Psychiatry & Psychotherapy Podcast - Psilocybin Therapy Part 1: History, Pop Culture, Safety and Side Effects, MDMA Studies, And Early Research

Episode Date: December 9, 2020

Psilocybin has been increasingly part of western consciousness. As the scientific community explores its therapeutic use and safety in controlled settings, there are a lot of people outside of that community who are passionate advocates for its recreational use. If we are to be knowledgeable about this subject, it is useful to know the sources that our patients are getting their information from, the history of its use, and what we currently know about its safety. By listening to this episode, you can earn 1.75 Psychiatry CME Credits. Link to blog. Link to YouTube video.

Hello and welcome to the psychiatry and psychotherapy podcast. I'm here to talk about getting rid of burnout, increasing job satisfaction, and feeling like an expert in what you do. One thing that created a lot of burnout and angst for me was trying to get continued medical education right at the last minute. So why not join the CME membership and do CMEE while listening to this podcast? Go to Psychiatrypodcast.com. Sign up, sign in, take the test, and the certification is email to you in seconds.

All right, welcome to part one of the psilocybin therapy. podcast with Nadav Klein. Can I say you're an expert? I think you're pretty expertly at this point. He is a resident at Ohio State University, a third year. He's planning on applying to palliative care fellowship next year. I say he's an expert because he literally, I mean, at this point, we have like 69 pages of single space notes from about, I would say 50 to 70 articles. And in this first episode, we're going to go through some introduction, we're going to go through the receptor, the history of psilocybin. We're going to talk about, gosh, what people are saying in the public. Guys, if you're listening to this and you're like, I'm not interested in this topic, your patients

may be interested in it, and it may be nice for you to be an expert on this compared to your patients, and you probably won't be unless you do a little bit of digging yourself. you know people like joe rogan people like terence mckenna in his book food for gods uh you know people like you know places like the goop lab uh have been talking about this you know michael paulin there's a 60 minute episode on it so this is out there but i think the way that we're putting it together is to really stick very close to the research so in this first episode we're going to talk through some of the pop culture stuff going on we're going to talk about the safety the adverse effects, the side effects of this. We're going to talk about, you know, how common

are those side effects. And we're going to go through some of the history of the research up until one of the early studies. Let's see. We're going to talk, we're going to stop right before we talk about, like, cancer patients and the use of this for depression. So in episode two, you know, please expect some of the more recent trials, some of the more recent research. Yeah. So So, Nadav, anything you want to say about part one, things you're excited about them learning from this, big takeaway points? What would you say? First of all, I really appreciate you labeling me as an expert. It's what I strive to be.

But, you know, a lot of this, you know, we talk about the history and we talk about what's going on in our culture. And it's just, it is out there. You know, it's out there in podcasts, in articles, in newspapers, it's being voted on in elections. It's, I really think it's going to be part of psychiatry in the future. And if we don't know about it, then we're behind. Yeah. Yeah. And so I think part of, you know, our, part of my take on this is I'm coming in here without, without any

desire to make this better than it actually is or worse than it actually is. I'm trying to just look at this data, look at the information as objectively as I can, as a psychiatrist, who maybe is a little bit hesitant to jump on board like some people. I think some people are like just gung-ho, charismatic. I'm probably not in that camp. I'm looking at this as like, okay, show me the research, show me the studies. Okay, I'm okay with you doing the research. Show me the studies. Let's look at it. You know, try to convince me. I don't know. Where would you say you are coming into this first episode. So I'm probably more excited than you are.

This was very much, this was very much a passion project of mine. I really wanted to pull in all the objective data and I really want to provide the best care than I can. And there is something about what I see about the possibilities that psilocybin has to offer relative to the other medications and the other therapies that we have right now, that it offers something new and exciting, that as someone who wants to do palliative care in particular, this is a tool in a potential toolbox that we do not have yet. Yep. Yep. And I think you have been excited about this. And I'm really glad you're excited about this because honestly, like, you've, how many hours do you think

you're into this. Like, it's, it's countless at this point. Yeah. It's countless. So it's a lot of hours. Yeah. Yeah. I, I appreciate the work that you've done. This will all be on the website in the resource library. It's, it's up there, guys. For free, you can capitalize on just very nice, concise notes that he took and really just going through from the very beginning to like up in the recent 2020 articles on this. So I'm really excited about it. Let's start now. So maybe start out. Tell me what it means when we say psychedelic hallucinogen. So the thing is, is that a lot of people combine different things together. It can be a really broad category. Some people include cannabis, MDMA, ketamine, and psilocybin. All these different substances, they rarely cause hallucinations, particularly when they're

used at common doses. Basically, they all alter consciousness, which is why people refer to them all in the same category. What we're going to be primarily talking about is what some people termed classic psychedelics, which are all mechanistically serotonergic 5HT2A receptor agonists. And we're going to be primarily talking about psilocybin, but there is going to be other substances like LSD or DMT, which are going to slip in here and then. Yeah. And, you know, other terms, psychotropics, psychedelics. Yeah, any other words that are used?

Yeah, so people use entheogens, which means the divine within. And it depends on who you're talking to, but people use psychedelics or psychotropics or entheogens all to describe the substances. Okay. And so tell me about this 5HT2A receptor agonist. So the way that we discovered that this receptor even exists was because of these substances. And it was back in the 1940s and 1950s that we became aware of it. And we're really just now learning a lot more about it. In terms of the, we actually use more substances which block the 5H2. H2A receptor, and those tend to be our antipsychotic medications, and particularly the atypical

or second-generation antipsychotic medications. Yeah, yeah. So the psychedelics are like acute agonism of this receptor, whereas the, you know, the second-generation antipsychotics are like chronic antagonism of these receptors. And what does that do for us when we chronically block it? So the reason why they're called atypical antipsychotics is because theoretically, they decrease the amount of dopamine in the areas of the brain which cause hallucinations, but can increase the amount of dopamine in other areas of the brain, which decrease the risk

of motor symptoms with the antipsychotics or elevated prolactin levels, both of which caused issues with the first generation antipsychotics in particular. Yeah, and we looked at this one paper, Carehart, Harris, and Nut 2017, anything that you want to mention about this paper looking at these receptors? Yeah, so this is largely a theoretical paper. As with, we're going to get to this a little bit later on, but the brain is, you know, a really complicated organ, and the things that we understand about it are really rudimentary right now. And so they're basically creating a model of how they are understanding the 5HT1A

receptors, comparing it to the 5HT2A receptors. And what they propose is that passive coping is, or like tolerating a source of stress, is primarily mediated by, the 5HT1A receptor, and that modulates our stress. The receptors tend to be located in our stress circuitry, that's what they call it, which is mostly in the midbrain, the limbic system, and the cortical areas, and it tends to be inhibitory in nature. And they compare that to the 5HT2A receptor, which they proposes active coping, which leads to enhanced plasticity. a more creative thinking in the brain. And so the 5HT1A receptor is mostly moderated by the things that we usually use for depression.

So the SSRIs and the 5HT2A receptor is what is changed by the psychedelics, which is what we're going to be talking about mostly today. Okay, yeah, let's jump into the history of psilocybin. So I really wanted to talk about kind of where, the earliest we could find this, right? And also looking at who's talking about this? Because there's a lot of pop culture discussion on this, you know? And I have to put out there that I have like, neither of us have any ties to the psilocybin industry.

We have no conflicts of interest. You may hear people out there who are like totally gung-ho about this. That's not us. We're trying to, or I don't know, I think you're probably a little bit more go-hung than me. But I'm trying to look at this as like someone who is assessing, you know, is this a good idea? Where are we in the research? How far are we along? And yeah, so tell me about the history of it.

Now, I just want to say that I am gung-ho about this, but I'm also doing this partly because I really wanted to look into it and see, I want to provide the best care that I can to the people. people who I'm caring for. So, yeah. And as we work together, I could tell, like, you were willing to look at the critiques of different articles. You know, you were like, this is the gospel. We need to push out this information no matter what. Okay, let's keep, let's, walk me through the history.

Yeah. So different natural psychedelic substances, I'm talking about psilocybin, ayahuasca, which is DMT or peyote, where the active ingredient is mescaline. they've played different roles in the development of philosophy and religions and in many cultures around the world. And it's really unclear, just a lot of the things that these have been used since prehistorical times. But many people have argued that it's been a catalyst for the development of the earliest cultures and theologies and creative developments among humans. So there are really old artifacts that indicate that there was psilocybin use thousands and thousands of years ago. So we have murals dating from 9,000 to 7,000 BCE in the Sahara Desert that are located in south-east Algeria, where they're depicting these horned beings as dancers, and they're wearing clothes with geometrical design.

and they're holding mushroom-like objects. And in this other image, there is another character holding a mushroom with lines extending from the mushroom directly into the center of the dancer's heads. Yeah, that's interesting to me. I think we'll put all this once again on the website so you guys can see these pictures for yourself. And yeah, tell me about this Spanish town. What do they find there? So the Spanish town of Villar del Humo, there are 6,000-year-old pictographs with several mushroom species in the pictures, and they've been possibly identified as a mushroom species called psilocybe Hispanica,

which is a species that's native to that area. And, you know, none of these things are definitive or prove anything in particular, but they are indicative that, you know, the earliest things that people were drawing, where were things, or some of them at least, were things that included mushrooms, seem to be central to what they're trying to show. Yeah. That's the argument, right? That's the argument.

That's the argument that people make in different books. And, okay, what about the Greek culture? What did you find there? So as far as we know, we don't know that much about a lot of the things that we're going to be talking about. But one of the things is the Elysinian mysteries. And so in the village of Ulysses in ancient Greece, for more than 2,000 years, there was a religious right for Greek citizens to participate in an all-night ceremony every September that involved a drink of some kind of special potion. that was known as Kaikian. And we don't know that much about this ceremony,

but we suspect that it was a hallucinogenic brew. There's one description of it from the second century that says, of all the divine things that exist among men, it is the most awesome and the most luminous. Yep. Yeah. I don't doubt that people are using these within rituals.

And I think this is one example of this. There's another example of the Soma in ancient India, which was a drink. So there are Vedic hymns that discuss a drink or food that open the doors of divine experience. And here are some quotes. Good fruit containing food, not any intoxicating drink. We drink you. You are the elixir of life. Achieve physical strength or a light of God.

achieve control over senses. In this situation, what our enemy can do to me, God, what even violent people can do to me. And there's references to immortality and light and their characteristic of what some people experience in psychedelic experiences. Yeah. And this is anthropologist Gordon Wasson, who commented on this. And we're going to touch base. So Gordon Watson will come up a little bit later, but he was one of the earliest, he was somewhat of an amateur anthropologist that brought awareness of psychedelics to the Western world, European world.

Okay. Tell me about this, this Aztec tradition, God's flesh. Yeah, so in the Aztec tradition, there were mushrooms, which were called Tionanakato, and then include mushrooms, ayahuasca and peyote, and they've been used for ceremonies for indigenous first people in the Americas for as long as we know. And so there have been species that have been identified based on vases and murals and other objects that have been found from the Aztec era. It seems like the plants were primarily used by priests and other nobility,

and they would ingest them and engage in prophecy, interpret visions, and healing. When the Spanish conquistadors came to town, they pushed a lot of these underground because they were primarily religious rights, and the Spanish tended to be wanting to convert the indigenous populations to Christianity. But they were first, these ceremonies were recorded,

first in Western culture, by a Franciscan friar, Bernardino de Sangan, who was in Mexico in 1529. And it was basically buried underground until in 1955, Gordon Watson and his wife traveled to O'Haka in southern Mexico. And they wrote an article in Time magazine, which we're going to link to. And it brought more awareness of the use of psychedelic mushrooms and the ritual rights that were used to the European and Western world. Yeah. So one thing that I like to consider is that as, you know,

experts, psychiatry experts, psychotherapy experts who listen to this, you know, we should be more knowledgeable about this than in the general public, which I don't think a lot of psychiatrists actually are at this point because of experts going on to people like Joe Rogan. So tell me a little bit about what you found there. There's a bunch of episodes. He's kind of a fan. And so the reason why I think we mentioned this is because it's out there in the pop culture, right?

These are ideas that are being discussed that your patients may know about and heard from experts. Yeah. It can be tricky to know more than our patients about some of these things because they've invested a lot more time in it than we have. And just with anything that our patients can bring to us. But here's at least some of the ways that they're getting that information. And so Joe Rogan, he's discussed psychedelics with many of his guests, among them. I just have a brief, a couple of them that I've heard, where he's talked with Dennis McKenna, Rick Doblin, who is one of the leaders of the maps, Michael Pollan, Dr. Andrew Weil. And on the format, they often are talking openly about the use of psychedelics.

And among those, you hear really powerful personal. experiences of people like Mike Tyson, who he talks about his experience with 5MEO DMT, which, and he describes it as something that turned his life around, and it helped him transition from being a fighter to being able to engage in life in a way that he was looking forward to how he could spend his time. And Paul Stamitz, who is one, like a mycologist, he studies mushrooms, and he's one of the foremost experts in the world, he relates a story where when he was a teenager, he took in very large dose of mushrooms,

and he stuttered his entire life, and then he stopped stuttering after that experience. So, yeah, I like, so it's, you know, I mean, if you want to hear the gospel of psychedelics, you know, we'll put these links up, you can listen to these episodes. And I mean the gospel, because these people like are the true believers right they like 100% think that these have value and

that this is kind of like a big thing that we're missing and it can be tricky because Joe Rogan often talks about it in a way where he's he talks about the importance of safe use and doing it in a safe environment but then depending on who he's talking to it also talking about using it in at a concert or in a in a party environment in one way in a way that we would not that no therapeutic experience is likely to be created from. Okay, so Stamett says, I don't think it should be something that people party with. And Joe Rogan says, damn, you were doing so good. I know, they were like, they're talking about how much they,

they were talking about like how useful they can be. And Stamitz was just like, you know, he was walking it back a little bit, being like, you know, we really have to be careful about how much. using this. Yep. Yeah. All right. You know, I wanted you to look at this a little bit just because it's like a, it's a

theory popping around that I've heard the stone-aged ape theory. Tell me about that. So it was first proposed by a guy named Terence McKenna in his book called Food for the Gods. And it's been reintroduced and popularized more recently by Paul Stamett. And the simple idea. well, it's basically reducing a very complex evolutionary theory into a simple idea where mushrooms were a catalyst in propelling humans into the modern era. And the way that the theory

goes is that mushrooms tend to go in animal dung and animals and people were tracking animals for hunting in the savannah. And there's like evidence that, you know, people would be using dung to be tracking these animals and mushrooms are growing in the dung and people are using these mushrooms and that's how they're having these psychedelic experiences. And the psychedelics offer,

it really depends on, there hasn't been much evidence or there hasn't been much science, on some of these ideas, but there have been on others where people are experiencing increased visual acuity, increased creativity, increased sexual activity. There's the development of abstract ideas and representational ideas like the development of language and expanded consciousness and ways of communicating. And there's also an extinction of a maladaptive fear response. So if people who are using these psychedelics or these mushrooms on the savannah are getting these benefits,

they're more likely to reproduce, they're more likely to be successful, and thus propelling people into a more cognitively developed. Right. So that's the, it's the narrative that is out there. And, and yeah, we're going to go through all the studies to look at, you know, what the reality is, like, does it change personality? How much does it change personality? And we'll talk about all those things to see, you know, what's legitimately known versus, you know, what's just kind of postulated as, you know, increased reproductive, you know, was this increasing someone's reproductive drive to use these drugs?

And therefore, the people that used them reproduced more and, best, better. Hard to say. Yeah. I'm actually probably more a fan of the idea that like those that worked together, you know, if you throw one person into a jungle, they're the biggest prey. If you throw a group of people that are working together, they're the biggest predator. So, you know, did different things increase the ability to be less individually competitive

and more cooperative? You know, I think those are the things that really drove us forward. Throwing rocks together, right, would be one. Yeah, so I don't know. I think, I don't know if this resonates with me entirely, but we're putting it out there as like, hey, this may resonate with you. You may be curious about this. Okay, Goop Lab. Yeah, so there's been a couple of popular culture things that have come out about psychedelics.

So the Goop Lab, which is a Netflix show, in their first episode, they talk about the therapeutic experience of using mushrooms. And basically it shows people going through a dramatic and meaningful experience. They talk about the idea of integration and therapy, but they don't really show any of it. They talk with a MAPS facilitator, and then they have a message from one of the people who've participated in studies in one of the research studies that we're going to be talking about. So it's it's kind of like the another example of this is out there. People are watching this.

People see the results of it. They see this antidotal like cases, you know, one single person going through this successfully over and over again, right? And this is, and this influences people. You know, this influences how people view things. There's a 60 Minutes episode, which is really similar, which shows it's basically focused around the research, but they also interview individual participants. And then there was this very popular book called How to Change Your Mind by Michael Pollan.

And he discusses the recent history of psychedelics, how it moved in the 1960s, and it's placed in the 1960s in the cultural revolution and the resulting backlash and the recent resurgence in the field. And then he also discusses his own personal exploration with these psychedelics. and tries to describe how it's functioning and how it changes his mind, how it changed his mind, other people's mind, and expands consciousness. Yeah. All right. So let's talk about what the psychedelic experience is like. And just, you know, we're going to look at some of the Wikipedia stuff, just pop culture.

Anyone can edit on here. I think there's some validity here. So let's start. I like Wikipedia. So what it says is that psilocybin can strongly influence the subjective experience of the passage of time. Users often feel as if time is slowed down, resulting in the perception that minutes appear to be hours or time is standing still. Users having a pleasant experience can feel a sense of connection to others, nature, and the universe. Other perceptions and emotions are also often intensified.

Users having an unpleasant experience or, quote, a bad trip, describe a reaction. accompanied by fear, other unpleasant feelings, occasionally by dangerous behavior. In general, the phrase bad trip is used to describe a reaction that is characterized primarily by fear or other unpleasant emotions, not just transitory experiences of such feelings. A variety of factors may contribute to the psilocybin user experience or a bad trip, including tripping during an emotional or physical low or in non-supportive environments. ingesting psilocybin in a combination with other drugs, including alcohol, can also increase the likelihood of a bad trip. And then they go on to discuss the difference between about the nature of the hallucinogens, the hallucinogenic experience.

So they're often pseudo or non-psychotic hallucinogens. They can experience changes in visual perception, from imagery with closed eyes or optical illusions, elementary hallucinations in synesthesia to picture-like scenery with hallucinations, their visual changes are almost always recognized as not real. And so that was taken from an article, which we're going to discuss later. Stradius et al, 2011. Okay, so yeah, talk about this Malone 2018 article on what is a psychic-egedalic experience. So in this article they write, people experience previous traumas, their own near-death or death experiences, a deep connection with themselves or other people and the work around them, other experiences with profound personal meeting.

You know, this reminded, a lot of these things remind me of things that you talk a lot about on the podcast, which are, you know, in bringing a sense of meaning and into people's lives and how important that is for the therapeutic experience. And, I mean, that's one of the things that I find most exciting about reading this, what people have done and what people are finding. So I pulled a couple quotes of which, like, everything that can be taken from man, but one thing, the last of the human freedoms, to choose one's attitude in any given set of circumstances to choose one's own way. And that's from Victor Frankel. And then Nietzsche writes, he who has a why to live can bear almost anyhow. And so that's, I mean, that's what I think that the Malone article is often getting at, is getting at where that people are finding that they're, they're finding meaning in these experiences. And we're going to talk about how meaningful people find these experiences a little bit later. Yeah. Well, I think, I think if you're re-experiencing traumas and you feel emotionally safe and you feel a connection with others, like that's going to change the nature of trauma. I mean, that's what, I do in the psychotherapy that I do, you know, when people feel a huge decrease in shame for

their experience through the therapeutic alliance, through the connection, through the empathy, through the different ways of reducing shame, then they feel that connection with you and that that actually changes the nature of how they experience the trauma. It's not going to be experienced traumatic. Again, you know, they're not retelling a story that's traumatic and they're also experiencing trauma and the retelling of the story. So yeah, and then I love these quotes, man. I mean, you get me excited about these quotes. He, he who has a, why to live for can bear almost anyhow. I mean, if you have reason, purpose, meaning, whatever it is, you know, I mean, you can get through some really tough things. And then Victor Frankel, you know, to choose one's own

way, there's an aspect of free will, a free choice, of, you know, making a choice. You know, making a choice, moving forward, and doing that even in a horrible environment, right? And that's really the beautiful thing about what he witnessed in the concentration camps was people loving on each other, even in the midst of this most horrible of all horrible circumstances. Yeah. Incredible strength of character can be witnessed in bad circumstances. this character, character is manifest.

Maybe thousands of different experiences that led to that moment where those people were kind and compassionate in the worst of circumstances. You can practice those things every day. But when the times get really tough, can you continue to manifest that? Okay, let's talk about this article, Hendrix at all, 2015. So this is moving on to like the safety and adverse events that we, that people see in studies and also among populations. So the Hendricks article is, it's a population study where they use, it's a national

survey on drug use in health who's completed by 192,000 individuals showing that psychedelic drugs such as psilocybin is associated with reduced odds in the past month of psychological distress, past year suicidal thinking, or past year suicidal planning, and past year suicide attempts. If you look at the article, and this is something that Dr. Peter, you were pointing out, about they're controlling for age, sex, education, income, risky behavior, and every other drug. Because when you look at who, like the populations of who has lifetime use of psilocybin, who doesn't. It's primarily white male, young to middle-aged, healthy individuals, people who are higher income and are using a lot more substances. Right. Well, I think there's a couple things going on

here. I actually had one of my research mentors look at this as well, and we were discussing it, because the amount of people who used the psychedelics also used like marijuana. I think it was like... I think it was 98% over 98%. 98%. And they were using other drugs

and they were... And the group in general were more likely to do high risk things. So in this study they're basically controlling for all of the different drug use but then I'm thinking to myself

okay so how did they control for that because that's like it really comes down to like that 2% of people who aren't using, who are maybe only using this right, which we don't even know if that is 2% because it, you know, just because they don't use marijuana, they could be using cocaine or they could be using this or that. So there could be some problems in this study in regards to that.

The other thing is this correlation does not equal causation, right? We know that for sure. And we don't know if the model is, we don't know model specificity because they're not testing for model specificity. So is the correct model looking at this data, or are they using the correct model to look at the data to map the data in the most accurate way? And so what my mentor was saying, Dr. Cashner, was that there are ways now that you can use many different models to map the same data, and then you could look at the models and how they compare to each other. And they didn't do that in this. So those would be the critiques of the study.

You know, I think it's good to put that stuff out there because, hey, if you're listening to this, you might be wanting to do research on this in the future. And so you might be thinking, okay, how do we look at this in the most accurate way possible? Okay, let's look at the next study. Kind of similar. The next one is also a population study. This was came out in 2013. It was 130,000 adults and it was basically they came out with similar results where there is no relationship between the use of psychedelics and panic disorder major depression mania social phobia general anxiety disorder gorophobia PTSD or psychosis yep so the same issue is I would have the same issue with what I just talked about with the prior study is that

the respondents who use psychedelics have increased risky behavior. They do have increased use of pretty much every other drug a lot more than the controls. Yeah. And so then, you know, did you properly control, you know, kind of like all the other aspects or, you know, so on so forth. So, okay. We don't know which way the correlation, but here I. In this one, I pulled out the graph. So it was like 98.2% had used cannabis compared to 33% of the general population.

And, you know, that goes down the line. Opie, it's 46.2% versus 7.7%. And all of the substances are just much more frequently used. So, you know, they're trying their best to control, but it's hard to know what it actually means. Right. And then even like the percentage of people who used psychedelics who had an extremely stressful event recently, that's 52% compared to the control 33.9%. So they're saying that after you control for all the other drugs, that it's the decrease stress. But, you know, the people who are using this are using a lot of other drugs.

are they experiencing things more stressful that aren't stressful? No, I don't know, you know. So I think there's like, it's good to read this as someone who's thinking about all the potential areas of, you know, where the study breaks down and where, you know, what it can and can't say, right? Yeah. The next study I have, here is the, it's by Scriabin at all in 2018, and this was a literature review about hallucinogen persisting perception disorder, which is a DSM diagnosis, and gives three case reports of it.

So for the DSM criteria for the hallucinogen persisting perception disorder, the first thing is that they have following cessation of the hallucinogen, the people continue re-experiencing one or more of the perceptual symptoms that were experienced while intoxicated with the hallucinogen, including geometric hallucinations, false perceptions of movement in the peripheral visual fields, flashes of color, intensified color, colors, trails of images of moving objects, positive after images, halos around objects, macropsya and micropsya. which is when images in the visual field are appearing much bigger or much smaller than that you typically are.

Awesome. Yeah. So that's a risk, right? That's a risk that it's like when you give your informed consent, you know, it's like you may have, you know, Alice in Wonderland syndrome. So that's the first criteria. And in the next article, I'm kind of mixed these two together, in the Baggett at All article, which is abnormal visual experiences and individuals with histories of hallucinogen use, which is a web-based questionnaire, they found that of around 2,700 participants, about 50% of participants had drug-free visual experiences like the ones we just described. So 50% of users are having these perceptions afterwards.

The second criteria, which is that it has to cause clinical, clinically significant distress or impairment in social, occupational, or other important areas of functioning. And in the web-based questionnaire population, almost 5% of users found the experiencing, disturbing, or sought mental health care for it. Yeah. I actually had a patient who came to me after he had a really bad trial. trip. He was at a party. He took a drop in his eye and then was told that it was LSD. And he, and then everyone was laughing at him. And he was, he described this very, very distressing event where he was felt completely outside of his body. And the, so the environment was like the worst environment you could possibly imagine.

to have a trip, right? Because everyone's laughing at him. Yeah. You know, it's now the joke of the party. Like, he's tripping. He didn't want a trip. And after that, he wouldn't drink from a water fountain. He wouldn't trust public spaces.

He didn't want to go to bathroom in public. And after three sessions of working with him in his trauma, I considered it like a trauma-like experience. He completely went back to normal. No drugs, no further treatment. He came, I think, one month after our last session, after three sessions, and he felt completely, felt completely normal again.

That's awesome. So, yeah, what were you thinking about when I was telling that, when I was talking about this? I was actually, a little bit later, there are other situations in the studies where people have negative effects, and then it's really only through the therapy afterwards that they're able to consolidate the experience

and understand it, and they go back to normal. but they need the professional help. Yeah, okay. So yeah, let's keep going this next study. So this is the Stuterus at Al, which we touched on before. This is 2011 study of acute, sub-acute, and long-term subjective effects of psilocybin in healthy humans, a pooled analysis of experimental studies. So this was a lab that over the course of a decade had 110 healthy individuals receive 227 doses of psilocybin.

Ranging from low to high doses. Two of the subjects dropped out of the studies after reporting strong experiences of either anxiety, fear of loss of ego control, emerging negative memories and thoughts during acute drug effects and were therefore not willing to participate in any further psilocybin sessions. So that's two. So basically two percent of the people who were going through this. Yeah. Then seven participants had negative changes.

in psychological well-being. So this is an additional seven participants. Six noted mild changes in concentration, memory, reactivation of problems, or becoming more pensive or introverted, which I thought was interesting that they noted that as an issue. But they did not think that it was significant enough to seek help for.

So that was six of them. And then one participant who was a previously stable medical student contacted the researchers after a high-dose session because he was having emotional instability, anxiety, depressive feelings, which he attributed to suppressed memories, thoughts, and feelings that he confronted during the session. And he was set up with a psychotherapist and his symptoms resolved completely within a few sessions. So kind of a similar experience, except this guy, even within the study, was having symptoms that he wanted to talk about afterwards. You know, there's two thoughts that come to my mind.

One is, I knew you were really into this before we started this. So I'm really glad you're reporting both sides of this, you know? And the second thing is, you know, Hippocrates talked about side effects of treatment. And it's a history, it's a tradition in medicine to look at outcomes and say that they're not always good. You know, if you get more into like the cultish belief of things. things, you know, it's like they never report any bad cases. Like, there are no bad cases. There's absolutely none. There are no side effects of marijuana. You know, there are no side effects of these things. So, you know, I think this, this is a great discussion because we're trying to

point out there are risks here. And there are some people who couldn't tolerate doses of psilocybin. And there are people with long-term. sequela where they're seeing things. Some things look really small or some things look really big, which would be concerning for some people going into this sort of, you know, do I want this type of treatment? Okay. I'm just a couple more thoughts with that is, I mean, I've been reading recently, I mean, the same thing with meditation or just talk therapy, there are side effects, the things that

people experience where people, if they're going through trauma therapy. and I have a patient like this who's going through trauma therapy and she's going through a really rough patch right now because she's re-experiencing things and it's she's more anxious now than she was beforehand but it's going to yeah yeah when you process trauma with someone though they'll feel worse often the day the week after and sometimes it's too much it's too much to handle And, you know, there are bad therapists out there. If you look at the bell curve of effect size, most therapists have a very narrow effect size. They're all going to be helpful.

In general, irrespective of treatment modality, you know, 0.7 effect size after, you know, 15 sessions is pretty average, you know. And if you're a little bit not as good, maybe you have a 0.6 or 0.1.4.5. five, you know. But there are, in these studies where they look at different therapists and the effectiveness, there are like the occasional therapist who all of their patients actually get worse, you know, like out of the 100 or 200 people that they looked at in this one study, like every patient got a little worse. And it's like, okay, what's happening there, you know? It's like the therapeutic alliance and amyotryptylene study that I've heard you quote before. There's the, yeah, psychiatrist, psychiatrist effect, emipramine versus placebo.

And they looked at how the different psychiatrists compare to each other. And there were some psychiatrists who were so effective that their placebo was better than the amypramine from other psychiatrists. And that shows that, you know, like therapeutic alliance, how we, you know, like if the patient feels completely on heard, if they feel horrible when they leave. This affects even how effective the medication will be. Okay, so yeah, break down this 2008 guidelines for safety, human hallucinogen research article by Johnson. Okay. So this is the human hallucinages research guidelines for safety 2008. So this, I don't know whether this makes sense, it makes sense to give some context. So There's like just a couple of different groups that are doing this research or that have historically been doing this research.

And so this Griffiths, Roland Griffiths, is the PI for the Johns Hopkins group. And we're going to see like a couple of names over and over again. So Griffiths is there at Johns Hopkins. And then Carhart Harris is at the Imperial College of London and doing a lot of the imaging studies, which we're going to look at. And we've already seen a couple of things. But for this study, they're talking about how to use this safely, and they're warning about the potential risks of using hallucinogens. And those include panic or fearful reactions resulting in dangerous behavior during the drug experience, precipitation or exacerbation of enduring psychiatric conditions, long-lasting perceptual disturbances, which we've talked. touched on already, and development of pattern of abuse on hallucinogens. And when they talk about

abuse, they make it clear that they mean people abusing it and they're making, they're putting people themselves or others at risk, like they're driving or they're, it's interfering with their work school or their relationships. And not dependence, not substance use dependence. Yeah. And then also, you know, does it increase the risk? risk of using other substances as well, which may be more risky than hallucinogens. Right. Because from the other prior papers, we saw that if they were using the hallucinogens, they were more likely to use cocaine, more likely to use, you know, opiates.

Yeah. So my intuition would tell me that it's a correlation of people who are trying illegal substances and not a gateway drug, like, but, yeah. Well, it's probably not the first drug they've used. But, you know, what we're talking about is using it in a professional setting, which, who knows, maybe that will have other unknown side effects as well, you know, like, because it really hasn't been broadly done. I mean, not like on a scale that they've used it in the black market, at least. Right. All right.

Okay, keep going. So for, in terms of like the dependence factor, there's little risk that it'll lead to physical or psychological dependence. Almost all addictive substances have some kind of interaction with the dopamine receptor or mechanism in the brain and psilocybin has almost none. And it seems to actually, we'll talk about this later, but it seems to actually be well suited for treatment of addiction of substances and minimizes addictive behavior. and we'll touch on some of those studies. Not that it minimizes the behavior in that large population study. It seemed like they went together, right? They definitely went together in those population studies.

Okay. All right. So tell me about this next study, 2016, survey study of challenging experiences after ingestion of psilocybin mushrooms. So this is a survey of almost 2,000 individuals who had just their experiences overall, positive and negative. And the mean age of people were, it was 30 years old, it was 78% male, and it was all done through an online survey. They note that only 2.1% of the responders were taking it under conditions that were similar

to a lab laboratory setting. And so that's, you know, you're talking about preparation and having an appropriate mindset, having your physical comforts being taken care of, having support of others, a trusting guide who is experienced in psychedelic experiences. So almost 98% of people are not having it in that experience. Yeah. So one of the things they asked, they asked about, like, you know, their worst trip and they asked about their best trip, and the median, the people's median responses was between six

and ten prior psilocybin experiences. And so, 84% of people in these uncontrolled cases reported a benefit from these experiences. 39% rated it as among their top five most challenging experiences in their lifetime. So challenging whether or not that's positive or negative, that sounds really emotionally intense. It sounds very intense. Very intense. 40% said that it was one of the top five challenging events in their life. Okay.

And then for negative outcomes, 11% said they put themselves or others at risk of physical harm, so that's them driving or doing other risky behavior. 2.6% behaved in a physically aggressive or violent manner. 2.7% received medical help during the trip, and 7.6% sought treatment for enduring. psychological symptoms that continued over a year after the trip. So that's high, you know, it's... That's, yeah, like, so eight, almost eight percent had enduring psychological symptoms

that continued greater than one year after the trip, and they sought treatment because of that. Okay. Of these 2,000 individuals, three people attempted suicide, and three people had psychotic episodes. So of the three cases who had psychotic-like experiences, they were all white males between the ages of 18 and 21. One was diagnosed with schizophrenia. One was eventually diagnosed with bipolar disorder, and one had a psychotic episode. Those undiagnosed. So, you know, this is the population who are most at risk for their first break of a psychotic episode.

Yeah. It's interesting in the studies we'll get to later where they, you know, treated people with psilocybin and therapy. They asked about family history of psychosis, bipolar, and excluded those people from the study. Yeah. So it's true. Like almost all the studies that we looked at, they're taking, I think it's second generation, almost all the, not second generation, but first degree relative with bipolar disorder or bipolar spectrum illness. and a second-degree relative with a psychotic illness. So a degree relative, that's like a first degree is like a father, a sibling, or a child,

and the second degree is like an uncle or an aunt. The other thought about the suicide here, this is kind of, this is pretty intense that three cases attempted suicide. Even with SSRIs, which we know, you know, like the risk of suicidal thoughts increases in those younger than 25, maybe from 1% of the placebo to 2% in the people that take the SSRIs, there's no cases in those big studies

of like 10,000 people plus that they were looking at where people actually tried to commit suicide. You know, and the other aspect of this, which, to be fair, it's like, were they using other drugs at the same time? Who knows? They actually talked about, I didn't take it out,

but I think 50% of people, It was like between 40 or 50% of people were using cannabis at the same time. So there definitely was other substance use and other things going on. Right. So is there, and the other thing is like how pure is the psilocybin that they're taking, the hallucinogen that they're taking? Because, you know, often if they're taking street powdery stuff, you know, it could be laced with all sorts of things.

Fentanyl is something that's very commonly now being laced in all sorts of things. of drugs, which is very dangerous. And I think people accidentally overdose on things laced with fentanyl because, you know, it's like, what, 100 times stronger than heroin? Like, are you going to trust a drug dealer to dose that properly? Probably not, right? So we'll talk about psilocybin specifically because it's mostly in mushroom form. So just with these three suicide attempts, it's just good in the context, two of them had

a previously diagnosed depression and had suicide attempts in the past. One of them tried to overdose on benzos and woke up in the ICU. One tried to shoot himself. And the last one had some kind of unspecified suicide attempt. There were two people who had increased suicidal ideation. And then on the positive side, there were six respondents who reported that they had, they previously were having suicidal thoughts, but they completely remitted after the psilocybin experience. So, okay. So to be clear, because I appreciate you pushing back on me. against this. So you're saying that it's not like they're taking some powdery substance here. They're taking mushrooms, so it's probably not laced with something else.

Yeah, that's what I'm saying. And we'll talk about, we'll talk about it a little bit later, but basically there are very few instances that are recorded at all about psilocybin, mushrooms being laced with fentanyl. I looked at this. I asked you to look at this in particular. No, and I think that's important because, you know, when someone's taking a Xanax bar, It's a slurry of, you know, and it's a street Xanax. It's a slurry of stuff. But, and when someone's taking marijuana, I think there's only a couple cases that I could find where there's, like, laced with fentanyl.

But on the other hand, you know, something like a mushroom, it's probably just a mushroom, right? It's probably not laced with anything else. Okay, keep going. So as a reminder, this was the Johns Hopkins group. And they compared that data, which was a survey data based on their own experiences in their lab. And as of May of 2016, they had had 250 volunteers in more than 380 psilocybin sessions. And of those 250 volunteers, three people had contacted researchers for negative outcomes and experiences afterwards that they thought were associated with the psychedelic experience.

One of them ended up having hyperthyroidism. One of them had ended up having an anxiety attack, which was screened by the AD. and one of them deferred help from the Johns Hopkins team and instead sought their own spiritual counselor and their symptoms resolved within five months. So in the controlled setting, it seems like the outcomes have been pretty safe. They were less.

They were less. And this is a smaller group than the 2000 people. One hyperthyroidism, I wonder if that person had the hyperthyroidism before and if that was causing the anxiety even before. So it's like, you know, do we properly screen the people getting treatment, make sure they're not having endocrine-type stuff before we try to give them psychotherapy, psychiatry treatment?

Yeah, okay. So then this next study is a Gable study from 2004, and its comparison of acute lethal toxicity of commonly abused and psychoactive substances. And so basically there's a graph here that we're looking at, which on the x-axis is the toxicity and on the y-axis is how what the dependence potential is for these different substances. And on this graph, they put LSD and psilocybin on the very bottom left, which is putting it as very low, very low lethality and very low dependence potential. Yep, so the high lethality type of things are the heroin, morphine, cocaine, alcohol, MDMA, and then, you know, goes down from there. So caffeine, they put as more, you know, it's easier to overdose on caffeine on a high dose than LSD psilocybin.

That's what they put on this graph. For like cannabis, they put very low lethality risk, but, you know, a moderate low dependence potential, but higher than LSD or psilocybin. Yeah. Most people don't get dependent in the same way with marijuana. It's more like they get an attachment to the actual event, the drug. Okay, cool. This is helpful.

Yeah. The way that he, just so like we have an idea of how he got to like the dependence potential because he, you know, he's got like nicotine right at the top. He compares how many people who try the drug will continue to use it despite a desire not to. The second criteria is if people experience withdrawal symptoms when the drug is not available. And at the top here would be like alcohol, heroin, and barbiturates are there. And then the third thing is how strongly people want to repeat the drug experience because of euphoria, sensuality, novelty, or whatever other reason they want to repeat this experience. Here was, and then I put in a little bit of a anecdote.

Okay. Let's hear the end. So there's no reported deaths from overdose of psilocybin or LSD, but there was an Indian elephant in the Oklahoma Zoo, who in 1962 was given almost 300 milligrams of LSD, which is 3,000 times the human recreational dose, and that elephant died. There is some question about whether it was the LSD that killed it or the drugs that they tried to give the elephant to revive it. so you know don't inject your cat with LSD or with large quantities large quantities or don't take large quantities of all to yourself it's not not a good idea right the most LSD is like very potent

so they're not giving very much at all to people yeah it's like a drop it's like a hundred micrograms very very small amount yep very very small so that's a very very small so that's huge that's a huge dose so what about lessons from that we can learn from the mdMA trials so mdMA trials are ongoing they're in they're completing phase three trials right now and they're using it to treat PTSD and it hasn't gone there there was like a really big hitch that happened a few years ago. So yeah, give us all the graphic details, please. Yeah. This is this is this is the podcast where people start to like disengage and this will kind of help bring the back in a little bit. So a few years ago, one of the guides in the MDMA trials had a year-long sexual relationship with

one of the participants. Which was facilitated with his wife? Yeah. So all. All of the MDMA trials are facilitated. I don't know if this was all. It's definitely, it happened here, and it's definitely happening now, but all of them are facilitated by one male and one female, usually facilitator. And in this case, the therapist was with his wife who facilitated this participant, and then the male therapist had a year-long sexual relationship with the participant. It was ongoing MDMA therapy during that time.

or was the sexual relationship outside of the therapy office? So it started after the MDMA component of the treatment, but and while like after like the therapy component was done, but it was still while the follow-up period was going on. So what we know is that it started during the follow-up period and continued afterwards and the participant, it was off the coast of Canada and the participant moved to the island, where the therapist and his wife were living,

and the participant continued to have therapy by these therapists and also was having an ongoing sexual relationship with the husband. The wife became aware of it at some point and didn't report it, but tried to make it stop. That's as far as we know. and then it was reported to the maps, who was the group conducting the study, and there was a suit that was filed

that named both therapists. Okay. Yeah. Well, that's good on, so the maps regulated it. They actually filed a suit. They didn't just sweep it under the rug. Is that what you were saying?

Yeah. Well, it was the... The patient filed the suit. The patient filed the suit. Oh, okay. The patient found the suit. Just some things to keep in mind. So I have a quote here from the quartz article, which is where I got a lot of this information. It was between that and the MAPS website.

Catherine McLean was one of the researchers who was really evolved in the psilocybin studies at the Hopkins and not with the Hopkins group. And she talks about how MDMA in particular increases the effects. in the feelings of attachment that people have by decreasing the amygdala activity and increasing oxytocin. And so they feel closer with people than they do in normal circumstances. And their MDMA is known to elicit sexual arousal and emotional intimacy, which is different than psilocybin, which doesn't have the same mechanism of action. But these do sometimes get lumped together, but it's still like this is something that we need to really be careful of. Whenever we're doing therapy, it's really just important to keep up really strong sexual boundaries with our patients.

I pulled this other article because just in therapy in general, there's an unequal relationship, and there are legal standards that are put in place where, you know, therapists are not able to have any kind of sexual relationship with their patients even after they terminate treatment. And that's unique for therapists and psychiatrists. So this was a study that I found and that it was a study where they asked therapists how many of their patients reported having sex with a previous therapist. Oh, wow. Yeah. Okay, what are they find? So they found that 4.4% of therapists had inappropriate sexual relationships with the people that they were treating. And they had 7% of male therapists and 1.5% of female therapists.

And, you know, this is a really difficult, this is not people reporting on themselves. This is not people reporting it themselves. But they, you know, it's likely underreported. It's something that's really taboo. it's a really difficult thing. It's a serious issue that we have to keep in mind. And this is why we have strong boundaries in therapy. Yep.

Yeah. I actually, I've had therapists reach out to me, probably because I have a podcast. And one person in particular, they didn't want to tell me who they were. And I never, you know, kind of anonymously had a conversation with this person who was really struggling. And it's, so yeah, it's going on. Sexual transference exists.

You know, when you get close to someone, there's this bond that's created. And it's, you know, especially if patients have been sexualized early on in their life that's intensified, where it's like sexualized, meaning like they got attachment connection to other human beings through sex.

And so that makes it a lot more dangerous for them in any type of, of relationship where they're getting very close to someone. You know, is this going to be a relationship with boundaries that's going to be life-giving that's going to be for them or is it going to be for the, you know, meeting the own, the gratification of the person giving the therapy, right? Which is where the boundaries break down. Okay, so this was good to include because it's like, hey, this is going to go on, period, right?

This is just going to go on. We know it's going to go on. are people who are giving MDMA going to have increased potential for this? Potentially, just because the drug actually elicits feelings of very close emotional intimacy. I've had friends who have taken it and they say it's something beyond anything that they've ever experienced intimacy-wise with the people that they're using it with. interestingly i have a patient who has taken a group of people to a you know to a location and they all use it together in a hotel room and they just talk right and um he described to me that they were able to talk in the same way that he was able to talk to me as his therapist like without shame

with that connection and and yet these were people not trained to be therapists He was leading them in this, so to speak. But I'm sharing that because I think that the connection that people get from MDMA is something that can be in a similar way found in a good therapeutic alliance where the person has incredible amounts of reduced shame for their normal sort of experience of talking about things which are very shame-inducing. it makes just like the privilege of the therapeutic space and being able to do that like you yes you just end up talking about these things that because of the boundaries it's only because of the boundaries that were we allow patients to talk about their sex lives and their shame and and we need to keep those boundaries because you're going to make things so much worse I think that makes me think I value this this ability to have this relationship so much that the boundaries for me are just absolutely

100% necessary for me to continue, right, so that I can continue to have this type of meaningful work. For me, that's, I mean, that's at the end of the day. It's like, I realize, like, if, if, if I was to succumb to, you know, have a sexual relationship with the patient, I could potentially lose everything. Like, I could lose my job. I could lose the ability to, to make income. I could lose my marriage, my relationship with my kids. So the cost is very high. But if his wife is allowing this to happen almost, you know, or, you know, that seems like. So in this case, the, he was, he let his credentials lapse and it was his wife's credentials.

So in the, yeah, so in the therapy, they needed only one. Yep. one licensed therapist and another support person who didn't need to be licensed. And so he had let his license laughs already. But yeah. I mean, gosh, I think we could talk about stories of famous, famous therapists that had had relationships with clients or graduate students or, you know, like, there's a very colored history. That'll be a separate episode. If you want that episode, let me know.

And I will make that episode. Maybe you can help me make that episode. That would be a fun of the dark history of psychiatry and therapy. Yeah. So after that fiasco, what did MAPs change? So they created a code of ethics, and now they have specialized training for therapists and a consent form for the MDMA trial that specifically include, includes something that says, you may also feel closer to your therapist or more trusting of others,

or you may feel love and sexual feelings towards your therapist. This can happen with any psychotherapy, but may be heightened by MDMA. Your therapists are aware of the effects of the drug. They have been through training on how to appropriately care for someone who has taken MDMA on a code of ethics that prohibits any sexual relations between therapists and participants, including after participation in the study, ended. Good. Yeah, and they also talked about the use of touch that we only offer touch such as touch if they fall within our scope of practice and competence. You know, because sometimes, like, in so, like, somatic experiencing, they'll do different, like, pushing of one hand against another

and stuff like that, so they're not, like, completely eliminating that as an option. Yeah, I've seen in the way that they demonstrate the psilocybin therapy, they have people, like, touch. someone on the shoulder or, you know, holding hands with somebody and breathing with them just to ground them. Grounding them, yeah. That makes sense. Cool. Yeah, anything else from that? No, I just, you know, I feel like, I mean, that looks really bad on the MDMA trials. That was one instance. They've been, they've done this on hundreds of people and it's a very, it's a new situation. And I think it seems like they're dealing with it pretty well. Like they came out. They immediately recognized the, what had happened and you know it's a difficult thing when you're delving into something new.

Yeah. Okay, let's talk about harm reduction. Yeah, so for harm reduction for the use of psilocybin or LSD or MDMA for that matter, if anything you're getting off the street, you should be

testing it for safety and there are test kits that you can buy online and there's a link in the show notes that we have put. Yeah, I want to include this. Just because I feel like someone's going to be listening to this, trying to educate themselves on how to do this without getting the proper credentials, right?

I mean, that's always a risk. This is medical information. We're not giving you medical advice here, as in with all my episodes. But, you know, the harm of potential fentanyl overdose, stuff like that, depending on what you're getting, you know, stuff like that, I think, is important to educate the population on. Yeah. So for psilocybin specifically, it's very rarely available in a pure form.

It's almost always available in the form of a mushroom. All the studies that we're going to talk about use it in the pure form, and they all have it synthetically created in labs. Yeah, and it's just not that available. For psilocybin, the recreational dose range, is from 0.1 to up to 5 grams of dried mushrooms because it depends on the species and the individual strength of the specimen

because there are over 180 different kinds of mushrooms that produce psilocybin, and they all have different potencies. Generally, the cost is generally between, this is what I got off of Aeroid, which is a website that has a lot of information about street drugs, but it's about $20 to $40 per an eighth of an ounce, which is $100,250 per ounce. And an eighth of an ounce is around what a dose would be.

It's pretty cheap. Yeah. I mean, you talk about like the cost of ketamine clinics, you know, it's pretty high, pretty high cost. I think it's important to talk about this just because, like, what is, you know, what is out there? What are people doing? Well, it's pretty accessible at this cost. I would also think that, I mean, if you're just looking at ketamine in its raw form, it's probably also probably in a similar range.

It might be even cheaper. Yeah, ketamine's cheap, but it's just the injecting, having staff, all the extra costs like that. That's what's expensive. I mean, there's a reason why people. who are not psychiatrists are opening up ketamine clinics because it's very profitable. Right. And they're doing it on anyone who wants it done rather than like maybe a strict screening like a tertiary care center would do. I mean, that's always my concern with stuff like this is you're going to get some person on the periphery who's, who's entrepreneurial, who's doing this not to really first and foremost help people, but to make money, gratify.

First and foremost, their own needs. They're not going to act as a fiduciary, you know, where they're looking out for the best interests of the person. You know, they're not going to screen the person for, you know, are they, are their relatives with the history of psychosis that might put them at increased risk? Okay. So what else do you find about the underground therapy? Because I was curious about this. I asked you about this, like what's going on? Yeah.

So it definitely exists. Michael Pollan talks about it in his book. And that's probably where it's most popularized. But the way that it's not so readily available, I kind of searched through Reddit for people talking about how much it costs. And basically the numbers that were quoted there were, it's like $450 to $750 for the session without any preparation or post-integration sessions. And then if with things that you have,

have that you're just increasing the price from there. And in terms of its accessibility, it's really hard to find. The people who talk about how to find a therapist, an underground therapist, they talk about how they basically attended a lot of conferences and did a lot of networking. This specific thing is a guy from Australia, and he goes, he flies to Europe, he flies to the United States, he's going to all the different conferences that he can find to find somebody. It's hard to find someone who's going to do a really good job underground. That's some dedication. Yeah.

That guy has some dedication. And you're going to find people who are searching. They're searching for alternative solutions. Then maybe what this, you know, standard care hasn't helped them as much as they would like. For contamination, you mentioned this before and about this being concerned, particularly with other. substances of potential abuse where I looked through Google searches for cross-referencing fentanyl or car fentanyl with psilocybin. And on like page 8 or so, I found something in Quebec where there was, they did find that there was some fentanyl on some mushrooms. But it doesn't, it's really uncommon.

in. Most of the articles that came up were times when they busted somebody for fentanyl and then they traced it back to a house that also had a bunch of mushrooms in it. So on this one article,

the article title is, why the beep is fentanyl showing up in LSD meth and cocaine? Yeah. That's interesting that they found it actually on the mushrooms. Unfortunate, right? it's but you know there are risks of getting things in the black market and uh unless you know

someone who's growing it themselves you know or who's an expert i think that's where it's like you know if this this one guy who's like search going to conferences meeting people trying to network right it's a lot of a lot of effort um and so i here's this thing also about LSD and contamination with LSD. And when I first started looking at this, I think when we were preparing for the episode, I was like, you know, this isn't going to be really an issue because it's dosed in microgram amounts and even fentanyls, not dosed at that amount. But there are other drugs.

You know, as we've been, as we've advanced technologically, other drugs have been discovered. And so there are new contaminants. specifically there's one called N-B-O-M-E, which is also active at very small doses and can mimic effects of LSD and has been sold as LSD. And the differences, the way the experiential difference is, based on what I read, was that there's less introspection, but it produces a lot of very strong visual and sensory effects. there's a few more side effects, physical side effects like basal constriction. And then one of the ways that a lot of people I saw were talking about how to determine that LSD itself is tasteless while NBOME tastes bitter. But I would test things before you taste them.

I would use a test kit if you're going to be using any substances off the street. Yeah. part of the, I mean, the only, like, car fentanyl, for example, could be another example of something that could be laced, you know, which is like a very, very small dose of car fentanyl could be toxic. You know, worst case scenario, obviously this is probably going to be pretty rare. But, you know, once you kind of go into that world of the black market, you don't quite know what you're going to get. Yeah. Okay, let's keep going. So talk to me about the research in the 1950s, 1960s.

Yeah, so this wave of research that's been going on in the last 20 years is not the first time this has happened. So Albert Hoffman discovered LSD in 1938, working as a researcher for a pharmaceutical company in Switzerland. And between the 1950s and 1960s, there was a lot of research that was done with Hulu's. and it was particularly with LSD, where there were over a thousand papers that were published. There were a few conferences. It was prescribed for treatment for over 40,000 patients over that 20-year period. And most of the research was they were treating alcoholism, narcotic use, recidivism for people in prison, and as just an adjunct for psychotherapy, creativity, sleep.

autism and schizophrenia. You know, as was the nature of medical research back then, there were no randomized clinical trials, and all of these had varying levels of success and were likely to be susceptible to all kinds of biases, which we're going to get into in the later papers. Okay. Wow. So no randomized controlled trials back from then. But a lot of people took it. A lot of people took it. Yeah. They were giving it to a lot of people. Yeah. And it was all put to a stop by the Controlled Substances Act in 1970. Dun, dun, done. Yeah. It's like, it's like we had this, there was like this almost, they were like, they thought it was going to be this renaissance. And then it got shut down after LSD got leaked into the cultural revolution. So this law created a classification system that is supposed to, you know, be dependent on the criteria of the potential for abuse and its current acceptable medical uses in the United States and international treaties, with Schedule 1 being the most restricted, and Schedule 5 being the least restricted.

And it made LSD and psilocybin Schedule 1, which ended research. Yeah, so last research trial being completed in 19. 76. And the next one was done in 1994. So there was a big gap of no research. Yeah. So Schedule 1 substances, which is what psilocybin and LSD were both put into, it indicates a high abuse potential and no medical use and severe safety concerns. You can think about how silly this is, really, okay? It just doesn't make sense anymore for what we know about these things, right? Schedule 2, hydrocodone, cocaine, methamphetamines, dilauded. I mean, these are like the big guns, right?

These are the, especially like things like, you know, things that should only be prescribed by doctors here, fentanyl, you know, that kind of thing. Whereas like Schedule 1, the thought that marijuana is like a Schedule 1 substance is like compared to methamphetamines, to me it just blows my mind. Yeah. So Schedule 1 is only. almost all substances that shouldn't belong there. The other schedules, they maybe, you know, they're, you know, they're trying to figure out a system,

but everything in Schedule I really seems like it's inappropriately placed there. It amazes me that schedule, all the way down at Schedule 4 is benzodiazepines. I would put that almost as like a Schedule 2. I would put Schedule 1, I'd probably move methamphetamines up there, fentanyl, stuff like that, opiates, cocaine. Well, Schedule 1 means that there's no medical use, and we know that there is medical use, because you can use them for painkillers.

It's just Schedule 1 should probably be eliminated, and then just from there. Right. I mean, okay, you could use cocaine for nasal procedures to restrict blood flow, okay, maybe. But what I'm saying is, like, in the dangerousness in terms of, like, addiction and that kind of stuff.

Definitely. So then the question is like, why was psilocybin placed in Schedule I? And the things that I read about were mostly talking about the context in which the law was written. So it was during the Cultural Revolution. It was during the Vietnam War. And the political entities believed that these drugs, marijuana and LSD and psilocybin, were threatening the moral fabric of the country. And so they made it illegal.

Yeah. So Terence, Terence McKenna, who is a psychedelic advocate, said, Psychedelics are illegal because they dissolve opinion structures and culturally laid down models of behavior and information processing. They open you up to the possibility that everything you know is wrong. Like one of the things... Wait, wait, wait. As you say that, you flashed a little bit of fear right at the end there.

What is your thought there? You know, it's a really, it's a scary idea for a, what, I guess, I don't know, I flashed me. I don't, I don't recognize, I didn't feel fear, I don't think. You flashed fear, man. Your mouth went horizontal. That's a micro-expression of fear. Sorry, most people don't like their emotions being called out real time. Don't do that in therapy.

Okay. So, I mean, something about like the moment, right, of everything that you thought was true being false immediately. It's, it is a little bit, the fear that I would have there is it opens you up to brainwashing, right? It's true. I mean, defenses, psychological defenses that keep people. from being open, keep people also from, this is coming from someone with very high openness on my Big Five, like you.

It keeps you from maybe accepting things that would be wrong or harmful or destructive. So, I mean, there are certain things that, like, if you lose that ability to have those defenses, but I'm not sure that psychedelics really do that. And we're going to get to, like, how it changes personality later. and honestly it's not like a huge shift.

Yeah. Yeah, I mean, one of the things that people do experience, I mean, one of the people talk about is that if you have a lot of young people taking these substances, then they're not going to want to fight a war across, on the other side of the world. Like the idea of going to fight a war after feeling really connected with the world and feeling like what you're being told by society isn't accurate is just much less. likely. Well, you, I mean, if you want people to fight a war, you, you increase the disgust towards the person that you're fighting the war against. Right. You know, these are,

these are subhumans. They're not humans. These are cockroaches. You inspire disgust, which in our political climate, bi-directionally, that's going on a little bit on both sides, which is a little bit scary. It's really scary. Honestly. I mean, it's like, if you don't believe what I believe, you are now subhuman. Okay, if someone is subhuman, you might be willing to hurt them. And we're seeing some of that, you know, actually happening, right? So be very aware when you hear political figures dehumanizing the other side. Dehumanizing.

That's crucial. And if you listen to, I've heard some military leaders talk about what they talked about in front of their men day in and day out. What did they highlight for when they were fighting ISIS? They highlighted all of the disgusting aspects of them chopping off heads. You know, they would show them videos, show them pictures. And it's, you know, okay, yeah, I agree that people who do that are horrible, right? And maybe that is a good idea to fight those people. before that comes to your

homeland, right? But at the same time, it's the emphasis on that over and over again that allows people to overcome the psychological barrier to hurt another human being. Yeah, that's just a little side note there. Yeah.

Okay, let's get into the modern era. Yeah. Clinical trials. Yeah, so as we mentioned before, the first trial was in 1994, but the first really controlled trial was published in 2011. But before we get into those,

I want to talk about the structure of the therapy, because it's pretty, it's for almost all of these, it's fairly uniform, where there are two therapists throughout the process, often, usually one male and one female, and the psilocybin experience is embedded within psychotherapy. So they have one to two multi-hour preparation therapy sessions beforehand. And reading these articles, a lot of these sessions, there were like two, four, or five-hour sessions where they're creating the mindset. You'll hear a lot of people will talk about the set and setting of the experience. So that's the mindset and the physical setting in which the experience is happening. And it's preparing people, they're preparing people, there's an expectation that this could be a profound experience. And so they're reviewing people's life story, the most meaningful experiences of their life, who the most impactful people in their lives are. What are the things that are most important to them? The role of religion and spirituality. What have been their most

important successes and failures? So they're really, it's kind of like this global perspective about their life and, and preparing for, without being directive, for some kind of significant experience to happen. And then during the session itself, they, encourage introspection. In contrast to some of the MDMA trials, which there is therapy going on during the trial, it's people are lying down with eye shades on a couch with a predetermined, with a predetermined musical playlist. And the experience itself lasts between four to six hours, and they're encouraged to just be completely internal. And then after that psilocybin session, they have integration sessions and those either two up between usually between two and four

integration sessions you know either the day after or like the week after the weeks after the psilocybin session this is great so they're kind of priming them right priming them with this pre-session what are the most meaningful experiences of your life what are the most impactful people in your life so all of this is kind of like now associated with this experience they're talking about you know what is the role of spirituality, religion? What are the most important successes or failures in life? They've talked about these things. These are things that are potentially now going to be on the mind of the person in this study

as they lie there, as they sort of reflect. I mean, you think about just even lying in a single spot for four hours, it's kind of a unique experience in our culture, right? We're so bombarded by the white noise of news and the white noise of everything. right and so to really reflect that that might have some value in and of itself think about a multi-hour session with therapists that might have value in and of itself um that sounds like really good therapy you know really intensive therapy yeah there's no i think there's no question it's there these therapists are experts at what they do and are really familiar with the experience

and it's being given in ideal circumstances, which is the case in most pilot studies. Absolutely. And I think there's having worked with people doing research here at Loma Linda, like the men program, you know, I understand what it's like to do research because the therapists are very missional. And then, you know, you work in another program and the therapists are getting a paycheck. they may or not believe and have commitment to the modality that they're doing, but they're doing it because it's necessary. The research track that I run, like the therapists really, really, really want a good outcome

on every patient that we have because we're doing research off of it. So they're willing to go the extra mile, see the family outside of the normal build hours, right? Stuff like that. I think that does make a huge impact. Okay. So this is where we're going to take a pause. I think there's a lot of information already, a lot of things to digest. I would highly recommend at this point. If you still have questions about what we've talked about, if you still want to look at some of the data for yourself, jump on the blog, Psychiatry Podcast.com. You should be able to find it pretty easily. Just search psilocybin, Psychiatry Podcast, Silocybin, David Puter. You'll find it. jump on the episode notes and just take a little deeper dive in anything that you're specifically curious about. And I think that that would be a great way to prepare for part two. Nadav, any big takeaways from part one, any big things you want to throw out there?

I think, you know, this is a lot of information that we have. And I really think that the best information that we have, the most exciting thing for psychiatry, is in the next episode. what's been shown. Oh man, that's a good, that's a good like trailer there for the next one. This is just to wet your appetite, guys. This is just to get you excited for the things to come. Okay. All right, we'll leave it there.