How Psilocybin Helps us Learn with Andrea Casanova

Alisa Nappa August 21, 2024

Today we sit down with Andrea Casanova who recently published a paper exploring the influence of psilocybin on subconscious and conscious emotional learning. Does eating magic mushrooms help us grow intellectually and emotionally as humans? Does it depend on the dose, set, and setting? Tune in and shroom in to find out more.

TRANSCRIPT

Unknown Speaker 0:00 Alex, Unknown Speaker 0:12 welcome, welcome. You are listening to the mushroom revival podcast. This is your host, Alex Dorr, and we are absolutely obsessed with the wonderful, wacky world of mushrooms and fungi. We bring on guests and experts from all around the globe to geek out with us and go down this mysterious rabbit hole to try to figure out what the heck is going on with these mysterious fungal beings. And today, we have Andrea to talk about Unknown Speaker 0:40 how psilocybin could potentially improve our learning capacity, and how Unknown Speaker 0:48 this this study is, is very interesting, and I'm really curious, because, you know, it really depends on the dose and and I would love to get into that more. But before we jump in, Unknown Speaker 1:02 who for people who don't know who you are, like what? What are you up to? Where are you? Where are you tuning in from? Unknown Speaker 1:10 Hello. Thanks for having me. My name is Andrea. I'm a medical doctor doing my resident residency in psychiatry in Switzerland. Unknown Speaker 1:19 Well, Switzerland is the country where LSD was discovered in the 1940s by Albert Hoffman. He was this chemist, and many don't notice as well that he synthesized psilocybin. Unknown Speaker 1:31 This all just came out after I discovered all this mushrooms, and it was quite a nice coincidence, seeing that in my home country there was a lot of things going on, and Unknown Speaker 1:44 it has a lot of history with this. Unknown Speaker 1:46 I worked with part of my thesis during my studies in a team which did, or is still doing, psychedelic research. It's a professor called Franz holenweider who was one of the guys who restarted the psychedelic research in the 1990s Unknown Speaker 2:02 and my thesis was just one part of I participate in a study where we gave psilocybin to some health participants, and we did some stuff with it. We can talk about this, I think, yeah, but, but first, I'm curious, how did you get introduced to the world of mushrooms and psilocybin of mushrooms. Well, I think in the end, it was just a YouTube algorithm which Unknown Speaker 2:28 recommended to me a random lecture of Terence McKenna. I don't know if you know him. Oh, yeah, definitely. He's a psychedelic philosopher or psychedelic Bard, indeed. OD, I don't remember which one, but as I was recommended a lecture many years ago, Unknown Speaker 2:45 four hours long, and in the beginning, I just I didn't understand much it was going on about the mystery of language, the transcendental object, the end of time, and many other things. And there was, Unknown Speaker 2:55 I wasn't I was not getting what he was going on in the beginning. It all sounds a bit Woo. Woo. In the beginning, it sounded so magical, but at the end, I was hooked for his narration style and and I felt like there was something deeper to it. And Unknown Speaker 3:12 yeah, I and then doing my studies, I saw that there is research going on. And as I said, there is some history in my country with psychedelics. And I think this is quite helpful for research, despite it being harder many other countries the history of it helps that there is more research going on in Switzerland, maybe, than other countries, definitely. And then I I asked, then there was lucky coincidence that there was a position open for, for one of the, for one of the, Unknown Speaker 3:45 one of the studies that were going on, Unknown Speaker 3:48 yeah, that was a few years ago, and then we started the study that took us about three or four years, all in all, to quite long. And then, you know, some data analysis. And the paper came out about a month ago. Unknown Speaker 4:01 What? What are the current laws in Switzerland, with psychedelics and specifically soul seven things are changing so rapidly recently I can't keep track of what, where places are legal and Unknown Speaker 4:14 medicalized and things like that. It's, yeah, the laws are been changing the last few years so rapidly I can't keep track. Everything is changing so much, indeed, in some countries, faster than others. In Switzerland, it started in 1990s with fallen by them, but my professor, we restarted the research in this country, and since then, it has been growing in also other universities in my country. But the the legal status is still illegal. You cannot possess it, you cannot consume it, but it is allowed for research. And there is like a gray zone which allows psychiatrists, which have a special license, they can ask for a single patient. So if a single patient comes to you with single amino script. Unknown Speaker 5:00 Patients come to it's not given out as a license for a psychiatrist, but it's given for a specific patient, that if a patient is, for example, treatment resistant in some kind of disease, Unknown Speaker 5:12 mental disease, then you can ask the government if they allow a special license for this one patient, so you can apply it legally. So it is still illegal to actually consume it. It is legal to do research with a lot of caveats, a lot of ethical things, sort of ethical workup. You can actually use it in rare cases, in psychiatric treatments, actually, just to a small point here as well, in the clinic where I'm working there. Also they started using it as well. So it's not only single psychiatrist in the practice. Now they also start to introduce it in the clinic. So it is there, specifically, it is in the Depression ward that is used for some treatment resistant cases as well. And it's not yet in like in other countries, Unknown Speaker 6:02 where it's Unknown Speaker 6:04 quite restrictive too, and so it was pretty hard to get the permits required for this study. Yeah, it was, and it was one of the hard parts. It was quite strenuous for my supervisor, actually, to ask about an ethical committee, Unknown Speaker 6:20 because it took some years, I think, one to two years, to just wait on the ethical Unknown Speaker 6:26 how was it called just the ethical? Ethical committee allows, gives the green light. But since the research has been going on already in the lab, of course, it's facilitated. If you just come as a newbie and say, I want to do some research with with this substance is much harder. So it speaks if you already have some history of it, it speaks that you already know how to handle the substance. You can handle the possible negative consequences or the very positive consequences as well. Unknown Speaker 6:53 That makes it harder, but it is possible, and it is applied to few universities in my country as well. So for people who haven't read your paper or heard of your latest paper, can you give kind of a brief synopsis of what you're studying, maybe some key results that that you found? Unknown Speaker 7:11 Sure? So the paper you're referring to was published a month ago as part of my doctoral thesis that told us the start is called the influence of psilocybin, subconscious, unconscious, emotional learning. Unknown Speaker 7:26 So we had some ideas of wanting to test psilocybin with regards to learning, since it is being now applied more frequently in psychedelic assisted psychotherapy, and my team is neuropsychopharmacologically interested, but also medically interested. So it's more about ground research, seeing how receptors work, but also if it can be successfully applied in therapy. And we wanted to see if there is any changes in learning, since you want to give psilocybin in a psychotherapeutic session, then see if, if learning can occur better, worse, Unknown Speaker 8:03 or Unknown Speaker 8:04 just a study how learning changes with it, Unknown Speaker 8:07 some results with it. It came out that we gave it with three different dosages. It was weight dependent, but still, the dosages can can still work differently, even if you receive a higher dosage of being a bit more if you have more weight, one result that you mentioned the beginning, I think, in introduction, was that, surprisingly, the higher dose of psilocybin, which is 20 milligrams of psilocybin, that yields better results in a learning task. Unknown Speaker 8:40 Just to say what actually we were measuring is that we were doing this in in a learning task. It is a probabilistic fashion which is measured with we give healthy participants, we give them psilocybin in Unknown Speaker 8:55 double blind fashion, so we don't know when the participants don't know if they receive the substance, and it's a crossover study. Two weeks afterward, you receive a second one, which is just mannitol, the sugar. And Unknown Speaker 9:09 participants had to undergo first some measurements, which was part of the main study about TMS and EEG measurements, and just transcranial magnetic stimulation and EEG measurements. And after a few hours, then they went on, and Unknown Speaker 9:27 they started with the learning tasks, which consisted of them being bombarded with many symbols, and the symbols yielded sometimes money and sometimes they did not, and they had to find out which symbol was better than another one. And while under the influence of psilocybin, of course, maybe, as you know that the mind is in an more open and more spacious in a more maybe colorful environment, and it's a little bit more destabilized. And we wanted to see if. Unknown Speaker 10:00 Can Unknown Speaker 10:01 infer Unknown Speaker 10:03 if you can have if you can preserve some strategies, if you can still Unknown Speaker 10:08 learn Unknown Speaker 10:11 in which in which direction you want to go. And this is one of the hard parts, because, for example, money is something that may lose significance under psilocybin, this was the main incentive that you give. You give money if you are successful in doing this. And actually, some participants, they said that, well, for them, it wasn't important about gaining or losing money after, all right, they were just going after the fun, the nice green lights, which were flashing when you were successful in getting finding the better symbol. Unknown Speaker 10:40 All right, that was just a learning task, and what when, additionally, part of the title was subconscious, conscious and emotional learning. And in the end, it came out quite complex, but we wanted to see, since we were already doing a learning task, how emotions were influencing learning. Since in the same group, there was a paper published seeing with that fearful faces or less recognized, since the amygdala, one part of the brain is reduced, the right amygdala is reduced to recognize less the fearful faces. But in other studies, we were seeing that the fearful faces where we're giving a more positive result with regards to learning short term, so to see how this actually changes with regards to psilocybin. Unknown Speaker 11:32 So yeah, that that was what I was curious about. So if you can give kind of an example, or a couple examples of what someone would see on the screen when they're doing this, this test I was reading that they would be shown two symbols with social cues, a neutral and fearful face. So what, what kind of symbols are they shown? And what? What is the what is the task? Like you said, Pick the better one, what, what does that mean and what? What symbols are they shown, and what would be the right answer and wrong? Unknown Speaker 12:07 All right. Participants who are starting this learning task were first presented just with a fixation Cross, which where was going into two symbols. Two symbols were Chinese symbols, Unknown Speaker 12:19 and we altered them sometimes for the chance that maybe someone actually knows Chinese. And these two symbols were just left and right in the screen, and you had to choose left or right, and then immediately you got a result. Unknown Speaker 12:35 Result was, if it is the better, if you gain money or if you lose money with this. If you found a successful symbol, Unknown Speaker 12:43 what I didn't say now that before the symbols appeared, there was a social cue in form of an emotional, emotional face, which was either neutral or a fearful face. And these were presented either consciously or subconsciously. So this means that they were presented either quite fast, if they were subconsciously so they remain remain hazy. So it's one study found out that subliminal cues can actually foster learning. So since you, you are, if you, if you are under the influence of subliminal cues, sometimes there is an activation, since there is something going on which you cannot quite understand and which which forces you to actually be more present. And Unknown Speaker 13:31 we wanted to see if there's also influences psilocybin as well. So to go back to your question, how the task was going on, there was a fixation cross. There were two symbols. What is a fixation cross? Just across, just across, to see that the task is starting. Okay, and then the task was starting and you were about, you had to choose, if you had to choose which symbol you preferred more in the beginning. Of course, you didn't know which one of these two were much better. And so you just choose one of these, and then Unknown Speaker 14:03 there was an immediate feedback if it was better or worse. And by better or worse, what do you mean? Unknown Speaker 14:12 I mean that if you got the correct symbol, that means, this means that you got a result, a feedback that you gain. You gained some money. You gained, for example, in our in our task, you gained some monetary reward. And the other symbol was inferior, which would take away money. But this was also a bit more difficult, because it was a probabilistic fashion. So the better symbol, the one giving you money, was only giving you money in 70% of the cases, while the other, the inferior symbol was Unknown Speaker 14:46 removing, was taking away money in 70% of the cases, and 30% of the cases were giving you money as well. So it was all a bit uncertain, and this level of uncertainty required the participants to always be proud. Unknown Speaker 15:00 And always adapt the strategies. For example, if you find the correct symbol, so I say correct symbol, the one which gave you some positive monetary reward. A number of times you say, I will always choose this symbol. But then after the fifth time, it gives you a negative reward. And then you who maybe thought I found, of course, the correct symbol. Have to readdress it and see if you actually want to change it. For example, if it comes a second time, five times you get you get it correct. Correct means plus 10 francs, for example, which is our currency here, and then two times minus 10 francs. What? How do you? How do you continue? Do you choose the other symbol or not, and we will compare this with people then Unknown Speaker 15:44 psilocybin and the placebo to see if there was any change someone could Yeah. So heroes about to ask, you know, would you show the same, you know, say, say, you showed two symbols. They pick, uh, Unknown Speaker 15:59 quote, unquote, the right one. They got the money the first time, and they're like, oh. And then the second screen, they see that same symbol again. You know, I would pick that same symbol being like, Oh, that was right the last time. I don't really get the test, but I'm gonna pick that again, say it was right the second time. Like, Oh, okay. They want me to pick that symbol again and again if it was wrong. Like, how are you measuring learning? Because it seems like it's random. So what? Unknown Speaker 16:26 Where is the learning? And maybe I have to be on more psilocybin right now to understand it. But Unknown Speaker 16:34 yeah, like, how are you measuring learning? If it's random, Unknown Speaker 16:39 it is not fully random. It is more likely that one symbol was giving a higher reward, and the difference of the randomness and this higher probability was captured by the probability of you finding which one of these two symbols and we always chose in one single task, we always choose the same tools which we shown did show the same two symbols. The Unknown Speaker 17:05 probability of you finding which one is better, and in the beginning, since you don't know, it was 50% of course, it was random, either left or right, and the amount of learning is if you, Unknown Speaker 17:19 if you more frequently than not. Do click the button which is better. And so we do find you. You gage which symbol is better or not. And we plotted this with a learning curve, which just goes up if you already in during the task. Unknown Speaker 17:37 Do find out that one symbol is better, and if you don't, then, of course, it remains either flat or it goes down the line. And we can plot this, and in the paper, you can see that it goes up for both so for psilocybin and for placebo. After a while, after some learning happens, you find out that one symbol gives positive results more frequently and the other gives negative results more frequently, finding out this, this difference, this historical learning, actually is. So it's all quite complex you understand, and yeah, even more complex with conscious and subconscious views, with neutral and fearful things. So in the end, it's very complex to talk about. In the end, it was all modeled, and there was a lot of statistics grown on it, and the results then came up and can be read in the paper. But if it is this quite complex to understand that the first time to talk about it, so Unknown Speaker 18:33 the the conscious and unconscious social cues, the neutral and fearful faces, what effect did those have? You know, flashing them on the screen beforehand with the fearful face, Unknown Speaker 18:49 make people second guess and pick the wrong Unknown Speaker 18:53 symbol. Or what? What results do you get from that? Unknown Speaker 18:58 So, in a start, this without psilocybin, it was seen that fearful faces can actually increase attention, arousal, vigilance, and can actually accelerate short term performance. Another study of our group show and did show that fearful faces were less recognized. So we assumed that there was less recognition, of course, of fearful faces and those less learning with fearful faces, Unknown Speaker 19:22 but we didn't see this in this study. Unknown Speaker 19:26 What actually came out is that subconscious cues, which in other studies were some kind of incentive of being more present, were more destabilizing in our study, since they probably just required too much attention in trying to categorize this emotion cue. And one hypothesis is that there is an reduction of top down thinking. There is this idea of bottom up and top down information flow in the brain. And with psychedelics, there is less top down, top down reduction. And since there is this reduction in this. Unknown Speaker 20:00 Harder. It takes longer to actually categorize some information, and hazy cues require much more attention than if they were quite clear. And so these subconscious cues were detrimental actually in learning, they were not so they they were actually worse than other cues with psilocybin and with placebo Unknown Speaker 20:22 and but overall, there was not. There was another large difference. So overall, because it was also quite a surprising task, that in all the different dosages, despite the higher dose, even faring better, there wasn't a large difference of psilocybin and placebos. There was no statistical difference. And there was no difference as well in Unknown Speaker 20:47 comparing the highest dose and placebo. Unknown Speaker 20:52 Compared the highest dose, it was better than placebo. But overall, if you compare everything, then there was the difference. But if you only compare the higher dose, the 20 milligram dose, than it was actually better than placebo in learning. That's quite surprising. In the end, I read somewhere in the paper that the medium dose actually did worse. Unknown Speaker 21:14 And this the second you you get to the highest dose, they you know, it significantly goes better. Unknown Speaker 21:21 How did, how did the lowest dose do? Unknown Speaker 21:24 The lowest dose only two participants. So in total, there were 13 participants. Since the lowest was only given to two people, it's hard to actually say something about it, but there, Unknown Speaker 21:37 yeah, it was. It was better with placebo than with with 10 milligrams of psilocybin, with 15 milligrams, so just a medium dose, their placebo was better, and with 20 milligrams, the highest dose we gave. Unknown Speaker 21:53 And, yeah, this is a cavity. Of course, people were a bit heavier receiving this, but still, the effects sometimes seemed even higher, even if you are a bit bit from the heavier side, even if 20 milligrams, you can have more effects than 15 milligrams. But this was a bit better. This was statistically better than placebo. Surprisingly, do you have a theory of why that is? Do you think that people on the medium dose kind of had more of a Unknown Speaker 22:24 they were, they were like, maybe mixed like, they had a foot in quote, unquote reality, and then they had a foot in psychedelic land, and they were kind of maybe overthinking things, and Unknown Speaker 22:36 maybe using those two worlds to like, overthink the the different cues and symbols. Whereas if you're on a highest dose, you're just kind of, you're fully in you're like, trusting your psychedelic intuition, and you're like, fucking, I'm just gonna do that. Whereas maybe a medium dose, you're kind of in both worlds, and you're more prone to, like, second guessing and overthinking, potentially, that's my theory, but I don't know. I'm curious to hear yours. It's a great theory, and we can approve it for now. And you say that maybe, if you are in psychedelic land, learning actually flourishes. It can be and I would like to see another study actually seeing the higher dosage and even higher dosages comparing and maybe easier and maybe easier learning tasks. Unknown Speaker 23:21 It is a great question, because I don't know how actually this precisely, but one hypothesis is that higher doses lead to just greater receptor activation. Psilocybin activates a few receptors, mainly the two, a receptor, the one, a receptor of serotonin. And if you have more activation, then you may amplify the intensity of the experience. Maybe be more present because of that. You can also maybe, as you say, be in this hazy stage of one foot in, and then there are some conflicting inner voices still there. And if it is high enough, these conflicting inner voices are maybe not present. And then you are in the psychedelic flow and can go into the learning field. But I also have to say that it was weight adapted. So it is impossible to see if someone with 15 milligrams with a lower weight had a similar or less experience as someone which wasn't 20 milligrams was a bit heavier. I personally saw some participants which were tripping quite hard with 20 milligrams, despite them being heavier. This is why I said in the beginning that it might be that they were sometimes giving higher experiences, stronger experiences. What Additionally I want to mention here is that, of course, there are multiple hypotheses how psychedelics actually work, and some of these have come out recently, some already, probably years, and one of those is the default mode network, and it's part of the brain, or the complex of the brain, part which is Unknown Speaker 24:58 responsible for the sense of self. Unknown Speaker 25:00 And this internal dialog. With psilocybin, you can, you disrupt this default mode network activation, you reduce it, and with a higher dose, it may, it may more significantly disrupt this default mode network. And with this you maintain, usually, a sense of self. And with this reduced, and maybe less of that. Unknown Speaker 25:23 Then, as you said, maybe you're just in, you're just in, and you're going, Unknown Speaker 25:27 I'm also, yeah, I'm also curious about, Unknown Speaker 25:32 like, confidence level as well. I I've had this interesting phenomena where, Unknown Speaker 25:39 and you know, like you see it in TV shows and things like that, where you see, like, a lot of times they, they poke fun of it, of like, people smoking weed or something, and thinking they have like this, like, really profound realization or Revelation. Unknown Speaker 25:55 But really, they're just really high, and it's actually, like, a really stupid idea, but they, they think that they're having this, like, really profound, like, insight, you know. And I've had that experience where, like, I'm on a high dose of mushrooms, and I think I'm, you know, and I'm certain every atom in my body, I'm like, this is I am so clear right now. And I'm like, I figured it out, and whatever. And then, you know, days later, I look back and I'm like, that was the dumbest thing, Unknown Speaker 26:23 you know. And like, sometimes it's actually good, great, you know. It's like, a really profound insight. It's really amazing. And other times it's just, like, off the fucking rails, Loony, like, just dude, what do you you know? And I'm curious, like, if that potentially had a Unknown Speaker 26:42 something to do with the learning, and I'll give a little example, like I I used to microdose psilocybin every single day. And when I started college, I took, I never took chemistry before ever. And I started with college level organic chemistry. And the professor was like, You should not take this class. You've never taken chemistry before. Usually people will take high school chemistry, then take, you know, like college level chemistry, one then organic chemistry. She's like, this is way too big of a leap, and it was micro dosing. And I'm like, super confident. And I'm like, no, no, I could, yeah, I could do it. And then, literally, the second I ran out of micro doses, I failed the class and everything, like, when I was not on psilocybin, just stopped making sense. And I was like, what? How have I been in this class for like, two months and skating by? Because nothing makes sense to me right now. And I think it never made sense. I just feel like my psilocybin self was, like, convincing myself like, oh yeah, I got it. Like, this is totally makes sense. But really, in actuality, it didn't. And there's that, like, false sense of confidence sometimes that Unknown Speaker 27:59 people on plant medicines or like substances get Unknown Speaker 28:03 where, like a sober look person looking at them like, and third person is like, No, you're kind of idiot, right? Unknown Speaker 28:13 I don't know if that I read at the end of the paper that Unknown Speaker 28:18 and this might go against what I'm saying, but that Unknown Speaker 28:23 maybe in the discussion that you're talking about, like people on psilocybin were Unknown Speaker 28:29 at like, Unknown Speaker 28:32 like, Unknown Speaker 28:33 having more second guesses. Is that correct? I don't know if you remember what I'm talking about. I read it super late last night, so it's a little blurry this section of the paper, but Unknown Speaker 28:45 something about, you know, in following up with with people on psilocybin, that they were second guessing themselves and saying that they were maybe a little more impaired than they really were, and that you Were seeing them as as as getting all the right answers. And then they were saying that in their experiences, it felt like, yeah, that they were, like, really high, really, like, out of control and not getting the right answers. And you're like, Well, based on the data you're you're doing well, so yeah, yeah, that's a great example you brought of your college, and this is this question of subjective and objective performance. You feel like, subjectively, you're full of confidence, and you can conquer the world, perhaps, and then objectively, just just talking nonsense. It makes no sense with the talking, but for you, it is full of meaning. Everything is connected, but no one can understand you. For me, the most important take and take away from the study was that despite participants feeling that they were performing quite bad because they were a bit impaired in thinking usually, of course, when you learn you're not in you're not giving, you're not taking 20 milligrams of psilocybin. So of course, the participants it was a novel experience. Unknown Speaker 30:00 Experience. But despite that, they were quite they were performing quite similarly to placebo, quite similarly to just sugar. Unknown Speaker 30:10 And for me, this was the main takeaway, because you have this sense that maybe you are Unknown Speaker 30:16 you are delighted because you're comparing yourself your usual way how you learn, but objectively, objectively, the performance was there. The performance was comparable, and sometimes even better than psilocybin, sometimes worse with the low medium dose, with the better with the higher dose, it was better. That, for me, was quite surprising, and this shows this for me, shows this discrepancy of how you subjectively feel you're performing, and objectively, objectively how, actually, how well you're actually performing. And I assume in some cases, of course, it may be quite a stabilizing and it depends what kind of things you want to tackle for despite it was hard to actually, for me to explain how this learning task works, it is quite simple. If you just sit down and have to click left and right button. And everyone can do this, of course, would agree. But if you want to do some, if you want to tackle some more important questions, maybe then it is harder to see that you're objectively doing well on psilocybin, maybe then just talking nonsense, that nonsense despite you feeling fully confident, and in the end, it's just you just wrapping around some some random things in the wall. And makes no sense to other people, but for you, it's totally, fully there. And that was quite interesting, just for me to see. So I'd love to get your take on this. I assume you speak multiple languages. Is that correct? Yeah, yeah. English is not my main language. It's quite rusty right now. So yeah, Unknown Speaker 31:45 have you heard and because I've heard this before, where you know people who who are teachers in different languages, they recommend that you Unknown Speaker 31:57 get drunk and try to speak another language, or, like, at least get tipsy, because it helps like you're that confidence level to just not overthink things, and just you have the confidence to just, like, just say it, you know, and not feel like you're being a buffoon, like, like, incorrectly speaking a language. And that actually helps learn languages. I've heard that a lot of times. And Unknown Speaker 32:24 you know, Unknown Speaker 32:25 another, another side thing is that, you know, for people with cannabis, I read this study recently, that Unknown Speaker 32:35 it seems like either like half the people smoking weed, they'll get super anxious and paranoid or really relaxed and, you know, carefree and and social and be able to whatever. The study that I read, I don't know how many years ago now it it showed that depending on where the majority of your cannabinoid receptors were in your brain, and this changes with age, is if you have more cannabinoid receptors in your fight or flight sector of your brain versus your I think rest and restore area, you're going to have more of a paranoid, anxious response when you smoke weed, just because that's where more the cannabinoid receptors are in your brain. And it's really just brain chemistry and location. And I'm curious that being said, like, given my, Unknown Speaker 33:27 um, some of my reactions with, with being on psilocybin, and like having this, like, sometimes, not all the time, like, overconfidence, where my, Unknown Speaker 33:37 uh, objectively, my performance is, hindered at sometimes, sometimes it's opposite. And then people in the study where Unknown Speaker 33:45 objectively, their performance is really well, but subjectively they're a little self conscious. I am curious with everything I just said, if we have receptors in our brain that, Unknown Speaker 33:58 and I don't know if you've read anything, or if you've thought about this that you know in people like, say, those people in the study who were subjectively thinking that they're doing pretty poorly, like they're just having more receptors fire off in their fight or flight sector, and they're having more of an anxious response, Unknown Speaker 34:18 whereas other people that are like, Yeah, I'm fucking killing this ever they're having more receptors in their like rest and restore, and it's really just brain chemistry, and I'm curious if that has an effect on learning. Unknown Speaker 34:33 If you would know what kind of receptor activation profile you have, you can do yours with you, Unknown Speaker 34:39 if you then you would know actually, how you would react, yeah, just the first, first part of your your comment, I think that's great to say that when you are in a substance, you're given a lot of teachings. And then, of course, the question just gathers, if it's necessary to actually have the substance, if you just, you're you're actually thrown into a state or. Unknown Speaker 35:00 More receptive to this, but is it actually necessary to be on the substance? Is this catalyst actually necessary, or is it actually possible without the substance? So one large field which doesn't really exist much, I think we're not talked about in the psychedelic field of psychedelic research is meditation. But much of the research, much of the insights, Unknown Speaker 35:20 are the same. Unknown Speaker 35:23 Can be reproduced with just meditation, of just sitting, as opposed to taking substance. But of course, it's much easier to get it, to get a substance, and it's just in and out, and then you're you're there for a few hours, you say, in psychedelic land, and get out. But it's not per se. Is it per c necessary to actually have this perhaps. With regards to the receptors, it's quite complex. Psilocybin activates the multiple receptors. And I don't know if you can say this is just receptive activation. Saying it's two a activation in the cortex, one a activation in the limbic system, which actually induces this experience. I think the brain is much more complex than that, and this is why a lot of research exists, because we just don't know, and it might be too complex a model or too unnecessary a model to actually try to say, this is, this is like this simplistically, materialistically, it is because of this. What I want to say is just very complex. We don't really know there are multiple receptors going on in psilocybin Sybil, it's mainly the two a serotonin receptor, which is mainly in the cortex, one hyphae. Is that the two a receptor promotes active coping when it is activated, and the one a receptor, the One A serotonin receptor promotes passive coping. And these things depending, of course, if you have more of the two, a receptor, more of the one, a receptor, every human is different in that regard, will also, to a degree, affect your responses. But you have much more than just receptors. Also, we all have a much more complex inner orchestra, and depending on how what is, what music is going on there, you will have another experience, irrespective of how many, if you have totally more receptive to someone else, absolutely and just as an aside, what is active and passive coping. Unknown Speaker 37:15 So this is a Unknown Speaker 37:17 paper which came out from Robin Carhart Harris. So a few months ago, I think Unknown Speaker 37:24 just trying to practice this dual role of serotonin receptor, of main dual role of serotonin on how it works, depending on which receptor is activated. Unknown Speaker 37:37 Too familiar, because I mentioned a few months ago, but what I gathered from that is that the one a receptor promotes when it is activated more of an passive coping mechanism. So for example, you're just going on with Unknown Speaker 37:50 with life and accept what things, the things come to you without actually trying to change them. You just there and maybe suffer through it. Unknown Speaker 38:01 If the one a receptor is activated, then also, Unknown Speaker 38:06 if I remember correctly, there is a reduction of stress. And because of that, there is more coping, which is possible with the two a receptor. On the other hand, it is more, as I said, active coping. And if I remember correctly, Unknown Speaker 38:21 this two a receptor in that paper, specifically, they said that because it increases entropy, so this chaoticness, Unknown Speaker 38:31 the chaotic state of the brain, you have less rigidity, and with that, you have more flexibility and have more of an active way to actually change your environment and just adapting to an environment. And this is the question, if it is correct to actually classify this but they saw that this one a receptor goes to the activation of this receptor. One A leads to your adapting to the environment, whereas the two a receptor um, may give yourself a changing change. It changes your environment, yeah, but I haven't read much research about it as well. This was just one paper read some months ago with I mentioned, I don't know if this was debunked or actually improved upon, but I found it interesting to see, because for our paper, specifically, SSRIs and they work mainly on the one a receptor, which could promote this passive coping, while psychedelics mainly work now. So the main activation, of course, they activate also the one a receptor, but the two a receptor is mainly responsible for effects. This was shown by blocking the two a receptor mainly that the psychedelic effects were diminished or just reduced completely as well. So we want to see if SSRIs, which were, of course, given for depression, that Unknown Speaker 39:49 one a receptor, how this is affected differently by giving a two a receptor, agonism by psychedelics. Wow. I Yeah, definitely. Unknown Speaker 40:00 Have to read carhartt's paper after this. That sounds really interesting. Unknown Speaker 40:04 Yeah, that's that's crazy. And I know you brought it up a few times Unknown Speaker 40:11 about, you know, only having 30 participants, and you wrote about it in the paper that you would like to do future studies with more statistical significance. What other things would you like to test for in the future? What other follow up studies would you like to do? Unknown Speaker 40:29 Yeah, Unknown Speaker 40:31 so of course, if you have infinite money, then, of course, you say, then we can just improve upon everything. And in that regard, that just more more participants Unknown Speaker 40:44 than more frequent doses. Since it is quite time intensive to actually give psychedelic substances to people, and quite labor intensive as well, many people have to be there and give a safe environment for us. It was quite a tiny room with a lot of noises going on, and you were, there were many cables around you, and Unknown Speaker 41:05 the setting was quite hard and but still quite it went very well. Unknown Speaker 41:11 It would be nice. I It would be nice if there was a Unknown Speaker 41:15 research going on specifically for that. For us, it was a tiny room. It wasn't that. It wasn't specifically nice for for psychedelic sessions. If there was Unknown Speaker 41:24 a room in nature, a room away from from disturbing, Unknown Speaker 41:30 disturbing influences, the way these substances can be compared other substances as well. And for me, not only, not only mushrooms, is interesting. I would also not I would also introduce meditation as something which is quite interesting in the study, as a study to compare, of course, on substance as well. Unknown Speaker 41:51 For me personally, I'm quite interested also, just to read a bit more about this receptor activation profile on the role of these different receptors, despite it just possibly not leading No, not bleeding anywhere. But it is nice to just have something to stand upon, although it's not really necessary, but I like as well to Unknown Speaker 42:11 geek out on these different receptors. And yeah, that'd be good. But yeah, if, if more money would be there, I think then some research is going on now in Switzerland, which they change from psilocybin to so in another city, they give LSP, who have been given LSD for a while now, they start to give other substances and to see what research can can come out of that. And then, in the end, we have a lot of a lot of papers about different about different substances, and then the goal is to apply this in psychotherapy. So ideally, you want to, you want to go somewhere. So for me, this is personally important, that it can be applied somewhere, and not just be taken in, in your in your room or somewhere to just Unknown Speaker 43:01 self medicate, but if this can be applied successfully in psychotherapy, for example, and Unknown Speaker 43:09 what would you say was the hardest part of this research, getting the initial permits for, you know, you said a year or two, was it getting funding for for the research, was it Unknown Speaker 43:22 analyzing the results like, what? What would you say is, was the nails on the chalkboard for for this, this research, I think the nails the chalkboard was not for me, personally, was for my supervisor, who had the largest part of actually asking the ethical committee to approve for this research, and despite it already coming from a group which did some research on psychedelics. It's, every time it's it takes a lot of a lot of time for it to accept, I think, one to two years for it to be accepted. Of course, in the meantime, just wait a lot of things. Unknown Speaker 43:56 Just wait for the receptor to start and yeah, that was the hardest part for me. Personally, I think it was quite a time, time intensive, because you had to be there Unknown Speaker 44:05 for one every participant took almost one full day, and we gave it two times. It was 60 participant. I wasn't present for all the 60 measurements, but there was a for many of them, and it was just quite, quite time intensive, intensive. Unknown Speaker 44:22 And as well, what is also, what was also hard, was just to balance complexity, to see how much we wanted to measure and how much we can actually analyze with these measurements and without having been done. So there wasn't much research with learning. So there wasn't one task of MSP with reinforcement learning on the suicide it has been done to my knowledge, and so we were the first to actually apply this without knowing if we were gathering too much data, if it was just too much to giving all these emotional cues. In the end, it just came out in the statistical analysis that it was quite. Unknown Speaker 45:00 It quite quite complex in the end, to model everything. Unknown Speaker 45:04 And it was hard to talk about this right now, how now the talk was going on then now this was also at one step. Took one step longer than just to measure, to analyze everything correctly. Unknown Speaker 45:21 But yeah, Unknown Speaker 45:23 yeah. Well, thank you for making this study and crunching all the numbers, getting the permits, doing, doing everything, and for your supervisor as well. Unknown Speaker 45:33 I'm, yeah, I'm super curious about follow up studies for this, and I think this raises more questions than it does answers, which I feel like the best research does, and Unknown Speaker 45:44 that's the goal. That's the goal, Unknown Speaker 45:47 yeah, and the more you know, the more you you know you don't know. And, and I think that's, that's the learning, learning curve for humanity and life itself. So where can people follow your work? Any follow up studies get in touch with you. Any anything that you and your team is doing, Unknown Speaker 46:05 yeah, if you have any questions, and more on, on if you have any questions, how I explained it? Because I think it wasn't quite easy for me to explain this as well. Unknown Speaker 46:15 You can write me an email, and you can find this all on my website, which I just put up Andrea casanova.ch Unknown Speaker 46:23 This is my guess. CH is the Swiss ending. And then if you want, you can also subscribe there. I will then post very roundly if there is some new research going on. Unknown Speaker 46:35 Sweet. Well, thank you. Thanks for coming on, and thank you everyone for tuning in and shrooming in for another episode of the mushroom revival podcast. If you like this episode and you learn something fascinating, you have more questions, definitely, please tell your your friends family, have a conversation about it. You know, Unknown Speaker 46:57 it's really a cultural movement at this point, and just having more conversations about mushrooms, about psilocybin, about psychedelics and and getting more people aware of of these phenomena and these organisms. And yeah, if you if you like the show you want to support, we don't have a way to donate directly financially. We don't have a Patreon or anything set up like that, but we do have a mother company, mushroom revival, and we have a whole line of organic, functional mushroom products from capsules, powders, tinctures, gummies. And we have a special coupon code just for the listeners of the podcast. And that code is pod treat for a surprise discount code. If you don't want to spend any money, that's totally fine. We have a giveaway going on, and we pick a winner once a month to win some mushroom goodies. We also have a ton of free content on our on our website, from hundreds of blog posts to free ebooks that you can download. And we also have my newest book on the site as well, the little book of mushrooms. It talks about 75 different mushrooms with some beautiful illustrations. And if you're in the US, we're in bookstores all across the US, including non bookstores as well, like Urban Outfitters, we're in there as well. Unknown Speaker 48:15 And yeah, Libra review, it goes a long way. And as always, have a beautiful rest of your day, much love and may the spores Be With You. You. Transcribed by https://otter.ai

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Backed by world renowned mycologists100% Mushroom Fruiting Bodies3rd Party Lab Tested Backed by world renowned mycologists100% Mushroom Fruiting Bodies3rd Party Lab Tested Backed by world renowned mycologists100% Mushroom Fruiting Bodies3rd Party Lab Tested Backed by world renowned mycologists100% Mushroom Fruiting Bodies3rd Party Lab Tested