Welcome back to the podcast. I am joined today with three guests. We have Liam Browning, returning Daniel Liu and Daniel Quivos. We are going to be talking about cannabis, depression, anxiety, cognitive function. I'm going to be letting Liam ask some questions and jump in a little bit more than usual today. We have an amazing handout on this. If anything that we say is remotely interesting to you, currently it's at 51 pages. We are going to try to not get into the weeds too much, but present up to date what we know about this. So let's begin. Liam, what's the first question? Yeah, the first question. I just wanted to first start off by saying, like, just as we talked about in last episode, cannabis is being used in unprecedented breed. So we really wanted to dive into this discussion from the perspective of trying to understand and where patients are coming from with this as well, going in between a lot of the different perspectives out there because there's the perspective that's overly negative and then there's overly positive perspective. And before we start, I just wanted to share what a lot of patients are seeing from dispensaries. I thought it'd be interesting to pull up a product from the first dispenser that I found. I just Googled dispensary near me and then clicked on the first thing. And they're marketing the effects as energetic, happy, creative, focused, inspired for these gummies. And then I pulled up a flower that's 28% THC. So again, this is far higher than we've seen historically, whereas more so like 5% and they're marketing this product as something that helps make you calm, happy, relaxed, and energetic. And then it also gives us breakdown of all these different terpenes that they say are associated with different mood profiles and that you have to find your right fit based on the terpened profile. So I just want to open that, open the discussion and saying like, a lot of patients are turning to these substances for relief from anxiety, relief from depression and to improve their mood.

So, you know, with that being said, I just wanted to give providers and anyone who's interested a look at what patients are seeing then also for us to dive into what the evidence is actually saying so far. So Danielle, did you wanna open us up with with what we found about cannabis and depression?

Yeah, so I think to start with, there is good evidence that depression and cannabis use, this ordering cannabis use are associated with each other. It's been seen time and time again in pretty sizable studies, one big cross-sectional study that collected information from 2005 to 2016,

when over 16,000 adults found that people with moderate to severe depression had almost two times the odds of using cannabis in the past month. And over three times the odds of using cannabis daily are almost daily. And it's interesting because later in this as the study went on, the association that was seen between cannabis use and depression actually got stronger and marijuana was legalized during this time and maybe people started perceiving that cannabis can be helpful for depression, like just like the dispensary that you were just talking about demonstrates what patients are seeing. So, more patients started turning to cannabis when they started feeling depressed and the association was stronger over time. Also see there's a new meta-analysis published this February on 22 studies that showed that compared to people who didn't use cannabis, people who use cannabis are 1.29 times more likely to have self-reported or clinical depression. And then there's a meta-analysis done in 2021 of epidemiological studies in the United States and that show that people who are dependent on cannabis or who abuse cannabis are anywhere from 2.3 to 4.8 three times more likely to have a depressive disorder than people who don't have this dependence. It does raise the question and is this just an association? It doesn't take into these studies, don't take into account a lot of other factors, like what came first or people who are depressed, just have the tendency to use more cannabis or is it like the cannabis that's causing the depression? And like Liam was saying a lot of people have either overly negative view or an overly positive view, neither of which are really fully supported by the literature. Yeah, so again, with these studies, they're cross-sectional nature, they're looking at one time point people who are using cannabis right now and defining them based on if they have used disorder comparing that to people without use disorder. And they're essentially seeing that they have a three to five-fold increased risk for having depression. And then some of the other studies are saying looking at depression, patients comparing those with people without depression and then saying yeah they're far more like likely to use cannabis by about two to threefold. But again, as Daniel was mentioning, that these studies are cross-sectional, so it doesn't necessarily tell us what happened first as someone using cannabis and then becoming depressed or vice versa. So that's why we got to look at other studies that look at some of the Bradford Hill Craterium, as we discussed where the Bradford Hill criteria is good for cross-sectional and epidemiological research where it's looking at the dose response relationship between a risk factor and an outcome and then also looking at temporality does cause perceived effect. Strength of association are we looking at a very strong association between the two outcomes and then also biological gradient and so on. So Danielle, did you want to break down some of the studies that did look at some of these Bradford Hill criteria? Yeah, there are a few, just a few studies that are really highlighted these temporality and dose response relationship more than the other studies, and that helps

us to establish like causality a little bit more. If we can establish this temporality where cannabis came first and then depression that helps to contribute to the argument that perhaps cannabis contributes to depression or with dose response. cannabis is associated with the depression that also contributes to the argument that perhaps there is this causality. So thinking about the studies through the lens of Bradford, Hill, there was one meta-analysis done in 2014 that looked at 14 longitudinal studies that follow people over time. And this study showed modest dose response relationship between cannabis and depression. And like I said, dose response is one of those Bradford Hill criteria that we look at. So people who were heavier marijuana users were at an increased risk of developing depression. And from 1.17 was the odds ratio risk for people who were later marijuana users and those who are heavier marijuana users at an odds risk ratio of 1.62 times increased risk of developing depression. And then another study that we wanted to highlight is a twin study that's commonly cited. And the special thing about twin studies is that they can control for confounding factors that in ways that like a lot of other studies can't, you know, the twins are raised by the same parents, often raised in similar environments and similar genetic makeup were the same if they're monosigatic twins. And there's a twin study that was done on over 6,000 twins. And this study demonstrated that the twins who used cannabis more frequently had a significantly higher incidence of major depressive disorder. Even after adjusting for covariates, this odds ratio was still significant. So it does show the dose response relationship and it's comparing twins. And that was even with, when looking at the monozyigotic twins only, so those with the same genetic makeup,

this significance was still seen in an increased incidence of major depressive disorder for people who were using cannabis more frequently. There's also another study that was done in Minnesota that looked at more than 3,000 adolescents

and again it twin study, similar environments, similar genetic makeup, and this study showed even though it didn't show changes in the incidence of depression, it showed that there were significant changes in outcomes of educational achievement. So people would have, who were used cannabis more or who used cannabis would have decreased GPA, decreased motivation for academic achievement and increased like problem behaviors in their academics and increased disciplinary issues as well. Yeah, again, and these twin studies, they're looking at twins, monosagetic twins, one twin who smoked more versus the twin who smoked less or used weed less. And essentially they found that the twin who used more, they had a lower GPA, lower academic

achievement, lower educational outcomes, but no differences in psychiatric outcomes later in life. So that tells us or at least suggests that if someone is using cannabis at a young age, they're far more likely to develop some of the like like the academic outcomes as opposed to depressed outcomes potentially. But then again, as Danielle just mentioned with the meta-analysis from 2014 that looked at these 14 longitudinal studies that the more cannabis that's used during adolescence, the more likely that they were able to find that someone was depressed. So you're seeing kind of both sides of the same coin here, where increased use can be associated with depression, but if you control for some of the genetic confounds, then potentially you don't see that same effect. But the one study that really jumps out at me is when you get to more potent use or frequent use, that increases the odds even more. And not all studies look at potency. And I think what we're seeing now in clinical practice is patients who are using 90%, vaping 90% THC, vaping, very, very potent stuff. And so higher potency, I think, needs to be factored in. Actually, recently, I was having a long discussion with a news reporter, and he showed me the email of a cannabis lobbyist, and the cannabis lobbyist had these are quotes from scientific studies that promote that it doesn't cause an issue like psychosis. And I look steady by study. I should Liam this as well. And I wrote them back. I spent like two hours probably way too long replying to him going point by point. You know, putting out the counter arguments that I think are truthful counter arguments. We'll see if the reporter uses them or not. But in this, I may need to publish my email at some point, depending on how the final paper comes out. But my points were like, hey, this guy is not paying attention to potency at all. Yeah, like I mentioned at the start of the podcast, we're really at unprecedented times with potency. Like the flower example that I gave was 20%. That's just the first example that I could find. So the studies that we're referencing are from the early 2000s. So that's not necessarily capturing that potency. And then... And we're having potency issues in other drugs as well, with fentanyl, for example, compared to normal heroin, I mean, the amount of fentanyl deaths, which I did an episode on probably about five years ago, like for seeing that this was going to be a huge problem in the US and it has grown to be a huge problem, a huge, huge, huge problem than it was when I first posted on it. so much more potent than heroin and morphine, you know. And so we are just becoming too smart for ourselves. You know, it's almost like the invention of the atomic bomb. It's like we are, it can sure. It's great if you're a country that uses it to win a battle. But if everyone's using it, not great, you know? Right. And I think the scary thing about cannabis is that the effects are delayed. So it's not like opioids where you see with a third wave of opioids when fentanyl became like the first wave was when people were being prescribed it from physicians, heroin came in and then fentanyl came in and you can see drastic graphs of overdose or the deaths and the amount of people who are addicted and that now with cannabis we're not seeing the same trends because I think the effects are just delayed on society and we talked about last episode how it does affect brain development. I think one of the stronger studies showed that there's a decreased prefrontal or cortical thickening when adolescents begin use. But I think the fact of the matter is at this point we don't have enough evidence to make really big, really good claims. So I think there's just a positive and the research that's out there. And I think as we move forward the next decade or so I think some of these questions will clear up.

I think as we move forward in the next decade or so, I think some of these questions will clear up. I think the evidence, like we see in these depression studies, is for increased potency, increased issues. That seems pretty clear. Okay. Let's keep moving because we've got a long way to go Yeah, Danielle, did you want to talk about suicide? I know that at least from my perspective, I've heard people say that cannabis is one of the only substances that doesn't increase risk for suicide. So could you maybe clear out some of that discussion? Okay, yeah, sure. Speaking very broadly, like there's a lot of studies that have shown that actually marijuana users have an increased risk of suicide compared to non-users. There are a lot of confounding factories. It's difficult to parse out cannabis individually as an independent factor that increases suicide risk. For example, people with lower socioeconomic status may have increased risk of suicide and also increased risk of cannabis use. There's also the confounding factors of drug use and increased stress series, depression itself. For the most part, when studies did control for other confounding factors, sometimes it was found that marijuana users were not found to have increased risk of suicide, but there are two well-designed, longitudinal studies that do control for exterior factors, confounding factors, and still do show some increased risk of suicide with cannabis use. There's one study on almost 7,000 adolescents that was based on like national survey data, followed participants starting from like age 14 to 15 through ages 16 to 17. And the study found that for people who used cannabis, at least monthly, they were more likely to have suicidal ideation or to attempt suicide two years later. And this study controlled for recent depression and other covariates suggesting that the effect of cannabis on suicidal ideation may actually be independent of depressive symptoms themselves, which is really significant, especially given how associated depression is with suicide, suicidal ideation. And there is also another study that followed over 3,000 adolescents

for over a year that looked to identify like what is what are the most important predictors for suicidal attempts. And interestingly, this study found that marijuana use and caregiver suicide attempts were out of the out of the predictors that they looked up. These were the only two predictors of a person's first suicide attempt that were independent. Notos response relationship was investigated in this study, but still a really notable study to look at. And the twins study we looked at also showed that like suicidality for the twin who used cannabis more frequently was also had an higher incidence. There is definitely evidence for that speaks to the contrary of the statement that cannabis is the only substance that does not increase suicidality. Right, so I think that in cases, people can be a little bit more dissociated with increased cannabis use, and I think that can kind of take them out of reality, or can maybe increase some of their depressive symptoms. Dr. Peter, did you have any patients in mind when this might have been the case where, you know, they had increased suicidal ideation with cannabis use because I can think of a couple at least. Yeah, definitely. I think that most stone people maybe that I know they don't get motivated to actually complete suicide, but I think it kind of adds to the just the anhydonia of the passive desire to die. I don't think any of these studies were actually looking at suicide completions, right? Just suicidal ideation. Okay. Yeah, suicidal ideation. Which is, you know, suicide completion is a lot more rare. Interestingly, I was thinking as I was looking at these studies, we know that SSRIs increase risk of suicidal ideation, not completion, suicidal ideation, and it's around the same odds, unfortunately. And yeah, so it's like, okay, once again, is it the people that are more depressed, use more THC and then have more passive SI, or is it the people that are just using the THC going to be developing more passive SI because they're using the THC? Any thoughts on that, Liam? How to... Yeah, I think that's difficult to parse out, but one of the studies did control for depression or the history of depression, they still did find increased risk. And of course, you can't control for every confound. Like, what is it that's leading to? And that a lesson beginning to use cannabis or some adult is beginning to use cannabis. So I think the literature that's out there is pretty limited. Like I couldn't find any studies looking at suicide completion. And if anyone finds one, let me know. And if it controls for confounds, then that's awesome. I think that's needed. But next, I think we can move to anxiety. So Danielle, did you want to walk us through what we found? Yeah, so what we found on anxiety. Most of the research is really on depression and psychosis. There's not so much research on the anxiety, but there was one perspective epidemiological analysis that adjusted for comorbid psychiatric disorders and sociodemographic factors. and it found very specifically that past year weekly cannabis use predicted panic disorder with agoraphobia, but not without agoraphobia. And then there was also another study that noted daily or almost daily cannabis use marginally predicted the onset of social anxiety disorder even after adjustments, but there's like I was saying there's not that much data on or not that many studies that investigate like generalized anxiety disorder and other are more common anxiety disorders. These were the two stronger, more controlled studies

that show. anxiety disorder and other more common anxiety disorders. These were the two stronger, more controlled studies that showed these very particular associations with very particular anxiety disorders, but other than that, odds risk ratios are just not very impressive and predictor relationships have been really sparse in the literature. So that's pretty much what we found with anxiety. Interesting that it would be with agoraphobia, meaning... And that with that, yep. These patients have had panic to the degree that their panic has caused them to change their behaviors. They don't want to go out. Be around a lot of people, of people. When people at panic attacks, they're looking for a reason for why they're having panic attacks, and then they reduce whatever they consider to be that which is causing the panic. Okay. So if they were driving when they had a panic attack, they will stop driving. If it's being in a large crowd, they will stop being in a large crowd there, really, so they're changing their behavior. So that specifically is what was linked to more frequent use of cannabis. Yes. Okay. Yeah. I think clinically too one thing that I'll add is I've seen a couple of patients with increased somatic symptoms with their increased cannabis use. So I think that's, I haven't seen any studies on that particularly, but I think that is something that's important to look into potentially. I think that the story so far is that we really don't have that much evidence clinically about cannabis use and especially the high potency, which is unfortunate at this point. Well, it's new, right? It's new. But there are a lot of studies on these things. I mean, these reviews are, you know, when you read through the reviews, they're citing many reviews. You know, these men and us, there's many studies that are metend, but specifically what you're saying is when looking at low potency versus high potency in the difference, is that correct? Yeah, correct. Like the way that cannabis is used currently, there's not many studies on a lot of the older literature. If it is using TUC in like in a randomized control trial, for example, they're using weak potency cannabis like the NIDA grown cannabis, which is about 10 to 12%. So even in the control trials that seem to be stronger studies, you're not actually using the naturalistic, you know, let's use doubt in society now it is. In one example of a randomized control trial that did use cannabis that I thought was interesting is for PTSD. So this was for using cannabis to treat PTSD symptoms and working at the VA where I've been out. I've seen so many veterans that they use cannabis to help their nightmares, help their hyper vigilance. Sometimes. Sometimes it makes their hypervigilance worse, but for the most part, they can call them their anxiety and help treat their nightmares according to them. But there was this one, rhinomise control trial that followed 80 veterans, and they essentially allowed them to smoke cannabis ad-libitum. So they were allowed up to 1.8 grams, which is about two joints per day, using either high THC, high CBD, a balanced THC to CBD cannabis, and then a placebo cannabis. And they looked at PTSD symptoms over, I think, three weeks, and they found a significant reduction in all treatment arms. And even in the placebo, the effect size was over one for the placebo and the high THC group. So that doesn't really tell us that THC is actually helping. It seems like it's comparable to placebo, at least, for treating PTSD symptoms. For those on YouTube, I'm pulling up the figure here. And really interesting that the initial high-TH CBD seems a little bit different on this side. Do you see that? But then in the end, this is post-sacation. but they all cross. The confidence intervals all cross, right? Right. So that's what you're saying is that the placebo is the same, essentially. Yeah, they're all improving on their PTSD symptoms. And I think what's notable about the study too is that there's a high brake, brake, blind rate is about 60%. So obviously, you know that you're smoking placebo versus a THC compound. So I think that's something to note as well. Yeah, so I think in a more nuanced research design, they would do probably like, in like 3% THC in like the control arm, and then like more like a 23% in the active arm.

Yeah. It's like 3% THC in the control arm, and then more like a 23% in the active arm. Yeah, and I think we'll be more helpful even is to use it naturalistically because I think a lot of veterans I talk to, they don't use just two joints a day. Sometimes it's all day every day. So I think looking at that approach as well, using more naturalistic, using the high potency, and then high dose as well. So I think if you use the high potency and then the high dose, then I think that's gonna have a way more accurate representation of what's going on here. Yeah. Yeah, okay. The other thing that I just did in clinical, when someone smokes, or let's say someone drinks for 40 years, the moment that they get sober, the PTSD is right there again, right? So it's like the alcohol may have helped them cope for 40 years and they may have been like, heavy drinker. But then the moment that they stop drinking, it's like their dreams are just right there as traumatic as ever. And these are like Vietnam vets that I worked with in the VA I'm thinking about. And I think the same is true from marijuana. It's like for some people it helps temporarily. And so they do it, but then what really helps is getting them an appartial, getting them sober, and then having them process, and their trauma on a sober brain with a group. That seems to be what's helped people get back to life overcome. So it's kind of like, I give this analogy, sometimes patients who are heavy marijuana users, it's kind of like you're floating in the ocean. Marijuana was that life raft that you saw, but there's a boat that came. And so you have to leave the life raft to get onto the boat. And the boat is partial IOP treatment, psychotherapy, you know? It's really hard to make progress with your cognitive processing, you know, how do you handle emotions when you're totally high all the time, right? Right. And we know that teachers can suppress REM sleep and that's important for emotional processing. So there are some studies looking at treatment outcomes for PTSD patients with engaging in trauma-focused therapy. There are a couple of trials that show those who use THC more likely to drop out, which I think adds up to what we've seen in the real world. But then there are also some other studies that show if the patients do show up, then they actually get equivalent outcomes to non-users of THC. So I, but I think in clinical practice, it's probably better to have patients come off the THC. When, when I would run this IO, IOP program, partial program that I did for like 10 years, we, the therapist, week three would be like, okay, this person is using marijuana, it's getting in the way of them being congruent with their emotional world. They couldn't get access to their true emotion. And so we would have that conversation with the patient, hopefully the connectedness that they felt with the group was strong enough for them to quit the connectedness they felt with marijuana. Because there is an attachment and a connectedness that often people feel with the drug. So, okay, let's keep going. Yeah, so kind of along those same lines talking about does THC improve anxiety and depression over the long term and PTSD as well Danielle did you want to tell us about some of the studies that I think were really interesting and that they allowed people to use them naturalistically. So do you want to tell us about what the design of the study was and then what some of the outcomes were? Yeah, so the first study is an observational study that used data actually from medical cannabis app. And the users of the app could put in their symptoms of depression, anxiety, stress, and then track those symptoms over time with the app. And because it's a medical marijuana app, they also would input their marijuana use into the app. And study took this data and found that 20 minutes after using cannabis, the patients would report alleviations in their symptoms of depression and end of anxiety. But when the longer term results were tracked, like two months later, these baseline symptoms were unchanged for anxiety and for depression,

the depression baseline symptoms were actually worsened over time. And then there was a single blind

randomized control trial in Massachusetts that found that getting a medical marijuana card led to increased cannabis use, which makes sense. When you have a medical marijuana card, you would use it more and see it as a medical thing. And actually to the point that it increased rates of cannabis use disorder. However, over a 12-week span, there were no significant improvements in pain and there were no significant improvements in depression. So, overall, evidence is suggesting that patients do experience like this alleviation of depressive symptoms in the short term, but these longer term improvements are not seen. And as Dr. Puder was mentioning earlier, there's this therapeutic work and work that needs to be done that can actually lead to a healing process. And if people are turning to cannabis instead to deal with depressive symptoms, anxiety symptoms, that prevents us from being able to actually work through those things and have a healing process. And now I do that I like to use and that I used, Janie and I recently taught a class in adolescent Ph.P. And that was about cannabis use because it was so common. Like I think all of all of the adolescents who were in the Ph.P. were using cannabis and it was finding saying that it was helpful for their anxiety for their depression and they told them I can you imagine that you had like a really huge Open wound on your leg and you found a product that makes your makes the pain go away of the wound You can put it on and it helps you to feel better in a moment But your legs are not actually healing, but you just keep using this product. What do you think's gonna happen if you just keep using this product, which stops you, like prevents you from healing, that makes you feel better in that moment. And one of the high school kids was like, oh, that's gross. The wound's just going to fuster. And I think that's exactly how I think about this. If cannabis helps people to feel better in the short term without the long-term benefits, it prevents them from engaging in the healing process that can require both therapeutic work and medications. Great, great. Yeah, really good. This is exactly what I've seen in my practice. And also, you can see why people would want to use it short term. It alleviates. And now with the ease of a high-potency THC pen that you can hide easily and take out between classes, take a puff. It's like the addictive potential is much higher than it used to be. Okay. Cannabis and sleep. Yeah, so like I mentioned, a lot of veterans that I have worked with, they use it because they're using night tears. They're experiencing night tears. One veteran that I talked to recently, he had such severe night terrors that he would wake up on top of his wife and choking her. So, and he found that cannabis was one of the only things that actually helped his night terrors we tried them on. Plombine, Prasosin, Sericwool, and he sleep-aid wasn't cutting it for him, but the only thing that seemed to help was the cannabis. And it seems like that's due to the fact that cannabis can reduce REM latency and duration so that, you know, nitere is happening during REM sleep. And we see that there's actually a decreased amount of sleep latency. So for people with insomnia, they can perhaps fall asleep a little bit more quickly with using cannabis if they smoke before bed. But I think other cases, other people would just be more anxious and wired. So knowing how the patient responds to this important. But these effects also might not persist due to tolerance over time because just like any drug people develop a tolerance

and it's not really clear whether that will lead to any changes in sleep long term. There haven't been any long-term RCTs in this topic. And of the studies that have been done, there's about 50 studies so far according to a scoping review. And 21% of these studies showed an improvement in sleep 48% showed worse sleep, 14% showed mixed results and 17% showed kind of as had no impact. To this point, it seems somewhat neutral for sleep, but at the same time clinically talking to patients who have used it, they tend to say that it helps with night terrors, but they feel groggy the next day. And again, we know that the reductions in REM sleep are probably not good long term for emotional processing and just for feeling rejuvenated and energized.

Yeah, so night tears sleep related violence part of PTSD very scary to the spouse. I know multiple spouses that ended up sleeping in different rooms, different beds, which I would actually advise. That's a good thing. It's a REM sleep behavior disorder, a type of parisomnia, which we normally do not move at all. We're completely immobilized in REM sleep. But in some people, they move, they act, they do things that they would, they act out dreams. And so someone like that, you know, they're acting, they could be acting out a violent dream, a trauma, traumatic dream, right? And so decreasing the REM sleep would be a goal. Now other things can do that too. Benzos, someone's choking their wife, maybe you're a little bit more aggressive with how you treat them. If marijuana is the one thing that's keeping them from choking their wife and they want to sleep together, I don't know if I'd be Wanting to decrease it

Maybe that's just me being practical, but I also would want them to be and get their PTSD actually treated

Some people when they they take certain medications. They'll have though

They'll do different sleep

behaviors as well and during rum sleep they'll go cook

They'll clean the wake up dishes be out, brownies will be burnt. Sometimes that's unlike the different, like the Nesta, Ambien type medications. So I've had patients wake up different types of sleep, like where they feel immobilized. So they'll still have the REM immobilization, but they'll be awake with the panic of some nightmare. That's very scary for people as well. So thanks for covering that. Yeah. Decreased REM sleep with cannabis, right? That's one thing you can remember. Yeah. And I think that's also sort of a link to how cannabis can lead to reduced cognition. If someone isn't sleeping that well, you imagine that if someone's groggy throughout the day, they're not going to be engaging in the activities that they normally want, what we want to do that can also increase the risk for depression as well. So in talking about cognition, we hear a lot in pop culture about how we will fry your brain, how you'll reduce your IQ points significantly and become a pothead in lazy all day. So Danny, did you want to add some context to this discussion with what the research is saying at this point? For sure. Yeah. With regard to the idea of like weed is the devil and it will be cause it, It will be the cause of all your problems the evidence doesn't Paint that picture. That's because the evidence what does exist is pre-limited with regards to like strength and either direction I think a literature review that Exemifies this was done by Scott and colleagues back in 2018 They did find that THC can have statistically significant effects on cognitive functioning, but these effects were statistically significant or clinically negligible. Furthermore, these effects, the difference between the two groups, did diminish given periods of affinance longer than 72 hours. So thus, those who used Canvas but were absent absent in for that time period, had outcomes that were not measurably different from those who didn't use cannabis. So what is the team for patients? To be frank, like I said, it doesn't mean you can say that cannabis is a double and the cause of all the problems. But if cognitive concern is a function and patients been using cannabis pretty heavily and regularly. You could say it could help to like abstain, but in terms of like clinical guideline grades, I would give this a solid C. But there was one study that I found that was pretty strong and it was a prospective cohort study done by Meyer and colleagues back in 2012 and they'd had a finding that was worth noting. They found that persistent cannabis use was associated with decline broadly across different domains of neuropsychological functioning and some of the participants who had consistent cannabis dependence experienced a decline in IQ points about half a standard deviation, which translates to roughly six to 8 IQ points. And that's even one control for use of education. Furthermore, and this is important for adolescents, ceasing Canvas use in adulthood was not shown to fully restore neuropsychological functioning for those who started persistently using Canvas into adolescents. And that's consistent with the hypothesis that canvass can have neurotoxic effects, especially adolescents, when the brain is undergoing crucial development. And again, this is a single study. So I wouldn't make a definitive statement or like try to make a case where rewriting clinical practice guidelines for anyone who's ever smoked a joint before. But it's worth noting so that clinicians can have conversations with their patients about the potential risk for decreasing IQ. It did decide to start Canvas, especially in adolescents. Yeah, I think this kind of echoes the point about starting cannabis use during adolescents has been shown to be linked to the reduced educational outcomes and occupational achievement too. So it's not to say that cannabis does not affect cognition.

I think that it does in the short term sense because if you look at studies where you have prolonged periods of abstinence greater than three weeks, that any study looking at less than three weeks, there's a chance that you'll see some effects in executive functioning and different types of cognitive tasks. But then when you take out the abstinence for three weeks in adults, then the effects tend to go away. But in adolescence, if someone's using it and they need to be on top of their game during school, you know, they're not going to want to pursue school if they're using cannabis daily, not able to focus on their homework. So I think that is definitely something concerning

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