Psychedelics — Microdosing, Mind Enhancing Methods, and More | The Tim Ferriss Show (Podcast) | Transcription

Transcription for the video titled "Psychedelics — Microdosing, Mind Enhancing Methods, and More | The Tim Ferriss Show (Podcast)".


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Start (00:00)

optimal minimal this altitude i can run flat out for a half mile before my hands start shaking can i also approach my question now i will see you in a perfect time what if i could be out of the way i'm a cybernetic organism living tissue or a metal anthoscour me tell me ferris show hello boys and girls this is tim perris and welcome to a very bucolic episode i'm sitting outside with the birds and the bees the flowers and the trees of the tim perris show where it is my job to interview world-class performers or world-class experts people who are in the top of their fields and this episode is a panel the panel relates to psychedelic science and it was recorded at the 2019 milk and institute global conference and this particular panel was standing room only there were several hundred seats all filled and then the entire room was surrounded by people standing which was really surprising and also encouraging to me because this is a conference comprised of primarily investors many of the best investors and certainly most lauded and objectively in many respectful CEOs in the world very very unusual to see that type of crowd in that room and a few notes before we jump into it it was a fantastic experience a lot more to share another time on that we have a number of different types of participants in the panel we have incredible scientists we have investors and we also have writers who have experimented with micro dosing and there are a few visuals that are referenced in the beginning a number of slides that are presented you don't really need the slides to understand what is being said and I'm a nerd for the science you will be able to find those slides and links to the studies at with all of the other links to everything mentioned in this episode so if you go to and search psychedelic you will certainly be able to find this episode and find all of the visual references but you do not need them to get the gist of what is being said in the first say nine and a half minutes if you want to skip directly to a first person description of micro dosing and what that is like or what it can be like I should say and certainly not recommending that you do anything that breaks the law wherever you happen to be color within the lines would be my recommendation but if you are curious nonetheless for informational purposes what such an experience is like that comes up around nine minutes and thirty seconds in and without further ado because I do make because I do make for fucks sake I do make much ado about my introductions I do enjoy this very wide ranging and detailed conversation about psychedelics and psychedelic science thanks for coming everyone I'll keep my introductory remarks pretty short but I'd like to begin with a show of hands how many people here know someone who is depressed despite the fact that they take antidepressants anyone?

Understanding The Role And Impact Of Psychedelics

An encouraging psychedelics story (03:25)

alright how many people have anyone in their lives affected by addiction alcohol, opiate or otherwise? alright so the entire audience for both questions lest we start on a complete downer let me give an inspirational story and it relates to Catherine McCormick a name not many people know I'd recommend that everyone look her up on Wikipedia she was born in 1875 in Michigan she was educated at MIT as an undergrad where she lobbied the administration to change a requirement that women were hats with feathers because they were a fire hazard in labs she said very true so they changed that she also inherited a good portion of the international harvester fortune and in 1953 she met a man named Gregory Pincus who was developing an oral contraceptive he had lost his funding because his backers didn't see any profit in sight and over the subsequent years pretty much single handedly financed that development and in 1957 the FDA approved the pill for menstrual disorders so that was sort of the strategic first indication and then later we know what happened and the reason I bring this up is that in total she provided two million dollars of funding and today's dollars is around 23 million over many years and it was an uncrowded bet through which she was able to completely bend the arc of history and I will give some disclosures now so in 2015 I stopped all my early stage tech investing and redirected almost to my entire focus to psychedelic science for reasons that I think will become clear in this conversation and have been very involved with both Hopkins and Imperial which has been incredibly gratifying so with that let me introduce our panelists we have Christian Angadomair, founder of a Pyron investment group we have Robin Carhart Harris, head of psychedelic research center of psychedelic research department of brain sciences Imperial College, London Matthew Johnson, associate professor of department of psychiatry and behavioral sciences, Johns Hopkins University School of Medicine and Iyellit Waldman, author of a really good day subtitle "How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life" so let's begin Matt with some of your slides if we can bring those up and I'll let you take it from here Sure, slide three so really important before we get into the meat of some of our other conversations to let you know that we've been ahead as a field in terms of understanding, being very clear about the risks

The key to responsible research (06:02)

there are downsides so you ask any Jedi knight about the force they're going to tell you in addition to knowing the good side you need to be aware of the dark side and how to keep it at bay, same thing with psychedelics the so-called bad trip is real, there are other risks as well but we published a paper over a decade ago that has now essentially become the bible of how to conduct these studies that's been used by institutional review boards at a growing number of universities and I was at the FDA last week, they are using these guidelines to evaluate novel protocols recently published another paper assessing the abuse liability and risks of psilocybin and thoroughly reviewing the scientific literature and suggesting that psilocybin, which is the active agent and so-called magic mushrooms, if it's approved ultimately through phase three trials as a medicine, that it belongs in schedule four based on the data rather than schedule one so we're aware of the risks, we're paving the way we've analyzed the data in terms of some of the, now we've got the dark side out of the way what's the light side, we can look at some of

Effect on mental health and addiction (07:21)

the efficacy data very quickly, so next slide number four please we published the largest, a couple years ago, the largest study examining psilocybin in the treatment of depression and anxiety associated with a serious life-threatening cancer diagnosis, these are people that are freaked out because they're going to die and this is essentially like the addiction work is picking up on older threads of research largely done with LSD back in the 60s you can, I'll tell you briefly about our results here on the right looking at depression results on the left and then anxiety results in the right panel the left most points on those figures under baseline those are the high levels that people had when they came into the trial and trust me, this is a clinically severe level of depression and anxiety post one, the next time point on both panels the red group has received a high dose of psilocybin, this is not a micro dose this is a very large overwhelming dose, something you don't want to be at a concert on you see a huge reduction into the non-clinical realm these people are not having problems at those lower levels around eight on the scale you do see a good reduction in the people in the blue group and that's a group that to this point has essentially received a psilocybin it actually is a very small dose that you could call micro dose and this trial really just designed to serve as the comparison condition and eventually a placebo so that's probably due to the very careful preparation, the rapport building and also some of the so-called placebo effect at the next time point post two that's a month after everyone has received the high dose so the people who had gotten the trivial dose in the first round they have now also received a high dose now they have dramatically decreased their depression and anxiety so they have not got the group that got it a couple months before and then the really mind blowing thing on the last point in both panels is at six months you see sustained reductions in depression and anxiety six months after treatment from a single high dose session and so in terms of depression there's understandably a lot of excitement around ketamine which is recently approved for the treatment of depression in that it has immediate antidepressant effects that last one to three weeks which is wonderful, get ready because we might be at an even higher plateau when it comes to sustained effects with psilocybin so I'll jump to the next slide these along the addiction angle we decided to do something novel that wasn't done in the 60s one of the interesting things is it appears that this isn't just specific to one drug or another like methadone for opioids or nicotine replacement for smoking but the anti-addiction effects of psychedelics seem to be broad-based they get to the psychological meat of addiction so why wouldn't it work for tobacco smoking? people who tried to quit smoking we ran a small open label pilot we had dramatically impressive results at six months we found that 80% of participants were biologically confirmed as smoke-free breath samples, urine samples you know we trust people but we verify those results held up to 67% at a year and 60% at an average of two and a half years after their target quit date and in this study they had three psilocybin sessions most participants just to tell you how impressive these results are the best medications we have such as varyneclin which is Chantix gets up into the range at six months at about 35% nicotine replacement anywhere depending on the state between 10% and 25% it was an open label study so we had to be cautious the real question is this warrant follow-up and the answer to that is absafracon lutely and so we're in the middle of that randomized trial at this point so this is just a taste of a number of trials that have gone on in the field that are telling the same story that the earlier era of research from the 50s through the 70s showed that there is huge potential of these psychedelics in treating a number of psychiatric disorders thank you Matt I know it let's jump to you because I'd like to contrast or maybe not contrast but add to the scientific discussion the personal discussion and your experience can you talk to how you ended up micro dosing what micro dosing is and what effect it had that's a very big question but I'll let you tackle it so micro dosing is the practice of taking a subperceptual dose of a psychedelic drug I mean you can make it or anything but in this case we're talking about psychedelics so when I say subperceptual I

Effects of microdosing (12:17)

mean you do not trip you do not have a hallucinatory experience you see no kaleidoscopic colors the idea is to take a dose that you cannot perceive of any effects but that there is something going on metabolically so I was experiencing serious depression and I had been on SSRI as I had been on mood stabilizers I had been on various medications and they weren't working effectively and so I decided to try micro dosing I had been a professor at UC Berkeley's law school and taught a seminar called the legal and social implications of the war on drugs during the course of which I read the psilocybin research I read the research that you know from the very from the 1930s on through the present day research and I was I was I you know made sure that what I was doing was safe I made sure that the drugs that I was taking were pure that is the most important issue when drugs are illegal you have no guarantee that what you get when you buy from the illegal market is actually what you think you're getting and I embarked on a 30 day experiment micro dosing with LSD so what I did was I took a one tenth of a dose if you want to say have a hallucinatory experience at Burning Man you're going to take somewhere between a hundred and two hundred micro grams LSD is a very potent drug so we're not talking milligrams we're talking micro grams I took 10 micro grams and I took it every three days and the effect was profound so the first day I had been in a suicidal intractable and hedonic depression for what seemed like forever because when you're depressed you have very little capacity to remember when you weren't depressed and the first day I took the drug I swallowed it early in the morning because LSD is activating and I didn't want to interfere with my sleep and nothing happened so I thought all right well this was a bust and I got to work and about after about 40 minutes or so I looked out my window and my dogwood tree was in bloom and I had this thought oh look the dogwood is in bloom it's so beautiful now it wasn't like the petals were bursting into color and taking off butterflies in the sky but I had been unable to appreciate beauty for months and I saw it and I understood it was beautiful and it made me feel happy and that was an experience that was really mind-boggling over the course of the next period that I was taking LSD micro doses it wasn't like every day was a really good day but many days were really good days and my set point of depression dramatically changed my productivity I wasn't in it for mind enhancement for productivity enhanced but my productivity changed dramatically the book that you can buy afterwards at the bookstore was the first draft of that was written in a month now I've done that before in periods of hypomania but I had never done that in a period of productive calm flow so I became convinced at the end of this experiment that this was a drug that had all the therapeutic benefits that are promised by SSRIs but I often say that if those anti-depressant commercials showed a fat person lying in bed not having sex that would be a more accurate assessment of their effects than a happy lady skipping through a field of flowers and I was a happy lady skipping through a field of flowers That image is messing up my segue but thank you. The microgram milligram difference is very important so please take close note of that.

How psychedelics work (16:48)

Robin let's jump to you next because I really want to get your perspective on plausible mechanisms, plausible explanations for how these compounds do what they do because it's not as though at least in the way they're currently administered in most cases they're sitting in your system saturating your system for say six months after the cessation of smoking. Could you talk to based on our current understanding based on your current research what is happening and maybe you could also touch on the the microbic brain? Sure, okay so the first thing to say is that these compounds are working on the serotonin system an important brain chemical that modulates a range of different important psychological functions we know mood especially but also cognition and states of consciousness and it's a particular aspect of the serotonin system that psychedelics work on in particular receptor subtype it's called serotonin to a receptor and we know from a broad range of different evidences that this receptor is involved in you could summarize it as adaptability, flexibility, plasticity there are a lot of these receptors in the cortex an aspect of brain that humans have so much of and so stimulating these to a receptors appears to at a higher level have an interesting effect on the regularity and the quality of brain activity so we can characterize conscious states in a way analogous to waves when we record brain activity it's very rhythmic and as our conscious states change that rhythmicity changes as we fall asleep or if we're knocked out with an anesthetic or we suffer some kind of brain injury you'll see that brain activity starts to look like sort of slow rollers on an ocean and related to that the richness of conscious experience drops away it's very predictable very steady there's not much going on we know if we look at normal waking consciousness that the waves look very different you know they're much more rapid as much more richness going on what we've discovered with psychedelics is that that richness is enhanced further and that was quite an interesting and novel discovery to our knowledge there hasn't been a state of consciousness found that shows that increase in the richness or complexity of brain activity above the level of normal waking consciousness that's a very mechanistic take on things another way to to look at this that's a way of characterizing the acute experience another thing to emphasize tying this in with a therapeutic work is that the quality of the experience that people have under psychedelics appears to predict very reliably the therapeutic outcomes and so you know these really amazing findings that the drug is well washed out of the body and yet people months on from these isolated experiences are reporting improvements in psychological well-being drops in depression and such like so what's going on there so just quite briefly to talk about the therapeutic mechanisms and perhaps slightly frame it in a in a slightly more sort of human and psychological way we can think of a range of different expressions of mental suffering as being underpinned by biases and beliefs whether it's in depression with negative cognitive biases we think we are worthless and life is pointless or it's eating disorders where we think we're ugly or overweight or obsessive compulsive disorder with those stamped in habits and so that there is this kind of commonality this trans diagnostic commonality that that seems to relate to a very range of broad range of different psychological disorders and what psychedelics seem to do acutely during the experience itself is they seem to relax beliefs and open a window for change for revision and if that opportunity is seized with the right kind of psychological support then you can work towards cultivating the healthy revision of these pathological beliefs and habits thank you and it's worth noting also for people who aren't familiar that if we're talking about psilocybin which in the case of studies is synthesized it's been used in the form of velocity mushrooms by for instance indigenous populations including the mazitex and exco for thousands of years

one could argue very very effectively so there there's a good question we're not going to dive into it right now but as to why almost every civilization accepting a few in Antarctica have used psychedelic compounds and certainly for rights of passage but also with an objective along the lines of these enduring effects that you talk about Christian let's talk about investment in this space and why you're involved I know that you based on our conversation certainly a very sincere interest in making these compounds more widely available to people who are suffering and your biotech company, a Thai life sciences is currently one of the largest investors globally aiming to bring some of these psychedelics including psilocybin back into the legal realm what prompted that and how are you thinking about approaching it? Okay let's start because you're many investors I'm a super coward until five years ago I'm not exactly writing I have never drank alcohol in my whole life and I come from Bavaria in Germany where this is like cultural actually appropriate to do so but I didn't because I was super I was a weird kid so I was super worried that my brain cells could die and so I didn't drink alcohol I've never smoked a cigarette I've never smoked a joint I've never known anything else till I run about six years ago some very very trusted friends tried to convince me of magic mushrooms and I was like you're clearly insane yeah I'm never ever gonna do that till but then they told me a lot about it actually what Matt and Robin said and I do invest a lot in biotech actually biotech is how I started my career I founded a biotech company so I was very inclined to read all the data and the data is very compelling so ultimately you later I gave in it was to to say that as well it was a jurisdiction where it's legal and it was under a very guided and very well set up protected session with a great guide and it was the single most meaningful thing I've ever done and experienced in my whole life full stop there nothing comes closer to it and which is by the way in a lot of studies I think it's a John Hopkins study where I think it was two-third of the people ranked it among them five most meaningful events in their life among birth of a child's death of a parent and I think one third round about ranks it among the single most meaningful thing so because I'm an entrepreneur I came out of the trip the first thing I did I called my parents because yeah I realized how much I love them and I never say it and the second thing is was like this should be experienced by more people and I do think that the only way to do it when we have a lot of we have a lot of anecdotal experience like myself and like I yell at and we have a lot of it's called a basic research but unfortunately never these drugs these various drugs have been brought to the FDA or in Europe it's called EMA sort of life cycle or sort of cycle how to approve any normal other drug you want to use for medical purposes so I was like okay this should be done is anybody doing that and so I'm embarked on the trip in a figuratively word and and met great people like George who founded Compass who had the similar thoughts that this should become a medical drug mainly for the treating of a treating depression and then other mental health issues this is where we are yeah Compass is in phase 2B I'm also back to the company which is bringing our ketamine hopefully on the market which is a sort of sub form of ketamine also for the treatment of depression and we're looking on other psychedelics or wider mental health drugs because I think if you look at the numbers and again investors are very numbers driven the whole mental health area I'm not just talking about psychedelics but as well as completely more or less neglected over the last 30 years because it was sort of the mind is a complicated thing and I farmer companies biotic companies so okay let's focus on cancer let's focus on the more tangible illnesses and also to be fair depression our few on depression and and mental health has changed over the last decades like 50 years ago what we now call a depression people would have said go on with your life go to the gym train a little bit get well yeah when when people came back from the second world war and were showing symptoms what we now would call post traumatic stresses order people said hey get on yeah so I think the the the few on mental health has changed over the last 20 years but also I think we live in a world where mental health is becoming a problem because our world where we live in is very bad for our minds especially for young people if you look at Instagram whatever yeah that whole sort of way we live and we have started living the last 10 20 years I think it's very very bad for for the state of our mind yeah and this is why the numbers rise we have 320 million people suffering from depression and these are just the official numbers and most probably the how you say the gray number is is what's higher it became if you count sort of the side effects like people not showing up at work and stuff like that it became the single most costly illness in the western world and for like 20 30 years there has been no innovation and all the drugs which are on the market are not curing but numbing it yeah and again let's go back to something personal like if if if a person gets very depressive because somebody loved one dies you don't want to take Prozac and Prozac tells you you don't care about the death you want to sort of dissolve it and solve it in a different way and I think this is where psychedelics have a very promising path to be a very valuable drug thank you and we're not going to probably talk about it very specifically today but the efficacy of MDMA for post-traumatic stress disorder is worth looking into and is really remarkable both MDMA and psilocybin now have breakthrough therapy designation by the FDA which is remarkable and if you look at the graphs look at the data for changes in PTSD severity from severe or extreme symptoms to asymptomatic they look very similar to the smoking cessation graphs it's incredible maps as an organization doing great work there

Treating PTSD with MDMA (28:16)

um Littim can I add a point to that is the it's somewhat ironic that I'm the resident drug user because like you Christian I don't do drugs other than these I don't don't smoke I don't like to smoke weed sometimes I take CBD because you know you can't get a macho without it nowadays but I don't like to experience any I like my mind to be sharp at all times but because I was teaching that one of the first sort of people who popularized MDMA Sasha Schulgen a chemist in Berkeley used to lecture to my class and Sasha and his wife Anne who was a therapist convinced me to try MDMA which is ecstasy with my husband as a tool of marital therapy and we've done it every couple of years since we have the strongest marriage of anyone I know we're sort of famous among our friends for having an incredibly strong solid marriage and I do actually we have four kids we have a lot of stress but the what MDMA does and why it's relevant I think to PTSD is it's somehow and these guys can probably talk more accurately to it it disconnects the emotional experience from the memory which allows you to deal with the trauma of memory without the intense overwhelming emotion negative emotional content so in the context of something that isn't PTSD but rather like the you know mundane PTSD of a long marriage it allows you to talk about your issues but from a place of connection and love so every couple years we spend six hours talking about everything that has come up for us from a place of absolute love and commitment and that sustains that one experience will sustain for as long as two years it's really remarkable thank you yeah it's not to delve too much into any current use wouldn't want to implicate anyone but MDMA is worth taking a very close look at there are risks associated with some of these yeah so there are some risks associated with these compounds these are not panacea's they are very effective or appear to be for certain conditions MDMA has certain say cardiac risk in some patients for instance since it is what is it methyl dye actually met them fedamine there is that I'm a beginning the chemical name wrong but then you have risks with say certain other promising psychedelics I began for potentially opiate addiction which I want to ask you about not specific to I began you have in case of ketamine some addictive potential which I've certainly seen and even experienced psychonauts so you have to be careful with how it's administered but the I won't talk too much about this but the toxicity profile of many of the classic psychedelics like psilocybin is is remarkably appealing so would you mind Matt just speaking to the the toxicity or potential toxicity of say psilocybin and also what could you could you speak to based on what you've seen with tobacco and other forms of addiction if you

Potential toxicity (31:41)

think there might be applications to say opiate or opioid addiction sure so for toxicity we can start at the physiological level this is true for psilocybin LSD dimethyl tryptamine or dnt which is in ayahuasca there is no known lethal overdose no dose at which there's any observable organ damage not even a potential mechanism for neurotoxicity that's pretty freakish cannabis is similar you'd be hard-pressed to find anything sold over the counter at CVS Walgreens that you could say this about you can't say it about caffeine aspirin most drugs you can't just take ten times an effective dose and expect to live or to be on on damage so remarkably freakishly robustly safe at the physiological level I would never say any drug is safe period it demand it it depends on what area of risk you're talking about so these are very in at sufficient doses profoundly conscious altering drugs very intoxicating if you will when you see harms they fall into a couple of categories one that's applicable to anybody that takes a high enough dose is what people out there call the bad trip in clinical research we refer to these as clinical experiences as challenging I'm sorry challenging experiences because in fact they can be very helpful themselves going through extremely difficult experiences nonetheless we try to minimize them but out there in the wild so to speak recreational use or what have you and it's certainly a small minority but sometimes an overwhelming anxious state can lead to dangerous behavior someone panics they run into traffic you know it was overplayed in the propaganda of the late sixties but falling from heights it has happened there are various hot rain drugs far more people have fallen from heights when they're drunk but nonetheless it has it happens so in terms of public health this ranks lowest amongst all the other major legal and illegal drugs but nonetheless there is a risk there so nice thing is you can squarely address that in clinical research and potential clinical use through preparation and monitoring it's never it's not take to and call me in the morning follow-up care the other major area of risk with these classic psychedelics is only applicable to a small percent one or two percent of the population who have active psychotic disorders such as schizophrenia or a strong signal for that predisposition and many of the kind of urban legends we may be aware of a folks that took too much of a trip and they never came back it seems very convincing that those folks had a predisposition at least such as you might be familiar with Sid Barrett the original singer of the Pink Floyd and in the earlier era of clinical research with LSD with thousands and thousands of participants the only people that had prolonged psychiatric reactions beyond the time course of the drug were those individuals with that psychotic predisposition it's also very fortunate like the bad trip side that we can squarely address this in clinical research and eventual clinical use they're extremely reliable psychiatric structured screenings that can identify that small percentage of the population that has this risk and then it does modestly raise blood pressure so we can't run people through the research who are at an extremely high level of cardiac risk I mean these are the same folks that might have a cardiac event if they go up several flights of stairs nonetheless that's a real thing and also in the area of risk we documented some systematic effects and increasing the chances of a headache within the day following use typically not in a severe category nothing that we would think would prevent people from using it clinically there's a very rare thing called hallucinogen persisting perceptual disorder extremely rare it tends to be well it's all the data show that it is exclusively associated with recreational use where there's typically multiple drugs including alcohol used and there may be a predisposition there it's never been observed in any of the thousands of participants in the older studies of the current studies so what I'm referring to are you've heard of the term flashback and that can mean many things but that what this refers to is having persisting perceptual abnormalities that severely hamper the quality of life and they're very distressing for individuals and it seems to be that that's it's probably related to a neurological susceptibility where other events not only psychedelic drugs but other medications other events could probably cause the same the same thing but you might have heard that that sort of rounds out the entire sphere of of with the known risks thank you and what about applications to say opiate opioid right and just if I could I'll add just a quick personal note so my cousin by marriage he had a hereditary disposition to schizophrenia and really abused LSD

Effect on opioid addiction (37:33)

all throughout high school and college and it would seem that it expedited the onset of symptoms of schizophrenia although very likely that he was headed there already it just hastened the path so I've seen that firsthand and now on the flip side I've also seen incredible abuse on a personal level that is representative of I suppose a sort of pandemic level problem in opiate abuse so my best friend Long Island died of fentanyl overdose my aunt died of Percocet plus alcohol not too long ago so this is something that's touched a lot of lives in this room are there any potential applications you think or research worth doing it would look at psychedelics and something like opiate or opiate absolutely it's a very promising area there was one study published in the early 70s using LSD with heroin addicted individuals there was you know we needed to do follow up but that was right at the point in society where the rug was pulled out from this research and the research wasn't allowed anymore but nonetheless there was a good initial signal of long-term success and that's part of this formula with I was describing earlier this picture of broad applicability to treat addiction of various types my colleague Peter Hendricks at University of Alabama Birmingham is showing initial positive results in treating cocaine addiction so opioids is an extremely promising area it's something that we want to look at it's an extremely promising area particularly in the midst of what's called the opioid crisis and especially since opioid addiction is resistant to treatment you know we have medication assisted treatments now that are more effective at keeping people off sort of resolving opioid crisis problems but without medication assisted treatment opioids you know this traditional treatments that we think of like narcotics anonymous they are grossly ineffective so our current opioid crisis will not resolve without wholesale accessibility of medication assisted treatments and I believe without really evaluating the potential of psychedelic drugs which is why I actually hope that this crisis might enhance our receptivity to detaking psychedelics down from schedule one which means that they're the most criminal drugs there is no a scheduled drug mean drug schedule one drug means there's no medical use and it's the most illegal drug down to schedule four so what kind of what other drugs do you think of that we could analogize that are on schedule four oh many of the benzodiazepines and the sleeping aids are in schedule four let me let me jump to Robin for a second because I think that we can we can talk about perhaps the broad applicability and perhaps some current diagnostic problems that we may have in psychiatry because if you look in the DSM and we could talk to all sorts of people who have previously been sort of at the head of mental health time insulin others where you have these disorders the psychiatric disorders so-called disorders that are very cleanly separate you have anorexia nervosa anorexia has the highest

On diagnostic categories (40:45)

mortality rate of any psychiatric disorder then you have OCD then you have this then you have that they're all very much side note could you speak to the explain with the default node network is if that's possible just speak to that because part of what is fascinating to me personally is that if we kind of zoom out to 30,000 feet as you mentioned earlier you have this kind of you have conditions associated with hyper rigidity and then you have conditions associated over here OCD anorexia etc these kind of compulsive behavioral or thought patterns and then I have other side you have this hyper fluidity which can be problematic like schizophrenia but can you speak to maybe explain for folks if possible the current thinking around the default mode network? Sure yeah I mean it's schizophrenia also it does have that kind of chaotic components but it also has a rigidity to it as well if you think of fixed delusions and so this is a remarkable thing that gets kind of glossed over in psychiatry that these diagnostic categories while they're there really to aid the clinician that's one view another view is that they're aiding something else perhaps drug discovery and such I can perhaps to some extent a myth that there are these crisp distinctions that have crisp underlying biomarkers that following the the classical biomedical model we can come in with a magic bullet and solve solve a situation and if that was true then we wouldn't be seeing the mental health crisis that we're seeing at the moment prescription rates of psychiatric medications are going up at record levels yet we're not chipping into the problem so you know we do need some kind of major paradigm shifting events here are kind of blacks one event that that really changes things and you know I think our collective view is that psychedelics psychedelic therapy is is that it's this hybrid model that's not just a drug treatment it's more holistic than that it's about managing context giving a drug that produces this suppleness of mind and then managing context to try and move people out of the kind of you know entrenched ways of thinking and and behaving into something broader and more open so the default mode network is in a sense you could say it's the most it's the strongest candidate that we have in the brain for what you might call the biological substrate of the self or the ego it's a system that engages when we disengage so to speak well we disengage from attentive focus but we enter a kind of daydreamy you know internal imaginative state but this is very much tied in with with self and and the narratives that we build about who we are that we start to believe in a kind of absolute way that guides and drives our behavior but can be so narrowing you know ego sees narrow and short and what you see under psychedelics is that this network breaks down it literally albeit temporarily disintegrates and people see broad and they see the bigger picture analogous to the so-called overview effect you know that astronauts have described when they are up in space they look look back at the whole of the earth and then they can put things in perspective and think you know why was high squabbling with my wife or my work colleague and you know it's about seeing that that bigger picture so here you know we've got this opportunity through brain imaging to start to put a bit of meat on the bone you know to help you know lift the lid on this black box that's the brain and start to show people that this isn't magic it might feel like magic psychedelic therapy but it rests very firmly on nature on biology and I think it's useful to to add that to the conversation and help kind of ground the conversation about about psychedelic therapy yeah one point because both are yellowed and and Robin just touched something important where this group of yellowed and a group of Robin that most psychedelics it's not true for all of them but are a very holistic treatment so partly the setting and the guide and however you experience is equally important so why this is my opinion especially for example on magic mushrooms that yes they should be available as a medical treatment but not over

Prescription vs. over-the-counter (45:48)

the counter this is nothing somebody should do alone especially when you're depressed and by the way we all I think one risk is that most people very passionately like all of us talking of psychedelics we're not depressed and it's a different experience when while when you read observations of treatments of depressed people they might go through it's called it catharsis or to to a challenging they might have a challenging trip nevertheless the trip is healing them and and the guide is very important so this is why I just want to add that yeah I personally think yes it should be available as a medical truck this will be working on but it should be available under professional care like with psychiatrist or in clinics but not over the counter definitely not over the counter I know I agree with you entirely you know my book I have a whole sort of chapter about paradigms for decriminalization and you know my ideal paradigm for for psychedelic decriminalization would be for lack of a better word the psychedelic spa where you would check in and get that buttressing because in all drug experiences but particularly in psychedelics the set and setting as you say

Decriminalization and the psychedelic spa (47:04)

are critical set is what you bring to this experience and setting is the setting in which you experience it so like you know the canyon ranch of psychedelics with fit with you know licensed trained support team I'm not sure you have to be a therapist per se but someone with experience and training in supporting an individual ideally with preparation both before and after which is not to say that I think all people require that but that is that is much more likely to engender a positive response an interesting number is the Netherlands it is legal you can access psilocybin

Regulation And Decriminalization Strategies

The Netherlands problem (47:59)

magic mushrooms in the Netherlands legally in coffee shops and the Netherlands have the same mental health crisis than every other country in the world so just the fact that psychedelics are available yeah unfortunately do not change the mental health crisis is really like the professional and if I experience it with people like I would look at my parents or or friends with depression they not making that leap they rather go to their doctor because they trust them and then the doctor should be the one who's also administering that so I'd like to touch on something you said actually but that we've sort

A sustainable business model (48:39)

of covered in a few different ways but offer a framing that I think is helpful and that is that rather than think of good or bad trip think of safe or unsafe trip because the in many cases the difficult experiences are when you see the truths you prefer not to see and you look at the behaviors that may be in your blind spot and that can be very uncomfortable as in the case when a smoker's like wow that's disgusting I saw that I'm killing myself and they have to look at that hard truth difficult but safe and that depends a lot on the context and the providers and and so on a question for you Christian how do you think about creating business models around compounds that can be so effective with a single dose or two doses because I know you want this to be available to a great number of people that requires a sustainable model of some type and there are many different ways to approach it you know maps has one with say a B Corp that does drug development then there are for-profit options how do you look out for temptations like taking something it is so effective with one or two doses and create creating something that requires a maintenance dose multiple times a week is it the therapeutic wrapper that kind of spa elements and context around which you build a business how do you think about that well first and meaning that sounds maybe cheesy or I was saying English but like if you're investing in biotech you really want to make a difference because I do I would take investments and I'm always very happy about biotech because if you succeed in bringing a drug to market you really make a difference in the world so so I think it's not I think this is a little bit the most that everybody thinks biotech investors are like evenly plotting how to make the most out of it at least this is not how I think about it like we want to cure people and hopefully we're gonna make that happen the second the market is so huge meaning I said we have 320 million people and most and the number is rising and I think there are more people who are not diagnosed so so even if and I would be very very happy if it's a single dose to the side which is which is helping those people even if that's the case the market is is huge yeah then you have the decide business models or the as I said the spas and the the clinics you can build up yeah because it is all about the holistic thing and and then even and we don't know yet meaning for a lot of things we also have to say like we have very good indications but we don't know yet what is the right dose this is for example what compass is trying to figure out at the moment it might be yeah and I'm not saying that because it should be like commercially but it might be that you say oh if somebody was depressed you should do it every year again we don't know yet we try to figure that out yeah but there is enough business and I think in general like even if you go aside and look at meditation at like calm for example like I think the whole mental well-being like treating people who are ill have mental health issues but also keeping people healthy yeah in our current environment and and this will get worse my personal theory is that that our brain has like an in-built actually resilience or like an immune system which is based on faith love and and purpose and if you look what our world is happening we take these three things away communities are dissolving families are dissolving so you have cheesy this at a little bit less love in the world yeah yeah then most people know that the world will look so different in 20 years that that they don't have a purpose anymore the bus driving the bus that in 20 years most likely his bus will be driven by an artificial intelligence yeah and and then we have a dramatic loss of faith in every sense like religion and in in any spiritual dimension and it all will make people more impressive so so I think you said the market is growing so I'm not worried about about how often you have to take it okay market is growing for better for worse now I'd like to come to you first all this I'll make another personal note and try not to directly implicate myself here but so my family has a on both sides quite a bit of severe depression

How to reclassify psychedelic drugs (52:54)

and I'd say every six months or so as an adult I've had a major depressive episode almost killed myself when I was an undergrad at Princeton I've written about that if you guys want to check it out in the last five years I haven't had a single major depressive episode and here we are on this panel I'll let you guys draw your conclusions not to say that that is going to be true a hundred percent of the time but given the fact that in one could argue that there've been incredible advances scientifically and cardiology and neurology all these various fields and then you look at psychiatry and there's been very little I mean aside from SSRIs some time ago and now ketamine which is very interesting I think for acute suicidal ideation and chronic pain especially but there's there's very little that has happened and so I'm I'm very very vested in this space math the reason I wanted to come to you next is that you mentioned schedule one and schedule four one question that people might have on their minds is well wait a second if these are so great if they have such low toxicity how did they end up in a category schedule one which is no known medical application high potential for abuse among other things which of course based on the data I disagree with but like how did that happen and how do we get out of that and I'll just say one more thing because we're running short on time which is you know my not so secret agenda is to set the conditions over the next three to five years with private philanthropy and so on so that I can then work separately to try along with other people to help get federal funding for this stuff which is not currently forthcoming so how did we get to this very difficult and expensive position of operating from schedule one and how do we potentially get out yeah this the quick answer is that psych that it was really because of the association with the counterculture and everything associated with it in the late 60s early 70s and I would say that that the culture was essentially traumatized from that kind of early introduction of psychedelics and and their work casualties when they were used broadly there are also plenty of people said it changed their lives for the better and they're still here to talk about that but this this came about right at the time when the federal framework for controlling scheduled drugs the controlled substances act was being developed and there is no there are some flaws in that system there is no category for example of having no accepted medical use but mild to moderate abuse potential you know you jump from having no accepted medical use and high potential for abuse in schedule one to schedule two something like cocaine or methamphetamine which are schedule two as as having high high potential for abuse but some accepted medical value in those two drug are used medically and are approved so there's really no framework now you know psilocybin the language is important here it we squarely know at every level of science the defects in the mezzolimbic brain structures involving dopamine the epidemiology reliable animal models of reward we know that these aren't drugs of addiction solidly but they are they can be drugs of abuse and that simply means using a way that can can harm you or the people around you so you know couple teeny teenagers go out driving on mushrooms that's abuse or you get into a pattern of interviews with your family relationships etc so they really don't belong in the again the controlled substances act is is rather ambiguous you know they refer to abuse potential which can include addiction potential but also other risks so they do have risks you could argue they have you know these classic psychedelics mild abuse potential but the other side of that is there's there's no accepted medical value when the controlled substances act was originally adopted it wasn't clear what that really meant and through judicial precedent it became solidified that that what that means is FDA approval for an indication so that's where we're at now so until one of these draw until psilocybin is approved for an indication it's going to by definition remain in schedule one what are the most promising indications currently or those that are furthest along based on the data on the most promising indication would be depression and anxiety you could call it psychiatric distress associated with a life-threatening cancer diagnosis that's what the most modern most advanced research with psilocybin as a therapeutic has been focused on there's three randomized studies in that category and then secondary to that sort of as a class are psilocybin in the treatment of of smoking cessation as a smoking cessation medication I showed you some data treatment of alcoholism a colleague Mike Bogan shoots it in why you has done some great work with that and and then Robbins published work on depression outside of cancer so all of those those three things have been those are published results with open label non-randomized pilot study so they all look very promising but they haven't gone the published data hasn't reached that level of you know large randomized trials yet all of these disorders are associated with being stuck in a narrow mental and behavioral repertoire and as Robin suggested I think that's why we're seeing efficacy with these nominally different disorders psychedelics have a way to blast one out of that narrowed mental repertoire thank you I I where would you hope what would you hope this this field that is probably speaking psychedelics to look like a few years from now do you have anywhere you'd like to see it wait you know because I went I was a lawyer and I I was a criminal law professor and so I think through this criminal justice lands and I remember

Looking Forward: Future Prospects

Hopes for the future (59:16)

a period where decriminalization of marijuana seemed incomprehensible we first started working and I was working with the drug policy Alliance on state initiatives to decriminalize marijuana it seemed remotely possible that in some very liberal states you might have a medical model and absolutely impossible that you would ever have a recreational model and I don't know about you guys but I've been to these pot clubs which are like Apple stores and the bud tenders are you know showing you weed that in my lifetime as a teenager in New Jersey I never saw anything approaching so there is a kind of their their the shift is possible I think we could see a medicalized model specifically for psilocybin the reason that this research is happening in psilocybin and not LSD is because of the sort of fear associated with LSD but they operate wouldn't you say Matt almost identically in the brain so I think we will see over the course of the next decade a and maybe even less a shift to a medical approach maybe maybe changing the schedule or maybe on a statewide basis having this as we did with marijuana marijuana still schedule one federally it's still a crime federally but we have different model state by state and I think that we are a long way from a decriminalization model for other for drugs generally but I do think psychedelics because of the research that these gentlemen are doing does have great potential for medical applicability and I actually think what can drive that more effectively than anything else are the individuals in this room and others like this which is why I'm speaking to you and I imagine that's why Tim is here as well maybe the rest of the panel because what we need is a model of investment and corporate pressure to change laws I mean that's the way it works in America when there is a wave of capitalist interest it's a lot easier for laws to change so we are up on time closing comments real quickly check out the research this these are not panacea but they are the most exciting thing that I've been focused on for the last several years it's worth looking at you have a chance if you're interested in being on playing field at having a Katherine McCormick level of impact it's a big deal so please take a look check out everybody on the panel and I yell it and I will be doing book signing over there there are a couple chapters and tools of Titans on the psychedelic stuff as well and thank you all for coming and ladies lady and gentlemen thank you for that hey guys this is Tim again just a few more things before you take off number one this is five bullet Friday do you want to get a short email from me and would you enjoy getting a short email from me every Friday that provides a little morsel of fun for the weekend and five bullet Friday is a very short email where I share the coolest things I found or that I've been pondering over the week that could include favorite new albums that I've discovered it could include gizmos and gadgets and all sorts of weird shit that I've somehow dug up in the the world of the esoteric as I do it could include favorite articles that I've read and that I've shared with my close friends for instance and it's very short it's just a little tiny bite of goodness before you head off for the weekend so if you want to receive that check it out just go to four hour work week dot com that's four hour work week dot com all spelled out and just drop in your email and you'll get the very next one and if you sign up I hope you enjoy it. you

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