Welcome to Stuff to Blow Your Mind, a production of I Heart Radios How Stuff Works. Hey, welcome to Stuff to Blow Your Mind. My name is Robert Lamb, and I'm Joe McCormick, and we're back with part four of our exploration of psychedelics. Robert, have we ever made it to a part four on any series on this show before? Oh? I don't think we we have really. I mean, there have been cases where we've had, like an informal series where each episode is more or less self contained. So uh yeah, I don't know. I can't think of one off hand that that has been a four partner. On the other hand, we could have gone to eight parts on Dune maybe well may yeah, certainly they're there are There's so many topics that we could have divided up more, or we could have uh dwelt on in greater length. Uh you know this one though, I mean the curious things. I feel like we've gone in fairly deep, but we still are are only providing like basically a surface outline and everything you know, and and leaving lots of room for listeners to then to go out and explore topics and portions of this topic and greater depth. Well, yeah, with rich subjects like psychedelics, I guess, especially anything dealing with the mind, you run into the problem that the deeper you go, the more you uncover that you should you know, like you're always just opening up more cases instead of closing them. Right. It's it's like saying we were gonna we're gonna do an episode on consciousness. Yeah, yah, it's you could sort of do an outline episode of it, and I imagine we've probably done episodes that are essentially that in the past, but ultimately consciousness is an ongoing series on this show, and the same we said for a number of different topics. But hey, if you're just jumping in, you should probably go back listen to those other episodes. First, we did uh Psychedelics parts one through three before this where what do we talk about, Robert, Well, we talked about what psychedelics are and also what what drugs are. We talked about how psychedelics factor into traditional societies, how they factor into ancient and modern history, and ultimately how they factor into both the hopes and fears that individuals and groups of individuals have had for humanities future. Yeah, and so in the last episode, In Part three, we focused a lot on the twentieth century and how there was research in the nineteen fifties and nineteen sixties looking into how psychedelics could be used in say, psychedelic assisted therapy for treating conditions like alcoholism. How a lot of psychiatrists in the nineteen fifties saw its potential as what they considered a psychoto memdic, meaning that it would mimic the conditions of psychosis that would allow them to empathize with their patients. But then, of course it turned out to be something rather different than just mimicking the effects of psychosis. And then we talked about sort of in the in the mid sixties to about nineteen seventy, where the way of crashed psychedelic research encountered a lot of backlash, and for several decades it's sort of was was forced into the underground, and it's only in recent years that it's experience its two resurgence, And that's what we're going to focus on today. Yeah, now, I do want to throw in just a quick note that I don't want to leave anybody with the idea that all psychedelic research ended with Nixon's control Substances Act of nineteen seventy and then didn't pick up at all until after the nineties. Right. We've made that point in previous episodes, I think, but that most of it had been driven underground. Right. I was actually found a good source. And this has a nice visual for you know, the ups and downs of the research with the Beckley Foundation. At Beckley Foundation dot org, they have a nice overview, a nice graphic. Now, this uh, particular organization was founded in by Amanda Fielding. I don't know if you remember Amanda Fielding. Oh yeah, she uh. I think she talks to Michael Pollen in his book How to Change Your Mind, which we've been referring to throughout the past few episodes. I'm sure we'll refer to several times again today. But she talks to him, I think at some point and says something like, look, I understand I have an image problem. I'm a druggy with a hole in my head. Right, she underwent Trepid Nation. We have an episode in the that we did in the past Entrepid Nation. But but the foundation itself is a UK based think tank you and accredited in g O and it's dedicated to global drug policy reform and psychedelic research anyway. As they point out, the Control Substances Act of nineteen seventy effectively ended all government sanctions psychedelic research and brought everything down to a mere trickle um, but you still had some research going on that The lowest point identified um um on this website is seemingly in the mid nineties. That it was, you know, it was also very low and like the mid eighties, and now we're at the point where the research is even surpassing the previous high point, the previous heyday of the late nineteen sixties. I've got an informal theory that you will see an almost perfect correlation in in the twentieth century timeline between the quantity and quality of action movies produced by Hollywood and the lack of psychedelic research being done. It's like the your Speed came out, there can't have been much psychedelic research going on. That's that would be interesting to compare those timelines for sure. Now I thought maybe the first thing that would be good to get into today is a question about neurochemistry, the question of what's actually happening in the brains of people who take psychedelics like LSD and psilocybin. We've talked a lot about the the anecdotal phenomenological reports people have. You know, what what do people commonly say about their experiences on these drugs? But what's causing them to have those experiences chemically in the brain? Right, because it's all obviously going to come down to neurochemical in situation. You know, the magic mushrooms are not actually magic, h the machine, they're not actually working on your mind. Uh, there's something going on chemically inside the brain. Yes, But to go back to another point we've made repeatedly already is the importance of set and setting. Uh. Psychopharmacology should acknowledge that, especially with some drugs, psychedelic being some of them, that the context is going to highly influence what the chemicals due to the brain, and that in many ways these chemicals should be thought of as um not necessarily the cause of particular experiences, but facilitators of experience of varying degrees of intensity. Uh. So, these psychoactive compounds are of course different from one another. LST is not exactly psilocybin, psilocybin is not exactly d MT, and so forth. Uh, so what's found about one doesn't necessarily apply to all of them, but there do appear to be some important chemical similarities in the brain, and so I want to talk about serotonin and serotonin receptors. On the neurochemical level, there appears to be this really important connection between certain psychedelics and the endogenous neurotransmitter serotonin. Serotonin is also known as five hydroxy trip to me and the role of serotonin in the brain and the body is fantastically complex and still not full understood, and I think partially because of its role in the history of research on mood and depression, serotonin is often thought of as an internal chemical that creates happiness or positive mood, such that if you don't have enough of it you get depressed. But I think it turns out that this is a monumentally oversimplified and largely incorrect view. The most commonly prescribed antidepressant drugs these days are s s R EYES, which stands for selective serotonin reuptake inhibitors, and what they do is they block the reabsorption of serotonin in the brain, increasing serotonin levels overall. But we shouldn't draw the wrong conclusions from this. It is not simply a case that more serotonin equals more happiness or more serotonin equals less depression. In fact, ending up with too much serotonin due to drug interactions can cause a potentially fatal condition known as serotonin syndrome. One key interacting interaction and where it can occur is is with ayahuasca and certain antidepressants, which is a reason that is often stated like, you should be very careful if you are engaging in what's some called freelance um therapeutic psychedelic use. Well, yeah, exactly. I mean that's one of the things that we alluded to, and I guess we'll talk about more as the episode goes on, is that even though we've established that psychedelics have relatively low recognized risk when compared to many other drugs, it's not impossible for them to represent risks, especially when you think about how they may interact with existing psychological conditions or other drugs that you might be taking. Right. So back to serotonin. While serotonin does seem highly involved in the internal regulation of mood, it's mechanism is somewhat complicated, and it's also involved in a number of other processes throughout the body. And brain that aren't directly related to mood, at least as far as we know. For example, digestion the like the vast majority of the body, serotonin is found in the gastro intestinal tract, and it has something to do with the regulation of bowel movements. I'm sure some comedian out there has a great joke about like their depression slash bowel movements serotonin thing. I don't know, I haven't put it together in my head, but run with it somebody. Uh. But serotonin also has a lot of other uses in the body. It apparently somehow seems linked to the regulation of sleep to bone metabolism, so you know, like the creation of osteoblasts and osteogenesis, uh, sexual arousal, blood clotting. So there's a lot of stuff going on. And according to the psychedelic researcher Robin L. Carhart Harris, who's going to show up in research that we will talk about later, quote, a compelling unified theory of brain serotonin function has not yet been established. This is likely due to the exceptional complexity of the serotonin system, with its fourteen plus receptors, over twice the number identified for any of the other major neuromodular systems. So they're all lot of different basically holes in the body and the brain for that molecule to put its peg into, and they probably all do slightly different things or maybe largely different things. Nevertheless, it is clear that serotonin plays some important role in psychiatric disorders like depression, and one recent theory I thought this was pretty interesting. It's probably not conclusive. Again, we don't have a agreed upon the theory of serotonin yet, but one recent theory is that, in Carhart Harris's words, serotonergic processes are important for quote, mediating an individual's sensitivity to context. So, you know, serotonin might play this important role in the brain for like increasing the salience of contextual things in the environment. But where does psychedelics come in. So what happens is the classic psychedelics appear to bind to a specific subclass of serotonin receptor known as the serotonin to A A receptor, and these receptors are found concentrated in the human cortex. The cortex is the outer layer of the cerebrum the brain, which is associated with a lot of higher brain functions like sensations. You know, the visual cortex the auditory cortex. It's associated, you know, it's where you have centers for speech and language, for voluntary action and stuff like that. So when you take a psychedelic like LSD R psilocybin mushrooms, the active compounds make their way into the brain and they sort of play act as serotonin binding to these serotonin to A receptors. Now, because we have such a limited grasp of the role of serotonin to begin with, we don't fully know how to interpret the neurochemistry here, like what's happening with the serotonin two A receptors that's associated with or creating this psychedelic experience. But Robin Carhart Harris hypothesizes something really interesting. So Carhard Harris says that quote serotonin differentially encodes behavioral and physy logical responses to uncertainty. So under this model, you have like another serotonin receptor, a different one, the serotonin one A receptor, and Carhart's Harris says, quote that provides basal control during normal conditions via moderating emotion and anxiety and promoting a generalized patience. But the two A receptor, which psychedelics have these agonist properties for you, the psychedelics go in the two A receptor Quote is hypothesized to engage more during conditions of crisis when the above mentioned default mechanism becomes suboptimal e g. When an individual's internal and or external milieu become so changeable and or inconsistent with his or her prior beliefs and behaviors that significant revisions become mandated. In other words, Carhart Harris is hypothesizing that psychedelics provide a neurochemical hyper stimulation two receptors in the brain that normally work during situations of crisis and change to quote relax prior assumptions or beliefs held at multiple levels of the brain's functional hierarchy perceptually, emotionally, cognitively, and philosophically e g. In terms of biases. In so doing, it opens a door to heighten sensitivity to context, an ideal precondition for effective change. So that was really interesting to me. Like to be clear, we still don't know if this hypothesis of what's happening is correct, but it seems informed by what we do know about serotonin receptors and about the neurochemistry of psychedelics, And I guess the idea is that they sort of mash frantically at buttons in the brain that, naturally, when pressed, caused the brain to break internal habits, associations, and traditions at every level, from the senses to the beliefs. Interesting, so in the same way that a basically like a traumatic experience can change or alter our our our pre conceptions about the world, or in the same way that glimpsing something marvelous like seeing the Grand Canyon for the first time might have some at least minor change in the way you think about about the natural world, like the the psychedelic state is kind of um like leaning into those uh uh, those kind of experiences though, that the facilitate change. I think that's right according to this hypothesis at least, And this does seem to ring true to me based on everything else we've read. Uh it's kind of like how I think we've talked about this on the show before, how it really seems like it's easier to break habits or make changes in your life while you're on vacation or we in in any other kind of it doesn't have to be just vacation while you're external contextual circumstances are different. You know, you're faced with a different environment, different stimuli, maybe you're meeting different people, you're facing different challenges or problems. That seems to give rise to processes in the brain that make us better at changing what we've done and how we've been before. And it makes sense, right, because if we is an organism, we change location, we change what, we change set and setting, you know, we we end up having to update our priorities and our our judgments about where we are and ultimately who we are. And so it seems like under this hypothesis, psychedelics maybe doing something like that, but in an even more intense and chemically focused way, right, And yeah, it's interesting and in a way that does not necessarily require an experience of trauma or or some sort of you know, tremendous physical travel. Well, but there are interesting parallels to trauma. I mean again, this is something that's very common in the report, so that, like we've read about with the participants of the March Chapel Experiment, uh, people very often report having some kind of experience of dying or going through some great alma during their trip. And yet after their trip on the whole. They report positive effects and changes in their mindset and in their life. So I don't think we should necessarily discount the relationship to trauma. There. There may be sort of not physical traumas, but but emotional and psychological traumas that gets simulated or run through in the brain during the psychedelic experience. Yeah. I mean, so many of these accounts that we've read or you know, acquainted ourselves with, they do involve at least a challenging portion of the overall trip. Maybe the trip itself is not a quote unquote bad trip, because again, that's that's kind of disingenuous to get into the idea of like purely a good trip bad trip scenario. Um. So yeah, so much of the time there is a you know, for lack of a better word, a monster. But sometimes you have to defeat a monster, right, I mean, it's it's it's kind of the the old hero's journey. Well, this is one of the things that's commonly reported by psychedelic guides people who do psychedelic assisted therapy that Michael Paulan talks about this and how to Change your Mind a good bit about UH one effective strategy of guiding people through their meditative experience on on psychedelics is to encourage them to approach challenging experiences in their minds. So if you know, they're faced with something that scares them, don't run away from it, go toward it. And this actually tends to cause people to have very empowering experiences of discovery. I'm reminded of the the original ending to Alan Moore's v for Vendetta. I don't know if you ever read the comic book. I don't believe saw the movie, but yeah, I don't think I don't think this made it into the film. But in in the book, there's an individual who ends up um like taking LSD I believe it was LSD and visiting the side of you know what is essentially like like a labor camp or uh in order to like fully process, like, you know, the state of the world and his relationship with it. Really am more of a like a shamanistic h um kind of psyched delic encounter, but one that is intentionally traumatic because the character feels that they must they must confront something that is troubling and traumatic in their life. Yeah, I think there could very well be uses like that. That are that are legitimate and take best advantage of the psychopharmacology at work here. All Right, on that note, we're going to take a quick break, but we'll be right back, thank you. Okay, we're back. So we've been talking about the neurochemical action of psychedelics and and some ideas about what may be going on in the brain there with their relationship to a certain serotonin receptor, the serotonin two A receptor. But there are also ways of going beyond the neurochemical level and just looking at the neurological effects of psychedelics through brain imaging studies. Right yeah, I mean nothing spells good trip more than getting somebody on psilocybin and sticking them in an fMRI machine. Right, but you can't. I mean, I wonder what those subjective experiences are like. Surely somebody has studied that, like asking for the uh, the experiential reports of people have been in the fm R I But I mean, the studies are are quite useful looking at where, you know, where does the blood flow change, what what's receiving oxygen in the brain. Pollen talks about this at length in his book. One of the most interesting things is that psychedelics apparently tend to reduce activity in one of the most interesting networks of the brain, which is the default mode network. Adversary, Well, normally you'd be thinking, okay, psychedelics must be causing increased activity somewhere, right, But here it's fascinating to see where you know, the brain may be empowered by suppressing certain parts of it. So the default mode network is a brain subsystem we've talked about before. It involves different regions all over the brain, So it's not just like one little node somewhere you know, it's happening all over, but it's a set of interlinked and and related nodes of the brain that work together, and it's normally believed to be most active when we are not engaged in any other particular task. It seems to be highly associated with an idol wandering mind, but it is not only active when we're mentally unoccupied. It's not only when our mind is wandering or idle that we use the default mode network. Activation of the default mode network is associated with many kinds of deliberate thought processes, especially self referential thought processes, so like autobiographical and self evaluative thinking, The default mode network seems highly involved in knowing facts about yourself and in understanding and evaluating characterizations of yourself. If I give you a list of adjectives and ask you to think how they apply to you, we will probably see activation and regions of the brain that are associated with the primary activity of the default mode network. Right, and pretty much anytime you catch yourself thinking, contemplating, worrying over who you are and how others perceive you, Uh, this is the network that is in play, right. Uh. The default mode network also seems to be associated with forms of meta cognition, so like reflecting on your own emotional states and thought processes, which this in itself I mean not to really categorize any of these isn't isn't is good or bad, but but certainly metacognition in and of itself, being able to think about your emotions and be self aware, I mean, it's a uh, it is worth pointing out, yeah, that even though it's a lot of worrying is caught up in the default mode network. You can argue them that a certain amount of our ability to to stop and uh and think about how we're thinking is also tied up there. Sure, I mean, yeah, the default mode network is I mean, it's quite clear we have it for a reason, right, It probably it does something useful for us. It probably just comes with a lot of downsides too. It probably allows us to be philosophical and to you know, to do a lot of stuff that we value about human culture and human mental abilities. But it just also tends to be highly involved in ruminating on what's wrong with yourself and the world and your life and all that. Right, And the next example is a key example of this. Well, yeah, so the default moon network seems to be highly associated with mental time travel, thinking about things that happened in the past and episodic memories of those things, and then imagining events in the future, which is all this is key if we're going to to navigate the world, be at the world that we've built for ourselves or even just the natural world. Uh, you need to be able to we need to be able to to mental time travel to to think about the lessons we've learned and prepare for the challenges ahead. But of course, as humans, we take this too ridiculous extremes, and we get trapped in the past or trapped in the future, and uh, everything that is between those points is just stretched out to the point of writtin well to mention rumination again as a you know, psychological phenomenon rumination. In a way, a positive version of it could be thinking about plans for the future, trying to think through what you should do and figure out the best thing to do. That's an important skill that we have with our brains. But also that leads to people just imagining, you know, like recursive thought patterns of the way all the ways things could go wrong in horrible ways that are not actually useful. Right, Well, I mean ultimately too, it's you know, the idea of pursuit of happiness, the idea that we should be happy. That's um you know, that's that's a that's also a human complication, right, It's really part of the evolutionary model, right. I would guess one of the easiest ways to make yourself unhappy is to try really hard to be happy or to think about how to make yourself happy. Absolutely. I remember, moments of the purest joy are going to be the times when we're not actively seeking and grasping for it. Yeah. Another thing that seems to be associated with the default mode network is thinking about other people. It's important for theory of mind, so imagining the mental states of others trying I'm thinking, what is Robert thinking. That's theory of mind, but then also in making judgments and evaluations about other people. Yeah, and of course this is this. This is one of those things that's involved and some of the noblest and most sought after human experiences. You know, this isn't This is tied up in in in love and UH and and family, but it's also caught up in like the worst inclinations of humanity as well. Yeah, and so the default mode network, we've bashed it before, but obviously it's not bad. And I guess this is sort of a sidetrack, but I have read somewhere that the concept of the default mode network is one coherent brain subsystem has been criticized or challenged by somebody. So no, I think not all UH neuroscientists would accept that the default mode network is actually a coherent network. But right, like a lot of these things, it lends itself to being used as mere metaphor for making sense of our our environmental processes. And in a similar way that serotonin can be sort of misinterpreted. Is you know, but but perhaps, but perhaps I think that the default mode network, if it, if it is being misused as metaphor, uh some of the times or even a lot of the times by people, maybe it's a little more useful or at least less harmful a metaphor. Well, I do think it's still largely accepted within neuroscience, you know, but I'm not talking about it like it's not being you know, a valid theory, but more like when I when I'm engaging with it, like to what extent am I engaging with it as a metaphor for how my mind? Oh? Yeah, I see, yeah, yeah, um, but yeah, yeah, I mean it's just so interesting that this would be a major effective psychedelics on the brain, the suppression of activity in the default mode network. Like, could it be that suppression of activity in the default mode network, which is so largely focused on the self and metacognition and thinking about the past and future and the evaluation of self, that this suppression is what causes all these subjective reports of ego loss or ego dissolution on psycho psychedelics, boundary dissolution. Yeah, and again, if you don't remember from we talked about it in the first episode of the series. Ego loss or ego suppression is one of the most interesting common reports of people, especially on higher doses of psychedelics, and the best way to I mean, that's kind of inherently ineffable, but the best way to describe it, I guess, is the experience of having experience without a self, to have the experience or of sort of being without being an eye or a me. And of course, isn't it interesting that we also encountered this in dream as well, except maybe not that first night of sleep in a new location. I remember study that came out several years ago that that pointed out that what do you see, uh, with increased activity on that first night of slumber in a new location, the default mode now work. Oh so you're dreaming with a higher, higher state of awareness of self and self other distinctions, right, or at least it's too revved up to allow like a proper night's sleep to take place. So yeah, so the ego loss thing definitely suffers from ineff ineff ability. But to whatever extent we can understand it, it seems to involve a reduction or loss in the sense of self is a distinct other, separate from the rest of the universe or from nature, or from whatever is being observed. It's kind of ego loss is pure experience without a me, And so I guess you can see if if the default mode network is being suppressed, the default mode network does all the stuff we're just talking about, that may be what's active there. And it's also worth pointing out that there are studies showing that meditation tends to reduce activity in the default mode network. Absolutely. We've talked about some of that research on the show before, and as we discussed in previous episodes, there are some strong parallels between the psychedelic experience caused by drugs and the you know, the experience of master meditates. Are people who achieve you know, like the greatest points of I don't know what you call it, the peaks of conscious experience as as sought after by by meditation, like mindfulness and stuff. Oh yeah, I mean it comes back again to this idea that mediccognition is part of the default mode network. It's like, yes, you can, you can potentially turn to pharmaceutical on pharmacological keys to the to the locks that that imprison you, but also the key is already in the cell like that, the key is is present arguably within the default mode network itself. The one thing, at least seems to me, I mean, you're much more experienced with meditation than I am, is that the meditation route seems to take a lot of work, right, Like, it takes a lot of practice and people can't always necessarily get there on their own. Um. Yeah, I mean it does. But then again, I think I think one of them, I'm not trying to knock it, but no, no, no, But I think the other side is that, like we have to drive home that with um, with psychedelics like the you know, again the importance of set and setting and intention that this is not necessarily the easy road either. I mean, it does seem to be the case that with with psychedelics, you can you can induce a state like this, uh a lot quicker. But at the same time, it's not it's it's not easy. It's just not like hitting the Nirvana switch on somebody's brain. Uh and uh. And there's gonna be a certain amount of work involved there, and there's gonna be there're gonna be some risks. Well, maybe we should talk about what the science says about those risks when we come back from another break. Thank thank alright, we're back. So we've we've spoken at a lot on this show in these episodes about like particular examples of individuals taking a psychedelic substance and having some sort of mind altering experience, life altering experience. But we haven't really talked about any of the sort of uh, you know, cautionary tales of the psychedelic experience, for one part, because those stories are pretty prevalent in our culture due to the backlash and the moral panic surrounding psychedelics. But but I but I did think it would be helpful at this point in the episode to focus briefly on one example, um, and that would be I think one of the more famous examples of of of of psychosis, schizophrenia Schizzo effective disorder being linked to the psychedelic experience, to the consumption of a psychedelic substance, Beach Boys co founder Brian Wilson uh uh, brilliant musician, but has also lived with Schizzo effective disorder since the mid sixties, with his symptoms reportedly remote, emerging shortly after he took LSD and after after he had taken it, after these symptoms began to emerge, he would he ended up having to struggle with auditory hallucinations from that point on, still struggles with them today, I understand now. At the same time, it's worth noting that he's had a lot of positive things to say about the spiritual and creative influence of psychedelics, but his case does seem to stand as a cautionary tale of psychedelic how psychedelics can affect someone with a predisposition for schizophrenia or schizoeffective disorder, or at least the perception that they could have played a role there. I mean, because I think we still don't know for sure exactly what that interaction is, but it does or not, But but it is. It's certainly it seems real enough that everyone mentions it and urges everyone to exercise caution in that area. If you do have a, say, a family history of schizophrenia. Absolutely, I mean, I'm all for exercising caution. We I think we've said this in every episode before, but we do want to reiterate that we are just trying to be descriptive in these episodes. We're not telling you that you should take psychedelics. That's a decision you can only make on your own and hopefully in with the consultation of a medical professional and like learning, doing your own research and all that kind of stuff. So you should make sure that if you are going to go down this path, you understand the risks for yourself and you do all the digging you need to do there. Now, it does seem to be the case that there are plenty of reports of of experiences on psychedelics being timed to make it seem as if they have triggered symptoms in people with a predisposition for psychosis, and of course psychosis we should probably define that. I found a good definition by the National Alliance on Mental Illness that psychosis is quote disruptions to a person's thoughts and perceptions that make it difficult for them to recognize what is real and what isn't um and so so psychosis is a symptom, not a disease. It's a symptom of conditions like schizophrenia and schizo effective disorder. But the I think an important thing to emphasize there is that psychosis is understood as as causing problems recognizing reality which is not necessarily the same as the kinds of experiences the perceptual disturbances that people might have on psychedelics where you can see things but you know, in many cases know that they're not really physically present. But I guess the question is, is there any empirical evidence about whether the use of psychedelics actually causes psychosis? Uh, there's a little bit. So I was reading a news feature for the journal Nature by Zoe Cormier which pointed to two different studies from recent years finding no link between psychedelic use and symptoms of psychosis or other mental health complaints. So these studies are not necessarily definitive, but this is what the evidence, at least as measured here, seems to indicate. So the first study was published in the Journal of Psychopharmacology and by Johansson and Crebs called Psychedelics not linked to mental health problems or suicidal behavior of population study. Here, the authors reviewed survey data from a huge population study comprising more than a hundred and thirty five thousand adults in the United States, and the cross checked the use of LSD, psilocybin, and mescalin. So the study only applies to those three drugs not necessarily to others. Uh, those three drugs versus reports of mental health problems. UH. And I should know that almost twenty thousand of the roughly a hundred and thirty five thousand adults in study had to use psychedelics, so that's about fourteen percent. They found no correlation. Quote after adjusting for sociodemographics, other drug use, and childhood depression, we found no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression, and anxiety. We failed to find evidence that psychedelic use is an independent risk factor for mental health problems, So that's one thing now. On the other hand, Cormier's article also cites an interview with Charles Grobe, a pediatric psychiatrist at the University of California, Los Angeles who is also an advocate for some use of psychedelics in certain clinical settings, and Grobe seems generally encouraged by the findings, but warns that we shouldn't conclude that there are no risks and says that individual cases of negative effects from psychedelic use do occur. One example, he gives his hallucinogen persisting perception disorder or hp p D, which is sometimes described as like the never ending trip. It involves like repeated or incessant or invasive disturbances of the visual field or shimmering lights or seeing dots or something also known as acid flashbacks if you will, uh Grob gives a quote saying, quote, I've seen a number of people with the symptoms following psychedelic experience, and it can be a very serious condition. Right. Uh. You know, we have an older episode from years back on this that I think was based in part of a two thousand thirteen study, and if I remember correctly, that study found that, you know, it's that it was extremely rare, uh and in a large part blown out of proportion by anti drug messaging, because of course that was part of the moral panic, is that everyone's going to take LSD and they're going to you're either gonna force yourself through a key hole or you're gonna deal with acid flashbacks the rest of your life, or it's gonna be the Blue Sunshine scenario. Right, but oh man, blue sunshine has got to be the best and ugliest psychedelic exploitation cinema. Yeah, and thoroughly not like non psychedelic really, but still worth seeing. If that movie, that movie is a tan shag carpet, it is just hideous starring Zalman King. But I I do have to to mention too that I remember when we aired this episode, and this was I think an episode I did with Julie Douglas back in the day, we did hear from a couple of listeners who insisted that they had experienced acid flashbacks at some point in their life. So, I mean, the the accounts are out there, there is uh, you know, at least they're at least accounts of people dealing with these and and you know, claiming to deal with the reality of of acid flashbacks. So um, you know, perhaps more studies needed. Well, I mean, according to grow Is, it's not like that they're serious doubt that some versions of these things exist. The evidence seems to show that if to whatever extent these problems do exist, they're rare enough that they don't really show up statistically right. Well, then you know, and also wonder too, like what other factors are involved there, Like if if you have had a psychedelic experience and it was meaningful, as a lot of them end up being they ended up being something that stick with you and they give you a glimpse of, you know, something that is in some way hallucinatory, and then later on you have some sort of hallucinary UH experience that is tied to another UH situation, like you might have a tendency to interpret it as being linked to that original use. Well exactly, Yeah, there's a correlation causation issue here. I mean the authors of the first study, Crebs and Johansson I mentioned, they point out that these symptoms of hpp D also occur in people who have never taken psychedelics that you know, so there could be there could be a causality issue. Decide another study. There was a study by Hendricks at All in the Journal of Psychopharmacology and called Classic Psychedelic Uses associated with reduced psychological distress and suicidality in the United States adult population. So this study looked at an even larger sample, about a hundred and ninety thousand survey respondents. It also found that the use of those three psychedelics was not and again I mentioned earlier, it was LSD, psilocybin, and mescalin, so not not necessarily applying to the others. Those are the classic psychedelics, I guess, so the psychedelic classic, not to be confused with your classical psychedelics, not new psychedelics. Anyway, this study found that those three psychedelics were not associated with any adverse mental health outcomes. The study actually found some evidence to the exact contrary, People who had at some time used LSD or psilocybin had a lower life time risk of suicidal ideation or suicide attempts, though it's not clear that the psychedelics cause these lower rates of suicidal thoughts and behavior. Maybe there's some factor not controlled for that makes people both less prone to these problems and more likely to try psychedelics at some point. But it is worth noting that the use of other non psychedelic illicit drugs was mostly associated with increases in risk for past months, psychological distress, and suicidal thoughts and behaviors. The psychedelics appeared to be the exception. They were the drugs that that did not cause increase mental health problems. And so, to go back to Cormier's article, this was written up with a with a quote from one of the authors of the paper saying quote the author was Matthew Johnson, saying, quote, we're not claiming that no individuals have ever been harmed by psychedelics. Anecdotes about acid casualties can be very powerful, but these instances are rare. Uh. And he says at the population level that the data about the harms of psychedelics have been overstated. So again, we're not advising any particular plan of action or telling people to take psychedelics. I would say the bottom line from my reading on the risks of psychedelics is that there do appear to be some risks, but the risks are rare. There are risks to any drug. Any drug you're going to take, you should research from science based sources and and if possible, get medical advice before embarking on um. But then also those risks that do exist seem to be relatively low and relatively rare compared to the risks of lots of other known drugs. Yeah, ultimately, basic decisions on science and not on whatever the last horror movie you saw or or or comedy you know, you could go either way, right, depending on what you're watching. You can get a very skewed view of what a psychedelicy is and what kind of experience you can expect from them. Aren't Psychedelic comedy is generally more horrifying than psychedelic horror. I'm trying to think of what a good side. Well, you know, you're talking like the Monkeys movie, like head and uh and so forth, or Yellow Submarine. I don't know for a comedy. Okay, do we did? We run into the problem we envisioned we might, which is that we thought this was going to be the last part and then we only got halfway by the time we're what like fifty minutes now, Yeah, yeah, I think we're gonna need to cut this episode off. There's gonna be one more. So for everyone out there who is enjoying this, uh, this ride of psychedelic episodes, well then rejoice because we have one more for you. Um, for the rest of you, Well, just bear in mind, there's only one more. I mean, you can't get off. You gotta go all the way to the endpoint right right. Yeah, And our next episode, we're gonna we're gonna discuss some of what's been going on in the twenty one century where we are now in the psychedelic renaissance, and where we might be going in the future sounds great. In the meantime, if you want to check out more episodes of Stuff to Bow your Mind, head on over to Stuff to Blew your Mind dot com. That's where you'll find them all. You also, of course, can support our show in a few different ways, but the best way to do it is to tell your friends about Stuff to Blow your Mind. Uh. To make sure you have subscribed to this show as well as our other show, Invention, which is an exploration of human techno history and uh and I think we're planning to do an episode soon or have already done an episode on penicillin, depending on when you listen to this. Yeah, we will not have already done it. We will have done it. We will do it. I'm not sure where we will have agreed to do it. We will have agreed to do it. It sounds to me like you're struggling with mental time travel. It can be difficult with a two podcast schedule at any rate. Support Invention. Support Stuff to Blow your Mind by subscribing, leaving nice reviews, leaving some stars, and telling your friends about it. Huge thanks as always to our excellent audio producer Maya Cole. If you would like to get in touch with us with feedback on this episode or any other, to suggest a topic for the future, or just to say hello, you can email us at contact at stuff to Blow your Mind dot com. Yeah. Stuff to Blow Your Mind is a production of iHeart Radios How Stuff Works. For more podcasts from my heart Radio, visit the iHeart Radio app, Apple Podcasts, or wherever you listen to your favorite shows. H

Welcome to Stuff to Blow Your Mind, a production of I Heart Radios How Stuff Works. Hey, welcome to Stuff to Blow Your Mind. My name is Robert Lamb, and I'm Joe McCormick, and we're back with part four of our exploration of psychedelics. Robert, have we ever made it to a part four on any series on this show before? Oh? I don't think we we have really. I mean, there have been cases where we've had, like an informal series where each episode is more or less self contained. So uh yeah, I don't know. I can't think of one off hand that that has been a four partner. On the other hand, we could have gone to eight parts on Dune maybe well may yeah, certainly they're there are There's so many topics that we could have divided up more, or we could have uh dwelt on in greater length. Uh you know this one though, I mean the curious things. I feel like we've gone in fairly deep, but we still are are only providing like basically a surface outline and everything you know, and and leaving lots of room for listeners to then to go out and explore topics and portions of this topic and greater depth. Well, yeah, with rich subjects like psychedelics, I guess, especially anything dealing with the mind, you run into the problem that the deeper you go, the more you uncover that you should you know, like you're always just opening up more cases instead of closing them. Right. It's it's like saying we were gonna we're gonna do an episode on consciousness. Yeah, yah, it's you could sort of do an outline episode of it, and I imagine we've probably done episodes that are essentially that in the past, but ultimately consciousness is an ongoing series on this show, and the same we said for a number of different topics. But hey, if you're just jumping in, you should probably go back listen to those other episodes. First, we did uh Psychedelics parts one through three before this where what do we talk about, Robert, Well, we talked about what psychedelics are and also what what drugs are. We talked about how psychedelics factor into traditional societies, how they factor into ancient and modern history, and ultimately how they factor into both the hopes and fears that individuals and groups of individuals have had for humanities future. Yeah, and so in the last episode, In Part three, we focused a lot on the twentieth century and how there was research in the nineteen fifties and nineteen sixties looking into how psychedelics could be used in say, psychedelic assisted therapy for treating conditions like alcoholism. How a lot of psychiatrists in the nineteen fifties saw its potential as what they considered a psychoto memdic, meaning that it would mimic the conditions of psychosis that would allow them to empathize with their patients. But then, of course it turned out to be something rather different than just mimicking the effects of psychosis. And then we talked about sort of in the in the mid sixties to about nineteen seventy, where the way of crashed psychedelic research encountered a lot of backlash, and for several decades it's sort of was was forced into the underground, and it's only in recent years that it's experience its two resurgence, And that's what we're going to focus on today. Yeah, now, I do want to throw in just a quick note that I don't want to leave anybody with the idea that all psychedelic research ended with Nixon's control Substances Act of nineteen seventy and then didn't pick up at all until after the nineties. Right. We've made that point in previous episodes, I think, but that most of it had been driven underground. Right. I was actually found a good source. And this has a nice visual for you know, the ups and downs of the research with the Beckley Foundation. At Beckley Foundation dot org, they have a nice overview, a nice graphic. Now, this uh, particular organization was founded in by Amanda Fielding. I don't know if you remember Amanda Fielding. Oh yeah, she uh. I think she talks to Michael Pollen in his book How to Change Your Mind, which we've been referring to throughout the past few episodes. I'm sure we'll refer to several times again today. But she talks to him, I think at some point and says something like, look, I understand I have an image problem. I'm a druggy with a hole in my head. Right, she underwent Trepid Nation. We have an episode in the that we did in the past Entrepid Nation. But but the foundation itself is a UK based think tank you and accredited in g O and it's dedicated to global drug policy reform and psychedelic research anyway. As they point out, the Control Substances Act of nineteen seventy effectively ended all government sanctions psychedelic research and brought everything down to a mere trickle um, but you still had some research going on that The lowest point identified um um on this website is seemingly in the mid nineties. That it was, you know, it was also very low and like the mid eighties, and now we're at the point where the research is even surpassing the previous high point, the previous heyday of the late nineteen sixties. I've got an informal theory that you will see an almost perfect correlation in in the twentieth century timeline between the quantity and quality of action movies produced by Hollywood and the lack of psychedelic research being done. It's like the your Speed came out, there can't have been much psychedelic research going on. That's that would be interesting to compare those timelines for sure. Now I thought maybe the first thing that would be good to get into today is a question about neurochemistry, the question of what's actually happening in the brains of people who take psychedelics like LSD and psilocybin. We've talked a lot about the the anecdotal phenomenological reports people have. You know, what what do people commonly say about their experiences on these drugs? But what's causing them to have those experiences chemically in the brain? Right, because it's all obviously going to come down to neurochemical in situation. You know, the magic mushrooms are not actually magic, h the machine, they're not actually working on your mind. Uh, there's something going on chemically inside the brain. Yes, But to go back to another point we've made repeatedly already is the importance of set and setting. Uh. Psychopharmacology should acknowledge that, especially with some drugs, psychedelic being some of them, that the context is going to highly influence what the chemicals due to the brain, and that in many ways these chemicals should be thought of as um not necessarily the cause of particular experiences, but facilitators of experience of varying degrees of intensity. Uh. So, these psychoactive compounds are of course different from one another. LST is not exactly psilocybin, psilocybin is not exactly d MT, and so forth. Uh, so what's found about one doesn't necessarily apply to all of them, but there do appear to be some important chemical similarities in the brain, and so I want to talk about serotonin and serotonin receptors. On the neurochemical level, there appears to be this really important connection between certain psychedelics and the endogenous neurotransmitter serotonin. Serotonin is also known as five hydroxy trip to me and the role of serotonin in the brain and the body is fantastically complex and still not full understood, and I think partially because of its role in the history of research on mood and depression, serotonin is often thought of as an internal chemical that creates happiness or positive mood, such that if you don't have enough of it you get depressed. But I think it turns out that this is a monumentally oversimplified and largely incorrect view. The most commonly prescribed antidepressant drugs these days are s s R EYES, which stands for selective serotonin reuptake inhibitors, and what they do is they block the reabsorption of serotonin in the brain, increasing serotonin levels overall. But we shouldn't draw the wrong conclusions from this. It is not simply a case that more serotonin equals more happiness or more serotonin equals less depression. In fact, ending up with too much serotonin due to drug interactions can cause a potentially fatal condition known as serotonin syndrome. One key interacting interaction and where it can occur is is with ayahuasca and certain antidepressants, which is a reason that is often stated like, you should be very careful if you are engaging in what's some called freelance um therapeutic psychedelic use. Well, yeah, exactly. I mean that's one of the things that we alluded to, and I guess we'll talk about more as the episode goes on, is that even though we've established that psychedelics have relatively low recognized risk when compared to many other drugs, it's not impossible for them to represent risks, especially when you think about how they may interact with existing psychological conditions or other drugs that you might be taking. Right. So back to serotonin. While serotonin does seem highly involved in the internal regulation of mood, it's mechanism is somewhat complicated, and it's also involved in a number of other processes throughout the body. And brain that aren't directly related to mood, at least as far as we know. For example, digestion the like the vast majority of the body, serotonin is found in the gastro intestinal tract, and it has something to do with the regulation of bowel movements. I'm sure some comedian out there has a great joke about like their depression slash bowel movements serotonin thing. I don't know, I haven't put it together in my head, but run with it somebody. Uh. But serotonin also has a lot of other uses in the body. It apparently somehow seems linked to the regulation of sleep to bone metabolism, so you know, like the creation of osteoblasts and osteogenesis, uh, sexual arousal, blood clotting. So there's a lot of stuff going on. And according to the psychedelic researcher Robin L. Carhart Harris, who's going to show up in research that we will talk about later, quote, a compelling unified theory of brain serotonin function has not yet been established. This is likely due to the exceptional complexity of the serotonin system, with its fourteen plus receptors, over twice the number identified for any of the other major neuromodular systems. So they're all lot of different basically holes in the body and the brain for that molecule to put its peg into, and they probably all do slightly different things or maybe largely different things. Nevertheless, it is clear that serotonin plays some important role in psychiatric disorders like depression, and one recent theory I thought this was pretty interesting. It's probably not conclusive. Again, we don't have a agreed upon the theory of serotonin yet, but one recent theory is that, in Carhart Harris's words, serotonergic processes are important for quote, mediating an individual's sensitivity to context. So, you know, serotonin might play this important role in the brain for like increasing the salience of contextual things in the environment. But where does psychedelics come in. So what happens is the classic psychedelics appear to bind to a specific subclass of serotonin receptor known as the serotonin to A A receptor, and these receptors are found concentrated in the human cortex. The cortex is the outer layer of the cerebrum the brain, which is associated with a lot of higher brain functions like sensations. You know, the visual cortex the auditory cortex. It's associated, you know, it's where you have centers for speech and language, for voluntary action and stuff like that. So when you take a psychedelic like LSD R psilocybin mushrooms, the active compounds make their way into the brain and they sort of play act as serotonin binding to these serotonin to A receptors. Now, because we have such a limited grasp of the role of serotonin to begin with, we don't fully know how to interpret the neurochemistry here, like what's happening with the serotonin two A receptors that's associated with or creating this psychedelic experience. But Robin Carhart Harris hypothesizes something really interesting. So Carhard Harris says that quote serotonin differentially encodes behavioral and physy logical responses to uncertainty. So under this model, you have like another serotonin receptor, a different one, the serotonin one A receptor, and Carhart's Harris says, quote that provides basal control during normal conditions via moderating emotion and anxiety and promoting a generalized patience. But the two A receptor, which psychedelics have these agonist properties for you, the psychedelics go in the two A receptor Quote is hypothesized to engage more during conditions of crisis when the above mentioned default mechanism becomes suboptimal e g. When an individual's internal and or external milieu become so changeable and or inconsistent with his or her prior beliefs and behaviors that significant revisions become mandated. In other words, Carhart Harris is hypothesizing that psychedelics provide a neurochemical hyper stimulation two receptors in the brain that normally work during situations of crisis and change to quote relax prior assumptions or beliefs held at multiple levels of the brain's functional hierarchy perceptually, emotionally, cognitively, and philosophically e g. In terms of biases. In so doing, it opens a door to heighten sensitivity to context, an ideal precondition for effective change. So that was really interesting to me. Like to be clear, we still don't know if this hypothesis of what's happening is correct, but it seems informed by what we do know about serotonin receptors and about the neurochemistry of psychedelics, And I guess the idea is that they sort of mash frantically at buttons in the brain that, naturally, when pressed, caused the brain to break internal habits, associations, and traditions at every level, from the senses to the beliefs. Interesting, so in the same way that a basically like a traumatic experience can change or alter our our our pre conceptions about the world, or in the same way that glimpsing something marvelous like seeing the Grand Canyon for the first time might have some at least minor change in the way you think about about the natural world, like the the psychedelic state is kind of um like leaning into those uh uh, those kind of experiences though, that the facilitate change. I think that's right according to this hypothesis at least, And this does seem to ring true to me based on everything else we've read. Uh it's kind of like how I think we've talked about this on the show before, how it really seems like it's easier to break habits or make changes in your life while you're on vacation or we in in any other kind of it doesn't have to be just vacation while you're external contextual circumstances are different. You know, you're faced with a different environment, different stimuli, maybe you're meeting different people, you're facing different challenges or problems. That seems to give rise to processes in the brain that make us better at changing what we've done and how we've been before. And it makes sense, right, because if we is an organism, we change location, we change what, we change set and setting, you know, we we end up having to update our priorities and our our judgments about where we are and ultimately who we are. And so it seems like under this hypothesis, psychedelics maybe doing something like that, but in an even more intense and chemically focused way, right, And yeah, it's interesting and in a way that does not necessarily require an experience of trauma or or some sort of you know, tremendous physical travel. Well, but there are interesting parallels to trauma. I mean again, this is something that's very common in the report, so that, like we've read about with the participants of the March Chapel Experiment, uh, people very often report having some kind of experience of dying or going through some great alma during their trip. And yet after their trip on the whole. They report positive effects and changes in their mindset and in their life. So I don't think we should necessarily discount the relationship to trauma. There. There may be sort of not physical traumas, but but emotional and psychological traumas that gets simulated or run through in the brain during the psychedelic experience. Yeah. I mean, so many of these accounts that we've read or you know, acquainted ourselves with, they do involve at least a challenging portion of the overall trip. Maybe the trip itself is not a quote unquote bad trip, because again, that's that's kind of disingenuous to get into the idea of like purely a good trip bad trip scenario. Um. So yeah, so much of the time there is a you know, for lack of a better word, a monster. But sometimes you have to defeat a monster, right, I mean, it's it's it's kind of the the old hero's journey. Well, this is one of the things that's commonly reported by psychedelic guides people who do psychedelic assisted therapy that Michael Paulan talks about this and how to Change your Mind a good bit about UH one effective strategy of guiding people through their meditative experience on on psychedelics is to encourage them to approach challenging experiences in their minds. So if you know, they're faced with something that scares them, don't run away from it, go toward it. And this actually tends to cause people to have very empowering experiences of discovery. I'm reminded of the the original ending to Alan Moore's v for Vendetta. I don't know if you ever read the comic book. I don't believe saw the movie, but yeah, I don't think I don't think this made it into the film. But in in the book, there's an individual who ends up um like taking LSD I believe it was LSD and visiting the side of you know what is essentially like like a labor camp or uh in order to like fully process, like, you know, the state of the world and his relationship with it. Really am more of a like a shamanistic h um kind of psyched delic encounter, but one that is intentionally traumatic because the character feels that they must they must confront something that is troubling and traumatic in their life. Yeah, I think there could very well be uses like that. That are that are legitimate and take best advantage of the psychopharmacology at work here. All Right, on that note, we're going to take a quick break, but we'll be right back, thank you. Okay, we're back. So we've been talking about the neurochemical action of psychedelics and and some ideas about what may be going on in the brain there with their relationship to a certain serotonin receptor, the serotonin two A receptor. But there are also ways of going beyond the neurochemical level and just looking at the neurological effects of psychedelics through brain imaging studies. Right yeah, I mean nothing spells good trip more than getting somebody on psilocybin and sticking them in an fMRI machine. Right, but you can't. I mean, I wonder what those subjective experiences are like. Surely somebody has studied that, like asking for the uh, the experiential reports of people have been in the fm R I But I mean, the studies are are quite useful looking at where, you know, where does the blood flow change, what what's receiving oxygen in the brain. Pollen talks about this at length in his book. One of the most interesting things is that psychedelics apparently tend to reduce activity in one of the most interesting networks of the brain, which is the default mode network. Adversary, Well, normally you'd be thinking, okay, psychedelics must be causing increased activity somewhere, right, But here it's fascinating to see where you know, the brain may be empowered by suppressing certain parts of it. So the default mode network is a brain subsystem we've talked about before. It involves different regions all over the brain, So it's not just like one little node somewhere you know, it's happening all over, but it's a set of interlinked and and related nodes of the brain that work together, and it's normally believed to be most active when we are not engaged in any other particular task. It seems to be highly associated with an idol wandering mind, but it is not only active when we're mentally unoccupied. It's not only when our mind is wandering or idle that we use the default mode network. Activation of the default mode network is associated with many kinds of deliberate thought processes, especially self referential thought processes, so like autobiographical and self evaluative thinking, The default mode network seems highly involved in knowing facts about yourself and in understanding and evaluating characterizations of yourself. If I give you a list of adjectives and ask you to think how they apply to you, we will probably see activation and regions of the brain that are associated with the primary activity of the default mode network. Right, and pretty much anytime you catch yourself thinking, contemplating, worrying over who you are and how others perceive you, Uh, this is the network that is in play, right. Uh. The default mode network also seems to be associated with forms of meta cognition, so like reflecting on your own emotional states and thought processes, which this in itself I mean not to really categorize any of these isn't isn't is good or bad, but but certainly metacognition in and of itself, being able to think about your emotions and be self aware, I mean, it's a uh, it is worth pointing out, yeah, that even though it's a lot of worrying is caught up in the default mode network. You can argue them that a certain amount of our ability to to stop and uh and think about how we're thinking is also tied up there. Sure, I mean, yeah, the default mode network is I mean, it's quite clear we have it for a reason, right, It probably it does something useful for us. It probably just comes with a lot of downsides too. It probably allows us to be philosophical and to you know, to do a lot of stuff that we value about human culture and human mental abilities. But it just also tends to be highly involved in ruminating on what's wrong with yourself and the world and your life and all that. Right, And the next example is a key example of this. Well, yeah, so the default moon network seems to be highly associated with mental time travel, thinking about things that happened in the past and episodic memories of those things, and then imagining events in the future, which is all this is key if we're going to to navigate the world, be at the world that we've built for ourselves or even just the natural world. Uh, you need to be able to we need to be able to to mental time travel to to think about the lessons we've learned and prepare for the challenges ahead. But of course, as humans, we take this too ridiculous extremes, and we get trapped in the past or trapped in the future, and uh, everything that is between those points is just stretched out to the point of writtin well to mention rumination again as a you know, psychological phenomenon rumination. In a way, a positive version of it could be thinking about plans for the future, trying to think through what you should do and figure out the best thing to do. That's an important skill that we have with our brains. But also that leads to people just imagining, you know, like recursive thought patterns of the way all the ways things could go wrong in horrible ways that are not actually useful. Right, Well, I mean ultimately too, it's you know, the idea of pursuit of happiness, the idea that we should be happy. That's um you know, that's that's a that's also a human complication, right, It's really part of the evolutionary model, right. I would guess one of the easiest ways to make yourself unhappy is to try really hard to be happy or to think about how to make yourself happy. Absolutely. I remember, moments of the purest joy are going to be the times when we're not actively seeking and grasping for it. Yeah. Another thing that seems to be associated with the default mode network is thinking about other people. It's important for theory of mind, so imagining the mental states of others trying I'm thinking, what is Robert thinking. That's theory of mind, but then also in making judgments and evaluations about other people. Yeah, and of course this is this. This is one of those things that's involved and some of the noblest and most sought after human experiences. You know, this isn't This is tied up in in in love and UH and and family, but it's also caught up in like the worst inclinations of humanity as well. Yeah, and so the default mode network, we've bashed it before, but obviously it's not bad. And I guess this is sort of a sidetrack, but I have read somewhere that the concept of the default mode network is one coherent brain subsystem has been criticized or challenged by somebody. So no, I think not all UH neuroscientists would accept that the default mode network is actually a coherent network. But right, like a lot of these things, it lends itself to being used as mere metaphor for making sense of our our environmental processes. And in a similar way that serotonin can be sort of misinterpreted. Is you know, but but perhaps, but perhaps I think that the default mode network, if it, if it is being misused as metaphor, uh some of the times or even a lot of the times by people, maybe it's a little more useful or at least less harmful a metaphor. Well, I do think it's still largely accepted within neuroscience, you know, but I'm not talking about it like it's not being you know, a valid theory, but more like when I when I'm engaging with it, like to what extent am I engaging with it as a metaphor for how my mind? Oh? Yeah, I see, yeah, yeah, um, but yeah, yeah, I mean it's just so interesting that this would be a major effective psychedelics on the brain, the suppression of activity in the default mode network. Like, could it be that suppression of activity in the default mode network, which is so largely focused on the self and metacognition and thinking about the past and future and the evaluation of self, that this suppression is what causes all these subjective reports of ego loss or ego dissolution on psycho psychedelics, boundary dissolution. Yeah, and again, if you don't remember from we talked about it in the first episode of the series. Ego loss or ego suppression is one of the most interesting common reports of people, especially on higher doses of psychedelics, and the best way to I mean, that's kind of inherently ineffable, but the best way to describe it, I guess, is the experience of having experience without a self, to have the experience or of sort of being without being an eye or a me. And of course, isn't it interesting that we also encountered this in dream as well, except maybe not that first night of sleep in a new location. I remember study that came out several years ago that that pointed out that what do you see, uh, with increased activity on that first night of slumber in a new location, the default mode now work. Oh so you're dreaming with a higher, higher state of awareness of self and self other distinctions, right, or at least it's too revved up to allow like a proper night's sleep to take place. So yeah, so the ego loss thing definitely suffers from ineff ineff ability. But to whatever extent we can understand it, it seems to involve a reduction or loss in the sense of self is a distinct other, separate from the rest of the universe or from nature, or from whatever is being observed. It's kind of ego loss is pure experience without a me, And so I guess you can see if if the default mode network is being suppressed, the default mode network does all the stuff we're just talking about, that may be what's active there. And it's also worth pointing out that there are studies showing that meditation tends to reduce activity in the default mode network. Absolutely. We've talked about some of that research on the show before, and as we discussed in previous episodes, there are some strong parallels between the psychedelic experience caused by drugs and the you know, the experience of master meditates. Are people who achieve you know, like the greatest points of I don't know what you call it, the peaks of conscious experience as as sought after by by meditation, like mindfulness and stuff. Oh yeah, I mean it comes back again to this idea that mediccognition is part of the default mode network. It's like, yes, you can, you can potentially turn to pharmaceutical on pharmacological keys to the to the locks that that imprison you, but also the key is already in the cell like that, the key is is present arguably within the default mode network itself. The one thing, at least seems to me, I mean, you're much more experienced with meditation than I am, is that the meditation route seems to take a lot of work, right, Like, it takes a lot of practice and people can't always necessarily get there on their own. Um. Yeah, I mean it does. But then again, I think I think one of them, I'm not trying to knock it, but no, no, no, But I think the other side is that, like we have to drive home that with um, with psychedelics like the you know, again the importance of set and setting and intention that this is not necessarily the easy road either. I mean, it does seem to be the case that with with psychedelics, you can you can induce a state like this, uh a lot quicker. But at the same time, it's not it's it's not easy. It's just not like hitting the Nirvana switch on somebody's brain. Uh and uh. And there's gonna be a certain amount of work involved there, and there's gonna be there're gonna be some risks. Well, maybe we should talk about what the science says about those risks when we come back from another break. Thank thank alright, we're back. So we've we've spoken at a lot on this show in these episodes about like particular examples of individuals taking a psychedelic substance and having some sort of mind altering experience, life altering experience. But we haven't really talked about any of the sort of uh, you know, cautionary tales of the psychedelic experience, for one part, because those stories are pretty prevalent in our culture due to the backlash and the moral panic surrounding psychedelics. But but I but I did think it would be helpful at this point in the episode to focus briefly on one example, um, and that would be I think one of the more famous examples of of of of psychosis, schizophrenia Schizzo effective disorder being linked to the psychedelic experience, to the consumption of a psychedelic substance, Beach Boys co founder Brian Wilson uh uh, brilliant musician, but has also lived with Schizzo effective disorder since the mid sixties, with his symptoms reportedly remote, emerging shortly after he took LSD and after after he had taken it, after these symptoms began to emerge, he would he ended up having to struggle with auditory hallucinations from that point on, still struggles with them today, I understand now. At the same time, it's worth noting that he's had a lot of positive things to say about the spiritual and creative influence of psychedelics, but his case does seem to stand as a cautionary tale of psychedelic how psychedelics can affect someone with a predisposition for schizophrenia or schizoeffective disorder, or at least the perception that they could have played a role there. I mean, because I think we still don't know for sure exactly what that interaction is, but it does or not, But but it is. It's certainly it seems real enough that everyone mentions it and urges everyone to exercise caution in that area. If you do have a, say, a family history of schizophrenia. Absolutely, I mean, I'm all for exercising caution. We I think we've said this in every episode before, but we do want to reiterate that we are just trying to be descriptive in these episodes. We're not telling you that you should take psychedelics. That's a decision you can only make on your own and hopefully in with the consultation of a medical professional and like learning, doing your own research and all that kind of stuff. So you should make sure that if you are going to go down this path, you understand the risks for yourself and you do all the digging you need to do there. Now, it does seem to be the case that there are plenty of reports of of experiences on psychedelics being timed to make it seem as if they have triggered symptoms in people with a predisposition for psychosis, and of course psychosis we should probably define that. I found a good definition by the National Alliance on Mental Illness that psychosis is quote disruptions to a person's thoughts and perceptions that make it difficult for them to recognize what is real and what isn't um and so so psychosis is a symptom, not a disease. It's a symptom of conditions like schizophrenia and schizo effective disorder. But the I think an important thing to emphasize there is that psychosis is understood as as causing problems recognizing reality which is not necessarily the same as the kinds of experiences the perceptual disturbances that people might have on psychedelics where you can see things but you know, in many cases know that they're not really physically present. But I guess the question is, is there any empirical evidence about whether the use of psychedelics actually causes psychosis? Uh, there's a little bit. So I was reading a news feature for the journal Nature by Zoe Cormier which pointed to two different studies from recent years finding no link between psychedelic use and symptoms of psychosis or other mental health complaints. So these studies are not necessarily definitive, but this is what the evidence, at least as measured here, seems to indicate. So the first study was published in the Journal of Psychopharmacology and by Johansson and Crebs called Psychedelics not linked to mental health problems or suicidal behavior of population study. Here, the authors reviewed survey data from a huge population study comprising more than a hundred and thirty five thousand adults in the United States, and the cross checked the use of LSD, psilocybin, and mescalin. So the study only applies to those three drugs not necessarily to others. Uh, those three drugs versus reports of mental health problems. UH. And I should know that almost twenty thousand of the roughly a hundred and thirty five thousand adults in study had to use psychedelics, so that's about fourteen percent. They found no correlation. Quote after adjusting for sociodemographics, other drug use, and childhood depression, we found no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression, and anxiety. We failed to find evidence that psychedelic use is an independent risk factor for mental health problems, So that's one thing now. On the other hand, Cormier's article also cites an interview with Charles Grobe, a pediatric psychiatrist at the University of California, Los Angeles who is also an advocate for some use of psychedelics in certain clinical settings, and Grobe seems generally encouraged by the findings, but warns that we shouldn't conclude that there are no risks and says that individual cases of negative effects from psychedelic use do occur. One example, he gives his hallucinogen persisting perception disorder or hp p D, which is sometimes described as like the never ending trip. It involves like repeated or incessant or invasive disturbances of the visual field or shimmering lights or seeing dots or something also known as acid flashbacks if you will, uh Grob gives a quote saying, quote, I've seen a number of people with the symptoms following psychedelic experience, and it can be a very serious condition. Right. Uh. You know, we have an older episode from years back on this that I think was based in part of a two thousand thirteen study, and if I remember correctly, that study found that, you know, it's that it was extremely rare, uh and in a large part blown out of proportion by anti drug messaging, because of course that was part of the moral panic, is that everyone's going to take LSD and they're going to you're either gonna force yourself through a key hole or you're gonna deal with acid flashbacks the rest of your life, or it's gonna be the Blue Sunshine scenario. Right, but oh man, blue sunshine has got to be the best and ugliest psychedelic exploitation cinema. Yeah, and thoroughly not like non psychedelic really, but still worth seeing. If that movie, that movie is a tan shag carpet, it is just hideous starring Zalman King. But I I do have to to mention too that I remember when we aired this episode, and this was I think an episode I did with Julie Douglas back in the day, we did hear from a couple of listeners who insisted that they had experienced acid flashbacks at some point in their life. So, I mean, the the accounts are out there, there is uh, you know, at least they're at least accounts of people dealing with these and and you know, claiming to deal with the reality of of acid flashbacks. So um, you know, perhaps more studies needed. Well, I mean, according to grow Is, it's not like that they're serious doubt that some versions of these things exist. The evidence seems to show that if to whatever extent these problems do exist, they're rare enough that they don't really show up statistically right. Well, then you know, and also wonder too, like what other factors are involved there, Like if if you have had a psychedelic experience and it was meaningful, as a lot of them end up being they ended up being something that stick with you and they give you a glimpse of, you know, something that is in some way hallucinatory, and then later on you have some sort of hallucinary UH experience that is tied to another UH situation, like you might have a tendency to interpret it as being linked to that original use. Well exactly, Yeah, there's a correlation causation issue here. I mean the authors of the first study, Crebs and Johansson I mentioned, they point out that these symptoms of hpp D also occur in people who have never taken psychedelics that you know, so there could be there could be a causality issue. Decide another study. There was a study by Hendricks at All in the Journal of Psychopharmacology and called Classic Psychedelic Uses associated with reduced psychological distress and suicidality in the United States adult population. So this study looked at an even larger sample, about a hundred and ninety thousand survey respondents. It also found that the use of those three psychedelics was not and again I mentioned earlier, it was LSD, psilocybin, and mescalin, so not not necessarily applying to the others. Those are the classic psychedelics, I guess, so the psychedelic classic, not to be confused with your classical psychedelics, not new psychedelics. Anyway, this study found that those three psychedelics were not associated with any adverse mental health outcomes. The study actually found some evidence to the exact contrary, People who had at some time used LSD or psilocybin had a lower life time risk of suicidal ideation or suicide attempts, though it's not clear that the psychedelics cause these lower rates of suicidal thoughts and behavior. Maybe there's some factor not controlled for that makes people both less prone to these problems and more likely to try psychedelics at some point. But it is worth noting that the use of other non psychedelic illicit drugs was mostly associated with increases in risk for past months, psychological distress, and suicidal thoughts and behaviors. The psychedelics appeared to be the exception. They were the drugs that that did not cause increase mental health problems. And so, to go back to Cormier's article, this was written up with a with a quote from one of the authors of the paper saying quote the author was Matthew Johnson, saying, quote, we're not claiming that no individuals have ever been harmed by psychedelics. Anecdotes about acid casualties can be very powerful, but these instances are rare. Uh. And he says at the population level that the data about the harms of psychedelics have been overstated. So again, we're not advising any particular plan of action or telling people to take psychedelics. I would say the bottom line from my reading on the risks of psychedelics is that there do appear to be some risks, but the risks are rare. There are risks to any drug. Any drug you're going to take, you should research from science based sources and and if possible, get medical advice before embarking on um. But then also those risks that do exist seem to be relatively low and relatively rare compared to the risks of lots of other known drugs. Yeah, ultimately, basic decisions on science and not on whatever the last horror movie you saw or or or comedy you know, you could go either way, right, depending on what you're watching. You can get a very skewed view of what a psychedelicy is and what kind of experience you can expect from them. Aren't Psychedelic comedy is generally more horrifying than psychedelic horror. I'm trying to think of what a good side. Well, you know, you're talking like the Monkeys movie, like head and uh and so forth, or Yellow Submarine. I don't know for a comedy. Okay, do we did? We run into the problem we envisioned we might, which is that we thought this was going to be the last part and then we only got halfway by the time we're what like fifty minutes now, Yeah, yeah, I think we're gonna need to cut this episode off. There's gonna be one more. So for everyone out there who is enjoying this, uh, this ride of psychedelic episodes, well then rejoice because we have one more for you. Um, for the rest of you, Well, just bear in mind, there's only one more. I mean, you can't get off. You gotta go all the way to the endpoint right right. Yeah, And our next episode, we're gonna we're gonna discuss some of what's been going on in the twenty one century where we are now in the psychedelic renaissance, and where we might be going in the future sounds great. In the meantime, if you want to check out more episodes of Stuff to Bow your Mind, head on over to Stuff to Blew your Mind dot com. That's where you'll find them all. You also, of course, can support our show in a few different ways, but the best way to do it is to tell your friends about Stuff to Blow your Mind. Uh. To make sure you have subscribed to this show as well as our other show, Invention, which is an exploration of human techno history and uh and I think we're planning to do an episode soon or have already done an episode on penicillin, depending on when you listen to this. Yeah, we will not have already done it. We will have done it. We will do it. I'm not sure where we will have agreed to do it. We will have agreed to do it. It sounds to me like you're struggling with mental time travel. It can be difficult with a two podcast schedule at any rate. Support Invention. Support Stuff to Blow your Mind by subscribing, leaving nice reviews, leaving some stars, and telling your friends about it. Huge thanks as always to our excellent audio producer Maya Cole. If you would like to get in touch with us with feedback on this episode or any other, to suggest a topic for the future, or just to say hello, you can email us at contact at stuff to Blow your Mind dot com. Yeah. Stuff to Blow Your Mind is a production of iHeart Radios How Stuff Works. For more podcasts from my heart Radio, visit the iHeart Radio app, Apple Podcasts, or wherever you listen to your favorite shows. H