands. Who's currently a practicing clinician, mid-career, senior, early-career clinician? Don't hold back. I'm going to ask you a couple of questions. And who's in training right now, in terms of costs? So kind of almost 50-50-ish. And who has treated a patient who you would say is really struggling with cannabis use, in terms of really meeting cannabis use disorder criteria? So the great majority. And who has treated patients who have struggled with cannabis withdrawal, in terms of problems related? This is an interesting thing to me. I teach a lot of classes. I teach a lot of classes. And a lot of them don't think that cannabis withdrawal exists. And I have my patients, who know everything. They don't think cannabis withdrawal exists sometimes, too. So we're going to try to give a whole overview. But as the title on Michael's, the title slide for the whole talk, for the series today, is really focused on cannabis use disorder and cannabis-related problems. I'm going to start with a bit of a history of cannabis use disorder. And then I'm going to talk a little bit about cannabis-related problems. I'm going to start with a bit of an overview, just in terms of the cannabis landscape in the US and where we are currently. It's constantly shifting. So this is a little bit of a 101. The slides may be a little bit more basic. And then I'll try to hit some highlights, in terms of interesting things. And I think this will be most interesting, the more interactive it is. So this is a small enough room. At any point, please raise a hand, especially for a point of clarification, or if there's a question related to what I'm talking about. And I'll try to also ask some questions as we go along, just to make it more interactive. We do have a few cases throughout, across the four presentations. Dr. Das was sick and not able to make it in person. But we have her content to go over together. And then at the end, if we have time, we also have some QR codes for pairing off, just where you are, but just to talk through on the sort of clinician-patient dyad side of talking through some cases. So hopefully, this will be interesting and inform your practice. But we're also really interested in hearing from all of you. This is the kind of slide that I kind of cringe putting it up. It's like the requisite sling slide. And to me, this is like practicing in the 90s, or the aughts, in terms of the generation or two of cannabis and the way patients talked about things. What's new in recent years, every year, this number, I've been giving this talk long enough that we started around 100 cannabinoids, and now we have over 140 cannabinoids. And the point is that this, you know, cannabis sativa is a very complex plant. It's not, you know, alcohol is the opposite, right? Ethanol is a two-carbon molecule. It's just, it is what it is, basically. But with cannabis, you have all of these cannabinoids, terpenes, all these other chemicals. There's this interest in the entourage effect, which may be real, or just a bunch of smoke, unclear. But the point is, cannabis is not just one thing. And so you really have to be thoughtful in terms of talking to the patients, ask the patients what they are taking, what they think they're taking. I think you all know this, but the testing and labeling is completely, is often inaccurate and not reliable. So it may say it's 10 milligrams of THC. It could be anything from zero to 100. And so the patients are often pretty adamant. They know what they're taking, but you really can't rely on the packaging alone. So it's really a new world, and I think THC, CBD, most people are familiar with. Briefly, and I have one or two slides on pharmacology or in the pharmacode, the physiology of cannabinoids in comparison to endocannabinoids. So THC and CBD have gotten a lot of attention, and in part, that's because, I think we can, familiar with the Overton window. The Overton window, in terms of the drug war, has shifted. So 20 years ago, we could talk about the drug war, and plenty of people knew that this had been kind of a mess, and there'd been over-incarceration of folks, and it was racially targeted. And now, I think that's a very mainstream thing to be talking about, and so not a surprise, there is this preoccupation with THC, because THC is often incorrectly described as the only psychoactive, or between CBD and THC, the psychoactive cannabinoid. But what does that mean to be psychoactive, right? Anything that works in the CNS is psychoactive. The point was that THC, in particular, is what causes the high, the euphoria. It can lead to more hallucinatory and paranoid symptoms as well. And the thing to know, and we're not gonna talk about synthetic cannabinoids today, but THC is actually a partial agonist at the CB1 receptor. I didn't know that for years, so I think it's intuitive to think, or the way we talk about it often suggests that THC is a full agonist at CB1. It's actually more of a partial agonist, and the main point there is that the synthetic cannabinoids, back during the whole heyday of K2 and Spice and all these things, those were full agonists at CB1, which is part of why people were so dysregulated cognitively and behaviorally with the synthetic cannabinoids. So CBD is a negative allosteric modulator at the cannabinoid receptor. So what does that mean? Basically, it means that when THC is in the presence of CBD at the cannabinoid receptor, it actually modulates or sort of decreases the activity of THC. The point there is that THC alone, in the absence of CBD, is gonna be stronger, basically, in terms of its effects. Some people are gonna say more potent, some people would say stronger. THC and CBD share a common precursor. I'm not gonna belabor this too much, but CBG at the bottom, so CBG and Delta-8, these are kind of the new hip cannabinoids that people are talking about. And I said there's 140 others. For those of you who've been in medical or recreational cannabis shops in the last 10 years in particular, you've probably seen, there's also, it's endless, right? There's THCA and THCV and this and that. There's tons of them. But the point is that CBG has become a bit faddish, especially if you're interested for people on the West Coast. And CBG is the common precursor to THC and CBD. And the idea is that it acts a little bit more, some of the emerging science, but the lore around it is that it acts a bit more like a CBD in terms of its effects. So people may have more, may have more anxiolysis or feel more relaxed, but it's less of the THC effects, especially the unopposed THC effects that can lead to euphoria and whatnot. And then Delta-8, and I have a slide on the federal law, Delta-8 in part came about because of the 2018 farm bill, which in part legalized hemp. And the idea with hemp, which is a cousin to cannabis, is that it's under something like 0.2% THC. But what that also meant is that from using hemp, people could extract Delta-8 THC, which is not schedule one, like Delta-9 THC. So THC at the top, for those of you who don't know, is Delta-9, shorthand for Delta-9, it says THC. So the idea with Delta-8, sort of like CBG, there's this idea that it's kind of like THC light, that it's Delta-9 light. So fewer side effects, better tolerated. So all of this stuff pops up in the news, and these are the kinds of things that you may have, that your patients may ask questions about. So I think this, in some ways, is kind of a replacement to the older slide, in terms of the slang, when marijuana was largely more consistent. And I'll just hammer that point one more time. So up until the 90s, right, if you think about the 60s, 70s, 80s, for the most part, cannabis was cannabis. And the reason we're saying cannabis, it's a scientific name, and it sidesteps marijuana, however you spell it, which has more problematic connotations in terms of its history. So in terms of cannabis, it was largely consistent in the U.S. People would go, older people would go to their grandkids, and otherwise kids would go to other kids, and they would get cannabis through these illegal networks. And, or people would grow their own, right? But ultimately, it was whole plant cannabis. And then people could perfect ways to figure out how to grow stronger cannabis, or use different parts of the plant and smoke it, and then in the 90s and aughts, the vaporizers, people would go and order vaporizers from Germany or Europe, and the idea with vaporizers is that you can heat the cannabis without incinerating it, and so the cannabinoids are released and they're inhaled, and you actually get more bang for your buck in terms of the, because you don't degrade the plant material, as opposed to incineration when you smoke it, right? But the point was, more or less, cannabis was cannabis. Some people would make products with the cannabis in terms of edibles, for instance. But what was that? They were mostly making a cannabutter, making brownies, sort of the archetypal cannabis-infused food. But it was just with whole plant cannabis. The point is that we're in a completely different world now, right? So people go into a store, and there's tens of thousands, if not more, products in the U.S. now, and these are often distillates. So it's no longer whole plant cannabis that can be smoked or vaporized or put into a fatty sauce, like a butter-based thing, and then cooked. People are going in and they're getting a gummy bear that can have 100 milligrams of THC in one piece of food, right? So it's a totally different world, and this has some connotations that are gonna pop up throughout the slides. Sorry to belabor that, but I think it's important context here. So in general, there's two cannabinoid receptors, CB1, which is predominantly in the CNS, and CB2, which is predominantly in the periphery. And the point is not to memorize the slide as much as to emphasize that, just like with any other major neurochemical neurotransmitter system, this is interconnected with all sorts of other neurotransmitter systems. It's not like there's THC, it goes to CB1, it does one thing, and that's it. I mean, this is all wrapped up in a lot of things. And so the cannabinoid receptor, CB receptor, is a G-protein-coupled receptor. It's actually the most common G-protein-coupled receptor in the CNS. So this is incredibly important in terms of development through adolescence, so there are implications in terms of adolescent use for THC, especially during pruning in the sort of mid-teen years in cognitive development. So taking a step back in terms of epidemiology, a couple things to note. So not a surprise to the extent that cannabis is still illicit. It's the most used, most widely used illicit drug in the U.S., many tens of millions of people. And my team at Columbia and others have replicated this where what's really changed in the last 20 years with the liberalization of access to cannabis through medical and recreational channels, it hasn't increased the prevalence, has not really increased the prevalence of youth use. What's really changed is adults and older adults, so people in their 40s, 50s, 60s, who otherwise would have never accessed cannabis are now able to go into a store and get it. You know, Martha Stewart, just as an older adult, is selling her gummies and things like this. And so there are all these markets that have sort of been created that would have never appealed if it was restricted to the whole plant cannabis up through the 90s and aughts. And what's really changed is not just that adults, there's a higher prevalence of past month, past year use among adults, but that among users, and this is a key thing to know if you don't know it, and it's highly relevant to our clinical practice. Among users, what has dramatically changed is daily use. The percent of people among active users, an active user typically means past month or past year, which is kind of wild. When you think about it, someone uses cannabis once in the last year and they're an active user, but that's how NSDUH has set up the SAMHSA survey to monitor these things. So among active users, daily use or near daily use has really increased dramatically. And when you think about active users, the risk of cannabis use disorder, the textbook has long said that it's one in 16 adults among people who are regularly using it as youth, teenagers, it's one in 11, so higher rate of cannabis use disorder. But when you look at daily users, it's 30 or 50% of people who will meet criteria for cannabis use disorder. And so in general, in the last 10 years, the number of people has more or less doubled from around five to 10 million people who have cannabis use disorder in the US. So federal law, I think everyone's familiar, at the federal level, cannabis, THC, remains schedule one, which specifically means that there's a high potential for abuse and no currently accepted medical use. And other schedule one, so LSD, heroin, psilocybin, MDMA, of course, a lot of things on that list are being reevaluated and there's also a lot of interest in psychedelics right now for medical and psychotherapeutic purposes. I mentioned the farm bill, I was close, I said 0.2, but hemp has to be under 0.3% THC to be considered hemp and be allowed to be grown. And this has contributed to the Delta-8 and also CBD, this explosion of CBD products. So the FDA has taken action against dozens of companies in the US that have been selling CBD-based products and a lot of that, it's not even because they're selling these unregulated CBD-based products, it's really because they're making claims about therapeutic indications for the CBD products that are not supported. And this is in part, so there's the farm bill, but then also in 2018, Epidiolex, which is a CBD concentrate, came to market and initially it was schedule five. And so that led a lot of people to think that there was now a legal gray zone because if the FDA is saying CBD is schedule five, then that means it's not schedule one, even though THC remains schedule one. And then it was around 2020 or 2021 that they actually descheduled, the DEA descheduled Epidiolex completely. And so that sort of created this whole area of confusion in terms of how to regulate CBD. One thing to be aware of for justice-involved or criminal legal-involved individuals is that typically anyone on probation or parole has to follow all federal and state laws. So even for someone in a state that has adult recreational access, because of the federal schedule one illegal status, that's part of why a lot of people are still at risk for violating parole and being sent back to carceral settings for using cannabis, even if it's legal in their states because at the federal level it's not. This is the kind of slide you can put it together and six months later it's no longer accurate. So the point is that the great majority of states have legalized some form of cannabis for medical purposes. Usually that does not have an age restriction. And then almost half the states have legalized for recreational, and that's always gonna be adults 18 and above or 21 and above. And the states have a whole mix based on medical and recreational structures for how they regulate this in terms of other limits on content or dosing or packaging. And one thing to know about in terms of, some of you are probably familiar with excise taxes, but the idea is that often in a given state, the recreational products or recreational locations that are selling have an additional layer of taxes, 2, 5, 7% beyond the medical shops. So the joke in Colorado is that the locals get a medical card and the tourists who are coming out skiing and hiking go to their rec shops and pay higher taxes. So medical use, I won't belabor this. The main point is that for decades we've had FDA approved medications, Dronabinol, Schedule 3, Nabilin, Sesamate, which I think is out of production. I mean I don't think they're making Sesamate, Nabilin anymore. I think they may have discontinued. But anyway, so there's a Schedule 3 and a Schedule 2 form of synthetic THC basically that were approved for nausea, vomiting, AIDS related cachexia, and then most recently Epidiolex that I had mentioned. But then obviously most people are gonna be using what's available locally through shops or black or gray markets or growing their own. Okay, so the great majority of people who use medical cannabis, this has been consistent for many years. It's for chronic pain or neuropathic pain. Kevin's written, Dr. Hill's written some of the more substantial reviews on where the evidence base is. The National Academies of Science and Engineering and Medicine has a report. And what's a little bit of a surprise if you think back to how Marinol or Dronabinol was first coming to market, which is for nausea, vomiting, and AIDS related cachexia, is that the strongest evidence base is actually probably for chronic pain, neuropathic pain, and also for spasticity related like to MS for instance. But this is the most common reason people report using. Now the important thing to know, especially because most of us are psychiatrists or psychiatrists in training, is that there are no psychiatric indications. And just was it last year in the American Journal of Psychiatry there was a review reiterating this. And I often find in the subsequent section we talk more about psychotherapeutic stances and how to talk to patients about their use. But I often find myself talking to patients about cannabis the same way I talk about alcohol or maybe benzos. Where sure, it helps you fall asleep. It helps you feel less anxious in this moment. You're having a stressful semester at school or you start to work at this new job or something. But long term, typically what happens is that people build tolerance. They find that they need more and more to achieve the same effect. And if anything, when they're not using they're actually finding their stress levels are higher. It's harder to sleep. And so you sort of, people can wind up, not everyone, but some people wind up kind of painting themselves in a corner where all of a sudden they're still not sleeping while they're still anxious, they're still stressed out. And yet now they have what's become a pretty expensive and consuming habit. The same way it can happen with alcohol, it can happen with cannabis. So it's not to demonize it, it's just that it's a real risk for a subset of people. So the red warning bar here is pointing out that I have this itemized list of which psychiatric indications some states allow. But there are also other states, my home state, New York, where they have this sort of all comer category for anything that would be recommended or authorized by a licensed clinician. It would be allowable in that state. So it's really sort of throwing the doors wide open. So in terms of assessing cannabis use, I'll talk more about this in Dr. Das's slides later on, is that you really do wanna get an understanding of what the patient's using. And I had this slang slide early on. I've had trial participants at Columbia and patients, and they'll talk about a blunt or smoking or a joint. And it's worth having them really explain what they're talking about. And I think if you're curious and non-judgmental and they can tell that you're trying to help them, people are gonna be, especially if this is a big part of their life, they're gonna be able to talk pretty fluently and openly about what they're using. But the main thing for trainees is what I say is don't hold back and be too apprehensive about having people define their terms because you could see 10 different patients, each of them says they're smoking six blunts a day, and it could be totally different things. And so it's worth just asking them what they mean by all of this and getting a better sense of it. Oops. All right, and so then I'm gonna go through sort of briefly this list. So, all sorts of different ways people can consume now. I was belaboring this earlier, but the point is that it really is different than prior generations in terms of the many different ways people can consume. In terms of cannabis use disorder, this also means I've had several patients come in, one literally his fiance sent him in the month before they got married, and she said, I found this whole trove, thousands and thousands of milligrams of edibles, and I had no idea that he was totally addicted to cannabis. And so, similarly with the pills, and when, not as much now, but certainly in the last 20 years, it was often patients would come in, they were taking tons of oxycodone, all his spouse had no idea, parent had no idea, coworkers had no idea. There are just ways for people to conceal, whether it's a discreet vape pen, or with edibles, you know, ingestibles, where people can have really high tolerances and really high levels of ingestion, and yet people around them have no idea. So it's kind of a different world. Okay. So these are, you know, I think this is self-explanatory. I'll talk more about this in Dr. Das' section, but I think you're all familiar with the 11 criteria for a substance use disorder. One of the interesting things in the DSM is that they don't specify, you know, what the substance is, it's sort of the same 11 criteria. So we'll talk more about how that compares across different classes of substances later on. And so just a real brief case here. So let's say you're practicing in a state. A few years ago, a medical cannabis program was legal, so you know, cannabis for medicinal purposes is legal, but the staff psychiatrist is not sure if anxiety is an indication for using medical cannabis, and is worried about medical legal liability. You explain this to the patient, and let's say, you know, this 35-year-old man, he gets frustrated, he says, fine, I'll just go to the vape shop and buy some without your help. So what, has anyone encountered this? Okay. So what are thoughts? There's some chuckling. I mean, this is a pretty common sort of scenario broadly, but what do you tell a patient? What are your options? I mean, I know this is a bit vague, vaguely written, but what do you do as the clinician? Yeah, please. Except that you really can't control the patient's behavior. Like, hey, this is really your choice if you want to do that or not, and if you want, I can tell you about some concerns I have and some, what I know, but you can't feel like you're gonna enforce them to take your medicine. So I think part of your point is ultimately, patients are gonna do it, they're gonna, people are gonna do it, they're gonna do. Yeah. In the VA, for example, where cannabis is still, smoked cannabis is still very much a schedule one. Because of the way that VA practice is practiced, you really can't, you can recommend, you can educate, you can do all sorts of things, but in terms of not being willing to work with patients, in the VA of 2023, you're really compelled to accommodate in some way. I mean, if you're in a private practice somewhere, I think you do have some options. But in the VA, for example, which is where I live and work, you really don't. You have to, again, kind of accommodate and educate and do what you can. You're pointing out the VA is a bit of a unique situation in terms of federal, with the federal law and what you can recommend. And yet, there's still been a bit of a shift in terms of the culture attitude, in terms of educating patients, talking more openly about it. Anna, yeah. I'm from New York and I found that in my practice and private practice, they don't even ask. It's more expensive, and so it's like asking whether or not they can have a little coffee. So it doesn't even look, maybe two years ago, they would ask for that card, but they just smoke it. I just think that's maybe a little bit of an ask. I just have to know to ask them. But it's not a must. Yeah, I think part of the opportunity here is, if anything, is to reinforce to the patient, I'm glad you're letting me know that you're doing this, because I think historically, people would have concealed this and not told the clinician. Yeah, please. Yeah, I've been sort of, my patients, like, look, I've seen a harm reduction approach in saying, basically, if you're gonna go get cannabis, at least look at CBD, as opposed to THC, straight up. There's less indications of it potentially really affecting your stress response systems down the line, so let's at least look at that, if anything else. So recommending that people are going to get cannabis products to look for CBD, so we haven't talked about ratios, but look for products where it's either CBD or have more CBD in the ratio to THC, from a harm reduction perspective, yeah. Yeah, please. Now, I'm not a clinician, but looking at this case, wouldn't you rather, so I assume this is a general supply, it wouldn't be addiction, because that's one of the consequences, right? So wouldn't you wanna actually address the anxiety of possibly offering alternative treatments, like prescriptions? Like, for instance, in Canada, cannabis is a bit expensive to go to the store, but if they can, if they have a prescription, I think it's a cheaper option for their anxiety, unless they want cannabis for other reasons than anxiety. Yeah, so pointing out that we do have evidence-based treatments for anxiety, so if this is a general psychiatrist, for instance, it would be totally within their wheelhouse to give recommendations, treatment recommendations. Yeah, so you wanna treat, like, in that department, try to get something to have, so if it's a sort of one-size-fits-all deal, like, whatever the standards of treatment are. I mean, I'm just, sorry, I'm not a clinician, so I'm not talking from experience, but I'm just making sort of recommendations in this case, what would you logically try to treat for anxiety? Oh, yeah, no, it's a very important point, and this is a truncated case, and it initially, not, I mean, this is sort of relevant, but initially, the patient was on something like 10, 20 milligrams of Lexapro, had a partial response, and then says, well, maybe I'll just go get cannabis, and that part of the history or not, I totally agree. The opportunity here is to explain to the patient whether evidence-based treatment, in the same way a patient who wants a bunch of Xanax for their anxiety, explain, well, you know, it's not actually FDA-approved for chronic treatment for anxiety, even if it can be useful in certain, or Klonopin can be useful in certain circumstances. Yeah, yeah, final comment, yeah. Can I just clarify, is there anything inherently different between the two different products that you might get at, like, a medical dispensary versus a recreational dispensary? Because if they're both available in the same state, in this case, like, I'm wondering if Mr. Jones were to go to a medical dispensary with, you know, a prescription or a medical card for this, two comparable products, is there an inherent difference between the two? You see what I'm saying? Yeah, so it's a great question. I'm repeating some of these just because it's recorded, and so, question about, are the products really different between the medical dispensaries and rec dispensaries? And, I mean, one of the jokes is that you have the same building, and there's a door on one side for medical, a door on the other side for recreational. It's all the same products. It depends on the state. So we had a study in health affairs, now it was maybe 10 years ago, but we looked at, at the time, there were 14 states that had active medical cannabis programs. And these started with 96 or 98 in California, and, right, they have voter-based referendum to the propositions. It was like a paragraph was passed. You flash forward 15 years, New York State passes a medical cannabis program, it was 120 pages of regulation because the state legislature debated it and passed a bill. So it's totally different worlds. And so, in New York, and this is still more or less the case, they do require FDA-level testing and labeling of the products. And so that is potentially a difference where if you have a patient in a state where there is that state level of regulation, then you can be more certain that whatever the person thinks they're buying is actually what they're buying and consuming. And if the medical shop now has a recreational shop because now the state's allowed recreational, then it's probably, they're the same level of quality. But if you're in a state that doesn't have that level of regulation and oversight, then, I mean, there are several published. Sally Hopkins went out to the West Coast, and there are other groups that have done this around the country. And it's pretty consistent that when they test things in the lab, it's not how it's advertised, just in terms of what it is, beyond what they're claiming it would actually do for people. I have a comment about the question. Please, yeah. So I'm in New York, as you are. And so this question comes up, there's two reasons why this is something to talk about, is that if you get a medical cannabis, it's cheaper than if you get recreational. And they tag on about 20 to 25% in taxes or whatever. So actually, medical cannabis is not cheap. You can go to a, you can buy it on the street corner, it'd be less money. Okay, so one of the reasons that they request for a medical cannabis card is to save money. The other thing, though, is that in New York, and this may be in other states too, is that there's all kinds of shops around the city that are selling cannabis that are not approved cannabis stores, if you know what I'm saying, right? And so, and we don't know what's in those. Okay, so that stuff is not regulated, and they're trying to close those places out in New York City. And it's really actually a challenging issue, because you don't know what's in some of that weed sometimes. So just a couple things to help. Yeah, very true. Thank you. The final thing I'll say, and this is from a talk that Dr. Hill and I often give at APA is that we don't really talk about drug-drug interactions or hepatic clearance of cannabinoids. And this, for most people, this is probably not that big a deal, but it should just be on your radar that there are some of the cytochrome, like in the P450 system, that there are a handful of cytochromes that do clear some of our commonly prescribed medications, including SSRIs and SNRIs, where THC and CBD can have interaction. So it is something that's worth being aware of, especially if you have a patient who has a certain response, and then they add in a cannabinoid of whatever kind, and then their response to their prescribed standing meds change. Okay, Dr. Hill, you're up. All right, so I'm going to talk about effective pharmacotherapies for cannabis use disorder, so I've got the short talk. So I want to thank Michael for inviting me. Also, for joining Robin and Smita, as always. It's a lot of fun. In terms of my disclosures, I've written a couple of books on cannabis and consulted some organizations, including the NFL. I'm the co-chair of the NFL Pain Management Committee. A couple of things I want to say about cannabis use disorder. I'm the co-chair of the NFL Pain Management Committee. A couple of publications that we've come out with over the years, so Robin and I wrote that in Focus Psychiatry, maybe five years ago, and then I think Robin mentioned the AJP paper that came out late 2021, and actually we've got a book chapter, Michael and I, on cannabis use disorder in some collection, Journal of Neurological Sciences or something, so there might be more to come in these areas. So the take-home point, really, no FDA-approved medications. However, as we were talking about earlier in the cannabis special interest group, I think that being willing to talk about these issues is a great opportunity to try to steer people towards maybe more evidence-based treatments where appropriate. So when thinking about how to treat folks who have legit cannabis use disorder, I think ultimately, hopefully, we're gonna be at a point where we're thinking about a combination of an effective pharmacotherapy or pharmacotherapies plus a behavioral intervention. I'm partial to CBT. Again, I think we're gonna hear more about at least motivational interviewing and other behavioral modalities to treat CUD, but I think that combining these two and talking about this with your patient, right, think that you would come in using cannabis multiple times a day, many years, and to think that a bottle of medication is gonna solve that problem, much as ridiculous as it would sound for alcohol use disorder or OUD, this is really a similar situation. We need to do a lot in order to try to change behaviors that have been ingrained in somebody for a number of years. So I think there are medications we're gonna talk about, N-acetylcysteine, gabapentin, abiximols, which isn't available in the United States, cannabidiol, we're gonna talk about those just a little bit. The idea that should you, if you're in a position where you're addressing all these other issues that they may have, right, any CUD usually doesn't occur in a vacuum, so if your patient with cannabis use disorder has an anxiety disorder or a mood disorder, you wanna address those as best you can. If you're doing all those things, ideally, hopefully, they also have a therapist, then I think it's fair to think about perhaps a medication. Oftentimes there's not a lot to lose, but I do think you need to be realistic about what you're gonna achieve. And then moving forward, certainly you're gonna monitor their cannabis use. So I think that's one thing that hopefully you hear more than once over the next few days is that no matter what SUD you're treating, it's imperative that you're monitoring their use, biochemical verification of abstinence or whatever level they're at. So I like quantitative levels. I use saliva mostly when I'm treating patients with cannabis use disorder. But again, you gotta say that up front. Look, this is something that we're going to do and I want you to tell me how much you're using, but we're gonna test you anyway. I mean, we have to do that. Self-report in SUDs, not very effective, unfortunately. So it's just something that you have to do. Additionally, if we're treating these other co-occurring disorders and we're testing and perhaps using a medication, we like to use mutual help where appropriate. So marijuana anonymous, or you can use AA, or whatever, it doesn't matter. But the idea that if you can bolster what we're doing with multiple efforts, I think you have a better chance. So N-acetylcysteine, antioxidant, glutamate modulator, Kevin Gray, down in the front row here. Thanks for coming, Kevin. He published an important study in American Journal of Psychiatry in 2012 where they used N-acetylcysteine 1,200 twice a day plus contingency management, something we were talking about earlier today. And those participants were almost 2 1⁄2 times more likely to produce THC-negative urine. So that's hard to do to have people, question? Yeah? Yeah, if you might go back to the previous slide. Sure. I've never found it really helpful to get quant levels. What is the goal for getting those in your mind? Yeah, so to me, I think that if somebody comes in and we're gonna treat their cannabis issue, they're smoking 20 plus times a week, I think that, and as much as I would love it if we're able to have a negative qualitative test, I don't know how realistic that is sometimes. So to me, I think that if you're using 20 plus times a week and we're able to get down to a place where maybe they're using a couple of times on the weekend and therefore not having a negative qualitative test, I think that's still a clinically significant reduction. So it's kind of where I'm still hoping, and we talked about this earlier today too, I'm hoping for at least a limited period of abstinence. I want, if I'm treating somebody who's mandated by their employer to have treatment for their cannabis use disorder, I'm doing everything I can to try to have them not use at all. But I recognize that, again, when you're talking about using dozens of times a week, if we're able to get to a point where it's much less and that's verified in their level, then I think we've done something, right? We're still trying to get them to be at zero, but I don't know how realistic that is for everybody. I don't want to go down the rabbit hole. Yeah. When people use, does their want level go through the roof and then it dies off quickly? Where if they used five days ago, it's gonna be similar to if they used two days ago? Yeah, no, I think that's an excellent question. To me, where I'm, so everybody's different, how they're processing this and your levels could be different depending on what the patient is, but I think that if you're interpatient quantitative levels, I think that's a useful way to monitor their levels of use relative to the visit. And saliva testing, comment on that? I mean, I like it, it's easy, right? So you can, depending on the company that you're using, you just give them a swab, they put it in their mouth, you pack it up, FedEx it, boom, you get a result. I mean, it's not the only way, but I think it's pretty easy. In terms of sensitivity, specificity versus? I mean, I'm not representing the companies, but I think it works pretty well. Are you talking about a quantitative level? Yes, yeah. It's a narrow window of detection, so it's saliva THC, so you get very small window. Urine has a residual, which is good enough, but it's just indifferent. Yeah, yeah, I just like, I mean, again, I think the point is, I think really, you gotta have some way you're gonna measure what they're doing, and as long as they know that's gonna be part of the treatment plan, I think you're in a much better spot. As you may see, there are a lot of patients out there being treated for a lot of SUDs that, just not being monitored, and there are a lot of reasons for that. People are still saying, we stopped testing during COVID. Well, that period's over, so we really need to, I think we need to use this as part of an effective treatment plan, but the way that you're testing, I'm less concerned about that. So back to NAC, the positive study in 2012 was not replicated in 2017, but I think that when you think about risk-benefit, this is a medication that really the potential risks are not many, so that if you're doing everything else, I think that this is a fair medication to try. We've had some people do well. I mean, it's not a panacea by any stretch. Also, this is something that people can get without a prescription. You know, there are companies that make it, and there's certain companies that Dr. Gray used that I think are probably better than some of the other companies. So I think that's a good, it's a good choice, but I think you have to have realistic expectations when you think about using meds to treat cannabis use disorder. Gabapentin also has a positive study, Barbara Mason, who is relatively local, 1,200 a day for 12 weeks, reduced use, self-report in by lab testing, and also withdrawal symptoms. She also had a positive study for gabapentin for alcohol use disorder as well. So again, if somebody's already on gabapentin, and possibly they're on a dose lower than 1,200, I might, you know, go to 1,200 with them. The Dixamoles, again, not FDA, not available in the United States, but a positive study, you know. So the idea that you might use a cannabinoid to replace another cannabinoid, I think is one that, you know, has some merit to it. And so, you know, with this study, was, you know, relatively positive, well-tolerated. Question is, you know, could you use more, more of nabixamoles to do better? Oh, I think I skipped one. Cannabidiol as well, something that could be used, as Robin mentioned, negative allosteric modulator, multiple receptors. I think one cool thing that we talked about in the AJP paper in 2021 was the idea that because it affects multiple receptors, the dose that's necessary to affect those different receptors is different. So I think that's something to think about when you're, you know, thinking about using cannabidiol to treat a variety of ailments. You need to think about what receptors you're targeting and the dose may differ. However, you know, using 25 milligrams, you know, is probably not gonna do much. So really, no matter what you're treating, you're gonna need in the hundreds. And then also just to clean up a point that was made earlier, I definitely think that CBD has less risk than THC, but it's not without risk, you know. So you need to think about drug-drug interactions. You need to think about checking LFTs if people are on CBD at a level where they're above, you know, a couple hundred milligrams. In the back? Yep. When you're sourcing CBD, is there a product you're not buying? Not particularly. So what I say to people, you know, if we're gonna use CBD to treat anxiety, let's say, or treat cannabis use disorder, I don't use it to treat cannabis use disorder much. You know, I'll say, here are some companies that you could look at. I'm not gonna, you know, promote any one particular company, but I say, look, think about what formulation you might be interested in, and then think about what the cost is. So one of the issues with CBD, whether or not it works, whether or not we're talking about the potential risks of it, the fact of the matter is it's pretty expensive to use because you can't use Epidiolex off-label and have anybody pay for it. So it becomes almost prohibitively expensive for most people, and that's why I think the trials that I've had with patients who have used it have been pretty brief. But, you know, the Freeman study suggests that, you know, this is something that possibly could be further developed for cannabis use disorder. And then Meg Haney had this paper come out earlier in 2023, I think. So signaling-specific inhibitors, Aeolus Pharma was the company, and they showed, they had animal studies where they decreased self-administration of cannabis, and then also human lab study, I think it was, showing less subjective effects of cannabis. So there are other medications in the pipeline. I would say that, again, you know, one of the things that I like to say is that when you've got, as Robin mentioned, if you've got millions of people with cannabis use disorder, you'd like to have more interest, I think, in developing a pharmacotherapy or pharmacotherapies that might work for these folks. So yet another case for us. A 28-year-old man, past medical history of depression, presents for a consultation about his cannabis use at the request of a significant other, smoking cannabis four times a day, miss work, some family responsibilities. He has a therapist. He's prescribed Sertraline for his depression. You recommend the addition of the following medication that is FDA-approved for cannabis use disorder. So that would be E, unfortunately. So hopefully that changes. I think that's just an important take-home here. You know, At this stage, we don't have, and we've got pretty good tools for alcohol use disorder and opioid use disorder, but that's not the case here. So, overall, no FDA approved medications, but I still think that using pharmacotherapies for patients with cannabis use disorder is important because they probably have other issues that need to be addressed. If you do use a medicine to treat cannabis use disorder, I think you need to have realistic medications on all sides. And, you know, again, there have been some excellent studies that have been done, but overall, I think that we could do better. And there are a lot of reasons for lack of progress in that area. And so, these are available. You know, you guys can check out these references. And now, I think Dr. Williams will present some EDA slides. Thanks. Dr. William Williams. So, Dr. Das sends her regrets, and she is also on the APA Council for Addiction Psychiatry, or has been for years. And so, it brings a lot of great content that complements what we're presenting on. So, the focus of the next 10 slides or so will really be on engaging patients and thinking about how to talk to patients. And again, you know, the more questions, the better to make this interactive. So, we want you to, and I think it sounds like a lot of you have experience of comfortable assessing cannabis use and cannabis use disorder among your patients. And I'll touch on some in my, in particular, but just talk in general about some of the idiosyncrasies of working with patients with cannabis use disorder specifically compared to other substance use disorders. So, I think this list of 11 is familiar to everyone, perhaps for trainees, just to emphasize that one of the things that shifted, so that, you know, the DSM-IV TR came out in 1994, and so it was about 20 years before the DSM-V came out. And in that time, our understanding of substance use disorders changed dramatically, in part because of neuroimaging and other lines of investigation. So, with the DSM-V, the nomenclature on a substance use disorder, right, part of that is to invoke this idea that it really is a spectrum in terms of severity. So, among these 11 criteria, if people meet, you know, two or more, three to five, six or more, it's specified as mild, moderate, or severe. And one thing that's a bit different, though, with cannabis use disorder, I think Kevin kind of baked this into that case that he just shared, was I think the spouse or the wife of the patient had called. And this is something where it's not uncommon with substance use disorders to have a spouse, a loved one, a good friend, a parent, call on behalf of the index patient to try to help them get into treatment. There's nothing wrong with that. But there is a sort of a flavor of that where I've had, over the years, especially friends and spouses call for the index patient, where it's very apparent to them that the patient's really become debilitated by heavy, constant cannabis, cannabinoid use, whatever the products are. And the patient really doesn't have insight into it. And that's never a surprise with substance use disorders. Patients may have some level of, whether we think of it as a lack of insight or denial or ambivalence in terms of how they talk about their relationship with their substance use. But I think part of what's different with, and we have this in the focus article and the annals in the clinic article, is that often the way that cannabis use disorders manifest, it's more along the lines of negative symptoms, right? So it's sort of withdrawal, where patients aren't doing as much as they used to or could be doing. So it's kind of, you know, showing that you can't, you don't really have the counterfactual to know what they could have been doing otherwise. There's all sorts of studies that have shown that patients, people who are using, you know, cannabis heavily when they graduate from high school or college and they go into the workforce, that they tend to settle, they tend to receive lower paying jobs, for instance, that they're less engaged with activities. And so this is where it can be hard compared to, you think about psychostimulant use disorders, where traditionally there's more externalizing behaviors. I haven't had a patient who's injecting heroin come in and say that they don't have a problem with heroin. They may have reasons for why they want to continue or try to control their use. But with cannabis, it can really be different. And so there can be some subtleties in terms of how these 11 criteria manifest for a patient. One thing I'll also caution, and I think this would be an interesting topic for conversation for this group, is that you can't, I think most of you would notice, but you can't ask patients, it's not as simple as asking patients, do you ever have cravings? Or if a patient's been cutting down successfully, are they struggling with cravings? We talk about cravings all the time, and it's literally, you know, one of the words or terms in the DSM. And it may be obvious, but cravings, people really understand what cravings are differently, and some people don't use that, or patients don't use that word at all. And so you have to poke around a little bit to really get them talking about what they're thinking and feeling. And, you know, you can think sort of a general example, you have a patient working, let's just say, kind of a normal hours, full-time job, and at the end of the day, every day, this person denies having any cravings, and yet by the end of the workday, by 5, 6 p.m. or something, this patient's, you know, all they're thinking about is being able to get home and whatever it is, alcohol or cannabis or something else. But it doesn't occur to them that that might be in the craving category. And, I mean, that can show up in so many different ways. I'm sure people have all sorts of anecdotes about that. But the point is to, even though the 11 criteria may be the same across different classes of intoxicants, it can really manifest differently based on what the person's using. So, I think a lot of this is self-explanatory. So, I'll hit some highlights that stand out to me. So, one is, and I think part of why we needed motivational interviewing was because, just broadly speaking as a field, not as much addiction psychiatrists, but mental health clinicians, psychiatrists, physicians, clinicians. We developed all these bad habits around substance use disorders and addiction. So, you think about a patient coming in, garden variety patient or clinical setting, some mood and anxiety issues with an abusive spouse. We don't say to the patient, you have to break up with a spouse or I'm not going to see you next week. Like, that's crazy, right? But we do that all the time. Not necessarily us, but in terms of patients that come in, they have this, you know, problematic relationship with heroin or cannabis or whatever it is, and there are plenty of clinicians out there who say, well, your drug test is positive, so we can't treat you in this mental health clinic. You have to go across town to the IOP or whatever it is. And so, I think a lot of MI was sort of getting the field or fields of, you know, people to realize that we had these really problematic behaviors as clinicians and therapists that were undermining patient success. And so, I think when we try to align with patients, one of the ways to get an N is figuring out what matters to them, right? So, what's the goal? And it's hard, even in this room, it's probably hard to find someone who has perfect sleep, you know, doesn't feel like they're wasting money on something, isn't stressed out. Like, people always have something that's bothering them in life, whether they attribute it to the cannabis use disorder or not, in terms of working with patients with cannabis addiction. And so, if you figure out what they're interested in, being able to, you know, finish their work more quickly, get better grades, you know, save money, whatever it is, have fewer arguments with their spouse or parent, there's going to be something there. And so, you have to work with a patient to figure out what's most meaningful to them. And then, if you can get traction around that, that might actually be your entree to addressing the cannabis use itself. One other thing about, well, let me go into screening and assessment first, and then talk about change. So, there are, as with most things, there are structured, you know, questionnaires or instruments to screen for potential cannabis use disorder, or to assess and follow patients, in terms of their response to treatment. This is the CUDIT, very similar to the audit. It's basically an elaboration on the CAGE questionnaire, but specific to cannabis, and it can be scored, especially for trainees. Remember, screening is very different than diagnosing, and the idea with a screen is that it's a very simple tool that can be pushed out universally, and then it tells you who not to worry about. So, if someone screens negative, those 70 percent of people, 80 percent of people, you don't have to worry about. And then, you can focus your attention on the 10, 20, 30 percent of people who screen positive, because those are the people who may be at risk for having the cannabis use disorder, in this case. And so, I showed the CUDIT, but there are all sorts of other scales. Kevin may have other thoughts. I don't think there's necessarily a gold standard. The way that you might think about a PHQ-9 or Modris for depression, there's not really a gold standard for cannabis. And one thing, not to get too soapboxy, but if you think about the PHQ-9 as an example, it was developed by a pharmaceutical company based on the DSM criteria to try to help improve screening and detection of depression so that they'd sell more antidepressants, which is not necessarily a nefarious thing. But the point is that the PHQ-9 is really tethered to the DSM criteria for the diagnosis, and then as people respond or remit to treatment, then their PHQ-9 score goes down. And I think part of the problem is that we have a preoccupation with drug testing and addiction treatment, in part because a lot of programs, that's how they get their revenue, is by billing for drug testing and unnecessary drug testing. At the same time, to Kevin's points, there are plenty of patients where it's extremely helpful to trend their, especially quants, to trend their drug tests, or for people whose goal is abstinence and they are abstinent or they're required to be abstinent because of a professional program, to follow them and show empirically that there's continuous abstinence and objectively monitored drug treatment, addiction drug treatment, tends to have better outcomes than non-objectively, meaning using like drug testing or saliva testing. And at the same time, I think there's this hope that we can look at other measurement-based care and other patient-reported outcomes to track response to treatment, and I think it's hard. To cut it short, I think it's hard with cannabis use disorders or substance use disorders because it can look so different based on who the person is, their life situation, all of these things. So, we have all of these screeners and scales, but they're not widely used for cannabis use or cannabis use disorder in general. So, there's substance use leads to psychiatric conditions, psychiatric conditions lead to, or symptoms lead to substance use, and it goes bidirectionally, sort of the Steve Ross, who I don't know if he's here this year, but his sort of list. And so, I often sort of rule of thumb, if people have a major problem with one substance, usually there's other substances involved. Not always the case. Clearly, cannabis and nicotine, cannabis to a lesser extent, alcohol, are going to be common combinations. So, it's always worth having that on your radar. And then, I think part of one of our points here is that you may have a patient who has really serious problems, you know, for instance, with cocaine or heroin, opioids, and so they don't see the cannabis use as a problem. One thing I will say, and we found this at Columbia across Adams here, Adams Saga, who spoke this morning, had a bunch of opioid trials, there's all sorts of different epidemiology, clinical trials, and usual care settings that have shown that if anything, patients who are in treatment for opioid use disorder, for instance, who have regular, not necessarily meet CUD, but who have cannabis use, if anything, do better in treatment. They're more likely to get on to Vivitrol, they stay in care longer, all these things. So, there may be some unmeasured confounds in terms of why that's the case, but I've worked with two of our largest, for instance, OBOT treatment programs in the U.S., and typically about 30 to 40 percent of the patients are testing positive for cannabis throughout care, and yet they're doing really well, and they stay in care for even for years. So, there are all sorts of different ways this fits together, and isn't necessarily cannabis use, but the point here is that people can think relatively about which substances are really causing them the most problems, and may not focus, same way so many of our patients, they're not, their goal when they enter care for cannabis or heroin or whatever, is not to stop nicotine, even though ultimately that may be a goal for them later on, okay. So, I think this is a short list of obvious candidates in terms of psychotherapeutic modalities. One thing, and as Kevin Hill mentioned, Kevin Grace here, my understanding is the evidence base, if you think about youth, is that they don't actually do great with MI for substance use disorders, and so this is where there can be some nuances in terms of working with adults versus youth around substance use. But in general, CBT, CM, motivational, you know, MET or MI, are going to be more of the evidence based approaches, and I think we're happy to talk more in more nuance about the ins and outs of any of these modalities, and I'm sure some of you probably are trainers for these things, but have other experience that you might want to share with the group. But I think at this point, I'll hand it over to Michael and he's, Smita does have a few resources here, real quick, if anyone wants to, and I think you have the slides through the conference programs, but NIDA, CDC, SAMHSA have resources, and then the APA also has resources on cannabis online for professionals, but for families. So, thank you, and I'll hand it over to Michael at this point. All right, well, thank you, Robin. So, I'm going to be talking a little bit, going beyond cannabis use disorder, what other sorts of cannabis-related problems might be out there or medical conditions that we should be aware of. And so, I'll be talking about intoxication, psychosis, hyperemesis syndrome, and then just mention other sort of risky behaviors and other sort of related medical conditions that can come up. And so, this is probably a list that's very familiar to many of you all, but there's, of course, acute intoxication effects from cannabis that can include anxiety, increased appetite, distorted perceptions, slowed reaction time, even nausea, and vomiting. And for some people, especially of those who have a history of psychotic illness or family history or people who are using products that might have a higher potency of THC or higher THC to other cannabinoid ratio, we might see that intoxication, which can last for a few hours on average, could develop into something more severe, like a cannabis- induced psychotic disorder. Something to keep aware of in terms of a presentation of psychosis, for example, in acute care setting, is that we're seeing more synthetic use of cannabinoids and sort of the severe psychotic effects from that. And one thing to note with that is that with synthetic cannabinoids, even if the urine qualitative test comes back negative, that doesn't necessarily mean that they're not using cannabis products like synthetics that don't turn out positive. So, these qualitative tests, they do test for THC or Delta-9. There is a lot of structural similarities with Delta-8, so it might pick up that as well. But in terms of the synthetics like JWH-018 and I think like AB Funminaka or Spice, all those things, you know, require a send-out. So, you know, with those kinds of presentations, for example, we had seen in Boston a prolonged period of induced psychosis after one-time use of a synthetic that required multiple months of hospitalization, ECT, and, you know, it's not something that's super common, but it's something to be aware of out there. And so, some people do develop acute intoxication. Some people develop an induced psychotic disorder or a prolonged psychosis period where there might be more severe hallucinations, so going beyond perceptual disturbances, and this can last for days or weeks. And this is a DSM-5 diagnosis under schizophrenia and other psychotic disorders. And I talked about some risk factors, and I'll just briefly mention management using benzodiazepines, second-generation antipsychotics, in rare cases, ECT could be helpful as well for that. And this is sort of a very kind of basic comparison of primary psychosis, so schizophrenia, and induced psychosis. So, I talked about how cannabis can lead to an acute intoxication phase, even a prolonged psychotic disorder, but there's also some evidence of an association with inciting or early presentations of primary psychotic disorders like schizophrenia. So, you know, as clinicians, it's important for us to be able to maybe figure out what's going on and address the underlying sort of causes of that. And so, looking at the comparisons of these two, you know, of course, in primary psychosis, your urine toxicologies aren't always positive, and antipsychotics might improve symptoms, but in cannabis-induced psychosis, antipsychotics may not always improve symptoms as if they're continuing to use cannabis products. And with primary psychosis, you oftentimes have much less insight around the hallucinations and delusional aspects that come with cannabis use, whereas they're usually, with the induced psychotic disorder, there is some insight around what is going on around that as well, and you have less of the negative symptoms and other sorts of aspects of a primary psychotic disorder, but very difficult to tease apart when a patient is still actively using, but just some tips to keep in mind with that. So, I'm gonna be segwaying into hyperemesis syndrome, and I'll talk about this case in a bit. So, hyperemesis syndrome affects about two to three million people who chronically use cannabis to date, and there's a male predominance. This is in comparison to withdrawal syndrome, which actually has a female predominance, so that's kind of one thing to keep in mind. Genetic predisposition for hyperemesis syndrome is based on five gene mutations that lead to paradoxical overstimulation of endocannabinoid systems. So, I'm gonna just briefly go through the pathophysiology of hyperemesis syndrome and how it's different from withdrawal syndrome. So, it starts with chronic heavy use of cannabis. This leads to overstimulation of, I think Dr. Williams talked about the CB1 receptor, which is pretty prevalent in the CNS, and this leads to an activation of an ion channel called TRPV1. When this gets inactivated, there's central and vagal effects that essentially leads to impaired gut motility, increased gastric acid secretion, and derangement in intrinsic control of nausea and vomiting. So, there's these downstream effects that lead to nausea and vomiting that occur from modulation of this ion channel, and then there's also a THC-specific induced splenic vasodilation, also cutaneous vasoconstriction. This is called cutaneous stealing syndrome, and that separately leads to an abdominal pain as well. So, you have nausea and vomiting, abdominal pain. And, as I mentioned before, with cannabis use, or even with withdrawal, there can also be nausea and vomiting as well, and some people might have pain. So, you can already see how this can be a challenge to sort of tease out between withdrawal syndrome and hyperemesis, but I'll get to that in a bit. Some of the phases of hyperemesis syndrome include an initial phase when people are actively using and starting to develop some morning sickness or dyspepsia lasting from months to years. So, going back to like, what can we do with patients who are sharing that they're chronically using cannabis for their anxiety? And, you know, one thing is sort of just asking like, oh, like, are there any side effects from using this? Like, are you noticing any adverse effects or negative symptoms? And, you know, if they're starting to share like, oh, I don't know, like, they might not even relate this at all to their cannabis use. Many of them, many patients may relate it to something else completely different, but, you know, if they're developing dyspepsia and morning sickness, that's something to point to and maybe, you know, talk to them about like, oh, maybe this is something going on with overstimulation of your cannabinoid system. Maybe we can talk about how we can reduce that a bit through harm reduction methods or other sorts of psychotherapeutic interventions. So, and there's initial phase of months to years of that. And then there's, that then evolves into the second phase where you have recurrent episodes of hyperemesis with abdominal pain, and that occurs every time someone starts consuming cannabis. So, this is sort of a pathophenomenic picture of just like, just daily, especially with patients who are using it, you know, vomiting, abdominal pain, some patients have to come in to the hospital, you know, to get treated for dehydration and metabolic derangements and things like that. And these episodes can last for 24 to 48 hours. Also, pathophenomenic is taking hot showers might help this as well. And, you know, oftentimes with patients, you know, coming to the hospital or get treated somehow in the outpatient setting, there might be recovery phase, you know, when there is some ambivalence around, okay, do I stop taking cannabis? And, you know, maybe let this go away, or do I continue some of that? There might be some recurrence of symptoms and ED visits as well. And over time, the symptoms can go away with reduction in abstinence of cannabis, but that is a prolonged period. And so, this is a challenging conversation with many patients in terms of talking to them about the relationship of the nausea and vomiting and the use. As you can imagine, one of the sort of cycles that some patients might get in is that, oh, but cannabis helps with my nausea because like, you know, when I'm nauseous and I use it, I have less nausea, so that's why I use it. And so, sometimes there can be like this kind of a mixture of what's going on, there's some withdrawal going on, there's some hyper-emesis syndrome, and so this is a careful kind of conversation to talk about what might be helpful. And in terms of what might be helpful in relation to hyper-emesis syndrome, there's three categories of treatment. The first one is supportive treatment, so addressing the metabolic derangements, replenishing fluids. There's also treatment of the nausea and hyper-emesis syndrome. Interesting thing to note is that conventional antiemetics, like the dopamine modulators, dimetoclopramide and ondansetron, are not effective for hyper-emesis syndrome, but there is some evidence for even D2 blockers, like haloperidone, droperidol, and benzodiazepines for hyper-emesis syndrome, so just kind of something to note if you have someone outpatient that has vomiting, GI has seen them, primary care has seen them, they tried, it's not over, and it's not working, like what might be going on beyond that? And then treatment of abdominal pain, so capsaicin, I think some of you all might have heard of that as like a poor question or something like that. PPIs can be helpful as well, and of course hot showers may reduce sort of some of that pain and anxiety that come with that. So I mentioned some of the similarities and challenges differentiating hyper-emesis syndrome withdrawal syndrome. This is kind of a nice chart put together in the International Journal of Emergency Medicine, just taking a look at some of these differences. So with hyper-emesis syndrome, you have onset of symptoms rather quickly after initial use, whereas with withdrawal, it takes a while for it, or about a day for it to sort of kick in with the withdrawal, so understanding when they last used cannabis, the hot showers and relief of symptoms is something that would point to hyper-emesis syndrome, and then you have gender predominance and relief as well. And then in terms of the clinical course, also important to get a history of, is this something that developed over time? Do you see these phases of change with their symptoms, and how does that relate to their course of use? So these are all sort of different ways to differentiate these. Another interesting thing is that for hyper-emesis syndrome, it doesn't correlate with the quantity of cannabis use in terms of the severity of hyper-emesis, whereas withdrawal would correlate with that. So I'm gonna just go through quickly a case. So this is a 25-year-old male with a history of cannabis use disorder presenting to the emergency room with abdominal discomfort, nausea, vomiting, recent weight loss. CBC, lipase, LFTs are normal, and the basic metabolic panel's consistent with hypovolemia and hypokalemia. Abdomen slightly tender. Patient reports his last use of cannabis was around 12 hours ago. So after providing fluids and electrolyte collection, what is a possible reasonable next step in management? So A, gabapentin, so lorazepam, capsaicin, zofran, capsaicin, henadol, dronabinol. So how many of you all say A, gabapentin, B, lorazepam, C, capsaicin, zofran, D, capsaicin, henadol? Okay, yeah, the correct answer here is D. So again, zofran and other traditional antiemetics are not necessarily helpful for hyperemesis syndrome, but there's some evidence for D2 blockers and capsaicin can be helpful for the abdominal pain. So thinking about hyperemesis in that kind of way can be helpful. Some other key aspects was the amount of time that happened from last use, which points you to hyperemesis as opposed to withdrawal syndrome. And so, yeah, and there's other kinds of induced medical conditions that can happen. I think many of you all have seen EVALI in the news. It's likely secondary to inhalation of vitamin E acetate, which is a thickening agent in THC products. And you can see on shortness of breath, chest pain, cough, hemoptysis, and some bilateral diffuse ground glass infiltrates in a chest X-ray. Some people might require intensive care for that. So just something to be aware of when discussing risks around use. There's a lot we can talk about with this slide, but I'm just gonna briefly go through it. And there's sort of a nice review that Dr. Kevin Hill and I put out there in 2020 in a journal of family practice on this sort of topic, if you wanna look into that. But some of the risks to consider include cardiovascular, so there are some increased risks of arrhythmias, and even cases of myocardial infarction. There's been some cases of over-ingestion of edibles, especially because of the delayed release of edibles. And since it is absorbed in the gastrointestinal system, some people use it, don't feel the effects right away, and so they use it more, and they can actually develop some pretty acute medical conditions or psychiatric conditions from over-ingestion of that. From a pulmonary perspective, there's some evidence that could exacerbate bronchitis and thicken sputum. There's also some evidence in terms of adults' acute and chronic membrane-executive function impairment related to chronic and heavy higher-potency use. In pregnancy, using during first and third trimester may be associated with decreased infant performance and other infant neurocognitive issues. And then under the age of 25, there's some sort of long-term studies that suggest there could be an association with use of cannabis under the age of 25, especially heavier and higher-potency use and affecting brain development, cognition, executive function later on in life. So these are just some of the risks to consider. Some other risky behaviors to talk about is just cannabis and driving. Definitely heard some patients talk about, you know, oh, but I use my cannabis to help me to drive. You know, it helps my anxiety. And so it's important to have these conversations about what the effects of that can be on driving. I think there was an article in Annals of Internal Medicine or maybe JAMA Internal Medicine just looking at cannabis use and how there can be up to four hours afterwards impairment in executive function and driving, even beyond the point that people feel like they're impaired from it. So just important to have these conversations right now, you know, with patients about this and doing some psychoeducation around that. So we were gonna do some role play and some cases, but I think, you know, we have a great room in terms of ranging from medical students to experts in the fields who've run clinical trials on this. I think we're actually just gonna open up the floor to discussion and Q and A, especially being mindful of time as well. So yeah, if you all want to take a look at the cases, I have QR codes for two different cases and handouts that you all are free to practice with the people you came here with or with, yeah, anyone sort of at your institution. But I think, yeah, given the interest of time, we wanted to make sure we had enough time for Q and A and discussion. I'll open up the floor to that and yeah, see if anyone has any questions about what we discussed. Do you ever see prolonged hyperemesis after people stop using cannabis? Like I have a patient who definitely starts vomiting when she uses cannabis, but then her GI symptoms seem to persist for weeks after she stops. And I'm wondering, is that a combination of withdrawal and hyperemesis or something else? Yeah, it's a good question. And I might, I'll give an answer and maybe pass it off as well to Kevin and Robin. But yeah, I've definitely seen weeks or months out people having GI symptoms related to the hyperemesis. And I think maybe part of that, and correct me if I'm wrong, is that you have this sort of regulation, receptor modulation going on that takes some time to re-regulate just kind of like how we see like in terms of like re-regulation of receptors and chronic other substances like benzodiazepines. And it might take some time for them to feel normal again. Yeah, there's definitely some of that happening. And yeah, but in the initial phase, there can be a mixture. Yeah, I've talked to some of the ED physicians about this, is seeing this mixture of like withdrawal and hyperemesis. And it's kind of confusing in that initial stage. So there's some, yeah, some, yeah, it could be all of that together. I don't know if you guys. So the, so the vomiting ends though? Is that what you said? The vomiting continues with less. Oh, no, I've not seen that. I mean, I think that, you have? Yeah, I've had a patient that was in the hospital for a week and vomiting. And I also thought it was interesting. He's super anxious. I mean, like my patients who have this syndrome are anxious. So I think to like say that's one way to tease it out, like is like they're not psychiatric symptoms of having this syndrome. Not true. I mean, they're very distressed. Yeah, this woman is certainly very anxious. Yeah, and my guy's, you know, hospitalized in the last one was four or five days before they could get him out. He was vomiting. And I've had some experience before coming here with chronic vomiting syndrome, idiopathic, if you will, like not induced by cannabis or anything like that. And they usually respond to something like good ol' Librax, which is a combination of Librium and Clindanium. Usually they end up in the ER and they get labeled as opiate seekers. And once you put them on this kind of very mild combination, the whole thing just goes away and tends to keep away for a long time prior to hearing about this. Yeah, I think, yeah, great thing to note that, yeah, there can be psychiatric symptoms that come even from the experience of hyperemesis syndrome, anxiety as well. That slide was definitely, as with anything where you try to dichotomize these diagnoses, it was oversimplified. But yeah, that's interesting. I haven't heard that sort of intervention of Librium. Yeah, Dave? So, I don't know if you guys are seeing this, but we're saying stuff like that, kind of like what they call canorexia, where you have these cannabis users that develop a condition where they can't eat unless they're high. And then when they stop eating, they stop smoking, they oftentimes have four, five, six, seven days where they can't really eat. They often get full halfway through their meal and can't finish the meal, and they go up, and they don't get any pleasure out of food. So, I don't know if anybody else has seen this. I've not. It sounds like you had a case series there. Yeah, I guess I should. So, wonderful talk, and you're all such great speakers, too. So, it's just really fantastic to hear you all present. I was reading an article recently that was part of my board certification, and they were talking about how, in Colorado, cannabis use was associated with an increased risk of suicidal ideation and suicide attempts. And I was wondering if you could comment on that, if you've heard about that being something that we should be maybe incorporating into our clinical practice to talk about as a risk, or is this a serious thing we need to also think about with cannabis and adolescents? I mean, it's definitely real. I mean, you're referring to papers that I've seen, as well. You know, will those be replicated? It's hard to say, but, I mean, like anything, people make bad, impulsive choices when they're inebriated, and I think we should expect the same when people are under the influence of cannabis. Yeah, I would echo that. I don't know if it's clear. I'll let Kevin tell you what he's looking for. All right, so I'll just echo what Kevin said, that, you know, if you look at, I don't know if this is on or not, but if you look at patients who are hospitalized with SMI, discharged to community, risk of homicidal or suicidal acts, you look at other people, chronic suicidality, anxiety, mood disorders, intoxicants for intoxicants, and so I think just in general, if someone is intoxicated, they're gonna be more disinhibited, more labile, potentially, right, or at least in certain moments, so I think there's a real risk there, and the news has, not to make it too political, but I think the news has been swept up in this narrative in terms of the very clearly flawed, failed, horrible drug war and the mass incarceration of people, but I think it's a bit of a non sequitur to then say that we should have full legal access to any cannabinoid any manufacturer wants to make and sell for whatever purpose, and so we're gonna wind up in this place where there's sort of loose access to all sorts of things of varying quality, and obviously some people really are gonna have trouble with that, whether it's addiction or harming themselves or someone else, even if it's by accident. Great question. Yes. Yeah, I'm an addiction psychiatry fellow, so still in training, but regarding Zofran, I guess in just clinical practice, is it really not effective at all for people who generally have hyperemesis and try to get it in the emergency department or something, in your clinical experience, is it not cut down on it at all? Yeah. I still use it. I mean, I'm symptomatically treating people, if they describe ongoing nausea and vomiting, I've given people who've had repeated ER visits related to hyperemesis scripts for ondansetron, and it's not like I felt like it was worthless, so I mean, I'm curious what other people say. I mean, I think we're still searching for state-of-the-art treatments for this condition, but I think it's worth a try in compazine, but as you said, there's published data suggesting maybe it's not strong in that. Is there any data on olanzapine at all? You say olanzapine? I haven't seen any on olanzapine, but. No, just, so a few studies, and it's something that, again, has not been studied well, but just a few looking at haloperidol, that's it, so would olanzapine work? I mean, I think you'd have a decent chance, probably, but it's not been published that way. Lisa? Can you speak about capsaicin? What do you do with it? You rub it on, you can taste it? Yeah, it's icy hot, you know, not bad. But where are you rubbing it for these patients? Well, it's the same, I mean, they're taking showers, and they're getting the same effect when they're taking showers, where, you know, you're getting some type of. It improves cutaneous circulation, so it's drawing the blood back towards the surface, away from the organs, so it decreases abdominal pain. Do you tell them to rub it all over their body? I think the abdomen. Yeah, I mean, I've not recommended capsaicin, but I know that patients go into the ER, and they sometimes can get that. You also may be getting better from the gaining period, right? If that hot sensation or that cold sensation gets in first, it's going to block a pain sensation. So you may be getting better. That's probably how Ben-Gay works, icy hot works, rubbing. I just looked it up, you know, Google capsaicin, and there are some tablets that could be taken, but there's some liver damage associated with the tablets. I was just wondering if you could talk about that. I think it's topical. I've not seen tablets being used. Yeah, I think topical was the case. Yeah, we're talking topical. Good question. Yes, you in the back. So I think there are a lot of GI patients. You mentioned the effect on GI motility. Can cannabis cause gastric recess or enough slow emptying in GI doctors with diagnosis? And would you guys recommend people with proven slow gastric emptying or diagnosed gastric recess stop cannabis? That's a really good question. I don't know if any GI experts are cannabis GI. So the question was, yeah, can cannabis lead to gastric recess? And would you recommend stopping cannabis in a patient who has gastric motility issues or gastric recess? Yeah. Does anyone have any idea about that? I mean, I would just think, what other treatments have been tried? You know, if you're working your way down the list and you're still using a lot of cannabis, certainly worth a shot. Yeah, we'll get back to you on that one. Yes. See, I want to change directions a bit. I came for this because four years ago, I remember California had this meeting who was going to legalize it. UCLA professors, you know, what the hell are we even getting to talk about because federally it's illegal? And it was a really good discussion. Well, now four years later in Minnesota, where I'm from, we passed recreation use. Of course, we have up to two pounds, by the way. Who has two pounds to five? Well, he does. But in Minnesota, anyway. It's just, they didn't learn anything. I mean, it's just ridiculous. The big question I had, too, was intoxicated driving. How do you discuss, is any testing, anything going that much into who, I've seen some, police have shown me to do some, you know, some, like the drunk driving walk. But is there anything scientifically that's been done yet for that? Yeah, so the question is, are there any tests for roadside, like cannabis intoxication, in terms of assessing for driving? Yeah. Not by itself. So we talked about this in the last hour, too. So in my mind, I think that you have to be able to hold people accountable for making those kind of decisions. So clearly there's no, a couple things. Number one, a blood level of THC is not a good proxy for impairment. However, if we're talking about using multiple data points where you can combine a blood level for THC plus field sobriety testing, so field sobriety testing in and of itself, some people will argue it's effectiveness, but again, I'm not saying that you're using it by itself. So to me, I think that if you're a law enforcement official and you have, number one, a justified stop, two, a blood level, three, failed field sobriety testing, I mean, if you got all three of those things, I think that's pretty good. I mean, I wish we could do better, but I think that's, I think you're doing the best you can with the available technology under those circumstances. I would also say a couple other things. Number one, I believe that if we really wanted to develop technology, we could. I think we've chosen really, like many things with cannabis, we talked about the medicines available for CUD. I mean, we've chosen not to take this as seriously as we could. I think a lot of people are making a lot of money on this, and we've chosen not to mitigate the risk as much as we possibly could. And the other thing I would say is, I've debated how to keep people accountable for driving under the influence, and when people rightly poke holes in the blood level, the per se level, or field sobriety testing, I always ask, well, what do you recommend? And those people will never suggest anything. So they're kind of hoping for people to be able to do whatever they want. And in Massachusetts, I'll just say, because we talked about this earlier too, in Massachusetts, we had a situation where a state trooper was killed by somebody who just went to one of these dispensaries, and we tried to pass a law, and I wrote an op-ed with my local police chief to try to pass this law, and we couldn't do it. So I think it's a difficult spot where we know that more and more people are using cannabis, and again, I personally think adults should be able to do what they wanna do, as long as it doesn't hurt other people. But here we are in a predicament where we are potentially at risk because people are driving under the influence. So it's not a great place to be, and I really don't see it changing. I think Kathleen Meany from Minnesota had mentioned that there are studies, there are people trying to develop better technologies, but I don't think the rate and scale of that work is really where it ought to be. It's a time distortion, one of the biggest problems. It delays your time, hence getting bad accidents. Is there any way to measure that? Again, I've seen earlier tests where they had people do, we'd run through a driving test, and then come back, get stoned three times worse in terms of what they did, and a lot of it was just good distortion of time. Is there any way to measure this? No, I mean, so again, the data's pretty clear that cannabis, there are a lot of factors, your experience and what else you've done that day, but cannabis adversely affects your ability to drive. I mean, the errors that you make are different than the errors you make when you're under the influence of alcohol, but it's not, I think Michael mentioned earlier, some people believe that they're driving better, and that's not the case. So we're having more and more states, as Robin showed, more and more states with these policies, more and more people are using that have never used before, and we're gonna see what the consequences are, unfortunately, and I think that we should be doing more to mitigate these risks. Okay, we're out of time, we're out of time. All right, well, I think we're out of time, so thank you, everyone, for joining us today, and for this great time. Yeah.

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