::::::::Psychedelic Medicine ::::::::::::::::::: From Tradition to Science:::::::

  Greetings. Welcome to you all. My nameis Leo and I am visiting your fair city from Marin County, California just north of SanFrancisco. To begin, I thought we'd try a little experiment in holding space to seeif we might deepen our sense of connection as together we ready to explore, to seek throughscience some understanding of medicines held by tradition as representing the deepest ofmysteries. With your permission, I'll guide you through a brief meditation using toolslong understood as central to psychedelic journeying, breath and sound. I invite youto come fully into this moment to close your eyes to trust that you, that we, are rightwhere we need to be. Here, nowhere else. With eyes closed, bring your attention inward toyour breath, filling your stomach with oxygen. Slowly inhale and exhale releasing all worry,every concern, inhaling, exhaling simply breathing trusting that all is well. Feeling your chairholding, supporting, enabling you to relax to let go as you continue to breathe. Withyour eyes remaining closed, if you have had personal experience with psychedelic medicine,administered either clinically or taken ceremonially, please raise your hand. Hmm it's nearly halfof the room. Thank you. Please lower your hands and open your eyes. I welcome you toPsychedelic Medicine: From Tradition to Science. What do we mean by this from tradition toscience? There is a long section in Michael Pollan's remarkable new book, referencinghis conversation with the eminent research scientist, Dr. Roland Griffiths of Johns HopkinsUniversity. A pioneer in psychedelic research, Dr. Griffiths trained in behaviorism His Schoolof Psychology ultimately dismissive of subjective experience. From this unlikely entry point,Dr. Griffiths has emerged as a champion of the undeniable potency of the phenomenologyof psychedelic experience as quote "so profoundly reorganizing and profoundly compelling thatI'm willing to hold there's a mystery here we can't understand." "You go deep enoughand far out enough in consciousness," he says to Michael, "and you will bump into the sacred.This reliably happens to believers as well as non-believers" My personal and professionalinterest here is to advance the paradigm and healing modalities of transpersonal psychologyfounded some 50 years ago by Dr. Abraham Maslow, Stanislav Grof, Anthony Sutich, Jim Fadimanand others. Basing its theoretical frameworks on the studied observation of patients innon-ordinary states, plus respectful engagement with Eastern spiritual philosophies and globalindigenous traditions, transpersonal psychology recognizes the power and primacy of first-handspiritual experience in the treatment and nurturing of psychological health. Indeedtradition approaches psychedelic medicine through the profound subjectivity of spiritualexperience. Certainly, we've lost this perspective in mainstream medicine. Science, of course,demands the objectivity of clinical research rightly pursuing agreed-upon standards ofefficacy and safety. As we explore psychedelic medicine as potential remedy to the egregiousstates of mental health in America, we have an opportunity to do so in the spirit of rapprochementbetween tradition and science. As we move further into this current psychedelic renaissance,we might hope to do so with respect for the wisdom that tradition and science alike bringto the endeavor. Thank you all for being here today. For the 1,000 plus of you watchingonline,. Thank you, to the Harvard Brain Science Initiative, the Harvard Medical School, theMultidisciplinary Association for Psychedelic Studies and our host the Broad Institute ofMIT and Harvard, for making possible this gathering today. And I'd like to say a veryspecial thank you to Delara Chizari, a PhD candidate here at the Broad Institute, whoseefforts have been absolutely instrumental in bringing us all here together. Thank youand Delara. - Thank you for the kind introduction, Leo, and hello everybody. For over 7,000 years,psychedelic plants have been used by various indigenous cultures in ritualistic healings.I'll let you sit with that for a second... So, this contrasts pretty sharply with theSchedule I categorization of those same substances in the United States. As a neurobiologist,I was very intrigued by this and looking more deeply, I learned that there is a large bodyof psychedelic research from the 50s and 60s that have been largely forgotten. Over thepast decade, research on psychedelics has reemerged with leading institutions includingJohns Hopkins School of Medicine and the MAPS foundation. Their findings have illustratedthe potential of psychedelics, both as therapeutics and as tools to study different states ofconsciousness. Research in psychedelics has also highlighted the role and the power ofcontext and experience in healing--something that has often been underutilized by conventionalWestern medical practices including psychiatry. This understanding and the growing body ofresearch has been impossible to ignore and yet, as undergraduates and even as doctoralstudents in neuroscience and in medicine, the amount of education that we get in thisarea is almost non-existent. Over 500 scientists here at the Broad,Harvard Medical School andMIT expressed interest in attending our event today. There are many of us who want to learnmore and discuss this topic. So, I'm standing here today in the hopes that we can once againcreate space to talk, collaborate, and consider research initiatives in this area. Last Ichecked, there are also at least 1,000 of you who are watching online and thank youfor joining us. Both the live audience and online participants can ask questions andupload questions by visiting slido.com and use our event code 4008. Without further ado,I would like to, very briefly and incompletely, introduce today's speakers, seven of the leadingfigures in psychedelic medicine therapy and storytelling. First, we have New York Timesbestselling author, Michael Pollan. His most recent book, How to Change Your Mind, takesa deep dive into psychedelics, its history, research and the personal experiences of patients,scientists and even his very own. Next is the founder and executive director of thenonprofit MAPS Foundation, Dr. Rick Doblin. He brings unmatched expertise in the legalizationof psychedelic medicine and has been working for decades to develop medical, legal, andcultural contexts for people to benefit from the careful uses of psychedelics. Most recently,the MAPS Foundation has achieved the landmark of phase III clinical trials for their testingof MDMA-based therapy of post-traumatic stress disorder in veterans and other trauma survivors.Next, Dr. Anja Loizaga-Velder, is a Mexican-German psychotherapist and an adjunct professor atthe National Autonomous University of Mexico. She's also the director of research and psychotherapyat the Institute for Intercultural Medicine, Nierika. Her remarkable work involves collaborationswith indigenous healers to investigate the therapeutic potential of the ritual use ofpsychedelic plants. Next is Dr. Matthew Johnson from Johns Hopkins School of Medicine. Dr.Johnson is an expert on drugs and addiction and risk behavior, having published over 100articles and chapters. For over 14 years, he has conducted psychedelic research includingpsilocybin studies of mystical experience, meditation, and cancer-related depressionand anxiety. He and his colleagues at Johns Hopkins are leading a new era of psychiatricmedicine in the United States. Most recently, they have proposed that psilocybin be changedfrom a Schedule I drug to a Schedule IV due to its high therapeutic and medicinal potentialand its low toxicity. Next is Dr. Franklin King. Dr. King is an attending psychiatristand clinical research fellow at Massachusetts General Hospital and an instructor in psychiatryat Harvard Medical School. He's pioneering a new research initiative at Mass Gen to studythe clinical use of psychedelics. Our panel will be moderated by Dr. Julie Holland. Dr.Holland is a psychopharmacologist, psychiatrist and author with a deep expertise in drugsand behavior. She was also an assistant clinical professor of psychiatry at the New York UniversitySchool of Medicine and since then, she has been the medical monitor for multiple therapeuticstudies involving MDMA and cannabis in the treatment of PTSD in American veterans andother trauma survivors. Last, but not least, here with us via video-conference is the headof psychedelic research at Imperial College London and soon to lead a similar center atOxford University. He will begin the afternoon with a brief keynote lecture on our understandingof how psychedelic therapy actually works. Please welcome Dr. Robin Carhart-Harris. - Thankyou everyone and thank you Delara it's a real pleasure and privilege to join you. I justreally wish I could do it in person but I was committed to a couple events in Canadawhere I am right now. Sat in some offices in Vancouver so sorry I can't be there inperson, but I'll do my best from however many miles away I am at the moment. And what I'dreally like to do to contribute to this event is to provide the background and an overviewabout the brain mechanism the therapeutic mechanisms and psychedelic compound. And hopefullythat'll provide some useful material for the subsequent discussion and also to help groundand I think perhaps naturalize this phenomenon firmly in the scientific and medical domain.So let's start very simply with some basics. What are psychedelics and what does psychedelicmean? Well it's an neologism, a made-up word, that combines two words psyche the soul ormind and delos which is referring to making manifest, making visible. And so we combinethese words as Humphry Osmond did in the 1950s to denote the key property of these compoundswhich is to make the mind visible, to make manifest aspects of our minds that are ordinarilynot fully conscious, not fully accessible to conscious awareness. Another way we canthink of psychedelics is to provide you with some examples of classical psychedelics. Wehave psilocybin here found in the psilocybin species of mushrooms, so-called magic mushroomsand it's pro-drug of psilocin which we'll see in a moment works on the serotonin systemin a particular way. And really that's where the initiating effects of these compoundsbegins. sumatryptamine that can be taken intravenously or smoked we give it intravenously in ourresearch. It's also included in the Amazonian Peru ayahuasca where the DMT is combined witha vine that contain inhibitors of certain enzymes that otherwise would break down theDMT. So it's a way of rendering the DMT orally active and then we have LSD the prototypicalpsychedelic that really kicked off the modern wave of Western scientific interest, significantinterest in psychedelics discovered in 1943 famously by Albert Hofmann. And then thingsreally starting to gain traction into the 1950s 60s and then there's another story tobe told about them about how these compounds fell out of favor with the medical and scientificestablishment. But what unites these compounds as well and perhaps critically and most concretely,is their pharmacology. These are tryptamine psychedelics that work on the 5-hydroxytryptaminesystem, the serotonin system, 5-HT. You can see that their molecular structures sharestrong similarities with that of the naturally occurring neurotransmitter neuromodulatorserotonin and that's offer hints really about how these drugs are working in the brain.They're mimicking serotonin. They're kind of hijacking the serotonin system and they'restimulating a certain aspect of that system. So what aspects of the serotonin system arethey stimulating? Well serotonin itself, it should be said, is a particularly complexneuro modulator. It has at least 14 different receptor subtypes which when stimulated naturallyby serotonin do quite different things. Some of these receptors actually counteract theeffect of each other but there's one particular serotonin receptors that we now know withreally quite a high degree of confidence, appears to be critical to the action of psychedelics.We know this because if we block this receptor by giving a compound what we call an antagonist,a blocker, that's relatively selective to this receptor, selectively block this receptor,then we give a psychedelic, whatever the psychedelic whether it's LSD, psilocybin, DMT, effectivelyyou'll abolish the characteristics, objective and behavioral effects of that psychedelic.Just one of these is really important grounding principles about the science of psychedelicsthat this serotonin 2A receptor subtype is so key to the action of these psychedelicsand it helps bring everything back down to earth. If you block this receptor all theincredible, fantastical, psychological effects of these compounds just don't happen. So Ido think it's a very important principle. Where are these receptors? Well they're heavilyexpressed in the cortex that aspect of our brains as humans that's so massively expandedin our species and really defines us in terms of how our brains are different from otheranimals. And more than that we now know through recent, relatively recent advances in brainimaging that the 2A receptor is most heavily expressed in the highest level aspects ofthe cortex. So these are aspects of the cortex that subserved really quite high-level functions.Things like imagination, things like self reflection, reflecting on ourselves, reflectingon our path, our autobiographies. Also contemplating the future perception, so imagination. Thesekind of functions that are arguably species specific that humans do to do quite an exceptionalextent. That's where you'll find these key receptors. The psychedelics work on most heavily,express. We also know that the affinity, say the finding potential the stickiness of psychedelicsfor this particular receptor subtype correlates very strongly with their potency. So for exampleLSD, very high affinity, very potent, you only need a very small amount of that compoundfor it to have psychedelic effect. And then this other follow-on question which of courseis critical let's treat it as a low level first. What does serotonin 2A receptor agonism,that means activation, that means stimulation, what's a serotonin 2A receptor stimulationdo? Well we now know quite compellingly that it seems to promote a generalized plasticityboth at the level of anatomy, low level anatomy, in terms of growth of new neural connectionsbut also functionally as well, promoting a flexibility of mind, cognitive and behavioralflexibility. And take it to a higher level, promoting things like divergent thinking,a certain aspect of abstract creative thinking. So that's where we are. And to contextualizeall of this and now where we are in terms of the therapeutic development let's justrun through a brief history of developments in psychiatry and psychopharmacology. We hadthe monoamine oxidase inhibitors arriving in the mid-1950s, a key moment in the so-calledpharmacological revolution in psychiatry as drug treatments begin to really gain tractionand influence. But the pharmacological action there is quite broad. We have a drug that'spromoting not just serotonin but other important brain chemicals like noradrenaline or norepinephrineand also dopamine. Then we have the SSRIs coming along in the 1980s. Drugs like Prozac.And starting to make another significant difference, drugs that have somewhat less of the problematicside effect profile and crucially are more specific in their action. Instead of promotingthe availability of monoamines in general all these different chemicals, they're promotingthe availability of a specific neurotransmitter and that's serotonin 5-HT. And now we're goingfull circle and coming back to looking at psychedelics seriously and it's importantto reflect here that here we have a class of compounds where granted their pharmacologyisn't always selective, they can stimulate other brain stem brain neurotransmitter receptors.But we know importantly that the 2A receptor is key. So we can consider this is kind ofprogress in the precision of the pharmacology of a particular drug intervention. But itwould be wrong to characterize this as just a drug of course and let's again just runthrough how things have developed in throughout the 20th century in terms of psychiatry, psychoanalysisand death psychology dominating the first part of the 20th century. The pharmacologicalrevolution coming along in the 50s and now we find ourselves again full circle consideringan intervention that involves a drug but a drug that opens a window of plasticity, awindow of flexibility in mind and brain in which psychological interventions may wellbe much more effective. All these developments have helped us understand something importantabout serotonin itself, I would wager. Though in terms of what serotonin does that's beena mystery for quite some time in psychopharmacology. Unlike with other important brain chemicalslike dopamine where we have a slightly firmer footing, thinking of this compound in relationto reward and value related are a surprise. Serotonin has got people scratching theirheads for quite a while and ideas of course have been raised. The idea that serotoninworks to moderate stress has been very influential. That it can moderate negative affects particularlyfor example dampening the responsiveness of an important fear system in the brain theamygdala for example and also that it aids patients that it works against impulsivityhas also been gaining traction. But some recent work that's really interesting me is thisnotion that serotonin has an important interaction with environmental factors. So for examplegenetic work showing the certain variance in certain aspects of the serotonin systemonly really kick in and have a significant effect, given certain environmental conditions.So for example childhood adversity and then certain genes being associated with mentalor mental health outcome. Also the work of the likes of Igor Branchi, who's coined thisterm the double-edged sword of plasticity in relation to serotonin that if you increaseserotonin levels as you might with an SRI, for example, a Prozac-like drug, you won'tnecessarily then choose a positive mood but rather you make people more sensitive to context,more sensitive to their environment. If that environment is favorable then they may dowell, if you for example up the dose of an SSRI but if it's adverse they may do actuallyworse. So it's an important nuance in how we're thinking of serotonin and I would addas well it's helping us understand this certain aspect of the serotonin system that the serotonin2A aspect. And saying more specifically that it's perhaps stimulation of this particularreceptor that accounts for that interaction between serotonin. Now I'll just run throughhere an overview of the recent clinical work that's been carried out with psychedelics.So we can look at the safety profile of these compounds that they're non-addictive, thatanimals won't self administer them, that they have low toxicity. We think of a compoundlike psilocybin, a very low physiological toxicity, much lower than ketamine for examplethat's starting to gain traction as a rapid acting antidepressant. Also the antidepressantsand other therapeutic effects appear rapidly, very quickly, and also that the effects appearto be enduring something that might confer a significant advantage to classic psychedelicsover an intervention like ketamine. And then these significant improvements in well-beingthat were really brought to the fore by the the Hopkins team giving a single high doseof psilocybin to people who've never taken a psychedelic before and then seeing theseremarkable enduring increases in psychological well-being that appear to be mediated by thequality of the experience that people had under the psychedelic. Also drops in suicidality,something that we've seen in our clinical trial when looking specifically at this particularcomponent. And then population studies, the likes of Peter Hendrix looking at suicidalityand psychological distress in a very large population of people, close to 200,000 individuals,carrying out surveys and finding that psychedelics counts as an anomaly in the sense that thosewho had used psychedelics actually had better mental health outcomes than those who hadn'tand that's of course is an incredibly challenging finding in that it contrasts the associationthat we tend to make with other drugs of potential misuse. And there the rule is quite reliable.The more you take of these drugs, the worse your mental health outcomes. Classic psychedelicsappears to buck that trend. And so there's the first significant study that kicked offthe wave of modern controls trials, clinical trials with psychedelics occurred in 2006.It's a study looking at psilocybin for OCD, very small study, but finding promising effectsthere. But really the significant work has been looking at end of life distress, anxietyand depression outcomes. Charlie Grob at UCLA kicking this off, publishing in I think 2011,a crossover study, placebo control, showing significant effects with single, I think,treatment session with psilocybin, a significant improvements in depression scores at six months.And then we have the recent studies. You have Peter Gasser with LSD and then we have therecent studies from NYU and Hopkins, published in 2016. Very nice design for placebo controlledstudies with control compounds that have a degree of activity to them. Niacin in theNYU study and a very low dose of psilocybin in the Hopkins work. And so things are startingto really look quite exciting at this point and the addiction work, Matt Johnston lookingat smoking addiction and remarkable outcomes there. 80% abstinence rate I think is it twelvemonths, I think, Matt could correct me on that, after I think two treatment sessionswith psilocybin. These are really remarkable outcomes in the context of leading treatment.Michael Boganschutz looking at psilocybin for alcohol dependence again very impressiveoutcome. We've looked at depression, we looked at particularly severe depression treatment,resistant depression. People who tried on average 4.5 different antidepressants thathadn't worked. 90% of the sample that tried some psychotherapy of the multiple differentpsychotherapies had a couple of patients who tried 11 different medication, average durationof the depressive illness, they reported to be over 15 years. So really quite stubbornintractable depression and yet we saw really quite significant improvements appearing rapidlyafter two treatment sessions with psilocybin a week apart. A low dose 10 milligram followedby 25 milligrams a week later juxtaposed with psychological thought preparation. Of coursecare during the experience of music and such like and then integration work afterwards.We've seen very large effect sizes with this intervention, Cohen's d values of 2.3 at fiveweeks. And so enough, even though a major limitation of this study with its open labeldesign, there wasn't a control condition so we can't say with confidence that this isimpressive effects, I choose specifically to psilocybin that might seem the obviousinference but you know there's a lot of other things going along the psychological supportand such like. But even so it's enough to deserve further research and that's wherethings are going now. So our next trial at Imperial, we'll be comparing two treatmentsessions with a full dose of psilocybin 25 milligrams again with psychological supportsinside and throughout against a leading SSRI escitalopram six weeks of escitalopram orthe two treatment sessions of psilocybin with controls for all the different aspects likeplacebo captions every day, controls for escitalopram captions for example. Now things aren't justyou know sitting in this domain of a lot of promise and hopes for investment to come in.That investment is coming in now. So we have a company based in the UK investing heavilyin psilocybin treatment resistant depression, a multi-site trial across Europe startingquite soon in communication with regulators also conversations going on with a few organizationswith the FDA as well. So things are really started to gain traction. So that's wherewe are and given all of this it's very timely and appropriate that we have some kind ofmodel to address this potential question of how this treatments working and you'll havenoticed that there are multiple indications here. So it's not just depression, it's notjust addiction, it's OCD and potentially other indications as well, eating disorders perhapseven phobia. And so is there something a kind of unifying principle here perhaps that mighthelp us understand how one particular intervention might be effective for a range of differentdisorders. Well first we can start by thinking, well maybe there's a common ground among thesedifferent disorders. And one way we might think of that is to take inspiration froma leading model arguably the leading model of how the brain and mind works. The so calledpredictive processing model. This is a model that tells us that our interactions with theworld involve essentially two players in some sense. The predictions of beliefs that wehouse in our minds, has to begin with and then what we experience. And that if there'sa mismatch, we will then update our beliefs. But the key principle here is that it's ourbeliefs that very much dominate how we experience the world. It's really the kind of bottomline. It's not that we have a direct line to reality so to speak. So much of our experienceof the world comes from these mental models that we house in our brains. We know thatthrough a lot of different things like optical illusions for example. Why do we see theseoptical illusions if it's not for the the models that we house in our mind. And so inthe context of psychopathology, we can think of this process going awry, we can think aboutbelief becoming to influential, resistance to updating based on evidence, becoming veryrigid and stuck and then dominating our thinking and our behavior. It's very easy to thinkof that in the context of depression for example with a negative cognitive bias where we seethe world through these very pessimistic eyes. Then eating disorders where we have thesebeliefs, you know, that we're overweight or we're unattractive and phobia again theseirrational beliefs that can become so rigid. So given these conditions you know what mightbe a solution? Well it stands to reason logically that if we could only revise those beliefsthen we might really have some. But in order to revise belief we need to be able to relaxthem initially and so how do we do that? Well like I said at the beginning, we now knowwith confidence that the serotonin 2A receptor is key to the characteristic, the signatureeffects of psychedelics. It's the initiating event. But then there's this is other curiousquestion. What goes on afterward? Now some people will tell you that it's mystery, perhapswe'll never know. I tend not to agree with that. I don't think psychedelics work in anysupernatural way. I don't think they work by magic. I think they work based on the lawsof nature and that we can naturalize this phenomenon, we can demystify this phenomenonand because of that make the best use of these compounds. And so what happens when you stimulatethe 2A receptor? Well I said it induces this window of plasticity, I've described it elsewhereas an entropic state. You can think of this in relation to temperature, how you can heatup a substance and make it more dispersive then the the phenomenon becomes harder topredict, it becomes more chaotic. And so if we come to sample that phenomenon, we experienceuncertainty because it's chaotic. We don't know what it's going to do. And so this isa really quite a natural mapping between what's going on at the physical level in terms ofan induced chaos that we can see in the brain. We see brain activity becoming more complexmore entropic harder to predict and people have this, they embody a state in which theirordinary assumptions start to kind of disperse and they feel a very acute uncertainty andlack of assuredness about themselves and about the world. At least that's what happens initially.And in that state of relaxed beliefs, introducing this model at the moments I called REBUS,those who are savvy with psychoanalysis might see a link there. It's a bit of a fudge interms of the acronym but it stands for Relaxed Beliefs Under Psychedelics. And I think thisis the kind of foundational phenomenon. So if we can relax our high-level beliefs, beliefsin ourselves, our ego for example, then we can be more sensitive to both what's withinour mind, so context in that sense and also environmental context, people that we're with,the music and all these different factors. So that's really the mediating process andit has to be emphasized, it is a process that perhaps doesn't end during the acute psychedelicexperience itself but starts bleeding into the integration work as well. But how canwe experience insight if we don't first relax the way the system may be including our clearvision. And so that's really critical that there be a relaxation even a collapse of theseincluding factors like our ethos and then in those conditions have the possibility tosee over these otherwise blocking occluding factors to experience spontaneous insight,how that can be directed in certain ways. There's only really I just want to emphasizethere's initially a relaxation of these high-level beliefs in a hierarchical sense. RememberI emphasized that these 2A receptors are in the highest aspect of the cortex. There areother things that we could characterize in a hierarchical way that are targeted by psychedelics,certain neurons that can be considered key integration units, the layer 5 for pyramidalneurons, very important brain cells, very key computational units in the brain. Alsoimportant rhythm, the algorithm for example, that so dramatically collapse under psychedelics.And then it leads onto if we have a relaxation of beliefs that we can revise them, we canrecalibrate them, we can have beliefs that are more in tune with data. Data that canbe within us, our emotions, our bodies proprioception, interception, but also more connected andin tune with of course the world out there, other people and perhaps even some philosophiesand perspectives on the world beyond just person-to-person interaction. So this is whereI'm working towards a conclusion that there is, its initial relaxation working towardsthe revision of beliefs. It very much resonates as what our patients and I think others sayin the context of psychedelic treatment that it feels like a kind of rebooting, a resettingof a system that's being in a sense malfunctioning, becoming stuck in it's functioning. You havea patient from my trial here say, it was like when you defrag the hard drive on your computer.We know that psychedelics acutely disintegrate key brain networks like the default mode networkassociated with these high-level functions where the 2A receptors are most densely expressed.So there's that disintegration within networks that happens acutely. So then if you lookafter people have come down from a psychedelic, here we're looking the next day after treatmentwith psilocybin for treatment-resistant depression and we see that these networks reintegrate.So it's very natural I think to make that extrapolation. We didn't record during theexperience but ethically could you really do that when you're trying to treat peoplewith depression with psilocybin. You know you don't really want to shove them in anfMRI scanner. But here we're doing our scanning one day after the treatment and we've seenthis reintegration of the very same network that disintegrates acutely. We also see thatthose who responded back to the treatment were those who show this reintegration effectmost markedly. Now this is something that's also been seen with electroconvulsive therapyand granted this is a very different treatment model from that but ECT is, if we just lookat efficacy, does have a particularly you know high efficacy for at least dropping depressivesymptoms. That's not a defense of ECT, it's just to say that that's what the evidencetells us. It is effective at reducing depressive symptoms. So it's interesting, I think, thatthere are overlaps there. But of course there's much more to psychedelic and what is it thatis more. Well by definition these compounds are mind revealing. That's what first drewme to this work, reading Stan Grof's book Realms of the Human Unconscious. Just beingabsolutely blown away by that and then it changing my life really and making me realize,I was studying psychoanalysis at the time, making me realize that this is what I hadto dedicate my life to. And so this spontaneous insight that emerges on the under psychedelic,we found that it correlates with better outcomes in our depression trial patients here saying,I had fresh insight into things it was as if the scales dropped from my eyes. So a relaxationof that conclusion. And this term epistemic transformation that now after the experienceand perhaps also during although things can be quite chaotic. But there's a kind of realizationof revelation, there's been a shift in perspective and ability to see the bigger picture. Nowsomething's known and it can't really be unknown. The mind is unfurled, it's opened up and we'vebeen able to see more of it. And so here just showing that insight scores are correlatingwith depressives, drops in depression scores at five weeks when the effect size was maximal.So very exciting and just to end on this graphic here is the simplest really possible energylandscape or attract the landscape I could show. It's called the fixed point attractor.You can imagine this all having some dynamics rolling around in space. It's gonna fall intothe depression right and it's gonna be hard for that ball to get out and so how couldwe change the landscape so that there could be greater freedom and the ball if we thinkof the ball as where the mind is at any particular moment, how could we change this landscapeso that it can move around more freely. Well we can pull it tighter, we could flatten theattractor landscape and so we're developing based on our brain imaging work now, resultsthat'll soon be published that actually show this a flattening of the attractor landscapethat systems configurations in the brain that are ordinarily dominant become less dominantunder a psychedelic. So that the mind can wander more freely under these compounds andagain this may well account for the ability to have spontaneous insight that appears tomediate the therapeutic effects. So I'll just end it there and thank you all for your attention.I don't know if there's time for questions but I'm really happy to have contributed tothis. It's a team effort here, I say here, back in London with the wonderful group thatI work with. It's a real pleasure to work in this domain and it's a pleasure to contributeto this event. So thank you very much. - Well Robin thank you very much for joining us.Well Robin thank you very much for joining us. Really very insightful. And we're gonnabid you adieu now and get our panel rolling. Thanks so much for your time and we'll seeyou again soon. - Thank you, all the best. - Cheers. So I think to all our panelistswill invite you all up with Julie moderating. As they're coming up just want to mentionagain if you have questions that you want to submit for the panelists visit slido, S-L-I-D-O.com and the code is 4008. - Thanks all for coming. My name's Julie Holland I'm a psychiatristin New York City and I've edited a book on MDMA and a book on cannabis which I do considerto be a psychedelic and I'm the medical monitor as Delara said of some MDMA PTSD studies andcannabis PTSD studies. How I thought we would start is for everybody just very quickly saylookin' at a you Rick. Say a little bit about what you're doing now but then what drew youto this field and if we could start with Anya please. - Good afternoon this is working?Can you hear me? My name is Anja Loizaga Velder I'm a German Mexican psychotherapist workingin Mexico and we are bridging the traditional indigenous medicine with psychedelic medicinesand we call it intercultural medicine. So that's the line of work we are working in,trying to reach more the recognition of the indigenous roots of this kind of work andall the contribution that could be made if we take a closer look of the wisdom that isstill alive in those traditions. - And maybe a word or two about what drew you to thisfield in the beginning, how you got interested in psychedelics, way back in the beginning.- I got interested through experiences I had in the Amazon. When I was 18 years old I gotintroduced to the ayahuasca so this was really life-changing for me and so I got engagedof trying to bridge this with Western psychology in psychotherapy and exploring more the potentialsof this medicines. - [Julie] Can you explain ayahuasca for people who may not know whatit is? - Yeah ayahuasca is a plant compound from Amazonian medicines which is a mixtureof two plants vine Banisteriopsis caapi and leafs from the chacruna. There's up to 80other additives that could be there but those plants are the basic plants of the ayahuasca.They contain DMT and beta-carbolines. - Thank you, Matt. - I'm Matt Johnson, I've been atJohns Hopkins since 2004, conducting research with psilocybin and some other psychedelicsstudying things like mystical experiences and healthy normals, cancer patients withexistential distress, depression, anxiety, smoking cessation as was mentioned. That'ssome work we're continuing with, had some very promising results, hoping to expand thatto some other addictions. We've started some work on anorexia, hopefully very soon. Sowe're moving in a number of directions. And in terms of what got me interested, I'd sayI studied drugs and behavior and I study addiction. A lot of aspects of drugs you know, cocaine,nicotine, alcohol, uppers, downers all-around-ers and their connection to you know risk behavior,addiction, you name it. If you're interested in drugs and behavior, either you're interestedin psychedelics or you don't know anything about psychedelics you don't know anythingabout the history, the indigenous use, you haven't talked to anyone who lived throughthe 60s. So my interest is in psychedelics as behavior change agents. Which I reallysee all of this work whether it's nominally addiction or whether it's mood disorders,eating disorders, I see these as behavior change agents. - I grew up in the 70s anddrugs were just all around and I too was very interested in drugs and behavior and I remembersort of seeing how oddly people would act or behave if they had had LSD or PCP and thesewere things that were sort of somewhat common in the 70s in suburbia. So I sort of feellike that's how I came to it is that I was sort of somewhat surrounded by drugs and itmay have been a little bit self-selected. And then I went to University of Pennsylvaniawhere they had a major called the Biological Basis of Behavior where I learned psychopharmacologyand more about behavior change with drugs. But while I was an undergrad there was a newdrug on the scene which I was very excited about. I didn't think there would ever bea new drug in my lifetime, I mean I, you know, there seemed like there was already enoughwith LSD and mushrooms and cannabis and I thought that was plenty but while I was anundergrad studying drugs and planning on being a psychiatrist there was a new drug MDMA.And how I learned about it was that therapists were giving it to their patients as a catalystto make the therapy go deeper and be more efficient. And that was around the time thatI met Rick Doblin and he will speak soon with you. I'm gonna let Michael speak now becauseI think we're having some technical difficulties with my microphone. See if they're havingthem with yours. - Thank You Julie. - Thank you is that you? - Wait, it's more me. - That'sghost Julie. Well I've had a long-standing interest as a writer in altered states ofconsciousness which grows out of my interest in our relationship to other species and plantsand in particular and I've been struck by the fact that one of the things we use plantsfor and have for thousands and thousands of years, has been to change consciousness. Andthis is common among virtually all cultures. And that struck me as a very curious humandesire. What is it good for? What's the value of changing consciousness? So that was inthe background when I touched on that in a book called Botany of Desire in a chapteron cannabis. And then I started learning about the research that Matt and Roland Griffithswere doing at Hopkins and specifically about the study of cancer patients which is a mind-blowingpiece of work. And I wrote an article about that for The New Yorker and I intervieweda great number of people who were really right up against death, against their mortalityand on a single psilocybin trip they had experiences of such power and transformative power thatthey had completely reset their understanding of their own mortality and were able to inmany cases diminish or even eliminate their fear. And this struck me is so improbableand so important that I became intensely curious about the process. What was the science behindit? How could we possibly account for these changes? And that led me down the path thatbecame my recent book, How to Change Your Mind. But it really began with those cancerpatients and my interviews with them as well as the researchers at Hopkins in NYU. - WellI got into this field primarily because of fear and politics. Growing up in the 60s Iwas educated about the Holocaust, I was scared I would be a victim, I was a young boy duringthe Cuban Missile Crisis and then also in the tail end of Vietnam. And so I just feltlike the murderous nature of the human species was potentially gonna make me a victim andall of us victims and we see what's happening with the environment. And I stumbled on psychedelicsand felt that they were tools that could promote a sense of identification beyond all the waysin which we defined ourselves through our religion, through our country, through ourgender, through our class, all the different ways that we separate ourselves from eachother and define ourselves. That this sort of psychedelic mystical experience, the senseof unity and connection had profound political implications that would be in the directionof compassion. And I felt that these tools when I first woke up to them in the early70s when they're being suppressed that they had incredible political value for human survival.And that's what really caused me in 1972 at age 18 to focus myself on bringing back thisarea and that was really through reading Stan Grof and the work that he pioneered with psychedelicsand transpersonal psychology. And so he really inspired me and was someone who would liketo be here. He had a mild stroke. He's doing really well now but still learning about readingand talking so he couldn't be where here with us today and just said that if anybody wantsto hear about him, I spoke to him earlier today, that he did an interview with Tim Ferriss,a podcast that's gonna come out in November and he recommends you to listen to that. Andwhat I ended up doing and what I'm doing now is started basically a nonprofit pharmaceuticalcompany because these drugs were abandoned by government, pharmaceutical companies, majorfunding organizations and so MAPS is on the verge of starting phase 3 for MDMA-assistedpsychotherapy for PTSD. We've raised $27 million all in donations and we're starting phase3 and we're moving to work in Europe as well. And just to give you a sense of how thingsare changing on Monday I was in Orlando and I gave a talk at the International Associationof Chiefs of Police and it was about MDMA for trauma among police officers. And thesame strategic sense I have also President Trump, he was there as well and for differentkind of reasons and so I think that we're on the verge really of medicalizing thesedrugs and I think that that's the doorway into reducing the fear that people have aboutthem and to show that we can create contexts where the benefits outweigh the risks andhopefully it'll lead to a reintroduction of these tools into our society for therapeuticuses but beyond that for personal growth and spirituality by millions and millions of people.- So I'm Franklin King. I'm a psychiatrist right across the river at Mass General Hospital.I work part time in research and part time doing clinical work. The focus of both ofthose right now is sort of at the interface of medicine and psychiatry. I completed afellowship that really looks at how people respond to medical illness from a psychiatricperspective and the manifestation of psychiatric medical symptoms, medical symptoms as a responseto stress, depression, anxiety. What I'm working on for next year is my first study in psychedelicsworking on an imaging pilot at MGH, hopefully involving some of the study subjects for MAPSso we'll see how that goes. But as far as psychedelics and why I've been interestedin this, this is something I've been following with a lot of interest since medical schooland really the reasons I'm interested in psychedelics are the same reasons that drew me to psychiatry.I'm fascinated by you know what is inside people's minds and how we can use those, thesubstance of the mind to heal people and I think if you learn about what psychedelicsseem to offer for promise for healing people there's a great deal of potential there. Sothat's really what I've been seeing and I'm really happy to be here and excited to seethe progress over the past few years. Research is just exploding in this area. It's reallycool. - So Franklin when you look to the future and like what's your dream job? What's yourabsolute fantasy dream for what kind of research you could be doing if Mass General was likewhat do you want to do? Just tell us what you want to do and you can do it. What wouldyou choose? - Yeah sure. So part of what I really like, I spent a lot of time in residencyfocusing on psychotherapy so that's actually a big component of what I'm interested inand at the totally opposite end of the spectrum, I'm also interested in the neuroscience andwhat we can learn about consciousness. So my dream job would really be working in atranslational research center where I could be both working as a psychedelic psychotherapistfor patients but also working on research initiatives to really understand. I thinkthese medicines not only are treatments but as Dr. Carhart-Harris was talking about, theyoffer us a lot of insight perhaps into the mechanisms behind really what is anxiety?What are the domains that underlie depression, trauma, not just how to heal these thingsbut what they actually are from a phenomenological level. - So speaking of phenomenology, I actuallywant Michael to explain a little bit about default mode network and your understandingof it because you go in depth in the book talking about default mode network and maybejust this idea of like shaking up the snow globe and what that would mean. - Yeah pickingup on what Franklin just said and referring back to Stan Grof who I think we need to thankfor, with Leo's help, bringing us all together. One of the things that got me started on thesekind of questions as to what psychedelics reveals about the mind beyond the therapeuticapplications is a line of Stan Grof's that I think has influenced all us. And I forgetwhen he wrote it, I think in the 70s, but he said that psychedelics would be for thestudy of the mind what the telescope was for astronomy or the microscope was for biology.It's an incredibly audacious thing to say and I thought it was really overstated whenI first heard it but I increasingly don't think it's so overstated. And that these substanceshave the potential to open a very interesting window. When you disturb a system as witha particle collider, you can force it to reveal its secrets very often and I think that that'ssomething that is happening. And I think that Robin, who you just had the privilege of hearinglecture, is making really profound strides in. One of the areas that he only touchedon briefly is when he began imaging the minds of people on psilocybin, using at first fMRIand then some other modalities. He was surprised actually, the field was surprised, to discoverthat contrary to the expectation that psychedelics would simply boost mental activity acrossthe board, psilocybin, and this proved to be true for LSD as well, diminished it, quietedaction, in one particular important higher brain network called the default mode network.This is a network that really was only identified 15 or 20 years ago and it links parts of thecortex, prefrontal cortex with older systems involved in memory and emotion. And it seemsto be responsible for activities having to do with the sense of self, self-reflection,time travel, which is very much involved in having a sense of self. The autobiographicalmemory, the way we construct stories about who we are and fit information from our livesinto that story. It's also a sort of bestrides the mind in kind of the top of the hierarchyand seems to be kind of a very important traffic hub and when that network is silenced or atleast quieted very interesting things happen. When you see that happening on an fMRI whatthe patient is reporting phenomenologically is a dissolution of the sense of self to agreater or lesser extent. So that seems to kind of support the idea that that's what'sgoing on in the default mode network. But when that happens, when that system disintegrates,other networks within the brain sort of strike up conversations and are able to exchangeinformation in a way they don't normally which might explain the prevalence of things likesynesthesia where one sense is cross-wired with another or hallucination. So that wasa very important insight I think into consciousness and in our sense of self that already psychedelicshave helped us to see and no doubt there will be a lot more like that. - So Matt I kindof want you to pick up a little bit on this idea of ego disintegration and default modenetwork, quieting and this idea that other parts of the brain become sort of hyper connected.I was hoping you could talk a little bit about why ego disintegration is important and alittle bit about the mystical experience. - I think it's taking that hub off line asMichael said. You know it's like this, a bus driver that doesn't allow anyone else on thebus to talk to each other. They have to relay messages to the bus driver and without thatbus driver you know everyone else is not allowed to communicate. And so you're kind of kickingthat bus driver off for a second then people can start chatting and getting rowdy. So Ithink that that more has been looked at on the the positive side. The sense of unitywhich is a core feature of the mystical experience which is a construct we've looked at in anumber of studies now. But this is more speculation here, I think that disintegration is alsoan inherent part of the so called bad trip. The challenging experiences which is somethingwe've more recently started to focus on, we've developed a validated scale to assess thenature of these experiences what are the constituents and starting to look at some patterns there.But I kind of you know with that pulling that sense of self out, I kind of I see that senseof self that seems to be the biological correlate of it is the default mode network functioningit seems. That's kind of the ultimate carpet that's pulled out from somebody. That's whereour minds are full of models of heuristics and the self is the ultimate model at thecenter of everything and it's key probably. And to be clear this is part speculation basedon the research but so many of our human problems, so many of our psychiatric disorders thatdon't have a really great correlate in nonhumans, you know really have to do with sort of thenecessary evil of that very strong sense of self. It's very useful but it has, gosh itcan be full of kinks. And so when you acutely disintegrate it, you could have this oceanicboundless experience of unity where one feels connected to the universe, to everything,you fill in the noun, God, whatever you want to call the everything or it can be an incompletelyjarring experience. We found that on the positive side when the sense of unity or the the fullerconstruct of mystical experience is endorsed with unity, transcending time and space, it'sa sense of paradoxicality, ineffability, positive mood. When someone rates those qualities asvery strong after their psychedelic experience we see that healthy normals, people withouta diagnosable problem, they and the people around them are saying that they are betterfunctioning over a year later. They're easier going, they handle problems better. We seethat cigarette smokers are more likely to be biologically confirmed as abstinent fromsmoking. We see that cancer patients are more likely to have less depression symptoms andanxiety symptoms and other studies there seems to be that trend for the alcoholism work thatMichael Bogenschutz has done as well. So there's something very special about this sense ofunity. about this acute experience and that's really the, I see that as the paradigm shiftthat psychedelic medicines offer to psychiatry and the rest of medicine is that this really,there's probably some ongoing biological change but one can look at it psychologically asa medication facilitated learning experience. This state of plasticity very much in linewith what Robin was describing where, yeah, under the right circumstances it could bedangerous for things to go a little bit more into chaos but in the right conditions pushingthings towards the right direction with the right safeguards in place, you can drop thatsense of self acutely in the right way and that can lead to some wonderful outcomes andsome of those kinks tend to be kind of taken out of the system. - So I know with the Hopkinsresearch, they really showed definitively that the more intense of a mystical experienceyou had the better the outcome. Whether you're quitting smoking or whether with Bogenschutzyou're quitting alcohol or you're quitting being afraid of dying. But if you have thissort of ego disintegration and the sense of unity and connection that you come away feelingbetter. And a couple of things I mean one is that you know at the peak of a psychedelicexperience for some people they feel like everything is connected and they are partof that connection and that's a blissful feeling. And one thing that you see in surveys of peoplewho use psychedelics is that they feel more connected to the environment and they aremore sort of eco conscious and I know that MAPS is looking at using MDMA in a conflictresolution. But this idea that if you sort of quiet the self and the sense of self andyou're more committed to everything being connected you may be a better citizen. Aninteresting research showing that when you present people with their own political viewsthat they agree with, their default mode network kind of lights up and they're like that'sme and that's what I believe in. And it may be that if we can bring that down a littlebit and bring some of the beliefs down and have people be more open to some other politicalideas that that may also be better for us. But I want to ask you Anja, if you're comfortablespeaking about ayahuasca in ritual context and some religions using ayahuasca as a sacramentand this idea of unity and connection not just to the universe when somebody is peakingon psychedelics but also just connected to the clan, to the tribe, to the group that'shaving the ayahuasca and social cohesion. I was wondering if you're comfortable talkingabout any of that? - Yes, sure. - Okay. - Yeah, I think this is one of the contributions actuallythat traditional medicine can make to modern psychedelic medicine is the group part. Ayahuascaand as other psychedelic plants that are used in indigenous people are used a lot also forsocio-therapeutic processes. Oftentimes the family is present too, of a patient and thenthere's a lot of group dynamics that happen in ayahuasca ceremonies which I do believethey have a big therapeutic value. Interestingly in such groups where ayahuasca is administeredit happens very frequently that an experience of one member of the group is complementaryto the experience of another member of the group. So in a group integration process thiscan be used therapeutically to enhance the individual therapeutic experience. I thinkalso the fact that as human beings we are social beings like this group container speaksto the social part of the soul and that indigenous people have intuitively just very subtly developedtechniques to create a group consciousness within a ritual. So you wanted me to speakabout the ayahuasca religions. There is syncretic ayahuasca religions where ayahuasca is usedin a very structured context in very huge groups and it's really impressive to see howwell-structured those religions can contain the collective non-ordinary state of consciousnessand directed into in this time like collective blissful states of religious ecstasy. Butalso if there's individuals that having a difficult time that go and touch dark innerspaces, they are very carefully taking they took a part in a special therapy room wherethey accompanied in a very centered and individualed way to pass those difficult spaces they mayexperience. So those models I think they could be adapted into modern psychedelic therapyin a way that could reduce costs for those application because it's very costly to havetwo therapists for one patients. And I do believe a lot also of the therapeutic valueof the group as such if this is really taking care of in the appropriate way. This is likethe most important factors because on the other hand groups that are too big and thatare not contained are conducive also too dangerous psychedelic experiences. So it's a fine line.- I know I skipped you Rick and I want to come back to you. You had mentioned fear andpolitics and I wanted you to talk a little bit about this conflict resolution and alsothe the couples PTSD work. I know this is MDMA and not psilocybin or LSD and I thinkofficially MDMA is not a classical psychedelic but I think if you're using the definitionof mind manifesting then I think that MDMA is a psychedelic. It certainly works on theserotonergic system and it certainly gives you that feeling of connection and unity.But could you talk about the conjoint studies and a little bit about the new conflict resolutionstudies. - Yeah, you know part of the work that we're doing to help mainstream psychedelicsand MDMA in particular is reaching out to various therapists who work for the VeteransAdministration who have developed different non-drug therapies for treating post-traumaticstress disorder. And there's one particular approach called cognitive behavioral conjointtherapy. Conjoint meaning couples. And it's where one member of the couple has PTSD butit affects the relationship. And so through the work of Richard Rockefeller and his cousinSenator Jay Rockefeller who was on the Senate Veterans Affairs Committee, we got to openup some doors for us at the Department of Defense and that the VA and they suggestedthat the first study that they would permit their researchers to do was to blend MDMAwith this cognitive behavioral conjoint therapy. We had to pay for it. The vets had to comeor the subjects had to come from outside the VA and the people had to use their academicaffiliations not their VA affiliations but we were able to get permission to give bothmembers of the couple MDMA. So this was the first move from individual psychotherapy withtwo therapists a male-female team for one patient to moving into at least two peoplegetting MDMA at the same time still with two therapists and that worked actually tremendously.And so we've been able to demonstrate that in this context that they're both able todiminish the PTSD symptoms in a substantial way from the person that has PTSD and alsoincrease the couple's relationship. And we're starting to sort of back our way into couplestherapy. You can't medicalize psychedelics for couples therapy because it's not traditionallya disease. They have a difficult relationship we can, feels that way sometimes but we canonly medicalize for you know major diagnoses. But that was a step towards understandinghow this drug can be used, MDMA, in both couples therapy and PTSD but also in furthering conflictresolution ideas. And so you know one of the clues that came to us about this was whenMDMA was first developed as a therapeutic drug in the middle 70s to the early 80s andthen it sort of escaped from that and became a party drug Ecstasy and then got criminalizedin the U.S. in '85 and I was involved trying to protect the therapeutic use of it at thattime. Then it started moving to Europe and particularly to England and it was being usedin a lot of clubs and bars in England in particular and what people noticed was that the soccerfans that would go to these bars and drink and fight with each other-- - The hooligans.- The hooligans. And that diminished. And this was the only place where Catholics andProtestants would get together in certain areas and do MDMA together. And right nowthere's groups, small groups of Israeli Arabs and Israelis Jew's doing ayahuasca togetherand doing MDMA together. And so MDMA diminishes fear about difficult emotions. It makes peoplebetter listeners. It's make them more empathic. It releases oxytocin and prolactin that promotesa certain kind of bonding and so the idea that we can use MDMA and potentially otherpsychedelics as well in conflict resolution context is something that we're very muchinterested in exploring. And I think it's at the very early stages. Again it's verydifficult to medicalize that but it's something that we can do experiments with and we'rehoping to realistically think about who would come and volunteer for these kind of studies.It's not gonna be the people that are on the opposite ends of the spectrum that hate eachother so much that are unwilling to even talk. It'll be kind of the people that are closestto the people on the other side and want to learn more about them. So in a sense we'regonna be training the trainers. We're gonna be working with peace activists from bothsides and trying to help them realize their own biases and their own fears and help thembecome better connected to the others and then also then broaden it out in that way.So we are focused primarily on developing MDMA as a treatment for PTSD and then fora whole lot of other things. But I think this idealistic vision is not completely ungroundedor fantastical. I think there's a lot of evidence to suggest that these drugs can be used inconflict resolution situations and I would say just one thing about the difference betweenthe way you described about the mystical experience being the key to therapeutic outcomes. Thatthe depth of the mystical experience with classic psychedelics correlating with therapeuticoutcomes and that's a fundamental difference between the research that's been done withpsilocybin and the early work with LSD and the work with MDMA. And so what we found isthat there is no correlation between the depth of the mystical experience and people do havequite profound experiences in that nature and using the same measures as is used inpsilocybin. People score pretty high on this dimension of mystical experiences but there'sno correlation between that and therapeutic outcomes from PTSD. What it really involvesis taking people's memories of their trauma and helping them confront them in a differentway where they're not so terrified and they could process them. So I think that in a conflictresolution situation, you're not losing your sense of self, you're not immediately goingto these ways when which you're all connected but you're able to kind of manage yourself.I think people will be able to use the MDMA in these initial stages of conflict resolutionand then eventually what we'll do is administer other drugs as well. And so I think that'sreally the direction that we're hoping to go in. - I want to touch on a couple of thingsyou said. I mean you mentioned oxytocin and my little ears go bling. I'm very interestedin oxytocin and I know that with ayahuasca or with psilocybin or LSD at the peak whenyou feel like everything is connected and you're connected with the universe and thatkind of feeling of connection that is a high oxytocin state. With MDMA which is also ahigh oxytocin state, it's a little bit more grounded and less out there and more likeyou're connected with your partner if you're doing conjoint therapy or you feel very connectedto the therapist and this enhances the therapeutic alliance. And that is one of the outcome markersfor how well people do is if there's an enhanced therapeutic alliance between a clinician anda client, you're gonna have a better outcome. And one of the things that MDMA seems to particularlyget at because the oxytocin sort of dampens the fear response and the amygdala is lessfear and more love and more openness basically and more trusting and more bonding which doessort of again get us back to this kind of us and them mentality. And if we're all onthe same team we can work together but I did I wanted to talk to you Franklin about you'reinterested in psychotherapy and you're interested in psychedelics. I'm wondering if you feelas I do that MDMA is particularly well-suited to be a catalyst to make psychotherapy godeeper and go faster be more efficient. Do you have any sense of that? - I mean I thinkit depends on what you're trying to treat and what you're trying to accomplish. Onething that seems clear though is that the outcomes that we're seeing from all of thesestudies that are coming out are really major changes in response to depression, to endof life anxiety, to PTSD symptoms and these are things that for many of our patients,we can accomplish them with medicine, we can accomplish them with psychotherapy, but itoften takes time. It takes multiple trials particularly from psychotherapy alone in orderto sort of get to these states. You know I did the Part B MAPS training and part of thatwas really just watching a lot of the therapy sessions with these veterans with PTSD andthey were really sort of having revelations about their trauma that you would be overjoyedto see in the clinic but you would spend two years of intensive weekly therapy and thiswas happening in a single session. So I certainly think from the realm of trauma and sort ofgetting someone into a state where they feel comfortable processing some really difficultexperience that they've had that really has kind of left an imprint on the way they thinkabout their world. And that sort of goes to what Robin was talking about, about alteringbeliefs, traumas, you know more than probably anything else. Stamp they're, sort of, theyleave their imprint on the way we see the world and the way we interpret everything.And I do think probably for PTSD, MDMA seems particularly well-suited for treating traumabut in terms of perhaps things like anxiety, particularly end-of-life fears about destructionof the self that may be why psilocybin perhaps is more well suited. Something that's a littlebit more introspective that lets people get a little bit deeper not into trusting butinto meaning and sort of more existential aspects of existence, so. - Katherine MacLeanrefers to psychedelics as sort of like death rehearsal because when you have that ego disintegrationand you don't exist anymore it's very frightening and uncomfortable. Maybe Michael you wantto talk about being in the void and what that feels like. But after that sort of not existingand being in the void, optimally you have the bliss of the light and things coming togetherand sort of feeling that and I forgot where I was going with this actually. - You wantto report from the void? - But if you want to talk about, I got lost in the void whichsometimes happens. Why don't you talk about the void and I will remember what I wanted.- Okay well as part of my own experience and after interviewing many people who'd had transformativeexperiences on psychedelics, I became naturally intensely curious to try it myself. I hadhad very limited experience with psychedelics at the appropriate age. and for various reasons.But now I was eager to see what it was all about and I also as a writer that's kind ofhow I work. You know when I wrote about the cattle industry, I bought a cow. So writingabout this I had to dissolve my ego. So I had a series of guided psychedelic trips.I could not participate in any of the above-ground trials so I had to resort to working withunderground guides and there is a extensive community of very serious therapists who wereworking underground illegally and I found my way into this community and worked withseveral different people, using several different medicines. The relevant case though that I'llshare with you, is a guided psilocybin experience that I tried to make as much like what wasgoing on at Hopkins as I could in terms of dose and setting and everything. And you shouldknow I was terrified before every one of these trips, I had a sleepless night, I argued withmyself was this a crazy thing to do, I went to my cardiologist before I made a move. Iwas a very reluctant psychonaut and I would I realized every time this happened that itwas my ego actually trying to stop me from this assault on my ego. But fortunately forme it failed and I managed to go ahead and have the kind of experience that I was hopingto have and on a high dose psilocybin trip, I'm gonna cut to the chase. But I did havethis kind of shocking experience well into the trip of feeling my sense of self go upin a puff of little Post-it Notes. And I and well for a writer I guess it was. But therewas another but there was a perceiving eye nevertheless. Even though I saw my sense ofself fall apart, somebody there was another first person that had opened up and it wasthe first person that I had never had any acquaintance with that was completely finewith what was happening, felt no sense of panic, no desire to pile those little slipsof paper into a you know pull them back together and then I looked out again and I saw myselfspread over this imaginary landscape like a coat of paint and it was a remarkable experience.It was not frightening at all. It might have been if I weren't in such a safe environmentwith a guy that I trusted. I mean without question this very risky letting yourselfdisintegrate but and I think that that's a key to psychedelic therapy, is creating acontainer where you feel safe enough to let go and that's a fundamental difference betweenthe so-called recreational use of these drugs and the therapeutic or spiritual use of thesedrugs. And I remember afterwards I came back for an integration session with my guide andshe said what happened that was note worthy and I told her about this dissolution of selfand the surprise of it was that I said I found there was another ground on which to standthat wasn't my ego. I don't know what it was. Aldous Huxley would have said it was the mindat large maybe it was some trans-personal consciousness. I tend not to believe that.And she said, "Well isn't that worth the price of admission?" And I said, yes except it'sgone, my ego is back in charge, in uniform, on patrol. And she said, "Well you've hada taste "of this other way to be. "You've had a taste of a non-ego centric consciousness"and you can cultivate that." And I think that's a really important lesson about thesesubstances that you know if you're involved in psychotherapy or psychiatry and in anyway there are many things that are anomalous about this. One is you're essentially prescribingnot a drug exactly but an experience of a certain kind. So how you use that experiencegoing forward becomes very important. For me I asked her how could I cultivate thisand she said meditation. And it's no accident I think that a lot of people who experimentwith psychedelics find their way into meditation as a way, a non-pharmacological way, to connectwith a kind of consciousness that is less egocentric. And I have, you know I think somedaywe'll look at psychedelics is a very good way to kickstart a meditation practice. Iwas never very good at it before and I know you're not supposed to be good or bad at meditating.But I'll say it I'm better than I was. - It made you a better meditator. Matt and Anja,I'm gonna want both of you to talk about this idea of a psychedelic experience and the egodissolution as sort of like death practice. You, Hopkins specifically, work with peoplewho are anxious about their death and the psilocybin isn't necessarily gonna changethe course of their medical illness but it is gonna change the course of how they dealwith it, how they respond to it. - Yeah I was telling Michael earlier, I think the cancerpatients are really sort of give me participants for this stuff because they have been dealingwith those big questions so intensely about their death, about the meaning of existence,about you know what life is gonna be like for their loved ones afterwards. This is not,you know, we always have the intake interview where your goal isn't to scare someone butit would be easy to see where they think that would be the goal. You lay, it's really heavylike, you can have the most terrifying experience of your life, you could you know you nameit subjectively and it could be happen to your heart pulled out of your chest, you feellike your body is just being torn apart, you name it it can happen. But you know thoseso often with the cancer patients, you know like yeah right you're just describing mylife for the last you know whatever X number of years with these issues they've been dealingwith. So yeah and we have a lot to figure out but so often people do, when they do have,now to be clear we do everything we can to minimize the challenging experiences by creatinga safe container, the solid rapport but nonetheless about a 1/3 of the folks on a high dose willhave what people could call a bad trip. We frame it in this context as challenging. Itcould be a learning experience. But people so often in the cancer state particularly,found that these were powerful learning experiences when they occurred like you know, they sawtheir own destruction and they came through went out the other side. It's sort of theultimate catharsis in dealing with a potentially terminal illness. So I think we have and we'vesince conducted research in many people in the broader population who have had so-calledbad trips and in part to develop our scales but we found that it's very common for peopleto hold their most difficult psychedelic experiences as amongst the most meaningful experiencesof their life and among the the greatest learning experiences of their life. So yeah they canbe, we have a lot to figure out, you know we're not at that you know some work thatactually went on in New Mexico years ago actually, tried to target difficult experiences forthis purpose. I don't think we're there yet. I'm not sure if that would be the, you knowthere's a lot of ethical questions surrounding that. We try to minimize it but if you givehigh enough dose, you're gonna have these very difficult experiences where you can havecall it what you will, ego death. - And I think some people have on the other hand likereally profound experiences of love and openness and connection just on the other side of that.- Right, yeah and sometimes people get the impression that's a great point that it'sone or the other. These are five, six hour sessions. - Right, usually get a little tasteof everything. - Right. - My sense is, please correct me if I'm wrong but certainly frommy patients reporting to me that in general psilocybin may offer sort of fewer challengingexperiences than something like ayahuasca. Is that your sense of it at all or not necessarilyAnja, that sometimes it's a little trickier with ayahuasca than it is with psilocybin.- I think it depends more on the setting actually and on the preparation of the people. I thinkit's not like substance specific but I do want to echo what Matthew just said aboutthis characteristic of difficult psychedelic experience that are passed through in a containedway that they really help people to become more resilient to difficult life experiencesbecause it's like they get the self efficacy, I can deal with difficult emotional spacesand there's another way through. That's what I have observed a lot with my patients. Andin this way I do believe that psychedelics prefer to death because that's a very difficultlife experience in this way and but also even for births. Like I've witnessed other womenwho had psychedelic experiences before giving birth that they had much easier births processeslike really letting go in this way. So I think there's also this other spectrum of life thatpsychedelic can expand our consciousness to spaces that we have not experienced. And anotherbenefit I see in the contained use of psychedelics is for people with difficult grief, especiallyayahuasca in the sense, I think ayahuasca has this characteristic, indigenous peoplerefer to ayahuasca liturgy as the refine of the soul or the wine of that. That many peoplehave this experience, they get in contact with a beloved one that has passed away andfind relief for the grief, find understanding, find the acceptance they had not found before.So also I think this could be another important therapeutic application. - I'm glad you mentionedbirth. It didn't occur to me but I mean that is another very high oxytocin state and ifyou have natural childbirth you can see all the sort of special drugs that your brainleaves set aside just for that, just for being in labor and it may be that the experienceof really letting go and learning how to let go and learning how to not exist and sortof get out of the way, can really help people not only train for death but train for childbirth.I think it's a good idea. Who here is comfortable talking about neuroplasticity? Anyone, anyone?- Sure, yeah. - You do a little, I'll do a little. I'm very interested in neuroplasticityand certainly at least in a Petri dish we have seen that ayahuasca, DMT, 5-MeO DMT,psilocybin, LSD, are all capable and cannabis and CBD are all but maybe not MDMA are alland MDMA turns out, are capable of sort of stimulating the growth of either new neuralconnections or actual nerve cells, neurogenesis. So we're talking about psychedelic assistedneurogenesis, neuroplasticity, I think this is gonna be a very big deal and I don't thinkthat there are too many other treatments in psychiatry where you're actually seeing newneural connections and new sort of circuitry and networks formed. Did I leave anythingfor you to say? - Yeah I'm very interested in it too. Although I something I think Ican add to it is that neuroplasticity can take so many different forms and neurogenesisthe growth of new neurons or a specific type of brain cell is just one of those ways. There'sbranching, there's new connections being formed then we kind of go up an order of kind ofa layer of analysis then we could talk about new networks being formed. So I was I thinkthe paper published on psilocybin at least the in vivo paper in rodents on psilocybinneurogenesis wasn't convincing. But I you know it would be great to see more work alongthose lines. But we do know that neurogenesis is not always a good thing. I mean the growthof cells isn't always what you want. I mean cancer. So I guess I just want to kind ofin case you know this doesn't turn out to be a key mechanism I just want to say it's,in terms of conveying to the public you know neurogenesis sounds like really like that'sit, like growing brain cells has to be the answer. And so I'm a little more cautious.I'd want to see more data and it could be that this is playing out in a number of differentby a number of different mechanisms. Clearly there's learning going on. - I'm glad youmentioned learning because I think we should circle back and maybe Rick you can talk aboutthis sort of re-consolidation of memory idea that some of what, keep in mind that mostof the psychedelic research that's going on it's in the context of ongoing therapy. Thereare multiple sessions where you're preparing somebody for the experience, then they havethe experience and then there are multiple sessions where you are processing everythingthat they learned or that they experienced. But I think unique to MDMA-assisted psychotherapyis this opportunity to go back to the trauma and sort of debrief the trauma but reconsolidateand Rick I want you to talk about that a little bit. - I don't think that that's necessarilyunique to MDMA though. I think that probably happens in these other drugs too and whatwe're really talking about is psychedelic medicine where people could get differentdrugs at different times in the course of therapy. It's not like this drug is perfectfor this and should only be use for that and these drugs shouldn't be used for this orthat. So I think it's really about psychedelic medicine and making that available to clinicians.I think what happens with MDMA for PTSD and memory re-consolidation is that basicallywe have these traumatic memories, people with PTSD have them and they can't really escapefrom them and these memories are linked to very painful emotions. And under the influenceof MDMA the painful emotions, the experience of them is diminished. People can rememberthe trauma and actually memory is enhanced for the trauma so a lot of parts of the traumaticexperience that people didn't have consciously available. And then you're looking at themfrom a position of safety, of peace, and able to process them. And then memory is more like,we used to think that memory was like a book and you would take it off the shelf and youwould look at it and you would just put the book back. And what actually is happeningis you're sort of taking to book off, consolidating it from different parts of your brain, andthen you have to republish the book and you store it back again. And under the influence of MDMA for PTSD,people are able to replace the emotional content. So, the episodic memory is enhanced for thetrauma, but then the fear that's attached to that is replaced by this sense that thememory is from the past. It's not happening at the moment. It's not always about to rehappen, and when the memory is reconsolidated you've switched the emotional tone to it,from that sense of peace and having it in the past. So then, after the therapy, you bring backthat memory, you're able to not react to it in such a way that it's re traumatizing againconstantly, but it's changed and it's in the past. So, I think that's the process and that'swhy that process requires people to be grounded in their biography and that's where I thinkthat the mystical experience is not correlated to outcome because it's about this episodicmemory and replacing the emotional tone to it. I just wanted to add one thing about the egodeath concept idea, which I think Stan Groff has really described it in a great way of:the ego becomes transparent to the transcendent, but it doesn't disappear. So, I think theseterms that we use like ego death and complete disillusion ... I mean, the way, Michael,that you described it, you're located in a different place and it's more like the Copernicanrevolution where people thought the Earth was the center of the universe and then itturns out, actually, you know, the Earth is not the center of the universe and we rotatearound the Sun and the Sun rotates in the universe as well. I think that's the switch that we need tomake from our egos: that we as our own individual love's are the center of the universe andthe most important thing and we're sort of disconnected from history, and you becomepart of this larger sweep. But we still have birth and death, we still have our own individuality;we don't ever really lose that. And even in these ego-disillusioned states, there's stillsome part of us that's still watching, that's still paying attention, and I think that makesit less scary a little bit. If you think about it not as ego death and who I am is gonnago away completely, but it's more this transparent to the transcendent. Michael, I just want to ask you a little aboutthe book and your experience writing the book. You met, sort of, all my friends basically.You know, you worked your way through a good chunk of the psychedelic community, and Iwas sort of curious who, what was the most fun interview you had where you just reallyenjoyed yourself and it was fun? And then, who was, and I think I may know the answerto this, but who seemed sort of like the most buttoned up where you just couldn't get, like,they just wouldn't relax and kind of give you ... Like, they had a script they werefollowing and you felt like you couldn't get underneath? Can you give me a hint? No. Well, we'll see. We'll see what, if you'relike, uh-huh? I had a wonderful time working on this book.I mean, it's, well you have had a taste of this community. It's a very interesting groupof people with a variety of perspectives. I mean, you're hearing some similarities,but there's some interesting divisions between people who come out of this work believingin a transpersonal idea of consciousness and others who, Robin used the word, denaturalizedthe experience and really want to ground it in biology, and I think that's one interestingsplit. And so, God, I mean I interviewed a lot ofthe people we're sitting with. Rick was enormously helpful to me and I've described hi as a journalist'sdream. He'll say anything and he never goes off the record. But also, Matt helped me enormouslyin understanding the psychological mechanisms that work here, and sharing his research.And Julie, too, I interviewed. So, I learned a lot from everybody. I found there was a great spirit of generosityin this community, of transparency in this community. So, yeah, I mean ... I just, Ilearned so much and I knew nothing about these issues. I had never written about mental healthor the brain, and so I relied on a lot of people to give me an education. I mean, a key interview for me was AllisonGobnick, who's not here, who is a child psychologist, a developmental psychologist at Berkeley,and she really helped me understand the neuroscience: the predictive coding, the Bayesian brain,concepts like that. But she also had a very interesting theory about the consciousnessof children which she regards as another altered state, and indeed it certainly is if you'vehad kids. And that she really believes that there's a dialectic between using the mindto explore the environment or exploit it, and kids are wired for exploration and notthe kind of purposefulness, directed thinking; attentive, focused thinking that you needto exploit the world. And that the mind of the child is very psychedelic in her view. She really thinks four year olds are justtripping all the time, and she's very convincing about that and it's a very good model forthe kind of thinking which is much more experimental, many fewer priors ... very, you know, lesspredictive. They haven't learned the models of the mind that Robin was talking about,that we've all been talking about. So, therefore, they're taking in information from their environmentand they're trying radically different ideas to solve problems that we don't. And in fact,four year olds can learn certain things better than adults can if it involves thinking outsideof the box. So that's the ... just to give you an ideaof the kind of range, but I'm really curious to know, who did you think was buttoned up?I would be happy to - Well, I definitely consider Roland Griffithsto be fairly buttoned up - Oh, Roland? But no, no. No, but more than that would be Bob Jesse,who you specifically said he went off the record a lot, which I could see. I mean, he'sreally, he picks his words very carefully, he's gonna - Bob Jesse. Bob Jesse, who is probably watchingthis, is an unsung, behind the ... I mean, Rick is a very well known, key figure in therenaissance of psychedelics. Without him, I don't think it would have happened, andhe's been knocking his head against the same wall since 1986 and finally it is yieldingand his head is still intact. But another figure you probably have not heardof is Bob Jesse who is a former computer engineer who had some really powerful psychedelic experiencesin his youth and devoted himself to trying to bring back research into the classic psychedelics,and in fact he had a lot to do with launching the work at Hopkins and finding a researcher,in Roland Griffith, who was willing to take a huge reputational risk. Roland was a very, is a very prominent drugresearcher at Johns Hopkins, but I actually found both of them ... you know, they wereharder interviews than this guy, but eventually fascinating. Roland got into this work becausehe had had a mystical experience of his own. Not through psychedelics, which as far asI know he's never tried, but through his practice of meditation, so very interesting biographythat gets someone into this. So, Roland and Bob were really key figures.But yeah, Bob is a very careful individual. I describe him as someone who chooses hiswords with tweezers. Right. And in fact chooses your words, too. If youuse a term like - Let me stop you right there, right? Yes. What do you mean by perception, right? Let's bookmark that. Why did you, why I'dyou use the word recreation in a negative context? The word recreation is a very positiveword, and so on. So, it was just a wonderful cast of characters, and I've met two new onestoday and so I feel like I profited enormously from the people I met in this world. You talked about children sort of seeminglike they're always tripping, and I remember I wrote in Weekends at Bellevue at one point,I was taking my daughter Molly around, who was a toddler, and I said that it was likeguiding someone that was tripping down the streets of New York City. Like, you cannotbe in a hurry cause she just wants to look at everything. But you know, that reminded me ... Oh, andalso I remember talking to my husband Jeremy about this, that we, you could also make thecase that a toddler, maybe instead of tripping, they're just kind of stoned where they havefresh eyes and everything is sort of interesting and, you know, as if they've never seen itbefore because they haven't. Yeah, it's wonder. Wonder. It's first sight. Or awe. Yeah or awe. Right. And awe is, I think, there's a very interestingpaper that a psychedelic researcher named Peter Hendricks just published - I saw that, yeah. Where rather than talking about the mysticalexperience, which is off-putting to many scientists, he argues that the key mechanism is awe. Theexperience of awe gives us a sense of ... it's a human emotion. I didn't realize that it'sone of the fundamental biological human emotions, and that it tends to shrink our sense of self.We feel smaller. If you have someone draw a picture of themselves on a piece of paperand then show them images of Yosemite or some, you know, awe-inspiring scene and ask themto draw themselves again, they'll get a lot smaller, and that ... It's also a very prosocial emotion in that it brings people together. You subordinate yourself to the, call it,activity. So, I don't think it's any different than the mystical experience. Right. I think we're talking about different vocabularies.I also think ego disillusion is, in a way, a synonym for the mystic experience. I thinkwe're groping for words to describe a phenomenology that I think is across the board. Right. So, Peter Hendricks, who wrote thispaper on awe and I think it's like the International Journal of Psychiatry, it was a journal Iwas familiar with - That's right. Yeah. But he, the work he's doing right now,which is great, is giving psilocybin to basically homeless cocaine users, primarily crack cocaine,and getting really impressive results which probably aren't surprising to us. I wantedto ask you, Anja, because we're talking about children and I know that in a lot of theseayahuasca based religions that children are allowed and invited to participate. They drinka little bit of the ayahuasca. I was wondering could you talk about this a little bit? Iknow it's a little taboo in our culture but in other cultures, it's not. Yeah, I think the important part is that there'sa cultural difference. It's not ayahuasca only. Also, the Huichol people give a littlebit of peyote to the children in the indigenous cultures where ayahuasca is still part ofindigenous medicine. They also hive a little bit of ayahuasca to the children in the ayahuascareligions. Brazilian ayahuasca religions have adapted this and they do the same. Those arevery small micro doses only, but they are believed to enhance this intuitive part ofthe brain in the children in this way. They're really small doses and controlled group ceremonieswhere they ingest it. I know from a few studies who have followedup on those children and, there is no adverse effect that has been found on those practices.Rather, there's some Brazilian colleagues who have studies ayahuasca using adolescentsand they have found that they are more resilient to those troubles that adolescents, thosechallenges that they are facing and they are more resilient to drug abuse, also. So, that'smaybe something interesting to rethink. Obviously, it's ... it's beyond our current Western paradigmto practice ayahuasca or other psychedelics with children, but I think it's importantto observe what other cultures do and just see what we can learn from this. I also wanted to add on the question you askedme previously and those difficult experience with ayahuasca in comparison to difficultexperience with psilocybin. There is one important aspect that ayahuasca is very physical andthere is this strong body-oriented aspect, I call them, from a more psychotherapeuticperspective, because it's not only on the body; it's really like if you would do a body-orientedpsychotherapy that there's many emotions that are processed through the body. And thesephysical processes that ayahuasca can induce, they really bring people to the state of surrenderingeasier than other psychedelics because it's something ... you cannot do anything but just,like, surrender to this vomit, to this strong physical part of the experience, also. So,I think this is important also to mention. Yes. You mentioned micro dosing and we absolutelyneed to talk about micro dosing, but I know that Rick wants to speak a little bit aboutadolescence and ritual. Am I right? Yeah. Go right ahead. Well, it's just that when you try to makea drug into a medicine, sometimes the final phase is phase three to prove safety and efficacy,but sometimes the FDA wants additional information and they'll require that in what's calledphase four studies. So, once the drug is approved, then you have to do some additional things.And so, the FDA is actually requiring us to study MDMA in adolescents with trauma. Andso, if that works, if we can prove it in adults, then we need to prove it in 13 to 17 yearolds. And then if that works, then we have to go even younger and the theory is that,once you're traumatized, the sooner that you can address that trauma maybe the easier itis to deal with and the less you pile on, more and more problems as they grow older. So, it's just to say that even though it'ssurprising to some people, even in our Western cultural context, the FDA is actually requiringus to administer MDMA to adolescents. I wanna just quickly, sort of, tackle thisadolescent ritual. Michael, I know you talked about this in your book a little bit, thisidea that in our Western culture, we really don't ... maybe we have Bar Mitzvahs or BatMitzvahs but in general we don't really have this, a ritual where, you know, now you arean adult and now you are in the community. And sometimes what ends up happening, certainlyin my own suburban, adolescent upbringing, that the rites of passages ended up being,sort of, drug oriented. And you wanna talk about this? And then I wanna talk about microdosing perhaps with Matt and you also, if we can? Yeah, I think that for many young people inAmerica, psychedelics have been one of the most important rites of passage, althoughwe don't often think about it that way. And I think that that contributed to the backlash.We haven't really talked about history that much, but the backlash to psychedelics inthe 1960's. We had a very unusual situation for a momentthere where you had young people experimenting with psychedelics, having these powerful ritesof passage that put them in a place that adults didn't really know. You know, the traditionalrite of passage, whether it's the Bar Mitzvah or the vision quest, is usually organizedby the adults in a community and they bring the adolescent, after passing through thesevarious obstacles, to the adult world. In the case of psychedelics, you had a riteof passage organized by the kids that landed them in a country that the mind of the adultsdidn't understand and was very frightening to them. So, I think we had a very ... andthat's why we had so much conversation about the generation gap. I mean, the youth in thatperiod had an unusually distinct culture. Whether it was music, manners, sexual practices,you know, drugs; all different kinds of things, and this was very disruptive to the society. I don't think that can happen again. I thinknow you've got, and one of the reasons that we are having this renaissance, is that manyof the people in charge of our institutions are familiar with psychedelic experience,are not as freaked out by it as people were in the 1960's. So, that gives me some optimism,and Rick and I have debated this. Rick is even more optimistic than I am - Rick is more optimistic than anyone we know- Thank anyone. And persistent. But that's what it takes. And that, you know, for all the problems ... Imean, Timothy Leary had a lot to do with inciting the backlash in various ways. On the otherhand, as Rick points out, he had a lot to do with creating a world in which psychedelicscould be possibly normalized by turning on as many people as he did. I still think, though, that this researchhas to proceed with enormous care. I think that there are risks. They're not so muchin the toxicity of the drug, but in the fact that there is ... you have patients who arevulnerable to sexual abuse, for example, during sessions. You have the opportunity, you know,the possibility of bad trips that can lead to bad outcomes for people who are using thedrugs in an uncontained way. So, the risks are still there. I think thatthey've changed a good bit, so I'm optimistic and more optimistic all the time that ourculture may be ready to integrate these medicines into its mental health care and ... for onevery key reason we haven't talked about, which is that we have a mental health crisis. Todayis World Mental Health Day, actually, and we have increases in rates of depression,addiction, suicide; and we need new tools, and I think that there's an openness on thepart of psychiatry and psychology to look at some new tools right now because of thecrisis. I'm very open. I feel like this is, you know,we ... I hope I'm not overstating, but I really feel like there's a revolution happening inpsychiatry now where, all of a sudden, we have all of these other tools at our disposalthat we didn't before, including micro dosing. I definitely have patients who have gone offtheir ADD meds or off their antidepressants and they are just micro dosing. And, I don'tknow Franklin if you're comfortable talking about microdosage, if you have any thoughtsabout it, but I feel like we should cover it a little. Yeah, I think that we need to have more studieson micro dosing - There are none, so yeah. There's none. I think somebody is doing something,right? Right, The Beckley Foundation in London isstarting to organize, I think, an LSD micro doing study. Yeah. Do it yourself, yeah. But I think the most interesting aspect ofmicro dosing, I think it raises the question and you will find, in the psychedelic community,a lot of division on this as to whether the deep, raw, psychedelic experience is integralto the effects of what psychedelics can do, and that a lot of people, really we're seeingit more in the media now, who practice micro dosing and seem to be talking about how ithas a great benefit for them for a variety of issues. And that just sort of leads meto wonder, you know, when we start talking about ego disillusion and ego death, do weactually need to have that? And I think, you know, the drug companiesare gonna be one industry that's gonna be very curious to know this because when westart thinking about can we develop analogs of psychedelics that actually don't have avery potent psychoactive effect, but may actually achieve similar rates of remission in depressionand anxiety? I think that's a very interesting question. Just to define micro dose, I mean, traditionallyit's about a tenth, would you say? Yeah. A tenth or even a twentieth of, sort of, amacro dose. Are there any, Mike, are you, is Hopkins planning on doing any micro dosingresearch? Oh we plan on doing everything. What's next for Hopkins? We haven't started it yet but it's definitelyon the wish list - You're talking about it? We have, yeah we have some ongoing, yeah.We have, we hope to be doing some micro dosing but nothing is started yet. There's no protocol. So I encourage people to look at Matt Johnson'sarticle about using psilocybin in smoking cessation. These are people who couldn't quitfor a good 20 years and were able to quit in the context of psilocybin-assisted psychotherapy. Yeah. What's next for you, Matt? Well, the really cool thing about addictionsis these aren't, you know, we aren't thinking ... unlike the rest of most psychiatric medicationsand addictions, we're not talking about quelling the response to the nicotine receptor, mediatingreinforcement or craving, and there's not similar hypotheses about alcohol. These aregeneral mechanisms with no doubt a biological basis that probably have to do with the changesin brain network dynamics that we've heard about today, default mode network. Potentiallylong term changes. Maybe other types of biological correlates, gene expression. Who knows? But everything, and particularly a psychologicaldescription of what's going on, everything is pointing towards general mechanism: behaviorthat is stuck. A mental repertoire that is stuck and in that sense, I even think of depressionand these other disorders as addiction broadly defined. OCD? OCD. Anorexia? Anorexia. There's lots of times when my patients arestuck - Right. And I want a jackhammer, so ... and this couldbe that? Yeah, and this is like, you wanna be carefulwith that jackhammer and you can't use the jackhammer - Like any jackhammer. Right, but in the right container with theright like safety glasses and whatever - Read the manual first? Like, training, you know, yeah. So anyway, that's my prelude to saying like,you name the addiction. We're hoping to do some work with opiod addiction. Again, haven'tstarted but you know ... it's relatively early but Peter's having great success with cocaine.And cocaine, I mean, the National Institute on Drug Abuse has dumped ... it's money wellspent to try to find it, but they have spent hundreds of millions of dollars since the80's in trying to find - Without much ... right. A medication. With no approval. I mean ... youknow ... I mean literally about 100 compounds have been worked up into clinical, into humanclinical trials. Right. I mean, if this stuff holds up with cocaineaddiction, I mean, it's ... I often say in comparison to ketamine, like it's rightfullyconsidered a revolution in psychiatry. I think that's true. If ketamine is a revolution,just watch out for the classic psychedelics cause we're seeing effects that last, youknow, six months. This is what's the crucial difference betweenketamine and the classical psychedelics is with ketamine people do get better. They feelbetter right away. It doesn't last. They need more. But with some off these other studieswith psilocybin or LSD or ayahuasca, people are getting better and staying better. Yeah and in fact, you know, we don't knowthat they get worse at six months; we've just only looked out that long in the cancer workwith our trial and the NYU trial. So, you know - And the smoking cessation, right? You're lookingat people six months, 12 months after, and the same thing with PTSD - We looked two and a half years now - And they still don't smoke - 60% biologically confirmed. I mean, we testtheir urine, we have them blow into a machine - And with MDMA PTSD, you're getting somewherebetween 60% or 80% of people at six months or one year out that don't meet criteria forPTSD anymore. In any other branch of medicine, you would just be like these people are cured.Here we just say they don't meet criteria for the diagnosis anymore cause it's all sortof an ongoing ... No one's every cured in psychiatry, you're just a little better. Youstill have to come every week. We did a three and a half year follow up withsome of our people. Some of them are ten years now. Talk about the follow up to the Good Fridayexperiments that were here in this neighborhood. Can you talk about that? Yeah, yeah. And also, Michael, if we have a minute tojust maybe ... a minute? I know, I'm asking Rick a question. Careful. A few minutes to talk about Harvard's historyin all this. We should, it's probably the elephant in the room. We should get to itbefore we open up to Q & A, which we will. Well the first ... in the 80's when I wantedto do research, I had to do a senior thesis at college and I wanted to focus on psychedelicsand at that time the FDA was not permitting any research at all. And I realized that therewas something that had been done in 1962 with Tim Leary. It was the Good Friday experiment.It was at Boston University Chapel, at Marsh Chapel, where it was actually done with AndoverNewton Theological Seminary students and there was an attempt to learn whether psilocybincould produce mystical experiences by people who were religiously inclined in a religioussetting. And it was done by a fellow, Walter Pankey,who had died in '71 in a scuba diving accident after he had left Harvard and went to JohnsHopkins and was working there with the LSD research. And so, I realized that he wouldhave done, if he was alive, a long term follow up and when it comes to this question aboutmystical experience, the traditional literature on this says that the most important aspectof it is what is called the fruits test: what is the fruits of the experience? You can describewhat happens but what aspect, what impact does it have on your life, and then reallywhat impact does it have long-term? So, this was in the middle 80's so I decidedto do a 25 year follow up to the Good Friday experiment and I went to Andover Newton tosee if they would help put a little announcement in their alumni newsletter so I could contactthe students that were participating, and they refused to do that. They didn't wantto have anything to do with it and I thought okay, I'll go to their library and see whatpapers they have and anything like that. They didn't even have a copy of the dissertationand out of desperation I just wandered in the library and I found a list of the alumnias of 1973 and their addresses. So, I wrote a letter to 350 people and eventuallyI was able to identify 19 or the 20 people and track them down all over the country andwent to interview them - And this was before the internet. This waslike letters and stamps, right? This was hard work, right. But you find afew and they know a few others and yeah, it took a long time to do. Eventually though,one of the most important things was that people who were in the psilocybin group rememberedparts of the experience extremely vividly, also they validated the fact that this wasa genuine experience. So this was in the Nancy Reagan, "Just Say No" escalation of the drugwar in the 80's, and if there ever was a time where people would have been culturally motivatedto disavow the validity of that experience, that was then. And yet, they could rememberit and they also could say that it was valid and many of them had had non-drug mysticalexperiences afterwards that they could compare. They generally said that they preferred thenon-drug mystical experience cause they were more positive but that they felt that thedrug experience was sort of oscillating between this fear of letting go and also this sneezeof connection. But I think one of the things that I learned that was most important wasit validated the theory of change, for why I devoted my life to this. And it's a littlebit what you said, Michael, about how part of the backlash was because of when psychedelicswent wrong or people had difficult experiences that they couldn't handle. But all of the people that I talked to thathad the mystical experience from psilocybin talked about how that sense of unity motivatedthem to get involved in the struggles of the day. They became more involved in the CivilRights Movement or the beginnings of the environmental movement or the anti-Vietnam War movement.And so, I think really the backlash was because of psychedelics going right; because of thesepeople having these experiences of connection, getting involved in challenging the statusquo, and then having that become a problem. Now, I think Leary and others made the problemworse by saying it's the counter-culture, we're tune in, tune on, drop out, we're leaving.And then there was an arrogance. We've had this experience and other people haven't sowe know more. But I think really the essence of it was that there are ways in which theseexperiences as used ... Now, this was again used by religiously inclined people duringa Good Friday service at Boston University Chapel, and the person that was doing thiswas Reverend Howard Thurman. He led the service and he was Martin Luther King's mentor. So,that just shows you that in 1962 it was not that controversial, it was kind of accepted. So, it was a way for me to get involved instarting to do psychedelic research, because legally you can ask people about what theythought without having to get permission from anybody but an IRB, and it validated boththe experiences and the impact of it on their lives. Sort of long term, long term impact. Great.So, we are gonna open it up to QA but I believe we are using this system where we've got,sort of, curated questions I believe. We are, and maybe we'll open it up to theaudience briefly at the end. Okay. But people have been submitting questionsonline, both from the live audience and from the webcast. So what do we have, DeLara? So, the first question is: do the scientistsand doctors observing the initial therapeutic effects of psychedelic substances have a dutyto advocate for changes to current drug laws? Yes. Next question. I work in drug policy reform. Rick works indrug policy reform - Yeah we just published that paper that wementioned, or yeah, I think DeLara mentioned that it, you know, should this be approvedfor medical use, it really doesn't belong you know, in schedule I or even close to it.IV seems like the best fit if it's gonna be - So the issue with schedule I is that it issaying that there is no medical use. So, when you have psychedelics in schedule I, whenyou have cannabis in schedule I, it's illogical. So, I think many of us would like all drugsrescheduled with more science, less politics. Or, perhaps, not scheduled. But the currentscheduling does not make any scientific or medical sense. It is much more about politicsand fear and xenophobia and, sort of, pharmaceutical company greed and things like that. You know, I mean take this new CBD medicinewhich is being scheduled all on its own in one little schedule, but if it's not an FDA-approvedCBD medicine, then it's still schedule I. Illogical. Not, it doesn't make any sensemedically. Prescription THC, pure THC; schedule III. A plant that contains THC and CBD? ScheduleI. Doesn't make any sense. So, does anybody else wanna talk about drugpolicy? I could go on and on. Well they're two, I mean they're two separateissues. One is the, you know, incorporating psychedelics in medicine where there wouldbe a prescription, and the other is an effort, and perhaps the question was referring tothis, whether these drugs should be legalized, which I think is a much harder question. It seems to me important that there be a wayfor people who are not sick to have access. What Bob Jesse memorably called the bettermentof well people, which I do think the drugs can contribute to, and then the, you know,legalization of these drugs for everyone and I'm not sure where I am on that. It's a veryhard question. The drugs are very powerful. I do think that they need the kind of containerthat Anja was talking about. The virtue of legalization is you can regulate, whereasif you don't legalize, anything goes - Right. But then how do you regulate? And I thinkthose are hard questions and not as obvious as the rescheduling question. I just wanna add, I think another aspect ofthis ... and this could open up a whole nother can of worms, but who are these medicinesgoing to benefit? And I completely agree with you Michael, I think everyone who works inthis field would advocate for some kind of container. On the other hand, you know, assuming thatthe container is some sort of structured therapy, I think at least in the beginning there'sgonna be a great deal of difficulty getting insurance to pay for this. I think that'sgonna bring up issues of access and social justice in terms of who is actually goingto be able to get into psychedelic assisted psychotherapy, and I think that's really importantfor us to think of in the medical community so that this doesn't just become, sort of,a boutique treatment for the very wealthy that really nobody else can get to do. So,I think that's another aspect that I think clinicians are obligated to really be lobbyingfor in all of this, too. That's really important. Last weekend I wasat a psychedelic conference called Horizons and a women spoke there. Her name is MonicaWilliams and she specifically spoke about marginalized people not really having accessto these trials. And so, Maps is sort of enabling a group of people in Connecticut to focusom MDMA in the treatment of racial based trauma or racist based trauma, and having peopleof color and marginalized people come in and be research subjects because if you look atthe data, it absolutely sort of skews white and probably even white male, I would say. Ours is leading a little more towards female- Great. But yeah. In terms of patients you mean, orvolunteers? Yeah. Pretty even though. But I would ... just offerthat to some degree some of this might be unavoidable in terms of the boutique aspect.You know, probably not gonna be covered by insurance, so to some degree that might beunavoidable. And there are, you know, there are definitely risks like any powerful tool.And so, the flip side is that there will be casualties, as there are now. But I ... you know, these are kind of conversationswithin conversations. In the broader aspect, yeah I think it's very clear that the criminalizationof drug use, period, whether we're talking about psychedelics or any other drug has been,based on the data, a public health failure. I mean, so many of the harms have not beenminimized and the devil is always in the details, because I think when you make something acontrolled substance, you actually have very little control. We have control over tobacco.We have control over alcohol. So, you know, in terms of what does legalizationmean? It could mean many things in terms of how ... are these clinics one can show upto for the betterment of the well, or does this mean you could sell it, you know, atthe 7-11. So, the devil is in the details, but it kind of just touches on that biggerquestion of, you know, the unintended consequences of criminalizing drug use and basically criminalizingaddiction, which is a mental health disorder. Right, and it's a public health issue. Mm-hmm (affirmative). It's not a ... prison issue. Next question,please? What is the relationship experientially andpolitically between cannabis and psychedelics? Well, I'll just say that I think cannabisis a psychedelic. Experientially, MDMA is more different than the classic psychedelics.Cannabis is closer to the classic psychedelics than it is to MDMA. But there's a lot of thatsense of ... just, you know, the interruption of your chain of thought, the new materialcoming to the surface. But I would say politically, it's astonishing for people to realize thatwe have an open door at the regulatory agencies for research with psychedelics, but thereis fundamental political obstruction of research with marijuana. And there's been a monopoly,a federal monopoly, since 1968 on the production of legal marijuana for research purposes andfederally regulated research. So, we've been trying for the last 20 yearsto break the monopoly held by the National Institute on Drug Abuse, and they can onlyprovide mariajuana for research but they cannot sell their mariajuana as a prescription medicine.And so, the FDA requires phase three studies to be done in the exact same drug you wannamarket, and so as long as there is this government monopoly, the plant will never be able tobe made into a medicine and what we hear about the CBD from Epidiolex, that's imported fromEngland. So, we have no domestic production, no domestic supplies, and we're getting readyto sue Attorney General Sessions and the DEA to try to force them to respond to roughly26 applications from people around the country for people to grow marijuana for license. Obama permitted the DEA, two years ago, tosay they would end the monopoly and then when President Trump got elected and Sessions gotthe head of Attorney General, he's blocked the DEA from ruling on that. So, ironicallyit's easier to do research with psychedelics than with marijuana. Maybe we should have said at the beginningthat people may wanna silence their cell phones. What sort of education options or career tracksexist for those who are interested in pursuing a path that incorporates psychedelics? Are you ... I imagine you're navigating thisto some extent? Are you comfortable talking about this? Yeah I think you gotta talk with your institution.There's not, at least where I'm coming from, there's not any sort of educational path ortrack. But I think what I would suggest to anybody who is interested in this, given thatthis is still very new and still I think has a fair amount of stigma associated with it;I think it's just really important to talk to people in your institution first just sopeople aren't blindsided by what you're trying to do. Lobby your supervisors, lobby yourdepartment chairs, and talk to them and be open. I think having a rational, science-basedapproach, a clinical-based approach; these are the reasons that you are interested inthis - You know, one of the things I encourage peopleto do is to have, host a journal club. Get a bunch of articles showing these amazinglyhuge Cohen's effect sizes; show them the numbers, show them the data. You know, people understandjournal clubs, they understand statistics. Show them that this research is already goingon at some of the top institutions not only in America but around the world. I would just add that, I don't know if youwould call it a career path but maybe it is, but there's now a certificate program in Californiaat the California Institute of Integral Studies in psychedelic therapy, in being a guide,and they're graduating their third class already. And there is gonna be a demand for ... thereare going to be many phase three and phase two trials coming up, both in this countryand in Europe, and there is going to be a demand for people to guide those trials. Some of the people in it are MD's who aretaking this class. I met several oncologists who want to incorporate it in their practiceand therefore wanna learn how to be guides. But if this research continues on the presentcourse, you know, within five years or so there will be a career. Yeah, I'll just say that it's actually comingsooner than that in the sense that the FDA and the DEA permit a program called expandedaccess and President Trump just signed a law called Right To Try. And so what that meansis that if you have a disease that nothing has worked for and there's a drug that's beingstudies for that disease, you should have the right to try it before it's approved,at your own cost and at your own risk. And so, we've already had preliminary discussionswith FDA and DEA about this and so next summer, the end of next summer, we're going to beopening up expanded access where people can pay for their treatment. We have over 5000therapists who want to be part of our training program, and unlike other drugs that, manyof them once they're approved by the FDA, anybody can prescribe them, any doctor canprescribe them; that's not gonna be the way for psilocybin or MDMA. The only people thatwill be able to prescribe them and the only people that will be able to work with patientsare people that have been through a training program to learn about the therapeutic approach,because it's not the drug: it's drug-assisted psychotherapy. So, Maps has its own training program thatwe've been, so far, trained almost 200 people in how to work with MDMA and there's differentparts of it and we're training now. We've trained everybody we need for phase threefor the US. We're in the midst of training people for Europe and we're gonna start inMarch to train people for expanded access. And so I think really, the first time in 50years that if some people wanted to think about this as a career in therapy or in research,that it's really a reasonable thing to do. I wanted to say something about that on adifferent angle. On the education side, too really establish yourself ... and maybe thisis ... Well, this is true if you're gonna be a therapist too, I guess. Establish yourselfin the areas outside of psychedelics as firmly as you can. If you wanna be a therapist, learnto become a hardcore therapist regardless of psychedelics. If you wanna be a neuroscientist,you know, become a hardcore neuroscientist. If you wanna study addiction, study it withthe best addiction experts. If you're going into grad school and you have a choice towork with this person who just started some psilocybin research and you're interestedin psychedelics for depression, and you're other option is to study with a hardcore,like, well-established, great, depression expert? Work with the hardcore, well-established,depression expert and, you know, be patient and maybe bring the psychedelics on later.Really establish yourself. Just don't, you know don't jump at the first opportunity todo anything with psychedelics. Next question: is any of the research of psychedelicsand neuroplasticity, excuse me ... neuroplasticity and neurogenesis focused on treatment of Alzheimer'sor other types of memory loss? We have that, we're planning on doing workwith Alzheimer's patients with the primary focus looking at those sort of existentialquestions more so than the actual direct disease state, such as memory. But those will be secondarymeasures. But in terms of this, if you're seeing this pattern of an existential crisisthat we've looked at in, you know, cancer and is at play in other terminal illnesses... I mean, you can imagine, that's even worse. Not only are you dying, but before you dieyou're going to lose everything that you know while your spouse is having to wipe your rearend. I mean ... that is a heavy, heavy thing to deal with and so we're kind of hoping thatgeneral mechanism might be at play and we'll see improvements in quality of life. Especiallycause we know that coping with how one handles that diagnosis early on can have some effectin progression of that disease state. Just to bring it back to the question aroundthe idea that the ... the ideas of neuroplasticity and neurogenesis; this actually might providesome relief from Alzheimer's? Is there any indication of hope or anything there? Yeah. I mean, we couldn't say anything beyondwhat you just said that sounds plausible, but we don't know ... you know, we don't knowwhether that would scale up to be at play in Alzheimer's. I think the kind of, the bestthing to do is look at those softer measures which are, we call them soft but they're infact very important. You know, quality of life, how you're living on a day to day basiswhich we ... there's probably abetter bet that you're gonna see some movement thereand then sort of as a secondary exploratory measure, look to see some improvements in,you know, memory function and then maybe if there's a signal there then down the line,looking to see the biology that might underlie that. There's an enormous amount of promising ideas,but one of the limiting factors, the key limiting factor is funding. And so, pretty much everythingthat you've heard of today has been privately funded. There's not yet been major, or evensignificant minor, funding from traditional sources; from NIH or the pharmaceutical industry.And so, there's an enormous number of leads that need to be followed up on that are notcurrently being followed up on. Will double blind randomization ever be possiblefor this research? Can patients be blind to their treatments? If not, what alternativescan eliminate study bias? So, that's a really important question. It'svery hard to do a blinded study with psychedelics because ... for most people at some pointit becomes pretty clear whether somebody has had psilocybin or placebo. One of my ideasthat nobody ever adopted that I think is a good idea is just to dilate everybody's pupils.If nothing else, they'll all look like they're tripping. And, you know, we do sometimes usesort of active placebo, something like niacin that can give people a little bit of a rush,or Ritalin that makes people feel a little like [inaudible 00:49:34], so that it's sortof ... Sorry, that's a medical term. So, it somewhat resembles. But Rick, wanna talk aboutthe whole blinding problem? And I know, Michael, you mentioned it too and I was glad that youcovered it. Well, a lot of my dissertation at The KennedySchool was on how to address the methodological challenges of dealing with the double blindissue. And so, I thought I solved the problem and I thought it would be low doses of thetest drug versus full doses, and you wanted ... that would increase the blinding, butthe challenge was gonna be to find a low dose that wasn't so low, like a micro dose thatyou didn't even know you took it; but that wasn't too high that you got so much therapeuticbenefit that it would be hard to tel the difference between the two groups. And so, with MDMA we tested 25 milligrams,30 milligrams, 40 milligrams, 75 milligrams, 100, 125, 150, to try to find where was theproper control, and when we met with the FDA I started out by saying that there was anearly Harvard president that had a saying: he said, never forget, there's always a Harvardman that's on the wrong side of every issue. And I said, in this case, it was me. I thoughtI solved the problem but we found that the low doses of MDMA actually had an anti-therapeuticeffect because they made people uncomfortable. These are people that have been severely traumatized,unable to cope, and now here they are trying to address their trauma, but the MDMA activatesthem in the low dose but doesn't give enough of the fear reduction. So I said, both to the FDA and to the EuropeanMedicines Agency, that there is no solution to the double blind problem. And what youcould do is you either can let us have blinding and use low dose MDMA, but you're gonna makeit easier for us to show a difference between the therapy and the therapy plus MDMA. Thebest solution, I thought, was inactive placebo with full dose, with therapy versus full doseMDMA with therapy. And so, what the FDA said is that the wayto reduce bias in those circumstances is, the first point is random assignment: thatyou get everybody similarly motivated and willing to go through either the placebo orthe MDMA, and that once you have random assignment, that solves a lot of the issues of bias. Andthen the other part is how do you do the outcome measures? Who says whether they got betteror not? It can't be the therapists that are doing the measures themselves. So, we've workedwith the Boston VA that developed the CAPS, the Clinician-Administered PTSD Scale, whichis the recognized outcome measure, and so we have a group of around 20 CAPS raters thatare gonna do the ratings on telemedicine and they will be randomly assigned to whoeveris the next person to get the rating so that we're breaking the connection between therater following the person through the study and knowing where they are in the study, andalso the therapists aren't gonna be the raters. So, under those conditions the FDA said goahead and use an inactive placebo. They felt it was more important to see what the therapydoes by itself and see what you do when you add a drug, and they surrendered the factthat the double blind isn't gonna work. But I will share the one thing in our trainingof therapists we actually got a protocol where we can give MDMA to therapists as part oftheir training. And so we've had 60 people who have gone through that and they eitherget, they get two experimental days, two days apart, with a day of integration after. Theyeither get inactive placebo or full dose MDMA. And we have had two circumstances, both withpsychiatrists, where they were randomized to the ... The didn't know this, we didn'tknow this; they were randomized to the inactive placebo but they so wanted to have the MDMAand they had watched a week of videotapes about what MDMA is like. It's like they hadthese incredibly productive sessions. They actually had pupil dilation as well. Did they? And they had some blood pressure stuff goingand they convinced not only themselves, but experienced MDMA therapists were 100% surethat they had the MDMA. And that happened twice. So, both times with psychiatrists. So, the double blind is a powerful methodologyeven with drugs like MDMA, but these were people that really wanted so much to havethe MDMA that they convinced themselves and they had really ... The one psychiatrist thatconvinced, one of them, when he got the crossover and he was convinced that it was gonna bean easy day because it was gonna be the inactive placebo, after about an hour when he startedfeeling the MDMA, he couldn't talk for several hours after that. He was so stunned by whathappened and at one point he was pointing to the books on the shelf there and he wassaying, he was like going like ... like it's all in the heart, and it's like the booksare nothing and it's all in the feelings, and he couldn't talk for hours and everythingflowed more easily and deeper. But double blind is amazing. Boston VA that developed the CAPS, the clinicianadministered PTSD scale which is the recognized outcome measure and so we have a group ofaround 20 CAPS raters that are going to do the ratings on telemedicine. And they willbe randomly assigned whoever is the next person to get the rating, so that we're breakingthe the connection between the rater following the person through the study and knowing wherethey are in the study and also the therapists aren't gonna be the raters. So under thoseconditions the FDA said go ahead and use an inactive placebo. They felt that it was moreimportant to see what the therapy does by itself and see what you do when you add adrug and they surrendered the fact that the double-blind isn't gonna work. But I willshare that one thing in our training of therapists, we actually got a protocol where we can giveMDMA to therapists as part of their training. And so we've had 60 people have gone throughthat. And they either get, they get two experimental days, two days apart with a day of integrationafter. They either get inactive placebo or full dose MDMA and we have had two circumstancesboth with psychiatrists where they were randomized, they didn't know this, we didn't know this,they were randomized to the inactive placebo but they so wanted to have the MDMA and theyhad watched a week of videotapes of what MDMA is like, is that they had these incrediblyproductive sessions. They actually had pupil dilation as well and they had some blood pressurestuff going and they convinced not only themselves but experienced MDMA therapists were 100%sure that they had the MDMA and that happened twice. And so both times with psychiatristsso that the double-blind is a powerful methodology even with drugs like MDMA. But these werepeople that really wanted so much to have the MDMA that they convinced themselves andthey hadn't really. The one psychiatrist that, one of them when he got the the crossoverand he was convinced that it was gonna be an easy day because it was gonna be the inactiveplacebo. After about an hour when he started feeling the MDMA, he couldn't talk for severalhours after that. He was so stunned by what happened. And at one point he was pointingto the books on the shelf there and he was saying he was like going like. Like it's allin the heart it's like the books are nothing and it's all in the feelings and he couldn'ttalk for hours and everything flowed more easily and deeper. But the double-blind isamazing. - You know, I mean we could spend a long time talking about placebo responseand how amazing it is and how sort of underutilized and underappreciated the placebo responseis. In psychiatry it's a real problem because people you know if you're looking at likean antidepressant and placebo like sometimes as many as 30 or 40% of people get betteron placebo. Placebo's a big deal and you know how what is the mechanism of that? How dowe get better just thinking we're taking something that's gonna make us better? What's doingthat? - Another question and I think after this last question from this app here we'llpass the mic around, see if anybody has a question they want to voice. As psychedelicmedicine becomes more common, what kind of effects might we expect on recreational use?- [Matthew] I don't. - [Anja] I think that Rick. - [Computer] Goodbye. - Recreationaluse will get more structured because I do think that recreational use is also inspiredby what happens in psychedelic medicines. And people who take psychedelics don't wantto have a bad experience. So if they have more access to models of how to have a goodexperience and what is needed to have a good experience, I think recreational use willbecome safer. Speaking about ayahuasca rituals for instance like unfortunately there's manyayahuasca ritual spreading with facilitators that are not adequately trained to containsuch deep non-ordinary states of consciousness and if people would have a model of how welltrained facilitator guides group, they have better criterias to choose where in whichhands they give their mind. Because that's what they do, participating in a ritual islike you give your mind in the hand of a facilitator. You better choose and know how to choose who'sgonna take care of this vulnerable states you might cross in an appropriate way. SoI do think there is a retro alimentation that it's gonna happen hopefully. - I think wellalso we need to define recreational. I mean there's so many non-medical uses. There'sthe spiritual context or the religious context that you've talked about, that is one. Thereis the underground which has its own codes of conduct. And I have some concern that asdemand for these therapies increases and curiosity about them increases that there'll be lotsof people just hanging out a shingle saying, I'm an underground guide who don't know whatthey're doing. I mean similar to the ayahuasca-ers that are around. And then there are peopletaking psychedelics and going to a concert. So it's not one thing recreation. There'skind of a serious intentional non-legal use of these drugs and then there's a playfuluse of these drugs. And so I think it's very hard to generalize. - Well-- - Yeah there--- Go ahead, go ahead, Rick. - MAPS has what's called the Zendo Project which is psychedelicharm reduction. So I think recreational use as it is currently practiced, will be accompaniedmore by a group of people at these settings that are trained to help people who have difficultexperiences to turn them more into productive experiences. So for example we do this atBurning Man and festivals all over the world and this particular Burning Man we had 900people apply for 260 spots that we chose to help out. We had over 330 people come to usfor assistance. So I think once psychedelic medicine gets more established and the lawschange there's, it's not gonna eliminate all the problems, people are gonna come to this.I think one of the main dangers of recreational use is people take it with the intention ofjust having a good time and when stuff difficult comes up rather than welcoming it, I thinkthat's Anja what you're talking about. If people have a model this can be therapeuticwhen difficult stuff comes up they'll work on that instead of saying, oh my friends don'twant me to talk about this, I'm gonna stuff the feelings and people can end up being worseoff for long periods of time afterwards. But I think this model of psychedelic harm reductionwill become more established over time. - I just want to say one quick thing. As a psychiatristI know that these are very different models of use and that one is safer and one is lessstructured but recreation is therapeutic and I think that for instance if you go to a raveand a bunch of people are taking MDMA and you feel very connected to the group and youhave this sort of collective effervescence and you feel joy and you feel connected topeople and you don't feel isolated that's therapeutic. And I think that it's even medicallytherapeutic. So you know it's a spectrum. And there are things I think anytime thatwe are relaxed or resilient or handling stress, the sort of anti-inflammatory and just likesoothing ourselves, calming ourselves, that's the potential to be therapeutic even thoughit's in a recreational context. Did we want to see if any people have a question? - Sowe could take two questions. If you could line up at the microphone over there. I'mgoing to ask one more question okay then we'll take two from the audience. Is there anyonewho should not try psychedelics? - People with psychotic disorders. And here's the rubthough 'cause how do you know those. People with a predisposition for psychotic disorders.We know squarely in research that we have reliable tools through these structured psychiatricscreenings where you can identify people with even the predisposition. So I would say ifanyone has a question, I mean of course the advice is that there are risk and we're notencouraging anyone to use but whether it's in you know we know something about how thehuman animal responds to these compounds and so whatever setting it is in, people withthat psychotic predisposition those tend to be the people with the prolonged psychiatricreactions. It's also the case that anybody at a high enough dose can have a difficultexperience that can be destabilizing where they have to drop out of college where theyeither kind of life is taking a kind of a turn for the worst. And we've done some surveywork suggesting that is related to the degree to which this they had a sitter present andalso related to pre-existing, even non-psychotic psychiatric symptoms. So people coming inwith anxiety type issues tend to have an exacerbation if they have some lasting issue, an exacerbationof anxiety type issues or same thing for depression. So it's hard to tell. - Right. The safe, youknow, obviously I think it, it's obvious to us it's like if someone is schizophrenia,if someone is bipolar with manic episodes and those manic episodes have psychosis, ifyou've got a first-degree relative with bipolar mania or schizophrenia you're more at risk.Also if you're on psychiatric medicines, a lot of medications do not mix with these psychedelics,ayahuasca in particular because it has an MAOI. There are certain medicines that arereally dangerous to mix with MAOIs like antidepressants and with MDMA there are certain medicinesthat are very dangerous to mix with MDMA that you may not think of like cough syrup dextromethorphanor decongestants. So there are risks in terms of medication interactions and the thing tokeep in mind with all the research that goes on here is that these people are heavily screenedto make sure they're not on psychiatric medicines, that they don't have a psychiatric history,that their family doesn't have a psychiatric history and then we're showing these reallygreat robust responses. And when it's sort of unleashed on the general population andthere aren't all these sort of safety constraints in place there are bound to be more problems.- And there's some physical contraindication also, it's like a very high blood pressureor cardiovascular diseases or in the case of ayahuasca, gastrointestinal lesions likethis. And so it's important to watch out for those things too. - So what's your questionsir? - Yes it seems like we're in a wave now of increasing acceptance of the value of non-ordinarystates of consciousness, provided that they are induced by drugs and I'm curious if there'sany, this leads to any new thinking about the value of spontaneous non-ordinary statesof consciousness that would ordinarily be diagnosed as psychosis or other forms of justmadness. - That's a heavy and complicated question. I know sometimes people talk aboutthings like Kundalini explosions or things that feel natural and physiologic but they'releading to intense altered states. It would be lovely if we had more, if we gave peoplemore latitude about non-ordinary states of consciousness and accepted that there's alot to be gained in these states. I do think there's a lot of stigma and sort of labelingand I get what you're saying that you know sometimes we are sort of discounting something,like for instance, I used to work at the psychiatric emergency room at Bellevue Hospital and Ihad people come in who were in a manic episode who were really blissed-out and felt amazingand had things to teach me and I was ready to learn and they seemed like they were trippingbut they weren't tripping they were manic. But I definitely approached them that theyyou know were having a non-ordinary state of consciousness that they could learn fromand that I could learn from. It would be great if we had more of that in our culture. Rightnow we really don't. So maybe this will help show people that there are other ways of beingthat are potentially not just therapeutic for that person but therapeutic for our society.We have time for one more question and then we really have to wrap up because my mother'swatch says that it is six o'clock because mine's at home. - Hi so you mentioned theword meditation a couple of times through the panel and I was just wondering if thereis any current crossover in either studies or treatment that combines meditation andpsychedelics. - Yeah we just-- - Matt should address that. - Yeah we just published a,well we've had two studies, one is published. The published study was with novice meditators,people without a practice and we were addressing a number of questions about how someone adoptinga meditation practice, how that might interact with psychedelics. We had a trivial dose group,a high kind of full mystical experience type dose group, 30 milligrams body weight adjustedand then we had that same high dose group with a really extra layer of support withgoing from like six extra drug sessions to 26, including group discussions with otherparticipants which people really valued and which we hadn't done before, is normally notpart of this stuff. Essentially the short answer is in terms of the session itself andthis gets to the fruits kind of test that Rick was mentioning, the terms of the sessionitself rates of mystical experience squarely dependent on the psilocybin. I mean now keepingeveryone had the same sort of minimal safe preparation for the experience and the safeguardsbut in terms of, so under those conditions its the psilocybin dose that led, to havinghigh-dose, led to the full-blown mystical experience. But in terms of a number of pro-socialoutcomes, quality of life, altruistic behavior, the types of stuff a lot of people hope toget from a meditative practice, we definitely saw an additive effect. There was low dose,high dose, and then high dose plus the extra support. So we saw evidence on our hands thatthey definitely combined in terms of those long-term fruits and people often said thatthey're different ways of accessing the same type of thing and so we're still sort of dealingwith the long term meditator data but people definitely claimed even after you know fiveor 10,000 hours sometimes lifetime annotation that there was some profound value in havingthese these experiences. - One small point I'll add to that is one of the interestingfindings after Robin Carhart-Harris did his fMRI scans of people on psilocybin, a researcherat Yale named Jud Brewer who was studying the minds of meditators long experienced meditators,he recognized that the scans he was getting which involved suppression of activity inthe default mode network looked remarkably similar. So that there's some reason to suggestthat they're similar states at that level as well. - There's another study that wasconducted in the Zurich University by Martin Heidegger and his team with long term zenmeditators. And they found that the psilocybin deepened the meditation practice. So thismight be something you want to look up too. - You know you're talking about the fruits,Rick and I was just reminded of a couple of studies. One that showed that people who usepsychedelics have lower rates of intimate partner violence and another that there'sless recidivism and those people in terms of being imprisoned. - Yeah parolees are lesslikely to re-commit crimes. - Right, like a parolee is less to commit crimes or endup back in prison if they have psychedelic experience. So weird, interesting sort ofsocietal ramifications from these non-ordinary states of consciousness. I want to thank allof our sponsors, the Broad Institute and MAPS and Harvard an Mass General and Gift and Leoand I'm sorry but I'm totally, Delara sorry I just really had a brain fart there but don'tblame the drugs it's just gas in my brain. That's okay I'm smiling. And I would liketo thank all of our participants, Franklin and Rick and Michael and Matt and Anja andI'm Julie and we're gonna go have a little reception I believe all of us, yes all ofus will go so we'll have a chance to chat more and talk more and thanks everybody forcoming. Thank you.