Thank you. Hello everyone and good afternoon. Before we get started I just wanted to go over a few housekeeping items. Please use the chat box for any questions you may have. We encourage attendees to interact with each other and share comments and questions in the chat box. While the panelists are presenting, and we'll be taking some time at the end of our session today to answer some of the questions, anything we don't have time for we will address next week. You also have the option to upvote any questions that other attendees have so that our presenters are able to prioritize questions that are of greatest interest. Both the recording and the slides will be shared with you in an email following the event. You'll also receive a CME evaluation survey. This session is available for one AMA category one credit, and you'll get a follow up email after the webinar's conclusion with instructions how to claim your credit. Okay, so let's get started. Welcome to Clearing the Smoke, Cannabis and Mental Health, a two part webinar series presented by the American Psychiatric Association, the American Academy of Addiction Psychiatry, and New York County Psychiatric Society. My name is Jill Williams, I'm the chair of the Council on Addiction Psychiatry at the American Psychiatric Association. I'm also professor of psychiatry at Rutgers Robert Wood Johnson Medical School in New Jersey. This webinar is the first of a two part series that will provide psychiatrists and other clinicians with the most updated information available on cannabis and mental health. given the accessibility of legalized and recreational cannabis now in so many states. Today's webinar will give an overview and updates on cannabis use in patients mental health impacts as well as clinical practice recommendations based on the latest research. Next week's webinar will be a follow up session to address more attendee questions and talk about also policy implement implications and areas for advocacy and future work. I'd like to thank our speakers for their time and expertise. And again, we'll have time for question and answers at the end. I'm now going to introduce our three speakers. Dr Smita Das is board certified in psychiatry addiction psychiatry and addiction medicine. She studied chemistry and statistics at Stanford University completed her master's in public health at Dartmouth, and then her MD PhD at the University of Illinois. She completed her residency at Stanford and addiction fellowship at UCSF. She's a member of the APA Council on addiction and has been a leader in the Northern California psychiatric society. She's also now president of the APA district branch. Dr. Das is currently a medical director of psychiatry at Lira Health and a clinical assistant professor at Stanford School of Medicine. She's going to be followed by Dr. Arthur Robin Williams who's assistant professor of clinical psychiatry at Columbia University division on substance use disorders. He's an NIH funded research scientist as well at New York State Psychiatric Institute. He attended Princeton University School of Public and International Affairs for his undergraduate degree in domestic health policy and completed his medical degree at Pennsylvania, where he also earned a master's in bioethics, he completed psychiatry training at NYU Bellevue and as well as a night of funded a T32 research fellowship in addiction psychiatry at Columbia. He also serves as the director for the AP triple AP region to which includes New York. And then finally we'll hear from Dr. Kevin Hill who's an addiction psychiatrist and director of the division of addiction psychiatry at Beth Israel Medical Center, and an associate professor of psychiatry at Harvard Medical School. He completed a master's in health sciences from the Robert Wood Johnson clinical scholars program at Yale, and also completed the partners healthcare addiction psychiatry fellowship program. He's the author of two books on cannabis marijuana the unbiased truth about the world's most popular weed and co author of medical cannabis and evidence based guide. His research interests include the development of medications to treat cannabis use disorder, as well as cannabis policy so you see we have a great panel today. I'm going to stop and turn the presentation now over to Dr. Das. Thank you, Dr. Williams and I just need to say this very quickly, Dr. Jill Williams has been an amazing leader on the American Psychiatric Association's Council on addiction psychiatry so thank you for leading that and for being such a strong person within our organization there. So I'm really excited to open up this presentation today with the first small talk. This is a topic that comes up a lot for our colleagues for our patients and so, so it was fitting to come together as two organizations to put together this set of presentations. Next slide. And so for to begin with, we're just going to do a broad overview of cannabis and cannabis basics. I feel very fortunate that my colleagues will be going into more detail that this is kind of like a preview to some of the things that they're going to be saying. Next slide please. Great. So there is a vastly changing landscape when it comes to cannabis and cannabis legalization, everything from from states that have had what's considered medical or medicinal cannabis use, as well as recreational. This slide is already outdated because just in the last day, Virginia, voted to make cannabis legal for recreational use. So, very very fast changes there's, there are a lot of impacts that are happening. While federally cannabis is still considered an illicit substance and a lot of the slides that I will show with the epidemiology data come from federal data. And so they refer to it as an illicit substance on the state level, there is increasing legalization again for multiple with multiple labels on there everything from medicinal to recreational. So there is confusion where their policy is is moving forward, and yet practice wise and science wise we are still learning more about the impacts of these things and so part of what we're hoping to present today are the naturalistic studies there's in some ways these are all separate 50 experiments happening. When it comes to epidemiology, and we're able to look at how that data pans out over time. So what is cannabis to kind of set the stage here and again, my colleagues will be going over some of this in more detail, but cannabis is a complex plant plant it has many different parts to it and many different chemicals that can be extracted from it. And generally, we are often referring to the effects of the THC especially when it comes to mental health. So delta nine tetrahydrocannabinol is the main psychoactive compound. It's the only compound obviously there's hundreds in there and so the other ones that we often hear about for example our CBD or cannabinox dial. And generally, we will try to use the term cannabis and much of the work that we do because there is a long history which is an entire talk on the use of the word marijuana. I did want to pause here to just touch on CBD it'll be discussed a little bit more later as well. But CBD is largely unregulated so you've probably seen in the, in the, in stores or on in products that are trained that are sold online that they have CBD, and THC is supposed to exceed more than 0.3% in what's considered hemp. But we've had a number of studies coming out recently that show that CBD concentrations are often mislabeled in these products and these oils. So, generally, while people are using it for pain, anxiety, depression, there's no indication for them and so the FDA has had to make it make it clear to some of these, these industries that they cannot market in that way. And then it's not just a benign thing because it can, it is pharmacologically active and can interact with other medications. So on one hand, it's often referred to as a cure all. And on the other hand, it is something that is that is supposed to be benign so it this is a part of cannabis literature and cannabis research that's going to continue to expand, and we're going to hopefully see again the epidemiologic data play out. So let's talk about some of these modes of use. So traditionally when we think about cannabis we think about people smoking, and anything from kind of the word joint, and now, though, there is smoking in a different form vaping, for example, there's also edibles and so a lot of states with legalized cannabis will have outlets that you can go and buy chocolates gummies candies things that are concerning because they are appealing to young people, and we'll touch more on that later. So there's even more potent forms of cannabis so the cannabis that was largely popular popularized in the night in the late 1900s was is not the cannabis that is being used today. So we have hash oil concentrate wax, these are all things that all components that have very very concentrated THC, and while top grade cannabis is considered to be 20% THC, we're seeing these concentrates in at 40 to 80%. So this is just a slide highlighting what I was mentioning so this is using da seizure data but really if we look at the top, the top line there on on the right we have the, the THC content is getting stronger and stronger compared to the CBD. So what we're not discussing in in these talks generally is not going to be the synthetic cannabis derived medications for which there are FDA approved indications, and these are generally rare indications and the image there shows the most recent approval that that came along, and it was for drug based syndrome or rare seizure disorders. Next slide please epidemiology will touch on this to get a better sense of how common this is I think we all know, as a psychiatrist and those in healthcare that cannabis is very common but let's look at the numbers. Next slide please. Great. So, here I put Alyssa in in quotation marks because it is federally illicit but states are legalizing, and it is the most used federally illicit drug with nearly one in five people over the age of 12 using in the last year. There's also this myth about cannabis use disorder that it doesn't exist that people cannot become addicted to cannabis and we know this is false and there will be a discussion of this later in our in my colleagues talks, but nearly 2% of the population does develop cannabis use disorder. So I want to focus on young people and their use because this is very important, especially as it relates to development of cannabis use disorder and other substance use disorders. So we see that over time between 2017 to 2019, there has been an increase in in two things so one is in THC vaping so now THC is becoming more accessible people are able to use it in vape devices, and we see that younger ages for example 10th graders, 8th and 10th graders as opposed to 12th graders are really increasing their use of vaping. Similarly, they're also increasing their use of daily marijuana so this is something to be mindful of. Next slide. Because we are finding more and more that the data show us that earlier use of earlier first use of the substances is associated with development of substance use disorder. And this comes from a very recent paper actually that was just published in the last couple of weeks, where NIDA looked at NISDA data and found that while of course lifetime use rates are lower among adolescents compared to young adults, we see that when it is earlier initiation of cannabis, then cannabis use disorder is more likely. So adolescents who so in people who use cannabis earlier in their life, then in the months following that they're more likely to develop to develop cannabis use disorder. So this is very striking, not just for cannabis use disorder but also for other substance use disorders. And as we think about the brain and the circuits that are involved in the development of addiction, as well as the risk factors, earlier use is becoming more and more to be a risk factor for later use disorders and later impacts. Next slide please. So as I mentioned last year, however, the data that just came out in February is very similar in terms of the impacts of the pandemic on mental health, but I want to point out in this image from MMWR, people who are, there are people who are indicating that they started or increased substance use to cope with the pandemic. We can zero in on a few papers that have come out about cannabis use in this time, and people who have had mental health conditions have a higher increase of cannabis use during this time, and doses have also increased. The number of people who are under the influence of cannabis is also increasing now. And so there's many different things that can be moderating these effects, for example, isolation, anxiety, and so on. And we know that folks are feeling unwell and trying to find ways to cope and are turning sometimes to substances and so this does play out similarly for cannabis. Next slide please. I also want to point out that use of substances or substance use disorders are associated with worse COVID-19 outcomes. So this was an interesting paper that came out last year, looking at the impacts of substance use disorders on contracting COVID, rates and hospitalization rates and essentially our patients who are suffering from substance use disorders end up being impacted more by COVID as well so something to keep in mind in this very unique time. Great. And with that, I'm excited to pass it on to Dr. Hill, who will be sharing more details about cannabis and highlighting more of his research. So greetings from Boston just want to take a minute to thank everyone for coming out today also want to thank triple AP and APA for putting this on. Next slide please. So in my 10 minutes we're going to cover two major topics. Number one, what is the relationship between cannabis use and major psychiatric conditions and in the second half of my 10 minutes we're going to talk more about cannabidiol or CBD and so in the first half I'm really interested in three questions. Number one, does cannabis use increase the incidence of particular psychiatric disorders like depression, anxiety, and psychotic disorders. Number two, if you have, or if a patient has an existing condition will cannabis use exacerbate that. And then finally from a treatment perspective because so many of our patients and other folks are talking about using cannabinoids to treat these disorders, where is the evidence there on that question. Next slide please. So in terms of depression, as you'll see with most of the psychiatric disorders, the studies that have been done are all observational are largely observational so with depression in particular we see a relationship that cannabis use particularly heavy cannabis use increases the incidence of depressive disorders in a dose dependent manner as you can see here from the lever and paper. Secondly, if you have a depressive disorder cannabis exacerbates that. And then finally from a treatment perspective no interventional studies have been done, although in the spirit of being balanced, you know there's one observational study in cancer patients that shows that patients who use medical cannabis during their treatment had fewer depressive symptoms. In terms of bipolar disorder, again patients with cannabis use disorder, and those folks are more likely to have bipolar disorder so it's more a more common disorder in patients with bipolar disorder by several times. In addition, those that have started to experience symptoms of bipolar disorder at a younger age are more likely to have cannabis use disorder. And then those that have bipolar disorder use more cannabis more often. And then finally, if you have bipolar disorder, using cannabis during the course that disorder makes it worse right you have more symptoms, you're more likely to experience co-occurring substance use disorders as well. Next slide. Nice review of this topic really was published a couple of years ago, I collaborated with some of the good folks at the Center for Addiction and Mental Health in Toronto so Aaliyah Lukacs and actually she just published another nice paper that came out late 2020 in Canadian Journal of Addictions where it was a perspective study so patients with major depressive disorder if they're able to abstain from cannabis use for one month they showed an improvement in symptoms. So that's, again, a relationship that we'll see that if you have a psychiatric disorder using a lot of cannabis if you're able to reduce or stop your use of cannabis you're probably going to do better and that's why we should certainly encourage that among our patients. Next slide please. Terms of anxiety so we're all familiar and treating patients with anxiety a lot of folks feel that cannabis helps their anxiety and as we know you know that's not really the case although we can kind of appreciate why that may be true because as they use cannabis anxiety may go down but over time their baseline level of anxiety will increase. So, cannabis use is not associated with an increased incidence of an anxiety disorder, and if you have an anxiety disorder it doesn't necessarily mean that you're more likely to initiate cannabis use, however, as the Krupa paper shows in the second bullet, certainly cannabis use despite what a lot of folks believe exacerbates existing anxiety disorders and then similar to the Lukacs paper there was another paper that showed that if you have an anxiety disorder and you're able to stop using cannabis your symptoms will likely improve. And then the final bullet in terms of treatment with whole plant cannabis, there haven't been the standard randomized controlled trials, but one observational study of medical cannabis did show a reduction in the use of anti-anxiety medications. So the question becomes, should you use cannabinoids to treat anxiety? It's a more complicated question than one might think. So certainly there is no evidence in terms of randomized controlled trials that support the use of whole plant cannabis as a pharmacotherapy for anxiety. However, as Dr. Das alluded to earlier, we're gonna talk a little bit about cannabidiol. So CBD, which functions as a buffer of sorts to the potentially harmful effects of THC, overall has more appealing properties, anxiolytic properties that suggest that it may be a better option than whole plant cannabis or other cannabinoids to treat anxiety. In fact, there were a couple of studies that have come out within the last decade or so, which show some promise for CBD, particularly with social anxiety disorder. So as we'll talk about CBD in a minute, there may be instances where if somebody has treatment refractory anxiety, you may be considering CBD for them. Moving to psychosis. So of the psychiatric disorders that we've talked about so far, probably the strongest relationship is with psychotic disorders. So we've seen time and time again, probably are over 10 very large observational studies. And one review of those studies in 2018 showed that cannabis use essentially doubles the risk of developing a psychotic disorder in patients who are vulnerable. Second bullet, who are those high risk groups? People who start using cannabis at an early age, people with genetic susceptibility. So a family history of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features and those with trauma. So again, this is important for those conversations that we have with patients. So if you have a family history of a psychotic disorder and the patients in their teens or early 20s, there's an extra level of risk there. And as we also see, as again, I know there are hundreds of you who treat these patients. We know that once you trigger a psychotic disorder, it's really hard to put the genie back in the bottle. So I still follow a lot of these patients and then the issue becomes, are we gonna be able to help them stop using cannabis? Are we gonna help them be adherent to their medications? And it's just a very, very challenging population to treat. And as you can see, those who have a psychotic disorder and use cannabis, they don't fare as well, right? Earlier onset of psychosis, greater disease severity, symptoms persist longer, more likely to relapse. And I imagine there are many of you out there like me that deal with this group and it's very, very challenging. And they may acknowledge when they're doing well that cannabis is a problem or yes, I should take my medicine. But as you know, I mean, it's just inevitable that they kind of drift back towards that or they don't wanna take medications that have nasty side effects. And so it's a real, real challenge. Next slide, please. So overall, should you use cannabinoids to treat psychosis? So whole plant cannabis, no studies, no RCTs there. But again, I think CBD is different in the sense that it has some appeal there. It has some promise that we've seen in a variety of studies, both preclinical and clinical. And so again, the final bullet here, I wanna emphasize not all studies have been positive, but there have been a few positive studies that suggest that CBD as a monotherapy or as an adjunct treatment for people with schizophrenia, likely other psychotic disorders, something to consider. So that's something that has been done. People who are having trouble and have had multiple medications, should CBD be considered at that point? And so that's something, again, every case is different, but it is an option. It's certainly not a first-line treatment, but something to think about. Next slide. So let's talk more specifically about CBD. As Dr. Das mentioned before, it's FDA approved for three seizure disorders, Dravet syndrome, Lennox-Gastaut, and tuberous sclerosis. And I think this is a great example because when we think about cannabis and think about cannabinoids, there's so many more people using these compounds than there is evidence, but this is a great example of what you can do. So these RCTs that earned FDA approval for CBD, this one formulation were excellent and rigorously done. And that's really what we should shoot for. Unfortunately, the rate and scale of the research into cannabinoids and CBD in particular has not kept pace with the interest, unfortunately. A lot of states and companies that are profiting extensively from the sale of these products, and yet they're really not contributing for the most part to the science. So again, CBD, very promising. Most of the evidence is preclinical. This Pisanti review paper is excellent, outstanding. Another place I would direct you to, the World Health Organization has some excellent reviews of CBD and cannabinoids in their expert committee on drug dependence, PDFs that they've put out. So unfortunately, as I mentioned, there is an FDA approved version of CBD, but it's not gonna be approved by insurances to treat the conditions that you're likely treating. And so then if patients are gonna use it, they're using really an unregulated form. And Dr. Das alluded to this before. So it's not really regulated. It's often mislabeled. Marcel von Miller published an outstanding short research letter in 2017 in JAMA where he showed and his group showed only 30% of commercially available CBD products were accurately labeled. So that's too much CBD, too little CBD. You really don't know what you're getting. So as you can see, that's an issue. The Apocalypse paper in 2018 showed that you might get other stuff in those products. Could be THC, could be dextromethorphan. You don't know. So it's really a situation where we have to be very careful and I always encourage patients if they're using these products to bring them in, take a picture and let's talk about whether or not we really think that they're getting what they think they're getting. Next slide, please. Other issues, there's just a multitude of misinformation about CBD. On the whole, it has fewer side effects than THC, but we still need to be crystal clear because of the millions of people that are using it, we need to be crystal clear about where the science is. There really isn't much evidence, if at all, supporting the use of CBD as a pharmacotherapy for insomnia. Secondly, the creams, they're not absorbed into the bloodstream, so it's really an expensive OTC cream, over-the-counter cream like the ones that have capsaicin in them and things like that. So that topical anti-inflammatory, there's a use for that, there's a utility there, but for the most part, I see my patients who can probably ill afford to part with many dollars or spending a lot of money on these products, hoping for more than they're getting out of them. As you know, the companies often make outrageous claims about what these products can do, prevent concussions and things of that sort, which there's no evidence there, at least in a clinical sense, right? I mean, a lot of preclinical promising data, but you have to get to a point where you have RCTs to really think about expanding the use clinically. And then finally here, this issue that we've seen in a lot of patient populations that I work with, if you're using a pure CBD product, then you will not have a positive urine drug screen for THC. So what is the product? Are they using cannabis that has a higher concentration of CBD? Are they using a CBD product that has too much THC in this case that would trigger a positive urine drug screen? But that's a major issue. People lose jobs and sometimes million dollar jobs based upon this issue. So it's a major issue. Next slide, please. And then legitimate health concerns here. So again, I think on the whole, it has a relatively benign safety profile, but there is a concern for liver toxicity. So this Watkins paper that came out in 2020, they looked at one of the open label trials for the FDA approved CBD product. And what they showed that in 16 patients, seven of them, so almost half had increased liver enzymes. Five of those patients had liver enzymes that were more than five times normal. So one of the key points with CBD, a lot of people are using homeopathic doses. So five milligrams, 10 milligrams, that's not gonna do much, if anything. But if you're using the doses that actually are pharmacologically active in the hundreds or even more, sometimes in this study of 1500 milligrams a day, then you need to monitor LFTs. So again, this is not a risk-free medication. Just like any medication you use, there are risks and benefits and monitoring is required. Second bullet here, when patients are using, excuse me, using CBD instead of evidence-based treatments. I've had patients come in and they've had multiple medications for depression, even ECT, and they say, hey, look, doc, I'm done with all these treatments. I wanna use something natural. And that's not something I wanna be a part of, right? I mean, if you have treatment refractory depression, this is not gonna solve that problem. So there's a right place, there's a wrong place, or many wrong places in this case. And then finally, even if a patient is willing to do this with the supervision of their physician, again, they're not gonna be able to use the FDA approved version, most likely. It's not gonna be covered by the insurance. So it's very expensive, talking about using hundreds of milligrams a day. So people really need to know what they're getting into when they use CBD. Next slide, please. Finally, another risk here, drug-drug interactions. And again, Dr. Das alluded to this. So this was a paper that I collaborated with Dr. Prima Balachandran from Mississippi and Mahmood Alsoli. We published this paper in Journal of General Internal Medicine just a handful of months ago. And we talked about myriad drug-drug interactions, right? So again, a lot of promise, but there are issues, and I'd encourage you to check out that paper if you get a chance. And then my final slide. So overall, when we think about cannabinoids and mental health, there's a lot of interest, right? We got this much interest, we got this much evidence, at least positive evidence. So we have to be very, very careful. There is some evidence, right? There's not a lot of evidence, but there is some evidence, particularly when we talk about cannabidiol in terms of a pharmacotherapy for some psychiatric disorders, perhaps for treatment refractory anxiety, perhaps for people who have psychotic disorders and aren't responding to some treatments. So it's something that we need to think about. Hopefully, we'll see more evidence as time goes on. But overall, CBD, I do think it is a very promising compound, but it's not risk-free. We certainly should emphasize to our patients, if you're thinking about using it, you need to do it under the supervision of a prescriber, a physician, ideally. So hopefully, we'll be able to get that message across to folks. Thank you. So thank you all for joining today. This is the first part of a two-part series. So the second part is next Thursday. I'll keep my comments to under 10 minutes so that we have close to 20 minutes for a Q&A at the end of this. And then, of course, the chat box is also an opportunity. We can go to the next slide. An opportunity to put in questions on particular topics you'd like to hear more about. This, in some ways, Dr. Das had a great setup in terms of her content for me to go in with a little bit more detail in terms of what patients are actually being exposed to what they're using and how that may impact their psychiatric care. And if we have time for it, I can also talk more about cannabis use disorder, although that may also be a topic to reserve for next week. Go to the next slide. So thinking through what is a standard dose, when Washington and Colorado was for the first two states to legalize adult recreational access, initially, they defined a dose, so to speak, of THC as 10 milligrams. Oregon chose five milligrams. For context, and Dr. Hill had several slides on the FDA-approved medications, these typically come in similar doses, two and a half to 10 milligram doses for dronabinol, which is a synthetic THC. Nabalone, which is a controlled substance two instead of three, it's more potent, comes in a one milligram dose. And the next slide. Great, thanks. How does that compare to when people are using whole plant cannabis? And this is dated. Dr. Das went over the potencies that we see now, the strength of THC and cannabis on the black market and in recreational markets today. And in the late 90s, it could have been 8%, which would have been about a five milligram dose, but closer to 15, 20% patients are being exposed to double or triple what they would have been 20 years ago. And for naive users or non-users, typically two to three milligrams of THC is enough to produce a psychoactive effect. Not everyone likes that, but for users, I think there's been lore that the FDA-approved medications don't have enough strength to actually do anything, when in reality, especially for people who are new onset users, typically these smaller doses of just two to three can have an impact. Dr. Das talked about vaping. And the whole idea for people who aren't familiar with vaping is that you heat the plant material to a high enough temperature to release the cannabinoids so that they can be vaporized and inhaled without actually combusting the material. So there's less carbon exposure. It doesn't break down THC and CBD the same way that smoking would. So in general, people actually are exposed to much higher levels of THC when they vape compared to when they smoke. You can go to the next slide. I'll just mention, I was talking about THC in all of these prior slides, but we know that there are at least 120, 140 cannabinoids, other terpenes, other potentially physiologically active constituents in the cannabis plant. CBD, Dr. Hill talked a lot about, and it wasn't on the prior slide, but if we think about dosing for CBD, a lot of the studies would be the equivalent in humans of getting up to 600, 800 milligram doses. So it would be a mistake to equate one milligram of THC with one milligram of CBD. Let's keep going here to the next slide. There is guidance on dosing. I think we're a bit surprised. If anything, the guidance was more conservative in terms of starting at very low doses. This would be especially true for older patients, lower clearance for cannabis naive patients, and then thinking about titrating the dose based on treatment response. Let's go to the next slide here. Most patients, the last bullet emphasized that most patients attending medical cannabis dispensaries, and this may be changing in the more highly regulated states. New York has a very highly regulated program, Pennsylvania does. But in the earlier programs, usually the great, great majority of medical cannabis users had a history of recreational use when they were presenting. Many different products. I think we've gone over this. We can go to the next slide. So it's important to be asking patients. And as the prior presenters pointed out, a lot of times these products are not accurately labeled at all. I think this is intuitive. Clearly an edible onset of action would be much slower than vaping or smoking. Patients, medical cannabis providers tend to suggest that vaping is, especially for pain or for symptoms where patients want an acute response, that the quick onset of action for vaping is preferential to an edible. Edibles have been, in the popular press, have been associated with adverse events and high-profile stories of people who used edibles as the states liberalized legal access for adults to cannabis products. And I'll show why in the next slide or two. So let's go to the next slide. Transdermal, Dr. Hill pointed out, very little data. It doesn't go into the bloodstream for the most part. That's different with sublingual or buccal administration. And the mix of all is a sublingual spray that's not approved in the US, but there are sublingual drops that patients will use tinctures from cannabis dispensaries that I have not seen as much PK data on. The next slide. So this is something that I've found that audience members tend to be interested in. And I know that these slides are a bit small on the Zoom. The point is that, without trying to see the square versus the diamond, that when patients consume edibles with THC, both the C-max, the T-max, the area under the curve are all much, much greater when people consume the THC with food. Remember, THC is highly lipophilic, goes into the bloodstream, and the patients are exposed to much higher doses. In general, this isn't something I've heard clinicians, that colleagues are aware of, that clinicians talk to their patients about. And so for patients who choose to use an edible product, and we think about the risks potentially of impact on mood, anxiety, psychosis, clearly people can be exposed to significantly greater blood levels of THC and CBD when they consume those products with food. And that may, for patients at risk for mental health effects, may really increase the likelihood of those occurring. So I'll touch on this. Dr. Hill had a great citation that he recently published in the past year. There are drug-drug interactions between THC and CBD through the cytochrome system that does impact commonly prescribed psychiatric medications. So the next slide details, I think we're all familiar with 3A4 and 2C9. Go to the next slide. Great. That THC, for instance, inhibits 2C9. This could impact fluoxetine, fluvoxamine levels. THC is a 1A2 inducer. This could affect, if you look at the list, things that we commonly have patients using under our prescription or with Coordinated Care, others' prescriptions, but widely prescribed. And it's not completely clear how significant this would be, but I would certainly want to know, as part of the history with patients, have they introduced the cannabis products to their medication regimen and could that have actually impacted their response to the psychiatric medications? Clearly, there are patients for whom you would not want to recommend cannabis use. I think this has been covered in terms of psychiatric risk factors. Also, certainly, the national organizations that trade those from medicine and psychiatry have not endorsed the use of cannabis products for women who are pregnant or breastfeeding. With higher risk cardiac profiles, also, it's recommended to avoid safety-sensitive jobs. The next slide. So, I will, at this point, because we want to make sure we have time for the Q&A, cede the rest of my time, which would have spoken about some psychiatric side effects that Dr. Hill has already discussed in more detail, and the slides on cannabis use disorder, perhaps, for next week, in terms of screening and management for cannabis use disorder. Dr. Williams, I think you were moderating the Q&A. Thank you so much. That was really amazing. I learned a lot, and a lot of good new information out there. And we have many, many questions that have come in, some clarification questions, and also some just about implications of some of this information. So, we'll start with one for Dr. Hill. We had a clarification question about someone asking if using cannabis, is it true that it causes fewer depression symptoms? Can you clarify that? Sure. Good question. So, it depends on the study you look at, right? So, there was one observational study that looked at medical cannabis. So, I'm assuming whole plant medical cannabis in patients with cancer, and they, in that study, reported fewer depressive symptoms. That may be because the cannabis was treating other issues they had, nausea, for example. But again, the study from Toronto in 2020 by Lukacs et al., and the folks at CAMH, so they had patients who had depression using cannabis, and they were able to abstain from cannabis for a month. And if they did that, then they had fewer depressive symptoms. So, I think for the most part, I think if people are using a significant amount of cannabis, so again, the dose really does make a difference, but if somebody's using a lot of cannabis and they have a co-occurring major depressive disorder, then I'm going to recommend that they try to curb that or stop, if we can, to try to give the antidepressant a chance or whatever other treatments they're using. Thank you. Would anybody else like to comment on that? Okay. A lot of questions about medical marijuana. So, in medical marijuana studies, do we have information regarding the ratio of THC to CBD and the kinds of strains that are used? And I would almost expand that question to say, do we even know the content of THC in these products, and do they also contain prodrugs? So, I don't know who wants to take this one. I'll open it up to all our speakers. I'll take that. So, I think it really opens up our larger question, what is the quality of the evidence? What is the quality of the clinical trials that have been done looking at medical cannabis, right? So, we're talking whole plant cannabis, what you can get at a dispensary or a store, and there just aren't many studies, right? They're observational at best. Some of those observational studies have looked at the THC, CBD ratios, et cetera, but it really hasn't been done in a rigorous way yet. So, I think that's something that I alluded to in my talk, that if we're going to have millions of people using these products, if we're going to have people making millions, if not billions of dollars, shouldn't we find out, you know, is this an effective treatment? We can do, and I think that's what I said about the FDA approved version of CBD, right? There's a precedent there. We can get these answers. We can find out what medical cannabis or other cannabinoids would be effective in treating. We've chosen not to do it yet, and I know that, you know, I'm collaborating with some folks, and I know there are lots of top researchers around the country working on these things, but at this point, we really don't have a lot of evidence to support the use of medical cannabis, especially in psychiatric disorders. Dr. Williams or Dr. Doss, would you like to add a comment about that? Okay, no problem. Do we have REMS in states that legalize cannabis use? And I think this question is referring to the FDA mechanism to track serious safety outcomes associated with medications. REMS stands for risk evaluation and mitigation strategies. So, where are we with that? So, for those who aren't, and Dr. Doss or Phil might have more to say about REMS specifically, my sense would be that that's for FDA approved medications. I'm not sure if that structure exists for non-FDA approved medications, but just to piggyback on this question around safety though and safety monitoring, and I don't know the breakdown across states, but in New York State, anyone who's dispensed a cannabinoid from a medical cannabis dispensary, all of which have to be overseen by state licensed pharmacists. So, it's a different, much higher level of regulation and quality control. The state does what we think is FDA level testing of all of the products in terms of current good manufacturing processes. All of those cannabinoids that are dispensed go into the PDMP, and it's really within 24 hours, the pharmacist has to upload everything that was dispensed, and it shows up, there's this whole printout, and depending on which dispensary it is, it's more straightforward to understand what the content is. Some of them use shorthand in terms of the red products or yellow products, and then it's a little bit harder to know what it is. But clearly, having that in the PDMP is a very worthwhile thing, and for better or worse, it is a Schedule 1 substance, CBD, we think of as Schedule 4 because of Epidiolex that was approved at Schedule 4. But, you know, we know that there are risks associated with cannabis. It makes sense to have it in the PDMP. Yeah, I would just echo what Dr. Williams said, and I would also point out that New York State is an exception. It's not the rule. So again, we've got most states, frankly, in the United States that have medical cannabis policies, and there's a lot of hodgepodge about how they're doing it, and it absolutely should be a part of the PDMP in every state, and it's not. It's not in the Commonwealth of Massachusetts, for sure, and I've been a part of a number of states that have a lot of conversations with multiple states, and there's unfortunately an unacceptable variety of policies, frankly, when it comes to safety. And as Dr. Williams alluded to, even if you're a cannabis advocate, you have to acknowledge that there are potential for serious side effects here, and so we really should be monitoring it in a way that we're not. I'll also add, as far as I know, there are no kind of standardized REMS that are available for the reasons that Dr. Williams, Dr. Hill mentioned. I think it comes to one of the questions that was posed in the chat also about the term medical marijuana or medical cannabis and how the comment that these are not scientific terms, but industrial terms that are used in legislation. And so one of the things that we are mindful of when we're, this is a bit of a preview to some of what we'll discuss next week, but in thinking about policy and also statements, positions that we take as professional organizations, we need to be mindful of this terminology and also of the different players involved, because this is a very big industry too, cannabis, CBD, so on. So this is kind of a loaded comment, but yes, the terminology is important, and if we are saying, for example, that currently there are no FDA approved psychiatric indications for cannabis use, and we don't have enough data, then as physicians, we need to kind of be mindful of not referring to something as medical if there is not a medical use for it in our field. I know that there was a question in the chat also about APA, AAAP potentially having an opportunity for having more information for the public that's high quality information about the risks, about, you know, is there, are there real psychiatric indicators, you know, with high levels of evidence, and I'll just say for, I think our AAAP members may be more aware, but we did, and Dr. Hill and I lead the Cannabis Special Interest Group and worked with our public policy committee to put forth a very short and pithy by design sort of series of tenets for model state laws, and it wasn't because we were encouraging the states to liberalize access to medical or recreational cannabis, but really because of our concerns, thinking as addiction psychiatrists around mental health adverse effects and the risks of addiction, and having, you know, sort of common sense suggestions, so, you know, don't allow advertising for psychiatric indications when there isn't any evidence for those indications, and other things like that, which has been published through several of the AAAP newsletters and whatnot, but I think it's a wonderful idea in terms of thinking about the major medical and psychiatric organizations, what is our role in terms of trying to correct some of the narrative, in part because the media doesn't seem to have a critical lens for teasing this apart and the influence in business and whatnot. Thank you so much for bringing that up, Dr. Williams. We do have resources on cannabis, including toolkits and position statements that have been put forth by the different organizations that you can find on the APA and AAAP website, and that's included as the last slide that will be sent to you, so you'll have that, a link to those resources, so thank you for that. We have another question. Are there any big studies of CBD in the works for specific conditions, and I assume that means psychiatric? So, I mean, I could answer that. I mean, I think that there are trials that are ongoing or certainly planned that are using CBD and some other novel cannabinoids for substance use disorders, for example, so I'd say the answer is yes. I mean, I certainly don't believe that, again, the scale of those studies meets the level of interest, right? I mean, we've got hundreds of people who treat hundreds or more or thousands of patients, so we've got millions of patients sort of under our purview that are using these cannabinoids, and the amount of trials that are ongoing is really dwarfed by that number, so I wish it were more, but there are, again, they're really capable people working on these issues, but the funding is hard to come by, all right? It doesn't quite fit neatly under a lot of funding organizations, so it's a challenge to do this. Would you say anxiety disorders is another area where CBD is currently being investigated? That was my impression. Yeah, yeah, no, I think that's fair, and again, I would say, you know, just, and I'm not speaking for anybody else here, but, you know, as somebody who just just tries to treat the patients that come into my office, again, if somebody has treatment refractory anxiety, you know, I will talk with them about using CBD, right? If they've done everything right, they're working with their doctor, they've tried multiple medications, multiple behavioral interventions, I will use that, right? I mean, I think that as psychiatrists, we're comfortable in some instances using medications off-label, and so this would be probably another one, but I'm, you know, eager to see more definitive studies that can tell us more about whether or not this is an efficacious treatment or not. I may also add, so, you know, we all have different practice styles, and I think Dr. Hill would agree with me here, especially as he emphasized that, you know, if folks are doing kind of everything, that makes sense. What my concern is sometimes is that those evidence-based strategies are not fully utilized, and so it may seem appealing or easier, and it's really, you know, for our patients, our loved ones who have, for example, anxiety and depression, like, these are things that are really disabling and really tough, and it's hard to put in the time and the patience always to, you know, to do what we know has strong evidence, for example, cognitive behavioral therapy, use of SSRIs for these conditions, and so, you know, in some cases, when somebody presents into the office and they're looking for something that is kind of a magical fix, which we don't have as much evidence for, then, you know, I think it's a part of that discussion of partnering with them to, you know, acknowledge that they're wanting to engage in treatment and then being supportive of, you know, the things that they're doing and at the same time trying to emphasize and reemphasize the use of evidence-based treatments. Yeah, can I just piggyback on what Dr. Das said, and I totally agree with what she said, and I really believe one of the greatest things that the folks that have joined this can do, just by knowing more about cannabinoids, just by being willing to have these conversations, I think that increases the likelihood that you're going to be able to get people into treatment they may not otherwise get into, right? And as Dr. Das said, somebody comes in, they're interested in CBD for anxiety, and if you're going to have a sensible conversation with them, right, you're taking them seriously, it's a collaboration, you may find as a part of that conversation, no, they have not explored more than one medication or they may not have tried any medications, and so just by treating them as with respect and talking about this in a sensible way, just not by saying, look, no, I'm not willing to do that, it's not FDA approved, I think that you can get a lot of those folks, a lot of these conversations do not end with patients using cannabinoids, right? But just by having the conversation, I think you end up trying treatments that may ultimately work. Thank you. This is a great question. We heard a lot about Delta 9 THC today, but somebody asks, what is Delta 8 THC? Is it different or safer than Delta 9? Certainly it's been in the news lately. Yeah, so I would just say that, again, as Dr. Das said as a part of her talk, right, we've got hundreds of cannabinoids, over 140 in the cannabinoid plant, so we're learning more about these, you know, I have not seen enough rigorously done trials of Delta 8 to, I think, definitively make a comment about it, but I'm open to that possibility. I think it really just raises this other issue, right? If we've got three FDA approved cannabinoids, and there are hundreds of other ones out there, I think it's reasonable for a patient to wonder, hey, maybe Delta 8, maybe CBG or some other cannabinoid may be helpful. So again, it's just about having a conversation with them, being open to looking at the evidence critically, and then making a good clinical decision. Okay, thank you. We maybe have time just for one or two more. We have a question here, can anyone comment on cannabinoid hyperemesis syndrome? Is this just related to the THC or also to CBD? I'll, Kevin, just so you're not doing all of the heavy lifting, what, you know, and I'm not too close to this, but I think going back to what Dr. Das was talking about in the epidemiology, I think one of the most important take-homes today is not just that more Americans of all ages, but especially middle and older ages, are using cannabinoids, cannabinoid products, cannabis, but that among those people who are using the daily or near daily use of high strength products for many hours of the day. So it's not just the number of users that has changed. It's really just the tremendous volume of use that has increased dramatically in the US. And I think that's part of why we're seeing things emerge in emergency rooms that were more like unicorns in the past. And now all of a sudden, that, you know, it's not, I'm mixing all of the metaphors, but it's not a zebra, it's a horse. You actually have, you know, states where a lot of the patients coming into the emergency room really do have these presentations that didn't happen before there was widespread access to super high strength cannabinoids. So I, you know, that, I know there was a question about EVALI and the, you know, vaping injuring lungs. I think we're starting to see new things emerge that just didn't happen in the sixties to nineties. And it reflects this really wide range of super high strength products that are more or less not regulated. Okay. Again, we're running out of time, but I thought this was a good one. Can you please comment on any evidence supporting the use of cannabis as a treatment for opioid use disorders, as this is an approved condition for medical marijuana? They said in New York, I know it also is in New Jersey. I think it, Dr. Dasgood, I think it warrants a longer answer. Yeah. And I was actually going to give a very short answer as a preview. So in the council on addiction psychiatry at the APA, we're doing a talk during APA annual meeting with actually a similar title, but it goes into some very deep topics of research. And Dr. Riordan is talking about the experiences in Pennsylvania with cannabis for OUD and essentially I don't want to give away the punchline, but essentially that the decision to have cannabis as a treatment for OUD didn't pan out as something positive because it didn't impact efficacy or improvement. And also people were prone to develop cannabis use disorder because of the similar brain pathways. So that's a very short answer and another topic, another talk that folks can attend at the APA annual meeting. Great. Before we close, I just want to thank our speakers who participated today and shared their knowledge and expertise with us. I want to thank our partners, the American Psychiatric Association, the AAAP, American Academy of Addiction Psychiatry, the New York County Psychiatric Society. As I mentioned, we have developed resources on cannabis that you can find on the websites and hopefully that will be helpful for you. Our next session of the webinar will be next week on Thursday, April 15th. And we hope to even have more time for questions and discussion and we hope you will register and that we see you next week. The session next week will be moderated by Dr. Jose Vito, a child, adolescent, adult, and addiction psychiatrist from NYU. So thank you again for attending today and have a great rest of your day.

cannabis

mental health

cannabis legalization

CBD

depression

anxiety

psychotic disorders

evidence-based treatments

research