In this June episode of Psychiatric News Special Report, host Dr. Sulman Aziz Mirza speaks with Dr. Heather Murray of the University of Colorado about clinical considerations for cannabis use in inpatient medical settings. The conversation examines how high-potency cannabis and concentrates have changed the clinical picture, including intoxication, withdrawal, hyperemesis, psychosis risk, delirium, catatonia, medication interactions, and self-directed discharge. Dr. Murray also emphasizes balanced, stigma-free assessment and the importance of asking about formulation, potency, route, frequency, and last use when caring for patients across medical and psychiatric settings.

Transcript

Dr. Sulman Aziz Mirza (00:13): Everybody, welcome back to psychiatric news special report for the month of June. We have a wonderful article as we go into the summertime. clinical considerations of cannabis use in the inpatient medical setting. I'm your host, Dr. Sulman Aziz Merza, triple board certified adult psychiatry, child adolescent psychiatry, and addiction medicine. So this is gonna be a fun one. I I think it's something I get to put on my addiction medicine hat and then Partly my child adolescent had, and then the adult one as well, because we're seeing this in all settings. And I think it's something as we progress in 2026, and you know, substance use and especially cannabis use is becoming more and more prevalent. We all have to become just more aware of how this shows up in our world. So let's introduce our guest. Welcome our guest, Dr. Heather Murray from University of Colorado. I'll let her introduce herself. Her bio background and her blah blah blah.

Dr. Heather Murray (01:15): Hi, thanks for having me today. I'm excited to be here. so again, my name is Heather Murray. I am a CL psychiatrist at the University of Colorado, hospital and CU Medicine Psychiatry Department in Aurora, Colorado. I did medical school at Emory, have an MPH in epidemiology, and went to Denver for residency and my CL fellowship and haven't looked back.

Dr. Sulman Aziz Mirza (01:37): Yeah, it's it's a wonderful place. I got to I don't know how many people have a chance to like go out to Denver, Colorado area. I did part of my like going through the Caribbean Med School is they send you to rotations all over the country. And I did my my my twelve weeks of internal medicine in Colorado and I was like, Wow, this is earthy crunchy munchy Denver and Colorado and it's just beautiful out here going up to the mountains and so a wonderful, wonderful place. I encourage everybody to visit.

Dr. Heather Murray (02:06): Yeah, it's fabulous. And I will say the the people are so friendly here and the food has gotten a lot better in the last 10 years. Yeah. Or things are looking up in terms of the spice level.

Dr. Sulman Aziz Mirza (02:15): Yeah, I it was it was bizarre. I had it was with a good group of people and we were like we need to find like some Indian Pakistani food and I found we found this like this wonderful like Punjabi restaurant in Denver. I think it was like India's Pearl, I think was the name of it. And it was like fantastic. I was like, They have like good Punjabi food over in Denver. This is bizarre, but we'll do we'll take it.

Dr. Heather Murray (02:35): Yeah, I think a a little known fact about the area, Ro Roar and specif like specifically, is they have it's one of the most diverse counties in the country. We have refugees, immigrants from all over the world. And I think that just makes it such a special place and also has contributed to the food scene dramatically.

Dr. Sulman Aziz Mirza (02:53): Which which is always always key for finding a place to settle down and live. So All right, awesome. One of the other unique things about Colorado is the f it was, I think, as we all kind of know, is the first state to really fully legalize I think first state, right? To fully legalize cannabis, right? It was that or Washington.

Dr. Heather Murray (02:57): Yeah, exactly. For recreational use in particular.

Dr. Sulman Aziz Mirza (03:15): Yeah, so it's a it's a unique spot to kind of get into this topic and where this kind of article is coming into. So Doctor Murray, tell us a little bit about what made you focus on this specifically in the inpatient medical setting.

Dr. Heather Murray (03:29): Yeah, so you've already actually alluded to a big part of my journey to this topic. So I moved to Denver, Colorado for my adult psychiatry residency training in 2012, which was the actual year that recreational cannabis was legalized here in Colorado. because we were one of the first states with recreational use, anecdotally, I found that many of my patients moved here specifically because of the availability of cannabis. And during the following years, throughout residency, while a lot of patients reported improvement in quality of life. With cannabis use, I found a similar amount would also mention struggling with escalating cannabis use, particularly of high potency formulations that we'll talk a ton about. And actually started to identify correlation between high-potency cannabis use and adverse psychiatric and medical symptoms. I ended up doing my CL fellowship at Colorado as well, have been faculty at our large academic level one trauma center for the past five years. And during this time, the trend has only become more apparent. because of our university's location in Colorado, our department has some excellent research and subject matter expertise in this area generally. And I've been lucky enough to have been working with a few people on different projects. But one thing I found throughout this work is that there's actually not a ton out there available for psychiatrists working in the acute medical care setting or within my specialty of CL psychiatry. So I wanted to contribute to the literature through my own discovery and education. So that's what led me to this article.

Dr. Sulman Aziz Mirza (04:58): Yeah, it's it's definitely something we're seeing. Again, people who are doing a lot of clinical work, you know, it's it's just a byproduct of what's out there and what people have access to. You know, I say it all the time when I'm working, especially with teens, and you know, the the parents bring the teens into the office and they're like, Can you tell my child to like stop smoking weed? And I'm like, Well, it's not that simple, right? And a lot of times, you know, one of the avenues I have to go to and discuss is especially when parents are kind of like, well, you know, it's just cannabis. If they're trying to minimize it or they're saying, well, at least we'll I I'll be okay with them using that is like it's not, you know, your your daddy's cannabis nowadays, right?

Dr. Heather Murray (05:45): Right. That's so funny. I always joke with patients. I say, Well, it's not your mama's swag. because it's so different from what it was back in even the nineties, early two thousands. Yeah.

Dr. Sulman Aziz Mirza (05:55): And it's this idea, like I think there's you know, again and you have people who are gonna come for I wanna say contra, but people who are again people online who will say things like, it's natural and it's organic and you and that you should be able to like just use what's of the earth and blah blah blah. And it's like I don't think there's such a thing as like natural and organic, like the original cannabis flo plant that exists anymore. It is like become the most GMO planned out there. It has become so modified, so crossbred and high breded to become these high pointsy strains that are out there. I was like, there's no such thing as like again, natural organic cannabis anymore.

Dr. Heather Murray (06:41): Exactly. And yeah, it's so it's interesting because we, you know, humans have had a relationship with cannabis for thousands of years. And that relationship, I think, has been culturally special to so many people. But the reality is that, like you mentioned, it has been bred to be higher and higher potency. and that's something that we'll definitely talk about in a lot of detail. But I think the potency piece is particularly important. And we can actually see a lot of analogies to that with let's say, you know, looking at opium. Coming into heroin and now fentanyl with Kratom 70H, right? We're creating these really potent substances that actually have completely different mechanism of action and psychopharmological properties in the brain and the body in particular. They're like a different drug.

Dr. Sulman Aziz Mirza (07:29): Yeah. I mean, they are totally different drugs. Like I think like you bring up the kratom thing with kratom as well, especially we know that like low doses of kratom work as like a stimulant and higher doses work as an opiate. And, you know, I have plenty of people coming into my clinic who are trying to get off of opioids and they're like, Well, or I don't want to do suboxone or buprenorphine and I'd rather do kratom and then they they'll do that on their own and then they will say, Well, now I can't get off of the kratom now we have to go go to the buprenorphine and it becomes this back and forth ping ponging that occurs with it. So

Dr. Heather Murray (08:04): And it's very expensive as well. Both cannabis and Kratom. So expensive.

Dr. Sulman Aziz Mirza (08:08): Yeah. So it's not always like the best option of for for these patients. So

Dr. Heather Murray (08:13): But it's also understandable, right? How people end up there and they're doing the best thing in their perspective for their health, for their body. And so much of it I think does come down to, you know, how we market it both as a specialty within medicine, but also more from a public perspective. it's that's really important as well.

Dr. Sulman Aziz Mirza (08:30): Yeah. Let's talk about let's you know, we're we're talking about the potency. So yeah, tell us about the potency shifts and then that's, you know, one of the things the article, one of the topics of the article that really is really stands out. And think something if people are just either reading the article or listening to the podcast, like the the I think that's the biggest takeaway, if nothing else.

Dr. Heather Murray (08:53): Yeah, I I agree. That actually has been my biggest takeaway through my own learning and research over the past few years on this topic is that, you know, just because something is called cannabis doesn't mean it's the same drug as the other thing called cannabis. so like I mentioned, it's been used for thousands of years. The plant itself actually consists of over a hundred active compounds, including terpenoids, phytophytocannabinoids, flavonoids, cannabidiol, THC. So THC is the chemical most implicated for psychiatric psychoactive effects of cannabis, while cannabidiol is thought to be largely protective against these effects. So in the 1990s, when we measured the concentrations of THC in the average cannabis strain, it was about 4 to 5%. That was kind of as high as it would get. And then CBT is generally a lower concentration, around 0.2 to 0.5%. However, most recently, and this is The case in Colorado, for example, I've gone to dispensaries to see what is what is the potencies that I can get. I couldn't find anything below 20% concentration of THC. So we're really breeding these cannabis strains now to have super high concentrations of C THC. Well, some simultaneously, we're not also increasing CBD or these other protective chemicals, right? So you end up with a ton of this psychoactive substance and super high potency. On top of that, so not only do we have the flour with this high concentration of 20 to 40, 50 percent, we now create these concentrates for recreational use. so concentrates in general, you might hear them referred to as shard, oil, shatter, dabs, wax, and they can come in concentrations as high as 90 to 95 percent THC and can be either ingested or inhaled through vaporizers. So, pretty potent chemicals that really are. very new over the last 15 years or so. And I think part of the issue is that the industry and the regulation are outpacing research and medical and psychiatric understanding of these substances that it's hard for us to keep up as medical providers.

Dr. Sulman Aziz Mirza (11:04): And with that, I mean like it's you know, it it's ridiculous to see. Again, like you're talking about ninety something, I've seen like ninety-seven percent, I think. you know, it's it's just out of control. And it's like w we kind of lose sight of the fact that this is a substance that's going to negatively affect us, you know, especially, you know, like has been if if anything has kind of been like everyone talking around has been C B D is the good part of it and THC is the bad part. And it's like, well, why are we increasing the THC concentrations while dropping the C B D concentrations in in these plants and this and these substances? So it's like a little bit problematic, right?

Dr. Heather Murray (11:43): Yeah, absolutely. And I think part of the issue too is tolerance. You know, people develop tolerance and you just are they're asking for higher and higher concentrations, which have these just catastrophic effects from a psychiatric perspective on occasion.

Dr. Sulman Aziz Mirza (11:58): Do you feel like clinicians are keeping this idea of like the cannabis is this like low potency substance, like they're just holding on to this idea versus fully moving and understanding they're like, no, it's it's a whole different thing than what it was, like you're saying ten years ago, fifteen years ago, twenty years ago and beyond.

Dr. Heather Murray (12:18): Yeah, I, you know, I have certainly noticed a shift in the understanding. I would say in the last, we probably were a little bit ahead in Colorado just because we had it recreationally earlier. but as I think especially the last five years, I'm starting to see that it's part of the main culture of medicine. It's the primary understanding, I think, in medical practice that cannabis has just changed as a substance. but again, you know, that's 10 years after really the changes started happening. So it takes time. Anything, anytime research happens in medicine, there's a delay in translation to practice, right? And there are a lot of cultural factors at play there. People kind of want to see studies replicated, see the evidence determined over and over again. But I think that the culture is now shifted in medicine where people are really starting to understand this change in cannabis.

Dr. Sulman Aziz Mirza (13:03): Yeah. With for like inpatient docs, people who are inpatient psychiatric units or kind of like yourself, CL psychiatry. What are people seeing? I guess what are clinicians missing with cannabis related complications? How do they show up within the inpatient setting, especially for like people who are daily users, the Wake and Bakers per se?

Dr. Heather Murray (13:30): Right, yeah, exactly. I think if I if I think about it from the perspective of someone who, like starting with inpatient psychiatry or emergency psychiatry, right? So some of the most interesting experiences I had in emergency psychiatry here as a resident was seeing people coming to Colorado for cannabis tourism. and one of the effects, for example, were edibles. And so with edibles, it can take 90 minutes to two hours to start really feeling the effect of the cannabis. And that leads to people maybe after 30 minutes saying, you know what? Maybe it's just not impacting me that much and ingesting more and more of it. Plus, they're cookies, candies, they taste good, right? And you don't understand how you're gonna react to it. So I would see really profound panic attacks, anxiety. People would come in thinking that they had a pulmonary embolism, a heart attack. And it turns out it was, you know, panic from cannabis intoxication, as well as psychotic symptoms, right? So delusions and paranoia in particular. and I know we'll go into a lot more detail about the evidence there, but I think intoxication itself can certainly cause psychosis with the paranoia in particular. And then you also notice some people have a lot of cognitive blunting. So issues with short-term memory, spatial tasks, processing speed can be pretty, pretty remarkable. And then once someone actually gets admitted to the hospital, so let's say within like the first day or so. I think that we often underdiagnose or recognize cannabis withdrawal, which is a huge issue and has actually been associated with discharging against medical advice and is something that is treatable. And then on top of that, of course, it's, you know, sort of differentiating in this young person, maybe with a family history of psychosis, who has started using cannabis with new onset psychotic symptoms that haven't resolved with intoxication. Is this actually a new schizophrenia? Or is it more kind of a substance-induced psychosis and trying to parse it out in someone who can't, you know, has a hard time abstaining from cannabis use for more than a week or two on the inpatient setting? And then on the medical side, certainly, you know, considering diagnoses such as cannabis hyperemesis syndrome, could it be contributing to issues like encephalopathy or delirium as well as catatonia? And I think one of the biases that I often see within myself and others is people of certain ages. they wouldn't be using cannabis. But I think we have to remember kids find edibles, they think are gummies, they find brownies, cookies, they eat them. So kids can come in with cannabis intoxication. Older adults too, they use cannabis and sometimes are more likely to become delirious with cannabis use than someone who's younger and healthier. So I think there's a lot actually to consider from the psychiatric perspective and cannabis use. And you know, the struggle is that it's so new with these high potency formulations. A lot of us weren't taught these things in medical school or residency. So we're having to learn it along the way, which can be really challenging.

Dr. Sulman Aziz Mirza (16:27): Yeah. you you touched on a lot there, so I like, we'll try to break it up a little bit, but I'll I'll share kind of like a a funnyish story. so my elder, my uncle, he is dealing with some effects of a t type of adenocarcinoma, a type of lung cancer. and he's like, you know, he's fighting it. He's going. It's been a few years and he's going and and one of you know, my I have a cousin, his daughter, who is like a cannabis pharmacist. So she does she makes like some suppositories for him. And then, you know, whether it's you know, he he sh you know, will knock on wood and say, like, you know, he should have been gone a couple of years ago normally. You know he's he's in his nineties and he but he's chugging along and, you know, my mom's stock and myself and everyone's like, you know, he's he's going and we don't know if these suppositories are doing something or not for him, but like he's going. But the the s the funny part is or the story part is like, you know, my cousin was making some stuff at home and was using like a little a bowl to kind of create the suppositories and, you know, sh kind of gave it a little rinse. Then later ever, you know, my dad was over, my mom was over, somebody else was over, and they were making like breakfast omelets and they, you know, end up using the same bowl without giving it a proper rinse. So my dad is you know, to my knowledge, has never used cannabis before. He's like seventy something years old. And, you know, they eat the omelets and my I think one of my other cousins was over as well at the time. You know, a few hours later they start feeling ill and, you know, they're like, What's going on? My cousins like gets they get in the emergency room or the ambulance comes over, takes them to the emergency room. You know, it becomes the becomes the whole thing where like someone's having a panic attack. My dad is like, What's going on? And again, like you know Luckily it was just an emergency room, nobody got admitted and they you know, they did a the drug test and were like, it's cannabis and what's going on here and then they were like they know they're able to the detective work and find out what was going on. But and that's, you know, a funny story in the moment, but or in retrospect a funny moment, but in the moment everyone's kind of like freaking out and being like, What's what's happening right now?

Dr. Heather Murray (18:39): Right, especially if you don't know that that was what you were exposed to. It could be a number of things that are scary.

Dr. Sulman Aziz Mirza (18:43): Yeah. Yeah, especially like on someone someone who's like seventy something years old, kn naive to it, it's like a a whole whole situation. but you know, luckily all's well that ends well. But

Dr. Heather Murray (18:54): Well I'm glad to I'm glad to hear your uncle's doing so well.

Dr. Sulman Aziz Mirza (18:57): Yeah. So yeah, it's a good thing. which is it's interesting, right? Because we have we we talk a lot. I know in the in the preface of the article you talked about something about like this is kind of like some we're focusing a little bit on the negatives, but there are potential positives, right? So tell us a little bit about that. Like so and we'll pivot a little bit for that. Like some some of the positives that come from cannabis. What are some potential uses that we have. I think we we all know I think from medical school at least like, you use it for like appetite and like chemotherapy patients. But like aside from that, what else we got?

Dr. Heather Murray (19:35): Yeah, so that's of course the main one. When you think about jabinol, right? Sort of our medical formulation of THC. It's FDA approved for both the nausea and vomiting related to chemotherapy, but as well as appetite for folks struggling with HIV/AIDS-related illness. so those are two of the technical FDA-approved indications. But there also is some data for other symptoms. So, for example, spasticity due to a variety of neurologic illnesses can be managed with cannabis. and we'll talk a little bit more about this, but even within psychiatry, I think with short-term use, people do report improvement in things like REM sleep disordered behaviors, sleep onset, acute anxiety and PTSD symptoms. Though the long-term results turn out to be not associated with improvement, but I think it's important. That we recognize again, cannabis is very complex. Again, there are over a hundred chemicals. And I think that we need to be really nuanced with our take on it. It's not all good, it's not all bad. It's complex, like most things in life, and most things, especially in psychiatry. And so I really appreciate that you asked that question because I think there are a lot of people who have found incredible quality of life improvement with cannabis-related products. And I think it's important to validate that experience. While simultaneously making sure that we're doing the due diligence of researching some of the other unintended consequences or negative adverse effects, so that we can provide folks with a really balanced take of risks and benefits so they can make decisions that are best for them as individuals.

Dr. Sulman Aziz Mirza (21:12): Yeah, it's it's one of those things I get into the conversation with especially the teens, right? When they're like, you know, this is helping me for my anxiety. And it's like, Well, I'm I'm not gonna lie to you and say that I can't do that. You know, like you know, it doesn't make it's not genuine of me to kind of take that approach and say, Well, no, you're wrong, even though you're saying you you're saying that it's helping your anxiety, I I'm gonna tell you that you're wrong. Like, no, it you I've I've lost the rapport already from day one if I if I start off with that approach. So It's something, yeah, like you're right, we have to kind of balance. It is nuance. Nuance isn't always sexy when we're trying to like get clicks and headlines and all that stuff out there. But it's something that is we have to understand that a lot of it comes with exposure and then dependence, tolerance, all that comes along with with the cannabis use as a whole.

Dr. Heather Murray (21:58): Right. And I think actually another topic that is is important and fairly recent is that for the first time, cannabis use has actually outpaced use of alcohol, especially with kind of more moderate usage. And younger generations are really replacing a lot of alcohol use with cannabis. And I think an argument can be made from like a harm reduction perspective in that sense, right? Because alcohol is not benign despite it the fact that it has been so ingrained in our culture and legal for so long. so I think that you know, there are a lot of purposes of cannabis. So again, it's really about just making sure we have good understanding of these risks and benefits so we can really help counsel people.

Dr. Sulman Aziz Mirza (22:37): Yeah, I I always kinda like talk about that when I talk about like substance use and talks. So it's like we always asked to like do the opioid talks and like the cannabis talks. But then it's like we have to remember the alcohol is like it's on a whole different chart, whole different level. like It's a killer. Yeah. It's it's it's terrible. And we we just kind of like assume that it's there and then just be like we're just throw our hands up and just say we can't do anything about it. It's like no, it's we could do it. And then yes, it's it's great that like I get your you pointed out that like the alcohol use has dropped while cannabis has kind of like taken over that. So it's like again, is it the greatest thing? Maybe, maybe not, who knows? But it's it's something that we're seeing from a harm and point of view. Yeah, absolutely. So Yeah. You talked also about like withdrawal. So talk to us about the cannabis withdrawal because that's something that's Interesting, I think people don't always understand it or underestimate it at times too.

Dr. Heather Murray (23:33): Yeah, absolutely. So you're again, you're gonna hear this theme over and over again the increased pot potency, right? So I I think of it as dosage. so 20 years ago, you would have to smoke so much weed to get the THC concentrations that you can get it with casual use today. And so with higher doses, your body is reaching homeostasis with regular usage, similar to regular alcohol use, right? And so if you abruptly stop that, say with a medical admission, for example. All of a sudden, that substance is no longer in your brain. And often people will experience symptoms of cannabis withdrawal within about 24 hours of cessation. And so symptoms often will include things like irritability, anxiety, insomnia. they'll have difficulty with focusing and even somatic symptoms like nausea, tremors, or diaphoresis. It's really uncomfortable. I think part of the reason we overlook it is it's just not one of the withdrawal syndromes that leads to significant medical outcomes. And so it tends to be sort of minimized, right? Especially in the inpatient setting where we're really thinking about, okay, what is acutely going to harm this patient right now. However, because it has been associated in studies with self-directed discharge of patients, it can indirectly lead to adverse medical outcomes, right? If someone's sitting there similar to nicotine withdrawal and we're not treating it. They're totally uncomfortable. They just want to get out of the hospital, not be there anymore. And they might actually not treat the medical cause that led them to the hospitalization in the first time, which could lead to worsening and bad outcomes.

Dr. Sulman Aziz Mirza (25:10): Yeah, I I think a lot of people underestimate the effect of like that withdrawal and that that craving for it. I've had you know, like when I was when we had PHP where I was working, partial hospitalization program and teens coming for that, like I've had patients eloping from the building, running into the streets literally just 'cause of the nicotine and cannabis withdrawals and there's like people don't under don't under you know, they just don't realize that this is some of the effects of this is like people are It's really hard to just stop it and say, like, no, you have to just not use it while you're here for these six hours a day.

Dr. Heather Murray (25:45): Yeah, exactly. Like easy peasy, right? And I think too, especially if you have underlying psychiatric conditions that you're sort of treating with these substances, let's say PTSD, for example. And now we take this substance away, we put you in this acute medical care setting where you have very minimal agency. People are touching you without your permission, bugging you all the time. You're already becoming irritable. You have hyper vigilance symptoms, hyper arousal. It just can really exacerbate psychiatric symptoms in the hospital in particular.

Dr. Sulman Aziz Mirza (26:14): So on that like level, what could hospitals do, inpatient teams, what can they do to kind of manage withdrawal, cannabis withdrawal, to prevent these discharges, AMA discharges?

Dr. Heather Murray (26:29): Yeah, I mean, I think that cannabis, you know, screening should be a part of any medical and psychiatric screening interview on admission. Obviously, some people are too medically acute. Let's say after a car accident, they're admitted to a trauma surgical team. You know, oftentimes they do that sort of first initial trauma evaluation. And then once the patient's stabilized, they go back and do their second evaluation. The similar can be said for a lot of like our social and substance history in in patients. So once the patient's more medically stable, Go back and ask them these questions that are actually really important, particularly with substance use. And I think cannabis should always be included. And when we're evaluating cannabis use disorder, we're not just asking, like, hey, do you like smoke weed? you want to ask them questions like what formulation, if they know the THC concentrations, you know, are they doing things like the chai concentrates? Are they doing flour? You know, are they smoking? Are they ingesting, for example? So you want to know. Formulation and the potency, so you can have a better understanding of the dose. So, how frequently are they using it throughout the day as well is going to be really important. And then, of course, last time they used it. So, if they used it a couple weeks ago, I'm not worried about cannabis withdrawal. If it was, if they're using heavily daily and last use was yesterday and now they're feeling irritable, that might be the cause of it. And so I think from my perspective, like anything, if you're thinking about it. Then it's easier to diagnose it and easier not to miss it. And I think it's it can be such an easy thing to treat, in a sense, in the hospital. so there have been some studies actually, quite a few trials looking at treatment of cannabis withdrawal. there have been some antidepressants that have been looked at, and nothing has shown good effect aside from mertazepine, which might help with insomnia and appetite, but actually has no effect on cravings or rates of relapse. they've looked at baclefin, which can be helpful with cravings, but worsened sleep and cognitive performance. Gapapentin actually can be really helpful. That's one that I'll occasionally use, depending on what else is going on. In particular, this one trial found that it was helpful for improvement in cravings, withdrawal, and executive functioning. quitiapene is the only antipsychotic that I found studied. But it does in another trial was found to be significantly associated with reduced cannabis withdrawal symptoms, generally compared to placebo. And interestingly though, it did not improve sleep, which I was surprised by. Zulpinum, you can use to sleep for sleep as well as sleep architecture, which a side note, cannabis, like we mentioned earlier, it can help treat REM sleep behavior disorders. And part of that is because it actually reduces. It increases time to REM sleep as well as reduces the actual time of REM sleep. And so it can be really helpful for those behaviors in the short term. You can imagine how important REM sleep is for memory and learning and just feeling not fatigued the next day. So that's where Zulpinum can come in and be helpful in particular. Guanfacine has also been looked at for irritability and improved sleep. I actually really like guanfacine in the hospital, especially because I do see a lot of patients with significant trauma histories who have exacerbation of hypervigilance and hyperarousal in the hospital. So it's a nice go-to. There is some more evidence looking at NAC and to pyramate more long-term for cravings, especially in adolescence. And then given the benefit of agonist replacement therapy and other conditions, right, like opioid use disorders, alcohol use disorder, there has been a lot of focus in research on CB1 receptor agonists like drenabinol, which we mentioned earlier. And that has actually been found to be associated with decreased cravings, increased appetite, improved mood, and decreased tension in three separate studies. so they found that it works in a dose-dependent fashion. And so what I'll I'll often actually start with drenabinol, the really the biggest issue that I see is people underdose. So generally you want to start at minimum with a dose of 10 milligrams three times a day. And often what I'll see is like 2.5 scheduled twice daily, because those are often the doses we'll use before, say like lunch and dinner in patients struggling with appetite who have cancer. For cannabis withdrawal, you need to get up there with the doses. So start with 10, three times a day and don't be afraid to increase that dose quickly based on withdrawal symptoms. And then I'll I'll oftentimes adjunct to with these other meds that I mentioned, like the guanficine, the mertazepine, quatiapine, based on other medical and psychiatric diagnoses or symptoms, and trying to, you know, kind of theoretically hit multiple birds with one medication while they're in the hospital.

Dr. Sulman Aziz Mirza (31:12): It's it's you know, for all the psychiatrists and everybody else listening is like get your template ready of like how you know, optimize your template for how to do a substance use history. And like I I think what you're talking about it was like the right w right way to do it, like what there's what they're using, how they're using it, how much, how often, you know, and especially last use, you know, whether again like it's the week before or it's, you know, in the waiting room right before or the bathroom right before the appointment, cause That happened to me somewhat recently where I was like, I shared the bathroom. I was like, I smell something in here that shouldn't be here in this bathroom. And then now I see you in my office. I was like, I s I know what's going on here. So that that happens.

Dr. Heather Murray (31:53): Yeah. And actually really something to always consider if your patient has a a mental status change that maybe lasts for a few hours in the hospital. Super common for patient to take edibles, vape in the bathrooms, in their hospital rooms, right? Like family members will bring it in or they just have it in their belongings. So always have substance use on your radar for patients, even if they've been admitted for weeks to months.

Dr. Sulman Aziz Mirza (32:18): Tell us a little bit about I know people are familiar with cannabis hyperemesis syndrome, they are familiar with the term, but can you tell us a little bit about that a as a whole?

Dr. Heather Murray (32:28): Yeah, I think, you know, I think actually some of my residents will ask me, wow, why do you know so much about cannabis hyperemesis syndrome? You're a CL doctor. This doesn't make much sense. but I think that it we actually get consulted a lot for these patients. so backtracking a little bit, cannabis hyperemesis syndrome was only first described in 2004. So it's actually a really new diagnosis, really recent. and like I mentioned earlier, translation to practice takes time. Really, it's defined as symptoms of cyclical vomiting related to high dose cannabis use that's associated with compulsive use of hot baths and showers to control symptoms, which I'll expand upon in a minute. they do have something called the Rome diagnostic criteria that was updated within, I think, the last few years that requires symptoms to be present for at least three months. Episodes tend to last under a week. You have to have at least three episodes in the past year. And there should not be vomiting in between episodes. So you pretty much return back to normal functioning between episodes. a lot of these patients are young and healthy, and they'll just show up to the ER during an acute episode while they're in the emergency department. As long as the workup doesn't show any, you know, severe infectious, emerging etiologies, the doc will be like, okay, you know, nothing severe going on. Get some rest, drink some fluids, come back if these things happen. And because they Get back to feeling better within a few days, they often, you know, these patients often don't show up to their PCP to try to get a diagnosis. So, one of the issues with cannabis hyperemesis syndrome is that there's a super long delay in diagnosis, you know, you know, five to ten years for a lot of people going through this, which you can imagine is a long time to be suffering with chronic intermittent nausea. And the description of cannabis hyperemesis syndrome probably sounds familiar. it's really similar to cyclical vomiting syndrome. Some people actually consider it as a subtype. Of cyclical vomiting syndrome, but that where and where we know the exposure and the actual etiology and cause of it. so patients are often initially diagnosed with cyclical vomiting syndrome. And if you're again, if you're not thinking about it, you're not gonna ask about cannabis use. But when you are taking a history when it comes to cannabis hyperemesis syndrome, 90% of patients in one large study actually reported improvement with hot showers and their symptoms. That is a very specific feature of this diagnosis. Always include it when you have cannabis hyperemesis on your radar, because that is really, really specific to this diagnosis.

Dr. Sulman Aziz Mirza (34:56): Then the other part to so let's talk about you mentioned before kind of the correlation versus causation with cannabis and it's this hot button topic. I think you know, I don't know if we're ever gonna get like a real true answer on it, but you know, schizophrenic form psychosis, psychotic spectrum disorders and cannabis use, again, correlation and causation. We know that there is a correlation there that is undeniable is it causing it that's T B D, but can you expand expand on that a bit?

Dr. Heather Murray (35:34): Yeah, I mean, I think you raise really the three big questions that I think we have when we're looking at this is one, does cannabis directly cause schizophrenia? Two, are individuals with schizophrenia more likely to use cannabis to self-medicate? Or three, does cannabis increase the risk for development of psychosis in someone with genetic predisposition? Right. So I think those are the three questions that I have when it comes to the research. You know, I think the challenging part is that psychiatric research, especially for rarer outcomes, it's expensive, it's time consuming. And then you have ethical implications of giving people THC in a randomly contr randomized controlled trial and seeing if they develop a psychotic disorder, right? So most of our information at this point is based on epidemiologic studies. These are really helpful, like you mentioned, for determining association, but less indicative of causation. So it can be challenging because there are so many confounding factors. More recently, because of the increased prevalence of cannabis access use, these changing formulations, there has been a lot of research in psychiatry looking at cannabis use and risk for specific symptoms and diagnoses, with psychosis, I think, being the one that's been most heavily examined. a few things that I think stand out to me based on the research. One, it's well established that intoxication with cannabis can lead to psychotic symptoms while intoxicated, right? and then there does seem to be a dose-dependent nature to that. So we do have some more kind of prospective or retrospective studies that look more at this kind of causation question. they found that more frequent high potency use is associated with increased risk for development of psychotic symptoms. And by more frequent use, I'm talking at least weekly, more likely daily. There was in this one study that I examined, there was no association with risk for development of schizophrenia or psychosis in patients he used more recreationally, say once a month or a couple of times a year. so I think at this point, you know, the what my takeaway as a psychiatrist is that I don't know if it directly causes schizophrenia. But I do think that there's enough information that tells me that exposure, especially in people with a genetic predisposition, increases the risk for development of schizophrenia. And again, would they have developed schizophrenia regardless? It's hard to say because we don't have, you know, this kind of alternate world where we can do the exposure and not do the exposure. But I have enough data to say that that population in particular, people with a family history, particularly adolescent brains. That I'm really, really concerned about. And I think that the adolescent piece, as a child adolescent psychiatrist, you are well aware of this, is so important. So something to keep in mind is that CB1 receptors, which are part of our endogenous cannabinoid system, are really critical, both during fetal development, but again, actually during synaptic pruning and adolescence. And because of this activity, it's it's important for development of learning. For neurodevelopment. And we've found that people who have chronic exposure to CBD have downregulation of CB1 receptors during this critical neurodevelop developmental time, which has been associated to adverse outcomes in things like learning, occupational functioning, as well as even more long term IQ issues. And on top of that, that is probably a time that's incredibly important in the development of schizophrenia.

Dr. Sulman Aziz Mirza (39:08): Yeah, I like you mentioned, I I when my teens patient comes in there, I always tell him I was like, you know, if if we're having this discussion ten years from now, it's a different story, right? But right now, I always tell you guys it's like try to avoid it right now. Try to avoid like the heavy use right now. Yeah. 'Cause your brain is going through those changes and your risks are there. You know, I can I can't say for sure that this is what is gonna cause you to become a psychotic, but we We know that there is a relationship that exists. Association Napolie exists that we can't can't argue with really.

Dr. Heather Murray (39:44): Yeah, and I think like anything in medicine that does have such like polygenetic risk factors, you want to think about environmental exposures. What can I reduce environmentally to at least reduce the risk of someone developing, say, this cancer, this autoimmune disease? Same thing with schizophrenia. How can we reduce those environmental insults so that someone has the best chance of having this healthy, productive life?

Dr. Sulman Aziz Mirza (40:06): Yeah. On the opposite spectrum from like our teens and adolescents, we have like delirium and then also I mean, catatunia also pops in here and there, but like let's talk about delirium and catatonia because I think that's something that a lot of people don't always talk about with cannabis. They don't know what's associated with that.

Dr. Heather Murray (40:23): Yeah. So with catatonia and delirium, you know, I most of us as healthcare clinicians, we work through illness scripts. You know, these illness scripts are developed over time through experience and attained knowledge. It's a wonderful framework that allows us skills that are beyond what a Google search or even these large language models can reproduce. But sometimes our scripts can actually contribute to anchoring and confirmation bias. So again, I sound like a parrot here. Cannabis has changed so much in the last 15 years. So if we sort of grew up in this time of medicine where we learned about delirium and catatonia, you know, let's say in the early 2000s and the 90s, it was not something that was clearly associated. But when I did a literature review, what I found was really in the past 15 years, people are starting to write up case reports and case series. Yeah, it's not the most robust kind of evidence base, but I do kind of wonder. how that might be in relation to the increasing potency of cannabis. So for example, let me see if I can find it here. So there was a really comprehensive literature review that actually sorry, we might have to backtrack. I found it. Okay. I don't know if we could just edit that part out. Okay. so I did find there was a comprehensive literature review published in 2024, and they identified 26 cases, so case studies or case series of catatonia associated with cannabis or synthetic cannabis use. out of these cases, 84% were male, aged 15 to 36. Eleven had a history of synthetic cannabis use, 15 with recreational or medical use. Interestingly, you know, in the majority of these cases, they did a Naranjo score. And determined that the cannabis was the most likely etiology of the catatonia. And very few of these cases had any psychiatric history. And so when I think about synthetic cannabis in particular, we know that it's quite potent and it really binds strongly to the CB1 and CB2 receptors. And so when we compare that to these changing concentrations and potencies of cannabis in these modern strains and concentrations. I have to ask the question, you know, is modern cannabis more similar to these synthetic cannabinoids in some sense than it is to the traditional formulations of cannabis that we were using prior to twenty, thirty years ago. And if that's the case, then I I have a feeling we're gonna see more cases of catatonia associated with cannabis in cannabis withdrawal.

Dr. Sulman Aziz Mirza (42:58): Yeah, I I agree. I I mean I you know, I always kind of say when I'm talking w teaching to like the residents and everything and people online is like dose makes the difference. Right. What's you know, like the difference between like desoxin, methamphetamine that you pick up at the pharmacy versus methamphetamine that you buy in the streets is dose, right? Like that's that lithium.

Dr. Heather Murray (43:17): Look at lithium.

Dr. Sulman Aziz Mirza (43:19): Right. Again, lithium oritate that like people are like using as a supplement to like, you know, balance their mood out versus, you know, lithium toxicity. Like again, this this is the dose makes a difference with everything. And it's the same with cannabis, alcohol, et cetera, everything that's there. So good.

Dr. Heather Murray (43:34): And I think one one way I like to approach these, I cause you know, I think especially this is the case in CL and academic centers, we see some weird stuff, less common, rare things. And I always try to take a step back and think about okay, what is the possible underlying pathophysiology that's happening here? Does this make sense conceptually in a logical sense? and so, you know, we do know that THC can actually increase the brain's levels of GABA. And decrease glutamate. And so abrupt cessation from THC can actually put both of those neurotransmitters out of balance and theoretically develop catatonia. THC also impacts NMDA receptor activity, right? So again, that's something that we see in catatonic syndromes. It's part of our treatments. so I think if you know the theory makes sense, then it might be worth considering it and at least looking into data, starting with case series, case studies, collecting that and then going to higher levels of evidence.

Dr. Sulman Aziz Mirza (44:29): And another part that we have to like understand and realize is that like THC, C B D cannabis as a whole, like doesn't always play well with our medications, correct?

Dr. Heather Murray (44:40): yeah. definitely. Yeah, I think this was one of my biggest takeaways, actually, kind of going through and putting this paper together. so we've talked a lot about sort of, you know, the brain and the function of cannabis on different receptors. But one thing that's really important for psychiatrists and really any medical provider that's prescribing medications are going to be metabolism and drug interactions. so these usually occur through the SIP enzymes. So 2024 study actually found that most drug classes have the potential to interact with cannabis through CIP enzyme reactions. So THC is metabolized by CIP2C9 and CYP3A4. And it also acts as a competitive inhibitor for a bunch of other CIP enzymes. And then similar to cigarette smoking, smoking cannabis can produce these polycyclic aromatic hydrocarbons that then induced CYP1A2. Enzymes, so that can impact the metabolism of a ton of different medications, including including, of course, clozapine. so these different SIP interactions can then affect serum levels, both of the drugs, as well as cannabis itself. And I think we have to keep in mind too, THC is super lipophilic, so it stores in the fat for a very long time and can continue to leach out well after cessation. So you really want to think about interactions with cannabis like weeks to maybe a month or two after someone discontinues usage.

Dr. Sulman Aziz Mirza (46:05): Yeah, it's it's, you know, for all the med students who may be listening, it's another another thing to add to those charts about the CYP enzymes that we have to remember. And just again, as it becomes more and more prevalent, we have to be aware that it's gonna interact. And, you know, I think we see it a lot of times when parents come in again from to my office and they ask, like, can can the kids smoke on this or use this while they're taking some of their SSRIs? And it's like ideally not. But you know, like We have to be be realistic and understand that it's gonna happen and and the effects that are can occur with them.

Dr. Heather Murray (46:41): Exactly. And I think it's it's interesting. It's something that comes up a lot in transplant evaluations and not just because of the direct effects of cannabis and smoking on whatever organ systems involved, but because of the interactions with a lot of the transplant medications themselves.

Dr. Sulman Aziz Mirza (46:56): Yeah. And seizure meds too, right? huge seizure meds. And especially with like, you know the then investigations of CH or THC in seizure Medicaid as as an anti epileptic itself, that's something we just have to be aware of as well. Right.

Dr. Heather Murray (47:15): Exactly. And valproic acid, which is a very common med in psychiatry.

Dr. Sulman Aziz Mirza (47:19): Yeah. Do we as we kind of like wrap it up a bit, like s stigma. I know we're again like we we're the article kind of gives that a little disclaimer, kind of like then we're talking in the negatives about it. But like as we kind of like talk about that, how do we avoid recreating stigma around cannabis so that yeah, our patients can be honest and we can help them the best? Because you know, honesty is the best policy and you know, we we want our patients to let us know what's going on so we can help them the best and we have the most information to do so. How could we just kind of say, like, let's not stigmatize this and shame on you for using this and this is what happens if you do it.

Dr. Heather Murray (47:59): I know I actually even struggled in, you know, thinking about submitting this article for publication or even coming on this podcast and talking about it. You know, is you know, I'm I am talking about all these negative impacts in the medical setting. How might that contribute to stigma? Right. I don't want to be harmful in that way. So, you know, I think the big thing again is is taking that step back and remembering that life has so much nuance and gray in it. and in particular when it comes to even our medications we use, right? I mean. There are risks and benefits of so many meds, especially in psychiatry. I almost take the same perspective on cannabis. You know, what is the reason that someone's using the cannabis? Having that very non-judgmental approach with the patients, but also not feeling that internalized stigma myself, right? So if I'm tiptoeing around the cannabis use, I'm not normalizing it, right? And I'm making them feel judged in a way where it's this kind of dirty topic that we're talking about. versus me just kind of outright asking about it in kind of a normal manner, using language that people often use in the community and not trying to over medicalize everything. So I think coming at it as a from that very judgmental, motivational interviewing perspective, right? Trying to discover what is it about cannabis that keeps keeps you going to it? What is it helpful for? What do you like about it? You know, how is it impacting your life in a negative way? And having the patient tell you and kind of come up with that and really say it out loud to themselves. is really important. And then again, I think all we can really do as psychiatric providers is try stay as up to date on this very evolving wide breadth of literature on this topic and do the best we can to be a good consultant to our patients and give them a much as much information that's not biased on the risk and benefits so that they can make that well informed decision on their own. Yeah but yeah, never shame someone for anything like that. That's a good takeaway.

Dr. Sulman Aziz Mirza (49:50): Yeah, I'm I'm glad to hear that like we've got that overlapping in in regards to ask how we're asking the questions of like what what are you what's it doing for you? You know, like and just kind of like you ask that question a lot of times when you lead with that question of like instead of saying why are you using it, saying right, we're what's it doing for you? What what are you getting from it positively that changes the whole tone of the conversation and allows hopefully openness and then again being able to synthesize that information and come up with whatever treatments or helps that they're looking for and just yeah, understanding that part of it. So

Dr. Heather Murray (50:23): Yeah, exactly.

Dr. Sulman Aziz Mirza (50:25): Wrapping up again, big big picture. What are you hoping after like reading this article, listening to this podcast, what do you hope that psychiatrists, trainees, doctors as a whole, society maybe, what do they get from this?

Dr. Heather Murray (50:38): I think the big takeaway, honestly, is coming down to that whole conversation about dose and you know, what is the actual specific compound. so I think that remembering cannabis as a word can mean so many different things, right? It can mean sort of traditional 4% flour, or it can mean this 90% concentrate. And those two substances are completely different and have totally different effects on the body. so really getting down and asking someone, what are you using? How much of it, when, what's the frequency, right? what's the route of utilization? I think that thinking of it in terms of dosing is really key to help us from there extrapolate, okay, is this actually kind of a concerning dose and formulation? If so, then we can go down this route of education working on it versus maybe it's something that they're using infrequently, like once a month recreationally, and it's having no adverse effects, right? So I think that's probably my biggest takeaway. And then number two would just be to remember that if you're not thinking about it, you're not going to ask about it and you're not going to diagnose it. Right. So having this index of suspicion for cannabis being related to different issues, whether it's anxiety, insomnia, catatonia, vomiting cyclically, all of these different conditions that can be related to heavy cannabis use. especially as it becomes more and more common as it's recreationally legalized. I think we're only gonna be seeing more of these conditions. So as long as it's on your mind on your radar and you're asking about it, then everything kind of works out from there in terms of identification.

Dr. Sulman Aziz Mirza (52:16): Yeah. And I always kinda like to ask our guests on here, Doctor Murray, what do you like to do for your own self care? before just you know, we have to as we want to make sure that we have psychiatrists are around for a long, long time. So yeah.

Dr. Heather Murray (52:31): I I love that question. I have gotten super into native plant gardening, which I always joke that gardening in Denver is on hard mode because our weather is so extreme here. And we probably only get about five months of real flowering gardening weather. but I have been slowly replacing my entire yard with natives and this season especially have noticed so many more birds and pollinators that I am just delighted. So that has been my major self-care the last couple of years.

Dr. Sulman Aziz Mirza (53:00): Awesome. Awesome. Awesome. Well, thank you so much, Dr. Murray, for joining us on this very, very relevant and on topical topic. so this was our podcast for the month of June. You can find it online, psychiatryonline dot org. Again, the article is clinical considerations of cannabis use in the inpatient medical setting. please follow along with the podcast, subscribe on iTunes or all whatever the podcast apps are, give us a like, comment, and let us know what you'd like to see and hear in the future. And thank you again for joining us. Thank you.