Dr. Matthew Johnson: Psychedelics for Treating Mental Disorders | Huberman Lab Podcast #38

Transcription for the video titled "Dr. Matthew Johnson: Psychedelics for Treating Mental Disorders | Huberman Lab Podcast #38".


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Guest Introduction

Introducing Dr. Matthew Johnson (00:00)

Welcome to the Huberman Lab podcast where we discuss science and science based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and Ophthalmology at Stanford School of Medicine. Today I have the pleasure of introducing Dr. Matthew Johnson. Dr. Johnson is a professor of psychiatry at Johns Hopkins School of Medicine where he also directs the Center for Psychedelic and Consciousness Research. As many of you know, there is extreme excitement about the use of psychedelics for the treatment of various disorders of the mind. Dr. Johnson's laboratory is among the premier laboratories in the world understanding how these compounds work, how things like psilocybin and LSD and related compounds allow neural circuitry in the brain to be shaped and change such that people can combat diseases like depression or trauma or other disorders of the mind that cause tremendous suffering. Dr. Johnson is also an expert in understanding how different types of drugs impact different types of human behaviors such as sexual behavior, risk taking and crime. Dr. Johnson and his work have also been featured prominently in the popular press such as articles in the New York Times and Michael Pollan's book "How to Change Your Mind" and in a feature in 60 minutes about psychedelics and the new emerging science of psychedelic therapies for treating mental disorders. During the course of today's conversation, Dr. Johnson and I talk about psychedelics at the level of what's called microdosing, whether or not it is useful for the treatment of any mental disorders. We also talk about more typical macrodosing, what those macrodoses entail and he walks us through what an experiment of a patient taking psychedelics for the treatment of depression looks like in his laboratory from start to finish. The conversation was an absolutely fascinating one for me to partake in. I learned so much about the past, present and future of psychedelic treatments and compounds. And indeed, I hope to have Dr. Johnson on this podcast again in the not-too-distant future so that we can talk about other compounds that powerfully impact the mind and human behavior and perhaps can also be used to treat various diseases. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.

Understanding And Experiences With Psychedelics

Supporting Sponsors (02:10)

It is however part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Athletic Greens. Athletic Greens is an all-in-one vitamin mineral probiotic drink. I've been taking Athletic Greens since 2012 and so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or twice a day every day is because it covers my foundational nutritional needs. It has the vitamins I need, the minerals I need and the probiotics are important to me because there is now so much data about the importance of the so-called gut microbiome maintaining healthy gut bacteria and the ways in which those gut bacteria impact things like inflammation and keeping inflammation down in the brain and body as well as supporting things like quality mood, endocrine function, metabolic function, just so many factors. The great thing about Athletic Greens is that it also tastes very good. I mixed mine with water, a little bit of lemon juice and as I mentioned, I drink that once or twice a day. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and if you do that, you'll get the Athletic Greens plus you'll get five free travel packs. The travel packs make it very easy to mix up Athletic Greens when you're on the road, in the car, on the plane, etc. And you'll get a year supply of vitamin D3K2. There's now a lot of evidence that vitamin D3 and K2 are important for various aspects of metabolic health, cardiac health and so forth. So once again, that's AthleticGreens.com/huberman to get Athletic Greens, the five free travel packs and your year supply of vitamin D3K2. Today's podcast is also brought to us by Inside Tracker. Inside Tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. Of long-binable lever and getting regular blood work done. And now with the advent of quality DNA tests, you can get a lot of information about your genetics and how that also impacts your immediate and long-term health. The reason I'm such a fan of getting blood work done is that it is really the only way to understand what's going on in your system at a level that can really inform your decisions about your immediate and long-term health. The problem with a lot of blood and DNA tests, however, is that you get numbers back about your hormones and your metabolic factors, etc. But you don't know what to do with that information. With Inside Tracker, they have a very easy to use dashboard that gives you that information and then gives you some suggestions and directives about things you could change about your nutrition, about your exercise and other lifestyle factors that can help you move those numbers in the direction that's best for you and for your health. If you'd like to try Inside Tracker, you can go to Inside Tracker.com/huberman to get 25% off any of Inside Tracker's plans. Just use the code Huberman at checkout. Today's podcast is also brought to us by Belcampo. Belcampo is a regenerative farm in Northern California that raises organic, grass-fed and finished certified humane meats. I eat meat about once a day. In general, my lunch or my breakfast consists of some meat and that meat has to be a very high quality and generally I'll eat some vegetable as well. And then I tend to eat pastas and rice and things of that sort later in the day or in the evening in order to facilitate the transition to sleep. So I'm eating meat about once a day and I always insist that the meat that I eat be of the very highest quality and that the animals were raised and maintained humanely. While conventionally raised animals are confined to feed lots and eat a diet of inflammatory grains, Belcampo's animals graze on open pastas and seasonal grasses, resulting in meat that's higher in nutrients and healthy fats. In addition, they raise their animals in a way that's not just better for our health but also has a positive impact on the environment. They practice regenerative agriculture, which means the meat is climate positive and carbon negative so you can feel good about what you're eating at the environmental level and for sake of your health. You can order Belcampo's sustainably raised meats to be delivered to you by using my code Huberman at belcampo.com/huberman and entering my code Huberman to get 20% off your first time order. I'm partial to the ribeyes or the New York Steaks. So on one day I might have a ribeye, the next day I might have a New York Steak. I also really like the meatballs. I'm a particular fan of the meatballs. So again, that's belcampo.com/huberman and enter the code Huberman at checkout to get 20% off your order. And now my conversation with Dr. Matthew Johnson.

Psychedelics’ Defined (06:40)

Well, Matthew, I've been looking forward to this for a long time. I'm a huge fan of your scientific work and I'm here to learn from you. Likewise, big fan and happy to do this with you. Okay. Well, thank you. My first question is a very basic one, which is what is a psychedelic? We hear this term all the time, but what qualifies a substance to as a psychedelic? Nomenclature is a real challenge in this area of psychedelics. So starting with the word psychedelic, it just, if you're a pharmacologist, it's not very satisfying because that term really spans different pharmacological classes. In other words, if you're really concerned about receptor effects and the basic effects of a compound, it spans several classes of compounds. But overall, so it's really more of a cultural term or it does have a relationship to drug effects, but it's at a very high level. So all of the so-called psychedelics across these distinct classes that I can talk more about. The way I put it is they all had the ability to profoundly alter one's sense of reality. And that can mean many things. Part of that is profoundly altering the sense of self acutely. So when someone's on the psychedelic, so the different classes that can be the specific psychological classes that can be called a psychedelic are one that what are called the classic psychedelics. So in the literature, you'll see that term and hallucinogen and psychedelic are all have traditionally been used synonymously. I think there was a little of a tendency to stay away from psychedelics of the baggage, but there's been a return to that in the last several years. But the classic psychedelics or classic hallucinogens are things like LSD psilocybin, which is in so-called magic mushrooms. It's in over 200 species that we know of so far of mushrooms dimethyl tryptamine or DMT, which is in dozens and dozens of plants nesculine, which is in the peyote cacti and some other cacti like sand Pedro. And even amongst these classic psychedelics there are two structural classes. So that's the chemistry. There's the tryptamine based compounds like psilocybin and DMT and then there's the phenethylamine based compounds. So these are the basic two, basically building blocks that you're starting from either a tryptamine structure or a phenethylamine structure. But that's just the chemistry. All of the what's more important or at least to someone like me are the receptor effects and then ultimately that's going to have a relationship to the behavioral and subjective effects. So all of these classic psychedelics serve as agonist or partial agonist at the serotonin two-way receptor, so subtype of serotonin receptor. Then you have these other classes of compounds that you could call psychedelic. Another big one would be the NMDA antagonist. So this would include ketamine PCP and dexamethorif and something I've done some research with which folks might recognize from like robo-tripping guzzling like you know call syrup which is something kind of like high school kids are known to do and they can't get ahold of real drugs that type of thing. So a large overlap in the types of subjective effects that you get from those compounds compared to the two-way agonist classic psychedelics but then you have and by the way this description this framework I'm describing not everyone will agree. Some people will say no psychedelic only means classic psychedelic. So there's different opinions here, but you have gosh salvin RNA which is a kappa opioid agonist which again where does that come from? Salvia diva norm. It's a plant it became 20 years ago it sort of popped onto the legal high scene and there's a you know long history of this predating the internet going back to like the stuff one could order in the back of high times magazine and and most of this stuff like never worked you know or it's like Smoke enough of anything maybe a little bit lightheaded, but this is one of those things that popped around 20 years ago when it quickly got the reputation like holy shit the stuff actually works and works really strongly in these smoked extracts particularly people have these reality altering experiences on par with smoked DMT the classic psychedelic so often and that we did the first blinded controlled human research with salvin RNA so lots of entity contact so feeling that you in the experience of one is actually interacting with autonomous beings that type of thing and then you have Another big one I probably should have mentioned even before the you know salvin or an a um, but you have mdma which really stands in a class by itself, so it's been called an intactogen and and uh What does that mean? um, it means like uh Touching within it sort of eludes the idea that it can really put someone in touch with their emotions It's also been called an in pathogen and can it can afford empathy? um But I think intactogens probably that's the the term that I I tend to focus on and I know i'm not telling you anything you don't know but the for the for the um viewers that the primary mechanism of mdma is serotonin release and to a degree other mono amine release dopamine serotonin and so Structurally that's also in the phenethyl amine class which contains Mescaline the classic psychedelic, um, but also amphetamine so just you know like at all is is is in that phenethyl amine class and so this is another example where chemistry doesn't dictate I mean you can tweak a molecule it might have that same basic Structure but now you've profoundly changed the way it interacts with the receptors so in mdma does not you know exert its actions by I like to say by by by you know mimicking the baseball entering the glove the post Synaptic receptor side, you know acting as an agonist so mimicking the the the the endogenous neurotransmitter serotonin like the classic psychedelics do mdma works on the picture side of just basically throwing out more of the natural The endogenous dumping more serotonin flooding Yeah, synapse so I get the impression that The psychedelic space is a enormous cloud of partially overlapping compounds Right, um meaning summer impacting the serotonin system more than the dopamine system others are impacting the dopamine system more than the serotonin system Given that the definition of a psychedelic is that it profoundly alters sense of self At least that's included as a partial definition Can we break that down into a couple of subcategories so for instance? Hallucinating either auditory or visual um synesthesia perceptual blending the sense that um, you know you can hear colors Uh and see sounds for instance a common Report of people that take psychedelics Insufficiently high doses so hallucinating synesthesia and then In terms of sense of self, you know as a neuroscientist, I think okay.

Hallucinations, Synesthesia, Altered Space-Time Perception (14:09)

What does it mean to alter a sense of reality? Really what the brain does Uh in a very coarse way Um is to try and figure out what's happening in space physical space And that physical space could be within us or outside of us and what's happening in time? Right and um as a vision scientist the simplest explanation is when I move my hand from one location to another location It's measuring the space the location of my hand in space over time And then you get a rate and a you know speed and all that kind of stuff, right? Yeah That gets more complicated as you get into the emotional um realm But is it fair to say that psychedelics are impacting The space time analysis that the brain is performing and thereby creating hallucinations and thereby altering It's You know the blending of senses is it fair to say that? I think it's it's fair to explore that area and here here's what i'm thinking the the Clearly there is a changed relationship certainly at the right dose of orientation in space time I think as a as a You know, i'm primarily a behaviorist and in terms of pharmacol human behavioral pharmacology I'm I always go to comparative pharmacology. Okay. What can we say that is it truly unique about the classic psychedelic or psychedelics in general? So with that description i'm thinking, okay Alcohol can really screw up your you know time space uh orientation your balance Similar, you know, and in many ways and in those gross motorways like far worse You know, of course everything's dose dependent, but from the classic psychedelics, you know, obviously the benzodiazepines being very similar apple same thing so You know, I'd want to You know dig in a little more in terms of like maybe there's something more specific we could say about that relationship to time and space That the psychedelics are tinkering with but i'm not sure it's an interesting hypothesis The idea that that's a mediator that that's something that there's something fundamental about changing that the representation and time and space um There might be something to that. I mean, I think of these as is psychedelics is profoundly altering models, you know, you know, we're all you know, we're prediction machines and that's large so much of that is is top down and uh and psychedelics have a good way of You know loosely speaking dissolving those Models and and one of the the reality give us an example of one of like a model like like I know that when um I throw a ball in the air it falls down not up That's a that's a prediction that I learned as a child that I did not come into the world with a brain that um knew that relationship between objects and gravity but One of the first things that a child learns is the relationship between Objects and gravity and their trajectories. Yeah, and with a four-year-old. I mean I saw that at earlier ages like that experimentation of like oh, yeah, that's what happens You know, right so if you if he were to throw a ball of your child were to throw a ball and it went up into the sky That would be absolutely Mind-blowing it would be for an adult too. It'd be a pre psychedelic experience probably right and so there's a there's a There's a rule there. You're saying there's a kind of a prediction big there's a rule that that underlies a prediction that when that Rule is violated all of a sudden the circuit presumably for that prediction go like it doesn't have a mind-of-it- zone but somehow it creates a surprise element or a or a Ignition element and it's not filtered out You know uh and this might sound extreme, but there are these cases it was over overblown and sort of the propaganda the late 60s early 70s, but There are credible cases of people. I think it's very atypical of Sounds like they really thought they could fly and You know jump out of a window now far more people every year Fall just I mean who knows, you know, they they they fall and die out of you know from height because they're drunk You know, so this is extremely rare, but you know, there are some like pretty convincing cases there was one research volunteer in our studies that uh She Looked like she was in one of our studies like she was trying to dive through a painting on the wall. She was fine, but she Reviewing the video it looked like She really thought that she was going to go through that painting and Oh, so she was the other dimension. Yeah, so the violating these predictions um Yeah, I the reason I ask it the the question the way I did is because um given the enormous cloud of different substances and given the range of Previous experiences that people show up to a psychedelic experience with Uh, I feel like the ability to extract some universal themes is is useful Especially for people who haven't done them before right who might not have an understanding of what their Effects are like can we just briefly touch on? The serotonin system and the dopamine system I I want to acknowledge it as you already know that there are many neuromodulator systems in the body Oh, and you know, the opioid systems cannabinoid systems but There's something so profound about the serotonin system and the dopamine system because the way I define a neuromodulator is It's a modulator.

Serotonin & Dopamine (19:56)

It changes the way that other circuits behave and essentially it up Increases the probability that certain circuits will be active and decreases the probability that other circuits will be active in in a in a general sense so Compounds like lsd by sertric acid diaphragmide and psilocybin my understanding is that they primarily Target this serotonin system How do they do that at a kind of general level and Why would increasing the activity of a particular serotonin receptor or batch of serotonin receptors lead to these profoundly different experiences that we're calling Model challenges challenging pre-existing models and yeah, I mean at the end of the day It's a chemical and these receptors are scattered around the brain with billions of other receptors. Yeah What do we think is going on in a general sense? Yeah, yeah, and this is really the area of active exploration and we don't have great answers We know a good amount about the receptor level pharmacology some things about Post-receptor signaling pathways in other words just fitting into the receptor Clearly, you know serotonin itself is not psychedelic You know, or else we'd be tripping all of us all the time because when I eat a big low I get serotonin release, right? I mean there's a and a very different than I was thinking right My understanding of serotonin is that in very broad strokes that it it generally leads to a state of being Fairly it pushes the mind and body towards a state of contentment within the immediate Experience whereas the dopamine system really places us into an external view of what's out there in the world and what's possible Yeah, does that mean to do something? I mean that's consistent with my understanding and And I'll certainly not in terms of I don't primarily identify as a Neuroscientist definitely tell the you know the viewers that were far more neuro domain here than mine but in terms of how psychedelics and other drugs You know interface at the at the neuroscience level. Well feel free to explain it at the experiential level Yeah, I mean it doesn't have I think probably there probably are some audience members that are interested in is that the 5h2c? Is it the layer 5 neurons and cortex that conversation we could hold and that's an interesting conversation But just in terms of the experience of Serotoninergic versus dopaminergic drugs. Yeah, they they do seem to create Distinct classes of experience. So I think that's that's the right level for us to discuss them And in terms of how they and I like I'd like to explore the biology a little bit here and tell you like sort of what's known and what's from the ideas are Please um You have this path, you know as you know like you know These are levels of analysis and it's not which one is going on It's almost like for the particular question which level of analysis is most appropriate Is it you know is a question best addressed by the biology the the chemistry or the or the physics? That's how I think of like receptor level post receptor signaling downstream effects and other other neurotransmitters and then um in activation level effects and then um coordination of activation so you got the Clearly the with the classic psychedelics the two-way um activation We we do know that there are downstream effects in terms of uh increasing glutamate transmission So this is likely a commonality why you know ketamine is very psychedelic and slightly different way, but do people hallucinate on ketamine? Yes, yes, and it's more dissociative. So someone is more likely to sort of uh Be less behaviorally active if they have a really high dose they go into a K-hole and if they go in a really high dose like you get Does her call the K-hole conscious?

Ketamine & Glutamate (23:50)

Yeah, not in a hole, but a K-hole. Yeah, and very different um The K hole and ketamine is interesting because people can take kind of bumps and kind of dance on it with the sort of an alcohol level Strength of a effect and that's sort of the classic kind of raving, you know use of it But then those folks want to titrate their dose because uh if they do more of like a line You get up to like 7500 milligrams then you're talking about um, you know If you're on the dance floor, you're on the floor and your friends are trying to make sure people aren't stepping on you So that's like, you know, why do people want to take a dissociative anesthetic? Like to me, it's completely mysterious as to why someone who wanted to associate from their body People claim that these these these these in mda and tag in the psychedelics are extremely insightful You know in a very similar way to the experiences with the classic psychedelic So and ketamine is now legal for therapeutic right right spervato the the the intranasal form um marketed by jansen, which is esketon mean it's perspective. Yeah, it's prescription and um So people are taking in the nasal spray. Yeah, and then are they undergoing talk therapy while they're doing this typically not so it's this is very Interesting and there's so much work that needs to be done Um, it's not treated as psychedelic therapy and by that psychedelic therapy I mean You tell the person they're going to have an altered experience you tell them to pay attention to that experience That they might learn something from that experience and afterwards you discuss that experience With spervato The model is spervato is is esketon mean, okay, it's the the yeah the spray form of ketamine That's it's been FDA approved for treatment resistant depression, but it's you'll you'll probably feel different ignore that That's a side effect. That's an adverse effect Um just ignore it. Um, we don't think that has anything to do with the way it works Um, but just get this thing. It's it's a direct, you know, sort of chemo therapeutic effect in a sense. It's it's not Facilitating a learning process now. There's older work. There was a guy kripitsky in russia that did extensive work with Higher doses of ketamine. I should say spervato at the prescribed doses Isn't very it's a pretty low dose. It's in the mild psychedelic range, but it's not very strong But this older work that happened in the 90s and early 2000s in russia Um, they were using very high doses and treating it like a psychedelic You know treating it as if it was a psychedelic therapy. No, they were telling people you're gonna have this experience It's gonna you know, we're hoping you learn something from it. We're gonna help you through it We're gonna discuss it afterwards and they found incredibly high rates of success and some pretty well controlled Trials for both heroin addiction and alcohol Addiction so I think a whole lot of work needs to be done now And you see some of the ketamine clinics that are using ketamine off label a lot of them are you treating it like psychedelic therapy There's essentially no research at this point on that. Do you get better results? Um Straight abusive spervato. There's some good variability, but it's anti-depressant effects last about a week um, but the kick in immediately Now a week is a long time for like most most psychiatric drugs like you take it every day Right, you know, so that's amazing, but it's still just a week. We're seeing effects You know a year or more later with with with psilocybin and and some of the classic psychedelics That could be a pharmacological difference or it could be that they get a lot more mileage out of ketamine if they treated it Like psychedelic therapy and so that's some so what would that look like? um, really just like our our psilocybin You know sessions, which I know I haven't described but briefly You have anywhere from four to eight hours of preparation getting to know the people who are going to be the guides or the therapists in the room Yeah, maybe you could walk us through this So let's say I were to come to one of your clinical trials because these are clinical trials Right and in your at your lab at Hopkins And uh, would I need to be depressed or could I just be somebody who wanted to explore psychedelics? We've had studies for All of these okay and and a number of other disorders so healthy normal studies the the code for Not a problem to fix but we're all here That's what's amazing about psychedelics though because you if you administer them under this model and you develop a relationship and give a high dose of psychedelic You can be healthy normal without a diagnosable issue, but man We're all human and the issues seem to come to the surface So but we've done work with uh smoking cessation so people trying to quit tobacco and haven't been successful a variety of reasons So, um, maybe I'll just ask some very simple questions that would kind of step us through the process So let's say I were to sign up for one of these trials and and I qualified for one of these trials I'd show up you said I would do several hours in advance of getting to know the team that would That would be present during this psychedelic journey first.

An Example Psychedelic Experiment (28:00)

There's screening So it's kind of like a couple of days of both psychiatric like structured in psychiatric interviews about your whole Your past and symptoms across the the dsm the psychiatric bible to see if you might have Various disorders that that could disqualify you like the main ones being the psychotic disorders Schizophrenia and we're also including Um bipolar so the manic side of bipolar So but so after that's in also cardiovascular screening heart disease after that screening then the preparation where you get you're both You get you develop a therapeutic rapport with the people who are going to be in the room with you Your guides, um, but you're also then Dictically sort of explained about what the psychedelic could be like And that's kind of a laundry list because they're more known by their variability Then you know, it's gonna. It's not like cocaine like you're gonna feel stimulated You're gonna feel like, you know, you can do any it's like, you know or alcohol. You're gonna probably gonna feel more relaxed It's like I call them uppers, downers and all arounders and the psychedelics of all arounders It's like yeah, you could be you could have the most Beautiful experience of your life or the most terrifying experience of your life So it's this kind of laundry list of like the things that could happen. So there's no surprises I think it's so important for people to hear because um the all arounders they the You really can't predict how somebody is going to react internally, right? Um, I want to just briefly touch on something Because we we left that topic, but um It occurred to me that a lot of these effects of psychedelics and how they function, etc is still very mysterious But then I recall to mind that how most prescription antidepressants work is also very mysterious They increase serotonin or dopamine or epinephrine, etc But why they take weeks on and you know several weeks to kick in etc is also mysterious but going back to the the The experience of of coming to your laboratory. Okay, so Let's say that somebody passes all the prerequisites um and The and it's the day. Yeah comes comes the day that they're going to have uh this experience are they uh eating mushrooms like uh you hear about or are they taking it in capsule form and how What sorts of doses are you prescribing? Is there a dose response curve? Um, and then Secondary to that I'd like to talk about micro dose versus macro dose So how do they get the stuff into how do people Receive it and how do they get it into their body? So they receive pure psilocybin So the mushroom and there are many species the most private people have taken mushrooms in the united states It's it's most likely psilosob cubensis. They're easy to grow. They grow in calpadis It's easy for any Body to grow them in their closet. It doesn't take a thousand watt light like cannabis It takes like a little You know 10 watt light bulb and a tupperware bin. So those are what those are the types of mushrooms that people typically tape We're not administering those psilocybin is the compound you could draw a molecule psilocybin again based on the trip to mean structure Like that's a single molecular entity. So it's a white powder does it look like serotonin molecularly? Yes. Yes. Yes So if I looked at my where to show people the chemical structure of serotonin the chemical structure of psilocybin it would look quite similar Right, right and they're basically taking serotonin It a modified version of serotonin which makes sense, but then Again, this repeated theme of the chemistry doesn't always neatly line up because like meskaline looks more Uh like dopamine than it does like serotonin, but yet it At the receptor activation level the pharmacological neurological effect It's those are similar, but but yeah, I mean and what it does at the receptor is an alternate It's it's it's hitting the same switch, but then having an alternate response at the receptor Um, yeah So for people that don't necessarily understand the relationship between what we call ligand the thing that parks in the receptor and the receptor is the parking spot One of the reasons that you can get such a variety of effects from different compounds is for instance serotonin might affect a certain pathway at a particular rate and psilocybin might trigger activation of different components of that pathway at different rates since you can get vastly different Experiences from two things that look chemically similar. This is also a good uh reason why people shouldn't just assume that they can cowboy their own chemistry Right that what you see on paper and what you can mix up in a while is often vastly different Uh, then what you predict, right? And there's a dose effect curve that's really interesting some of our early work with psilocybin, um in healthy normals Um looked at a true placebo plus four active doses five 10 20 and 30 milligrams of psilocybin Body weight adjusted so you know those milligrams per 70 kilograms of body weight We've recently published a paper in our newer trials. We're we're dropping the body weight adjustment because our Going across hundreds of volunteers. We've kind of figured out that That you shouldn't really be you don't need to be adjusting by body weight. So so yeah, well brain size doesn't vary that much Individuals, yeah, yeah, you know, the end. This is a brain effect Mostly probably body as well. Um, okay. So the person in just the the powder or a capsule Okay. Yeah, and it doesn't take 30 milligrams as a small Fitted into a tiny little capsule and it'll take about a half hour But mean we're from 15 minutes to an hour to kick in and average Range was um Most of our studies are looking at where we we want a psychedelic effect are in the 20 to 30 milligram Range Um, again because we have adjusted by body weight and the average american is over 70 kilograms about 150 pounds Like people and in fact have gotten more like, you know 40 45 in a lot of cases, but um, it's still a small pill um there The session day itself is not full of For most of our studies is not full of tasks. We really want to look at the therapeutic Response obviously if it's a therapeutic study. We want it to be a meaningful experience and Research has found not surprisingly that you get a less meaningful experience when you're in an fMRI Or when you're doing a lot of cognitive tasks, um We've done some research on on You know a that type for sure and plenty of colleagues have But when you're in a therapeutic study or if you're trying to understand the therapeutic effects you have to recognize There is this this this trade-off of what you can do So our typical therapeutic model which again isn't just limited Necessarily to the therapeutic studies where we're trying to treat a specific disorder Um, it is is to you know have that preparation so you're the person feels very comfortable with their guides um Uh, I mean ultimately what I tell people is like Any emotional response, it's all welcome. I mean You could you could be crying like a baby hysterically like that's what you should be doing If that's what you feel like and so in a lot of ways sometimes people with psychedelic experience uh on their own It can be harder to train them in this model because in the real world people with psychedelic experience a lot of times the rule is You know hold your shit. So a You know several friends go to the party. They split a bag of mushrooms. It's like You know, there's a social pressure for good reason not to be the guy You know in the corner of the room where everyone's trying to just have a good time Relax like crying about your mother your other friends are they're having an experience too And you're being a drama king and blah blah blah and so like yeah compose yourself hold your You're doing I mean you're doing therapy for people. This is it's not just about the experience Right and the experience itself is very much shaped by By that that container by the environment and it's agreed to which one allows it to happen like One should let go of control. Yeah, let's talk about the the letting go of control and then as we march through this hypothetical experience that does take place in your lab, but so we're using a sort of generic case example if you will Um, the letting go of control is an interesting feature actually because uh one of the common themes of of good psychoanalysis Or psychotherapy of any kind is that there's a trust built between the patient and the analyst And that relationship becomes a template for trust more generally and trust in oneself It's actually the the end goal of good psychoanalysis is that the patient actually one of the end goals is that they develop an empathy for themselves Which almost sounds like an oxymoron, but if you spend a little time with that statement, it actually pans out so The psychedelic experience is one in which chemically you're under A new new set of conditions, right?

Letting Go’ with Psychedelics (37:30)

Yeah, let's coarsely space and timer are altered in some way a sense of self For instance, I might be going to a strongly interreceptive mode where i'm focusing on everything within the confines of my skin Whereas normally we're sort of interacting in space and pens and conversation and i'm sorry if I had occasionally i'll pay attention my breathing But i'm sort of dilating and contracting my focus for different things all the time The letting go of control It seems to me could be sort of the expansion of one perceptual bubble to the point where You're not actually worried that that perceptual bubble is going to pop or that meaning you're not worried about what people think of you Yeah, you're not worried whether or not your brain is going to explode even though a thought could feel enormous If i keep going like this it almost sounds psychedelic, but that's the idea here Or if i'm paying attention for instance to some somatic experience like The the coursing of waves of heat through my body that i'm not suddenly saying You know is that weird i'm actually just going deeper and deeper into it so it's essentially expanding our perceptual phenomena How do you convince people to go further and further down that path? What do you think allows them to do that because i think that that to me is one of the more unusual uh aspects to psychedelics is that normally the the social pressure but also just our internal pressure from our own brain is Pay attention to many things at once not just one Is that especially these days? Yeah, multi task Yeah multi task and the more that we focus on one thing the more bizarre that thing actually can appear to us Right, right? I mean even if it's the tip of your finger and you're not taking any psychedelic you spend a long enough looking at the tip of your finger You will notice very weird things right that i think of that as the classic psychedelic effect or one classic effect and one of you's many times of This example of why people should necessarily you know, uh, these aren't These one should be judicious in putting themselves in these circumstances someone could be you know Having a very strong psilocybin experience and they're trying to navigate their way in manhattan Cross in the street and they might be staring into the hand and realize like that's Their hand is the most amazing miracle like the entire universe has Essentially conspired to come to this one point to make this absolutely breathtaking It's almost like I think of the simplest form of of of well We know the simplest form of learning is habituation simply keep applying stimuli and there's less response like This is what organisms do this is what we have to do and it's like there's this habituation component that like this habituation yes like we wouldn't be able to get through life if we wouldn't be able to cross that street if we were like Whole like this is a miracle like so can you know? I'm so glad you brought this up I mean here i'm reflecting my biases of vision scientists But most people don't realize this but if you look at something long enough it eventually disappears To it doesn't actually disappear, but perceptually it disappears You have these little microscotts that ensure that it doesn't right but most of us don't look at any one thing for very long right the the brain's default is to perceptually jump around like crazy with the visual system with the auditory system we all ADD that people talk about ADD a lot is sort of baked into our underlying networks at some level And then we act we can force attention But it sounds like on psychedelics the one of the primary goals therapeutically is to really drill into one of these perceptual bubbles And expand that bubble and the safety it seems is the safety It's sort of like a permission to to do that without worrying that Something's gonna happen right because you know i've had people there on the couch um Yeah, I remember when lady said this is Probably uh 13 14 years ago said matt tell me again. I can't die like I feel like my heart is going to rip Through my chest. I mean she was feeling our name and I should say typically cardiovascular response is is modest the Pulse and blood pressure go up somewhat it can be dangerous for people if they're at severe heart risk and we do monitoring this We do you know we do their mind. We do a variety of devices. Yeah, so every half hour or so we we take they're on protocol and we You know space it out a little further further into the time course, but we take their blood pressure And they're pulse and if it goes over a certain level we have a protocol and we've had to do this only a few times But the physician comes in gives them a little nitric glycerin under the tongue And uh, you know knocks the blood pressure down a little bit doesn't affect the experience So we have it all in place even though they'd probably be found out of an abundance of caution Um, but but yeah, but someone can feel That I got i'm gonna die like I I have never felt my heart Beat like this before and like the experience of the breath can be just you know Absolutely fantastic and this sort of the breath is obviously interesting because it's this auto automatic You know control, but it could also be voluntary so people can get into a sense of like, oh, what if I It sounds silly like what if I forget to breathe exactly. Yeah, but people That can be so compelling And so one other reason get back to one of your questions It's like what do we do to kind of allow them to go further into these bubbles It's like one is is wearing the eye shades We don't call them blindfolds because that has a negative connotation like people can help and they're probably seeing a lot in there Anyway, so blind isn't the appropriate right right that's I've never thought of it These should be like inner sight shades Uh, but when you close the eyes the levels of activity and the retina actually are maintained It's sponta is just spontaneous activity and it seems and I'd be curious about your thoughts on this. I mean But the way I describe it is that the You know the mind's eye you know this kind of loose term we use can be on rocket boosters So a lot of times for some people like a compound like psilocybin for some people there's no Perceptual effect like if they're looking at this room, it would pretty pretty much look the same Sometimes folks like yeah things seem a little bit brighter now some people will say oh my god There's waves that wall is waving and these curtains that you know On these compounds people don't typically see pink elephants you do actually get that in another class I didn't mention the the anti-colonergics Sort of like atropenants capola mean those drugs those are those are the true hallucinations where you thought you were having a conversation Was someone who was never there?

Our Mind’s Eye (44:10)

That um We will definitely get to those but when the reason I kind of cringe and say oh my when you talked about those is that um knowing a little bit about the pharmacology of acetylcholine the The idea of manipulating that system to me sounds very uncomfortable Because uh like the whole idea of what witches and flying there was a whole history there You know hundreds of years ago so-called witches taking these agents and then Thinking they were flying around on broomsticks and things of that sort and and there's a lot of mythology around the broomsticks It's complicated, but but that sounds very unpleasant one thing I about the the serotonergic. Let's just for with psilocybin um So there's a person an expansion of a particular fairly narrow Percept it could be sound could be an emotion could be sadness could be uh historical event or a fear of the future And you've mentioned before that There's something to be learned in that experience. Yeah, there's something about going into that experience in it in an un um in an Undeterred way That allows somebody to bring something back into more standard reality. Yeah Given the huge variety of experiences that people have on psychedelics given the huge variety of humans that are out there But what are now very clear therapeutic effects in the realm of depression What do you think is the value of going into this? Fairly restricted perceptual bubble what we are calling letting go or giving up control because if the experiences are many but the Value of what one exports from that experience is kind of similar across individuals That raises all sorts of interesting questions and this is not a philosophy discussion. We're talking about biology and psychology here. Yeah, so Let's say I decide i'm going to focus on the tip of my pen. I mean in a psychedelic state I could fall in love with this pen. I do have an alike these pilot v5s and v7s very much But I could feel real love. Yeah for the pen Yeah, right. That's not an unreasonable thing to expect on a psychic in a psychedelic journey Right and in the context of your laboratory model, which I think is a great one That experience would be just as valid as me going into the experience of Some of the deep friction that I might have with a family member over my entire lifespan Yeah, and yet the export from that those two vastly different experiences Is one of feeling a better relationship to the world and oneself, right? So what is this telling how can the pen and the processing your childhood trauma both lead to right? Yeah, so what is this? I mean at that level it raises this question like First of all how why I mean or just what are your thoughts on that? So this is definitely in the This is in the terrain.

Redefining Your Sense of Self (48:00)

We're figuring out, you know, so there's no the educated speculations the best I can provide but I I think the best the the the the most I think the common denominator Are persisting changes in self representation. Okay. Tell me more about self representation. That's The way one holds the sense of self the relate the fundamental relationship of a person in the world I mentioned earlier that These experiences seems to alter the models we hold a reality and I think that the self is the biggest model that I am a thing that's separate from other things and that's I am defined by certain I have a certain personality and I I'm a smoker that's having a hard time quitting or I'm a depressed person that You know, these myself as a failure and all of these things those are models too and and I think I think that change in self representation may be an endpoint for these different experiences I mean, maybe the falling in love with the pen the whole idea that you're especially in contemplation afterwards and obviously I'm speculating here, but the whole idea that you could Have such a deep connection with this random obviously random aspect of the universe Could potentially lead to this you know transformed understanding of the self and like the pen may be a proxy for the The miracle of reality in a way that relies nothing on No supernatural thinking, you know, you can be a hard atheist and take this Ultimately, oh my god like that just like the pen This is you know, this is amazing the fact that we exist and so there could be an extrapolation chair And you use the pen, but I think it sounds so similar to all this Huxley's classic description and the doors of perception of the chair and the drapes like he took 500 milligrams of Mesclin. He was just like that a high dose of Mesclin. Yeah. Yeah, and that's uh, and you know, that's a heroic Dokes for sure and he's just going off on the chairiness of the chair like this chair is exuding the quality of being a chair And this is this expansion of the perceptual bubble a narrow a narrow Percept that then grows within the confines of that narrow percept The yeah, so sense of self is a very interesting Phenomenon and if we could dissect it a little bit Um, there's the somatic sense of self so the ability to literally feel the self Uh into this process we call interoception and then there's the the title of the self the I am blank Yeah, and I noticed you said that several times and it's intriguing to me have a good friend I don't think I can or should mention his name, but he had a very long and successful career um Within one of the more elite teams and within the seal teams and he um, he's a fairly philosophical guy Um, also very practical guy, but he has said many times Um to me that the most powerful words in any language are I am because whatever follows that Tense if you repeat it enough tends to have this uh kind of feedback effect on the on how you are in the world And it the first pass it it all it sounded to me a little bit like, you know Kind of like internet psychology type thing like the secret or something you say which frankly I'm just not I'm yeah, you know, so if you you kind of like the whole fake it till you make it like I don't actually subscribe to any of that But in dissecting that a little bit further with him. I came to realize that um that these words I am are very powerful. I don't think you reprogram your brain just by saying them, but how one defines themselves Internally not just to other people but how it won psychologically and by default in Defines themselves. I think is very powerful like um and depressed people As well as happy people seem to define themselves in terms of these categories of emotional states so I think it's it's so interesting that letting go and going into this perceptual bubble which is Facilitated by obviously a really wonderful team of of therapists, but also the serotonergic agent. Yeah allows us to um potentially reshape the perception of self. That's that's a tremendous feat of neuroplasticity, right? And I think Certainly more work needs to be done. You know, this is the the the horizon and I and I should credit uh chris let-a-b-a philosopher um in australia who um has a forthcoming book it might be out right about now or or soon within the coming months uh psychedelics and philosophy Um that's the title of the book. It's it might be psychedelic philosophy. It's really close Chris lather vie and we'll put a link to it right and and so his conclusion in this it's a really great book and he really Plays with the idea. It's like psychedelic experiences come along with a lot of supernatural stuff uh experience it can certainly go along with that but the idea is like can it can these experiences and including the therapeutic effects be explained from a naturalist point of view and and his conclusion is that that changes in self representation may be the commonality now that could go along with plant spirits and the buddha and chakras and whatever your model, you know system in jesus All of that but it could also uh be completely devoid of any supernatural and your religious um and we do in fact see all you know all of these varieties so I think there's something about this change in In sense of self there is it seems to be something on the identity level both with I think of the the work We did with cancer patients who had substantial depression and anxiety because of their cancer and also our work with people trying to quit cigarette smoking. I mean there's this Real there seems to be when it really works this change in how people view themselves like with smoking like Really stepping out of this model like I'm a smoker. It's tough to quit smoking cigarettes I can't do it. I failed a bunch of times I remember one participant during the session, but he held onto this afterwards said my god. It's like I can really just decide Like flicking off a bike. I can decide not to smoke and it's I call these duh experiences with psychedelics because people often Like in the cancer say you say I'm causing most of my own suffering like I can I can follow my appointments. I can do everything but I can still plan for the I'm not getting outside You know in the sunshine. I'm not playing with my grandkids I'm choosing to do that and it's like they told themselves that before and the smoker has told themselves a million times I can and so it sounds when it comes out of their mouths Any folks will say this is part of the ineffability of a psychedelic experience folks like I know this sounds like bullshit And this sounds like but my god. I could just side like they're feeling this gravity of agency and which I think is interesting because Regardless of the the the debates on the reality of free will I think The philosophy of that whether it's ultimately free free will like pure agency if that exists which I'm skeptical of or Just the idea that clearly we have a sense of agency There's something there whether it's the sense of agency even that is the human being has and That seems to be at times fundamentally like supercharged from a psychedelic experience this idea like I'm just going to make a decision Like normally like you tell a depressed person like don't don't think of yourself that way. You're not a failure. You're like it It's just yeah, it's like and well you can actually in one of these states have an experience We realize like my god just like using mdm a to treat ptsd and we're gonna be starting work with psilocybin to treat ptsd Someone could really reprocess their trauma In a way that like has lasting effects and clearly there's probably something you know Reconsolidation of those memories here. They are They are altered, you know very consistent with what our understanding of the way memory works So the whole idea of people can actually in in a few hours have such a profound experience that they They decide to make these changes and who they are and it sticks There seems to be something like that and that's profound. I mean I I think A few moments ago. I was I made some semi disparaging statements about things like the secret and affirmations and and the reason I I do that with with a with a nod to the fact that the people who are putting those ideas forward are well intention people is that the neural networks of the brain Put language last We we tell stories, you know and stories are very powerful, but I think one of the most cruel aspects of the whole self-help Literature and popular psychology is this idea that everything you say your brain and body hear it That's actually a very unkind or even cruel thing for people who are depressed or anxious to hear Because if they hear that and believe that and I want to be clear. I don't think it's true That they think that it's very hard to control thoughts Is it very hard to control thoughts? So somebody Um says, you know, I can't and then somebody says well now every time you say you can't your brain hears that and it reinforces it That's a very treacherous place to live. Um and Language is powerful, but neural networks the brain And the networks that underlie emotionality and perception and sense of self They don't change in response to language. They change in response to experience Yeah, and it just fundamentally you need there's some prerequisite You need certain neuromodulators present like serotonin or dopamine you need them to be at sufficient levels You don't need to drug necessarily do it. You could uh, you know, you give a kid a kitten or a puppy their first kid in our puppy and the levels of dopamine and serotonin I've never measured them, but we can be pretty sure that they are higher than baseline Uh-huh and that experience will reshape them right? Yeah, likewise with an adult in a certain certain instances. So I think I'm fascinated by this idea that a A somatic and a perceptual experience but a real experience of the sort that you're describing Is what allows us to reshape our neural circuitry and to feel differently about ourselves and uh, I know there's been um Really tremendous success in many individuals of alleviating depression Treating trauma with these different compounds. I wanted step from the The experience under the effects of the psychedelic so the person there with your team they go into this Expanded perceptual bubble if if things go well, they're able to do that to a really deep degree Maybe it's the the relive trauma.

Exporting Psychedelic Learnings to Daily Life (58:56)

Maybe it's the beauty of the their ability to connect to things in the world Now I want to talk about the transition out of that state And then the export into life because this is really where the power of psychedelic seems to be in the therapeutic sense Is the ability to learn truly learn from that experience so that the learning becomes the default that one doesn't have to remind themselves Oh, I am you know, they don't have to do an affirmation. I am a happy person I am a have you know, I was in a Bart Simpson like writing on the chalkboard Right didn't work for him doesn't work for this other stuff too, but So as they transition out of this state, I know that there's a kind of a heightened There's a so-called peak where everything seems to be kind of cascading in at such a level that um the person Just they can't really turn it off at that point. It would be challenging um and then they start to exit the effects of the drug Are those transition zones? Are those valuable much like is the transition between a dream and the waking state valuable because you're in a sort of mishmash of altered reality and new reality, right? What do you what do you do to guide people through the um Out out the tunnel as they exit the tunnel and I had to say like this is where we need more experimentation um, really the clinical model goes back to literally the night late 1950s And there's been virtually no experimentation on let's say, you know, randomize people to We're going to talk more during the latter half of the of the session versus not versus we have them You know, write an essay after their session versus not versus we have this amount of integration What's the discussion in your studies? Are they are they writing or talking as they're doing it? And it's called, you know, very loosey goosey, you know term integration, but for us means um As they're coming back from the experience to sort of five six hours in, you know, so this is the afternoon They've been dosed around nine o'clock. So this is like four o'clock or so Just some initial tell us about the experience do you want to not unpacking it totally? But kind of initially just have a little bit discussion before they go home So there's a little bit of that but then that night their homework is to write Something so it could be, you know a few bullet points. It could be You know 20 pages and we we get everything, you know in that range Um, but you know try not to be self-critical. It's not great It like just is just to process and for a point of discussion the next day So they write something they come in the next day For a one to two hour depending on the study integration session basically just let's discuss your Experience and depending on what study it's in like what you know, what might that mean? for You're dealing with cancer. What might that mean for your smoking? Um, you know or becoming an on Smoker so you encourage them to simply take it seriously and I think this is again a sort of One of the points that could be the antithesis of what some just kind of social users Um use. I mean this was written about by um houston Smith the scholar of religion in terms of these mystical experiences that can happen from psychedelics and how a lot of times The attribution to a drug effect is dismissed like the net even if one has this You know This sense of being one with the universe and it totally like shakes their soul so to speak You know, but the next day their friends like, uh dude you were screwed up too much acid for you Whoo, you know like man next time you needed to have a few more beers to like bring that down, you know, like this sort of like You know social You know reinforcement for dismissing the experience. Oh god. You're talking out of your head man like You know, even if it's you know good natured, but it's this dismissal. It's not like You know what you want to do, you know is like tell me more about that, you know You were crying at one point like in talking about your mom Let's talk about that. What was that like? Do you remember that like Are you doing that follow up or are you there encouraged to do that in their own life with the various people in their life? Both so we do that explicitly in the follow up where we have these discussions and I depending on What the situation is um, you might Encourage the person to kind of follow up. It's it's really the the basics of it is is supportive Therapy it's non-structured. It's you know use all that you know reflective listening and The sort of the humanistic psychology that you know unconditional positive regard for the person but but you know, I think if You know if someone feels inclined to you know apologize to their to their you know to their sibling about something it's like yeah, go ahead and call them up when it with something big like a relationship change i'll be like Sit on that two weeks don't make any big don't end any relationship. Don't quit your job. Don't make any big Do you also tell them not to start any relationships? I don't remember that ever coming up. What's your statement? I'm not joe. I was just wondering you know, it's but yeah makes sense why you like if they're dating and they're thinking like Ah, I might be time to take it to the next no. Oh, should I ask this girl to marry me if it did come up? I would say there too. Um, might you sit on that a week or two? Don't get a puppy. Don't don't get a puppy. Certainly don't get four puppies until you're I have a question about um flashbacks uh-huh, you know one of one of the Kind of uh things you hear is you know flashbacks and that that people do people get flashbacks and if so, what is the basis of flashbacks the um The on the street A lore about this is that somehow some of the compound gets stored in body fat tissues and then released later like a Is that complete nonsense? No evidence for that so probably complete nonsense Flashbacks are nonsense or the storage and body fat is complete The storage and body fat so to answer whether flashbacks are complete nonsense We have to define it.

Flashbacks (01:04:36)

So I really think these are multiple constructs that are going It's not the same thing that fall under that term There is a phenomenon that that appears real that's called hallucinogen persisting perceptual disorder. It's in the dsm A certain number of people very small number of people Of you know percentage wise who have used psychedelics will have these persisting perceptual disorders Like they'll see halos around things. They'll see some trails like, you know, like the after images following an object in motion um They'll see distortions in color and it'll be like anything else. That's a Disorder in the dsm. It has to be clinically distressing and it has to be persisting over some uh number of of months and And so very rare very mysterious some of the keys to that are Amazingly, it's never been seen in the thousands of participants either from the older era from the late 50s to the early 70s People in psychedelics days with LSD, psilocybin, masculine and it's never been seen in the modern era again now with Thousands of participants at a number of centers like ours, um throughout the world So it seems to be something that is For some reason happening in illicit use So that that brings in okay is the Polypharmacology, you know, like as you're drinking during any time. Did you take what you thought you did? What's the dose is what's the purity? But then also what I think is actually even more so than now what's likely going on is some sort of very rare neurological susceptibility There is one paper that um Is a case series of individuals reporting these symptoms and they didn't limit it to the to just people would have um hallucinogen history and the amazing thing about this is that a number of people Seem to have straight up hppd Diagnosis, hpp hallucinogen persisting perceptual disorder who have never taken a psychedelic. So it's often prompted by um alcohol benzodiazepines cannabis um even tobacco And and I believe in one individual No lifetime history of any it wasn't preceded by any of those uh, you know substance use is so I think it's I think of it like the precipitation exacerbation of psychotic disorders We it seems pretty clear through observation that some people with With either a predisposition or active psychotic disease that this can destabilize them Uh, the cycle like the same way that a life experience can destabilize those person more easily I think of it like that there's probably some pretty rare neurological susceptibility We have tended going this goes back to the 80s You know clinical practice it ended up in the dsm focused on hallucinogen because I I related to the the psychology of xenophobia It's always the weird other thing that gets the attribution you don't attribute to the thing like oh, yeah Did you smoke cigarettes? Did you drink? It's like well? Yeah, but I see lots of people drinking and not ending up with this like you take A crazy like drug and you can get people to believe all sorts of crazy stuff The biggest example of that is the the the cathanone derivatives so called bath salts And if you remember several years back. Yeah, what was your deal with florida? That that ate the other guys face. There is a homeless guy that like literally ate part of someone's face off like yeah While the crazy is a lot while the person was alive and all it took was one sheriff stepadee to say Well, I don't know but I bet it was some of that bath salts stuff that's been going on the only thing What was it was the only thing in his system? Maybe we can set the record straight for people. What what was this? Why would he say bath salts? And was it bath salts? It wasn't and and so the only thing in his talks was cannabis, which We all know Typically people don't eat people's faces off after they get stuck to hunger. Yeah, right? Right, so it's just an example of the xenophobia like today if you get on google images and look up, you know bath salts one of the most common Images you'll see is this poor guy's face being eaten off So we're just so ready to latch on just like the people of another culture that we don't know of it's it's very easy to assign attribution to a class that you're very unfamiliar with so I think they the psychedelics got that attribution with this very rare neurological Susceptibility the way that alcohol didn't so I think it's not specific to psychedelics But we don't really know we need but we look at it and our research have never seen an example of it But flashbacks can mean a number of other things I think the most common thing people experience is What we call state dependent learning? It's it's it's it's returning yourself to a similar context can bring back the same thoughts and emotions as the experience so, you know, someone used to be a mushrooms a week ago now they do something like they smoke some cannabis or they Or they take a warm bath Um or they're simply like relaxed it seems to come out of the blue and all of a sudden these Or where they follow a thought trail that takes them that reminds them in there and and they find themselves in that same experience again I think that's more state dependent learning. It's not the distressing component that is And it's typically not perceptual and then another class are just sort of um Perceptual anomalies within a day or two following the experience which is not hp Pd most people have You know joke that this is a free trip like you might see a few trails or halo's the day afterwards It doesn't last longer than that And it's doesn't screw you up. It's kind of fun like oh yeah, I'm still seeing some trip most people will say So it could mean any of those things so flashback is yeah, interesting. No, I appreciate you you clarifying that. I mean One very common misconception about neuroplasticity is that it's an event and it's not an event. It's a process and we have No understanding of the duration of that process however The experience of any drug or any life experience Right, even if trauma or a wonderful experience or it's a psychedelic experience doesn't matter sets in Motion a series of dominoes that fall and it's the following of those dominoes that we call neuroplasticity I mean that the reshaping of neural circuits could take years We don't know it's the the trigger and then there's the actual change And so I think that some of what you describe could be literally the reordering of circuitry that in some individuals might extend longer than others um and There is one phenomenon that uh, I've been told People experience and I'm wondering whether not any of the patients you've worked with or um people in your trials have reported this um, I've never done ayahuasca Which I'm assuming has some overlap with the serotonin system probably hits a variety So it's dm t yeah, that's right. That's right. M. A. Oh, of course Allow the dt to be orally right.

Ayahuasca, & ASMR, Kundalini Breathing (01:12:10)

I should have I should have um, recall that absolutely Well, I've never done it, but a number of people I know that have done ayahuasca Um as well as people I know who have done mdma A report an increased sense of what uh, sometimes called asmr These autonomic sense re meridian reflexes, which is and it's interesting a lot of people Um have these naturally and they hide These these are it's actually uh something that many people keep hidden to themselves um I'll just ask you if you can do it. So um some people are able to pass a like a shiver down their spine or up their spine Consciously, you know, like you can kind of like i'm able to actually pass a shiver up my spine I actually learned how to do this when I was a kid on a hot day I was standing on a field in sports camp. I was like, it's really hot here and I could actually create like a cooling Percept cooled perception some people I've told someone this once and then it this led to a discussion of oh I can do it, but I always hid that from people because it's actually somewhat pleasurable And this is a well-known phenomenon asmr And some people I know who have taken mdma therapeutically or ayahuasca Um will report that they um feel great relief from this they can generate these autonomic reflexes through their body more readily Probably i'm guessing because they were able to tune into a kind of deeper sense of somatic self Now on the internet asmr if you look it up It's a little bit like the basalt thing, but in the other direction like there were people that pay uh Let me let's just say there are accounts on youtube that have many many millions of viewers of um People that will whisper to them about like for instance, there's a people that will go listen to Uh, it seems to be women in particular whispering about like car mechanics or something or about or scratching So there certain sounds will do this whispering tapping finger tapping and people experience immense pleasure from it It's not really sexual pleasure, but it's this kind of deep core of the body that it's the autonomic nervous system down the crowd Probably what a certain number of people would call kundalini, which is another one scientifically, yeah, that's right people who do long duration kundalini breathing sessions Many of them will report later feeling as if they their perception of self is outside of their head That they're right that they're literally walk It's very uncomfortable for them that they feel like they're walking around with their sense of self Extended beyond the body and this is a neural this is a clinically described neurologic phenomenon Have any studies been done? I would imagine that person might actually like Would they duck? Oh, what is there like that would be an interesting that would be my lab would want to get into that's right body could clear But their projection wouldn't yeah the sense of self. I mean there's a there's a well-known phenomenon It's very uh in a few individuals very sad where people actually Avidly seek out imputation of their limbs because their limbs they feel don't belong to their body Oh, yeah, this is very sad and uh fortunately very rare, but also very sad condition Anyway, I think that the the the core of this conversation that we're drilling into is this notion of Reordering the self and it's and it's a relief to me to know that flashbacks are not something that is it kind of Forgive the term baked in to the to the psychedelic experience And I suppose that's a good segue to ask about other sorts of drugs Having said baked in the temptation is to go to marijuana or cannabis But but if we if we could I'd like to just ask about some of the more dopaminergic compounds in particular mdma Yeah My understanding is that mdma is a purely synthetic compound that you're not going to find mdma in nature So far So far dmt was first synthesized in the lab and then we thought it didn't exist in nature and then like uh, richard shulties

MDMA, DMT (01:15:54)

Founded it like everywhere So who knows a plan out there might be making mdma, but right as far as we know now know right and we'll talk about dmt and its sources within the body, but mdma um Could exist in elsewhere, uh, but has been synthesized and my understanding is that mdma leads to very robust increases in both dopamine and serotonin simultaneously which From a from a neural networks perspective is a very unusual situation Right normally because dopamine puts us in this xteroceptive looking outside ourselves seeking things in the world beyond the skin our own skin And dopamine excuse me serotonin tends to focus us inward. Those are almost mutually exclusive kind of neurochemical states Although they're always at different levels. So why would it be that having this Increased dopamine an increase serotonin would provide an experience That is beneficial and how do you to the extent that you can describe it? How do you think that experience differs from the sorts of experiences that people have on psilocybin or more serotonergic agents? Just broadly speaking. Yeah. Yeah in terms of that that balance in terms of the the effects generally on serotonin and dopamine Um, I can only you know speculate, you know, like sort of is that dopaminergic component Necessary for let's say we know that the amygdala is less reactive during you know under acute effects and that may play a role in uh, there's less sort of uh Control from from the amygdala in terms of like one's experience of memory. So it may be part of this sort of reprocessing Um, this re-consolidation of these memories in a different way where the amygdala is not like going crazy saying freak out like, you know Bider flight. Well, and I should have said it seems like MDMA is being used clinically anyway mainly for trauma Not just for depression Although part of that we really don't know Um, and maybe that MDMA is great for depression and some of these other and it may be that and i'm going to be looking at this soon That psilocybin is great for treating ptsd a lot of underground therapists Um, say that underground psychedelic therapist. So we don't really know We might underground. Oh because they're doing illegal, you know, but more like, you know a professional therapist would it just illegal Um, and this is a kind of a growing um thing. Um, so we don't really know which it It Speculating but it may be that MDMA for a broader number of people Is better for for trauma because the chances of having an extremely challenging experience what I call the bad trip Like really freaking out Is much lower with MDMA people can have bad trips, but they're of a different nature It's not it's not sort of like freaking out because all of reality is sort of shattering and it's less of this It can take so many forms with the classic psychedelics, but like Typically you'll hear something like I didn't know what was going to be like this no matter how hard you tried to prepare them that like This is like get me off this you're trying to LSD or so Siles have an eye watch. Yeah. Yeah, and just this sense of like I'm going insane This is so far beyond anything. I've ever experienced and it's scaring the shit out of me I can't have a toe hold on anything Even that I exist as as as as an entity and that can be really I think frankly Experientially, that's kind of the gateway to both the transcendental mystical experiences that the sense Of unity with all things which we know our data suggests is related To long-term positive outcomes wait. I want to make sure I understand so you're saying the bad trip can be related to the transcendental experience Right. I think those are both speculating, but you you have to pass through this sort of like You know reality shattering including your sense of self and one can handle that in one of two ways You can either completely surrender to it or you can try to hang on and if you try to hang on It's going to be more like a bad trip. So again, I wish there was more and hopefully there will be more experimentation There's a lot going on here in the black box in terms of the operant Behavior of how you are You know within yourself Choosing to handle like letting go, you know and eventually we'll be able to see this in real time with brain imaging Ah there they are surrendering to the psychedelic experience Here they are trying to hold on, but we're not there yet But I think it's a good clinical observation seems pretty clear That's something like that is going on and certain drugs like dmt smoke dmt can be so strong the reason I think that can be so Extraordinary you can compare to the others because it like forces people like there is no choice I never done it. I was told that dmt is like a high speed locomotive into the psychedelic experience and out of the psychedelic Yeah, and there's no ability to hold on to the self While you're in the the kind of peak phase is that correct a lot of people say that but Terrence mckenna who is kind of the classic bard on dmt effects. He would say the sense of self Was intact, but everything else the sensorium and what you navigated which you Oriented towards everything else changed basically, but it's hard to when everything's changing hard to say like what is the self that's changing? What is the rest of the world? Well in language is is totally deficient to describe experience anyway? Much less on a psychedelic What is mckenna's background like what is this qualification for being this? as you referred this bard of dmt so and we're talking about Terrence and there's also the brother Dennis who I know who's who's Can only imagine what yes their brother is like a parents passed away years a couple decades ago now But um, he's served the one who's known as being a bard and you can find hundreds if not thousands of hours of him On the lecture circuit in the 80s and 90s on youtube, but his background was really oh gosh I don't recall what his college degree was in but he basically um when he was like 19 he traveled to south america and um and actually on the initial trip with his his brother who was even younger than him with some other friends and just um In search for in dmt snuff that they had read about from in the harvard archives from the work of shulties um from a generation before but they had um discovered all of these mushrooms growing That down there the psilocybin mushrooms what they recognize and just took a lot of mushrooms and and um And talked about it talked about and terence was basically a very intelligent very well read um and in literature and culture Person that could be he was sort of the the next generations Tim leery someone who could really speak Get a little closer to the magnitude of what the psychedelic experience was like for people and he serves Like leery somewhat of a of an advocate. I mean he would tell tell people Folks you could see you know the equivalent of a ufo landing on on the white house lawn like it's right there It'll take five minutes. It'll shake everything in your reality You know he would sort of go people into doing it Well, certainly science and clinical medicine is are just but two lenses with which to explore These things in life, but what part of the reason I ask is I feel like um You know in the world of health and fitness Uh, you have this very extreme condition of like Arnold shorts and eggers and bodybuilders who have like 2 percent body Fenn they look like to most people they look kind of freakish. Yeah, especially now, right? Oh, especially now Especially now. Yeah, and yeah made Arnold look like yeah regular Exactly back in his day. Yeah, and you have contortionists who can put themselves into a small box and wrap themselves into a pretzel But from those two very extreme subculture practices um that I don't know anything about contortionism really but except that they get really bendy that but It's a community that included a lifestyle practices and nutritional practices and drug practices from those very extreme subcultures There's been an export which is that you know Weight training is healthy, right? The general public has done that or that yoga is healthy So contortionism to yoga, etc And I feel like a similar thing is happening in the realm of psychedelics where it was leery And huxley, I mean I like I'm from the Bay Area I'm not far from the Menlo Park VA where one flew over the cuckoo's is basically based on right Ken Kesey and those guys and the You know the there has been an attempt at creating this movement toward um Openness about psychedelics and their positive effects that this has happened before The difference is that now there are people like you inside the walls of the university or publishing peer-reviewed studies and things of that sort The reason I asked about McKenna was you know, it seems like McKenna and his brother um are but you know set Just two of many people Michael Paul and etc who have no real formal training in biology or psychology Um, the other guys who were at universities lost their jobs They were actually removed from places like Harvard and other universities for their kind of cavalier explorations, right?

Dangers of Psychedelics, Bad Trips, Long-Lasting Psychosis (01:26:00)

And now things are kind of returning so in the same way that bodybuilding led to weight training in every corner gym Yeah, men women and children And contortionism is one extreme, but people generally think that yoga is a pretty healthy practice, right? There these are matter of degrees, right? And now here you are inside the the um the walls have a very Highly respected university john's Hopkins. You're on the medical school side of the undergrad. So in the med school which um Is it you know a serious health institution? Um You know The question is to me, you know, what are the what are the valuable exports, right? And where does the extreme lie? I mean clearly there's a there's a problem with um tinkering with reality through pharmacology and there's a benefit it sounds like to tinkering with a reality through pharmacology and What's so striking to me is this is the elements of Atypical experience a typical representation of the self. Um, so For the for the average person, right or for kids that are hearing this kids that are in their teens, right? Yeah, what are the I want to talk about? What are the the dangers of psychedelics? Is something you don't hear a lot about these days and it's not because i'm anti psychedelic at all But what are the dangers right if if a if a kid or adult has a predisposition toward let's say a psychotic thinking right or um auditory hallucinations or um, whereas on the Asperger's side of the autism spectrum is there an increased risk of of bringing the mind into These states because it sounds like a very lay-byle situation Um, so could we talk a little bit about that and are there classes of these different drugs whether or not the mdm a lsd or dmt that are Um, that you think are particularly sharp blades and therefore need to be wielded particularly carefully. Yeah, so these can be profoundly destabilizing experiences and ones that you know ideally um Are are had in a safe container, you know sort of where where someone You know, what are the relevant dangers and what can we do to mitigate those so There's two biggies One and i've already mentioned it's people with very severe psychiatric illness not not depression not anxiety i'm talking about Psychotic disorders like schizophrenia or mn mania as part of bipolar disorder So And and diagnostically this has shifted so it's a little hard to say how many people today with bipolar would have been labeled as schizophrenia back in the 60s when some of this um early research or just clinical observation Was done so it seems very clear that folks with a predisposition or active disease They could be destabilized and so some of the cases that we know i've always Think of sid Barrett the first singer pink floyd um Seems pretty clear although i think the family i don't know what happened there So i should be sorry pink floyd fans i've never the songs are just really long. Yeah, you're more of a punk guy, right? Yeah So i've i've got my foot in a lot of worlds definitely in part in the floyd world but uh, but He basically went crazy early on he he'd have it seemed i don't think his family ever admitted it But he developed schizophrenia um classic pattern and and and he was doing a lot of lsd um, but You know like a lot of these cases it looked like he was showing all of the signs of You know some some some hints of Uh that he had that susceptibility before and often this is hard to disentangle what causes what because When do people typically not always but develop when's the modal period for first break? It's adolescence early adulthood. Yeah, and when do people start playing with drugs saying exact Time periods so it can be hard to to disentangle, but it seems pretty clear now i should also say There are cases of folks with skids of franny that safe psychedelics have helped them There's anecdotes for everything though. It's a big role those skids of phrenics say it's helped them I don't know because when skids of phrenics say things you have to i'm not yet I mean we all do compassion and respect for skids franny. It's a disorder of thinking So if they're saying it helped them Yeah, can you trust them? Yeah, I wouldn't be surprised if there was some kernel of truth in some cases, but they're just so It it seems very clear that the other side is there too And that that there ever is a therapeutic potential there for those disorders that That shouldn't be the first thing on our list We need to learn a lot more because of the level of risk before we start doing research to see if You know, so i'm gonna can help with skids of phrenia like I don't think that that may never be the case but even if it is you'd have to be even more cautious and Figure some more things out first with some of these other disorders What about bipolar? Bipolar disorder can it be exacerbated by these uh? Yeah, and it's it may be that that that sort of the manifestation of people having prolonged psychiatric issues after a Experience as as atypical as that is when that happens it it maybe that's that might be more like a manic episode than a psychotic episode and that can be a blurry line and it's it's The folklore is that you know people go on a trip and they never come back That's clearly not the case because you know the drug is metabolized like for anyone else in the next day There's not you know, it's virtually not the necessary circuitry I mean, right and there's still and I I really do think you know much like the positive um, you know, uh long-term effects that you know this class of problems is related to like the um to the experience and the De-stabilization that can happen from that from that Experience if it's not in that in the right container And again like these people are susceptible to you know, some people with that Psychotic predisposition they're lucky to be born to a great family Stable environment they maybe never have a full break or the one that they have is not nearly as bad as what You know someone that that is who's homeless and is coming from all kinds of early childhood trauma like the disease is probably going to be far worse You know, so you know the the site having a psychedelic experience is is like one of those destabilizing Experiences, you know, so Exclu- now fortunately, it's really easy to identify those people and we even like air on the side of extreme caution by Eliminating people with like say a first degree relative in some states even a second degree relative Given the heritability. There's some increased chance if your brother or your yeah So so in an abundance of caution, um even eliminating that I think eventually if it's approved for use Um FDA use that we could dial back on that as we learn more. I think it's again Over overly cautious, which is but you're really Yeah, it's the appropriate place to start at this point in time But you know if you you know give a skid or another structured psychiatric interview with a clinician seeing now And this person for a few hours to delve into their history and like you can very reliably determine at this person Has either you know a psychotic disorder or bipolar disorder or a strong predisposition So that's you know that you can screen for that and that's how you address that the far more likely danger is the bad trip Anyone can have this the most psychologically healthy person in the world probably Jack the dose high enough and especially in in in a less than an ideal environment You can have a bad trip you can you even get it in an ideal environment like ours at a high dose of around 30 milligrams of psilocybin After you know the best preparation we can provide about a third of people will say Essentially at some point they have a bad trip, you know, we at some point within the entire journey Right now they could have one of the most beautiful experiences of their life sometimes like a couple minutes later But at some point they had a sense of strong anxiety fear losing their mind Um feeling trapped something like that now Typically when people have that and the you know when they're just taking on their own Like a lot of things they're fine. They get through it You know they're more likely to be better off if they're not having to navigate the streets of man hadn't that you know Or and if they're with you know other people with friends Better that those friends aren't also dealing with their own psychedelic experience But probably having some friend of any type but what other on there is better than having nothing so Very dependent on contacts and so the tough thing here that that in in conveying to the public is that A lot of folks will say man, I've taken psychedelics hundreds of times and this is like your fear mongering and You know, there's no, you know, you're exaggerating the danger there. So I want to say it is atypical But sometimes and I have a file folder that grows Larger every year of these cases Either in the medical literature or from the news of people that freak out on a psychedelic and they They get hurt or they die. They run into traffic They they they fall from a height whether they thought they could fly or whether they just felt like they You can do when you're drunk or you're intoxicated on any substance. Sometimes that's that's unclear um or Gosh one of the craziest cases was a um a kid like an 18 year old or so In Oregon several years back that just he even wrote about I want to take the biggest he had done mushrooms for I want to take a Heroic dose the biggest dose I've ever taken he ended up just totally out of it ended up in a neighbor's house He was just totally disoriented disconnected from reality and the cops ended up killing him And it was just tragic obviously an overuse of force in that case because he was actually naked at the time this naked like 120 pound I think as a recall kid that ended up dying but well It's analogous to the you know, the reason I use the examples of like bodybuilding culture I mean people there have taken excesses of amounts of anabolic and diuretics and died Then the contortionist culture people have put themselves in a little plexiglass boxes to do you know At the extremes You're going to get deaths and at the extremes uh and as and one of the extremes is the sheer number of people with different biological Makeups Taking the same drug and so you can create extremes through numbers. You can take extreme you create extremes through dosage, right? It seems Um, well, this is why I'm such a fan of of the fact that people like yourself are doing clinical trials inside um the walls of universities not because uh, I think that psychedelics Only have utility in those environments, but because it's so important toward creating their transition to legality And to understand what legality means for a compound like this, right? Right model, right? I mean again, we'll stay with the anabolic steroids There's now testosterone and estrogen replacement therapy hormone replacement therapy is a common Medically approved practice, but that's vastly different than people taking their own stuff for diet or deciding how much they need to take right? Like we said, there's there's yoga and there's contortionism in a plexiglass box and you know thinking you're houdini or something So there these are a matter of degrees Speaking of dosage. I definitely want to ask you about micro dose versus standard or macro dose Tell me tell me that i'm wrong, but i'm always a little bit um I sort of a little i'm micro cynical If you will about this term micro dose and the reason is that Many people that I know who talk about micro dosing Are taking dosages of compounds that work at mike that are very powerful at microgram?

Micro-Dosing (01:38:15)

Levels so the word micro I think can be a little bit confusing to people because micro dose implies less than Something it's a mini dose right and yet some of these compounds are tremendously powerful at microgram concentrations so What it constitutes a micro dose and what is the value of so-called micro dosing if any and How does it differ from standard or what I can only assume is called macro dosing Yeah, and so lsd would be the the prototypical example of that super potent How much might what what size dosage of lsd will lead to hallucinations and kind of standard so through the entry point for psychedelic type effects which may not involve hallucination actually Most classic psychedelics don't lead to true hallucinogens as defined in psychiatry of you know Thinking you're talking to the person that's not there seeing the pink elephant No, it's more like tracers and things like it right and it Some people never get that even at a very high dose. So I think more broadly in terms of the psychedelic effects Which isn't just perceptual unless we get into the level of as you were alluding to earlier a broader definition of perception like One's models of the world the model of the self you can you can consider all of that perception in terms of you know truly not Sensation but the perception the construction of of putting together reality. So um Yeah, yeah, yeah, so Dis psychedelic effects are typically considered to start for lsd around 100 micrograms So a tenth of a milligram is 100 micrograms And so when taking 100 micrograms of lsd They on the nowadays people might mistakenly refer to that as a micro dose because it's micrograms But that's actually a macro dose of lsd right they might and that's one of the most common mistakes or Situations that people get into with microdosing as they intended to be a microdose, but it ends up being a full-blown You know dose now people do when they're working with lsd in their microdosing those shoot for something like say 10 milligrams, you know something in that range 10 20 milligrams of lsd so you know a 10 to 5th something of Kind of your entry level psychedelic dose People's ability on the street to do this You know I say the street as if they're on the corner But anyway like outside of the medical profession to do this like varies as you can they're not measuring purity and morality or things like that Typically and there's ways to do it So even if you don't ultimately know the dose that's in like the blotter paper of acid One could at least get a sense of like yeah having one of those tabs Is uh one of those hits is is a psychedelic experience and they could do something like put in water It's 100 8.0 aqueous soluble. You could vol you know make sure it all gets into solution and then volumetrically measure It's going to be homogenously distributed So you can you take one tenth of that volume of water after it's fully dissolved You know that whatever you started with you're going to have a tenth of that though So the people that are more sophisticated will do things like that and when they're working with mushrooms They'll grow a bunch of mushrooms and then they'll say put it in a coffee grinder I'm not telling people to do this by the way I'm just describing said don't do this at home, but like grind it all up So it's homogenous because you can have like you know sort of taking you know two caps in a stem Hey, this two caps in the stem that this buddy takes Is has a different potency than this two caps in a stem that the other buddy takes so People that are kind of in the know will grind it all up into a homogenous powder and they'll pack it into whatever size capsule And they'll know that and again even if they don't have Sometimes they might have a buddy that'll sneak it into the HPLC at their at their job or whatever if they have Not my life. That's never happened. Yeah, seriously never happened, but um, but they'll at least know that Hey, I've got a sense of what two capsules do. I've got a sense of what five capsules do and so but in reality Like that's not what people do They'll take a piece of blotter paper and they get a tiny little spare scissors Swiss army knife pair of scissors and they'll cut up the tab of ash Which is like you know a quarter inch square or something and they'll cut it up in 10 little pieces and it's like I got you have no idea like if it's equally distributed in that media. Yeah, and we can chuckle about it and um, but to me One of the reasons why this experiment around psychedelics this cultural experiment and this legal experiment We're seeing this now, but this was all attempted once before in the 60s and 70s The difference was it was all out in the street the people in Universities who were dabbling with this stuff lost most of them lost their jobs or were asked to leave through you know They lost their funding for this research And they had to move on to other topics. That's right So these are precarious times. I mean we're at it. We're at a we're in a key moment where Everyone assumes that this is all going to be legal in a few years, but I think that that's a premature assumption frankly, but um and I'm and let's touch on the legality and some of the things that are happening now, but What is micro dosing psilocybin versus um the sorts of dosages that you described before in the 10 to 40 milligram range Uh, I've heard of people taking one or two milligrams of psilocybin every day as a way to quote unquote And for those listening, I'm just making air quotes with my fingers Increase plasticity, which is it which is a term that I personally loathe because what does that mean? I mean, you don't really want your brain to be plastic because you need to make predict You need to maintain your ability to make predictions. Yeah, I mean or us like prediction your you need models of the world You need heuristics like plasticity is never the goal or be it plasticity is never the goal The goal directed plasticity is the goal right learning a language reshaping your experience to a trauma altering the perception of self, but plasticity is a process like Yeah, it's a phrenia is a lot of plasticity Right, right it might even be there's one theory that it's extreme ongoing plasticity And that's why people never create stable representations of anything. That's a kind of A minority view out there, but um So what's the business with micro dosing and is there any clinical evidence or peer reviewed published evidence? That it works quote-unquote to make people feel better about anything. So micro dosing is is Is the aim of taking again something around a tenth of what would be sort of an entry level psychedelic dose for whatever compound so um, so like yeah, with still some usually people almost never peep to people have like pure psilocybin like 1 milligram psilocybin would be in the range of a micro dose more likely people are gonna have you know mushroom so they'll like something like A half of a of a gram of mushroom. I know people they're doing this every day They're doing these every day. It's like in there like the same way that I take like i'm personally I'm not recommending other people do this, but I take some i'm a fan of lc. Oh carnitine lately I've been kind of experimenting with that a little bit, which is not a psychedelic compound I take it every day and they're taking their that's their cell size in every day. That's their supplement. Yeah, um, so So yeah, the claims are in their number of them There's two general ones one is is sort of acting In in place of the adhd treating drugs. So the psychomotor stimulants so like a better version of at all The other claims are essentially a better version of of the Traditional antidepressants a better version of prozac So be taking both for attention deficit and for depression Yeah, and the aspects of those disorders that you know, we all have a degree of you know Just like amphetamine is going to increase the focus of at the right dose of anyone who takes amphetamine pretty much whether you're adhd Diagnosed or not Um, the idea is that you know that there may not be a necessarily a clear divide between the Therapeutic need and you know positive psychology, you know, even improving mood and focus You know, uh, you know, so it's not necessarily correcting, you know Adhd but improving focus to supercharge, you know, your your life and so those are the claims. I am So so none of the peer reviewed studies that are have much credibility Um None of them have shown a benefit and they've tried now there were there's only at this point four or five studies that and I think for Things like this you really need Double-blind research because the effects I mean there was one study done in Amsterdam where people Knew they were taking psilocybin truffles basically same as mushrooms and more like the roots of mycelia microdosing them taking up what would be considered a A microdose and then doing some some cognitive measures before and after and the types of things that you know Like a lot of cognitive measures are measured on the order of reaction time in milliseconds I mean and the types of effects you get as you could imagine are ones that like would be You would totally expect could be there from either a practice effect or or an expectancy effect a placebo effect. So You know for something like these claimed, you know, you can imagine a sort of an increased focus, you know, an enhancement of cognition These are like going to be more subtle effects that you really need a Good placebo control for the handful of studies that have done that have shown They've ranged from finding no effect whatsoever to just a little bit of impairment like impairing someone's ability to do Time estimation and production tasks. So you want an accurate sense of time at least if you're navigating in the real world It's different if you're on the couch on a heroic dose for therapeutic reasons where you're safe But if you're crossing the street if you're getting you know In your work life. Yeah, which is why the way people are claiming to use that it helps them Be a better CEO like you want an accurate sense of time So if anything the data suggests that it makes it a little bit less accurate and and there's evidence that someone feels a A little bit impaired And they feel a little bit high. So in terms of you know You call that abuse liability and research not surprising you take a little bit of of a of a drug that can result in a Some type of a high and you take a little tiny bit of it. You'll feel a little bit high. So um You know, none of the so far no studies have have shown You know, so in increase in creativity Enhancement of any form of cognition Or or or a sustained improvement in mood now No studies have actually looked at the the System of microdosing that the aficionados are claiming and there's a couple of models out there but but folks like um Paul Stamets and others they'll have particular formulas They're like you need to take it one day and then take so many days off and take it every four days And I don't want to get into whose model is what but it's always something like that some pattern of use usually not every day And and the claim is that it's not just you know Sometimes people get benefit that first time when they take it But they really say you need to be on it for a while like a few weeks in you may start to notice through this pattern of Using it and you you're feeling the benefits on those off days like the three or or two days in between Your active doses. So those are the claims again. We don't know that there's any truth to that working But studies have not been done To model that so that's a big caveat. We as a feel I say we as the as the scientific field Have not done the studies to really model, you know what the real aficionados are claiming, you know You know where the therapeutic benefits come from that said it's it's it's almost assuredly There's a good amount of placebo there, but but the caveat to that is like almost everything in medicine or therapeutics There's and it's going to have some degree of placebo there. The leaf effects are are I have a colleague at stanford Alia crumb who has published really beautiful work on belief effects that Show that essentially you give the same milkshake to two people you Are two groups of people you tell them that one contains a lot of nutrients the other is a low calorie shake there They're the insulin response amazing very dramatically between the two or two two groups rather doing equivalent amounts of Physical movement and you tell one group that it's going to be good for them and help them lose weight and they lose on average eight to 12 pounds More doing the exact same Patterns of movement so and I think that these belief effects boil down to all sorts of kind of network-wide neuromodulation things that sort of The work at harvard suggesting that even if you don't have deception you give a placebo and say this is a sugar pill Right Tell them that right and they could still treat things. I think irritable. Wow was the first thing they looked at Right, and so there's a huge so there's a reality there Right, um, there's a necessity in developing drugs to make sure it's not only that but but in the actual practice of medicine Hopefully what you're always getting is some underlying direct efficacy plus The placebo that it enhances that now It could be that this is the real question is is the microdosing are those claims? 100 placebo or are they only part placebo and part Real you know quote unquote effect My bet is and this is totally based on anecdotes that I think there is probably a reality to the anti-depressant effects I find that more intriguing because of the suffering with depression, right? Even if it's an it it wouldn't be as interesting as I think what we're doing with high dose psilocybin or psychedelics to treat um depression it would be if this is developed in this reality it would be more like A better, you know perhaps a better SSRI a better prozac Similar more tools than fewer tools in the toolbox And it shouldn't be that surprise like even before the as going back to the tricyclics and the maoh Inhibitor is going back to the 50s like augmenting extracellular serotonin in one way or another For many people leads to a dereduction and depressive symptoms It wouldn't be that crazy for chronically stimulating a subtype of serotonin receptor That you have an anti-depressant effect. So I think if I have put my bets on it that there's if there's anything real It is in that category. Although I'm very open to like maybe there is something to the creativity to the you know improved cognition which covers many domains in and of itself, but um my My greatest hopes are on the On the anti-depressant effects that said in the big picture I think all of the most interesting thing about psychedelics are the heroic doses I mean the idea you can give something one two three times and you see improvements in depression Months later and in addiction You know over a year later and with these you know people dealing with potentially terminal illness I mean it's I mean i'm interested in big effects and I don't think you're ever going to get the really big effects There's also some concern that almost all of these common psych the more common psychedelics even county mdma They have serotonin 2b agonist effects and agonizing serotonin 2b Um has been shown to lead to heart valve um formation problems morphology issues so Vavulopathy and so this is why fen fen was pulled from the market the diadronk Yes, very effective diadron right right and it was the the portion of that combination that had the the the serotonin 2b activity that was was the problem and so We don't know so all of the the toxicologists i've ever spoken to about this would you know say and cardiologists say like look hey If there was some concern there, it's not applicable to the whole idea of you taking something a few times therapeutically within a lifetime But the idea of taking Something like you know twice a week For years. I mean even the the hippies back in the sixties weren't doing that right like there's not even these natural it and even if they Even if there was some heart valve disease problem. I that stemmed from psychedelic use Who's connecting those dots? That's not showing up in the clinical charts for anyone to figure out so there is and just theoretically there is more of a concern If if something's going to happen with with heart valves. It's more likely That that those issues would arise when someone's taking these things like yeah They say twice a week for the next five years And so I do want to throw that out to people to really consider right yeah, it's something I hadn't heard before that in in micro sound safer Microdosing as opposed to heroic or macro dosing and yet Unless uh and in the context of your lab and and other labs doing similar work Um, you've got this people checking blood pressure You've got people that are really monitoring your psychological and physical safety when people are out there micro dosing It sounds like there's the potential either through this serotonin 5 h2 to be Receptor or other mechanism that maybe there could be some common cumulative negative effects They um and I think that's an a really important consideration. So I'm glad you brought it up Uh, what about kids?

Risks for Kids, Adolescents & Teenagers; Future Clinical Trials (01:56:45)

So the brain is very plastic early in life. It becomes less plastic as we age Yeah, although it maintains some degree of plasticity throughout the lifespan. Um the the year 25 it not uh, uh the year 25, but rather the age 25 years, um is sort of an inflection point where Um, the rigidity of the neurofist system seems to really take off of course people don't wake up on their 25th birthday and Fine, they have no neuro plasticity whereas the day before they had a lot. These are you know, it's plus or minus Whatever it is a year or two, but um depends on the individual um however The big the young brain is very plastic And I could imagine there could be great Risks who knows maybe even benefits, but I'm certainly not Thinking about those. I'm mainly thinking about the risks Of for young people taking psychedelics. Are there any trials looking at people? Um in clinical trials, this would be under the age of 18 has anyone explored this in a rigorous way Um given the potential to exacerbate psychotic symptoms and bipolar symptoms and some people Uh Is there height and risk of that? What's the story with age of use and psychedelics for therapeutic purposes? There's no formal research Although I there's a very high chance that there will be and so this is one of the very interesting things folks may not Realize or appreciate about the FDA approval process So the FDA already in multiple instances has signaled that they're they want to see those studies before Well, not not before it's approved as necessarily as um, you know for for adults But they're going to eventually want to see in fact so the the maps group that's developing mdma for ptsd They've um Already signaled that that's kind of on on list of of interest um, and there's even some incentives and that in the fda um pathways for um for incentivizing folks to explore that that use in young people I know in some of the work that I helped with in pushing um, psilocybin into phase um Phase two b clinical research the fda You know said well, why why can't you give this to kids? It's like Are you aware that depression is a problem with with with adolescents like you know like and it's really interesting because this um FDA is very concerned about pseudo specificity The idea that you find pseudo-sposives you put out a drug and say oh, this is good for men, but not women This is good for black folks, but not white folks And now sometimes there's a very good rationale for that like when we're talking about hormones and for a specific You know for for for men versus women and there's certain, you know, uh issues, you know, uh, You know certain disease aids like maybe sickle cell anemia. That's more relevant. It takes acts things like yeah, exactly You know, but absent of something that they're very concerned about saying oh, this is for this type of person But not that type of person so age is one of those things and also this Recognition, you know much like the emphasis at nih with you know with you know with rodent studies and human studies that like you can't just say You're studying men or just went what you need a rationale if you're at least a folk Yeah to be clear to people there's uh, it's a recent switch, but there's a stipulation in every federally funded Grant that both sexes we don't refer to gender in scientific studies unless it's a study of gender per se We refer to sex meaning biological sex So that there's a stipulation that in order to receive and continue to receive funding you have to do Studies on both males and females of that species including humans And at least even if you're not powered for it at least looking at that in exploratory analysis like as a grant reviewer I'm charged with looking at you know, did they address like sex as a biologically relevant variable? Right does this say does the same drug have different effects in males versus females? Right and you could at least look at the trends even again if you're underpowered to look at those between subject type effects Which is a great shift that didn't exist in uh, you know 10 years ago Uh, sounds like we're both on grants panels As study section members you didn't have to do that now. It's a it's an important biological variable if you don't Uh, look at that you essentially won't get your your funding and age is a similar thing So it's the whole idea like man if something could help kids like what's the rationale? So I think there's gonna be now obviously you're gonna have in those studies At least just as much probably more it should be more You know of a caution cautionary approach. It's probably gonna be you know Would certainly whatever disease states are like they're gonna have to be probably treatment resistant at least as a first step, you know Hey, it's your side of aggression. Yeah. Yeah, and and so all of that in the mix, but hey You know if this stuff really helps people You know that are 25 or 30 like what's the rationale that it won't help a younger person You know and there's can these generic kind of concerns about the developing nervous system is more susceptible to Problem it cuts both ways because it's also more plastic generally and adaptable maybe resilient injury in certain ways But you know you hear the rhetoric about kids their brains and drugs and it's like the developing brain is a special concern Um, so yeah, but I think we're gonna be seeing research eventually. That's it's interesting. I went to the high school Um that is infamous sadly gun high school For having it the highest degree at least at one point of suicide suicide rate Wow Very large number of suicides. This was written up in the in the times and elsewhere. Isn't it very academically successful school It's a very academically deep pressure. Yeah, very academically demanding school. Yeah to a point where they've restricted Um, the kids will meet often at 6 30 a.m. Or 6 a.m. Before school for study groups and things of that sort So some of it may relate to that. Um, but I have to say that even prior to all that academic pressure Um when I went there, it wasn't the pressure wasn't like that that you know we had a an unusual number of suicides for whatever reason and You know and so the idea of kids being prescribed and when I want to be emphasized prescribed not just using but prescribed psychedelics for therapeutic purposes. I think might make some people bulk, but um The idea of kids killing themselves should also make people bulk and so I'm I'm relieved to hear that there's going to be a rational scientific safe clinical trial based exploration of this um I want to ask you about the current status of these drugs and compounds. I'm um Pretty active on social media more so on instagram than on twitter But as I have been on twitter a little bit more recently, I've noticed that there's a lot of Dialogue around your account and other people's accounts around a couple of themes related to psychedelics.

First of all What is the status of of the transition to legality for for prescription? purposes so medical doctors mds prescribing it legally for therapeutic purposes That's the first question the second question is what is the status as it relates to possession and criminal charges so uh for a long time I lived in oakland where we were one day told not Too long ago. It is now quote-unquote decriminalized is what I was told that double check people Um, but what does that mean and then the other issue and the third question and we can parse these one by one is this issue of Let's just say I'm aware of a lot of investor dollars going into companies that are essentially companies focused on psychedelics as therapeutics or psychedelics generally I have to assume that they are investing in anticipation of a shift in the legal status um And there's a lot of interest now like will psilocybin become a taxable Thing just like marijuana. So let's start with other question of like what is going on in the us legally uh, is it illegal to possess and uh Sell and use these compounds my understanding is you can still go to jail for having These compounds in your possession or for selling right so Even though it's a the the legal landscape is very different than with cannabis Um, there are some similarities. So one of the similarities is that regardless of what local Municipal, you know, whether the city or state has decriminalized Um and that that word itself can mean many things. So if the devil some some forms of decriminalization Is close to what folks would call legalization and others are like pretty weak You know just saying we suggest that the police make it their lowest law enforcement priority That's sort of turn the other choose kind of right But even the the cops can still choose to but someone could get pulled over for one thing searched And then by definition if it's illegal and they find it Right and they have they they have to do something about and that will probably be determined by You know like both judicial precedent is it going to be thrown out and just the local prosecutor You know even before like are they going to choose even app post arrest are going to pursue To really you know go after those charges make those charges Stick so I think that's still in play and it's going to depend on the municipality, but like cannabis Federally these are all schedule one compound, which means they're illegal That much means they're illegal The caveat to that just has always been the case since prop 215 in california with cannabis in 96 is that hey 99 of Drug enforcement is done at the local and state level the dia Which is the federal level of law enforcement is a tiny fraction of the arrests That got me most people that arrested for any drug are done by local or state level authorities But it's still technically you know illegal and so you can and they could be potentially depending on the ambiguity of the local law they even those local officials could charge you with a federal crime um and Theoretically the feds could always come in now, although you'll you know again a similar you know case with the whole cannabis history it was the the feds came in in the early days with the folks that were basically Highly visible they went after tommy chong for selling bongs But you know, I remember him being on the tonight show one time and I think it was back in the jaylinna days He says but oh long sanimonica board more like every shop sells bongs How did you go to prison for a half year for bongs? It's because he was and they're because he was famous He was you know tommy chong and and there was some high profile cannabis groups of you know That were distributing it and they were very vocal those were the ones rated by the dea in the early days Not the ones kind of keeping to themselves keeping it quiet and just doing their thing So there's always the potential for selective enforcement and so you know in like this initiative in organ, which is a state level Legalization of psilocybin therapy, which is really interesting You know part of their plan for two years is to figure out how to integrate with the federal level and I don't know how that's going to go because like unless you rewrite the controlled substances act it seems like the best you're going to get is a tolerance from the federal government um And you know and that could be very you know, hey you change administrations and this is psilocybin by prescription from a medical doctor or you're talking about therapists in cl um who have Masters degrees or phes or self-appointed coaches or something like that um administering psilocybin But without any Oversight so this is all getting figured out in the Oregon case and again There's that two-year period of like basically we're gonna figure this out and so what is it with Oregon There is the lot of you know I love the state of Oregon. It's but it's interesting how you have these pockets Um, Oregon vermont seems to be one, you know, you get these kind of pockets where people are Experimental with plant compounds Um, they seem to be green woodsy areas for in at least in my mind But there there's sort of a culture around plants and the use of plants as therapeutics and combine that with the west Just just more geographically of more of the the anti You know federalism the anti I mean the Oregon ranchers from several years ago that held up the uh, you know, the the whatever Wildlife place, you know, and that was a big showdown with the feds, you know and the car You know just kind of the west is kind of known for You know more of those issues. So you combine the two the hippie dippy california Oregon by Although i would argue it's becoming less hippie dippy the um, then although it was That there's always been a tradition not just in the culture around drugs, but um certainly in academia and in tech etc That the west And it has been a place where people have tried to throw off Traditionalism and kind of lineage and like who your parents are what school you went to and um And the past as a determinant of what's next and exciting about the future Whereas and here we are an east coast institution guy and a west coast institution guy. Um, I think that it's this idea of kind of Innovation and the future versus do we stay grounded in history and tradition? Right and of course there are great institutions on both sides. What's interesting is that um hopkins john's hopkins Medical school. I think of as a real like east coast academic institution. It is on the east coast, but here you are uh doing these very pioneering and important and exploratory And studies in a certainly not a hippie dippy environment Right. Um, very conservative psychiatry department even among psychiatry departments and as a psychologist in a psychiatry department Psychiatry is certainly more conservative than psychology Even within academics, but even amongst psychiatry departments. It's a very conservative Department, so we got the law at the federal level. We've got the law at the state and local level And then we've got this question of whether or not it's going to be physicians So mds People with phees or master's degrees or whether or not it will be kind of a free for all right? Um for for consumption and the life coaches and and and the general public. I mean right an abyss I'm not a pot smoker. I just it. It's never appealed to me. Um, that's just me and my my pharmacology, but um You know, you can buy cannabis most places in the us without a ton of risk. It seems right. Um Are we going to see a time in which? You can essentially go into a shop on uh abbot kenny boulevard in venice, california And right now you can go buy marijuana if you have a marijuana card that's my understanding I see a lot of people going in out of these stores Um, the police certainly have no problem with it. Is there gonna come a time where people can just go buy phees or do you think like do you an amsterdam and have a long time is coming? Um I think so at at at a certain point and uh, I don't know how long um it's hard to imagine our current level of drug criminalization holding up for And i'm thinking like large spans of time like really in a hundred years are we going to be doing this 500 years? Like how could that it's not going to be sustained but in five years for instance So I don't think so in the united states. Um, I I do think eventually You're going to see something like that because there's going to be no way and I think we're gonna I hope that we're going to eventually come so strongly We're going to move on from this model of criminalizing drugs that we're really going to focus on regulating drugs at the right level for that drug and I I like the word regulation better than Legalization so I mean I could imagine what one day regulation smart regulation might mean for psychedelics Maybe it could mean that there will be you know whether or not you have a diagnosis of a problem It may be that even for personal exploration you can do this legally But you first have to maybe take a court get a drive and this has been i'm not the first to say this but get equivalent of a driver license you have to go to Get some sort of training maybe your first number of experiences need to be with With trained guides who can facilitate it and then the public health information for anyone using this that This is what riskier use is all use is going to have risk. This is what riskier use is. This is less risky use These are the factors So I think eventually we're going to be getting for any but I would see the same thing for like methan fedamine and and You know heroin and cocaine like all of these drugs. It's hard to imagine the current approach of just feeding a black market And really exacerbating a lot of the harms from drugs, you know You know that happens under the current model. It's hard to imagine that maintaining that isn't to say I think it should be In all of the 7-Elevens, you know sold to kids at the other I would hope not But I do think it's probably not going to be soon in the United States I do want to make the major point that the even if psychedelics had never been made illegal I think the exact the trajectory of the medical research right now would still need to happen If it's effective as an antidepressant like We need it to be you know, there's all the evidence suggesting that whatever disorder we're talking about the efficacy is going to be increased And the risks are going to be mitigated drastically In the types of models we're talking about with the screening with the preparation With the integration of cognitive behavioral therapy or what have you depending on the disorder you're treating With the integration afterwards with the professionals. So um, it it We would be doing it anyway, so it's not like this versus that So I don't see it as a race between the decriminalization or legalization of these common versus their medical development some people who are psychedelic fans get get all Into a bunch about the medical development. They say you guys want to like You want to you want to keep it only for you know for your medical research and I retire and you want to be Yeah in control of it as academics and my take is I didn't make it illegal for anyone We're only moving the needle in one direction And again, even if it was already illegal And and because and I've done plenty of survey research of people reporting They took mushrooms for fun or for personal exploration and They said my god, why am I smoking and they quit smoking 20 years because of it or it's helped with their depression or it's helped with them Overcoming alcoholism or these different sometimes that happens out of the blue when people use psychedelics nonetheless Obviously the efficacy rates are going to be higher when you bring it into these medical models and it's going to be Safer so we're gonna you know So we need to be pushing that and my best guess is that mdm a is going to be approved Within the next three years and for prescription by a physician. Yes in And not just you know take two and call me in the morning But in the clinics the way that those those ptsd trials are being run So the mdm a would be approved for ptsd and every disorder needs to be looked at separately And it's going to only be approved for those things now There's been these questions and legalized and regulated or you know now we're getting into the nuance I think when people hear it's going to be approved in two years they think That they'll be able to buy and sell and use mdm a without legal consequences And I do not think that's going to be the situation has not the way it is and I will say that um I think the quote-unquote psychedelic community I mean that they've been doing what they want to and will carry on doing what they want to Anyway, right. It's not like the legal status has um has prevented them from doing what they're doing in fact unlike leery and Timothy leery and huxley and and you know and and some of the others that were very vocal and lost their jobs and some of we went to jail Etc I mean you got a lot of public figures now like mckenna and others who are just basically out there talking about psychedelics Michael paulin who is more of a writer foodie guy gone psychedelic dabbler writer guy um, I know he's he's kind of a polymath, but You know the league the legal status didn't seem to hinder their Um, at least online careers. I don't know. I don't know. I haven't looked at their bank accounts But that I'm imagining they're doing just fine. Right. So the fact that the work is happening inside of um big institutions. I think it's important that you point out and I'm just trying to underscore that that's that's in in no way antagonistic to what people are doing it's In support of a different sort of mission which is to explore the validity in different contexts in a really controlled way um, which I really you know It's I think it's a really important mission Um, I want to make sure that I ask you about the other really important mission that you're involved in with respect to psychedelics Which is not about depression per se but is about neurological a neurologic injury or head injury I realize it's early days for this, but I think um Uh, there's a lot of concussion out there sadly. There's a lot of tbi dramatic brain injury Yeah, not just from sports.

Psychedelics for Treating Concussion & Traumatic Brain Injury (02:18:35)

I think people sometimes forget that it's not the the major source of traumatic head injury is not football It's not hockey. It's not boxing. It's not any of that stuff. It's construction workers And it's people. I mean if you've ever seen the helmets the construction workers wear. I mean the jackhammer Yeah, jackhammer Yeah, I have a colleague that works on this in bioengineering and when you look at the you know We always think sports, but there are many people who make a living in a way that is um Over time is detrimental to their brain and they don't have the option of just not being a professional Athlete or something of that sort and if they're not doing the construction someone else needs someone else has to do it Right and we forget for some reason And I too didn't occur to me until I heard it like the people who are doing construction Um, and then of course with bike accidents and falls and things like that as well. So it's hairy military. Absolutely. So um What do you think is the potential for these compounds? Um particular psilocybin but other compounds as well for the um treatment and possible even reversal of Neurological injuries and what what sorts of things are you excited to do in that realm? Yeah, so this is definitely on the more exploratory end. So it's based upon so you know, this is sort of beyond the the improvement of psychiatric disorders like depression um, you know or depression and anxiety associated with the terminal illness Um or a substance use disorder the addiction. So those are sort of psychiatric, you know disorders. So this is you know, um, these you know There are anecdotes of of people saying uh that That psychedelics have helped heal their brain. You know, they've been in one of these situations like in sports A sport where there's repetitive head impact and they're claiming that You know using psychedelics has actually improved their cognitive function. For example improve their memory um including it improved their Their their mood. Um, but but it's kind of more of the you know, the cognitive function things like memory are now Cabi ideas if you've successfully improved someone's depression you can get some cognitive improvement too, but that's a more of a A weaker more indirect effect, but if you take these anecdotes and you combine it way across orders of analysis to the rodent research from Um several labs like david allson brian uh roth these folks that have shown different forms of neuroplasticity unfolding um uh After like sort of post acutely so after in the days following the administration of psychedelic compounds A note a variety of psychedelic compounds and even some non psychedelic structural analogs um, uh that you see these different forms of uh, neuroplasticity so um the growth of dendrites and new uh connections being formed with with different neurons so that those effects Maybe at play and they improve in the psychiatric treatments that we're dealing with That hat we don't know that it seems like a decent guess and we're going to be figuring out whether that's the case But another potential that that sets up is that maybe that's what's going on with um with with with these claims of improvements from your neurological issues that there's actually you know, uh Repair of the brain Uh from injuries underlying You know things that you know situations where those repetitive head impact perhaps there's a potential for for helping folks recover from stroke um and disorders like that um It is a wide variety of disorders now that it's a bit of magic and a bit of like It's it's something that the enthusiast kind of can do some hand waving and claim that this is already known It is more exploratory, but what i'm hoping to do is some work with retired athletes Uh who have been exposed but by the nature of their sport for example in an a athletes in the ufc who have been exposed to um repetitive head impacts like a lot of sports um a lot of uh, you know sports exposed people too and and and who are retired from the sport and are suffering from say depression which can in part result from those types of of That history of head impact um See if we can fix the depression, but then also as a cherry on top in a more exploratory Toriame see if we can have evidence of Improvement and cognitive function and associate like using mri See if it affects great matter over time These types of things to see if there actually some evidence of this improved um like this more direct repair of the brain But again, it is very sort of like we've got some rodent data. We've got some human anecdotes We we will Acknowledged its early days and we look forward to seeing the data. Um, I appreciate how cautious you are Intentative you are you're not trying any conclusions. I think um from a purely logical Uh and somewhat mechanistic perspective. I mean if we assume that lack of ability to focus or degradation in mood is The reflection of neurons in the brain. I think we can agree on that some Dialogue between neurons of the brain and that what needs to be changed is the nature of that dialogue ak neuroplasticity We know that reordering of neural circuitry Require in the adult requires these things like intense focus followed by rest, etc But the basis for that like beneath focuses the mechanism is a mechanism rather Beneath the the bin that we call deep rest is a mechanism and those mechanisms are neuromodulator driven. So to me you're um I'm not reviewing your grant. Um, but uh From a rational perspective, it seems that drugs that increase certain neuromodulators like serotonin or dopamine in a in a controlled way and then coupling that with learning of some sort sensory input of some sort It makes sense that that would lead to Could I should say lead to reordering of circuitry that would allow for better thinking better mood? Um many of the same things that you've observed in the clinical trials for for depression So the rationale is really strong. I think that's a very exciting area You know, I I get asked all the time about tbi and traumatic brain injury and right now You know, it's kind of um Uh, there isn't a whole lot that people can do and people are dabbling in the space of you know, um hyperbaric chambers and people will do sauna In breath work and you know and people are kind of you know clipping at the margins of what really is a problem that resides deep to the skull So I think um, I just want to applaud that the exploration I think it's great provided that exploration is being done in a controlled way. It sounds like that's what you're doing Um with the UFC. Yeah, so that's that you know, we they they were really gracious and had myself and and if you have my colleagues Out to their headquarters in vegas impressive place, right? It's in process. You know, there's a dialogue going on there I'm hopeful that there's going to be um some some work with them But it's it's in process now in terms of exploring that there's a real interest and I'm I'm just really impressed by the organization and their commitment to athlete health and um, we'll see yeah, I am too. We uh We have a uh colleague out there Uh, we're doing a little bit of work with them dunk in french who's a serious academic in his own right And I think when people hear UFC, they just think about the octagon and fighting and you know, pay-per-view fights and things but In talking with them and i'm sure you've had these discussions as well That they are very much interested in the health and longevity of their fighters They are also interested in the health and longevity of their fighters being a template for how to treat traumatic brain injury and improve human Performance in other sports and in the general public and I think it's not a an image of the UFC that is commonly comes to mind Because they haven't been you know particularly Uh verbal about it in the press, but I think it's great. They're bringing in academics I mean geeks like us going to the out to the UFC performance center I mean you do mma, but i'm basically just a geek walking through the place But the fact that they're interested in talking to scientists is really um I'm biased here, but a point in their favor um Along the lines of other Groups and individuals that have impacted the space that you're working in in this pioneering of of the psychedelic space uh, you know a few years ago. I think if someone submitted a grant saying I want to Study how?

Psychedelic Research And Participations

psilocybin impacts human depression I'm guessing having worked on these panels before that The the response might have been closer to well We need to do a lot of studies and rodents and a lot of studies and primates and then maybe just maybe we could explore These drugs because the national institutes of health actually has a a whole Institute devoted to addiction right of exploring compounds only in terms of their negative effects, right? Which is a very which is where i've gotten all of my NIH funding which is so interesting, right? And it's a super important institute. I want to be clear there amazing people there, but philanthropy and foundations have been very important in supporting pioneering research Uh, and so maybe we just talk a little bit about about that. So your lab receives Funding from taxpayer dollars through the national institutes of health. Is that mainly where your sort or your funding comes from? So Our group has gotten some funding from like say the national institute on drug abuse nida For some a small subset of the psychedelic work, but only for Some work A gear towards understanding these things as drugs of abuse course when you do a study though You can show us how they're Explored how they're bad Right, but when you're doing that you can explore like add You know the good stuff too, you know, um But but the the large majority of the work and the most interesting work has been funded by philanthropy Private philanthropy Now I still have some great support from nida outside of psychedelics i'm shifting more and more of my um My time towards you know focusing only on psychedelics and in fact us getting the the center level funding from um some really, you know big picture Philanthropists like helped me to start to make that transition But groups like to have to research organization denis mckenna, which is one of the founding members the brother terence mckenna Who's by the way an ethno botanist? That's what it is. What does that mean? Is ethno botanist? Um studying the essentially the anthropology of of of of psychoactive plant use So you know you get a degree in that? Yeah, yeah, yeah, you know hanging out with cultures and studying their use of these compounds in the traditional ways That Hopkins um there's that that degree exists at john's i don't i don't think that degree exists at Hopkins But i mean the the kind of the most And you know as you as you know from academia, i'm not you know, sometimes folks I'm not sure how many people's phe is actually in um ethno botany or it's actually in Something else, but the real focus is like my degree is general experimental psychology They're just decided they're gonna major in ethno botany, but you know the I mean one of the pioneers of the psychedelic area before leery and before and actually he was late even for the human researchers Like folks like hampry osmond and ara maha for and sydney cohen were earlier But even before those folks um richard shulties at harvard he was i mentioned him earlier in the conversation Discovered all of this now. There's these various tribes using I wascore yage a different name for the same thing Um throughout south america and these dmt containing snuffs and all of this so, you know, that was you know ethno botany this kind of this kind of intersection of anthropology and these psychoactive plant compounds so They have to research institute which dentists is a is a is a founding an active member of um a board member they have funded a lot of our early work. There's also an organization called the the um the bekley institute um based in england that a lady amanda Fielding is that has been the head of that has uh they provided the first funding for our psilocybin Smoking cessation research and the hefter came in and provided subsequent funding But it's and then there are other groups that counsel in spiritual practices a great guy named bob jesse Um funded some of the original work at hopkins looking at the nature of mystical experience outside of treating disease states or disorders, but just understanding these like like people take these compounds and Astonishingly, you know frequently will say that was the most important everything i've ever experienced What the hell is that? Yeah, I had someone mentioned recently. I think this might surprise me a little bit Certainly surprised me. I had a friend who um Adores his children. He's got three children. Yeah, doors his children How happy marriage and great great father. They're both great parents and he told me that as part of a clinical trial He had a dmt experience that he claims he said i'd love to tell you that it that the birth of my children was as profound But that was a more profound experience than the birth of my children any one of them and all of them combined And i was like wow now i've never done dmt by i was like wow that's a pretty strong statement now He did it in the context of one of these, you know clinical explorations um I assume that was part of a legal clinical trial, but the I mean that's saying something it's saying something I mean he's a very rational very grounded guy otherwise um but so philanthropy Foundations and then in most recently and so i just didn't yeah because i can't skip it our center Yeah, you can't skip it. You can't skip it in a half. I see that's like we I mean the hefter group the Beckley group I mean these are Wonderful. I mean these are people that have been holding the flame alive during the darkest hours like the right and same thing with With the maps organization on more than the mda side like holding that candle during the darkest years That you know so we but you know smaller organizations connected to smaller But growing over time, you know pockets of wealth Um, but you know we basically limped on limped along on a wing and a prayer Until recently when we got the 17 million dollar gift So that we could create a nominal center and as you know basically to the university that means you get a certain number of dollars And a lot of them you can call yourself a center, you know, it's a capital investment Um, uh, you know staff, you know equipment um salary support which has always been the huge thing for us um, but the 17 million dollar gift which was split between the The the the Cohen foundation so steven and al-xandra koan Uh, and they covered half of it in the other half the tim fairs collaborative basically tim And a few uh friends ponied up that the you know divided the rest of that half of that 17 million dollar gift and came together to just I mean it just it's completely transformed our the work that we've done in our ability to You know like to fully delve into this area and not worry that like oh If I focus on this rather than putting in another three Night of grants on some other topic that may or may not get funded like if I focus too much on the psychedelics Am I putting my career at jeopardy? But like so you're not only a tenured professor. You're also a full Endowed right so that came by the way when you say somebody is a fully endowed professor Want to be very clear what that means that there's funding all of the above but now I have no knowledge of your particular situation, but uh you you probably do Um, but sure the um and then these uh what we're essentially saying is that funding Which does not change somebody's salary level? I just want to be clear because I think the general public isn't Um, there's no reason why they would understand all the the nuts and bolts of how this works Academia is weird. Yeah academia is weird because we're not talking about increasing We're not talking about an endowment that or philanthropy that went to increase Um matt's salary that that's something that's set at the university level. Um, it's always been said and it Is at least it's still true now, which is that you know, nobody goes into science for the money at least not at the academic level um Not in academia, but um allows people to devote more of their time and energy to these exploratory Realms like psychedelic research or um in the case of my lab the work that we're doing with david spigles lab on on respiration breathwork and hypnosis For modulating brain states. These are not typically areas that the national institutes of health and other major organizations have institutions Set up to support now. There is an exciting initiative Uh, which is the ncc ih which is complementary health right um used to be in cam. Yeah, yeah And ih and now we're not just throwing out acronyms just to you know to bat back and forth acronyms But I think what we're looking what we're seeing now Uh is a movement toward Science and scientists and clinicians and the general public and philanthropy being engaged in this dialogue Which says okay, there are problems in the world depression head trauma uh Psychological trauma ptsd adhd these problems clearly exist The solutions are going to involve behaviors. They're going to involve nutrition supplementation social connection. However There are drugs. There are compounds that can change the brain and allow the brain to change its circuitry through experience and psychedelics are one of of Several others, but one of the you know powerful levers it sounds like and and I just want to say I think the reason I reached out to you and i'm and so excited to sit down and chat with you is because I see very few people inside the halls of academia who have thrown their arms around this Issue of psychedelics in a way and gone through the trouble of trying to find the funding to get it done Gone through the trouble of trying to set up clinical trials. I know what's involved in doing this. It's so complicated So time consuming and painstaking and you've made real progress. I mean you guys are publishing papers There's a new dialogue emerging that isn't just books on bookshelves and And you know psychedelic psycho not gurus on the internet who also play an important role But you're really moving this field forward and I know there are others as well There are colleagues in england and others as well. We'll we acknowledge them But I just want to say personally that I'm like Inspired and impressed by the way that you've gone about this and the level of rigor I mean when I ask you a question about serotonin Most people just kind of kick back to me. Well, yeah, you got receptors and you got a ligand But I mean it's clear to me that you care about the details and that you care about The future of this area and you also really care about these patients and these individuals So I know i'm speaking on behalf of a ton of people now and In the future that don't even know what they're going to receive as a consequence of this. I just want to voice a real sincere Thank you for for that effort. It's like your lab and your work matters and that's A really special and unique. I appreciate that I had a good colleague In fact shared some grant support under the multi-pi system years ago and and she she actually took a job at NIH as a as a as a review officer and I remember her telling me You know and she actually left when she had multiple r01s. So it's like she didn't know Our ones are kind of the the bread and butter big big grants that every Um, every card carrying It's a mark of respect in our community to have a one or several of these. Yeah. Yeah, yeah Yeah, you know and it's like you you eat what you kill in academia gets to what we're talking about later It's like you don't make more money by pulling more grants But you're able to pay the salary that like the university doesn't pay you Your salary your it goes through them You're just able to do more work. Yeah, and you're able to like and if you don't pull in the grants to cover your salary your job can come to an end even if you're Tenured at a place like Hopkins they can do tricks like slowly lower your salary over these so you just let you know Or they just take away your space. Yeah, they put you in a closet and give you no support for trainees and basically make life Hell for you. So you drive a cab in Baltimore and call yourself a full professor at Hopkins truthfully, but you may have no Ability to sure they're out there. But um, but yeah, I remember one of the things this colleague has said who is successful But left on top said I really don't know that I'm making a difference in the world and she did some great memory Research and and and and connected to drugs also connected to aging But she she said I don't you know, I don't I don't feel the impact of what I'm doing in the real world And it's you know, unfortunately there for a lot of academia what we do it stays in the iver tower You know the world is a you know Beautiful but messed up place and like a lot of this doesn't disseminate and and because of the various structures the way the world is set up and thankfully this I mean Because the work that that our group as well as a a few others around the the world over the last 20 years It's like you do have an emerging psychedelic startup industry now with billions of dollars of investment and yeah, that's going to Turn into both good and bad like, you know, it's upping the ante like there's going to be a lot of good and bad that comes from that but Any new technology is going to result in that but We've got psilocybin designated for two separate entities as a breakthrough therapy by the fda and people May not realize in the mda is designated as a breakthrough therapy for m for ptsd This is a really big deal. That's a very high. I mean pharma companies would pay millions of dollars To get their new drug a designation like that and what it means is it is early research is saying it shows a high potential For treating disorders that don't have very good treatments. So We're and we're probably again a few years away from both mda main probably a year or two after that psilocybin being treated for ptsd and Depression respectively. This is you know, we have to wait for the phase three studies But if the results hold up any even if the effect size is like halved of what we're seeing now It's still going to be a lot larger than what you're seeing with the traditional medications And so it's going to be approved if the day to hold up and it probably will from my judgment. So I feel like what i'm doing is actually having a positive impact In the world in a way that and I feel I feel lucky that I got interested in an area that Happens a plug into a place in the world where There is that opportunity where some you know great colleagues and friends are focused on areas where I wish they had the opportunity for their work to be disseminated. I wish that I mean I was lucky to be interviewed on 60 minutes because of this work and i was like, oh my god, I know so many there's a bit of You know imposter syndrome like oh my god, I know so many scientists that deserve You know more so than me to be had that level of exposure but if you happen to be in that place where it You got to do your best to to make it work to take advantage of that luck in that intersection of the world and to push it And you know, I've been lucky but also did take a bit of a leap of Faith early on I did have some advisors that told me like You've got a really promising pedigree early on like are you sure you want to focus Like you're like the psychedelic stuff. You've been you've embraced risk. I mean I think that I mean the world's changed since 2020 certainly but you know channels like social media Podcasts and things that sort you know your exposure is is because people are interested in these topics And that's why people like myself are are interested in Talking to you. I mean, you know at stamford There are now a few labs starting to explore psychedelics more at the mechanistic level, but um so in animal models excellent labs But also I can imagine and because of the pioneering work that you've done at Hopkins. It'll start to become more common I'm certain that people are going to have questions about how to get in contact with you and learn more um If people have trauma PTSD depression, you know, you It's likely that they're going to start seeking ways in which they can potentially participate in clinical trials You're very active on twitter active. I should say you've got other obligations, but where you are active on social media You're active on twitter.

Participating in a Clinical Trial, Online Survey Studies, Breathwork (02:44:23)

It's it's drug It's at drug downscore researcher, right? Right? Right? Okay. So the guner score researcher Um, that's how to find me great account by the way um Matthew and I recently got into a dialogue there about some of the deeper effects of psychedelics and the literature versus how they're being discussed in the general public and um, I follow his account It's a really wonderful account for whether or not you have a science background or not Um, if people are in and i'm going to try and persuade you to be more active on instagram But I don't know if i'll succeed in that try to get my instagram I get it. I'm running a lab too. I get it. You're busy, but but uh, we drug downscore researcher there as well Um, the same handle, uh, your lab at hopkins is pretty straightforward to find through a google search of your name Matthew johnson john's hopkins university are there portals for people to um To explore clinical trials, uh participation in clinical trials of various Yeah, and so in our group so you go to hopkins psychedelic.org That's the website and if you can't remember that just john's hop in psychedelic. Yeah, we will And you're going to find us. Uh, it'll be the first thing that pops up and we have Trust me if we have a study on something, it's going to be on that website. That means Um, he's very being very polite. So I will be a little bit more aggressive and say don't email him directly He won't see that email wait until there's a posting for a study and then sign up through the correct portal And I try to get back to those emails, but frankly and it's a It's because you know I'm lucky the area has taken off so much, but there are many days where I simply get so many You have to do research that I can't get to my day Yeah, if I answer all the so so yeah trust me if there and and something that a lot of folks don't get in being an academia Like we are it's easy to forget how people don't understand. We don't realize this This is experimental research. It's fda approved as an experiment, you know So we're working towards formal fda approval for straight up clinical use But right now someone can't bring me a case of some idiosyncratic thing and Say i'm suffering from this complex constellation Depression and yeah, i'm not a client and even if I was I wouldn't be able to treat them with psilocybin Or or to send them anywhere that was legal to to to to take it You know, so if if we're going to be treating you It's it has to be or anyone else in the United States or most other countries for that matter It's going to have to be under the guise of a very specific protocol this number of milligrams to treat PTSD to treat major depressive disorder to treat Um, you know treatment resistant Tobacco use disorder so nicotine addiction very specific studies. This is not one off treatment You know folks say like oh, I can pay to go out to vultimore if you see my oh my son has this You know complex like in their tragic cases, but you so if you're interested in a study go to our website if it's not on their website You know, we don't have a study on it. There are going to be forthcoming studies So i'm going to be starting studies on opioid addiction and PTSD and an LSD study for chronic pain It the day that those are open for recruitment they're going to be up on our website So that's where you look um to see everything in fact I would just recently a couple days ago put up a couple surveys say is also where we um post links to our survey studies So if you if you've had psychedelics and you've taken them for therapeutic intent intent for PTSD or for depression or anxiety You can find a link and also if you've done breath work for those reasons We have a link for a study of that type up there now, which is a holotropic style Very psychedelic type of interesting of a breathing technique that can lead to some of these Similar experiences so it's up there more broadly outside of our group because there's a growing number of groups in the us doing This re and in europe doing this research, but you can go to to clinical trials.gov And if you look in for the the main search term of of psilocybin or mdma or psychedelic plug in those terms Um, you can get a list of the growing number. I mean, I think there's I think there's over 40 maybe it's been a while there might be over 50 now I don't know but uh studies with just psilocybin going on right now on clinical trials.gov So check out clinical trials.gov to see what's going on, but it's going to be if you're going to do anything legal It's going to be in the context of a very specific study. It's not going to be one-off treatment Right. Yeah, and I should say just and not just legal but also supported in the right framework That you described of having a team, etc. Obviously people will do what they will do and um The scene. Oh, yeah, I will say if people I never encourage people to take drugs of any I don't encourage caffeine use every drug has its risk. You know, I encourage my own caffeine I'm yeah, but nobody else's I'm drinking up right now. This is great. Yeah. This is very strong. Mate is what we're drinking It does not led to a alteration in my perception of of self to the extent that we talked about earlier however This conversation wasn't a good example of how we can enter a perceptual bubble. I learned so much about psychedelics and the future of this for sake of mental health and other aspects of health Mate, thank you so much for your time for your knowledge And I think you put it best earlier for holding the candle in a very dark time and then now There's light. Thank you. Well, thanks for helping to spread that light. I really appreciate what what you've been doing Um, this is a great great medium that you have going on. So thank you for doing it. That's my pleasure Thank you. Thank you for joining me for my conversation with dr. Matthew johnson If you're enjoying this podcast and learning from it, please subscribe to our youtube channel in addition You can leave comments and suggestions for future podcast topics and guests in the comment section on youtube As well, please consider subscribing on apple and on spotify and on apple you can leave us up to a five star review and a comment Please also check out the sponsors that we mentioned at the beginning of today's episode.

Wrap-Up And Supporting The Project

Conclusions, Subscribing & Supporting the HLP, Supplements (02:50:38)

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