Dhru Purohit Show - Psychedelics: Treating Addiction, Depression, and Anxiety with Dr. Roland Griffiths

Episode Date: January 23, 2023

This episode is brought to you by InsideTracker and Pendulum.  Psychedelics were the subject of serious medical research from the 1940s through the 1960s, when many scientists believed some of the mind-bending compounds held tremendous therapeutic promise for treating a number of conditions, including severe mental health problems and alcohol addiction. But by the mid-1960s, research into psychedelics was shut down, a policy that would last for decades. After the blackout ended, the doctor we have on the podcast today was among the first to initiate a new series of studies on psilocybin—the psychoactive compound in “magic” mushrooms. Today on The Dhru Purohit Podcast, Dhru sits down with Dr. Roland Griffiths, a professor in the Department of Psychiatry and Neurosciences at Johns Hopkins University School of Medicine. Dr. Griffiths has conducted extensive research with sedative-hypnotics, caffeine, and novel mood-altering drugs. In 1999, he initiated a research program at Johns Hopkins investigating the effects of the classic hallucinogen psilocybin. The program includes studies of psilocybin-facilitated treatment of psychological distress in cancer patients and cigarette-smoking cessation as well as the compound’s effects in beginning and long-term meditators and religious leaders. In this episode, Dhru and Dr. Griffiths discuss his research on psilocybin in the treatment of psychological distress in cancer patients and cigarette-smoking cessation. They discuss the connection between psilocybin, spirituality, and consciousness and their potential for treating conditions ranging from drug and alcohol dependence to depression and post-traumatic stress disorder. In this episode, Dhru and Dr. Griffiths dive into: -The connection between psychedelics, spirituality, and consciousness (3:30) -The history of psychedelic research (12:32) -The reintroduction of psychedelic research by Dr. Roland Griffiths and others (16:31) -Why research participants rated their psychedelic experience as one of their most meaningful (20:57) -What is happening in the brain when using psychedelics (27:39) -How psychedelics can help us understand altered states of consciousness (33:13) -The therapeutic benefits of psilocybin for the treatment of addiction (44:20) -How a single dose of psilocybin substantially diminished depression and anxiety in cancer patients (48:56) -The future of psychedelics (52:11) -The downside and risks of psychedelics (1:00:18) -Learn more about Dr. Roland Griffiths and his work (1:04:28) For more on Dr. Roland Griffiths and his research on psychedelics, check out his website https://www.hopkinspsychedelic.org. InsideTracker provides detailed nutrition and lifestyle guidance based on your individual needs. Right now, they’re offering my podcast community 20% off. Just go to https://www.insidetracker.com/DHRU to get your discount and try it out for yourself. Pendulum is the first company to figure out how to harness the amazing benefits of Akkermansia in a probiotic capsule. To receive 20% off your first purchase of Pendulum’s Akkermansia probiotic supplement, go to https://www.Pendulumlife.com and use code DHRU20. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit megaphone.fm/adchoices

Hi everyone, Drew Prode here. Recently, there have been so many guests and experts of all areas who have come on this podcast to talk about the influence and the role that psychedelics have played in their evolution and healing journey. The psychedelic that's come up most common in these interviews has been psilocybin, the psychoactive component of magic mushrooms. Well, a few years ago, back in 2019, I got a chance to interview Dr. Roland Griffiths from Johns Hopkins University, who's considered to be the world's foremost.

expert in this field of study. I was re-listening to our old interview the other day and sharing it with a friend and there are so many gems that are in this interview that I decided to reshare it with the audience who might be interested in going deeper on this topic. Now before I tell you a little bit more about Dr. Griffiths, I want to acknowledge that Roland has recently come out and shared with the public that he's been diagnosed with what is very likely terminal stage for cancer. In fact, he did an episode with Tim Ferriss all about this. And after listening to that episode and resharing our first episode with a friend, I really got clear that one of the ways that I wanted to make sure that I helped

continue spread the message of Dr. Griffiths and his passionate work in this space was resharing this episode with my audience. I've also reached out to Dr. Griffiths to ask him if he would be open to coming back on this podcast to talk to us in a part two. and specifically for him to share how psychedelics have been part of expanding his perspective in the face of this looming mortality. I hope he agrees, and of course if he does, you'll hear about it first here on the podcast. Regardless, if Roland does not agree or can't make it, I just want to send my best to him in this very vulnerable stage of life. Well, I'm going to share a little bit more about Dr. Griffith's work.

He's a professor in the departments of psychiatry and neurosciences at Johns Hopkins University School of Medicine. His principal research focuses in both clinical and pre-clinical laboratories and has been on the behavioral and subjective efforts of mood-altering drugs. His research has been largely supported by grants from the NIH, and he's the author of over 360 journal articles and book chapters. He's been a consultant to the National Institute of Health and to numerous pharmaceutical companies in the development of new psychotropic drugs. He's also currently a member of the expert advisory panel

on drug dependence for the World Health Organization. Our episode, which was, again, recorded in 2019, was recorded at the Institute of Functional Medicine Conference. And I was so blown away by Dr. Griffith's presentation that you'll see my awe and amazement and all the questions that I get to ask him in this rear of that episode. Stay tuned and I hope you enjoy it. Dr. Griffith, thank you for being on the Broken Brain podcast.

My pleasure. You give a fantastic presentation today at the conference and blew a lot of people's minds on the work that you've been doing now for quite some time. I want to go a little bit more into the origin story because in the presentation, you mentioned that your interest in this field of work started with actually an interest in mindfulness and meditation. Can you tell us a little about that and where in your life that was introduced as a modality or practice for yourself? Yeah. Well, I traced that interest back to graduate school where there was a visiting meditation teacher that came by,

and I was intrigued. I was being trained in psychopharmacology, taking physiology and pharmacology and understanding drug effects and brain behavior interactions. and it just occurred to me that meditation was just a really interesting methodology. I mean, here's a methodology that's been developed over thousands of years for kind of plumbing the internal nature of our experience, our felt experience. And so I thought, gee, that would be interesting. And I went and took a beginning class in meditation,

and they started teaching about how meditative, meditation works and the physiology behind it and all kinds of thoughts that didn't come together with anything that I had learned about human physiology or human functioning. And so there was this kind of wild disconnect between the understanding that these meditation teachers had about physiology and brain science and what I thought is. and believed to be true based on physiology. But I was able to kind of suspend that and just say, okay, I'm going to take this as a metaphor for how to investigate the nature of mind.

And so dismissed their levels of explanation and just thought I would wait into meditation. Well, it turns out meditation is difficult to do. and it's not uncommon for beginning meditators to find it really quite aversive. And that was exactly the case for me. I sat down to meditate and three minutes felt like three hours. And I was out of there within the first week. But nonetheless, curious about what it was that our empirical science couldn't teach us about the deepest level of consciousness in mind.

And then about 20 years ago, I took a meditation practice up again in Baltimore, and for reasons that I don't understand, there's something that clicked this time, and I was able to move into states of consciousness that I hadn't here-to-fore experienced. And that got me just deeply curious about this whole inner explanation.

exploration. At that point, I had already spent over 20 years my career studying mood-altering drugs and drug effects and changes in subjective effects, yet there was something unique about the meditation experience and unique about those changes in consciousness. And it was that interest got me reading about different meditation traditions, about different spiritual traditions, about religious practice that had had no interest to me for me heretofore, that drew me into reading about comparative religion

and religious experience. And through that connection, I became reacquainted with this older literature on psychedelics. And psychedelics were claimed to produce some of those kinds of effects, and here I was a full, professor at Hopkins with credentialing in clinical pharmacology, so I knew how to study drugs.

And so this, you know, the opportunity to study a psychedelic and ask questions about the nature of mind and the nature of experience became very compelling to me. And that was our initial study. It was in Healthy Volunteers. And I have to say that I was pleased with my meditation practice. I was a little bit leery of the claims, frankly, that were made about psychedelics and the psychedelic enthusiasts who seemed to think that this was the answer to so many problems.

It just struck me as kind of a suspicious proposition. So I went in with a good bit of skepticism, but as the research has unfolded, it's very clear that psychedelics can be a very powerful opening to experiences and states of consciousness that can be accessed in meditation and prayer practice and breath work and drumming in all kinds of other modes. And I think these states of consciousness and the kind of resultant consequences of them can be profoundly important, both therapeutic. and more generally for understanding optimal behavior, ethical, and moral values.

It's a little bit of a history lesson. There was some serious medical research at some point in time looking at psychedelics, and then things changed. You talked a little bit about that. Can you just share with the podcast listeners a little bit of the background on some of the research that was conducted in the space prior to your landmark study? Yeah. So in the 1950s through 60s, early 70s, there were a whole series of studies, many of them with LSD, which is a classic psychedelic, some with psilocybin, some with mescaline, investigating this class of compounds.

There were a very therapeutic studies. There were studies looking at LSD in particular in alcoholism and in cancer patients. Some of those results looked promising, but these substances are very peculiar to work with because their effects depend really important on context, set and setting. And so depending on how these drugs are administered, what the expectations are, you can get very different kinds of effects. And so it wasn't like conventional clinical pharmacology studying a stimulant or a sedative or an opiate, which has a more narrow window of effects.

You can get broad and variable effects depending on these context variables. So the results were not particularly consistent, or although there were suggestions that it was therapeutically helpful. However, that work coincided with the so-called psychedelic 60s where these drugs became promoted for recreational use. And people like Timothy Leary, who was a well-trained and brilliant psychologist who had worked with psilocybin, decided to leave academia and promote recreational or non-medical use of these compounds.

And that coincided with the anti-establishment movement at the time, the anti-war movement at the time. And it coalesced into this fractioning of our culture into a pro-drug use and an anti-drug use. and it resulted in, in effect, a demonization of these compounds, overrepresentation about their risk, and functionally shut research down for a period of decades. And that's very interesting.

But funding was pulled back. These drugs were scheduled under Schedule I stature, so it became very difficult to get them. The academic institutions marginalized them. it really was an area that fell into academic disrepute to be interested in these compounds. And so it resulted in this peculiar situation where these very interesting and novel psychoactive drugs simply didn't get studied for decades. Now, if you think about it, and you think about the history of science and how science proceeds, that's astonishing to have

three decades in which this really interesting set of compounds, you know, is taken away from human clinical pharmacology. And so there it sat in this dormant phase for a long period of time. And then we and others re-initiated this research back in the late 1990s, moving very cautiously, into it because there was such a cultural bias against them and the thought that they were so potentially dangerous and harmful, which they turned out not to be, I mean, at least that dangerous and harmful, but it's very important to say that they are not

without very significant risks. But it was that early research, and the most promising applications then were in cancer, of patients, who were depressed or anxious because of a cancer diagnosis and in treatment of alcoholism. Those were the two most promising indications at the time. Take us back to that when those early conversations were happening in the early 90s of proposing funding to pick back up this research.

And my business partner and friend, Dr. Mark Hyman, is at the Cleveland Clinic. And I know different hospitals, depending on where people are at and doing their research, you have to go and present to a research board, what the idea is. What was some of the reactions when you told people that this is what you want to pick back up? Well, it was interesting, and it was very mixed. So I work in a clinical behavioral pharmacology research unit with colleagues who are great scientists, interested in pharmacology and interactions with behavior and subjective effects and behavior change. And what I would say is among my colleagues, there was a lot of variance.

I can remember presenting this idea. You know, I think I'll give psilocybin to people. And some of my colleagues went, oh, wow, that would be interesting. And others clearly thought, what? You're going to do, why would you do that? Isn't that dangerous? I mean, and so there's this kind of cultural dialogue there. And so there are individuals who are kind of open and curious about that,

some of whom have had experience with these compounds, others not, but they're just interested in altered states of consciousness. And other people have drunk the Kool-Aid, so to speak. They have taken in what was this public narrative about the dangers of these compounds and believe them. There's no reason that they shouldn't have. So there was variation even among my own colleagues. When I took it to our Hopkins Institutional Review Board,

that's our Ethical Review Board, they scrutinized it extremely carefully, and as they should have. I mean, that's their job, is to assess risk-benefit ratio. And they looked at it, They sent it out for external review. They sent it up to the dean of the medical school.

They sent it over the managing attorney's office. But I think to the great credit of Johns Hopkins, on balance, they decided, you know, okay, we can, we assess the risks and benefits, and you can proceed cautiously, proceed with the first five volunteers and report back to us, if anything untoward happens. And that's a perfectly reasonable stance, but one could easily imagine an institution that doesn't weigh science and rational decision-making as cleanly as Hopkins did and is more prone to making political decisions because there would

have been an institutional risk just because of the history of these compounds, that the easy response was not to approve, but it was approved. we went to the FDA and they scrutinized the study they approved it, the DEA approved it. So by 2000, we were approved to move forward to administer a high dose of psilocybin to people who had never previously had a psychedelic. And as best we can tell, such a protocol hadn't been approved for probably 30 years before of that type. Tell us a little about that study and some of the early,

findings that came from doing that research. Yeah. Well, I mean, that study was so interesting. So here I am coming into this, as someone interested in states of consciousness, interested in meditation, being reasonably skeptical about what these drugs do. I was working with a close colleague, Bill Richards, who had worked with these compounds previously at Maryland Psychiatric Research Institute. And so he had back in the 60s worked with these compounds,

and he had the clinical expertise. I had the scientific expertise. I brought in the scientific skepticism. But very quickly it became apparent to me that these were effects that were unlike anything I'd seen in clinical pharmacoccurricular. having studied, you know, I don't know, 40 or 50 different psychoactive compounds from all different classes, this just read out as something unique.

So what was unique about it? Well, one aspect that was unique is that people had experiences that map onto naturally occurring mystical or transcendent kinds of experiences that have been described throughout the ages by religious figures or mystics. And so the phenomenology of that is this sense of the interconnectedness of all people and things that's accompanied by a sense of sacredness and there's authenticity to it that is more real and more true than everyday waking consciousness. And so there's something unique about that experience that looks like these naturally occurring experiences. So that part was unique, but what was far more interesting than that is interviewing people

weeks or months after the experience. And I just can remember how shocking, frankly, it was to me to sit down the way. This first study was designed. Some people had exposure to psilocybin, others to a positive control substance. And then we interviewed them two months later, and then they could get, redosed with other compounds. And just talking to people about the psilocybin experience, two months after the experience,

and sitting down with someone and saying, so what do you remember of that experience? What was that like for you? And having, I can just remember this distinctly, it was the first or second volunteer telling me, you know, that was one of the most meaningful experiences of my life. I think of it every day. And I thought, what?

I mean, what is this person telling me? I mean, I've given all these compounds. I've never heard of anyone make an attribution two months afterwards that, you know, they learn something and enduringly so. I mean, if you just think of drug effects generally, I mean, take alcohol. You know, someone can have an experience of alcohol. and if you ask them a week later, oh, what was your experience Saturday night?

And they'll remember it. They're pulling from memory, and they might say, oh, it was great. We had a party, you know, I got drunk or I got high. It was, you know, and if you asked them two months later, what do you remember? You know, the memory's kind of fading, but they haven't learned anything that informs them prospectively going forward.

And these people were saying, no, this is one of the most important experiences of my life. And the first thing I thought is, wait a second, what kind of life experiences do these people have? Maybe they've done nothing. But then when probed, they would compare it to, say, the birth of their firstborn child or a death of a parent, something that you go, okay, that's really sileant. the level of reorganization and meaning that gets incorporated into these experiences? So I realized right off the bat we were dealing with something pretty astonishing just in terms of the human condition.

And it just got me deeper and deeper interested in the nature of these experiences. You know, and my first concerns was, well, how much of this is driven by expectations? how much of it, you know, is driven by the kinds of people we're bringing into this study. Is this real pharmacology, you know, and there are all kinds of controls that you can run, and we did that. And so as we ran further studies, it just got, it just got firmer and firmer, that this is a real effect, it's an enduring effect. It's fantastically interesting.

It relates to something to do with the, the normal human condition because these experiences map onto these naturally occurring kinds of transformative experiences. And so it raises all kinds of questions about the evolutionary significance of these experiences, you know, how they work, what's the biology of them and how they work, what are the implications for understanding biological psychiatry and neuroscience. There are all kinds of questions about that. And then what are the therapeutic applications? And there appear to be, you know, very possibly many and very significant therapeutic applications. And then what can these experiences inform us at the kind of the deepest level about the human condition,

ethics and morality because the core feature of this experience is that they feature the interconnectedness of all people and things. And that's front and foremost to many of these experiences. And I want to talk about both that and the therapeutic effects coming up. But first, I want to just take a step back. Help us understand a little bit about psilocybin. What's happening in the brain when somebody's taking it? Yeah. So when I sit down and do informed consent with volunteers, I very often say, you know, it looks like we know a lot about psilocybin, and we certainly know a lot more than we did 15, 20 years ago. But our real level of understanding is really quite shallow. So what we know about psilocybin is we know is we know. know with psilocybin and the other classic psychedelics, which include dimethylotryptamine, DMT,

which is active in ayahuasca, mescaline, which is active in the peyote cactus used by Native Americans, LSD, which is a man-made hallucinogen or synthesized lucidinogen. What we know is all those drugs have a central site of activity, a share of central site of activity, and that's the serotonin 2A receptor. And that's a receptor that's widely distributed in human brain, maybe the most common receptor site in human brain. It's evolutionarily conserved. It goes back. It's an ancient serotonin's ancient neurohormonal signaling system in brain. We know where those receptors are in brain from imaging studies. and importantly in cortex and level five of perennial cells in cortex,

but also in thalamus, clostrum, locus serrilius, in other areas. So we know where these receptors are. With imaging studies, we know what areas of brain are activated and what areas of brain are deactivated when someone takes psilocybin. and we also know something about connectivity within the brain when someone takes psilocybin. So, you know, the neuroscience of brain and brain network functions have worked out different network systems that are active. And some of those networks are differentially affected with the psychedelics. And one of the interesting ones is this default mode network, which is claimed under,

right, this self-referential processing, this self-narrative. And that default mode network is decreased substantially with psilocybin as it is with LSD. And interestingly, meditators, long-term meditators also show decreases in default mode network functioning. So this default mode network, just to interject, sometimes people think of it as like, this is like your ego. That's right. So it's, they, It can be described loosely as ego, it's self-referential processing. The way you respond to the world, behavioral patterns. Yeah, it's your default thinking, where your brain goes to when it's given nothing other than due to just chatter at yourself. And so it's it may underwrite a narrative function of and coherence.

of self, and that's decreased. And that kind of makes intuitive sense that these drugs bring you into the present moment that past and present disappear. They collapse into the present moment. And that's exactly what happens in meditation. And long-term meditators have practiced that. So that all makes sense.

So that makes a nice story, but I guess what I want to underscore is it's just a story. And we so poorly understand consciousness. And what I think of is I think these drugs are unique in their capacity to shine a bright light on what it is to be aware, what it is to be conscious. And I think if you think about that, I mean, that's a really profound thing. There's something called the hard problem of consciousness, and the hard problem is that consciousness may,

consciousness may not be reducible to reductionistic neuroscience. It's an open question philosophically and scientifically, although my materialistic-oriented colleagues from the sciences would push back on that. They would strongly think of. of consciousness is an epiphenomena of brain network function, but that's, it's not entirely clear. And if you weighed into that philosophical

and neuroscience literature, it really becomes quite a puzzle. But there's something, and so it's called the hard problems of consciousness. And right now, it doesn't appear to be solvable. It's hard, because we don't even know how to address the questions to answer it. And there's something about these drugs that shine a light on that experience of what it is to be aware that we're aware. And I mean, if you think a little bit about that, I mean, it really is quite astonishing.

I mean, here we are these highly evolved creatures who are sentient creatures, and we can navigate. the world and we, you know, can feel things, we can move things. We can think, we can deal with abstractions, we can make mental constructions, solve puzzles. And beyond all that, we are aware that we're aware. And that's why would that even be the case? Why would you need to have that? What function does that serve? And as you you lean into that question, awareness of awareness, you're really confronted with the, I think it's the deepest existential question of what it is to be conscious. What is it about our experience of sentience? Because it's actually the only thing that we actually know for certain.

That's the only thing we can validate. You can validate that you're aware that you're aware, you're aware, you can't validate that in me. You can't know that in me. And that's a starting point. And it just brings up this, you know, the deep question of, wait a second, what is this really about? I'm in this astonishing consciousness. I'm in this playground of being, how the hell did I get here? What does this mean? You're probably there too. And that's the interconnectness, the kind of the recognition that we're all in, as one of our long-term meditators said, that I thought was cute. We're all in the same pickle. It's like we all have this same dilemma. But it connects us in a really profound way, and it's deeply humbling. And I think it's what we all

all want to know more than anything, at least what I want to know more than anything, is, yeah, what is this about? Yeah, what happens when we die? Yeah, what is the nature of this experience? And where's it going? And so that, and these are the questions that are raised by that. And when you raise those questions with people, and if they haven't thought about those, it can be an existential shock. I mean, they're pulled out of their narrative frame, you know, all of their worries for the moment

and what they're trying to achieve and they want to get a new job or buy a car. You know, they're concerned about all the mundane things in life. And yet we're all sitting in this much bigger, you know, question that is nothing more than absolutely astonishing in the magnitude of the mystery that it raises. And therein, it speaks to some people who are comfortable using, you know, religion and spiritual language because it's the mystery, but you don't have to go there. You can just go into the absolute mystery of what it's about. But with these kinds of experiences and

with the kinds of shifts that can come about in self-narrative because of that, there can be profoundly positive changes, both for people who are suffering from, you know, classic medical or psychiatric conditions. Depression, other anxieties. Depression, anxiety, behavioral addictions of all sorts. But also more broadly for the human experience, because we're all. all in the same pickle. In fact, in your research, there's, you have the mystical survey.

What's the formal title of it? The mystical. Mystical experience survey. Mystical experience survey. And even people who, that you did research on, that weren't dealing with some sort of addiction, cigarette cessation, cancer, there were just, you know, no issues. A reportiveness of, you know, a deeply positive. positive mood that was reported, a sense of transcendence of space and time, a sense of we're all

one, that maybe we're all looking through the same experience, that maybe we're not separate in a way that we see ourselves as separate always. And those are profoundly impactful ways of navigating your core sense of identity in the world. I mean, I'm sure there's all sorts of implications of how does that change somebody's life when they start to understand and ask these bigger questions of what's important, what's not important, what deserves attention, what does not deserve attention. Did you have any sense that these experiences would be that level of depth? Like had you had any psychedelic experiences yourself to know that, okay, I have somewhat of a sense of what people might experience going through

these doses of psilocybin. See, I had no personal, informative experience that would have led me to believe that psychedelics did what they can do. I mean, my guiding experiences initially were through

meditation. But if you look carefully at the literature and the nature of these experiences, it's clear that this isn't just about psychedelics. This is about the capacity. of the human organism to have transformative experiences, and they can be occasioned under any number of different circumstances

like meditation or breathwork or prayer, practice, or drumming, or just human experiences. Yeah, just spontaneously, very often experiences. If you look back at the history of religion, experience and spontaneous mystical experiences. There are lots of accounts of people who had such experiences, you know, really unbeckoned and, you know, they just occurred. They were walking on the beach one night and all of a sudden,

and they'll describe these experiences with the qualities that we have. You know, Bill Wilson, who founded Alcoholics Anonymous, had such an experience when he was going under alcohol. detox and it was the basis of that experience that he founded AA and you know that's the 12-step program for treating alcoholics fully six of the 12 steps has something to do with higher power recognizing higher power surrendering to higher power and that and and that is you know akin to just the astonishment of the magnitude of the mystery in a way what you're saying is the way that I'm understanding it, please correct me if I'm wrong,

is that this is less about psychedelics and psilocybin and more of a reflection of what the human mind is capable of, these experiences that are happening regularly for all of us, and how under a microscope, so to speak, we can use psychedelics, psilocybin, you know, we can use these mood-altering drugs to sort of see what the mind is capable of. Exactly. So it's not to get attached because if you think that it's this outside thing, then there becomes a dependency or a focus on this outside thing instead of this internal thing that could be developed through various sorts of methods. Correct. Yeah. And I think that's really important.

Alan Watts, who wrote about psychedelics back in the 1960s, had a saying, or was alleged to have said, when you get the message, hang up the phone. And what he was saying there is that's about psychedelics. It's not about the psychedelics. It's a about the message. And my thought is that people who use psychedelics as a path and become attached to that as the only way to open is that just closes down and it constrains what they can become with it because it's not about psychedelics.

It's confusing yourself with the vehicle that you drive in. Exactly. As a friend of ours, Peter Crowen, who came on the podcast recently said, What are you? Is it you? You know, what are you using the vehicle for? You're not the car. You're just using it for a temporary purpose. Yeah. So, yeah, I think Ram Dass had the expression when, yeah, when you're already in Philadelphia, you don't need a bus to get there. I mean, so it's not that it's a vehicle. But, you know, importantly to this and to the whole issue of set and setting is the contextualization of these experiences and then what people, do with those experiences. So, you know, in the 1960s, there were lots of particularly younger kids that took LSD and other psychedelics and, you know, some of them had

astonishing experiences and changed life course, but many of them didn't and some of them were harmed by those experiences. But if it just laid on someone, these These experiences can be confusing, they're difficult to integrate, they don't have meaning. And so a lot of it is contextualization of the experience and trying to get traction with them about what the meaning is for changing one's narrative in life. And part of what you presented today at the conference here, which is focused on addiction, stress, pain management, is the therapeutic benefit. because, of course, there's this spiritual component,

and there's some people that are dealing with hard wiring in their default mode pathways in their brain, which can cause addiction, which can have pain if they're very far-stage in a cancer, other things, fear, extreme fear, anxiety of passing away. Can you talk a little about psychedelics and the potential for treating conditions in the therapeutic way

in some of the studies that you've done. Maybe we could start off with the addiction and smoking, if you wouldn't mind. Okay. Yeah, so I think it's, I think it is important that the wisest and most important use right now is for therapeutics. Because if we're going to make,

if we're going to really unpack these compounds, understand how they work. They have to engage the culture at some meaningful level, and therapeutics is, I think, the legitimate avenue into that. And these are very powerful compounds to approach therapeutic questions. So the two big areas that came out of the earlier studies were addictions and then anxiety, depression, secondary to life-threatening illness. So in terms of addictions, we have looked at psilocybin for treatment of tobacco dependence,

cigarette smoking addiction, and that's being done by my colleagues at Hopkins, Matt Johnson, and Albert Garcia-Romeo. And what we showed was in an initial pilot study of just 15 volunteers, that psilocybin in combination with cognitive behavior therapy produced immediate and long-duration absence from cigarette smoking. So six months, we had 80% absence rate biologically verified, which is unheard of in the cigarette smoking area. Cigarette smoking is one of the most difficult to treat addictive disorders there are. And so combining this with the intention to quit and the support involved produces these long-term enduring effects.

We're going on to do comparative efficacy trial with comparing psilocybin with nicotine replacement to look at that more closely. There's other work in the addictions going on right now at NYU with psilocybin and treatment. of alcohol dependence. And there's a small study going on with treatment of cocaine dependence with psilocybin. So all three of those appear to be promising

and it fits with the older studies and this idea that these experiences can help rewrite narrative and self-understanding in a way that can be very therapeutically helpful. So if you think about it, someone who's addicted to cigarette smoking, you know, will come in and they'll say, you know, I've a lifelong smoker. I've tried

multiple times to quit. I've tried vereniclin and nicotine replacement and cold turkey. I always laughs. And I'm addicted. And that's their history and that's their story. And with these kinds of of experiences, the experiences are so wide and so big that it appears to pull people out of that narrative. So they're no longer attached to just this locked in, fused idea that they're addicted. They can see the capacity to do otherwise. They can tolerate craving and discomfort in a way that they didn't think was here to four possibly, possible. They can reset life priorities in a way consistent with quitting.

So it's really quite astonishing what can happen. And we don't understand fully at the network level what's going on there. I'm framing it in terms of meaning and psychology and cognitive processes, but undoubtedly there's some something going on at network functioning brain levels that we don't yet understand. The other big application is in anxiety, depression, secondary to life-threatening illness.

And so we did a study that was published concurrently with a study at NYU in cancer patients who were anxious or depressed because of their cancer diagnosis. and we compared a pretty large dose of psilocybin to a very, very low dose of psilocybin in our trial. And again, we show that psilocybin produces these mystical type experiences, but with this transformative quality, but the important point here is that all our measures of clinical distress, that is, our classic measures of depression and anxiety,

go way down, you know, so much so. that about 90% of people five weeks after treatment showing clinically significant responses and about 60% are in complete remission, that is, they don't have any trace of anxiety. And that holds out to six months. So that's actually fantastically interesting, and it's really unprecedented within psychiatry if you think about it. I mean, this is a single session that lasts, you know, six hours at Johns Hopkins that is producing these enduring effects out to six months in a very clinically significant psychiatric condition. So psychiatry doesn't have

interventions of that sort. Certainly what we know, you know, the Metadepressants, for instance, may take weeks to work unless it's ketamine that can work more quickly, but its effects die out really quickly. And antidepressants aren't very effective. Psychiatry has, in very severe cases of depression, ECT, electroconvulsive brain stimulation. That's a pretty crude but very powerful. intervention, but that takes multiple sessions and it wanes over time. Its efficacy isn't particularly sustained. So what we have is a model here of a discrete intervention that produces

these dramatic and enduring effects within psychiatry. And frankly, it looks more like a surgical intervention than it does, you know, a psychiatric intervention. You know, surgery, you might expect to go in and have a hip replacement and be quite functional, you know, enduringly thereafter. And, and that may be the metaphor for what these kinds of interventions can bring to psychiatry. Now, to what extent they're effective in different for different medical indications is still open for investigation. And what would you like to see happening in the space for the research that's needed to really, I mean, there's people that are listening at home. Some people have had their own experiences with psychedelics, some positive, but also some negative. And I want to talk about some of the

challenges and the risks that are there for some individuals that you saw, even in your own studies, what would you want to see in terms of all this promise? You mentioned that there are two companies that are working on a, that have been approved by the FDA, I believe, that are, have the ability to begin the first stage of working on drugs that are based on this. What do we need more of in this space? Is it just really, we need a lot more money in the space for research to see and take out there?

Do we need governmental policies to change the classifications on these things to get the research that we need? Because there's so much promise. And what's an impediment to the promise just as there was the dark ages before you came in with your research, how do we support the future of this? Yeah. Well, that's a big question because there's so many different directions to go. So if we just take therapeutics, what do we need? We have two companies that have initial approval to initiate these clinical trials,

and those need to go forward. We need to see how that shakes out, whether efficacy is sustained under those very tightly monitored conditions. My guess is that it will be that these are going to be effective. but until you run those trials and look at rates of efficacy and rates of adverse events, you don't know for certain. But I would have some optimism that those initial indications, which are targeted at either treatment-resistant depression or major depression, are likely provable indications.

And then there are a variety of other indications, and so we've talked about the addictions. and that might be promising future indications, but there may be a vast number of other therapeutic indications. So we're initiating studies in anorexia and nervosa and early Alzheimer's. There are a number of other clinical targets that we would like to look at. But all of those just need to be investigated, and then they need to go through the regulatory and scientific gauntlet

that is required to get a medication approvable in our culture. So that's one area of critical importance. There's a whole lot that we need to understand about the basic science of how these work. So there's a lot of basic work to be. be done in terms of pharmacology and neuroscience, trying to understand the underlying mechanisms and what it is that accounts for both the acute effects and the enduring effects. And there's much that we don't understand about that.

There's, in terms of drug policy, the fact that these drugs are Schedule I compounds, which means that they're the most tightly regulated compounds creates a huge barrier to research, not only clinical research, but all basic science research, because one has to get special levels of approval to obtain the compound, and it has to be monitored very closely. And that is an impediment to conducting even the very basic neuroscience, you know, pre-clinical neuroscience with these compounds. So some of that structure needs to relax or be changed in a way to allow the science to move forward. I want to go back to an origin story a little bit. As a child, was there a fascination about what's real and not real? You know, so much of science

is, you know, looking at and like pushing one thing and how does one thing react. Was there any fascination with like the nature of reality were these these questions that you're asking yourself as a as a young man or as a child that you think we're part of what ultimately led to this fascination of first the meditation and then ultimately the space of mood altering and mind altering drugs well it's a good question and and i can't let's see i can't point to my own personal stories of kind of grappling with those deep existential questions, other than those that I suppose every child has to have when they sleep outside for the first time

and look up into the stars and realize, wait a second, this goes on forever, how does that work? And then I cease to think about that. And so I think, you know, And I didn't have a religious upbringing. I went to church occasionally. It wasn't an important focus for my family.

I ended up flunking out of confirmation class in sixth grade. But, you know, I would have to say, going back to my kind of curiosity about meditation in graduate school, that there's this deeper curiosity. about what it is that we know and don't know about our inner lives. And so that was there in background, but I would have to imagine that, wouldn't that be part of the human condition? Isn't that everyone's backstory at some level?

Maybe not, maybe so. I can't imagine it being otherwise, though, because those are the most fundamental experiences that we have. as conscious beings trying to figure out what this world's about. It just gets papered over so quickly as we get enmeshed in culture and in story and attached to identity.

And at least in our culture, then getting attached to grasping for recognition or achievement or, you know, financial gain their social prestige or however that comes out. There's people that are listening to this interview. You were featured in Michael Pollan's most recent book. And inside of there, he was very open about how he went essentially underground and started working with certain healers and doctors in this field who would be anonymous inside of

his book who were helping him go through these experiences and people who have also had those experiences with psilocybin or other modalities that are out there. And there's people that are listening to this interview and looking at the horizon are like, okay, well, I'm suffering with this right now, or I'm dealing with this component, or I have my own personal interest in having some of the same experiences of individuals out there. And we know that that's part of the dialogue. What would be the conversation that you'd have for them about their own interest

and experiments on their own and potential, side effects or downsides that can come with that. Yeah. So what I'm concerned about the kind of renewed and cultural enthusiasm about these drugs, that the downside and the risks aren't downplayed because they are there and they're very significant. So we ran a large-scale survey study of people reporting in great detail about their most difficult or challenging experience with psilocybin.

And this survey took over about an hour to complete, so people weren't completing it just on a whim. They felt impelled to complete it. Now, they were talking about their worst experiences, but this was 2,000 people. And what was sobering about that was that 10% of them said that they put themselves or others at risk because they engaged in dangerous behavior.

3% ended up seeking medical help. But I think most disturbing to me is that about 10% of people whose experience occurred over a year ago continue to report enduring psychiatric problems, depression or anxiety, that they attributed to the experience. So I think it's just very important to recognize that in unselecting, volunteers, I mean, we screen our volunteers very carefully, and so we're not going to admit anyone who we think would have a vulnerability to having problems.

And so, but in unselected volunteers, with unknown doses in conditions that aren't supported, these experiences can go awry and they can be damaging and enduringly so. Especially in sort of like recreational places where there's other drugs or narcotics that might be there or stimulants or. Oh, yeah. And people don't know what they're taking and something is going to be passed off as psilocybin and it's not. It's something else.

Some of these can be very toxic poisons. But even with pure psilocybin, you're going to end up with casualties, either acute casualties, deaths, you know, from engaging in dangerous behavior, or you very well may end up with permanent psychotic conditions in people who are vulnerable to schizophrenia, for instance. And maybe this is just enough to push them over into a schizophrenic process that is irreversible. So I think we have to be very cautious and sober about this.

I think what I would say to people who are interested in the exploration of consciousness is they needn't turn to psychedelic drugs. There are other alternatives. There is meditation. There is breathwork. There are a whole variety of ways of investigating the nature of consciousness. If the opportunity arises to participate in some of the, the studies, for instance, we conduct where people are really tightly screened and prepared

and supported during the sessions and after sessions, then I think people would find that really valuable. But I guess I would want people to be patient. And I'm an advocate for getting these compounds approved through our medical system. and injected into culture in a fashion that's going to be controlled and safe and then letting it unfold from there. And I think it's quite probable that it will. Dr. Griffin, thank you so much for being on our podcast. For those that want to follow your work and continue to see the research that John Hopkins is doing

and potentially even be supportive in the efforts, where would you have them look to continue to stay on the up and up of what I consider to be one of the most fascinating parts of medicine today that really has a lot of potential in the future? How can people be a part of it? Where can they follow the work? Well, thank you for asking. So we do have a center at Johns Hopkins, at least a group of investigators that are working with psilocybin. And I can provide you the link to. And we'll put in the show notes. That'd be great.