TrueLife - Bryan Roth MD. PhD. - Injecting Noise Into Neurons

Episode Date: July 17, 2023

One on One Video Call W/George https://tidycal.com/georgepmonty/60-minute-meetingSupport the show:https://www.paypal.me/Truelifepodcast?locale.x=en_US🚨🚨Curious about the future of psychedelics? Imagine if Alan Watts started a secret society with Ram Dass and Hunter S. Thompson… now open the door. Use Promocode TRUELIFE for Get 25% off monthly or 30% off the annual plan For the first yearhttps://www.district216.com/https://pdsp.unc.edu/rothlab/https://www.med.unc.edu/pharm/directory/bryan-roth-md-phd/Bryan Roth, MD, PhDMICHAEL HOOKER DISTINGUISHED PROFESSOR, PHARMACOLOGY DIRECTOR, NIMH PSYCHOACTIVE DRUG SCREENING PROGRAM, ESHELMAN SCHOOL OF PHARMACY FELLOW OF THE AMERICAN ACADEMY OF ARTS AND SCIENCES MEMBER OF THE NATIONAL ACADEMY OF MEDICINE OF THE NATIONAL ACADEMY OF SCIENCES MEMBER, LINEBERGER COMPREHENSIVE CANCER CENTERBryan Roth, MD, PhD, a Professor of Pharmacology at the University of North Carolina.Dr. Roth has been studying the molecular mechanisms of psychedelics since the 1980s. They discuss: serotonin 2A receptors in the mammalian brain; psychedelics & neuroplasticity; classic psychedelics (e.g. LSD, psilocybin, DMT) compared to drugs like ketamine & MDMA; TrkB receptors & BDNF; engineering novel drugs & psychiatric treatment methods; latest findings in psychedelic science. One on One Video call W/George https://tidycal.com/georgepmonty/60-minute-meetingSupport the show:https://www.paypal.me/Truelifepodcast?locale.x=en_USCheck out our YouTube:https://youtube.com/playlist?list=PLPzfOaFtA1hF8UhnuvOQnTgKcIYPI9Ni9&si=Jgg9ATGwzhzdmjkg

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

The poem is Angels with Rifles. The track, I Am Sorrow, I Am Lust by Codex Serafini. Check out the entire song at the end of the cast. Ladies and gentlemen, welcome back to the True Life podcast. I hope everybody's having a beautiful day. I hope the sun is shining. I hope the birds are singing and the wind is at your back. I got a great show for you today.

the one and only the legendary Dr. Brian Roth, the Michael Hooker distinguished professor of University of North Carolina, Chapel Hill, as well as a member of the National Academy of Medicine and the National Academy of Sciences. The Roth Lab, the man behind it, has an incredible team of people working with him, a longstanding interest in the design, engineering, and evolution of proteins for designated functions. The Roth Lab perfected the chemogenic technology. They have named DRED, designer receptor exclusively activated by designer drugs. This technology has afforded thousands of labs worldwide, the opportunity to discover how cell type specific modulation of signaling is translated into behavior and non-behavioral outcomes. Brian, Dr. Brian, thank you so much for being here today.

How are you? Good. How are you? I'm living here. Fantastic. You're on the, looks like you're over on the West Coast. Is that accurate? Yeah.

Today I am in Oregon. Yeah, so I spend part-time here in Oregon. I'm on the coast. I don't know if you can see. It's a little cloudy out there. I would turn the thing around, but you can see the ocean out there. There are whales out there,

cavorting in the waves and everything. Yeah, very nice. Yeah. What an amazing time to be out there in Oregon when you get to see the decriminalization of medicinal mushrooms happening out there. Yeah, yeah. Cilocybin is now legal in Oregon. again.

Imagine that. Imagine that. It's so crazy. Did you ever think that that day would come when you started working on psychedelics back in the 80s? Never. No. I never imagined it.

I never thought that these would ever, that psychedelic drugs and other drugs of abuse, basically drugs of abuse or use, whatever, find therapeutic indication. but here we are. It's a new era, right? Yeah, it is a new era. You know, it reminds me. So much of our research and discovering novel ideas comes from language. And I know in a previous podcast you had spoken to Nick about the terminology and the language we use, whether it's terming new things or in a heightened state of awareness, it seems that we find ourselves with experiences that are

ineffable. We don't have the words to describe them. And I'm wondering, how does that play out? Like when you are trying to find novel compounds, what's the relationship with novel compounds and language? So I don't think about that too much, to be honest with you. Right, right. But what I've noticed, so let me just, sure let me just sort of address this from a historical perspective okay I think that might be the best so before we had the word psychedelic there was the term psychoactive and psychoactive was a term

that was coined I think in the early 50s for drugs like LSD so LSD was known in the 50s amphetamines are psychoactive and so on. And it was just sort of a general term for drugs that modify the brain. And so ethanol would be a psychoactive drug, alcohol, for instance. Nicotine is a psychoactive drug. And in, I think in the middle 50s, there was the suggestion that the term psychedelic be used for drugs like LSD and mescaline. So at that time, LSD and mescaline were the only known psychedelic drugs.

And so they were distinguished from other psychoactive drugs that were known at the time, which include all the ones I mentioned, along with marijuana, at the time the active ingredient of marijuana was actually not known to be THC. And ibogane as well. So ibogane was also something that was known at the time. And the person who invented the term psychedelic had actually sampled all of those compounds. So they were all legal in the 50s. You could probably order them from a chemical supply.

house and he felt and others felt that had taken most of the people in that era had taken LSD they hadn't taken psilocybin and he felt that that these drugs like LSD were unique in that they had this mind sort of expanding or mind revealing aspect to them and when I got out in the field of when I started studying psychedelic drugs and their receptors in the early 80s, this had expanded somewhat. So there were among, in psychoactive drugs now we had drugs that were stimulants. So these are drugs like amphetamine, cocaine, caffeine as a stimulant. We had sedative, sedative hypnotic drugs, anxiolyics. These are drugs like benzodiavallium, benzodiazepines, things like that.

And then we had psychedelic drugs. No, sorry, then we had hallucinogens. So among hallucinogens would have been considered psychedelics. So these consisted of LSD, psilocybin, mescaline, DMT, and their analogs, which all mediated their effects. through a single receptor in the brain, particular serotonin receptor, called the 5HT2A receptor. So those were all considered psychedelic drugs. And then we had other hallucinogens that like ketamine, which are dissociative anesthetic agents

by nature. So ketamine, PCP, and ketamine pretty much the same mechanism of action, different duration of action, different sort of intensity of action. both have the same basic effect. And then we had drugs like scopolamine from amnita muscarina, which is another type of hallucinogenic mushroom. And these are technically drugs that cause a delirium. So I'm a physician.

And delirium, the delirium is something that is completely different from a psychedelic experience. So in delirium, by definition, people are not oriented to space and time or even person. And when people take psychedelics, if you ask them where they are, they still basically know where they are. They know the date. They know who they are. And that's not the case with drugs that induce a delirium. And then we have this other, this other interesting class of drugs called onurogens. We now call them oneeogens. And these are drugs that induce a dream like state. And these are drugs like ibogane and salvinorn A, which comes from the plant salvia divinorum. And then there's another class of drugs completely separate from hallucinogens

that we call intactogens or empathogens. And these are drugs. like MDMA or ecstasy. So up until, I don't know, four or five years ago, maybe three years ago, I would say this was the standard language that we used to describe these drugs. And then something happened. So now if you go to the popular literature

and even among scientists, many of the drugs that I discussed, Oketamine, the psychedelics, even ecstasy, are considered to be psychedelics. But I would, I mean, ordinarily we would just call those psychoactive drugs. But it's what I mentioned to others is that in the future, it will basically depend on how people, people use these terms. So if everybody in the world except for me decides that psychedelics include

ketamine, ecstasy, LSD, salvia, ibogaine, scopolamine, and they refer to those, then those will be psychedelics, basically. And then we would have basically serotonergenre. psychedelics, so these are drugs like LSD and then others. And it's a continual, I wouldn't say battle, but continual conversation I have with people that up until recently, all these drugs had a different meaning. And actually, if you look at how the Drug Enforcement Agency, the Food and Drug Administration and the European Medicines,

Association classifies drugs and how pharmacologists classify drugs, basically. They use the classification scheme that I use. So it's

I don't know what to do, basically. It's an interesting relationship to think how one influences the other. It seems to me that there would be lots of pressure to call this certain class psychedelics if all this class as being layered into a therapy in a retreat somewhere.

Like I could see a business interest wanting it that way. It's a sexy term. Sure, sure. It didn't used to be sexy. So before three or four years ago, I didn't use the term psychedelic in my papers. I used the term hallucinogen. Basically because it wasn't considered, a, I don't know, it was just not in common use.

It was generally more appropriate to consider them hallucinogens. And most people didn't really get this, you know, psychedelic versus non-psychedelic thing. So, yeah, so I think, so maps in particular, so there's this company, the multi, or organization, the multidisciplinary association for psychedelic studies, probably, have the biggest footprint in this area and they actually don't study psychedelics. They study, you know, most of their, most of their work is based on ecstasy. Right. And ecstasy is not even a hallucinogen.

So I've never taken it, but I've, you know, talked with, you know, a large number of people who've taken ecstasy. And it's really more like, you know, it has a stimulus. sort of a stimulant action so people enjoy dancing and and then also this this action of increasing empathy basically in a feeling of connectiveness so i like the term in pathogen uh but but really drugs like ecstasy really is is really closer in action to amphetamine um the the big difference between ecstasy and say methamphetamine for instance is that Ecstasy promotes the release of multiple neurotransmitters, noraphenephyrins, serotonin, and dopamine, to a great extent, serotonin.

So it's a very strong serotonin releaser, but also releases lots and lots of dopamine and norapenephrin. Whereas methamphetamine is pretty selective for dopamine, as is cocaine. But they basically have identical mechanisms of action. you know, differ in their subjective effects. And that's the same for cocaine and amphetamine. Cocaine and amphetamine have different objective effects, but you wouldn't call cocaine a psychedelic. Right.

Right. Agreed. I mean, nobody would. So it's, I think it's, my guess is it's branding and PR and this sort of thing. But the thing about it is, because of the way language works, if people use the term to include all those drugs, then they're all psychedelics, basically, by definition. It would be like if I decided to call the color green, gorn,

okay, if I made up this term gorn. Right. And if everybody in the world agreed with me, then it would be gorn. It would no longer be green. Right. The truth is what people agree on, right? It's a perceived reality.

For language. for language. Language. Yeah. Yeah. You know, this kind of is, it kind of ties

into the subjective effects of classic psychedelics. Like it's very difficult to measure what's happening in there, right? When we do use, we rely on these subjective terms, but it seems that in your lab,

you've figured out some ways to really figure out, maybe you can explain some of the testing you're doing in there to really understand what's happening. Like, is it really connecting to the 2A

or is it, is this new track beagle? going in there? What's the mechanism of action that you've seen of lately in some of the new papers coming out with the serotonin receptors and classic psychedelics? Yeah. So in terms of the psychedelic actions, so when somebody takes LSD, they have a psychedelic experience. That's immediately, that's what they, for the next 12 to 18 hours, basically. And same with psilocybin or mescaline or DMT. And so there's no question that the psychedelic, experience is mediated by activation of a single receptor in the brain. That's the serotonin 5HT2A receptor.

And the reason that that's known with great certainty is that human studies have been done primarily by Franz Volanviter's group at Switzerland starting in the 80s. So I think his first, or 98, I think his first paper was published in 1998 on this. And what he showed was that if he pre-treated humans with a drug that blocks 5HT2A receptors and then administered LSD or psilocybin, the effects were gone, basically. And similar studies are done and have similar experiments have been done in animal studies, basically showing the same thing. And in mice, you can genetically delete the 5HT2A receptor and the psychedelic drug-like actions are

gone, basically. So there's, I think there's no question at all that the psychedelic effects are mediated by the 5HT2A receptor. The question comes, though, how is this related to the potential therapeutic actions of these drugs? So we have the best data for therapy for psilocybin. There are now, I think, two or maybe three, fairly well-controlled phase two, what are called phase two clinical trials with psilocybin. Small number of patients still. But what they showed was that either one or two doses of psilocybin was effective at treating depression for periods ranging from 24 days to a year, basically, depending on the follow-up in the particular study. And of course, the beneficial effects of psilocybin

occur after the psychedelic experience is over. And so the question has arisen, are the beneficial effects mediated through psilocybin, you know, activating something downstream of the 5HT2A receptor or is it some other target in the brain? And there's a huge debate about this right now. And there was recently a paper, I think you're probably referring to suggesting that this growth factor receptor in the brain for brain-derived neurotrophic factor can also be modulated by LSD and psilocybin. So that's a brand new discovery, just reported in the last month or so by a group at Hopkins.

Very interesting work. We'll see, you know, I'm sorry, it was a group from Finland or host? Finland, yeah, Finland. Yeah. Very interesting results. This group had previously reported that antidepressant drugs like Prozac or fluoxetine. also can activate this receptor. I would say the, you know, which is interesting.

Yeah, yeah. If true, of course, Prozac doesn't, you know, doesn't ameliorate depression in a single dose, right? So, and doesn't appear to have as robust effects as psilocybin. So it's sort of hard to square that. with the idea that they both interact with the same site. And to my knowledge, no one has ever has independently replicated those findings yet. So my lab, we're trying to replicate them now.

And, you know, we'll let people know in the next few months if we can replicate them. But very interesting, you know, pretty interesting. If it's true, it's a really, really important finding from both a positive and a negative perspective. The positive perspective is that here's a site for antidepressants, which is completely distinct from a psychedelic drug site. And if that's true, then we can easily make drugs that target that site. And they, by definition, they would not be psychedelic because they're not binding to the 5HT2A

receptor. The downside is that Track B is found in every cell in the brain, including both neurons and glia. And there were previous trials with brain drive neurotrophic factor as a therapeutic agent, which failed because of very severe side effects. So I'm guessing that we don't want to activate Track B in every single cell in the brain, probably not a good idea. idea. And we know if we activate track B outside the brain, then this is associated with the increased risk of cancer. So the tract B receptor is an important site for potential carcinogenesis, both inside the brain and outside. So if psychedelic drugs are having some off-target action, at the track B receptor, that actually could be a bad thing long term for psychedelics.

I would say arguing against all of this is the fact that, you know, people, humans have taken psychedelics since the 50s. There have been no reports of, you know, tumors. We would have seen this in the epidemiologic literature by now. So I don't think that's a particular concern, but it will, you know, it'll just be, it's like, you know, it's a, it's one of these very interesting novel, innovative findings. And we just need to see how, how reproducible this is yet. But very, I found the paper amazing, pretty, pretty cool paper. And I, I sent it around to everybody in my lab. And I said, we need to start studying this today. I put three people on the project. So it's pretty exciting.

But we'll see. We'll see what happens. Yeah, it's fascinating. I've been burned before in this area. Well, that's the beauty of investigating it and understanding it. And I think it speaks to the heart of so many people have had a transformative experience under psychedelics that was at times confrontations. confrontational. And people believe that it's that confrontation or that transformative nature of confronting something that helps them overcome obstacles. And I think that when you read this paper

coming out of Finland, it's trying to in some way say, hey, let's take the magic out of the magic mushroom. Let's take the trip out of it. I think that's where people are kind of fighting against. What do you think? Yeah. So a lot of people are trying to do that. So we have a big project that is funded by DARPA, Defense Advanced Research Projects Agency to see if we can create drugs that are not psychedelic, but still activate the 5HT2A receptor and have therapeutic benefits. Why do they want to do that? I don't understand. Like, why? I think, well, the reason is basic, I would say the reason is basically psychedelic drugs are not for, first all, they're not for everybody.

True. And you wouldn't want to give them to somebody in a battlefield situation. I think that would be like the worst. Point taken, right? Giving psychedelics to people with guns is probably the world's worst idea. The other thing is that many people probably should not take psychedelic drugs because they may have a history of, they may have a history or their family may have a history of severe psychiatric illness like schizophrenia or bipolar disorder. And certainly, if that's in your history or if that's in your family, You don't want to take psychedelics because of the risks that those could induce a, basically, a psychotic state or tip someone over into schizophrenia or bipolar disorder.

There's a interesting first person account I just read, I think, was odd on stat or one of those sites or wired, maybe it was unwired, or somebody took psilocybin and had a manic episode. and basically was ill for the next two years with bipolar disorder. Wow. So it really occurs. And as well, there are, you know, a vast number of people who don't want to take, who don't want to take a psychedelic. So when I was practicing psychiatry, which I don't see patients anymore, many of my patients who suffered for depression,

uh, basically were, they would come to me and they would say, just give me a pill to make me better doc, basically. They didn't, they did not want to engage psychotherapy or anything like that and certainly did not want to have a guided mushroom trip. And finally, uh, with,

uh, with psychedelic, uh, there is, there is now the requirement to have qualified individuals there basically before, during, and after the trip. And we'll never have enough qualified guides to treat the billion or so humans that are at risk for severe depression and post-traumatic stress disorder and so on. And so we really need, you know, it's, it's, it's, really important to see if we can harness the power of these medications without the psychedelic

effects, just because there are so many humans, so many people that suffer from these severe disabling disorders that they're never going to be eligible or don't ever have the resources for us guided psychedelic experience. In the state of Oregon, I think it's $2,800 for a guided experience, which, you know, if you live in the upper west side of Manhattan or in, I don't know, Pebble Beach or something like that, or Mission Bay in San Francisco, $2,800 is not a lot of money. If you're out here in rural Oregon, $2,800 is a lot of money. Yeah, for a lot of people. It's a lot of money. Yeah, I agree.

And so there is this other need. basically. It seems everybody Yeah, it seems to me that the millions of people that are depressed and facing these

this overwhelming trauma or a direct reflection of the people in charge. Like maybe the people in charge took the mushrooms they could have an effect and then they could change the society we live in, right?

Maybe the DARPA team should be doing the mushrooms. Yeah. I think you should probably talk to Rick Doblin. So that's his vision. I love it. I love it. Yeah, it's, so if I shift gears here for a minute, I was talking with a friend of mine, Jahim Fiber, and he's got a company called April 19th, and they use AI to create some new drug design.

And he had a question that he wanted me to ask you. And the question is, which other receptors, like GPCRs besides 5H2A seem to contribute to the effects? of psychedelics the most? There aren't any. So we actually, there are drugs that are on the black market that are pretty selective for 5HT2. So in the 5HT2 family,

there are three receptors, 2A, 2B, and 2C. Okay. The 2B is found in the heart. And drugs that activate it can cover. osvalvular heart disease, which is a serious concern with psychedelics, which we can get to later. And the two C has nothing to do with psychedelic drug action. It regulates feeding and things like that. And these drugs are psychedelic. They're, you know, virtually indistinguishable from LSD when people take them.

So the only thing I can say is that there are some other receptors that sort of negatively impact the psychedelic experience. So drugs like 5 methoxytryptamine. This is the, this is the drug that's found in toadskin. Phidemia? This apparently causes amnesia for the psychedelic experience or at least partial amnesia. And we think that's due to its activity at 5HT1A receptors, but I would say that's by no means definitive. So there are certainly other sites that these drugs hit that can attenuate the

psychedelic experience. But I don't think there's any good data that interaction with any of these other receptors promotes the psychedelic experience. So it appears to be just 5HT2A. And

sort of related to this, there's a paper that was just published where people were given either LSD or psilocybin in a blinded fashion and on two different occasions. And they were asked to distinguish, you know, which one was LSD and which one was psilocybin. They couldn't tell the difference, basically. So the effects were provided you give a sufficient dose, the effects are basically identical. With the caveat that the effects of LSD last longer than the effects of psilocybin.

But they're virtually identical. DMT is sort of a different story. So if you read the first person accounts, people have, you know, lots of people experience these spirits or entities or multidimensional machine, if somebody calls them under DMT, that appears to be somewhat unique to that. It could be just a pharmacokinetic thing because DMT gets,

into the brain really quickly and activates the receptors almost instantaneously. We know from our work in mice that 5HT2A blockers block all the effects of DMT. There have not been those studies in humans, so we probably should wait until we have the human studies, but there's really no good evidence that, at least in terms of the psychedelic action, that this is mediated by anything other than the 5HT2A receptor. Here's another one point. There's a hypothesis that a metabolite of LSD, hydroxy LSD, binds strongly to dopamine D2 receptors, which contributes to some negative effects of LSD.

Have you found any evidence for this in your assays? So we actually, so LSD binds strongly to D2 receptors. So it's a really potent D2 agonist. And it binds so tightly that we were able to solve. We recently were able to solve a structure of the D2 receptor with LSD bound to it. So we haven't published it yet, but we have the structure. Nice. So I haven't looked at hydroxy LSDs pharmacology.

Be interesting to look at that. But actually both LSD and LSD. and psilocybin activate D2 receptors pretty potently. LSD a little bit better than psilocybin. So it's hard for me to believe that that might be the case, but, I mean, you never know until it's been studied in some detail. Do you, like there is some, I was reading some theories about, and this was just in a magazine.

I can't cite the paper. It's more anecdotal than anything. But there's been some research in some papers or magazines that I was reading. where people are using like a nasal 5-MEO to help with dementia. Do you think in the future that there's potential for classic psychedelics to be used in aiding neurodegenerative diseases? Yeah, well, we don't know until we have clinical trials, but or even there aren't even animal studies yet suggesting the effect.

And I can just say two things about that. The first is that we know that psychedelic drugs induce plasticity in the brain, but this is a characteristic of all psychoactive drugs. So every psychoactive drug induces plasticity in some neural circuit to some extent or another. And psychedelics are no different or are not distinguished in that way from, from other drugs. But they do, the one thing that's sort of a little unusual about the psychedelic induced plasticity is occurs very quickly after psychedelic drug administration and is fairly long lasting. And the same sort of plasticity that occurs with psychedelic drugs also occurs with antidepressants

and drugs like ketamine, which are used to treat depression. And so we think that this plasticity may be important for potentially the therapeutic effects. And the question is, if you look at a neurodegenerative disease like Alzheimer's disease or, you know, Neiman-Pic dementia, frontal temporal dementia, I mean, there are a ton of these diseases. If you enhance plasticity, is that going to be a good thing or a bad thing? And it's an interesting idea. We just don't know. I'm guessing not. That's my prediction. I'm guessing we're not going to use fivetoxy DMT to treat dementia. You know, just clinically, the last thing in the world you would want to do is give a psychedelic to somebody who's demented.

It would be a really bad. It's a really bad idea. Maybe 5 methoxy DMT. You know, for anybody who's contemplating 5thotoxy DMT for dementia, what I recommend is you go to this TV series, Hamilton's Pharmacopoeia. Are you aware of this? I am, yeah. So he has a whole episode on 5thotxy DMT. And in this episode, you can watch him and his friend take 5thotxy DMT.

and it is the most terrifying thing in the world I've ever seen. His friend basically is completely dissociated, rolling around on the ground, frothing at the mouth, and they were at the stream, and they had to basically roll him out of the stream before he drowned. So it's, and Hamilton Morris is just completely out of it, basically,

when he takes it. So it's, It's not like a benign drug. It looks pretty scary. And I've talked to people who've taken five methoxy dm. And this one guy basically said, he thought he was dying, you know, I mean, physically. It was a very, very, very, very frightening experience. It's an extremely intense experience.

So I think the people that are studying this should talk to someone who's actually taken the drug, then they may see how foolish this idea is. I think it's a very foolish idea. That being said, I have heard from my basic science colleagues that they're now seeing with some psychedelic drugs in mice model, some evidence of sort of, I would say, beneficial plasticity in disease in which there is diminished plasticity. Okay. So there might be something there. But I think for dementia, we need, you know, with dementia, by the time people are

demented, they've lost a significant number of neurons in the brain. Psychedelic drugs do not increase neurogenesis or the, you know, they do not enhance the number of new neurons that are being made, basically. So they're not going to grow you a new set of neurons. They may make the neurons that are there have more branches, whether that's going to be a good thing or a bad thing in a demented brain is hard to say. But it might be for things like hearing loss or tentatus or something like that. I would say mild hearing loss.

Maybe COVID, you know, people that are losing their taste. the sense of taste and smell with COVID might be, you know, maybe there. I haven't heard anything yet, but that might be something you would think about, but dementia would not be the, that would not be the thing I would go after. I can give you a little more context on this. Sure, sure. So for a number of years, I was an editor for the Journal of Clinical Investigation, which is, you know, arguably the, the,

largest journal for sort of preclinical research. And I handled all the papers that were in the area of neurosciences. And at least once a week, sometimes twice a week, I would get a paper for a new drug that cured Alzheimer's disease in mice. So in my five-year period, I saw maybe 500 papers that would cure. Everyone different. Okay. So I'm very skeptical about these sorts of things.

There are tons and tons of interventions that will, you know, ameliorate Alzheimer's disease or cognitive deficits in mice. None of them work in humans, basically. So we'll, you know, we'll just have to see. But I'm for that particular application, I'm a bit skeptical. There are plenty of other good applications. Have you seen any studies? It brings to me the idea that I wonder what happens in the brain at a near-death experience

because there's no shortage of people who have had this near-death experience and come out of a changed person. Yeah. So I had one. Oh, do tell, my friend. It did not change me. It had to change you a little bit, at least a little bit. I don't think so. I'll just tell you what it was.

So I was out. I have a, my brother is a trauma surgeon. Okay. And also is a, is in the active reserve of the Army. And in his army career, he went through sort of Ranger training. And one night, when we were vacationing in Montana, he, he convinced me that the thing I should do is to do a midnight dive with him with, with scuba gear in this lake in Montana. And I did that. and I ran out of air and it was dark and he didn't see that I was out of air.

And I kept going up to the surface to get air and he kept pulling me down basically because he thought he thought my ballasts were not working right. And he drowned me basically. And just before, so I'd basically given up. And the only thought that came to mind was my wife is going to be really pissed at me because she told me not to take that midnight midnight dive

because we were like 100 yards from the shore and as I came up I could see them there and I was thinking oh she's going to be really pissed there wasn't any my mind was very clear very calm there was no fear

it was just this is really stupid thing to do I'm going to die out here and my wife is going to be really pissed. This is how it ends, I guess, right? Who knew? But it sadly did not change me. Interesting. Other people report different things.

You know, I didn't see any tunnel of light. I was certain, you know, I was certain I was dead, basically. I didn't see any tunnel of light or anything like that. It was just sort of clear. clear awareness. I practiced Zen. Okay. And it sort of was like a Samadhi experience, basically.

My mind was completely clear. You know, everything was bright. But that was it. Like trying to drink the ocean through a fork. Yes. Yeah, there is actually a Zen Kahn. swallow the ocean in a single gulp.

What your brother wanted you to do? I was doing that. Let's say that there was a study in psychedelics that won the Nobel Prize. What would that be, do you think? Is there a study that could win a Nobel Prize? Yeah, I think, yeah, the, if they give a Nobel Prize for psychedelics, psychedelics, they should probably give it to Roland Griffiths and the group at NYU. Because they discovered the therapeutic effects.

They published these back-to-back papers in 2016. And that basically started the entire psychedelic renaissance. So before then, there was, you know, no interest, literally no interest in psychedelic drugs therapeutically. And that really opened the floodgave. One could also make the argument that the MAPS, this multidisciplinary association for psychedelic studies that have brought forth MDMA. Again, I was extremely skeptical that MDMA would be effective for anything. But if you look at the clinical trial data, the results are astounding. I have, you know, I treated many people with PTSD when I was a resident.

psychiatry resident at Stanford. And there's nothing we could do for them. They were, you know, they had, these are mainly Vietnam veterans experienced the most horrific things. I mean, you cannot imagine what they experience, what they've experienced. And in many cases, through no fault of their own. They were just passive bystanders, you know, and something blew up and their friend was completely obliterated, basically. And it was clear to me that we didn't have anything to offer them. The best we could help them with was we could give them certain types of antidepressants, which would suppress their ability to have dreams.

So they wouldn't dream in that, basically. But that was basically it. And then I saw the results, the phase three trial results, with Ecstasy published in Nature Medicine, I think three years ago. Amazing. Unbelievable, basically. And I've subsequently heard from many veterans who contacted me by email and elsewhere that these medications, these drugs are extremely effective for treating PTSD in the right setting. So I think MAPS gets a huge a huge slice of that as well.

Does it be my, if I, if Nobel committee asked me to nominate somebody, does it be the people I would, I would nominate? Yeah, I mean, it's, we would not be where we are today if it wasn't for those, those three organizations. Yeah. When you see the research like that on MDMA and what it's done for people, doesn't it make you curious to want to try it? Yeah, I thought about it. It's illegal, right? In some places. I'm sure we could find a location that's not, right?

Yeah, yeah. So, I mean, one of the things I was curious about is what a rave, what an authentic rave experience would be like. So I've talked to lots and lots of people in the rave culture. And they describe really a really intensely ecstatic and spiritual experience. And I thought that might be interesting to try, you know, basically if it was legal. And if my physician said it would be safe for me to take. There, ecstasy is not without its side effects.

Sure. You know, hyper, what's called hyperpyrexia, which is, you know, increased temperature. fainting and so on. You know, it's rare, but there are people that die from ecstasy. If they're not in a, in a coolish, a coolish environment, basically. So, yeah, so that's the only, that's the only one that sort of piqued my curiosity. Not enough to really try it, but it's intriguing to me. I don't, you know, I don't, luckily, I don't have any, any post-traumatic stress

disorder symptoms of any sort. I think it would have been, it would have been useful for me when I was a trainee, a medicine trainee. In that era we had, it was in the era before, before cell phones, and we had beepers, basically pagers. And when we were on call, the pager would go off, right? And immediately, my heart would start racing. I would get. So I sort of had like mild PTSD for the sound of beepers,

pagers. So it might have been useful back then, but I don't have anything that would be, you know, that would make it necessary for me to take ecstasy. How about yourself? Have you ever thought about taking ecstasy? I've taken a, I've taken a bunch of it. I've been pretty well-versed with psychedelics. I've taken my. mushrooms, LSD, a bunch of the analogs like Eflat, Ecstasy. I've tried a host of recreational drugs. And I've found that they have been really phenomenal in helping me work through my trauma. Obviously, I've used them in a recreational form.

But as I've gotten older, like I've really used, I'll give you an example. I've been a UPS driver. I was a UPS driver for 26 years. And in there, you know, I've found myself. at a state after my son died where I was really angry for a while. And I was really, there was a guy at my work and I was really mean to him all the time. But I thought I was just joking with him. I would say things like, oh, you're a big baby or you're really weak.

I would say mean things to him. That's pretty weak. And it was way worse than that. But here I am, my ego in check, trying to be all cool guy. Right. You know, and my friend pulls me aside and he goes, George, you're being a real dick to that guy. And I was like, do you think so? And he's like, yeah, that's why I'm telling you, man.

And I remember that weekend, I did a big dose of mushrooms. And I thought to myself, like, why am I being so mean to that guy? And it hit me in like a one-two punch. The first punch was, you don't like him because he's weak. And the second punch instantly is like, no, you're weak. And he reminds you, you're weak. And I went, oh, geez, I get goosebumps when I think about it, you know? And I was like, oh, my God.

And then, of course, I had to go apologize to him and be like, You know, I just wanted to apologize. I've been really mean and disrespectful to you, and I hope you'll accept my apology. You're a great person. I'm really weak, and I'm working on some things, and I want to thank you because you showed me that I'm weak, man, and I'm sorry.

Wow. But I would have never had, I may not have had that insight for a long time, or ever had I not been in a heightened state of awareness or in a state which that could have, what I could have thought. I saw myself at almost a third person point of view, And that seems to be something that is pointed out in different types of PTSD treatments when I read about other people.

When I talk about people that go and have these experiences, that seems to be something that's repeated. Maybe not in that exact form, but they're seeing themselves in a third person point of view. On the topic of ecstasy, yeah. Ivo games. Seems to be, have specific activity for that, at least from my, from. what I've read, there are reports of people basically experiencing what they did to other people from the other person's perspective. Yes.

Basically. And that, as you imagine, that is extremely powerful, right? Extremely powerful. Yeah. Well, think about that from a doctor's point of you. Like, if you have that experience, then I think you'll be able to better not only diagnose the person that may have something, but you'll have a real empathy with that person. I think that enhances your relationship with the patient in a weird sort of way.

Yeah, it may. And, you know, everything you say is very intriguing and consistent with what many, many people have told me, basically. And so I don't, you know, I think it's pretty clear that in the right circumstances, sure, these drugs can be, you know, quite useful. I like to call them medications now rather than drugs. Agreed. Because they're under, you know, they're under investigation by the FDA as medication.

Sure. And I think the challenge going forward will be fine, you know, to find the right patient cohorts for them, the right therapists, and the right indications. But, yeah, I mean, this is what I hear. It's particularly powerful talking to veterans who have, you know, gone on ayahuasca journeys or ibupane journeys. They have very powerful experiences as well, very, you know, in some ways very similar and end up with, you know, an acceptance and alighted. of that loge.

For myself, since we're into anecdotes, I practice Zen. Right. Okay. And for a number of years, well, for decades, basically, I had some issues with my father,

you know, typical, I'll say more, more extreme than sort of typical. I was in cycle analysis as part of my training to deal with this. And the amazing, so I go to these Zen retreats several times a year. And I remember after a particular Zen retreat,

I came out of the retreat, basically, and the anger was gone. It had totally disappeared, completely, gone. And I basically called up my parents in the next few days and expressed my gratitude to them for their help, basically. Nice. They thought I had gone crazy. But the thing that's interesting to me is that during that retreat, and actually during all my and retreats. My father has never came up for me.

Okay. So it wasn't like I dealt, it wasn't like I had a hallucination of my father during the retreat. It's just that it just fell away, basically. So I think what this indicates to me is that there are other, other, there may be other approaches.

which do not rely on this, basically the psychedelicized experience that might be the same. The downside with Zen is it takes about 30 years of training. So it takes a long time. It's not particularly user-friendly. Yeah. Any heightened state of awareness, right?

Anytime you're able to find yourself in a different state of awareness, you can see yourself in the situation in the world around you differently. It's a shifting of perspective. And I think the psychedelics, they rocket you to that. If you don't understand, if you're getting rocketed to this new space, it could be scary. But it's like any environment you're in, whether you're at a Zen retreat on day five,

it may take 25 years for you to get comfortable in the environment before you can explore it. The same goes with a psychedelic, substance. You may have to go on a few journeys before you become comfortable with the environment and you can begin picking things up and being, oh, well, that's my relationship. Or, hey, that's me being a knucklehead, you know? Yes. Yeah, I just, you know, getting back to this, I recently was at a scientific meeting. And one of my colleagues who suffers from severe depression had, he came to, he came to me,

and he looked different. Nice. And he's somebody my age, basically. And he said, he went under guided psilocybin experience, and he said it was amazingly effective, basically. This was a guy, I never, no way I would ever have. So he went to a, you know, a regular therapist. And it was in a place that it's legally.

basically. But interestingly, he said that the integration is the most difficult for him. The integration after the experience has been the most powerful. How does he define integration? What does that mean? I didn't get into that with him. You know, I didn't discuss what his issues were. I was just happy to see that he had a smile on his face and a twinkle in his eye.

Yeah, he looked different. you said. He looked different. There was no question. I could see it. I could see it. Tangible. Yeah. There was no question. Yeah. This is going to sound crazy, but I'm going to say it. I think if you did a large dose of psilocybin, the direction of your research would change dramatically. I've been studying psychedelics since 1983. I know. I know. I don't mean that. I don't mean that in a bad way at all. I'm just saying, I think it would. I know it. And I, please forget. give me for saying something like that. But I have to say it. I think it would fundamentally change so you don't know anything you don't I don't know crap man you don't know anything about my past let me just put it that way. Okay I don't I mean no disrespect there but I you can share some

with me. I'm not going to get into anything in my past but let me you know let me just say that that my interests always have been how how drugs are out. acting at the most fundamental level. And I've always wanted to study psychedelics, basically. I'll just put it there. Put it out there like that. Right. And, you know, we all have our own interests.

Absolutely. You know, every mind is different. We all have our own interests and our own opportunities and potentialities. And the way my mind works, the research that I do is the best thing for me to do. I'll just put it that way. Okay. Yeah. I'm stoked you do it.

It's fascinating. No one else is doing it, basically. So for years, I had the only grant to study LSD, literally the only NIH grant to study LSD, up until about three or four years ago. So I was the only person, almost the only person in the world that was studying these drugs at the, at a fund. mental level. And we don't, we, we don't know anything about how these drugs act in the brain. And, uh, that's, that's what I'm really, you know, I think that's where I can make the biggest impact. There are tons and tons of psychologists and therapists that are looking at the sort of trans personal and transformative aspects of these. And that's fine. That's, they can, they can do that.

I'm best at that sort of more basic research and that's, that's where I should be, basically. So that brings up once something, like once something attaches to the 2A receptor, is it just a level of cascading events after that? Is that when the incoherence comes in? Like, do we know what happens after that? Or like, so we don't, we don't really know.

That's one of the big things we're trying to find out. I can tell you what we think. I can tell you what my current understanding is. Okay. Please. So the 5HT2A receptors are found in the cortex. So who is the audience for this? Let me just so I know how to explain things.

It's a wide range of, I have a lot of people on LinkedIn that are doctors and psychologists, but then there's also a lot of recreational users like me or people that enjoy listening to psychology. So you have a wide swat. So I would bring it down to it. I'll bring it down. So in the in the cortex, that's the part of the brain that that we think with and gives us a perspective of reality. That's where these receptors are the most highly enriched.

And when LSD binds these receptors, it causes the neurons to fire in a very disorganized fashion. Okay. So it basically injects noise in the system. So what you have is that the part of the brain that's most critically involved in giving us our view of reality, there's now noise like this in it. Okay. And we think that is what caused, you know, our best guess is that that is what causes the psychedelic experience. They're no longer, the mind can no longer trust the internal. the external cues. And so now it turns its awareness into experiences that are derived internally

from the cortex. Okay. And what you see concomitantly is that in the visual cortex, so the area of the brain that's responsible for seeing the world, that gets shut down to some extent because people are now basically focusing on internally derived visual stimuli. Okay, swirl, whirls and things like this. And then the mind begins to create a narrative. And the narrative, for reasons that are not understood at all, Well, we don't know why it creates a narrative, but it does. Talk to anybody who takes a psychedelic.

There's a narrative, right? Right. There's a story, a story. That is imparted with tremendous meaning and significant. Okay. Right. And that's very peculiar for psychedelics. So marijuana, people who smoke marijuana, they don't say,

I smoked this joint and I had this transformative experience. They don't say it. I know. They don't say that. People who take crack cocaine, don't say that. Nope. People who drink alcohol don't say that. But people that take psychedelics say that.

So that's very, very interesting to me. And it's due to the drug, right? Because you didn't have that experience before you, took the drug. You only had the experience when you took the drug. So the drug is doing something in the brain that's, you know, creating this narrative and giving a tremendous significance and also relevance for your life. Yeah. So we don't have the foggiest idea once. And I, and so I get at this meeting, I gave a talk, I was the keynote speaker, I gave a talk on, psychedelics. And I said, as part of my talk, I said, we don't have any idea what's going on here.

And my friend who had taken psilocybin said, you're right, we don't have any idea. We don't have the foggiest idea what the heck is going on. And I think it would be useful to understand that, right? If these medications are going to be approved and used by millions and potentially billions of people, it would be quite useful to understand how they work in the brain, right? So that's what I'm focused on. Do you have any like, I know doctors and scientists aren't supposed to speculate. Do you have any ideas of what you think may be happening? No, I don't, I don't, I'm, I'm quite perplexed.

And I, I, so the technical term for meaning is what's called salience. So there's this term called salience. Okay. And so psychedelic experiences are filled with salience. And when I talk to the people that study salience, they tell me I need to study the locus serulius and noraphenephyr neurons. And I say to them, well, psychedelics don't affect the locus serulose or epinephrine neurons. And they said, well, it can't be salience. Then I said, well, it is.

There's no question. So, so this is, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's it's unchartered territory. We don't, you know, this is, this is, this is one of the reasons I find it really, really interesting. That's, you know, that's sort of where we are in terms of psychedelics, where, we're, we're in the dark age. in terms of understanding them. And, you know, it's just a really exciting time. See, it seems to me on some level.

Like, it's, it's, I think that that idea of meaning stems from language. Like, it seems to me the reason why you have such a powerful experience and it's a connection and meaningful to you as an individual on psychedelics is because for the first time in 50 or 40 or, or 30 years, you have the ability to reimagine everything. And if you just think about the way we're taught, like the phonetic alphabet in the world, the way we process information, you see something. And all of a sudden, you're given the title of that.

That's a bird. I'll give you an example. Like, let's say you're a baby, you're two years old and a bird flies into your room. And as a child, you're like, look at this magical flying beast flapping its wings. And your mom comes in and says, George, that's a bird. That's a bird, George. Okay, that's just taking everything away from me and has given me birds. that process has gone on for 50 years.

And when you take a psychedelic, that phonetic alphabet, the separation, the idea of exact repeatability is gone. And now you as an individual for the first time in 50 years are seeing something and giving it the meaning

that you want to it. That is an experience of a godlike experience, right? Yeah. Don't you crazy? Yeah. You know, so many people have these experiences where they're an omniscient experience or where they are the universe, right? Right. Yes.

Where there's no separation between them and the universe. When they breathe in, the universe breeze in. When they breathe out, the universe frees out. I have the same experience when I practice Zen. I'm just not having a psychedelic experience. So I. I completely get with what you're talking about. And it's, it's, it's marvelous, right?

Yes. It's a marvelous, it's a marvelous, wonderful experience to hear a bird for the first time, to really hear a bird, to hear just the sound of the bird, right? Just the bird or just see the bird. Yeah. Where you and the bird are one with the universe. It's wonderful. It's transformative.

how could you ever hurt a bird after that, right? Yeah. Right? How could you ever squash an insect after you've had that experience? So I'm with you. The thing I'm a little cautious about, though, is that I grew up sort of the tail end of the 60s. And many, many people I knew took psychedelics. Virtually everybody had took psychedelics at one time or another.

And had, you know, peak psychedelic experiences. There was tons of LSD around. It was reasonably pure. Many of these people are now Trump supporters. Don't eat the brown acid. I grew up in Montana. I grew up in a small town in Montana, okay? Okay.

LSD made it to Montana. Right. And I was on Facebook recently, and a lot of these old hippies are now huge Trump supporters. It's like the most, and, you know, anti-gay, you know. So it's, you know, if you would have talked to them in the 60s or 70s, they were very, liberal, open-minded people. But it didn't last forever. It lasted, you know, probably for a year or so, and then at most, and then they were basically who they were. So that's, you see, you see these things. A lot of people report these things. You know, so many people took LSD in the

60s that we should now have an enlightened society. Right? Right? All those boomers, I don't know. All those boomers, all those boomers took LSD. There were tons of them. Maybe a million boomers took LSD. Boomers are the state of supporters now. So this is the pushback I give people that if you look at long term, okay, unless, you know, maybe people need to take a booster once a year. I think it needs to be a relationship for life with it. So, but a single dose or a few doses just doesn't lead to any, any long-term transformation.

I can sort of give you two anecdotes about that. Sure. You might find interesting. Of course. In Alcoholics Anonymous and other 12-step programs, they warn about this, basically, that, you know, early, early in the program, you're going to, going to see big changes. But they say it's a lifetime journey.

And one of the ways they say that is, is a jerk or an asshole, basically. An asshole gets on the plane in Chicago, and an asshole gets off the plane in Detroit, right? Okay. So you can have this wonderful experience. You're still basically, you may still be the same person. and you need to guard against that.

The other thing was, oh, oh, so Mountain Girl. You've heard of Mountain Girl, right? It sounds familiar, but maybe I can't quite think what it is. Maybe you can flesh it out for me. I think that was Jerry Garcia's second wife. Okay. And she was also one of the first Mary pranksters with Ken Kheesey. Okay, right?

Cuckoo's next. Yeah. So she lives in Oregon. She lives in outside Eugene. I just read a, she's pretty famous in the psychedelic community, very famous in the great, I'm a grateful fan. So let's great. Nice.

And to know who Mountain Girl is. She said she takes psilocybin once a year. And this guy who wrote the, which I'm not recommending this. I'm just, right. Just telling a story. That's what she says. She takes it once a year to reconnect, basically, reorient. And this guy, Tom Robbins, this famous author who wrote all these marvelous books.

Another roadside attraction, I think, was one of his big books. He lives or lived in the Northwest and took mushrooms once a year, basically. So my guess is for really long-term, you know, long-term. transformation, probably you need to be in psychotherapy, practice Zen, group therapy. You know, I'm not going to recommend taking psychedelics regularly because we just don't know what the ramifications are for that. But that's my pushback is that the enduring, the enduring effects on personality don't appear to be that enduring for the vast majority of people.

This was noticed in the 60s when they did studies on LSD and psilocybin. People who are alcoholic initially would have a period of abstinence. And then unless they were in a 12-step program, basically would start drinking again. So there needs to be something, I think for most people, there would need to be something added to that. I don't think it's going to be like take five grams of mushrooms. call me in the morning and all your problems will be gone forever. I don't think that's going to happen. Yeah.

From what I have read about some of the beneficial effects that I have experienced is that it seems to me psychedelics help you confront an issue. Where in the world of addiction, people are running from an issue. People take, people will drink alcohol to get away or not think about their problems. They'll do cocaine to get away from these things. But it seems in a psychedelic experience, there's nowhere to run. that the problem is in front of you, but not so much in a way where you can't deal with it.

It's in a matter that's like, what if I did this or I'm kind of being a knucklehead? You know, it's almost like a friendly exchange between a different version of yourself and the truth. That kind of makes sense. Yeah, I think that's dependent on the person, right? Good point, of course. Yeah.

Yeah. So, you know, people with, that are insufficiently integrated, maybe they have a severe personality disorder, borderline personality disorder. It would be pretty problematic for them to have that experience. And one can imagine, you know, well, I've met people who have, quote, unquote, bad trips. And I think that's why all the regulatory agencies, so the FDA basically recently issued a guidance on psilocybin and other psychedelics. And they, you know, part of the, part of the, part of the FDA recommendations is there need to be guides. Yeah. So I, you know, everything you say is certainly consistent with, with things I've heard from many, many other people.

but I would caution listeners here not to do this on your own. Ideally, if you can make it out to Oregon, you know, make it out to, you know, make it out to a licensed practitioner, a licensed therapist, somebody who's gone through the training and has experience. You know, don't, don't in, you know, if you're a teenager, don't have two of your friends. sit with you. Probably not a good idea. Yeah. You know, certainly everything you say is

possible. Makes sense. Yeah. Sometimes, like when I read some of the literature about people finding novel ways to solve problems or having that aha moment that we talked about, sometimes they find themselves out in nature

and they're studying things. And there's a weird similarity that I think a lot of people have noticed that if you look certain types of mycelium, which is like the fungal growth of the mushrooms, and you can see how they move through the root structures of trees. They're providing nutrients to different parts of the root structures. And it seems that that is what happens in the synaptic activity of our brain when we consume mushrooms. It's moving energy around or dendritic spines or moving back and forth and changing shape. It seems like it's, it just seems like there is a pattern.

And maybe it's because I'm seeing patterns where there aren't any patterns. But can it be as above so below? Like, could we study what's happening in mushrooms below ground to see maybe what's happening in our brain when we take fungus like that? Or is that too far out there? I've heard a lot of people say these things. What I reply is DMT doesn't come from a mushroom. Right. Okay.

LSD does not come from a mushroom. and people have the same experience. So I don't think it's the mushroom itself. It's the drug. But what they, an MDMA, ecstasy also in, from what I've heard, improves, you know, people have this sense of communion, right? Yeah.

MDMA is an entirely synthetic molecule. So I, you know, it's, it's an interesting idea. There are lots of mushroom, you know, all mushrooms are mycelia. They don't all give us, you know, there's only a few that give us a psychedelic experience. A lot of them are poison. Some, you know, cause a dissociative experience like aminae and muscarina. So, yeah, I think it's, you know, it's an interesting story. you know it's helpful to people it's fine but I don't you know I've heard

right right yeah I think it's a story so it's again one of these stories the mind makes up and you know the storytelling yeah yeah yeah makes up a story this guy who who coined the term multi-dimensional is she knows I Terence McKenna. Terence McKenna. Yeah, he has, I urge people to listen to his, listen to him on YouTube. You only have to listen to a couple of his talks before you get the entire message. But he has, you know, he has this strange idea that mushrooms are like an alien life form and communicating with us.

anything is possible. I think they're just psychedelic mushrooms, you know. Right. Yeah. I think it was almost harkening back to Francis Crick's idea of panspermia. You know how like all of a sudden there's spores that come from another planet. And I don't know. There's some fascinating, fun ideas to think about that could be possible, you know?

And I don't know. Here's one about an addiction that I was thinking about. It's weird how in the world. of addiction, we see the treatment for that is almost to give somebody another medicine that keeps them addicted. And as a psychiatrist, it's so weird that how, I mean, I'm not a psychiatrist, but I'm always like to get your opinion on. It seems that we as humans have used that in the business world. And I'll give you the idea of like toner. Like they'll, you can buy a copier from Xerox and they'll give you the copier for almost nothing. But then you got to buy the toner.

it kind of seems like they've harnessed the addictive model of drugs or is that just a scaffold that we have humans move towards it's weird how that permeates both sides of us though right like it's in business and it's an addiction it's something that we do maybe yeah yeah

so I've heard this sort of argument before from people about all sorts of things in medicine okay and you know my I can only speak but my experience as a physician and the experience of people I know very well as physicians. Our goal is to help people.

Yes. And I also know people that work in the pharmaceutical industry, and their goal is to, you know, make a medicine that makes a difference for people. That's their goal, secondarily to make money. And with... With treating addiction, it's a really complicated thing. So you need there, there's physical addiction. And frequently, the best thing you can do for the patient where they are,

for the individual, where they are in their lives at that period of time, is to decrease their craving for the addictive substance so that they no longer engage in the really terrible things that they're doing to, to themselves and to others to maintain their addiction. And I don't think any physician that specializes in addiction disorders would say that their goal is to get them addicted to, so if they're a heroin addict to get them addicted to methadone. That's not the goal.

The goal is, the goal of our goal, is to get them off and have them lead a, you know, the life they want to lead. But that's not possible for everybody. You know, for a whole host of reasons. Sometimes there aren't, we don't have the support systems in place. You know, we don't invest any money in community mental health or community substance abuse matters. And we don't see it as a priority in our country. You know, and I think what we really need is we, we as a society, need to have a change in our hearts inside so that we can connect with people and help them, help them out.

And until until we're in sort of this, what I call an alternative Canadian universe is orthogonal to our particular. universe. Or, you know, alternative Netherlands universe or whatever, you know, Swedish universe. Right. You know, we're not going to get there. And, you know,

I don't know of any physician that thinks, you know, it's a good outcome that the person is now on be appropriate home, you know, or use buprenorphine versus heroin. So buprenorphine is now given a lot

to diminish cravings for opiates and help the recovery process. Nobody sees that as a final solution. It's a step. It's a step in the direction of recovery. And we just don't have, you know, blame it on your congressman. We don't have anybody that, you know, we don't have any advocates out there for people with severe substance abuse and mental illnesses in this country. And it would be great if we, you know, lived in a society where everybody could have access to an addiction network, addiction recovery network.

We don't have that here. That's what we need. The medications are effective. They're not, you know, they're not the final situation. And I actually don't know. I know of no physician that would say, yeah, I'm just giving this to me. I mean, there are physicians out there that have, you know, prescription pill mills in their office. But the vast majority of us out there,

know we're confronted with literally an unending stream of human suffering every day entering our doors and what we want to do is to diminish that suffering in some way and if it's a if if the only intervention we can give is a pill that we give that basically yeah okay and you know try to do our best but it's you know we live in an imperfect world sadly and So we have to have to just take advantage of the tools that are currently available. I think in the future, psychedelic medicines may be an instrument in the armamentarium. You know, certainly what I hear from individuals who have taken ibogaine who have taken ibogaine, who are heroin addicts or fentanyl addicts, you know, many, many, many people find after that the strength.

to leave that all behind. And it would be wonderful if we had some sort of treatments where everybody that came in the door, we could say, well, here's a prescription. Here's Joe and Sally, there'll be your guides, basically. And they're going to take you through a guided experience. And then we have a whole program afterwards for integration and aftercare

and maybe booster sessions at some time in the future. We don't have that right now. And so we, you know, we just have to do what we can with what we have. It seems like one of the biggest problems with trying to get new technologies or new drugs to market is like the clinical trial process. Do you think that maybe in the future we'll see like a way to streamline that? Like James Fateman has like the Fateman protocol where he, you know, he sent, he had everybody send in, you know, I forgot the exact amount of people he had. but he sent it out to the public, kind of farmed it out a little bit. Please send in the dosage you're taking, what you're taking it for.

And he created like this large swath of almost a survey type of protocol where people sent stuff in. And I realize it's not that accurate. And there's you're not controlling for all these variables. But might it be a way in the future to help bring clinical trials down? Or is there a way to restructure that to get the price down on clinical trials? Uh, I know I'm way out there, man. I don't know. I'm stoked to talk to you, Brian.

Clinical trials, yeah, that's, the issue with clinical trials is they need to be designed in a way in which you get an unambiguous answer at the end, right? You want a definitive answer. And, you know, the way, basically the gold standard are these placebo-controlled double-blind, large phase three trials. This has been modified somewhat over the years, primarily from AIDS activists and cancer activists, so that there are sort of alternative ways of doing things. But until we come up, you know, I'm open, you know, I don't do clinical trials. But I think the regulatory, you know, I'm sure the regulatory agency, would be overjoyed to find something that's more effective, faster, cheaper than our current way of doing

things. The problem that they run into is that they have to certify that the drug is safe and effective. And, you know, the worst thing possible would be to have a bunch of things on the market that are simply not safe. I mean, if they're not effective, it's not a huge, you know, it's, it's bad for the patient, but it's not going to cause, quote, or cause them any harm. It's not going to hurt them anyway. But, you know, serious side effects. I recall the fen fen thing many years ago. Yep. We don't want to have something like that again. That was disastrous. The litamide, the

same thing. So it's it's it's a balancing act. I just say sometimes so I have friends that work for the FDA, people from my lab that used to be in my lab. And again, their goal is, you know, to make sure we have safe and effective medications. That's their goal. They don't have any, they don't have any alternative. Right. Motivations or motivation. Yeah. That's all they want.

And, you know, we just don't, right now, we just don't have anything that is, that, that gives unambiguous conclusions like, similar to a double blind placebo control trial, which is going to cost a couple hundred million dollars, basically. They're extremely expensive to do. So that's where we are. That is. Brian, I just want to say thank you from the bottom of my heart. I really enjoy talking to you.

This is really fun. And before I let you go, though, where can people find you? Where can they check out some of the things that you're doing at the lab? So the easiest thing is just to Google me. And I think my Wikipedia page comes. up and you can get links from there. Okay. Yeah, that's the best way.

Or you can, people can email me. I get emails all the time. Just go to, you know, go to Wikipedia. It will eventually get you to my email address and then you can, you can send me an email. And I reply to them all. Even if my reply is, I know nothing about this. I can't help you, but here's somebody that really knows something about it. That's so awesome.

It's so awesome to get to talk to somebody who's on the forefront of, and been on the forefront for so long that cares about making the world a better place and is willing to talk to people. So I'm truly thankful for that. Sure. And hang on one second. I'm going to hang up with the people, but I want to talk to you briefly afterwards. Ladies and gentlemen, thank you so much for today. I hope you all have a beautiful day.

It's Monday. I want to tell everybody out there, listen to the voice in your heart and follow it. And things will always get better if you have patience. So that's all I got for today. Ladies and gentlemen, Aloha.