Cannabis and Coping: A Mixed Relationship

Margaret: [00:00:00] Hey, Preston. 

Preston: Hey, how's it going? 

Margaret: It's good. Another week. I don't know how to do the intro for our podcast, so you have to do it. 

Preston: Okay. Welcome to the podcast. We have an icebreaker or I heard you have an icebreaker. 

Margaret: I have an icebreaker. Which one of the good things about having a podcast with you is that it means I can make you answer such just dribble drabble questions that no one cares about.

But I love asking my friends this especially in health care. So 

Preston: Googling dribble drabble, but Googling it, 

Margaret: translating it, sounding it out. Uh, so today's episode is about. The endo cannabinoid system, marijuana, all of these things and the question I have for you, because I feel like it ends up relating to this and we'll talk about clinical pearls later is how do you help yourself physically calm down without substance of any sort, but you can use your endo cannabinoid system.

Just not your ex outer 1. 

Preston: Yeah. I feel this is a trick question because you don't want me to, you don't want me to share punching a [00:01:00] wall or, 

Margaret: or screaming at the top of 

Preston: my lungs in a Walmart because that's what I usually do. 

Margaret: Your cat in the background is just pawing at the tree. 

Preston: Yeah. Anyway, 

Margaret: no, I want you to be honest, but I actually like asking people this question who work, especially as therapists, because I feel like there's so much emotion all day.

And this is not just in therapy. It's in a lot of places that I'm so curious how they like, we talk about like thought processing and like the emotion, but that there's so much like physicality to emotion. And so I always ask people like, how do they get it out of themselves before they just go back into clinic?

Preston: So what's, this is. I don't know if this is necessarily healthy, but but so without substance, how do I call myself down rapidly like on demand is it's almost like radical nihilism. 

Margaret: Okay, say more. 

Preston: So I just kind of like if I'm stressed about a test or maybe how someone might perceive me or a comment I receive, I really just lean into how meaningless life is.

Margaret: You [00:02:00] sound like Caleb here. And how are you feeling? And it's 

Preston: like, whoa, you know, we're all in this like floating rock in the middle of. The universe like everyone I know and everyone I will ever know and everyone they will ever know will all die and no one will remember all 

Margaret: your worried 

Preston: about what this person said to me in line at a Wendy's how trivial is that and so then all of a sudden it it like really puts into context how like pointless my concerns are and then I feel better.

So 

Margaret: invalidation I mean 

Preston: you could call it a frame shift if you want but the problem is the consequence of it is that all of a sudden I have this like feeling of dread because all the things I'm excited about also don't matter so like darn it I really haven't like workshop that. 

Margaret: Uh, 

Preston: portion of it yet, but I only apply PRN, you know, and then I spend the rest of the day.

I try to undo that philosophy, 

Margaret: but what do you do with like the physical energy? Because I get that it shifts the physical energy, but like, do you know what I mean? Where it's like you spend all day and like, [00:03:00] maybe you're in like the something's going on on the unit or you're like, just had patients who are really going through things either up or down or whatever.

And you leave clinic and you're like, oh, man, I have all these emotions. I walk. I 

Preston: have to walk. You walk it out. 

Margaret: You hawker walk. 

Preston: Yeah. I do. Um, I just do laps around my neighborhood and when I'm on call and I can't do that, I will like type out a note and then a reward myself with like an 8 minute walk. And then I go right again.

And then I go walk some more. But like, I just, I just. One foot in front of the other. I just trudge in it. It works like it dissipates the feeling so that's kind of what I've been doing So as a I mean, honestly, like I would say nihilism and walking. You're kind of like synergistic 

Margaret: Love you. 

Preston: Yeah, they were doing what were they doing 

Margaret: besides nihilism and walking 

Preston: probably drinking too.

I would say that's true. 

Margaret: That is 

Preston: substance Okay, so Margaret, I want to know how you calm down without substance. 

Margaret: Yeah, well, I do punch the wall [00:04:00] Um I feel like I'm about to say something really cliche as a psychiatrist that is like when I read the body keeps the score I've read other books since then don't come at me for the people who about that book, but um the idea in sort of like the somatic therapies, I think what I took away from a lot of it is like Obviously, exercise is one, um, which is walking.

I also used to bring my, like, yoga mat and my, like, Pilates ball to call, like, 24 hour call shifts, and I would, like, put my mat out, and in between, like, notes or something or pages, I would, like, give myself 10 minutes to just be, like, I'm gonna do something that is a physical sensation rather than a psychological, emotional sensation.

I also walk a lot in Boston, mostly because I have to. I, you know, as cliche as it is, I do think, like, bubble baths and, like, saunas. I don't know if I believe in all the, like, I don't, I don't know what I think of them in terms of when people are really into sauna or cold plunges, but I will say, like, [00:05:00] water temperature regulation for me does a lot in terms of, like, relaxing and the other thing I think is, like, cooking for me, like, actually touching food and noticing, like, physical sensations and smells and colors 

Preston: helps 

Margaret: me, like, de stress the really, like, wound up emotional part of me.

Preston: Yeah, they're my tools. That was that was quite the journey. You took us on. I think we started at Pilates ball and ended at bubble bath cooking walking around. It's just a 

Margaret: question of how do you I feel like this didn't matter to me as much until I was an outpatient. Honestly, like outpatient full time third year.

Preston: I think there's something beautiful about the optics of being on a bubble bath. You have to it's essentially like a Baroque painting and you're like, I'm in this portrait. I must be relaxed. There's no way I can't. 

Margaret: Yeah. My friend, I was 

Preston: at Lifetime Fitness the other day and my friend, 

Margaret: um, she really 

Preston: wanted to like take me to this cryo chair and get inside of it [00:06:00] and it just, it like freezes and then it gets hot and then it freezes again and gets hot and I was like, this is so uncomfortable.

I looked relaxed. So I was like, honestly, I can still feel the stress leave my body, even though like my calves are like icicles right now. 

Margaret: It's kind of like when you want a hard run and you're like that itself is really stressful. But afterwards I feel great and less 

Preston: stressed. Yeah, I've never regretted a hard run.

I've never regretted a run. I think honestly, 

Margaret: that makes one of us. Well, so I think this is related to our episode because I think a lot of the time when I talk to my friends or my patients or whatever about like marijuana, it's as like something to help us stress relief or kind of like relaxing. And so I thought we'd start with Our internal systems relaxing before we do this episode on marijuana, and it's 

Preston: funny because a lot of that is mediated by the same biochemical properties.

Margaret: Exactly. 

Preston: It's the same mechanism. We're just hijacking it different ways. 

Margaret: Exactly. So, Preston, do you want to tell us more about [00:07:00] the endo cannabinoid system? 

Preston: Sure. And so I'll talk about this. Um, mostly in the context of marijuana, which is what we're gonna be talking about. So the endocannabinoid system is vast and we really know it to have these two receptors.

We have a CB one receptor and a CB two receptor. The CB one receptors are scattered all across your, um, brain in your nervous system. And the CBT receptors are everywhere. So they're in your spleen, they're on your blood cells, they're also in your brain, and they can have a lot of impacts on things like pleasure.

Pain. Nausea, appetite, and those are all the things that we classic associate, um, cannabis with. So we kind of understand that these receptors play a role, but the exact role that they have isn't very well understood. And how we uncover things in science is by just knocking something [00:08:00] out and seeing what happens.

So I think someone said in, in neurology that we learn about the brain one stroke at a time and that's kind of how. Yeah, it's really, it's really how we figure out how proteins work. So let's kind of look at the CB1 receptor and then we'll go more into how it affects something like pleasure. So, so this is a receptor that is a G coupled protein receptor 

Margaret: and 

Preston: yeah, so what's relevant about that is it means that.

induces a signaling cascade, which allows the cell to decide what it wants to do with it. And the signaling cascades can be different. If it was something like a GABA receptor, for example, that's a direct ion channel. So it has a direct impact on whatever it's touching. So a lot of the, the, the takeaway here is that a lot of things that affected by cannabinoid receptors are indirect and they have downstream effects.

When we look at how it relates to dopamine, there aren't cannabinoid receptors directly on dopaminergic neurons. [00:09:00] Interestingly, so we have a lot of dopamine neurons that kind of sit in our midbrain and they extend into all these different parts of our brain and like our mesolimbic system or meso cortical system, but none of them actually have CB one receptors on them.

So it turns out if you block CB one receptors, it doesn't have any effect on dopamine. Like people don't feel dysphoria if you block a CB one receptor or you CB one antagonist. However, If you activate it, and so, and the reason why I'm saying that is that some of these things have what's called like a tonic effect and tonic just means.

If it's hanging out or, or kind of actively turned on because things have a basal rate that they get turned on by it, then it's gonna have some downstream effects. So, for example, everyone in medicine is kind of aware of how dopamine inhibits the release of prolactin in the pituitary gland. That's a tonic effect, but that same relationship doesn't quite exist with CB1 and dopamine.

So, how does, how do [00:10:00] the two relate? So, for pleasure, for example, what we do know is that CB1 is on a GABA. Neuron and gaba is very inhibitory. So we basically have a break on the dopamine neurons that cb1 is just kind of sitting on. And when you activate it, you kind of cut the break line. So that's what you're doing every time you or stimulate that receptor.

You're kind of Disinhibiting, which is what we love to do in biochem. Like we biochemistry in general doesn't like activating stuff. It likes inhibiting inhibitors because it's much easier to function that way. So we so we inhibit a GABA ergic neuron, which ends up leading to downstream stimulation of the dopaminergic neuron.

Like basically we Unlock its handcuffs. Yeah. 

Margaret: And I think that to zoom out, I think everything you're saying, first of all, you're explaining it so much clearer than I could. Thank you, Preston. And this concept that for people who aren't psychiatrists or aren't [00:11:00] neurologists or neuroscience that listened to the podcast, this concept of sort of These different sort of locking key systems that are then in like circuits, not just in the way we talk about in terms of brain circuitry, but sort of like I'm thinking of those like the mousetrap game where it's like you can take this piece and put it over here and it's going to make it if it goes into this other part, it's going to make it go left or right that it's there's not a definite meaning to a neurotransmitter as much as it's like can can impact something else.

Like if you put an endocannabinoid Receptor and make it like yes or no on some other like neuron or neuronal transmission. It might do something different versus like just a straightforward like yes or no. Like, it's not like I think sometimes we think like gabapentin inhibits, but or not Gavin. Sorry, gaba like inhibits glutamate excites.

And that is an oversimplification in terms of like if you inhibit something that Is inhibiting, then the downstream of the GABA would be [00:12:00] excitatory. Um, so that's a, I didn't say that as clearly as Preston did, but I think that's a concept that comes up over and over again. And like, in like clinical neuroscience, that is not represented well, because it's hard to represent in terms of like pop culture around.

How the brain works. So yeah, I think 

Preston: a good analogy I use for that kind of framework of thinking is the temperature of the room that I'm in. If I, because I have on switches and I have off switches, right? So like glutamate's an on switch, gab is an off switch. If I turn off the heater, the room's going to get colder.

And if I turn on the air conditioner, the room's going to get colder. 

Margaret: Right. 

Preston: Right. But if I turn on the heater, I'll get warmer. If I turn off the air conditioner, we'll also get warmer. So whatever my goal is making the room warmer or hotter, I can use. The on and off switches at my disposal. That's kind of what our body does to achieve these things.

Instead of room temperature, it's like pleasure or fear or whatever we want, whatever goal we're trying to accomplish. So the other thing that's relevant actually is, um, glutamate is also [00:13:00] affected by these neurons. And it turns out that glutamate, which is an excitatory neuron, is also decreased when CP1 binds to it.

So I don't understand too much about this pairing, but what we find is that we essentially have. An on switch and an off switch on our dopamine receptors and both of them are hit by endocannabinoids. And I think the takeaway from that is that you and I are going to have different genetics for on and off switches and they're going to be affected differently.

So, for someone, they may have a huge sense, their on switch may have a huge sensitivity for cannabis and their off switch may not. And so because we kind of have this push and pull, that means it's not going to be the same function for a lot of different people. And the reason why I'm trying to draw attention to that, and this may, I may be off by like making this analogy, but it's that weed affects a lot of people very differently.

There are other drugs that have reproducible, consistent responses, but we can't pin [00:14:00] down cannabis in the same way. So like, for example, with seizures for some people, it decreases the seizure threshold. And makes them more likely to have a seizure for other people, it increases a seizure threshold and they're less likely to have a seizure for some people.

It induces anxiety for other people. It's calming, right? And I think we all just kind of getting this huge back and forth and both are kind of true. And you have to think about the genetics of of these individual receptors. 

Margaret: I think also, like, one of the things in one of the papers, like, one of the papers you sent me that I was reading is, like, the idea of the density of a certain, you know, like, for this, the endocannabinoid, like, CB1, CB2 receptors in different brain regions and therefore different, like, mixed impacts on, like, function of clinically observable phenomenon.

And the idea of using a substance that impacts those broadly is very different than what would be observed in like, why [00:15:00] we have like, we have these receptors for an evolutionary reason that is for like, very specific signaling that our brain does. I think one of the things I was reading around was like, sort of like location and Endocannabinoid receptors are kind of like knowing where you are in space, and that is really, really specific.

And this is a problem we have in all of psychiatry, which is that both our medications and then also substance, whether we're using it medically or not, is a hammer rather than a really fine tuned, like, neuron to neuron modulation that our brain does. 

Preston: I think hammer is a generous interpretation. I think it's like, yeah, 

Margaret: that's fair.

We're essentially 

Preston: like, like, we're trying to, like, we want to have this controlled burn in 1 part of the forest and the only option we have is like, to drop a hydrogen bomb on, like, the entirety of Oregon, you know, right? Right. 

Margaret: Hopefully it works. Hopefully it's better than not. [00:16:00] Yeah. 

Preston: Yeah, because because everyone's getting the same solution and like to be fair.

I don't I don't think our psych drugs are like hydrogen bombs But right the right they're so non discriminate. It can be frustrating that Flipping it's like you look at this control panel like in a cockpit and it's like, okay You can flip all the switches up like is that good for all of them for some in this corner might be but then yeah Who knows who knows for everything else?

Yeah. Yeah. It's frustrating. I think people want neat answers when it comes to the response of the drug. And we want neat answers 

Margaret: as prescribers. And I will say for people listening, like we do randomize control trials on these medications. And so the ones that make it through are the ones that more often help rather than harm and have like less side effects.

But so we're not prescribing things that we are afraid are going to just be awful. We know that when we 

Preston: run this nebulous, like chaotic thing through a system, when it comes out, the other side is [00:17:00] better. Yeah, why it's better. That's that's tough. But but we know consistently over time that things do improve when we prescribe these, which is the entire basis of psychiatry.

So I can talk a little bit more about some of the other mechanisms that can result in these syndromes. But before we kind of go into that, the clinical manifestations, I want to hear your take or you kind of describe some of the history of cannabis and how we've gone to this point in the country. 

Margaret: I'm going to stay at, like, kind of a You know, a thousand foot view on this.

And I think it's also going to be interesting if we have a conversation around it. And so the question, and this is not a trick question I have for you. First, Preston is what do you know about the war on drugs? Quote unquote, 

Preston: the word drugs. Okay. So you're quizzing me. This is good. 

Margaret: I'm not trying to, this is not, I'm not, I 

Preston: think it was started in the fifties If I had to guess, I want to, for some [00:18:00] reason, LBJ is coming to my mind, Johnson, and I remember there was like a lot of trials with drugs.

I want to say like weed and LSD specifically, like we were just studying the crap out of it. Like there were like 10, 000 studies with LSD in a five year period in the early fifties. And then I think we gave some years. To Stanford students, if I remember right, and the students, I mean, 

Margaret: it was, um, it was in 

Preston: Boston, uh, 

Margaret: I think, yeah, so the Marsh chapel experiments, this is not marijuana, uh, it was psilocybin, um, and that was in, uh, in April 1962, and it was at BU's Boston university's Marsh chapel, um, but it was like with Harvard and dah, dah, dah, dah, dah, and it was giving graduate students.

Uh, and being like, what happened? And anyway, we won't go into that in this episode. Um, but you're [00:19:00] right in that there was a lot of things happening and we were able to study psychedelics, hallucinogens like marijuana and things like that in a different way up until the 70s. Um, the war on drugs was more of a Nixon thing, and it was kind of like, As somewhat I think a reaction against, um, like the sort of time of like the hippie, like use of hallucinogens, dah, dah, dah, dah, dah, more of like a conservative reaction against.

But I think something here that we'll touch on at different points throughout this podcast is just how much like. The culture of something impacts why we're doing something in psychiatry. So when you're mentioning, like, in the fifties and sixties, they were studying all these things. Do you know why they were studying these things?

Like, why there was finally like psychiatric studies there? 

Preston: Yeah, we were seeing them as almost like these cure alls, if I remember right. Like, like, it was seen as like a possible cure for things like depression. 

Margaret: Right. But why did we care suddenly so much about depression? 

Preston: Um, I don't know. 

Margaret: That is actually a good question.

So, [00:20:00] World War Two, all the soldiers who came back, shell shock, PTSD, depression, like, the reason the VA has so much of the like stuff around PTSD research historically and still currently is because there was a ton of funding because after World War Two, when people came back, it was like, oh, these young men who are on the front and are supposed to be like, productive members of society are like, very mentally impacted by this.

Um, and so there was money and research in a way that was very different. And also just more widespread and widespread in the population that, uh, the government, I think, in some ways cared about. But then the 70s, there was this, you know, for many, many reasons that we won't get into politics about this war on drugs, the war on drugs being criminalization for possession and use, um, as well as distributing.

Um, and that is the reason why there's been limited research in terms of the endocannabinoid system and other things up until like the 2000s, 2010s and now. Because there [00:21:00] was no medical marijuana and there was not a, you couldn't research giving it. It was like illegal to do research, giving it to people.

Um, so that's some of the why there's like a paucity in terms of like, we're, we know so much more now from like the last decade of research, but that's also part of something that comes into clinical experience of what does cannabis THC or versus CBD, which we also should probably mention in terms of the difference there.

But like, how do we talk to our patients about it? And what is the evidence basis we're drawing on? Because there's this chunk of time where there was no research and like the heyday in some ways of research from like the 70s to the like mid 2000s. 

Preston: Yeah, I think there's this idea that or or the legalization of medical marijuana still kind of puzzles me, I think, because it outpaced.

Our evidence, like the medical understanding of how it could be helpful and seemed like this could be a catch off for someone who I [00:22:00] think it was first for cancer patients who are having trouble with pain and appetite and nausea and then it kind of like these are these are patients where they're on hospice and the doctors couldn't hurt, you know, but then we throw it into this entire category of like, as long as the doctor says it's cool, it's cool, it's cool.

Margaret: Uh huh. Yeah. Yeah. And that right now, I think the, the American Psychiatric Association, like their statement from, I want to say it was 2018 or 2019 and, and the American Medical Association on like, what are the evidence based uses of medical marijuana, not just anecdotally, but like, what are the ones we can get behind?

We all know that we use different things, especially in psychiatry, quote unquote off label. Um, but, yeah. And it's what you mentioned. It's like nausea, appetite, pain, or like for oncology. There's one. I think there's an indication in Ms as well. Um, [00:23:00] 

Preston: is that for Canada at all or for THC? 

Margaret: I don't I don't think it's it delineates actually at that point.

I think that's because this is like 6 years ago. I don't think they had fully. I think they just said cannabis, which but that gets us into something. What is. Do you want to talk about CBD versus THC and what is cannabis? 

Preston: Yeah, yeah, so why would I even bring that up? Well, I think this is something that's, I think, really frustrating and confusing to people.

When you're driving around and you see, like, free CBD, or like, I think I drive, I live here in Texas and I drive, Weed, as far as I'm aware, is not legal in Texas. It's legal in Colorado, where I grew up. 

Margaret: In Massachusetts, where it is, I think, legal. 

Preston: But you drive around and it's just like free CBD, 21 plus. And then you're like, is that weed?

There's a picture of weed on the billboard, but people talk about like something else. And so there, there are two [00:24:00] substances that people care the most about that live inside of weed. So one is CBD or, um, cannabidol. And the other one is THC or tetrahydrocannabinol and these are essentially the same structure with some variations in how their bonds are organized.

So tetrahydra meaning it has a couple more hydrogens and instead of a double bond, it has some single bonds. There's a few bridges made, but they actually come, both come from the same parent compound. They're just synthesized through different enzymes. CBD is the one that can stimulate your appetite. It has some effect on noise receptors in the peripheral nervous system, but it does not bind to the CB1 or CB2 receptor, so it's very important to understand.

CBD isn't psychoactive. THC, on the other hand, that tetrahydrocannabinol does [00:25:00] bind very tightly to both the CB1 and CB2 receptors. So we would expect a lot more of those neurotransmitter modulating effects to come from THC. And an important thing to understand too about this is that the potency of the weed you have depends on your ratio of THC to CBD.

So earlier in the 90s, That ratio is a lot more even and then because a lot of people are marketing weed specifically for its psychoactive properties, people are selectively breeding or using genetic modifications to. Increase the ratio of THC to CBD. So a lot of the marijuana that you find now, either in Colorado or Texas or things that are being transported in, um, south from south of the border have much higher concentrations of THC.

So that means that the stimulation of these downstream endocannabinoid systems is a lot more significant. [00:26:00] 

Margaret: Yeah. Yeah. And it's, I think the other thing that impacts us is like the way it's used. So like, if you grew, even if it was like, if you, if you grew, like. Cannabis or whatever, if you grew the plant and like that would give you a certain amount like this ratio.

That's like quote unquote naturally occurring. Although in like modern times naturally occurring, who knows? Um, but then smoking that versus a synthetic form that is not grown at all versus vaping. And in terms of like how much can be absorbed, like of smoking it versus inhaling it versus eating. It is also something that complicates the active potency and dose.

Thanks. 

Preston: And I think and these are things these mediums of ingestion aren't necessarily well regulated by the industry. So to kind of go back into what I was saying earlier about how [00:27:00] it became this almost like last ditch palliative intervention for people and that has now that's been kind of legalizing these different states.

Has almost adopted this new face at one of like alternative medicine So if you it's really interesting to see how like different types of weed are advertised like if you go into a dispensary I've only been in one dispensary, but they'll be like this strain is for your sleep. This strain is for pain this one will help you with nausea and it's like It's almost being treated like the different ratios of CBD THC or somehow now like supplements and there's not a lot of like Evidence to support any of these claims 

Margaret: Mm hmm.

Mm hmm. Yeah 

Preston: And so it's, it's interesting. It's almost like they're practicing medicine in a way by prescribing just like different variations of THC. 

Margaret: Well, I, I think that this is something we actually probably haven't, we haven't talked about yet on this podcast, which is like a larger question [00:28:00] of clinical care is, you know, there's Modern Western medicine, and there's like alternative holistic naturopath, all these like other things.

Um, and there's also the history of medicine of who gets to have a voice. What counts is valid science. What, you know, how do we test things and who has the resources to test different things? Um. And that I do think sometimes marijuana falls into this category of like, it's something that's been used for hundreds and maybe thousands of years in different ways and different religions and different societies and can, can there be a place for it in modern medicine in terms of how it's used?

And like, if we can experiment with it and see what, where it works and how and why, um, Yeah. But that a lot of people don't feel seen in modern medicine and modern medicine lacks a lot of answers and also maybe lacks a type of approach and I feel like marijuana is part of this larger conversation of how do we care for [00:29:00] people and integrate holistic thing or other parts of caring that maybe aren't classically like in med school and psychiatry and work with them on this and I think marijuana like this comes up a lot of like, yeah.

I have a lot of patients, I think, who use marijuana and how do we talk about it and how do we, how do we clinically integrate that rather than being like, don't do that or don't whatever, like, I don't think that's evidence based or blah, blah, blah, blah, blah, um, is a complicated question because I think, I think we can probably both agree like modern medicine.

Doesn't treat everyone fairly or well and doesn't always have the answers and we're sometimes not taught how to gracefully not have the answers as doctors. 

Preston: I think we're cagey when we don't know the answers, but it I think depends on how the patient fits in culturally with their relationship with marijuana.

I think. There are the [00:30:00] patients that I see who have almost like an anti pharmacy approach, and they're like, I don't want to use a drug to treat my depression. So instead, I yes, it's not natural. It's something in the lab. So instead, I'll smoke weed six times a day. And I think so, I haven't come across someone who has like a really strong cultural belief around marijuana.

I think most of the time when I encounter it, it's someone who I think has a lot of hesitancy about. Yep. Using psychopharmacology, but also has a lot of substance use from like sources that they feel more comfortable with. So, for me, it's kind of a conversation of like, why, why is this substance? Okay.

Versus this other one. 

Margaret: Yeah. Yeah, I was gonna say, I think that that really moves us until the final part of this episode today, which we'll do after the break, which is kind of like clinical pearls and how you and I talk to our patients [00:31:00] about it and just think 1 thing we can. Maybe both say is that there's not like a clear cut answer in the same way There's not a clear reaction like we were talking about with the neuroscience of it in terms of the response To the the to cannabinoids on or whatever to marijuana for people And so I do think you have to take a very personalized approach for many reasons for each patient that we see So after the break you will talk about that

Preston: If I'm your patient Margaret and I kind of Bring up to you that I'm smoking or wanna or something. Let's say I tell you deal with it helps with my anxiety How do you how do you kind of approach that conversation? 

Margaret: Yeah, I think I think I would approach it one. I will approach it like Whenever you do an intake with a psychiatrist, they ask you about substance as part of the kind of standard things we ask about marijuana's in [00:32:00] that, um, I think the first thing I try and do when I'm first going to know a patient is, is kind of suss out how much do they want to talk about it?

Um, and how much do they think it's If that's something that they feel like is fine, or if it's something that they don't think is impacting them, how do they use it? So some of it is pattern abuse. Um, some of it is also age and diagnosis that, uh, for the person I'm seeing. So, uh, there's a paper that I had been taught that was in Nature, I think, in 2018, that we'll have in the show notes, that was about, like, whether there's a difference in terms of, Marijuana or like, and like endocannabinoid signaling and having like environmental things change out like use of cannabis during adolescence, um, and that there may be something about sort of modulation of emotional reactivity, um, that.

Involves the endocannabinoid system. And so if you use marijuana during that time, like, will emotional reactivity and anxiety and stuff be impacted long term? Because it's a special [00:33:00] second period of plasticity. So let's say 

Preston: I'm 25. I'm open about it. I use it every day. 

Margaret: Are we going to do the role play thing where we 

Preston: can?

We can if you want to. 

Margaret: Yeah, I think I'm just just 

Preston: curious that the kind of questions are like the approach you take. Yeah, something like that. 

Margaret: So I think let's pretend what should we pretend you have like a like generalized anxiety disorder. 

Preston: Yeah, I'm in graduate school. I'm worrying about everything and I have fixated that every time I smoke weed right before I go to class, I feel a little bit better.

Margaret: So I'd say I might ask something like. You're, you know, you're mentioning this to me. I just asked you about substance. How do you feel about your relationship to marijuana? Is it where you want it to be? Does it help you? Does it sometimes not help you as much? Where do you, what do you feel like that relationship is like?

And is it how you'd want it to be? 

Preston: Yeah, exactly. And so I, I think I, I go to for that approach to like, what does the substance do for you? I [00:34:00] think just in general, if someone has a behavior, I try to figure out what it does for them. You can also 

Margaret: figure out where are they in terms of like, do they think it's a problem?

I mean, if we took it out of substance, which is so can be so like loaded with different meanings. If it was like someone was like, I like exercise, like I might be happy with like, Going to the gym twice a week or do it going on a run a couple times a week. And that's awesome. And if someone comes at me and is like, you actually should be doing all of these things.

Like, I'd be like, whoa, whoa, whoa. I didn't even think this was a problem. So finding out where they are in terms of how they feel about their use and if they think it's something that's not working for them. 

Preston: Yeah. And I think one thing that's interesting to me about marijuana is I think people have a really hard time finding, like coming to their own conclusion about the negative effects it has.

So. I think it's actually been easier for me with things like alcohol or opiates to [00:35:00] the, the patient will already have insight into like their substance and how it may be negatively affecting them because they're like, yeah, like when I drink a lot and I end up in the hospital or I'm vomiting on myself, like this is really bad.

Or if I get too high and have this respiratory depression or I know when I'm withdrawing how bad it is. But I think Marijuana, it's so delayed. When people have like rebound anxiety 18 hours afterwards, they may not be associating that with the negative effects of weed. And it's tricky because a lot of the effects of weed are alleviating negative symptoms in the moment rather than just like the introduction of euphoria.

And 

Margaret: so 

Preston: I find like when I ask people what it does for them, they almost have no idea that has negative effects. I think it only has positive effects. Because and it's easier for me to explain away the negative effects, 

Margaret: but I think something here is also the, you know, the lack of research that we know a lot about what alcohol does systematically and brain wise.

And obviously alcohol is a dangerous withdrawal, [00:36:00] which is worse for. So the classic question is, which is worse for someone, someone alcohol or marijuana. 

Preston: Yeah. I don't know. I think it's it's real understood that alcohol. 

Margaret: Yeah. Alcohol is a toxin to destroy your body systems. Yeah. 

Preston: Yeah. 

Margaret: Oh, but it's legal. And like, this is, 

Preston: I 

Margaret: think this is also the thing, right?

Like every visit we have, there's an ethic of time. So like, how much do we focus on marijuana? And is that truly like from a harm reduction and from the flourishing standpoint where we should be so focused with people is like marijuana bad, but if someone's like, if someone says like, I use marijuana a few times a week socially, or I use alcohol a few times a week socially, would you treat that the same?

Because I think I would. I'd be like, yeah, okay. 

Preston: Yeah, I'd be like, cool. Like, what can I help you with? You can move on from there. But then there are times where just like with alcohol, marijuana can be the the central problem for people. And that, and those have kind of like some effects that [00:37:00] I think are unsung.

Margaret: Yeah. 

Preston: Or I think like at least underrepresented. 

Margaret: How, if I was your patient and I said, um, like, you know, I don't actually know like, I like using it, but like I feel confused on like what it's doing. Can you tell me like, what is it actually doing? Let's say I have ADHD and anxiety or something like that.

ADHD mainly. And I want to know what are the risks? I actually don't know what I'm coming to you as my doctor to ask. Like, 

Preston: yeah, that's the second place I go after I kind of figure out what it does for them. Then I can just offer information. As try to do as unbiased as I can, but obviously, I have my own biases when I'm discussing this.

I'll say that, like, it's reasonable to want to make your anxiety go away because who wants to experience anxious feelings. And I think we kind of like everyone in the room agrees with that. You know, we don't want to be anxious. And so [00:38:00] it is true that, like, in the moment, marijuana can take away your anxiety and that's probably something you've experienced.

So we kind of agree on another fact. And then kind of what I'll bring up is that. Yeah. Using marijuana can be like quenching thirst with poison or like quenching thirst with vodka, essentially, and I think for a lot of my patients that analogy has stuck well because they do realize like, yeah, it does feel good in the moment.

But then it can make you more anxious afterwards. So you can be kind of like stuck on this cycle. And I just try it. That's, that's about like, as far as the mechanism is pretty much as in depth as I'll go into it. And I'll just kind of be like, Hey, it helps now, but you pay interest later. And then I usually try to make this like a multi visit conversation, 

Margaret: but 

Preston: just plant the seed initially and then kind of let them retake stock of how this may be affecting their behavior.

Margaret: Yeah, I think the most natural transition is often like. For me, it's [00:39:00] been like, oh, it's visit like 5 or 6 and we're talking about, like, the anxiety is better for the most part on this dose of like necessary, but I'm still struggling to sleep. And then we talk about that as do you ever use anything to help you sleep?

And they say like marijuana or alcohol. It happens. Alcohol too. Um, and then thinking about, you know, 1, is this something you feel like you're dependent on? And now you don't the way you're relating to it is how you would not want it to be. Um, And asking what they like about it. So, like, the youth experience, like, it's like, oh, I do this with my roommates and it's relaxing.

And we, like, laugh and talk about something. It's how we unwind at the end of the day, um, and and helping figure out, like, replacement things to do, which is why we started with the question I asked you about, like, how do you unwind? And this is a conversation I have with alcohol a lot, too, is like, how can we unwind?

There'll be some discomfort regardless, but also can we replace parts that are positive for you, but aren't the substance itself. 

Preston: That's always been the hardest thing for me is like bridging [00:40:00] to the non substance coping skills. 

Margaret: Well, I think the often exploring with people what they do when they don't have access to it.

So like I'll ask them like when you're on vacation, if you didn't bring it or like the times you don't use it or when you used to not, like how did you help yourself go to sleep? I feel like this comes up particularly with ADHD because of. Some, some of the inherent things in the ADHD diagnosis and the kind of like the liability for rumination and sort of energy dysregulation, but also because of stimulants, right?

Stimulants can last longer than we would clinically like them to. And so people will say using marijuana to kind of slow down or help the kind of crash of feelings when the stimulant wears off. And so that's been one where I noticed it a lot, and it definitely can have cognitive impacts that can make.

Life harder for people with ADHD in terms of like attentional regulation. And so I feel like with that, it's kind of like figuring out what is like a routine or a night, especially if it's for sleep or anxiety like daily. It's usually I found [00:41:00] it's often at night. There's exceptions. There are some people who are using it often like panic attacks, things like that.

But figuring out like, you know, what sounds like, like kind of having a trial and error experimental thing, not saying like, let's just T total get rid of it, but what if we tried making like a fun mocktail that night? This is for alcohol, but I've done this for weed to and like, you call this person or you go on a walk because you like seeing the sunset.

Like, it sounds kind of cheesy when I'm saying it, but that's why we experiment until we find some other options that make it feel less like it has to be the marijuana. I 

Preston: mean, I think everything, like, sounds cheesy when you, when you present it in the moment in the therapy session, and then it works later.

And then it works, 

Margaret: yeah. 

Preston: So it's like, deep inhale, slow exhale, and you're like, really, you're telling me how to breathe? 

Margaret: Shut up, man, I hate that I'm saying it too. And then you do, and you're like, okay, I 

Preston: do feel better now that I'm breathing. 

Margaret: I literally this week have said to a patient, like, I hate that I'm saying this too.

I'm sorry. Unfortunately, it works. [00:42:00] 

Preston: Yeah. Like we haven't come up with something better. I'm sorry about that. Yeah. So I think we've had this middle ground where it's like. If it's not having a frank negative effect on someone's life, how much do we, do we go into this conflict or this kind of conversation with them?

But then now there's this 3rd kind of category where so, so 1st category being like the occasional user, maybe like once a week. Along with alcohol and then we have almost daily use, but with this question of like, how it affects them and their dependence on it. And now we have this kind of 3rd category.

We have either problematic use or pretty deleterious effects from it. And I think a lot of people aren't even aware of these things. So there is a couple different syndromes. Or the things that can happen with cannabis use. The first one I want to talk about is, um, cannabinoid, uh, hyper emesis syndrome 

Margaret: or 

Preston: CHS.

This is something you've heard of before. 

Margaret: It sure [00:43:00] is. I worked in eating disorders for the, yeah. Yeah. 

Preston: Have you, have you ever met a patient that has that? 

Margaret: Not in like a residential, but it was setting, but I think an outpatient, I, maybe not full syndrome, but definitely like it started out helping their appetite and helping them deal with their anxiety.

And then it slowly changed into something that was no longer helping was actively. Harming and causing nausea and then but how do I come back and I'm anxious and that also makes me nauseous and I have a media phobia like, 

Preston: right? It's like, it's like you become indebted to it and it's another. It's another nasty situation where it's the only thing that alleviates the nausea, but then the nausea gets worse as you come down from it.

So we don't have any 

Margaret: idea why that happened. I just leave into you. 

Preston: Yeah. Yeah. So, so we don't understand like. Okay. Totally the mechanism as, okay. What we do know is that our cerebellum, which has a lot of implications in our sense of nausea, has a lot of CB one [00:44:00] receptors on it. We also know that there's this, um, vanilla endocannabinoid or vanilla endocannabinoid receptor that's fun, that is in the area postma.

Yeah, which is, that's our, if you're not aware is the air pressure was like our vomiting center. So it also has a lot of serotonin receptors, also has a lot of histamine receptors. So that's kind of why you can take something like Zofran, which blocks those serotonin receptors in your post treatment, which can help with nausea or like remeron blocks them as well.

But then also something like meclizine or Benadryl can help with nausea because it blocks those receptors in your post treatment as well. So in this whole area. There are also these like cannabinoid receptors. So the thought is activating the receptors. May decrease nausea in the short term, but then as we're stimulating them, we kind of up regulate receptors in the back and we make it hypersensitive.

So then as we come down and draw from it, we become more sensitive to this feeling of nausea. And so with chronic almost daily use, that [00:45:00] feeling of nausea can get worse and worse and worse. 

Margaret: Got it. So the hyper emesis is kind of like, okay. When you become dependent on it for calming you that when it's not there, you're going to notice more nausea and 

Preston: therefore more, 

Margaret: you know, vomiting 

Preston: the, the New York times daily did a good episode on marijuana earlier this week and 

Margaret: I saw that, but it's paid.

Preston: Oh, I pay for it. 

Margaret: Um, 

Preston: yeah. So my, my girl, Sabrina, I think she was discussing actually a patient who had hyperemesis syndrome and she went on this entire almost like. Wild goose chase work up with G. I. And all these things trying to pin down the source of her vomiting and the whole time she'd been using marijuana as a as a way of alleviating pain from her migraines.

And she was like, the only thing that made my knowledge better was smoking weed. So I just kept smoking more weed and then it get better. But then when she comes down from it and got worse, it was the point where she was just like curling in the fetal position, just [00:46:00] vomiting on the floor. They, they call it, um, scrambling is, is a term that can be used to describe it, which is where this sensation of vomiting is so painful that you're screaming and vomiting at the same time.

And 

Margaret: why, why is there like the munchies associated with marijuana? 

Preston: Um, I don't know, to be honest. Okay, fair enough. . So I do know that in the midbrain there are some CB receptors that relate to orexin. Okay. Hypocretin. And that has a role in our sleep regulation. So the sleep part makes sense to me at least, that there's some connection there.

Yeah. But I, as far as like stuff I've come across, I'm not sure about the, the appetite simulation. I think a lot of that is mediated by, by CB. D. 

Margaret: Yeah, 

Preston: there's something with like 

Margaret: leptin in some paper, but I couldn't, I couldn't know pine about it intelligently. So I won't, but yeah, but there's this mixed effect again, like multiple brain regions with like, just being like, what if we just [00:47:00] turned a bunch of random switches on and said, did that work 

Preston: exactly?

And so, so that's kind of how we came to this conclusion with the nausea and this vanilla endocannabinoid receptor, because a lot of it has implications in noise receptors, which are pain receptors and how we respond to heat. Okay. 

Margaret: So, 

Preston: weirdly enough, one, a common thing or a theme among people with CHS is this feeling of relief after taking a hot shower or a hot bath.

Margaret: Huh. 

Preston: So, there's some thought that maybe activating, using heat to activate these receptors can alleviate some of that discomfort. That's a, that's about as far as we understand. That makes sense. Then once you kind of move past CHS, there's some other like more. Significant adverse effects that we deal with personal perspective, like psychosis.

Yeah, right. 

Margaret: I think before sorry, before we go there, I think one of the common things that sort of like said pop culturally about marijuana is that [00:48:00] it's it's not a I think we cover this at the beginning of the episode in some ways, because we talk about how it does have a relationship to dopamine and that dopamine systems.

It's not just like addiction or substance dependent is not can come about in many different ways. In terms of impacting different pathways, but I think one of the things people say is like marijuana isn't addictive. And I think people say that somewhat less now. I think at least clinically, we kind of know, like, there can be the behavioral dependence as well as some of this dopamine modulation that may 

Preston: put 

Margaret: you on the spectrum of dependence on it.

Right. But what do you think about this idea that like marijuana is different than alcohol or opioids or other things? Because there's it's not like a direct dopamine stimulator. 

Preston: I think there was a great advertising campaign on cannabis is a half to say that it wasn't addictive. Yeah, they were really good at creating this perception that it's not [00:49:00] have it for me.

And I think there were some things going for that. One of those is that there's no life threatening withdrawal with it. And another thing is that just really Yeah. Just you can't die of an overdose on it either. So there's kind of thought that like, oh, it's it's safe. And then and people can replace it with other things.

So maybe that substance itself isn't addictive. And it does have this like indirect function. But when you think about the things that reinforce behavior, podcast. Or like almost like operate conditioning. I'm talking totally outside of like our pleasure reward system, which it does affect if I, if I'm punished for not doing something, I'm just more likely to do that thing.

Let's say I go outside and it's raining every day and I'm and I'm like, Oh, if I don't bring my umbrella, it's raining or if I don't, if I don't bring my umbrella, I'm just going to get wet. So I turn on my umbrella and I go outside while it's raining. So if [00:50:00] I like live in a place where it rains all the time, then I'm just going to kind of be rewarded continuously for like using my umbrella and then I can become like Almost like dependent on that in that scenario.

So, so I'm always like in the scenario where I want to use my umbrella. This is a bad analogy. Honestly, 

Margaret: I'm fine, but 

Preston: loosely. No, I'm like, I'm not following myself anymore. I think the point is that, like, if I stop doing something, I get punished continuously for it. So I'm just going to start using that behavior again without really realizing that.

All of the operant conditioning is happening almost like inversely, it's not, it's not with the behavior, but it's with the absence of the behavior, 

Margaret: I think of an example is like if I have a patient who's like every time I do something that makes me feel anxious, like if they have social anxiety, I have to use marijuana each time before I like hang out with my friends or something like it, it limits them.

I think this is similar to your metaphor. It limits them to the extent that it's like even outside of the [00:51:00] substance. Like if they were like, okay. I don't, I don't even know, but like the thing itself that becomes like, this is the only way you can do this becomes eventually hits the point where it contracts their life and that can be, that's again outside of this sort of like explicit substance pathway and more like you're saying, like a behavioral addiction, which I think we talk a lot about in different therapy modalities.

There can be behavioral addictions without any substance and therefore it's like that plus that, like behavioral addiction plus whatever marijuana as a substance is doing. 

Preston: Yeah, and I think it's just like our relationship with substances that relieve unpleasant feelings is different than substances that introduce Euphoric or pleasant feelings.

It's easier to see Marijuana as like the good guy when it is taking away anxiety Even though that anxiety comes back with interest later. Yeah It's hard to make that connection. And so I think that's kind of what I was [00:52:00] getting at that. Like, you can become like, operantly conditioned in that way. So I guess for my stupid umbrella analogy, it's like, every time you use an umbrella, it rains harder the next day.

So, really, what you have to do is you have to figure out, like, Oh, maybe if I just tolerate the rain on my own. Then eventually the sun will shine, but every time I bring my umbrella outside, it's just going to storm even harder. So then, so then now the next thing you know, you're just like stuck hiding under your umbrella and you're like, the umbrella is the only thing that helps.

And he was like, well, really, you have to let the, let the rain hit your skin. Like that, uh, Natasha, Betty, feel the 

Margaret: rain on your skin. No one else can feel it for you. 

Preston: Hillary Duff. 

Margaret: If you want to come on our podcast, we're glad to have you. I 

Preston: don't know much about Hillary Duff. 

Margaret: You watch the Lizzie McGuire movie.

Preston: Is that her 

Margaret: girl? 

Preston: There was a blonde woman in Paris. That's all I need are in Rome. She was in Rome. You're 

Margaret: thinking of Emily in Paris now, Rome, another, another [00:53:00] cultural spot we have to work on. And I'll work on learning what different flying metaphors mean. Um, do you have any final thoughts on. For people listening whether they are in health care and talk to people about marijuana use whether they are just people in health care.

I wanted 

Preston: to talk about psychosis. Oh, I'm sorry directing the conversation. 

Margaret: Well, we're reaching Go continue. So psychosis you say? 

Preston: Yes, so we know that psychosis is mediated by the lobesal limbic pathway. Or the mesocortical limbic pathway, which is basically all these dopamine neurons that sit in your midbrain and extend.

I 

Margaret: remember that diagram from med school. Yeah. Yes, yeah, yeah, I remember 

Preston: it. So if you trigger those. By inhibiting GABA on the CB1 receptors, you can induce a psychosis actually pretty significantly. And so I think what a lot of people don't realize is that as psychosis lives on a spectrum, it's [00:54:00] not just hearing voices, but as much as like making these absurd connections between stuff in the real world.

And so I know we talked earlier about the salience network and misidentifying So when people become paranoid while they're smoking weed 

Margaret: right 

Preston: that can be seen as anxiety But in a lot of ways that paranoia is actually a very mild form of psychosis 

Margaret: I like to think of psychosis as like what you're saying like the relationship of external and internal reality and like quote unquote reality But like what how do those align and like you're saying paranoia where it's like a different meaning for the same external stimuli 

Preston: It's really a misappraisal of the importance of the stimuli in my environment and there's a couple of things that like people should take away when they are thinking about like paranoia, psychosis, and we didn't.

And one of those is that [00:55:00] that should be assigned to you. Like, if you experience paranoia that your brain is predisposed or more vulnerable to psychosis, 

Margaret: at least in the setting. Yeah. 

Preston: Yeah, at least in general, 

Margaret: you think in general? 

Preston: Yeah. Um, I guess, I guess I'll hold off on saying so. I don't know. I really 

Margaret: don't.

My understanding is that we like the correlation is really, really like that. It's there. It's not nothing like that. It's not like there's if there's psychosis, it's no relationship, but it's 

Preston: I think what I'm drawing from is that if you can, if you generate a substance to do psychotic disorder from any substance, your risk of a primary thought disorder, later life is increased period.

Gotcha. 

Margaret: Okay. 

Preston: So that's so from that fact. , I'm kind of making the inference that like it's in layman's terms, it's showing like your brain is [00:56:00] predisposed to kind of go into this syndrome. 

Margaret: Mm-hmm . But see that makes me think of like for some people who are like respond to SSRIs and like there are some people who take SSRIs and they will never have like a manic episode from them, but there are some people who will.

But that doesn't necessarily mean they have like a bipolar disorder, although they may have an increased predisposition on a population level. But like, I just say that in terms of like, if someone's listening to this and they're like, Oh, I experienced that. Do I need to be worried that I'm going to develop psychosis without marijuana?

I don't want them to take that away necessarily. 

Preston: Yeah. And so, so they, they may not need to be worried about that particularly, but it's important for them to think about their long term risk with marijuana use. 

Margaret: With marijuana. Yes. Yeah. 

Preston: Or, or any kind of, um, like, Dopamine modulating psychoactive substance.

Margaret: So I agree. 

Preston: I think you and I are familiar with this subpopulation of I almost like call them. It's it's like a substance induced disorder or like it's so [00:57:00] effective, but almost like patients that have been chronically using things like methamphetamine or cocaine for decades. And then they kind of just never come out of their psychosis.

And now they're diagnosed with schizophrenia or schizoaffective disorder, though it's really been precipitated later in life. And these are people that you kind of go through their chart. And over the last 15 years, it's been substance to do psychotic or substance to do psychotic disorder. And then it kind of eventually no substance involved.

I think that's kind of the person I'm talking to whose highlight like who has. Who has like that kind of reaction to a drug like that, those, those are the risks that kind of can await from chronic use like this. The other thing to take into account is this relationship between how we metabolize dopamine and our risk of like later developing schizophrenia.

So, we do know that there's, um, dopamine is metabolized or it's anabolically [00:58:00] created from tyrosine. We hydroxylase we, um, break it down through these catecholamine pathways. It turns out that are like garbage disposal for dopamine is at different rates for different people and as well as the way we synthesize dopamine.

And so, interestingly, people that have certain genes in com T or catecholamine methyltransferase. And when you methylate something, just think about turning it off. So basically the janitor for dopamine. That gene is associated with different risks for both actually schizophrenia and Parkinson's and we target.

We inhibit that enzyme specifically to help people with Parkinson's. So genetically, we know these enzymes predispose people at risk for developing kind of these syndromes with psychosis, but then also. There's kind of 3 different groups of people that emerge with their different type of use and and psychosis just in general.

This is kind of like talking [00:59:00] broadly. So there's this 1st group who will develop a schizoaffective or schizophrenia regardless. They are unfortunately, like, going to precipitate psychosis. They have a strong 

Margaret: genetic and environmental combination at that point, minus 

Preston: substance, 

Margaret: that psychosis 

Preston: occurs. Yeah.

And when we think about, like, that genetic and environmental component. If, if you had two identical twins and one of them develops schizophrenia, do you, this is a quiz question. Do you know what the, the likelihood that the, the other identical twin will 

Margaret: at 60%? 

Preston: Yeah. Yeah. It's the range of studies between, between, between like 50 and 80.

Yeah, exactly. So there's this huge environmental component, but this, this, unfortunately, because of this circumstance, they'll develop it. Then there's this other group where, You could do cocaine. You would have coke for breakfast every day for the rest of your life, but you would not develop schizophrenia from it.

You right. You'd perish from some other means, but the group [01:00:00] that like we care about the most in this context and that we're kind of speaking to is the group that they would not develop. A schizophrenic or a psychotic disorder, but with their substance use can kind of be in a group that could go either way.

And we find that especially people 16 to 20 who smoke daily are at the largest risk of conversion later in life from this kind of like middle genetically predisposed group. 

Margaret: I think there's and there's still that active question that I think goes along with this of. Is it people who are drawn and have a stronger response?

Like, let's say a bunch of kids try like once teenagers try marijuana. Is it that the marijuana itself can increase that risk? Or is it that the brain of someone who may develop psychosis or has the predilection towards it will respond differently in the endocannabinoid system to me? And I don't I don't think we know that part, but similar, [01:01:00] right?

Like of correct this. Relationship is different for some people than others. 

Preston: We, we know that there is a correlation between them. And so it's, it's unclear to your point is, is the use of marijuana just like a red hair or is it just like a sign that they're going to develop psychosis? Like, is this, is it a symptom that we should look out for?

Or is it a contributing cause? And I think there's a similar relationship actually with smoking and schizophrenia. Right? Okay. 

Margaret: Well, I think that what we talked about earlier about the types of it too, right? Like, now that means something really different. Like, if you experience, like, it's so hard to know, as we said, the, like, type and dose that if someone experiences psychosis from.

Marijuana that their friend grew and didn't synthetically change this and they experienced psychosis from it versus someone who had has like a hyper high THC content is that risk the same? I think we don't we don't [01:02:00] know because that's a hard. That would be an expensive study to do. And we need a big population of folks to do that.

Um, But just that there may be different differentials there too, within like what type and what other things are going on. And also that like this, again, this adolescent plasticity period, I think that's also not a known thing. Like, if you do this when you're 13 and you have these genetic background versus when you're 18, would that be a difference in terms of correlating with the psychosis emergence?

Preston: Kind of exists as a big. Black box. Um, but I think the takeaway is that regardless of whether it's a sign of like downstream independent pathology, or if it's a central role in driving it, chronic use of marijuana is associated with these syndromes and should be something avoided, especially in adolescence.

And then it's kind of easier for us as medical professionals to take the step back [01:03:00] and say, like, okay, now, if someone is, like, past this point of brain development in the mid twenties, how much do we want to weigh the risk? And that's where it becomes a lot more bespoke to the patient. So, yeah, I think, Thank you for letting me get my 2 cents out.

4 cents. I learned 

Margaret: something. I loved it. 

Preston: Psychosis and the metabolism of dopamine. I think those are kind of everything that I had, or at least kind of wanted to cover right now. So, I think the big takeaways from from anyone who's kind of listening to this podcast is that. Cannabis affects everyone differently.

Some people can use it recreationally and really not see negative effects from it. And it's not always the top priority for someone who has a lot of things going on in their life. And then for some people, they can have really drastic medical consequences and psychiatric consequences from it. And it affects people so heterogeneously.[01:04:00] 

And that a lot of our understanding of it is really stifled by these, like, legal cages that have been, like, placed around looking at these substances, and I think that's also, like, why it's been given this almost anti hero type reputation in the medical community. 

Margaret: Yes. Yeah. I think the last thing I'll say is just like for anyone listening,

take in this information, see how it applies to you. Talk to your clinician. I think whenever we're in the world of like substance use or dependence on something, so much shame automatically comes along for the ride. And what I would say is like. There are ways to change our relationships with these substances and we don't do it alone.

We do it with people and that I don't think either of us would ever espouse using like shame as the way you like punish yourself or something like this. So [01:05:00] we want you to have a psychiatrist and as I think as podcasters, we want you to have a life that feels more and more like your own and meaningful.

And so, if this is an issue for you, you know, talk to people about it, see how you can change to talk to your clinicians about it and it can. It can get better because I think sometimes we take this away and are like, it's bad. And then people are like, but this is the thing that's helping me get through my life.

Preston: Yeah, and it's, it's easier for us with our clipboards and our emrs to just rip out someone's coping only podcast headphones. This 

Margaret: is our behavioral. 

Preston: Yeah, exactly. My the external attention I get from people. I'm on the same page. Like, I just want. I want patients to have a congruence between the life they want and the life they're living, right?

And if anything, like, I, I can offer information as to like, why there may be some things that are, or like shed light on why there's some reasons why that's not [01:06:00] happening, but ultimately, like. It's always their life and their decision at the day. And I try to be very like aware of that. Um, and then really like psychiatrists more so than other doctors, but just doctors in general are just consultants like you consult you come in like you're the CEO of your life.

You consult us. And we come in, we say like, this is some places where you can cut costs and here's what we think you should do. But then you decide and 

Margaret: we'll be with you there along the way. 

Preston: Yeah, yeah, exactly. 

Margaret: Cool. Well, thank you so much for listening to me. 

Preston: You're welcome. I think so. So now, now that I'm done talking to you and I have to go play with my cats, I'm going to get through the ending credits part really fast and naturally and candidly, like a, like a normal human being.[01:07:00] 

Not at all like a robot who isn't afraid. It feels like they're going to 

Margaret: throw up. 

Preston: So, like Margaret said, thank you so much for listening. Um, let us know how the show was. If you are enjoying us kind of like having these half didactic, half meandering discussions about substances, we can go into other ones.

Uh, if you learned something that you thought was beneficial or if you think it's a little too charged and you don't want to, to keep talking about you got too 

Margaret: nerdy about it and you're like. Y'all need to get out. 

Preston: Yeah, you like you decide you're the barometer for us. So you tell us where the pressure is at.

If our worth 

Margaret: depends on you. 

Preston: My worth depends on I can only survive off of positive feedback. So if you want to do that, come and chat with us on our IGN or TikTok at human content pods, or you can contact the team directly over at how to be patient pod. com. Thank you for all the listeners that left positive feedback and all the listeners that left negative feedback.

I reluctantly thank you. 

Margaret: You [01:08:00] give me something to process in my own individual therapy. Thank you. 

Preston: I will only remember you forever. If you want to watch the videos on YouTube, you can find them on my YouTube at It's Presro. Thanks for listening. I'm Preston Roche. 

Margaret: And I'm Margaret Duncan. 

Preston: You can find me at It's Presrow on TikTok.

And you can find Margaret 

Margaret: at BadArtEveryDay. 

Preston: Yeah, we should start calling you BadArt. Our executive producers, BadArt, yeah. 

Margaret: That's Dr. BadArt to you. 

Preston: Dr. Professor BadArt. 

Margaret: Dr. Queen, yeah. 

Preston: Our executive producers are me, Preston Roche, Margaret Duncan, Will Flannery, Kristen Flannery, Aaron Corny, Rob Goldman, and Shanti Brooke.

Our editor and engineer is Tracy Barnett. Our music is by Omer Benz V. Check out our show notes and see the references and resources we used to discuss the episode. If we got any factoids wrong or things in there, we'll make sure to highlight them. And to learn more about our program disclaimer and ethics policy submission, [01:09:00] verification, licensing terms, and our HIPAA release terms, go to our website, how to be patient pod.

com or reach out to us at how to be patient at human dash content. com with any questions or concerns. How to be patient is a human content production.

Thank you for watching. If you want to see more of us, or if you want to see, this is Lilac. She's my cat. She's going to be waving her hand at one of the floating boxes, which will lead to more episodes. Lilac, point to the other episodes. Lilac doesn't know what the internet is, but I swear they're there.

They, they probably exist for real. But in the meantime, I'm just going to pet Lilac and then I'm A dance in the [01:10:00] background.