Full episode transcript below. Beware of typos!
Nick Jikomes
Jonathan Shaffer, thank you for joining me.
Jonathan Schaefer 4:13
Thanks for having me. I'm excited to be here.
Nick Jikomes 4:15
Can you give everyone a quick intro in terms of who you are and what you actually do professionally?
Jonathan Schaefer 4:21
Yeah, sure. So my name is John Shaffer. I am a postdoctoral fellow at the moment
at the University of Minnesota Institute for Child Development. And what I do is I conduct research on the relationship between environmental exposures, which is just a term that I use to encompass both kind of lived experiences that people have and things in their environment that they come into contact with the relationship between those types of things and their later mental health. Interesting and so what's your what's your training and background? And are you a psychologist? Yeah, so I have my PhD in crime Michael psychology from Duke University. I've recently minted PhD. I got that in 2019. And then I have been at the University of Minnesota for postdoc pretty much since that time. Interesting. So what, um, what's just at a very, very high level? What have you been studying? What have you been interested in studying? And how did you sort of get into this as an interest area? Yeah, good question. So my research now, I said, I'm interested in environmental exposures. So that's a broad category. So kind of during my graduate and postdoctoral research careers, I've studied a number of different kinds of exposures. So in graduate school, I did research on the relationship between victimization and mental health. So things like maltreatment, victimization, by peers, sexual abuse, victimization, by like crime victimization, among other things. And then also published a few papers with colleagues in grad school looking at the effects of exposure to lead levels in early childhood, and air pollution as well. So those you can look up and find under my name easily enough, but as a postdoc, what my research is focused on instead, is specifically the effects of cannabis exposure. So this is a topic that I got interested in after starting like postdoc. I chose my postdoc for reasons that we might get into later. But essentially, I chose a kind of for, shall we say, like, methodological synergy between what I was doing as a postdoc and what I was doing as a graduate student. And it just so happens that the data that I have available to me as a postdoctoral fellow, are particularly centered around substance use and cannabis use in particular. So it really it's been a great position and has given me access to a lot of really great resources in terms of the data to answer these types of questions. And, of course, the fact that, you know, the US is seeing this, this moment, this sort of sweeping sea change in cannabis legalization means that these types of questions have captured a lot of people's interests, including lawmakers and policy makers.
Nick Jikomes 7:34
Ya know, some of the research you've done was piquing my interest because I work in the cannabis industry. So this is sort of something I've thought about a lot. And this is something that a lot of people have had top of mind for quite a while, actually, what is the relationship between brain development and substance use? In particular, we're gonna talk about cannabis today, but as a general topic, there's obvious importance to this area, right? What, you know, whether or not something can impact brain development is critical to understand. And as you mentioned, this sort of wave of legalization that's been happening for the last number of years, really sort of brings this to the forefront. Because, you know, for obvious reasons, more, more people are now having the opportunity to be exposed to and to choose to use something like cannabis. And so it makes perfect sense that we should be very careful to understand exactly what the effects on the brain and unhealth are of cannabis, especially if you're starting at an early age. So right. So the main thing I think we're going to talk about today has to do with your most recent research, which is more or less centered on this question of, does using cannabis in adolescents increase the odds of developing psychosis. And I would love if you could start off by just defining, defining some of the territory here for us. So let's start with psychosis. What exactly is psychosis as defined by psychologist?
Jonathan Schaefer 9:03
Sure. So just before I provide that definition, I also want to mention that my works looked at actually a bunch of different mental health outcomes. psychosis is kind of one of many, my most recent paper focused on psychosis. And the reason for that is because there's observational epidemiological research out there that suggests the relationship between cannabis and psychosis might be particularly strong. So what is psychosis? psychosis is a condition of the mind it's a kind of a constellation of symptoms, but the the main textbook definition would be state of mind where the the patient or the individual is having trouble. Trouble Telling what is real and what is not real. So this is where you see symptoms like delusions and hallucinations, delusions being kind of persistent false beliefs on the one hand, hallucinations would be experiencing kind of sensory input that is not there. Those are kind of two of the core symptoms of psychosis. And then you can also see additional things in some individuals like incoherent speech, inappropriate behavior. And oftentimes that can really mess up a person's life, even if the experience of psychosis itself is a relatively transitory one. And could you give us some specific examples that that people might have heard of that are clear examples of a psychotic state? Sure. So I spent two years after undergrad, I worked in a lab that was studying schizophrenia specifically. And it was a really fascinating job, because one of the things that I was responsible for was administering cognitive tests, to both individuals with schizophrenia diagnosis, and then healthy family members, and siblings of these folks, as well as healthy controls. And so in, in doing that job, I kind of got to encounter a lot of different, a lot of different people, a lot of patients and a lot of different manifestations of kind of what we think of as psychosis. So a few that, you know, have stuck with me over the years is I remember one individual kind of was operating under the persistent belief that he was in a romantic relationship with Emma Watson, the Harry Potter actress. And, you know, that in and of itself might be possible, or perhaps provable. But, you know, there were also other beliefs attached to that, which was that she would set him kind of secret messages, you know, reinforcing her affection for him that she would break into his room on the inpatient ward at night and leave him sort of special messages that only he could see she she would move, maybe, you know, his his clock on his bedside table ever so slightly, so he would know that she had been there. I met another individual who, another example. But the illusion believed that he was an angel, from a kind of different dimension, and was being sent here for some sort of special purpose. Third individual that I'll always remember, had the sort of fixed belief that everyone around him could read his thoughts, which made interacting with him very challenging, especially giving cognitive tests to someone who's kind of operating with that belief in mind. And observations also can take kind of as, as very to form as as delusions, I would say auditory hallucinations, I believe are the most common. So that will be, you know, hearing things that aren't there, such as someone calling your name or hearing voices. Sometimes, which can tell you nice or neutral things, but especially when they become problematic are often saying, you know, mean, or threatening things. But then you can see kind of a whole gradient there. And then on this more extreme end, you can even, you know, have folks reporting visual hallucinations, which is seeing individuals who aren't there. Other kind of perceptual abnormalities, the walls moving in ways that they shouldn't insects on areas, or objects or people that no one else can see. So it's really it's a pretty wide spectrum, just kind of united by these, this this sort of core definition.
Nick Jikomes 13:51
I see. So is it fair to say that maybe a general way to think about this is that psychosis or a psychotic state is when something's going on in the brain, such that the person's thoughts and behaviors and perceptions just are not matching up with their sensory environment?
Jonathan Schaefer 14:08
I think that would be fair. Delusions, you could argue is maybe less close to sensory input than hallucinations. I think it'd be fair to say there are probably multiple kind of separable brain mechanisms going on that contribute to what we generally call psychosis. But but kind of like you're saying that the core feature is this disconnect between the reality that the person is perceiving and the reality that kind of everyone else is perceiving.
Nick Jikomes 14:37
I see. And then, you know, the other thing I think I want to make clear here is, so you've already told us that psychosis is this sort of constellation of things, it can manifest in different ways in different people? Is it also fair to say that this is also we should also think about this as a kind of spectrum, meaning that, you know, on one side of the spectrum could be full blown. psychosis in a severe case of schizophrenia say, but on the other side could just be, you know, little sort of micro, micro psychotic symptoms that even normal people experience all the time. I think we all had the experience of, you know, I swore I heard my name, but but no one said it.
Jonathan Schaefer 15:14
Yeah, that's exactly right. And that experience is ubiquitous enough that if that happens to you, you know, once twice, couple dozen times over the course of Odin three year, probably nothing to be concerned about. So yeah, so there's a branch of psychological research that's called tax and metrics where people look at kind of psychiatric disorders or symptoms, and they try to answer the question using the sophisticated statistical methods of whether these, these constructs are actually separable categories of experience that have distinct kind of fixed boundaries to them, or just kind of broad continuum where people kind of slide from one end of the scale to the next, both like both between individuals, meaning different people will fall at different points along the scale. And then even within an individual, you know, they might be at a different point on this, this spectrum of the psychotic spectrum or any other spectrum over the course of their lives. And by and large what what taxa dimetric research tells us is that the vast majority of mental health problems do fall or are more kind of appropriately conceptualized as, as being continuous in nature. And so psychosis is no exception.
Nick Jikomes 16:32
The other thing that I think is worth clarifying up front, so multiple times, I've had the experience where I'm talking to a non scientist or non psychologists usually, but they'll be interested in this general topic. And they'll say, you know, say that they've read, they tried to read a scientific paper, and it could be about cannabis or psychedelics or some something like that. And they'll read something like, you know, cannabis is a staccato mimetic drug. And they'll say to themselves, wait a minute, like, I know a lot of people smoke cannabis. And that doesn't turn us schizophrenic like, you don't go into psychosis while you're high. So what exactly does a term like that mean when we say that a substance can be psychotomimetic.
Jonathan Schaefer 17:13
So psychotomimetic really just means can cause another term you might hear it's like psychotic, like symptoms. So relatively common, although not ubiquitous side effect of categories, cannabis consumption, at least for some people, or at some dosage can be paranoia. So people will report you know, if they're consuming a lot of cannabis, particularly if they're doing it maybe through edibles or more intense methods of administration, that they sort of hit maybe a relaxed kind of slightly euphoric feeling at the outset. But as the dose builds and builds and builds, you know, they find their their, their, their advocate a lot more anxious. And then accompanying that might be lots of anxious thoughts, like everyone's looking at me, or like, Oh, I feel weird. I wonder if you'll notice. And, and kind of, if you push that to an extreme degree, that that starts to resemble some of the paranoid thinking or processes that you might see in someone with a diagnosable psychotic illness.
Nick Jikomes 18:18
So it kind of does make sense. Like, even if you just think about normal paranoia, you know, if you smoke some weed or ingest some other jug, and you get paranoid, not that you're having like a full on true psychotic break, but you just think, hey, Everyone's looking at me, but they're actually not, that's a psych psychosis like symptom,
Jonathan Schaefer 18:36
right. And of course, the difference right between a sort of transitory psychotic state, and a psychotic disorder is that in one case, the effects or the kind of causes of the transitory psychotic state are very clearly the substance that the person just ingested. And those symptoms only happen when the person is using that substance. Whereas in the case of the psychotic disorder, it is more repeated, more all encompassing and impairing. And it can be exacerbated when a person is using substances, but then also the symptoms have to be present during periods where they're not using as well. I see.
Nick Jikomes 19:17
So so it is true that that certain substances, the acute consumption of them, when you're in the intoxicated state can produce mild or transient psychotic like experiences. I've also read that you know, substances can also including cannabis can also make the ongoing chronic symptoms of someone with a psychotic disorder worse, is that is that true? And to what extent do we know that?
Jonathan Schaefer 19:42
Yes, so that's a my specific area of research because I'm focusing on these kind of large population based studies rather than studies of, you know, say, inpatients with a psychotic disorder, but the my understanding of that research is that that is true. So if you do have a psychotic illness, generally it is a good idea to say Stay away from these cycle mimetic substances because it can exacerbate symptoms, bring on psychotic breaks and might even affect you kind of more intensely than others. Given that you your your, your brain sort of in its natural state already has a kind of predisposition towards going down these these sorts of neural pathways.
Nick Jikomes 20:20
Got it? So we've sort of established what psychosis is we talk a little bit about schizophrenia. The other thing I want to do up front is talk about cannabis use disorder. So what exactly is that? And how do we how do we define it? And how common is it?
Jonathan Schaefer 20:34
Yes, that's a great question. So that the kind of technical definition of cannabis use disorder has changed slightly over the years. So in the early versions of DSM we saw bifurcated in cannabis abuse versus cannabis dependence. And when you're talking about abuse versus dependence, it's sort of general distinction is is your use of the substance causing problems for you in kind of daily living his use of your substance causing legal problems? Is it causing role impairment? Is it you know, causing difficulties for you, whereas dependence typically refers to a more kind of physiological set of symptoms. So we think about things like tolerance needing more and more of the substance to kind of get the same effect, or withdrawal symptoms. So when you kind of take the substance away, someone starts to experiencing kind of ill effects from just the lack of the substance being there. So cannabis is an interesting one, because the withdrawal effects are in general, not nearly as pronounced as they are for other substances like alcohol in particular. So if you're extremely alcohol dependent, and alcohols withdrawn too abruptly, that can actually cause someone to, you know, need to be hospitalized and you know, die at the very extremes, whereas cannabis, that is not not really possible with just the way that cannabis is, chemistry works. But sort of those two conditions have been subsumed now under the general heading of a cannabis use disorder. So DSM five, the most recent version of the Diagnostic and Statistical Manual of Mental Disorders, no longer really distinguishes between abuse and dependence, they've just taken symptoms from both categories and kind of put them under a general subheading. And I think the reason for that is because usually, when you have abuse symptoms, you very often will have the dependent symptoms as well, they often go kind of hand in hand.
Nick Jikomes 22:36
So this general topic of the relationship between cannabis use and psychosis has a fairly lengthy history, people have cared about this for a while, I think there's been, you know, a pretty good amount of research on it. What's sort of made it difficult in my perception is that on the one hand, it's just sort of very difficult to get a truly definitive study out there. So like, no studies, perfect, a lot of it's based on correlation, and you can't really establish causality, and we're gonna get into that. And then the other thing, too, is, you know, there's there's sort of people with, with a leg in the race, right, there's some people that really want to believe one one way and some people that really want to believe the opposite way on this topic. And I think that that has also contributed to how, I mean, is it fair to say this is an area that's been controversial in the literature?
Jonathan Schaefer 23:25
Yes, I would agree with that. And because, yeah, like, like you're saying there definitely individuals out there with kind of a vested interest in how the research on this potential link shakes out, right? If you're, if you're a manufacturer of cannabis products. It's really good news, if the kind of link between cannabis and severe mental health problems like psychosis, turns out to be serious. Whereas if you're on the other side of the equation, you have objections to cannabis for personal reasons, religious reasons. Perhaps some kind of financial state coming opposing side, you'd like to see very much the opposite.
Nick Jikomes 24:11
Could you give us maybe a synopsis or some kind of general overview of what you know, what how is the research on this potentially, between psychosis and cannabis? How has it progressed over the last, I don't know, 10 or 20 years? And what are what are the main schools of thought been one of the major? What are the major results been and what have been their sort of gaps and limitations so far?
Jonathan Schaefer 24:31
Sure. So research on cannabis and psychosis by and large, has occurred. Well, I guess first we can bifurcated into observational research and experimental research. So in experimental research, you can do kind of the gold standard type of study for supporting what we call causal inference, which is coming Making sure that manipulation or exposure x in this case cannabis itself is is actually driving your outcome. Why? So in a in a randomized controlled study, you can do that you have a really strong ability to approach causal inference because you can take people, you can randomly assign them to have a little cannabis or THC versus not. And you can kind of examine the effects. And so the experimental literature on cannabis has been really useful as far as understanding the acute consequences of cannabis use. So this is where we get the knowledge that you know cannabis is associated with the short term psychotic symptoms in a number of individuals. It's how we know that cannabis influences hunger, sleep, pain sensitivity, and all these different types of physiological functions are eliminated limitation of the experimental literature is you. You can't give cannabis to human beings for prolonged periods of time, because of possible ethical issues or the possibility that you're actually doing people some harm, right. So all the research we have on cannabis as long term effects is either coming from observational studies of human beings, meaning cannabis exposure is not happening randomly in the population. It's happening because people being study are either choosing or not choosing to use cannabis. And they're, they're choosing the extent to use it as well. Or we have data from animal models, where researchers can expose these these organisms to kind of as much cannabis as they want for as long as they want, and observe the effects and in most cases, try to extrapolate those to human beings. So those have kind of been the two types of research that have dominated research in this this space. And of course, animal models of psychosis are difficult, and not a exact match to psychosis of the human condition. So it's a most of the influential research on this kind of psychosis Link has come from this kind of observational epidemiological tradition, where they're assessing, you know, groups of people say adolescents for their cannabis use in early life, and they follow them into adulthood, or into at least late adolescence periods of life where psychotic illnesses are more likely to develop or manifest and are asking the question, you know, is it the case that, you know, adolescents or folks who were using more cannabis at baseline, are more likely to develop these types of long term psychotic illnesses in later life or adulthood.
Nick Jikomes 27:54
So to summarize my understanding here, two major types of studies, one is the experimental study, the other is the observational experimental studies, you could actually then bifurcate again, so you've got animal studies where, you know, we can take lab rats or lab mice or whatever, and we can do real causal studies, we can give them well defined doses of drugs, you know, the rats living in a controlled environment, its entire life, we don't have to worry about all of those confounders that we have to for these other studies. But at the end of the day, you really can't know if the results you see in a lab animal are ultimately going to translate to a human being. That's right. On the human experimental side, you know, we can do clinical trials, interventions like that, those are good. You said for acute effects, because you know, we can have someone come in today, give them cannabis or give them some other experimental manipulation and measure what's happening right then and there. But you can't really do a 20 year long experiment on the chronic effects, because it's simply not feasible to
Jonathan Schaefer 28:51
do that. Yes, and particularly in you know, children and adolescents, you know, individuals who can't give their own consent to participate in those types of those types of studies.
Nick Jikomes 28:59
So, so that leaves us with these observational studies where you can follow people the long term, but you've got this other issue where you just cannot control for all of the variables that one would like to control for. And so you know, that this is obviously where we're going with this and your work. Can you summarize, like the history of the observational studies so far? And and what have the results tended to be and what what, what have the, the gaps in the controversies sort of always been that have have haunted this area?
Jonathan Schaefer 29:30
Yeah, great question. So that observational research on cannabis and psychosis, I think it's fair to say it's been pretty, pretty consistent. So you'll have different cohorts from different areas of the world and people will pretty uniformly find that individuals who are reporting more cannabis use, you know, baseline time point A are also more likely to be diagnosed with a psychotic illness or are more likely to report scientific symptoms at follow up time point B. And that tends to be true. Regardless of how you're assessing psychosis, so it's true if you're asking people to self report on their symptoms. It's also true if you're looking at medical diagnoses made by trained health professionals. There are medical registry studies that have come out of the Scandinavian countries where they're able to kind of make those linkages by actually pulling people's medical records in extremely large population samples. But kind of the issue, like you alluded to is cannabis uses non random in the population. So there there are characteristics that maybe aren't universally shared by individuals who use cannabis, but are more common in folks who use cannabis, and particularly those who use it heavily and from an early age. And so the big limitation of this, these observational studies, of course, is it's it's impossible to know really, whether it's cannabis itself that seems to be driving this association, or whether it is other unmeasured factors, that these folks using a lot of cannabis, and particularly using early sharing common that also makes them more vulnerable to psychotic illnesses later in life.
Nick Jikomes 31:28
So the literature has been fairly consistent overall from these observational studies over the years. In general, the sort of key result, I guess, being that there's a relationship between cannabis use and psychosis, in particular, if you are heavily using cannabis, starting early in life, there seems to be a fairly clear signal there that it's associated with an increased risk of developing some kind of psychotic disorder. But basically, what you're saying is, because cannabis use, especially heavy use is not random. This is a classic case where we really don't know if correlation is telling us there's some underlying causation or whether or not it's a coincidence, and there's something else. So I'm curious, what are like the plausible something else's that that one would think about for this topic?
Jonathan Schaefer 32:16
Yeah, great question. And before I even get to that, I want to note that like, the results that I just summarized are not psychotic, psychosis specific. So there's, there's a whole literature on cannabis use and associated life consequences. And it's in the epidemiological kind of observational world. Almost all of it is bad news. So you find that folks who use cannabis earlier are not only at risk for psychosis, but they're also at higher risk for depression, anxiety, other substance use problems. They're showing lower IQ, cognitive impairment, they are going less far in school, they're acquiring less prestigious jobs, they are winding up in career paths with lower income. So not cannabis specific. But of course, the kind of fundamental question that we need to be asking ourselves is, is this a direct result of cannabis use? Or is this something else and so some of those something else is one that I think about is it's very well established that rates of childhood adversity are elevated among individuals who go on to smoke cannabis, particularly at great length and particularly early in life. And we know that different types of challenges, diversity, exposure to say maltreatment, domestic violence, neighborhood crime, all of these things are kind of globally associated with both poor mental health, as well as kind of cognitive problems and probably worse chances later on in life. And then another potential factor is genetics. So we know that genetic risk of cannabis use and genetic risk of psychosis are to some level correlated, suggesting that genes responsible for contributing to risk of one of these phenotypes, one of these outcomes are also perhaps contributing to cannabis use.
Nick Jikomes 34:15
So So to clarify, that is the idea that it's possible or actually, that we know that there are genetic risk factors that have something to do with making your brain more likely to develop something like psychosis and make you more likely to develop a substance use problem with cannabis or something else?
Jonathan Schaefer 34:36
Yeah, that's right. That's what the results of those genetic correlation studies seem to suggest. Whether that is mediated by the brain, in other words, like there are genes that are having a kind of causal impact on on brain structure and functioning I think is a little less clear. It could be For example, that you have certain genetic variants that are just correlated with being, you know, raised in certain environments, and we could see the correlation arising arising for sort of those types of reasons. But, but yes, there, there does seem to be at least a possibility that there are, there's kind of what we call genetic play a trophy, which is the idea that there are genetic variants that are increasing risk for both of these, these phenotypes, these these outcomes at the same time.
Nick Jikomes 35:29
I see. And that's pretty common, right. So when we say that a gene is Playa tropic, we mean that it does a number of things, basically. And you know, it's very natural for people, especially non genetics, people to think about, like, you know, particular genes having very sort of specific and nuanced effects. But in reality, most of them do lots of stuff that affects many aspects of our lives.
Jonathan Schaefer 35:52
That's right, yeah. And you can find genetic correlations between anything you can it's really a question of magnitude, right? So yeah, it's very difficult to draw a straight line from kind of the current state of knowledge between like specific genes or genetic variances and these outcomes. But at least from the genetically informative studies that we have, there are at least raising this as a strong possibility that we should consider because if the link between cannabis use and psychosis is due to share genes, or any of these other kind of unmeasured third factors, it means that, you know, any kind of policy change, any kind of political intervention that's targeting cannabis use is really not going to move the needle on psychosis prevalence whatsoever.
Nick Jikomes 36:42
I see. So this is really a classic case of, you know, is this correlation or causation, we've got a strong and consistent correlation between early cannabis use and psychosis across many studies. But we've also got many potential, many plausible confounding factors, which are just difficult to control for. I know that one way that is often powerful for teasing apart some of this stuff, when we're thinking about genes and environment and all of these types of things, our twin studies, which is the type of study that I think you did, so can you explain what twin studies are for people and what they're generally good for?
Jonathan Schaefer 37:19
Yeah, so twin studies have a lot of different uses. But the reason that I really love twin studies, is because when you're tackling these types of questions, it's kind of a very, very specific type of research question that is, is kind of forms the basis of my research career. So they are their questions, you know, concerning the relationship between an exposure and an outcome, where you can't really rely on experimental results, because either it's unethical to do it in humans, or it's somewhat uninformative to do it in animals. And then you also can't really rely on just straight individual level observational results because of this problem of residual confounding. And so the the fact that you can't rely on experimental results suggests you, you have to turn to observational data in one way or another. But the way people traditionally do that, is they you know, follow cohort of individuals, they try to think about, they try to come up with a list of potential alternative explanations for the associations they're seeing. So for example, you know, I've mentioned, you know, there's the possibility that, you know, cannabis use and mental health outcomes could could come down to the fact of, or it could come down to kind of shared roots in increased exposure to some kind of childhood adversity. So if I'm running my observational study, I might go ahead and try to measure that I might try to develop a measure to get an sense of to what extent that participants in my study are exposed to domestic violence or maltreatment in the home. And then I can enter that measure into my statistical models. And I can say, well, I've controlled for that. And I'm still seeing my relationship. So I know that this particular thing isn't responsible for the association that I've observed. Problem with that, though, is that, you know, if we sat here, Nick, the two of us, I bet could probably come up with a list of at least 15 to 20, reasonable, plausible, and perhaps even data driven, alternative explanations. So we could create a very long list of measures of constructs of things that people in these observational studies would kind of have to go in, develop a measure for administer that measure, collect the data and add it to their statistical models. And at the end of the day, you're you're you really are just guessing you can't make a complete list. That's right, the list is always going to be incomplete. And then there's a further problem, which is that if you add enough covariates into your model, whether they're super important or not, eventually your main effect is going to dwindle down. zero, that's sort of a statistical certainty because you're just going to be removing bits of variance from your, your sort of explanatory pie piece by piece by piece. And eventually there'll be nothing left. So the kind of beauty of twin studies is that they introduce a set of controls into your models, without you having to go out and measure or explicitly include anything at all. So twins are born at the same time, they're born into the same families, they live in the same house, most of the time, they live in the same neighborhood, they go to the same school. And then the case of monozygotic twins are identical twins, they also share 100 100% of the same genes. So what you can do if you understand when modeling is you can kind of take your, your research question and rather than ask, is it true that people in my unrelated sample, the general population, is it true that people in that sample who use cannabis more frequently are more likely to experience psychosis? I can ask in the case of twins, if you have a twin that's using more cannabis than their CO twin, is that the twin who's more at risk for a psychotic illness? And asking that question is actually a lot more powerful and informative than the first question. Because when you're asking the second question, you're holding this whole suite of called potential covariance constant across your twins, because they share just so much in common.
Nick Jikomes 41:37
Yeah, so I guess the idea is, if you look at data from enough pairs of twins, let's just say that you're looking at identical twins, so they all share the same genome for each pair. They're all growing up in the same household. There's a bunch of environmental factors that you don't even need to measure directly, but you know, that they're going to be pretty well shared. You know, obviously, they were in the same womb, born to the same family, all of this stuff. And if you've just got enough of those twins, and you're measuring, in this case, a cannabis use and psychosis, if you're lucky, and a good enough number of those pairs of twins dissociate such that like one of them uses more of the substance than the other one, you can now sort of disentangle the effect of that one thing, knowing that you're pretty well controlling for genetics and, and as many environmental factors that you could possibly control for in a study like this. That's right.
Jonathan Schaefer 42:30
And I just want I want to offer one caveat with this, which is that even a coatroom control design, you're not controlling for everything, right. So if any of your listeners or viewers are themselves twins, you know, they will know that even twins, even identical twins will differ from one another in myriad different ways. They will have slightly different life experiences, they might have different personalities, you know, different IQs different make make slightly different friend groups kind of the whole nine yards. But what you what you can know, at least from a twin studies, that you're you're holding this one important set of covariates constant. And when you observe a within twin difference, the kind of explanatory universe for that difference has shrunk considerably. So it's either you're observing a causal effect of your exposure, in this case, cannabis, or you're observing an effect of one of these, what we call non shared factors on which twins conceivably different. And what you can do in a twin context also is if you have a very strong suspicion as to what another important non shared factor might be, you can introduce that as a covariate into your models. And that's a lot easier and more practical to do than my first example, because again, the universe of potential compounds and explanations is significantly smaller. So an example that that I'll give to make that a little more concrete is like in a lot of my research, I will, I will covary for other substances to make sure that I'm capturing the effects of cannabis specifically. So I might introduce into my models controls for twin differences in alcohol use or nicotine being kind of the two most common other substances
Nick Jikomes 44:15
I see. I see. So before we get to the results of your twin study, I think one important thing to say up front is, so you've had this sort of relatively long history of a pretty good number of observational studies being done, not necessarily twin studies, just observational studies to do with cannabis use in adolescents and psychosis. There's this link there. Some of them probably control for a very small number of possible confound some of them probably control for a medium amount. Some of them probably went to great lengths to control for as many as they could think of. Is there any systematic relationship between what the end result tended to look like in studies with a lot of controlled variables versus those with a few?
Jonathan Schaefer 44:58
Yeah, that's a great question. Question. And I'm not entirely sure I know the answer for the cannabis and psychosis literature specifically, but I, I can say I've been working on a paper reviewing the literature on cannabis and cognitive ability, and then cannabis and educational outcomes recently. And a very common pattern that you do see that people will identify in review articles, or any kind of summation piece is that a general pattern is the word covariates entered into the models, the smaller the effects become, which can point like we've been saying to the fact that this is not actually a, a simple causal relationship that we're looking at. But on the other hand, you know, I mentioned earlier, any model you've got, if you add more covariance, you're kind of taking away unexplained variation, you're, you're you're going to kind of see that effect no matter what. Yeah. So. So really, really isn't impossible to get to a firm, firm conclusion. Yeah, it's certainly difficult from the, from the individual level, epidemiological observational tradition, I think the best you can do is you can select a few very important covariates to rule out a few very, sort of salient or obvious alternative explanations. But like we were talking about earlier, there's always the possibility that there's a, there's a something you didn't think about something you didn't consider, right, yeah. Okay, so I think this brings us to your study. So So what was your study? How did you set it up? And why did you do it the way you did it, given everything that we've discussed so far? Yeah. So I have actually a few papers now that kind of follow this general strategy. So I was analyzing data from an observational longitudinal twin study that was conducted at the University of Minnesota, it's called the Minnesota twin and family study. And so what the Minnesota twin and family study did was they recruited cut out the Genesis, it was three cohorts of twins. In adolescence. They asked them to report on their cannabis use over the past year, and they did that multiple times throughout adolescence. And then in adulthood, they conducted a bunch of assessments, looking at twins, mental health, looking at their cognitive ability, looking at their socio economic attainment and achievement. And one of the measures that I thought was particularly interesting, given this controversy about cannabis and psychosis is they administered a measure of what's called psychoticism, which is sort of like taking that psychosis construct we talked about, but putting it on a continuum, because fundamentally, that's what psychosis is, it's something that's kind of present to a lesser or greater, greater extent across the population. And of course, in the clinical world, we sort of tried to find a cut point to segregate people into individuals who would probably benefit from clinical attention to treatment versus those who are probably okay without that. So I sort of took these collections measures, I had kind of cannabis use frequency and number of uses in adolescence and psychoticism and adulthood. And I, I analyzed the two different ways. So I asked first, the question of well do we see in our data, the same relationship that all these other epidemiological studies are reporting wherein twins who are using more cannabis are as adults also scoring higher on our measure of psychoticism. And then I wanted to take it a step further. And I wanted to actually exploit kind of the twin pneus of the data. And so I did what's called a co twin control analysis, which is where I look within the individual twin pairs. And of course, I'm aggregating across all of them. But within each individual twin pair, I'm basically asking the question, Well, is it the case that the twin is reporting using more cannabis is also scoring is more psychotic than their CO twin? Because that takes into account this kind of wide range of control variables that we keep alluding to?
Nick Jikomes 49:18
And when we're thinking about the study, can you say a little bit more about the cannabis itself? Do we know? You know, to what extent is this self reported data versus the usage being measured in some independent fashion? You know, anything about like, you know, the THC content or the type of cannabis being consumed, or is it just
Jonathan Schaefer 49:40
random questions? So it those two things are unknown. So there that's that's a limitation of this study, certainly is that we don't have objective measures with which to kind of verify the twin self report. We're sort of relying on them to be honest reporters of use and We don't know anything about THC concentration. But what I will say we we probably can assume with a reasonable degree of certainty is that the cannabis that these twins were using is probably just slightly less potent than a lot of the cannabis being consumed today because studies that have looked at changes in cannabis potency over time find, generally speaking, an almost linear increase in THC content as time goes on. So those are those are like two important things, I think, to keep in mind as we discuss the results of this study. And I'm happy to also talk about how that influences kind of how I think about these findings and future directions. Okay, well, can you walk us through the the basic results of what you found? Yes, it was pretty simple at its core. So when we looked at the, the individual level, which means when I ran my analyses in my sample, and I kind of ignored the oneness of the data, I treated them essentially, as individuals, but nested within family, I saw kind of a typical relationship that everyone else reports. So in this case, it was the twins who were using the most cannabis and adolescents, they were also kind of as a group or across the spectrum. Because it was treating them both as continuum. They were reporting kind of the most psychotic, like symptoms as adults. And so that fit nicely in with what folks had already shown you replicated previous results. And that's exactly what you would expect, right? That's, that's right. Yep. Yeah, because the literature has been pretty consistent on that point, up until this point. So that I went into kind of my cartoon control analyses and looked at whether it was the case that I also observed this within twin pairs. And when I went to that level, it it turned out that the kind of the the cost estimate for the causal effect of cannabis, or at least the estimate for the effect of cannabis, on psychosis, controlling for the twins level of cannabis exposure, was just about zero.
I see. So in other words, if cannabis was the driver of psychosis, you would expect that when you find examples of twins, where one is using cannabis, more than the other one, then you should see a higher rate of psychosis in the Twin using more cannabis than the one using a little bit of cannabis. Right, released a higher a higher score on our measure a higher psychosis. But yes, but you did not see that. That's right. So I at least on average, across the board, between those who reported using more cannabis, we're scoring just as highly on our measure of psychoticism as twins who were using less cannabis. So that sort of flies in the face of this hypothesis, that it's actually the cannabis exposure in adolescents, that is causing psychotic symptoms and psychotic illnesses that that stick with people for most of their their lives.
And because we're talking at least for a subset about identical twins, does that point to at least point to somewhat the idea that there could be some shared that this does or doesn't have something to do with genetics? Yeah, so there's sort of two explanations remaining to us, given these findings, would be that the association is due either to shared genetic liability. So genes that predispose people to use cannabis and also to psychosis or at least psychotic, like symptoms, or it's something to do with shared environmental factors. So it could be again, kind of harkening back to that possibility that I raised earlier, it could be greater exposure to childhood diversity. It could be, you know, socioeconomic status related, could be kind of myriad other factors. So we didn't dive too deeply into figuring out, you know, what, kind of is responsible for this association given we've ruled out the causal effect. But I, you know, I do think that could be potentially interesting work in and of its own in and of itself. But what we really tried to do with with this paper was get at whether there's really a strong case for believing that if I reduce people's exposure to cannabis, I'm also going to improve their mental health. And at least the results of this particular paper suggests that that is not the case. So can you give us a sense for the the size of the data set here was this was this a relatively large number of twins that you were able to look at? Yeah, so the total sample size was 1500 44. So we had the psychosis measure available in to whatever three twin cohorts so I've previously published a separate paper and looking at a more diverse range of mental health outcomes and other outcomes which are slightly larger than this one. Just because I was able to combine data across the three. So it's, it's certainly a decent sized sample. And we had pretty good variability across both of our our relevant measures. But of course, it also does pale in comparison to, say these large, like National Registry studies, which are, you know, often entire populations of small Scandinavian countries. So there is that. But of course, the The primary advantage is that those studies can't kind of tease apart causality in the same way that we were able to hear.
Nick Jikomes 55:35
Okay, so to summarize again, basically, if your study holds true, then we could ask the question, if you have two twins, two identical twins, and one of them starts to smoke pot when they're a teenager, and one of them does not. The one that does start smoking pot will not be at greater risk for psychosis, assuming these results hold. That's right. What would it look like? So how, how definitive Do you think a study like this is, is? Are there any ways that you maybe could explain the data in a different way?
Jonathan Schaefer 56:14
Yeah, so one of the major weaknesses of a study like this is, you know, it's a single, I mean, it's three cohorts, but they're all kind of coming from the same place at the same point in time. So we always have to worry a little bit about generalizability. And I mentioned earlier that there's some good research out there suggesting that the the THC levels and kind of the general potency of cannabis products is increasing over time. And so I think one major concern is, even though we don't see any relationship here, these were individuals, these were participants who were using cannabis, you know, predominantly in the 1990s and early 2000s. And so it's possible now that we are, you know, a decade or two away from that, that, we might get a slightly different pattern of results. If we're looking at adolescents, teens who are using cannabis that is stronger. And then there's also literature out there suggesting that among teens, or among people who use cannabis products, their frequency of use is increasing, relative to what it was, you know, yours or in this case decades ago. So one of the things I'm actually very keen to do is to try to replicate these results in different samples. So there's a twin study out in Colorado that is designed in a way that's very similar to data I've worked with from Minnesota. So I'm currently in the process of kind of rerunning some of these models in their data to see if they generalize to a different state with a different cannabis legalization status. And then there's a there's a large nationally representative cohort study called the adolescent brain and cognitive development study, which is just collecting data on a nationally representative sample of US teens right now. And so once those teens are falling into adulthood, I think it'd be really interesting to look at their cannabis exposure and how that relates to later outcomes. Because this cohort also has a subset of twins, which would let me kind of repeat the analyses that I did in the paper that we're discussing right now. Did this result, surprise you? Or were you expecting to maybe see this? So this particular result actually didn't surprise me. And the reason it didn't surprise me was because I had just finished writing a separate paper, which was looking at the relationship between cannabis exposure and adolescence. And like I was saying, a different set of mental health outcomes, cognitive ability, and socio economic outcomes. And so the results of that paper mirror this one pretty well, in that we looked at major depressive disorder, anxiety disorders, antisocial personality disorder, and drug use disorders. And we saw pretty much the same pattern as we did in this paper, which is to say, yes, in the general population, cannabis use associated with increased risk of these bad outcomes. But when you look within twins, the differences are no longer significant or drastically reduced.
Nick Jikomes 59:27
So that's interesting. So you so you've seen this not only for psychosis, or psychotic, like symptoms, but for all these other things as well. That's right. And I guess, you know, I could imagine, you know, there's a lot of people that would probably hear that and go like, Well, yeah, of course, you know, we all know that. You know, many people would say themselves, you know, we all know from experience that you know, that relationship was dubious, these people are all just self medicating. They're actually using the cannabis to help treat their mental health symptoms. So it's in some sense, the opposite of what, what others were concluding. Sure. Do you think that's a reasonable conclusion? Like would you conclude from your studies that there's no kind of mental health risk for adolescents if they start consuming cannabis?
Jonathan Schaefer 1:00:10
Yeah. So the the sort of theoretical model you're evoking with, with that notion of self medication is what we would call reverse causation, right. So it's not like cannabis use causes mental health problems, it's that if you're experiencing mental health problems, you might be trying to alleviate them somewhat by smoking cannabis. And so that is one of those sort of alternative explanations for these associations that we see in addition to the idea that they're just, they're they're caused by unmeasured third variables that people haven't identified. And so my work doesn't itself address the possibility of reverse causation. I think it fits anecdotally, with certainly individual patients that I've treated, or encountered in the world. And it's one of the reasons why I think longitudinal data that answers this question is so important, because another limitation of the research I've done is that we don't actually have baseline measures of psychoticism in these cohorts. So I think it would be really interesting to see, is it the case that, you know, twins who are showing some of these signs have very early onset, psychotic or psychotic like experiences? I think it'll be interesting to see if they are the ones who are more likely to use cannabis, because I think that would speak to your your question, Nick.
Nick Jikomes 1:01:40
I think another thing worth talking about here is your results are very interesting. And basically, you're not finding evidence for a causal link between adolescent cannabis use and the development of psychosis. But couldn't someone argue, okay, it's not an across the board thing. It's not that cannabis use is kicking up everyone's ability to develop psychotic like symptoms, but perhaps it does in a sub sub slice of the population that has particular say, genetic vulnerabilities to developing schizophrenia, and that's driving all of the other effects that people see in the other studies. Is that possible?
Jonathan Schaefer 1:02:17
Yeah. So that's a it's a it's an interesting argument, because that's that is one that is often made. When folks who are trying to defend this narrative that cannabis causes psychosis. So it's, it might not cause it in the general population will say, but it's possible there's a subset of particularly vulnerable people who are going to be really dramatically affected by it. I think to some extent that grows out of this observation that if you have a diagnosed psychotic illness, you're I think, more likely to experience psychotic symptoms if you do use cannabis like products. So I think that's partially maybe where this this story comes from. What I can say about that narrative, is it's really hard to empirically disprove right? Because if you're not naming a specific vulnerability factor, you guys say that there's some other vulnerability, right? And it's probably to be fair, it's probably a confluence of different factors, it's very unlikely that it's just one singular vulnerability factor that would account for kind of these differential effects that people hypothesize. But like I'm saying, it's, it's hard to empirically disprove because if I pick a particular vulnerability factor, and I look at it, and I see whether that holds true, you can say, well, you that that wasn't the vulnerability factor that I was thinking about, or I would have measured it in a different way. So we did a little of that in the paper that we're discussing, which is we, we had genetic data on all of our participants. And so we use that data to calculate what's called a poly genic risk score. So essentially, it gives a kind of crude estimate of a person's genetic risk to a particular condition. So in this case, we looked at genetic risk of schizophrenia. And we kind of calculated this value this risk score for each of our participants, and we use that variable to ask the question, you know, is it true that, you know, cannabis seems to interact with this genetic risk measure to create particularly, you know, large numbers, or particularly significant elevations and psychotic symptoms and these these genetically vulnerable individuals? And in this particular study, we found that the answer was no, the the interaction term wasn't significant.
Nick Jikomes 1:04:39
I see. Okay, so So not only do you have a twin study where you know, because you're dealing with twins, they have shared genomes, but you actually had some genetic data. So you were able to look at some genetic data for them. And for each person, you have a score, perhaps not unlike something that you might get on 23andme or a service like that. That's right kind of tells you what they're Risk for schizophrenia was, and you were asking the question, okay, we don't see relationship between cannabis use and psychosis across the board across all the twins. But if you then pull out the twins that have a particularly high schizophrenia risk score from the genetics data that you had, do they have this? And you're saying you also did not observe the relationship there?
Jonathan Schaefer 1:05:21
That's right. And what I want to get across probably to your viewers, and obviously folks can go ahead and read the article themselves if they're interested. But we, we really tried our hardest to find the relationship that I guess the the pro cannabis causes psychosis camp would want us to find. So I did sort of sensitivity analyses looking at, you know, only the twins who reported using the highest levels of cannabis, or only looking at the twin pairs with the highest level levels of cannabis discordance to really see if you know, if there's a really substantial difference in cannabis use, then do we see this effect. So we look at this interaction with a genetic vulnerability factor, kind of the best one that we can identify, given the state of literature. So far, we didn't see an effect there. So it really seemed like no matter how we sliced our data, the evidence of a causal effect wasn't showing up. So that gives me a little more confidence in communicating this story to you and to the wider world. Interesting, and you mentioned it earlier. But can you just say again, a little bit more on what's next? What kind of studies are you looking to do to follow up on this? Yeah, so biggest questions, I think are number one, can we ensure that this replicates across different samples, all of our participants came from Minnesota was a predominantly white cohort recruited in the you know, 80s 90s. There, they're using cannabis in a particular way at a particular time. And since that time, we've seen kind of enormous changes in cannabis use just secular changes over time, people are using in different ways, using different products, there are different potencies. And even though the kind of overall prevalence of teen cannabis use in particular seems to be going down, people who are using cannabis are tended to use it with a lot more frequency than they were kind of back in the day. So I think it's really important to double check to see whether the results hold given these kind of contemporary changes in cannabis use that are occurring right now. So those are those are sort of the next steps that I'm eyeing. And then in particular, I'm also really interested to not only investigate this cannabis and mental health connection, but I'm also trying to do some follow up work on the relationship between cannabis use and socio economic outcomes in young adulthood. Because one of my findings that we didn't really get a chance to discuss very much so far is that well, there isn't much evidence to support a causal relationship between cannabis use and these mental health outcomes. We actually were seeing patterns in our in our coach when control models that are consistent with a possible causal effect of teen cannabis use on adult socio economic accounts. So we're seeing some evidence that twins who use more cannabis than their CO twins are doing less well, socioeconomically speaking in terms of their education, their occupational status, and their income in young adulthood. So that is a finding that I'm keen to also follow up and see if that holds true across different samples and in different times. Interesting. So let's just say, you know, your results are published or they will soon be published, I think
Nick Jikomes 1:08:51
these are these are both published, those articles are referring to out there. So so so that's, that's fantastic. Congratulations. First of all, I know this is a lot of work. Thank you. So you've got these two studies out there, one that says no link that we can find between cannabis use and psychosis. And you've got another one saying also no link between cannabis use and these other negative mental health outcomes. So I'm going to pretend I'm, you know, a cannabis retail executive of some kind right now. And I've got a few million dollars in the bank and I say, Great, there's scientific evidence that there's no problem with adolescent cannabis use. We let them buy cigarettes when they're 18. So we should be lobbying to decrease the legalization age for cannabis or when you can buy it from 21 to 18. Do you think? Do you think that's a reasonable argument to make from the data that you've generated?
Jonathan Schaefer 1:09:41
Yeah, interesting question. So I think it's reasonable to conclude based on the data I've generated that link between the causal link between cannabis and mental health, if it exists, is not particularly strong. I hesitate a A little bit when people talk about, you know, extrapolating from these these results to say that early cannabis use in general is no problem, not something that we should not be concerned about. And the reason for that is because of these other findings that I mentioned, which is that there does seem to be some evidence that there's a causal relationship between cannabis use and how well you're doing, you know, financially, educationally occupationally as an adult,
Nick Jikomes 1:10:37
wouldn't it? It would be, it would be bizarre, would it? Not? If there was no effect of any kind, from heavy cannabis use during relatively early periods of life and brain development?
Jonathan Schaefer 1:10:50
Yeah, in some sense, although, you know, I think I mean, the the story that I, I think the data are kind of converging on, or at least my my sort of pet hypothesis is that the adult outcomes we're seeing that do appear to be related to cannabis use in a causal fashion. I'm not so sure that those are those associations are mediated by long term changes in brain or neuro development, I think it might be easier to just say they are long term consequences of you using a bunch of pot when you're a teenager, right? Because if you are using a bunch of pot as a team, and you're kind of experiencing the typical short term effects that we all know, is associated with cannabis use, you know, maybe it's kind of increased relaxation, decreased motivation. I wonder if the simplest explanation is just that impacts your performance in school. And that then impacts your kind of educational and socio economic attainment later in life. And that these effects are not so much about cannabis exerting really dramatic effects on brain development. And it's more about short term effects.
Nick Jikomes 1:12:08
limited in scope with long term consequences. I see. So so that idea would basically be saying that, and there's nothing, you know, intrinsically good or bad about this in any, like ethical sense, but almost the cannabis use would be a marker of how you were choosing to spend your time. Yeah, yeah. And, you know, if you're choosing to spend it on, you know, certain certain things and certain other things, that's probably going to have some downstream consequence, in terms of how, what these other outcomes look like.
Jonathan Schaefer 1:12:36
Yeah. And again, the reason I say right is because when we look at the behavioral outcomes that we would expect to really be yoked very closely to brain development, when we look at mental health, and we look at cognitive ability, sort of the the repeated finding, at least from my perspective, is when we do these causally informative studies, these twin studies, we're seeing small to nil effects. And that's not really consistent with this idea that cannabis has dramatic effects on the brain and the way it's organized and weight develops. That's not to say, now that there couldn't be a thresholding effect. I mean, this is this is again, sort of pulling an ad hoc kind of alternative theory out of thin air, but you know, it could be at a particular level of cannabis exposure, the effects on the brain really do become noticeable. And we start to see effects that are mediated by a more sort of neural specific pathway. I can't disprove that with the data that I have available. And that's one of the reasons why I think it's important to follow up on these results. But I would say that what the literature seems to suggest so far is the cannabis as it's generally used in the population of adolescents doesn't seem to be exerting these really terrible consequences on
Nick Jikomes 1:14:04
neural integrity or mental health. I see. Well, you did mention something early on of the discussion that you've worked on, that I'm completely I haven't looked at any of these papers. So I really don't know what the answers are, I can guess maybe which direction they go in. You mentioned that you'd worked with other. You've done other other research on other environmental variables that can affect a bad life outcomes for people. Those was environmental exposure to lead. And I'm wondering if we could switch gears and you can sort of unpack for me what we know in that area?
Jonathan Schaefer 1:14:42
Sure. So the lead literature is a little bit different than the cannabis literature because with lead exposure, it's really hard to bring twins to bear on this question. Because you know, your level of lead exposure is usually tied to the type of environment you you find yourselves and so whether that's because you're getting exposure through lead pipes that need replacing, like in Flint, Michigan, or you're getting exposure due to let it gasoline products, which was the case in the cohorts that we were looking at, because they were drawn predominantly from the 70s. And 80s members of a single family are going to be pretty similar in their level of exposure to these kinds of pollutants. So it's difficult to find enough variability across members of a family to apply some of these, these methods that I'm so excited about. So our papers looking at let an air pollution time those two mental health unfortunately, weren't able to make too much use of twin data. But what we were able to do at least was look longitudinally across time and just ask the simple question of, you know, is greater exposure to these toxicants in adolescence associated with worse mental health in adulthood. And so this case, we are, you know, not able to control for things using the sort of more powerful twin method, which is my preference, but we were at least able to do what folks typically do in these epidemiological studies, which is, we were able to come up with a short list of potential alternative explanations, we were able to develop a list of, you know, robust covariates, to enter into our models, and we were able to see that the end of the day, you know, even though we tried to, you know, get the effect to go away by introducing controls for other possible explanations, we found that this, this relationship seemed to be pretty robust. That is that there's a, there does seem to be at least a small, reliable association between your level of exposure to these toxicants in early life and worse mental health as an adult.
Nick Jikomes 1:16:54
You know, one of the things that I think is top of mind for a lot of people just sort of pull back or zoom out a little bit, is, you know, for the last two ish years now, we've all been in this interesting, new or new ish environment that has to do with the ongoing COVID 19 pandemic, my understanding, it's only a cursory understanding, but my understanding is, you know, mental health issues are basically getting worse across the board, just because people have had lots of stressors introduced into their life, based on how things have changed as the pandemic has played out. Can you comment on that, generally, is that actually what we're seeing are rates of depression, anxiety, other things actually going up? And can you maybe comment on, you know, what your recommended coping mechanisms might be for the average person given your professional background?
Jonathan Schaefer 1:17:45
Oh, yeah, that's a that's an interesting one. So I'm not super familiar with the literature that's coming out. Looking specifically at your question, which is, do we see empirical evidence suggesting that mental health conditions are increasing over the course of the pandemic? I can think of papers I've come across that would support that I think there have been at least a few that have reported, you know, more, you know, visits to the psychiatric emergency rooms of local hospitals. I'm sure there are others that have addressed this question, but they're not something that I pay particularly close attention to. But what I can say is that what I have done a lot of research on is just the the prevalence of mental health problems in our society more generally. So this is even this is pre COVID. And what this research does is it kind of compares estimates of diagnosable mental health problems that we get from cross sectional studies studies, where you're interviewing people about mental health at one time point, and longitudinal studies, which are the kind of studies that I work with most closely, where you're interviewing people about mental health repeatedly across the life course. And so what these studies tell us, and this is, again, pretty COVID. These are cohorts who for the most part, I think, grew up again and kind of the 70s 80s 90s. When you look at assessments that are conducted at a single time point, you get rates of mental disorder, that are about half that of what you get when you're asking people about mental health repeatedly over time. So in the cohorts that I work with, that have these repeated assessments of mental health, you find that a staggeringly high percentage of people meet criteria for a diagnosable mental health problem at some point over the life course. So in Minnesota twin and Family Study, I believe our rates around 70% in the demon study, which I've used to look at, some of these environmental toxicants rates are as high as 8083 85% of them. population. So when you think about COVID, occurring against that backdrop for me, I think about it as probably a global stressor that's taking an already highly prevalent problem. And yeah, probably probably make kicking it up just a little bit higher. As far as coping? That's a really good question. I think what's been most useful for me personally is getting back to some sort of exercise routine. It's trite, it's basic, but it's true. I think physical health has been huge in kind of maintaining mental health during the pandemic. I think staying connected socially with folks, as much as possible has been, again, huge and as restrictions of lifting. I found also, you know, says my mood, because I'm finally able to play this Thanksgiving was able to get together with some friends and some family.
Nick Jikomes 1:21:03
And yeah, yeah, I'm surprised that I'm a little surprised at how little emphasis at least in the mainstream, you see, placed on just physical exertion as a mental health in your mental health toolkit.
Jonathan Schaefer 1:21:23
Yeah. And that's one of those. Those questions that we can study using these really strong empirical designs right there, there are plenty of randomized controlled trials showing pretty definitively that exercise does have positive effects on mental health.
Nick Jikomes 1:21:41
And you sort of mentioned that, you know, even pre COVID, at least certain mental health issues have been on the rise for quite a while. Do you? Is that an area that you know more about in detail? Like, for example, rates of depression, anxiety? What have those been looking like, in the US at least over say, you know, a 10, or 20 year time period?
Jonathan Schaefer 1:22:01
Yeah, good question. So my research doesn't deal so much with kind of secular changes in incidence of disorders over time. But what the research I've done that suggests is sort of the the better that we measure mental health in our, in our research, kind of the more prevalent we find that it is. And so what you notice in psychology and psychiatry over time, is this, this shift in just how the field perceives these conditions. And my hope is this trickles down to the general population. And honestly, it could still probably do, if a little bit more tricky, like I think within psychiatry and psychology, but we've sort of moved I think, in the past couple of decades from thinking about, you know, mental health conditions as these these disorders that affect a small, unfortunate subset of the population to, you know, the National comorbidity surveys of the 1990s, which returned to the at the time very surprising finding that they affect roughly 50% of the US adult population, to now where we have findings from these multi decade longitudinal studies that are measuring mental health really closely, and doing it repeatedly over time, suggesting that actually, the proportion of the population that experiences a diagnosis about not diagnosable mental health problem is north of 70 80%. So I think public understanding of mental health has been changing. And our understanding of what it takes to measure mental health well has changed. What I'm less certain about is whether any of these changes reflect kind of increases or decreases in mental health problems over time due to different factors, including COVID.
Nick Jikomes 1:23:51
I see So So you would say that you don't know the answer to the I mean, it's difficult to answer the question. You know, when we look at rates of mental health issues today in the US, you know, to what extent is that us just getting better at finding and measuring things versus us just becoming actually more mentally unhealthy? Today, as I think
Jonathan Schaefer 1:24:10
that's that's always the question. Right? So the the studies that are kind of informative to this point, I, you know, I do know, they're they're ones that are kind of applying the same diagnostic assessment procedure repeatedly over time. And so those are the studies that you want to be you want to be looking at, obviously, to answer this question to see if the numbers are actually going up without a underlying change in the measurement system. And I think the studies that are going to be most informative to that point are going to be studies that are following a nationally representative sample prospectively rather than looking at rates of people going to hospitals or seeking psychiatric services or engaging with the mental health care system, right, because you could certainly see secular trends in people's willingness to enter psychotherapy, or go see a psychiatrist or seek help, without there being a corresponding change in the actual underlying rates of disorder. So I think it's important to be able to tease those apart.
Nick Jikomes 1:25:17
Well, the the work that you've done is very interesting, Jonathan, I think we covered a lot of good ground today. On the main topic, we discussed the relationship between adolescent cannabis use and mental health outcomes. Is there anything, anything you want to say at the end to sort of tie things together? Or point people to in terms of places they can go to learn more?
Jonathan Schaefer 1:25:38
Sure, yeah. So. So there are a couple different research groups, internationally that have been focusing on this question for years and years. One of them that I'm fortunate enough to be affiliated with the moment is the Minnesota Center for twin and Family Research at the University of Minnesota. So we are using our twin data to answer important questions about the relationship between cannabis and later life outcomes. Also looking at alcohol exposure, smoking use. So lots of interesting findings kind of coming out from that group on a daily basis. But that could be a whole nother podcast episode. And then there are of course, other groups that are also doing this work internationally. I guess I give a shout out to my graduate school mentors who have their own cohort of twins in the United Kingdom. So that's Terry Moffat and Ashlyn Caspi at Duke University, and they do a lot of this work as well. So I would say folks are interested in learning more about the state of twin research and its intersection with the cannabis world. I think those are two great places to start. And of course, you can always look me up on the internet, Google Scholar, Jonathan Shaffer, and then I'm also on Twitter at John Shaffer PhD, so you can always feel free to drop me a line there. And happy to answer any questions I get. All right, Jonathan. Well, thank you for your time. Yeah, thanks for having me. Nick. This is great.