TrueLife - The Future of Psychedelic Medicine: How Psychedelics are being studied for their therapeutic potential - Jacob S. Aday

Episode Date: February 7, 2023

One on One Video Call W/George https://tidycal.com/georgepmonty/60-minute-meetingSupport the show:https://www.paypal.me/Truelifepodcast?locale.x=en_US🚨🚨Curious about the future of psychedelics? Imagine if Alan Watts started a secret society with Ram Dass and Hunter S. Thompson… now open the door. Use Promocode TRUELIFE for Get 25% off monthly or 30% off the annual plan For the first yearhttps://www.district216.com/https://twitter.com/jacobsaday?s=21&t=TBaLvVG06U5aFMXdDV_qDQhttps://www.researchgate.net/profile/Jacob-AdayMusic: https://youtube.com/channel/UCYQVuBQEJwKViT4yIDoCMFQMy research is broadly focused on the cognitive and social effects of psychedelics as well as improving research methodology and safety with the drugs.Research into the basic effects and therapeutic applications of psychedelic drugs has grown considerably in recent years. Yet, pressing questions remain regarding the substances’ lasting effects. One on One Video call W/George https://tidycal.com/georgepmonty/60-minute-meetingSupport the show:https://www.paypal.me/Truelifepodcast?locale.x=en_USCheck out our YouTube:https://youtube.com/playlist?list=PLPzfOaFtA1hF8UhnuvOQnTgKcIYPI9Ni9&si=Jgg9ATGwzhzdmjkg

Darkness struck, a gut-punched theft, Sun ripped away, her health bereft. I roar at the void. This ain't just fate, a cosmic scam I spit my hate. The games rigged tight, shadows deal, blood on their hands, I'll never kneel. Yet in the rage, a crack ignites, occulted sparks cut through the nights. The scars my key, hermetic and stark. To see, to rise, I hunt in the dark, fumbling, fear. Hears through ruins maze, lights my war cry, born from the blaze.

The poem is Angels with Rifles, the track, I Am Sorrow, I Am Lust by Codex Seraphini. Check out the entire song at the end of the cast. Ladies and gentlemen, welcome back to the True Life podcast. We are here with the one and only Jake. Am I saying this right, Adé? Adé, Adé, yeah. Jake Aday, he's a PhD from UCSF, the Department of Psychiatry. He's been writing quite a bit on psychedelics.

I'm going to go through some of the articles and papers that he's been digging into, and it's going to be a wild ride. He's written pretty extensively on a lot of interesting subjects, so I'm excited to talk to him today. Jake, thanks for being here, man. Is there anything else that I left out in your bio right there? No, I don't think so. Yeah, thanks for having me.

I'm really excited to talk about the field, and, yeah, answer any questions you have about any of my papers or just the field generally. Okay, fantastic. Well, I think maybe we could paint a little bit of background by saying that a lot of your work focuses on cognitive and the social effects of psychedelics, as well as improving research methodology and safety with drugs. So, you know what? One of the papers you wrote talked about, it talked about the long-term effects of psychedelic drugs. And in conjunction, before you start your answer, I was playing with chat GPT. yesterday and I want to read to you what chat GPT told me about long-term psilocybin and then I would like

to hear maybe a rebuttal and then maybe you could talk a little bit about what you have learned from the long-term effects of psychedelic drugs. Yeah, absolutely. It'd be interesting to hear what the chat came up with. Yeah, that's what I thought too. So here's, and I heard prompting is, you know, it's worth its weight in gold if you can prompt the computer the right way. So here's my question. Act as a neuroscientist, a shaman, and an ethnobotanist to predict the long-term effects, of long-term high-dose psilocybin on the brain behavior and evolution. And here's what it kicked back to me. As a neuroscientist, long-term high-dose of psilocybin can lead to changes in brain structure

and function, specifically affecting neural plasticity, synaptic connectivity, and the regulation of neurotransmitter systems involved in cognition and emotional processing. However, there is limited research on the long-term effects of high-dose psilocybin use, and more studies are needed to fully understand its impact on the brain. So pretty good for a neuroscientist, right? I mean, for chat GPT. So I thought that was interesting. What do you think? Yeah, that's solid.

And conservative enough that I'm comfortable with it. Yeah, because we really don't know much about the long-term effects on the brain yet, psychedelics. You know, that paper you're referencing the long-term effects of psychedelics. It was published in 2020. And there wasn't a single long-term neuroimaging thing. paper at that point published. So like all of the stuff that's come out, it's just been the last couple of years. So it's like very new and we're very much still starting to to prod that area of what's what's actually happening in the brain long after the acute effects of the drug have worn off.

You know, in that review paper, I think there was one study that did a neuroimaging test the next day, but it's not really a long-term follow-up by any means. And yeah, some of the, some of the, you know, the big neuroscientists in this area have started to address this recently in the last couple years. You know, Robin Carrard Harris's group has done some post-acute neuroimaging findings and looking at brain modularity specifically. And the Hopkins group has been doing some long-term imaging work too. So yeah, it's starting to come out now, but still very new. So I like that the chat was kind of general and broad about what might be happening in the brain. That's not bad. Yeah. Yeah, they did a good job of compiling some papers. And in a weird way, it's sort of an alternative to

searching for things, but it puts it in a nice digestible format that you can kind of, you know, kind of play with a little bit. I'm wondering, like, do you think that, that is it possible that the long-term effects of the psychedelics can have lifetime effects? Like, would it be possible to maybe, I think you had written in a previously paper, can psychedelic drugs attenuate age-related changes in cognition? What, can you tell us about that? Yeah, yeah. Yeah, I'm glad you brought the paper out. It doesn't get talked about too much. So, yeah, thanks.

It was actually something I initially wrote for a developmental psychology class in grad school and then ended up developing it into a little bit more of a fleshed out paper and tried to actually publish it eventually, and we did. Yeah, there's definitely some people who report, you know, affects that are permanent seemingly after a psychedelic use, you know, whether that's changes in personality, whether that's changes in, you know, just how they look at the world. how they just feel day to day.

There's not everybody, of course. It's not a panacea. And, you know, some people feel better for a little bit and then rebound. But others, you know, do seem to have this permanent change in their, in their psyche. And so, yeah, I do think there are some individuals where they could have long-lasting effects. With older adults specifically, you know, I think that's a really interesting area of research to explore. And it's been pretty understudied. But, you know, we do know that if you can take some strategies early in life to improve your mood and your cognition, that there's much, there's tons of downstream effects that can be gained from that.

And so, you know, addressing your depression in your 20s and your 30s can reduce your chances of Alzheimer's later. And so, you know, if you have a very powerful psychedelic experiences that, you know, addresses your depression and seemingly, you know, maybe that could. benefits you long term down the line in terms of some things that you might not expect or think about when you're taking the drug. And then also, you know, there's the question of older adults themselves taking the drugs, which is pretty interesting as well. You know, the research is pretty conservative when it's starting out and, you know, there's a lot of age limits on a lot of studies. You know, some of the end of life distress studies obviously got around that. And so there is some precedent for older adults being incorporated into the research. But I think they are kind of

underrepresented and there are some unique considerations too for for that population yeah do we like so obviously i'm not a doctor of any means i'm just an enthusiast i love reading and participating exploring and experimenting and coming up with some ideas and so but from your perspective do we know like what is happening in there is it is there you know is there being like a a dump of neurotransmitters you know people talk about the default most network kind of being turned off and processing different information in different regions of the brain or when it comes to psilocybin are we do we know what do we know about what's going on in the brain yeah yeah so it's a great question um like i mentioned before we're still kind of in the

beginnings of this area of research but um we do know that for sure that psilocybin attaches to serotonin 5 ht 2a receptors and um those receptors are pretty widely distributed in the cortex and most densely in areas like the frontal lobe, medial prefrontal cortex. And we know that the psychedelics work on the 5HT 2A receptor for a couple of different reasons. First, if you block the 2A receptor and then give somebody a psychedelic, they're not going to have any trip or any psychoactive effects. So that's pretty telling. Also, drugs that have greater potency or greater affinity, I should say, for the 5HT

2A receptor. So they're able to find that receptor better than other drugs. Those ones with the higher affinity have more potency. So you only need to take a smaller amount of them to get the same effects. So for example, LSD has a much higher affinity for the 2A receptor than psilocybin. And so because of that, you take less LSD than you would need to take psilocybin to get the same effect. And so we really have a lot of converging evidence that the 2A receptor is really the most important, you know, signaling. pathway for psychedelics. There's others that are involved, but the 2A is the really at the heart of it.

And there's a lot of things we know about the 2A receptor outside of psychedelics. It seems to be a really important receptor in plasticity and responding to changes in your environment. And we know things like chronic stress sensitize the 2A receptor. And because of that, you know, when you're in a chronic stressed environment, you need to be able to adapt and to be plastic. And so there's a lot of different evidence suggesting that the 2A receptor is related to plasticity. And so when somebody takes a psychedelic, what we're thinking is happening is that there is these changes in plasticity where the brain's able to make new connections through these 2A signaling pathways. And this is going to disrupt hierarchically, hierarchically organized brain activity. And because of that, you're going to have, you know, deeply ingrained thoughts.

patterns and behaviors possibly disrupted. And that allows a chance for people to look at their problems from a new perspective and potentially for some of these insights and epiphanies to stick long after the experience has gone away because of those changes in plasticity. That's so fascinating to me. I recently heard this, I recently heard someone say that psychedelics remove memory from perception. And I thought to myself, why, that was a really astute way to put it.

You know, and it's just a, it may not be 100% accurate, but it's a good way for someone to get an understanding of what's going on. And it, that, that, I think that that would lead to some pretty incredible insights. If we just think about how conditioned we've been since the age of two, since we began using language and we began labeling things, if you can just have this 45 minute or this three-hour experience where everything that you remembered about something is, is kind of, glossed over and you get to see it anew and make new connections to it. Like that can be so beneficial for people that have, I mean, just regular day people, but specifically for people that are struggling. What do you think about that?

Yeah, that totally resonates with me. You know, people really do get stuck in these ruts, especially in things like depression, but also in things like substance misuse disorders, where, you know, there's just kind of this monotony and this kind of never changing. seems like of their patterns of behavior. And so a chance to see things in a new life from a new perspective, be really powerful, I think, for some people. And like you said, it's not just clinical populations. I think that could be pretty meaningful for, you know, just everyday people as well. I mean, I think that's not a good way of putting it individuals without psychiatric disorders.

Yeah. Yeah. And yeah, so I think that's something people are starting to explore is looking at healthy populations. We have a study here at UCSF where we're, you know, studying a healthy population giving them psilocybin or psilocin, and we're looking at a lot of their different outcomes. They're social functioning and their cognitive functioning, specifically things like their relationships with their family, their social values, their levels of gratitude, their social support networks, and then in terms of cognition, looking at things like cognitive flexibility and creativity, all things that are pretty beneficial to one's health, even if you don't have a diagnosis of something. So, yeah, we're hoping that there can be a lot of applications there.

Yeah, those are all great points. And it brings me to some, you've written, I think you've written quite a bit on the world of clinical trials. And I kind of want to talk a little bit about that, but I want to add into what you just said. You're talking about, you know, giving some, some everyday people, silicin or certain doses of a psychedelic, in order to monitor their relationships and stuff like that. But how do we get to this conundrum of measuring objective research from subjective research? Because it seems to me like a lot of the subjective stuff is really important. There are some things that you can't really, you know, put a needle on or put on a scale.

But like they're important. Like how do we get around that? Yeah, it's tough. That's a great point. And I think it's not like one solution. It's kind of being open to a little. a lot of different approaches and a lot of different ways of evaluating evidence. So, you know, I think kind of qualitative studies can really complement clinical trials where,

you know, we have actual interviews with the participants and you, you know, you write about the themes that came up in those interviews. You know, some things, it's great if you can have some kind of objective measure like a biomarker or a behavioral test, you know, that just seems to keep the scientist a little happier when you're trying to publish these papers. But, you know, like you said, it's not always possible to be able to get, you know, a behavioral measure of their relationships or how close they feel to others. You can't really capture that with a reaction time necessarily. You can try to capture it on, you know, one to ten, Lycourt scales or whatever.

But it's not going to be a very clean translation. And, you know, there's going to be a lot of nuance that gets lost, too. So I think it's important to, to not get, you know, too siloed into your one methodology and to really be. open to different ways of evaluating the evidence. Yeah. You know, on another, on another sort of slice of testing things and trials, it's always fascinating to me to get to hear the trip reports or the accounts of what happens. And there's so much spirituality that seems to be wrapped up in the world of changing ideas. And that can be a scary thing. I think especially for the world of science. Oh, yeah. For me, it's.

seems that, and this is just my words, it seems to me that science and spirituality are opposite sides of the same coin. And I feel like we're moving back towards that. And when you have this subjective experience, you're trying to explain, it's almost ineffable. You can't really explain it. But that's that spiritual side. And sometimes I think that that scares science. Like, whoa, whoa, we're not moving backwards here. We're supposed to be going forward. Yeah, exactly. You see like a sort of weird kind of thing happening there? Yeah, it kind of calls back to the early days of psychology when behaviorism kind of rose. And behaviors were like, no, we don't want to study the mind at all because we can't see it.

We can't measure it. You know, we're just going to ignore it and pretend it's not there and focus on what we can, you know, objectively observe. And yeah, I think there's a lot of parallels there. But I think it's it's a duty of science to kind of try to challenge itself and to answer those questions and to, you know, really push the boundaries of what we know and to not just give up essentially and say, no, that's just kind of outside. of our realm. You know, I think it's definitely a tough thing to, it's a tough not to crack, but it's something that we can iteratively learn about and make improvements on. Yeah. Come in from the world of psychiatry, you know, there seems to be, you know, my family has gone through a lot of turmoil, like all families. And we probably all know

people who have gone through different mental illnesses and been around different things. And it seems to me that, you know, people that have mental illness, sometimes they find a lot of, they find a path back to feeling better through religion or they can find a path back through, you know, I guess what I'm trying to say is that prior to psychedelics, it seems to me that religion was a crush for people to find their way back to a life worth living. But it seems to me psychedelics are also doing that. So, you know, I guess I'm still talking a little bit about the spiritual in that. Like, you have this religion. We have this religion system in our minds. And it seems that psychedelics, like, trigger that on some level. Is that fair to say?

Yeah, absolutely. I think that's a really interesting point to make. Yeah, it seems like maybe psychedelics are kind of emerging as like an alternative to religion in some cases in terms of, you know, able to get out of you know like a substance use disorder or a big rut in your life yeah it's really interesting to think about and why that might be you know obviously rates of religiosity are declining in the u.s and there's a lot of people very generally seems like people have a lot of issues with organized religion and so i could see um you know when somebody gets to adulthood they obviously have a lot of baggage there no matter who you are you have preconceptions you have biases

you have you have thoughts about religion you know it's that's impossible to avoid um and so i think having this kind of other option that's kind of a parallel but doesn't have the same baggage and is um at the same time being hyped up by scientists and um the news media and basically celebrities and everybody too you know that's suddenly very attractive i think yeah yeah that brings us to i mean yet another paper that you've written about psychedelic drugs and perception like maybe you could talk a little bit about that. Yeah, yeah, absolutely. So yeah, I started on that paper because when I began my PhD, it was actually doing more attention and perception research. And then during the first semester, I took a history of psychology class and it was taught by my

advisor. And he let me write a paper on the history of psychedelics and LSD specifically. And, you know, it did really well. We ended up publishing it actually. And so suddenly he was like, maybe we can make this a line of research in our lab. So the next step seemed to be, you know, synthesizing the things that we were doing in the lab with the psychedelic area. And so we're like, what's been done on psychedelics and perception? And so, yeah, we found that, you know, there's not much research that had been coming out in the more recent years

because it was more clinically oriented, but that there was this kind of huge body of research from the 50s and 60s on the perceptual effects of psychedelics that really wasn't synthesized at all. It was very, just kind of all over. the place, and, you know, especially because these articles came out, you know, 50, 60 years ago. Now they're kind of hard to track down and find a lot of the times, especially if you're not looking for them. And so, yeah, we thought it would be useful to just synthesize that really huge body of literature. And, you know, I think it was actually a little too much to take on,

to be honest, this was a little bit too broad of a scope for the paper. So it did take a very long time to get that published and to actually write it. But I think it was pretty interesting. Yeah, that we got to cover just every different sensory modality, essentially. As you might expect, visual processing had the most research on it and seemed to be perceptual domain that people had the most robust changes in perception. Surprisingly, but there was research on other perceptual modalities as well, though, so people did sometimes report auditory hallucinations or auditory distortions under the influence of psychedelics. changes in body schema. That was another thing that was pretty interesting because

you know, we didn't think anybody had really measured that very much and that was something my advisor was interested in. It was doing body schema research and so yeah, some people, you know, feel this kind of, you know, loss of their sense of their physical body. They tend to feel like they're kind of merging with their surroundings, which is something that kind of comes up in meditation too. So that was something we're really interested. And we actually did a meditation study on that looking at how to kind of track those changes in boundaries with EEG measures, which is pretty cool to study. And then there were also some olfactory changes, but not very much.

There's a couple of people that reported, you know, smelling things that weren't there or distorted smells and distorted taste as well. But yeah, those are the kind of the broad overview of the paper, I suppose. Yeah. And time was lastly, too, those also altered. If we go back to the meditation and the EEG studies and psychedelics, can you tell us a little bit more about that? Are you measuring brain waves or like what's going on in that study? Yeah, absolutely.

So the brain generates a variety of cognitive maps to represent the surrounding environment around us. And so that you know where the bathroom is in your house, even though you're not thinking about it, you know where the upstairs is. You know, you know how to get to your kitchen, you know, where your drink is, without thinking about those things. Things are all going on in the mind with how you're thinking about them. And one map that the brain makes is called peripersonal space. It's not something that many people are familiar with, but peripersonal space is essentially the region around your body within arm's length, essentially a bubble around your body. And we know this is a true map in the brain from a variety of different imaging studies. You know, this is even in monkeys, you know, they can do single cell recordings and see that certain neurons fire when things are in that bubble versus when they're not.

And so we and so essentially the brain prioritizes the space around the body, which is makes sense, right? You want to be able to take care of what's around your body first in the environment, especially in the evolutionary sense. And because we have that cognitive map that prioritizes the space around us, we actually have attentional and perceptional benefits for things that are occurring in that space. So you actually see things better if they're in that map space. You actually can respond to them quicker and things like that. And so the peripersonal space seems to be a really important bodily boundary. We were wondering if that bodily boundary is one thing that gets either deprioritized or

shrinks when people are under the influence of meditation or expands as we weren't really reassured the direction because people often report the sense of merging with their surroundings and a loss of kind of their personal bubble essentially and you can track peripersonal space with EEG so stimuli within peripersonal space are going to elicit a higher p3 amplitude which is a type of EEG signal then which is really to essentially attentional salience So if something elicits a higher P3, it captures your attention more. And we see that things within the peripersonal space elicit a greater P3 than things that are outside. Just another marker that this space is prioritized and considered special by the brain.

And so what we did is we measured their peripersonal space bubbles before meditation and after meditation. And we found that after meditating, people's peripersonal bubbles shrunk so that they were actually a little bit smaller. And we were thinking that this might be one thing underlying, they're, you know, phenomenal logical changes in bodily boundaries as well. But definitely need more research on that. And this is not something we really followed up, unfortunately, because, you know, I moved on to the psychedelic space more. And, you know, they took on a graduate student who's interested in other things.

But, yeah, it was a kind of interesting finding that tied into the psychedelic stuff in some ways. That is fascinating, Jake. I've never heard that. I've read quite a bit. I've never heard anything about that. And we all the time I hear about, you know, boundary dissolution and stuff like that. But that really kind of brings it home. And that would be a fascinating study to do on psychedelics or different psychedelics.

So is it when you when you're reading the EK, is it an EKG or EEG? Oh, EEG, yeah. So when you're reading the EEG, is it brain waves throughout the entire brain or different parts of the brain? that you're reading. That's a great question. Yeah. So when you're trying to localize the P3, you can look at specific electrodes or you can collapse specific electrodes and kind of average them. We were looking at a specific one towards the back of the head here. Yeah. And is that where the map is at? Or? Oh, we don't really know, I guess. With EEG, you can't get much spatial resolution because you're measuring electrical signals from the brain, right? And so the electric signals have

to go through your skull and then they reach the electrodes on top. And so there's a huge loss of clarity in the signal in terms of spatial resolution. So you don't really, you're not able to like localize activity with EEG very well. However, the timing is very precise because electrical activity is so fast. So you get, you know, hundreds of ratings a second. Whereas with like fMRI, it relied on blood flow, which is a much slower process than electricity. And so, you know, the spatial, the resolution, the temporal resolution with fMRI would be something like you get a sample every couple seconds, like two to three seconds, whereas with EEG you're getting hundreds of measures every single second. So there's tradeoffs between the two. But with fMRI, you can get much better spatial resolution and see actually where changes are happening better.

And was that EEG? Was it like a, were those waves like alpha or beta? Were they big waves, small waves, or like the dream state? Or is that relevant? So this is a like an ERP, an event-related potential. So this would be different than like a wave, essentially. This would be a signal that's evoked by a specific stimulus, yeah. Okay.

It's so fascinating to me. You know, and there was another paper again because you've written tons of them and thank you for writing them because they're very fascinating to read. I appreciate it. Thank you. Yeah. And for those watching or listening to this, his name is Jacob S. a day, PhD, you can look them up on Researchgate and check out the papers.

They're really worthwhile. And you could probably reach out to him and he'd probably love to talk to you. Yeah, absolutely. You've done some other interesting papers on pupil dilation. And I had this idea that I wanted to run by you. And this is just pure speculation. But I wanted to get a professional thought about it. And so my thought was that, you know, on LSD,

and sometimes psilocybin, I find that my pupils are incredibly dilated. And when you look at your pupils, I think of my pupil like a shutter on a camera. And if you're shooting in camera raw, like you're getting all this light in. We've seen all these new studies about light has memory.

And it just seems like you're processing so much more because you're getting so much more in. Are you processing more? Is it a way to like, I feel like you're seeing more when your pupils are very dilated. And I'm wondering if long-term pupil dilation has anything to do with, you know, processing more information and understanding more the environment around you.

What do you think about that? Is that just out there or what? No, it's interesting. Yeah, it's something that I don't know a whole lot about, to be honest. Yeah. No, and I see what you're saying. I think that, yeah, there's definitely merit to that. I guess what I could say for sure is that, you know, when your people's dilate,

you're letting more light in of course more rods are being stimulated and so we're going to have you know more saturated colors more visual acuity essentially my research on the eye has been more in looking at social gaze and um seeing how you know eye size and people size affect social gaze and attention um so that was what i was doing during my master's degree before i got into psychedelic research. So, yeah, I started doing like emotion and attention research, then started doing attention and perception research and then shifted to psychedelics. But, yeah, before what I was looking at is, you know, how different emotional expressions and their morphology of the eye changes and how that influences attention. So we know that, you know, emotional facial expressions, like fearful facial expressions capture attention more than a new.

neutral expression and you can measure that number of different ways. But if you have, there's the most basic test of that is the dot probe task where it's a computer task. There's a central fixation point they stare at and then two faces are briefly shown, one on each side of the cross. One would be fearful, one would be neutral. They'd only be up for like 100 milliseconds and disappear. And then a target comes up behind one of them. And what we see is that when the targets behind the fearful face, people respond faster than when it's behind the neutral face.

And the reason for that is because they have an attention bias towards the spatial region where there was a fearful stimulus or a threatening stimulus. And that's, you know, an evolutionary adaptation to respond to, you know, emotional stimuli quicker in your environment. But there's some nuance there as well. So we found that one of our studies that the degree to which Scalarra exposure was shown,

so Scalar is the white portion of the eye. It influenced degree to which people oriented towards emotional, facial expressions, and towards fearful stimuli. And so the thinking is that the more white is shown in a fearful expression, the easier it is to see where they're looking, and that facilitates quicker responses. And, you know, supporting that, you see that, you know, creatures and animals that have more scler exposure typically are more social and would use that kind of gaze-orienting communication. more often. It's fascinating to think about, you know, most people, or at least me, I never thought about what affects the Scolera would have on my decision making or communication, but it's a fascinating thing to get into.

How much actual communication is happening with the eyes, and especially in today's world where it seems like we're all focused on a screen. Yeah, exactly. You know, it's weird to think. I wonder if you were to speculate, do you think that, do you think that? This is just kind of on a side note. But if you were to speculate, do you think that the world of communication is becoming,

even though it's easier for you and I to talk, you know, via the platform, what do you think of the long-term effects of communication these days? It seems like we're not in person as much. What would you speculate is happening to our communication? Yeah, yeah, it's a good question. Yeah, I think, yeah, I think you're right.

I think there's definitely some detriments to our communication that are being lost through the, just the virtual interactions. You know, in our lab here at UCSF, I could see that, you know, when people get together in the lab and in person, like the, there's just so many more opportunities to get to know each other informally, you know, just a little walks down the hallway or whatever,

getting between rooms. You know, you don't get that, you know, when everyone's meeting in a Zoom room and, you know, the little, you know, pauses before meetings and after meetings, you know, you can't really have little chats in an open Zoom room because, you know, everybody's listening, essentially and it's just awkward to have a one-on-one conversation with 30 people and just sitting in the

background. So yeah, I definitely think there's a lot that's been lost there. And then one other thing that you made me think of is masks because a lot of our non-verbal communication also relies on the lower portion of our face as well, you know, our smiles and our frowns and, you know, those also involve the lower portions of our face. And so, yeah, it's interesting to think about maybe what's happened with our non-verbal communication over the last few years when people have been relying on the eye region more than ever and also you know communicating not face to face anymore you know you got to think that that's those things two things together have really radically changed how we interact with each other and even if it's in some subtle ways that we don't notice all the time and

it's kind of happened gradually over time you know I think there probably has to be some changes there yeah it makes me think of like the world series of poker like those guys are always trying to cover up their entire face. It's like COVID's a COVID in some level is perfect for them because I got to wear a mask and my glasses. I don't want anyone to see my face. If you think about it, some of those guys are masters of facial communication or reading facial tics and eye contact. Yeah. Small smirks on the smile and nostril flares and things like that. It's kind of crazy to think about. Yeah, it's true. Very attuned to the nonverbal signals. Yeah. Yeah. I think that this is just me speculating, but prior to us starting, we had mentioned that psychedelics are becoming such a broad

aspect of study that we could almost use psychedelics in every field of exploration, whether it's artwork or sports or what do you think would be some other exciting things to study in different fields with psychotals? If I gave you unlimited money, Jake, and you could do a study on psychedelics in any field, what would it be? Oh, man, that's a big question. Take a moment there to think about it. Yeah. Man, I guess, yeah, I guess I have pretty particular interest in just the broader pro-social effects psychedelics can have, not necessarily the clinical applications, but the degree to which people can, you know, feel more connected to nature and to the universe more broadly. I'd like to see how to facilitate that. You know, most of these clinical trials have happened

in laboratories, in hospitals, and very, you know, they try to pretty up the room. a little bit, but it's still kind of synthetic and sterile. So I would love to go to like Yosemite or something and do a study there, you know, give people psychedelics in a very awe-inducing nature environment, see if we can really, you know, just really hammer in that connection to nature aspect of it and really kind of hone in on it and try to, you know, just facilitate that by throwing as many bells and whistle down it as possible. I suppose in some ways people are kind of doing this with these retreats and Central and South America, you know, they're going into the jungle and obviously not taking it in a in a synthetic or sterile environment at all. So we see that, you know, from the naturalistic studies

of people doing that, that people do often benefit and feel more connected to nature. So, yeah, I think there is, you know, some precedent there. But I would love to take, you know, what we've learned from the clinical trials and, you know, combine it with what we know from those naturalistic studies. and just really do, you know, a really souped-up version of a psychedelic nature intervention. I think that would be really cool. Yeah, that leads me to the idea of, you know, James Fademan wrote a book called The Psychedelic Explorer's Guide. And in that book, he invited everyone to be like a citizen scientist in a way. Like, he invited everyone to write down your, you know, the things that have happened to you when you're microdosing and send it into his website.

And it just, you know, it seems if we take that and we pair it with the world of decentralization that seems to be emerging today, you know, might we be, might we be on the precipice of decentralizing clinical trials? Like, why couldn't the people at the retreats be writing down information? Why couldn't the people that are, like you and I be writing down our information? And, you know, I realize that there's a lot of subjectivity there. But isn't there also subjectivity in the actual clinical trials? Do you think it's possible for us to get away from this really rigid clinical trial setup and somehow decentralize it in a way that would democratize it, make it, you know, so more people could, just with the sheer amount of information, I got to think that there's some real good nuggets in there from us to learn from. What do you think about, is it possible to decentralize clinical trials in some way? Yeah, yeah, I think so. I think that's a really cool idea. I think there still needs to be like, you know, scientists. involved. Right.

Kind of overseeing and, you know, planning it and, you know, because there still needs to be some structure to it and things need to be collected in some kind of systematic way still. But I don't think we need to rely on clinical trials is the only way to gather that evidence for sure. And I can tell you myself from my experience doing both naturalistic studies and clinical trials that, yeah, there's tradeoffs. So, you know, I did a ayahuasca naturalistic study from my dissertation where I just, you know,

gave people surveys that they were attending an ayahuasca retreat in Costa Rica, the week before they went, the week after they went, and the month after they went. And there were really any cost to the study other than paying the participants, which, you know, I did a raffle and certain number of participants want a certain amount of money. And collectively, it was like under $1,000. So like the month that I gave away to the participants. And now I'm doing a clinical trial that's, you know, approaching like a million dollars. And so the scale there in terms of the cost is enormous. You know, what you're getting out of it maybe is not as, there's maybe not as much of a gap between that. So I think there is, you know, ways to make the most of your money and to not just

rely on clinical trials because you can get really useful information from much cheaper methods as well. And, you know, what's interesting is with the clinical trials is everybody knows that the participants are unblinded, right? So it's not even a real double-blind trial. And so we're essentially, you know, getting almost the same quality of evidence at these naturalistic retreats for really a fraction of the cost. Obviously, you still want some kind of control group, if you can as well. But in terms of, you know, blinding, that's not happening anyways with clinical trials. So that's, you know, that's, I think there's a lot to gain from not just being myopically focused on clinical trials. Yeah.

Yeah, I talk to a lot of people that are beginning to establish retreats. And some people have some really cool ideas like this. There's a company called Wake and what they are doing. They're partnering with people to try to utilize different, you know, brainwave technology or the EEGs to figure out ways in which to, you know, try to pin down exactly what's happening and then compare that evidence and stuff. But one of my questions to them, and I'll pose the same question to you is, do you think some things get lost in cultural translation?

Like, let's say me from, you know, from Caucasian acres goes down to Brazil, and I'm listening to these Akaros and this beautiful sounds, but it's in, it's like I'm going to Spanish 5 and trying to participate in the class. I don't speak Spanish, I mean, I speak Spanish, but maybe I don't speak Italian.

Sure, yeah. So if you go to another country and you try to listen to the lecture, you may be picking out words, but you're not thinking in that culture. So I'm wondering, you know, might there be a big difference between someone who does an ayahuasca ceremony in a traditional Hito in Brazil versus someone that does a ayahuasca ceremony

in a Christian church in Iowa? You know, do you think there might be some differences there just because of the culture? And what would be the benefits and negatives on that? Yeah, great question. Yeah. Yeah, so we know for sure that there are a lot of non-pharmacological aspects in psychedelics that influence people's effects and that the you know the set and setting are

very important you know that's something that's kind of dogma in the field essentially you know we we know that this is true um and so yeah so that being the case there has to be some differences um and these people's outcomes i would think you know um you know i would in terms of benefits and detriments to each of those two approaches. I'm not sure exactly. I think, you know, I think there's probably something to be said for all the work that goes into going down into South America and Central America to do these retreats. You know, there's a little bit of cognitive dissonance there where, you know, you're telling

yourself, oh, I'm taking all this time off, I'm spending all this money, I'm going through this huge hassle to go out down there. I better get better, right? Yeah. there's kind of that unconscious aspect of it, of cognitive distance and insur. I wouldn't be doing these things if it wasn't going to make you better, right? And so, yeah, the more effort you put into something kind of unintuitively, the more likely it is to actually benefit you.

But yeah, but also, you know, there's that method I just described also came out a lot of cost too, right? A lot of time, a lot of money, a lot of hassle. And so there's probably some people, who could get enough out of, you know, doing the same thing in the United States where maybe it wouldn't be as powerful or, you know, maybe not as many of the people attending such a ceremony would benefit. But there probably still likely be some benefits. And the cost saved would probably make up for the difference in benefits, I would say, in a lot of cases. So, you know, it's a lot of, it's a lot of. a case-by-case decisions, I would say.

Yeah, there's, I guess if you're already getting leverage on yourself, the possibilities for change are just exponential, right? Like you'd go to this brand new place. You've never been in your life. It's like a vacation. Yeah, that too. Yeah. It's a tropical area.

You're like, whoa, you're already in a state where change can affect. It's already affecting you. You're already changing just by going. That's a great point. Yeah. And a lot of these places have you, you know, do certain diet for the month beforehand. You don't have caffeine or, you know, you don't have caffeine or, you're or alcohol and they abstain from sex and a lot of them too.

And so those are obviously all going to affect your behavior and your outcomes too, right? So there's a lot more that can often go into those other kinds of retreats. It seems like I don't know a whole lot about the, you know, the ayahuasca ceremonies going on in Iowa or in the United States. Yeah. But at least with the ones in the central and South America, there's a lot of prep and other things that go into it beyond the ayahuasca. Yeah. There's meditation and there's classes on site. there for like seven to ten days you you meet a bunch of new people you make friendships you get to

learn this meet the staff um who are very friendly of course and so yeah there's all kinds of things beyond the ayahuasca that are going into those retreats it's so amazing like when i hear you talk about it like it just it brings me back to this idea like it's so spiritual in a way like you're meeting new people you're doing something for the first time a lot of people and that's almost like a rebirth. It's almost giving you permission to be reborn. And there's that same nomenclature and you're a born again Christian or you're born again, you know, and like they're just, they just tie together so, they just fit seamless together in so many ways. And I could understand why that would scare people in some ways. Because for some people, religion is very scary.

You know, maybe people have got, you know, you think of Jim Jones, you know, or these people that find themselves in like a cult or something like that. And, you know, it's, it's interesting. But I think that we have to have the courage to try to change. We have to have the courage to at least look deep within ourselves. And if you don't feel right, then there's probably something you need to address. And by not addressing it, you're making it worse. And if these types of experiences will allow us to confront the change.

I'm not saying you have to do the change, but if you can confront the change, the threshold guardian as James Campbell likes to call it. You can confront him, you've got a chance of moving up to the next level. And I really think that that's what's going on in the world of psychedelics. And as a psychiatrist, I'm sorry, go ahead. Oh, no, no, I'm sorry. I was just going to say, I can also see why people, you know, would be a little bit scared, like you said at the beginning of that,

about, you know, dying and being reborn again. Because even if they have issues or problems in their life, there's probably things that they like about themselves, too. And they might be scared to lose those things or, like, like maybe an aspect of themselves that they like might be changed. It's hard to predict before you go through it, what's going to change or not. That is a great point. How much, in your opinion, how much of the difficulties in life do you think come from people fearing change,

whether it's something they think they like about themselves, they know they have to change, but they're holding onto it for some reason? Do you think that that's a big part of, or do you think that that, contributes to mental illness. Yeah, for sure, yeah. Holding on to things, I think that's often a big part of like cognitive behavioral therapy or acceptance in the committee, commit to learn how to let go with things when they need to be let go of. You know, mindfulness, meditation, of course, kind of tries to address that as well.

Yeah, and so, yeah, I think that is something that underlies a lot of pathology. That's something that, you know, Robin Carr Harris has put forth recently as well, is that, you know, there seems to be a common factor to a lot of different mental illnesses. And maybe that's, you know, biased habits, essentially, which would be kind of like what you're talking about, where, you know, whether it's depression, whether it's substance misuse, whether that's OCD or anorexia. There's people who are very deeply ingrained in certain habits and, you know, not very open to change, I suppose. So it seems like perhaps psychedelics can target all these different types of disorders and such because they're, you know, kind of targeting this common factor of, you know, giving people to accept their issues and to, you know, like you said earlier in the talk, look at their issues from a new perspective and a fresh light. Yeah, that brings up an interesting point, too. It seems to me that, you know, when you read the studies, and I understand why these restrictions are on studies. There's restrictions like if you have bipolar disease or if you have schizophrenia or if you have a history of family mental illness, then maybe the study is not right for you.

And I can understand why we want to segregate those people. However, it almost seems like those people might benefit most from psychedelics. So what a weird way to exclude the people that may need it. How do we go about rectifying that? Yeah, there's so many things to balance, I think, for psychedelic researchers. And I think that's the main reason those populations were excluded the first, in this, you know, in the rebe beginnings of the psychedelic renaissance, I should say, is because there's things that researchers had to balance, which included, you know, making this trials as safe as possible,

you know, getting regulatory approval, you know, trying to, you know, just essentially make sure that there are no adverse events and trying to do it, like I said, already, as safely as possible. And so I can see why, just out of an abundance of caution, you know, that certain populations might be excluded, and especially because there are case reports of individuals with, you know, either schizophrenia or bipolar, in some cases having negative experiences of psychedelics. But there's not really solid research there, to be honest. It's not very concrete. There's some sparse case reports and stuff, but there's not really concrete evidence so far on the relationship between psychedelics and reactions

among people with psychotic or bipolar dispositions. And so we're starting to kind of start to look at that a little bit more now that we've, you know, kind of gradually built up to it by exploring a lot of different vulnerable populations first. So here at UCSF, there's going to be a psilocybin therapy study for bipolar type 2, which is the less severe form of bipolar disorder. So there's type 1 and type 2. Type 1 involves, you know, mania. and depression, type 2 involves hypomania and depression, which is essentially just a less

severe, less intense version of mania. And so it makes sense if you're going to start looking at bipolar patients, patients with bipolar, then to start with the type 2 and to see how they respond and move on. And so specifically, the study is going to see if we can target the depressive aspect of their bipolar diagnosis, because we know from other studies that, you know, psilocybin therapy has potential for treating depression. And then, um, We'll see what happens in terms of safety outcomes and other unique things that might come up with population as we, as we progress very slowly with this very small phase one study. Yeah, it's fascinating to me.

It's one another reason why I'm so excited about this renaissance that we're having and using the different plant medicines is that it seems that, and this is just my speculation, but it seems to me that for a long time, the pharmaceutical industry, which I'm happy they're there. They've created a lot of great things that help a lot of people become better, and I'm thankful for that. However, it does seem at times

that the business model for pharmaceuticals is to sort of a coping strategy. Like if you take something for ADHD, like modafinol, riddlin, or some sort of, stimulant. It's or something for depression, like an SSRI. It seems that these particular medicines allow you to cope with what you have.

And it's like, I feel I hate my life, but I take this pill. I can go to work and I can still do my life. Yeah. Which is one way to get through it. But what I have found on psychedelics is that, again, you're confronting the problem. And if you look at some of the research with PTSD or depression, you're seeing people take to sometimes one particular experience and like, oh my gosh. you know what? I realize I'm a dummy. I realize I'm a dummy guys. Congratulations. I'm a horrible person and I got to fix that. I did it. You know, and you come to this idea of like, oh, it was me. The whole, guess what you just take the mask off? It was me. Yeah, I'm here.

And you're able to figure out what the problem is and at least begin solving. You may not solve it the first time, but at least you can take steps to solving it versus taking a pill that's like, okay, I fucking hate it. Let's go. Just take this thing. Exactly. It just dampens the symptoms temporarily until your next pill time comes. Yeah. So, yeah, I'm excited for that because I think that that is the revolution, or at least one of the avenues that's revolutionizing medicine. It's like, look, this is allowing us to see at least the truth and the truth will set you free here. And I'm wondering if there's, I think that that's a measurable thing, right? Like you can measure someone that has to take a pill forever versus someone that has a objective or a subjective experience and no longer has to do it. That's got to be an experiment in itself somewhere.

What do you think about those two different methodologies? Yeah, yeah, it's interesting. Yeah, I think with the pills, it seems like, I don't know, you can, I don't know, you can, yeah, you can blunt the symptoms, you can ignore them. But I think the thing, like you said, was psychedelics is, yeah, you confront them head on. aside from that improving the clinical symptoms like you said it might make people make other changes in their lives that are really important and you know make it so that they're not just going to a crappy job because they're blunted and don't feel how bad it is you know they have the

experience and they actually change that crappy job and they're actually living a more fulfilled life and yes that's that's kind of separate from the clinical improvement but it's also a huge and, you know, of huge importance to the person. So I think that's really interesting. And, you know, in some cases, you know, maybe that would be considered a risk as well, that people would, you know, change their careers or change their marital status or change their sexuality in some cases

after a psychedelic experience. Yep. Most of those people don't know that that's going to happen before going in. And so, you know, that's kind of an arguably underappreciated risk, I think, than something that maybe should be more, widely disseminated in the consent forms and to the white or public that, you know, there could be pretty major life changes that people make as a result of these type of experiences that you would not expect with an SSRI or something like that.

That's a great point. I never, you know, I never thought about it. A very typical lawyer who becomes a painter. That would be taking LSD. That would make the world better. If more lawyers became painters. Right. That's what I'm saying.

Yeah. In some cases, that's probably a good thing. In other cases, maybe maybe it was a bad thing for that individual. But it's, again, kind of a case by case. thing yeah yeah well they could do both he could be a lawyer for painters yeah that's true that's got to be out there yeah yeah it's it's fascinating to me because i do see and you know i know when i take psilocybin it it comes i found and i think most people agree with this like it the onset is on way like it comes in wave like it slowly like you feel the come up and then you're like

okay okay i'm good and then all of a sudden like the first wave hits you you start everything starts breathing and then you down some crazy thought rabbit hole. Like, oh, man, I knew that I knew that thing. Or maybe I am an alien, whatever your trip is, you know. And then it kind of backs off and then it comes again. And it almost seems to me that the same way psilocybin affects change in the human individual, so to does change happen on our planet. And like if you look at the first explosion,

of psychedelics in like the 60s or the 50s, like maybe that was like the come up and then the first wave. And now like this is the second wave, right? And we're working towards this peak experience. And it just when I think about it like that, that's another thing that psychedelics makes me do is it makes me see myself in the entire world around me. You know,

and maybe that's the peripersonal space or maybe that's the eyes being wide open and you can take in a little bit more information and see in the trees breathe. It really, one of the things seems to be this, this idea of wholeness or this return to the one right there. I'm not sure how to explain my thoughts on that, but what do you think is this return to wholeness? Do you see, do you see psychedelics making the individual sort of feel like they're one organism with the world? Or is that something you've experienced? Yeah, it seems like it.

Yeah, people kind of, like you said at the beginning, are you able to take a step back a little bit? Yeah. Yeah, and just feel more connected very generally. I saw somebody posted on Twitter the other day about how to describe the changes in time perception of psychedelics. And I wish I could quote it perfectly. But it was something like the sense of the barriers between past,

present and future seem to be eliminated, which seems to be what you're saying. There seems to be this oneness, this wholeness. Yeah. that is experienced, yeah. And I think that wholeness of oneness, yeah, can have pretty important implications. You know, people often feel disconnected in psychiatric disorders.

And, you know, maybe that's one thing helping them clinically improves that they suddenly feel a part of something much greater. Same thing with terminal patients who are at the end of their life and have a significant psychedelic experience where, you know, beforehand they have the sense of their self-dying, this single entity of their self dying. But afterwards, they often have the sense of, no, I'm part of everything. So just this one little parts dying.

All this other parts of me are still alive and live on. And so I think that could be very powerful as well. And then, of course, you know, the changes in nature relatedness to probably also connect to those feelings of oneness and connection. Yeah, that's a whole other avenue of people, like, especially in a world where the demographics are so many, like 10,000 baby boomers retiring a day. And sometimes I think a lot of the problems we see in this world are a direct reflection of a generation about to die.

You know, there's so much anxiety out there. And there's so many, you know, our grandparents and our parents are getting older and they're on the precipice of having the mortality experience or whatever you want to call it. You know, they're there. And, you know, that's a whole other apple. that you're beginning to see people move towards in using psychedelics as people confronting that. Have you had any experience or heard any about some of these particular trials with psychedelics and end of life? Not a whole lot personally, yeah.

Now, I've read the papers, and I think they're pretty interesting. But yeah, I guess it hasn't been something I've ever written about or not something that we're studying in the lab here, surprisingly, because it seems like we're exploring basically every indication possible of psilocybin right now. We have studies with bipolar patients, patients with Parkinson's, depression, substance abuse. So there's all kinds of directions that the lab is exploding into. But yeah, personally, I guess I don't have a whole lot of expertise in the end-of-life area. There's another aspect of it, too. I think that therapy has been good for couples, for individuals, people with mental illness.

and in some ways, I think that the use, I think people have, there's been great work done with couples therapy and MDMA. Yeah. I also know that, you know, when you are in a psychedelic, on the come down of like a psychedelic, like psilocybin, you tend to get into this philosophical stage where maybe hour four, hour five, you're really starting to ask some interesting questions. At least that seems to be a pattern for me. And I'm wondering if, if anybody has been. gun pioneering, you know, therapy, like talking to people, whether it's sitting down one-on-one or in a group and talking about the issues that they have. And if so, is there a premier time to do

it? Like, it seems to me like the late stages of the coming down period would be the best time to talk to somebody, but maybe some of the programming or maybe some sort of the conversation could happen in the beginning or the middle. Is there any kind of literature on that? Not a whole lot of literature, I would say. I would say just in personal experiences, you know, being in the dosing room that at the peak, people just aren't able to verbalize very much. They're not able to hold conversations. You know, they lose track of what they're talking about very quickly. Yeah. Can hardly finish the sentence sometimes.

So I don't think that, you know, there's going to be a whole lot of meaningful therapeutic intervention at that point, I think. Yeah, it's just hard to communicate. and that's kind of a central tenet of therapy is to communicate with each other. But yeah, I definitely think during the beginning stages and the later stages of this experience and people are able to talk a little bit more, that that could be useful. And also, it's a little bit drug dependent as well. So with something like MDMA, people seem to be a little bit more lucid and a little bit more cogent during the drug experiences and they actually are able to verbalize themselves a little bit better.

Yeah. As we're talking about different kinds of drugs, there seems to be an explosion in ketamine as well, which is a disassociative. Can you maybe help people in the audience explain the difference between something like psilocybin and a disassociative like ketamine? Yeah, definitely. It's, you know, the distinction in the lines between psychedelics and classic psychedelics and other types of hallucinogens is a little blurred. and there's a ton of debate about what, you know, to call MDMA and ketamine, whether they're psychedelics, whether they're just hallucinogens, whether they're second generation psychedelics, whether they're atypical psychedelics, you know, it's kind of an open area right now that's still being debated. But ketamine is distinct in its pharmacology compared to the classic psychedelics in its acute effects. It doesn't have the same affinity for the 5HT2A receptor that I mentioned before. that's characteristic of the classic psychedelics.

Ketamine, you know, it does seem like there definitely are therapeutic benefits, but they don't seem to be as long-lasting, it seems like, as with the classic psychedelics, that people tend to need to, you know, readminister the treatment on a more regular basis as opposed to the psychedelic interventions, which are just, you know, a very limited number of times. And ketamine also has a little bit greater potential for abuse as well so people can get addicted to ketamine in some cases, which is very rare with the classic psychedelics like psilocybin. I have yet to come across the shroom addict, I have to say. I'm sure they're out there.

And for some periods, people probably do abuse them. But, you know, in terms of comparisons, you know, it's, there's much less potential for abuse there, it seems like. So yeah, there's definitely just some distinctions between ketamine and the classic psychedelics and MDMA as well. So you've written too about what people call Blue Mondays. And for those who may not know, and tell me if I have this wrong, it's this idea that if you take MDMA, like a couple of days later, you kind of feel like all, oh, doda, like all clumsy and stuff like that. And I know that I've fallen victim to that. I don't know if it was a subjective thing that I felt or maybe you can talk a little bit about that. explain what it is and then talk a little bit about that paper that you wrote.

Yeah, definitely. So yeah, like you said, Blue Mondays is this kind of phenomenon that people talk about where they tend to feel blue or depressed in the days after taking MDMA or ecstasy. And, you know, this is something that, you know, I didn't have a whole lot of familiarity with before doing this paper. But, you know, the lead author, Ben Sessa, who's a really big MDMA researcher, great researcher in this area. He had done this pilot study of MDMA therapy for alcohol use disorder and mentioned that he had collected mood ratings in the days after dosing.

And so maybe that could be a way of looking at this potential Blue Monday's phenomenon. And he personally has had this theory for a while and now that there's a lot more that goes into Blue Mondays than just the MDMA. And so specifically, you know, when people take MDMA, It's often cut with a number of other substances. And so you're not actually getting pure MDMA in many circumstances. Additionally, many people, when they take MDMA recreationally, they combine it with other drugs and alcohol. And so that also kind of clouds the source of the Blue Mondays. And then lastly, people when they take MDMA often also take it at nighttime and

clouded or very crowded and hot nightlife settings where they're dancing, they're sweating, they're staying up very late and they're not getting sleep. And so it's kind of not surprising the next days that they're kind of feeling a little blue. And so, yeah, so there's reason to think about how much of these blue monies are specific to MDMA versus how much is it a consequence of the context that MDMA is often taken in. And so, yeah, in the clinical trial, you know, those confounding factors aren't present. They're not taking it at night. They're getting sleep.

They're not getting dehydrated. They're getting pure MDMA and they're not combining it with any other. substances. And with that being the case, we found that these participants didn't show signs of Blue Mondays afterwards. And so, you know, that doesn't mean that Blue Mondays don't exist necessarily. This is a, you know, this is one study and it's kind of a small sample as well, but it does kind of support that theory that perhaps there's a lot of other things that go into the Blue Mondays besides the active MDMA. That's a great point. I'm glad you brought that up. but it's more of someone just destroying their body versus like that actual one thing.

It's probably all these other things too, you know? It doesn't, yeah, it doesn't occur in a vacuum. Yeah, there's a lot of other things going on typically. But I will say, I think the title of that paper probably should have been tempered a little bit. You know, I think we call it debunking the myth of Blue Mondays. Right. Like I said a second ago, I think that's a little strong because I think, you know, the evidence is still kind of tentative and there needs to be more research there still.

Yeah. Right. But it's a good attention getter and it draws in people to like, wait a minute. This is not. Oh, okay. Yeah, that's actually kind of right. Yeah. That's what's exactly what happened.

Except the problem is most people don't read the paper. So they just see the headline. They're like, oh, these guys. That's a huge problem in our world. Like, I think the majority of people just read headlines of everything and they never read the articles or papers. They just go, oh, well, that must be what it is right there. Exactly. Yeah.

And it's hard, too. though because there's just so much information competing for your attention that you can't click on everything and you can't read everything so you know i get why people do that i do that too of course course yeah that you know i was talking to someone a while back about the problem of specialization and it's amazing that we have all these incredible people that are very specialized in searching this one thing but sometimes it makes it so difficult for the right hand to know what the left hand is doing because if you're so specialized you have to be so focused you're not paying attention to anything else that's happening, can very easily find yourself down just this weird road of,

you know, echo chambers and not in consciously pushing away information that could be relevant. And maybe in some level, that's, maybe psychedelics could be an answer to that. Maybe that opens people up and opens up their mind. And if it does remove memory from perception, then maybe that's a way to kind of bring us back together. But it's an interesting phenomenon. Yeah, yeah. And it's, it's harder, it's becoming harder and harder to avoid. know, these algorithms kind of picking what we're exposed to now.

You know, it's harder to go out of your way to get exposed to things that you wouldn't otherwise because, you know, you're constantly being shown things that are being picked for you, essentially. Just a really new and interesting phenomenon, yeah. So in San Francisco, do you guys have, have you guys decriminalized psilocybin over there? I believe that happened last year. Yeah, I live in Berkeley, actually, just outside in the East Bay. but I remember that they were talking about it or going to vote. I'm pretty sure that it happened.

Yeah. In Oakland, it's decriminalized. And I think Berkeley was going to vote on decriminalizing very soon or recently, too. So kind of the whole Bayer area has kind of been getting on that train. Yeah, it seems, I'm curious to get to see the effects of it. I know in Colorado, they have Prop 122 and they've decriminalized it. And, you know, there's these weird sort of avenues where you can't. and give somebody psilocybin or you can sit with them while they have a trip,

but there's still some interesting parameters around it that, well, people are trying to figure out how to get things done. But I think it does create a space for people to begin exploring and, you know, hopefully navigating some of the, doing some of their own people that are, and this is obviously not for everybody, but for some people, maybe you can begin to explore your own consciousness and explore your own problems

a little bit if you feel comfortable doing it. How do you see legalization playing out? Is it a benefit or is it maybe something that could be hindering the long-term pathway for psychedelics? Yeah, yeah, it's another good question. I've mixed feelings about it, I suppose. Yeah, in one hand, it seems like things have been moving along very smoothly for psychedelic science, right?

You know, in terms of the regulatory pipeline, things are just going wrong as smoothly as possible. MDMA's just had its phase three trials finished. seems like it's going to be approved next year psilocybin you know the phase two studies uh at least usona's just finished dating can data collection and so and there's obviously lots of good publicity around psychedelics right now people are really excited there's a lot of um just hope around psychedelics right now and so you know on one part of me is like why mess with a good thing why why jump the gun um but at the same time you know there's people that can't afford to wait you know um there's people who are dying every day from these disorders

and every day that we wait to do that, there's going to be more people that die. And so, you know, it's hard thing to balance, you know. You know, I think that there's enough evidence out there now that's pretty compelling that I can see why people would, you know, want to start experimenting with these types of therapies on their own. Oh, you got a cat there. Yeah.

What's that, Freddie? He loves, he heard us talking about psychedelics. I got, read it here oh nice yeah yeah they're super awesome i love uh you know they're they're little beasts but i love them yeah yeah they're great little friends and low-maintenance pets yeah i agree i agree they're uh they're fun to be around and stuff what you know what i had another question for you when does it it seems to me that it's incredibly difficult to thoroughly understand the psychedelic content in a mushrooms.

Like, you know, how do you measure the psilocybin or how do you measure the silicin in there? And is, is that, are people using like for ACOD DMT or silicin in the studies? Is that way they can measure it? Or do you know what's going on in those ways? Or people just, because you could have a, you could have an eighth of mushrooms, but it could be totally different than this eighth of mushrooms. You know, it seems, how are people measuring that? Are they using straight, you know, silicin in there?

What's going on? Yeah. So, yeah, so most studies have been using psilocybin in their studies, the actual psilocybin molecule. Which, like you said, can vary between mushrooms. So, you know, even within the same grove, one mushroom will have a certain concentration of psilocybin. Another will have another. And you don't really know which is going to be which without actually doing some kind of chemical analysis, which and most people aren't going to do. it's just not a very clean method of drug administration.

And so that's why we use the psilocybin molecule itself instead of giving people, you know, fungi. Yeah. But the problem is that that's still not perfectly clean. You know, I don't know exactly how they isolate the psilocybin from the mushrooms or make it synthetically, you know, in the lab. That's just a level of biochemistry. I'm not very familiar with. But yeah, like I said, I do know that they're using the psilocybin molecule in most studies. The exception would actually be the study I'm leading right now, which is the study comparing different methods of administering psilocybin and psilocin.

So what we're doing is we're having 20 healthy participants go through four dosing sessions. Each dosing session is about a month apart. And in one of the dosing sessions, they're going to receive 20. 25 milligrams of oral psilocybin, which is the typical dosing method that everybody's doing right now. It's a pill. That's 25 milligrams. It's pretty much a standard dose. And we're going to be comparing that with a pill of oral psilocybin, as well as two sublingual doses of psilocybin.

And the reason, you know, we want to use selosin is that there are differences in how people metabolize psilocybin into psilocybin. And psilocybin itself actually isn't psychoactive. It has to be converted into psilocin to be able to attach those two A receptors. And so when you eat mushrooms typically or take a pill of psilocybin, it goes into the stomach and a phosphate group gets removed and gets converted into psilocin. And then psilocin's what actually goes to the bloodstream and is able to attach to those receptors in the brain. There's differences in how people metabolize psilocybin into psilocybin, meaning two people given the exact same amount of psilocybin, even if it's, you know, 25 milligram pill,

are going to have different amounts of psilocin in the brain because of their differences in how they metabolize it. And also they're going to have different amounts of slosin at different time courses. And so for the same reason that, you know, that we prefer the oral pill of psilocybin over the mushrooms, it would be ideal to have the psilocin over the oral pill of psilocybin because, again, we're just kind of refining the dosing and making a little bit cleaner and making it a little bit bit more consistent between individuals. Because right now, like I said, if you give two people 25 milligrams of oral psilocybin, they're not going to have the same amount of psilocin. So it'd be ideal if you could have a more predictable method of dosing somebody where people respond more consistently

to a certain dose because they're not having those differences in how they metabolize the drug. And so the reason people, you know, that obviously raises the question of why haven't people just been using psilocin all along? That makes more sense to if you could. can just do that. And the problem is it's very hard to make a stable version of psilocin. So it degrades very rapidly. But the company that's funding our study, filament health, has developed this patented formula formulation of psilocin that has a much more stable in that you could actually keep in a pill bottle and it would not degrade very quickly. The last thing that's kind of notable is that the psilocybin and solosybin and solosylos,

and our study is actually taken from real mushrooms that they grew in a laboratory. And all these other studies, there's no real mushrooms ever involved. They're just making the psilocybin in a test tube, essentially, in a lab with other ingredients, essentially. They don't actually need the mushrooms to do that. So, yeah, there's a couple unique things about that study. But the main thing is that we're thinking that psilocyin will result in more consistent effects between individuals because we're removing the inner individual variability and how they metabolize it. And then also because we're removing that period where they need to convert psilocybin into psilocin,

we're anticipating, you know, faster onset effects and a shorter experience, essentially, and which would be kind of clinically helpful because it would save money and time by, you know, cutting down the duration of the trip a little bit. Yeah, that's fascinating. Okay. So here's another question I have for your study that might be worthwhile. You know, I was asking the question to a few people, like, why does the psilocybin trip come in waves like that? And the best answer I got is, well, that's how it's metabolized. So it metabolizes, and then a wave comes. And a metabolize it and a wave comes.

So if you have psilicin, I wonder if the frequency in between waves would change versus psilocybin. Because maybe that is breaking down that phosphate, and then you're getting that another you know, push to to the receptors. But if it's, if it's more of a clean, straight there, maybe the frequency in which the waves come would change. I wonder if that would be worth documenting in there. Yeah, that's really interesting. I never thought about that.

You know, I've two, yeah, I've too, been, you know, familiar with this idea of they're being waves to the experience. Yeah, definitely I've heard that from a number of individuals. Never really thought about what might be underlying that, though. But I think what you're saying makes a lot of sense, yeah. Metabolization, right? Because that makes the, that makes the, It's like, oh, you take, and that is also why, like, if you read the literature from people,

some people that I really enjoy reading say, diet is everything. If you do it on an empty stomach, the intensity is going to be better. Well, that seems to me metabolization, you know, and so, you know, the stronger the trip, for me anyways, and these are all subjective, but the most intense experience I've had were eating like a diet high in bananas for like a couple of days, a staining from sex, which is also keeping the neurotransmitters in there, and then almost fasting a little bit. And that just means instant metabolization.

That's what it sounds like to me. So I'm curious if that could at least be a reason for the waves and if so, might psilicin, you know, cut down or intensify the frequency or change the frequency of waves on there or something. Yeah, I would love to know that. Yeah, I would love to too. I think the first step to uncovering that is just to figure out how to measure waves essentially.

You know, how do we quantify that? Because that's the first thing you have to do is you have to be able to measure that somehow. Do you think pupil dilation? Like I don't know. Like maybe some sort of, maybe you might be able to measure. Do your pupils dilate when the trip gets stronger?

Or is that just a factor of light? Or I think on some level, you know, I try to go into my trips with my phone now. And like I'll do like a recording of like, and no one wants to hear these. but I mean, but you can begin to start talking about like rapid onset ideas or at least, okay, now I'm back. You know what I mean? Like you can begin to measure it in some weird way. Yeah, that's a really good idea.

Yeah. That's an interesting study idea to have people do that throughout their trip. Yeah. Obviously, we can't write things down very well. I know I'll let people try, but you want to look at the writings later. It doesn't make sense or just jumbled or whatever. Yeah. Or you don't have a pen there.

at that point in time, I don't even want to look at this notebook. But if your phone is always on record, you can begin, like that's something that I've always tried to do is, is I think that the, the, at least for me,

one of the goals to bring something back from that place, something that you can share with people. And a lot of times you come back with gibberish, but every now and then you can bring something back that is this shiny object that you could show people, like, look at this thing that I found. Yeah, exactly. You know?

Exactly. Reminds me of kind of just a little funny story. Yeah. Paul McCartney, the first time he took LSD, he thought the next day he said, I remember learning the secret to life and I wrote it down. He went and looked at the piece of paper and it said, there are seven levels, I think is all it said. He could not figure it out, but he was like so sure when he wrote that down that he had figured out the meaning of,

life. Yeah. And like I think that I don't think that's uncommon. Like I think all of us who have gone through big doses are like, I get it. I totally get it. And then you come back and all you have is the remembrance of understanding. Yeah. Maybe that's all worth it.

Yeah. But sometimes that's enough, right? It's enough to know that you had that experience. It's like MLKs, I've been to the mountain top or the burning bush. Like you've had this transendip. moment of knowing so you know it's there and it almost brings us back to faith it's interesting yeah exactly it's so amazing Jake I'm having an absolute blast my friend you know I I got a hard out coming up but I feel like I could talk to you for like another couple hours that works well yeah

yeah I was going to say I would love to come back I think I could continue this conversation for all day too yeah okay well before we go where can people find you what do you got coming up and what are you excited about yeah um So, yeah, I'm pretty active on the academic Twitter space and psychedelic space. Try to post all of our articles there and provide some updates on our ongoing studies every now and there, too. Also, you know, you can find a lot of my papers on ResearchGate. Just, you know, if you could Google my name, Jacob Aday, Researchgate, you should be able to find that. And our lab website is psychedelics.ucs.org.org.

edu so very easy to remember um if you want to see you know studies that might be able to enroll in or just exactly what we're up to right now and um yeah i'm hoping to to make it to the psychedelic science conference next summer i think that's the next the big psychedelic gathering that'll be at so hope to see you there too yeah i got my my next one of my next things to start start traveling a little bit so that's hopefully i'll be able to do that in the next year or so so awesome fantastic well ladies and gentlemen I will put Jake's information in the show notes. Reach out to him if you have some good ideas or you want to talk or you want to read some of his papers. I highly suggest him.

He's got a bunch of them out there. They're all very interesting. Ladies and gentlemen, if you're writing papers or if you're into psychedelics, reach out to me on the True Life podcast. Reach out to Jake. Let's make, let's amplify the good ideas out there and make this a place of change. And that's all we got for today, ladies and gentlemen. Thank you for your time.

Aloha.