Psychedelic Medicine: From Tradition to Science

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Greetings. Welcome to you all. My name is Leo and I am visiting your fair city from Marin County, California just north of San Francisco. To begin, I thought we'd try a little experiment in holding space to see if we might deepen our sense of connection as together we ready to explore, to seek through science some understanding of medicines held by tradition as representing the deepest of mysteries. With your permission, I'll guide you through a brief meditation using tools long understood as central to psychedelic journeying, breath and sound. I invite you to come fully into this moment to close your eyes to trust that you, that we, are right where we need to be. Here, nowhere else. With eyes closed, bring your attention inward to your 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 chair holding, supporting, enabling you to relax to let go as you continue to breathe. With your 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 half of the room. Thank you. Please lower your hands and open your eyes. I welcome you to Psychedelic Medicine: From Tradition to Science. What do we mean by this from tradition to science? There is a long section in Michael Pollan's remarkable new book, referencing his conversation with the eminent research scientist, Dr. Roland Griffiths of Johns Hopkins University. A pioneer in psychedelic research, Dr. Griffiths trained in behaviorism His School of Psychology ultimately dismissive of subjective experience. From this unlikely entry point, Dr. Griffiths has emerged as a champion of the undeniable potency of the phenomenology of psychedelic experience as quote "so profoundly reorganizing and profoundly compelling that I'm willing to hold there's a mystery here we can't understand." "You go deep enough and 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 professional interest here is to advance the paradigm and healing modalities of transpersonal psychology founded some 50 years ago by Dr. Abraham Maslow, Stanislav Grof, Anthony Sutich, Jim Fadiman and others. Basing its theoretical frameworks on the studied observation of patients in non-ordinary states, plus respectful engagement with Eastern spiritual philosophies and global indigenous traditions, transpersonal psychology recognizes the power and primacy of first-hand spiritual experience in the treatment and nurturing of psychological health. Indeed tradition approaches psychedelic medicine through the profound subjectivity of spiritual experience. Certainly, we've lost this perspective in mainstream medicine. Science, of course, demands the objectivity of clinical research rightly pursuing agreed-upon standards of efficacy and safety. As we explore psychedelic medicine as potential remedy to the egregious states of mental health in America, we have an opportunity to do so in the spirit of rapprochement between 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 bring to the endeavor. Thank you all for being here today. For the 1,000 plus of you watching online,. Thank you, to the Harvard Brain Science Initiative, the Harvard Medical School, the Multidisciplinary Association for Psychedelic Studies and our host the Broad Institute of MIT and Harvard, for making possible this gathering today. And I'd like to say a very special thank you to Delara Chizari, a PhD candidate here at the Broad Institute, whose efforts have been absolutely instrumental in bringing us all here together. Thank you and 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 the Schedule 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 body of psychedelic research from the 50s and 60s that have been largely forgotten. Over the past decade, research on psychedelics has reemerged with leading institutions including Johns Hopkins School of Medicine and the MAPS foundation. Their findings have illustrated the potential of psychedelics, both as therapeutics and as tools to study different states of consciousness. Research in psychedelics has also highlighted the role and the power of context and experience in healing--something that has often been underutilized by conventional Western medical practices including psychiatry. This understanding and the growing body of research has been impossible to ignore and yet, as undergraduates and even as doctoral students in neuroscience and in medicine, the amount of education that we get in this area is almost non-existent. Over 500 scientists here at the Broad,Harvard Medical School and MIT expressed interest in attending our event today. There are many of us who want to learn more and discuss this topic. So, I'm standing here today in the hopes that we can once again create space to talk, collaborate, and consider research initiatives in this area. Last I checked, there are also at least 1,000 of you who are watching online and thank you for joining us. Both the live audience and online participants can ask questions and upload 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 leading figures in psychedelic medicine therapy and storytelling. First, we have New York Times bestselling author, Michael Pollan. His most recent book, How to Change Your Mind, takes a 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 the nonprofit MAPS Foundation, Dr. Rick Doblin. He brings unmatched expertise in the legalization of psychedelic medicine and has been working for decades to develop medical, legal, and cultural 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 testing of 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 at the National Autonomous University of Mexico. She's also the director of research and psychotherapy at the Institute for Intercultural Medicine, Nierika. Her remarkable work involves collaborations with indigenous healers to investigate the therapeutic potential of the ritual use of psychedelic 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 100 articles and chapters. For over 14 years, he has conducted psychedelic research including psilocybin studies of mystical experience, meditation, and cancer-related depression and anxiety. He and his colleagues at Johns Hopkins are leading a new era of psychiatric medicine in the United States. Most recently, they have proposed that psilocybin be changed from a Schedule I drug to a Schedule IV due to its high therapeutic and medicinal potential and its low toxicity. Next is Dr. Franklin King. Dr. King is an attending psychiatrist and clinical research fellow at Massachusetts General Hospital and an instructor in psychiatry at Harvard Medical School. He's pioneering a new research initiative at Mass Gen to study the 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 drugs and behavior. She was also an assistant clinical professor of psychiatry at the New York University School of Medicine and since then, she has been the medical monitor for multiple therapeutic studies involving MDMA and cannabis in the treatment of PTSD in American veterans and other trauma survivors. Last, but not least, here with us via video-conference is the head of psychedelic research at Imperial College London and soon to lead a similar center at Oxford University. He will begin the afternoon with a brief keynote lecture on our understanding of how psychedelic therapy actually works. Please welcome Dr. Robin Carhart-Harris. - Thank you everyone and thank you Delara it's a real pleasure and privilege to join you. I just really wish I could do it in person but I was committed to a couple events in Canada where I am right now. Sat in some offices in Vancouver so sorry I can't be there in person, but I'll do my best from however many miles away I am at the moment. And what I'd really like to do to contribute to this event is to provide the background and an overview about the brain mechanism the therapeutic mechanisms and psychedelic compound. And hopefully that'll provide some useful material for the subsequent discussion and also to help ground and 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 psychedelic mean? Well it's an neologism, a made-up word, that combines two words psyche the soul or mind and delos which is referring to making manifest, making visible. And so we combine these words as Humphry Osmond did in the 1950s to denote the key property of these compounds which is to make the mind visible, to make manifest aspects of our minds that are ordinarily not fully conscious, not fully accessible to conscious awareness. Another way we can think of psychedelics is to provide you with some examples of classical psychedelics. We have psilocybin here found in the psilocybin species of mushrooms, so-called magic mushrooms and it's pro-drug of psilocin which we'll see in a moment works on the serotonin system in a particular way. And really that's where the initiating effects of these compounds begins. sumatryptamine that can be taken intravenously or smoked we give it intravenously in our research. It's also included in the Amazonian Peru ayahuasca where the DMT is combined with a vine that contain inhibitors of certain enzymes that otherwise would break down the DMT. So it's a way of rendering the DMT orally active and then we have LSD the prototypical psychedelic that really kicked off the modern wave of Western scientific interest, significant interest in psychedelics discovered in 1943 famously by Albert Hofmann. And then things really starting to gain traction into the 1950s 60s and then there's another story to be told about them about how these compounds fell out of favor with the medical and scientific establishment. 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-hydroxytryptamine system, the serotonin system, 5-HT. You can see that their molecular structures share strong similarities with that of the naturally occurring neurotransmitter neuromodulator serotonin 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're stimulating a certain aspect of that system. So what aspects of the serotonin system are they stimulating? Well serotonin itself, it should be said, is a particularly complex neuro modulator. It has at least 14 different receptor subtypes which when stimulated naturally by serotonin do quite different things. Some of these receptors actually counteract the effect of each other but there's one particular serotonin receptors that we now know with really 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, effectively you'll abolish the characteristics, objective and behavioral effects of that psychedelic. Just one of these is really important grounding principles about the science of psychedelics that this serotonin 2A receptor subtype is so key to the action of these psychedelics and it helps bring everything back down to earth. If you block this receptor all the incredible, fantastical, psychological effects of these compounds just don't happen. So I do think it's a very important principle. Where are these receptors? Well they're heavily expressed in the cortex that aspect of our brains as humans that's so massively expanded in our species and really defines us in terms of how our brains are different from other animals. And more than that we now know through recent, relatively recent advances in brain imaging that the 2A receptor is most heavily expressed in the highest level aspects of the 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, reflecting on our path, our autobiographies. Also contemplating the future perception, so imagination. These kind of functions that are arguably species specific that humans do to do quite an exceptional extent. 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 psychedelics for this particular receptor subtype correlates very strongly with their potency. So for example LSD, very high affinity, very potent, you only need a very small amount of that compound for it to have psychedelic effect. And then this other follow-on question which of course is 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 stimulation do? Well we now know quite compellingly that it seems to promote a generalized plasticity both at the level of anatomy, low level anatomy, in terms of growth of new neural connections but also functionally as well, promoting a flexibility of mind, cognitive and behavioral flexibility. 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 contextualize all of this and now where we are in terms of the therapeutic development let's just run through a brief history of developments in psychiatry and psychopharmacology. We had the monoamine oxidase inhibitors arriving in the mid-1950s, a key moment in the so-called pharmacological revolution in psychiatry as drug treatments begin to really gain traction and influence. But the pharmacological action there is quite broad. We have a drug that's promoting not just serotonin but other important brain chemicals like noradrenaline or norepinephrine and 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 problematic side effect profile and crucially are more specific in their action. Instead of promoting the availability of monoamines in general all these different chemicals, they're promoting the availability of a specific neurotransmitter and that's serotonin 5-HT. And now we're going full circle and coming back to looking at psychedelics seriously and it's important to reflect here that here we have a class of compounds where granted their pharmacology isn'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 of progress in the precision of the pharmacology of a particular drug intervention. But it would be wrong to characterize this as just a drug of course and let's again just run through how things have developed in throughout the 20th century in terms of psychiatry, psychoanalysis and death psychology dominating the first part of the 20th century. The pharmacological revolution coming along in the 50s and now we find ourselves again full circle considering an intervention that involves a drug but a drug that opens a window of plasticity, a window of flexibility in mind and brain in which psychological interventions may well be much more effective. All these developments have helped us understand something important about serotonin itself, I would wager. Though in terms of what serotonin does that's been a mystery for quite some time in psychopharmacology. Unlike with other important brain chemicals like dopamine where we have a slightly firmer footing, thinking of this compound in relation to reward and value related are a surprise. Serotonin has got people scratching their heads for quite a while and ideas of course have been raised. The idea that serotonin works to moderate stress has been very influential. That it can moderate negative affects particularly for example dampening the responsiveness of an important fear system in the brain the amygdala for example and also that it aids patients that it works against impulsivity has also been gaining traction. But some recent work that's really interesting me is this notion that serotonin has an important interaction with environmental factors. So for example genetic work showing the certain variance in certain aspects of the serotonin system only really kick in and have a significant effect, given certain environmental conditions. So for example childhood adversity and then certain genes being associated with mental or mental health outcome. Also the work of the likes of Igor Branchi, who's coined this term the double-edged sword of plasticity in relation to serotonin that if you increase serotonin levels as you might with an SRI, for example, a Prozac-like drug, you won't necessarily 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 do well, if you for example up the dose of an SSRI but if it's adverse they may do actually worse. So it's an important nuance in how we're thinking of serotonin and I would add as well it's helping us understand this certain aspect of the serotonin system that the serotonin 2A aspect. And saying more specifically that it's perhaps stimulation of this particular receptor that accounts for that interaction between serotonin. Now I'll just run through here 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, that animals won't self administer them, that they have low toxicity. We think of a compound like psilocybin, a very low physiological toxicity, much lower than ketamine for example that's starting to gain traction as a rapid acting antidepressant. Also the antidepressants and other therapeutic effects appear rapidly, very quickly, and also that the effects appear to be enduring something that might confer a significant advantage to classic psychedelics over an intervention like ketamine. And then these significant improvements in well-being that were really brought to the fore by the the Hopkins team giving a single high dose of psilocybin to people who've never taken a psychedelic before and then seeing these remarkable enduring increases in psychological well-being that appear to be mediated by the quality 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 particular component. And then population studies, the likes of Peter Hendrix looking at suicidality and 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 those who had used psychedelics actually had better mental health outcomes than those who hadn't and that's of course is an incredibly challenging finding in that it contrasts the association that 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 psychedelics appears to buck that trend. And so there's the first significant study that kicked off the 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 effects there. But really the significant work has been looking at end of life distress, anxiety and 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 the recent studies from NYU and Hopkins, published in 2016. Very nice design for placebo controlled studies with control compounds that have a degree of activity to them. Niacin in the NYU study and a very low dose of psilocybin in the Hopkins work. And so things are starting to really look quite exciting at this point and the addiction work, Matt Johnston looking at smoking addiction and remarkable outcomes there. 80% abstinence rate I think is it twelve months, I think, Matt could correct me on that, after I think two treatment sessions with psilocybin. These are really remarkable outcomes in the context of leading treatment. Michael Boganschutz looking at psilocybin for alcohol dependence again very impressive outcome. We've looked at depression, we looked at particularly severe depression treatment, resistant depression. People who tried on average 4.5 different antidepressants that hadn't worked. 90% of the sample that tried some psychotherapy of the multiple different psychotherapies had a couple of patients who tried 11 different medication, average duration of the depressive illness, they reported to be over 15 years. So really quite stubborn intractable depression and yet we saw really quite significant improvements appearing rapidly after two treatment sessions with psilocybin a week apart. A low dose 10 milligram followed by 25 milligrams a week later juxtaposed with psychological thought preparation. Of course care 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 five weeks. And so enough, even though a major limitation of this study with its open label design, there wasn't a control condition so we can't say with confidence that this is impressive effects, I choose specifically to psilocybin that might seem the obvious inference but you know there's a lot of other things going along the psychological support and such like. But even so it's enough to deserve further research and that's where things are going now. So our next trial at Imperial, we'll be comparing two treatment sessions with a full dose of psilocybin 25 milligrams again with psychological supports inside and throughout against a leading SSRI escitalopram six weeks of escitalopram or the two treatment sessions of psilocybin with controls for all the different aspects like placebo captions every day, controls for escitalopram captions for example. Now things aren't just you 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 heavily in psilocybin treatment resistant depression, a multi-site trial across Europe starting quite soon in communication with regulators also conversations going on with a few organizations with the FDA as well. So things are really started to gain traction. So that's where we are and given all of this it's very timely and appropriate that we have some kind of model to address this potential question of how this treatments working and you'll have noticed that there are multiple indications here. So it's not just depression, it's not just addiction, it's OCD and potentially other indications as well, eating disorders perhaps even phobia. And so is there something a kind of unifying principle here perhaps that might help us understand how one particular intervention might be effective for a range of different disorders. Well first we can start by thinking, well maybe there's a common ground among these different disorders. And one way we might think of that is to take inspiration from a leading model arguably the leading model of how the brain and mind works. The so called predictive processing model. This is a model that tells us that our interactions with the world involve essentially two players in some sense. The predictions of beliefs that we house in our minds, has to begin with and then what we experience. And that if there's a mismatch, we will then update our beliefs. But the key principle here is that it's our beliefs that very much dominate how we experience the world. It's really the kind of bottom line. It's not that we have a direct line to reality so to speak. So much of our experience of the world comes from these mental models that we house in our brains. We know that through a lot of different things like optical illusions for example. Why do we see these optical illusions if it's not for the the models that we house in our mind. And so in the context of psychopathology, we can think of this process going awry, we can think about belief becoming to influential, resistance to updating based on evidence, becoming very rigid and stuck and then dominating our thinking and our behavior. It's very easy to think of that in the context of depression for example with a negative cognitive bias where we see the world through these very pessimistic eyes. Then eating disorders where we have these beliefs, you know, that we're overweight or we're unattractive and phobia again these irrational beliefs that can become so rigid. So given these conditions you know what might be a solution? Well it stands to reason logically that if we could only revise those beliefs then we might really have some. But in order to revise belief we need to be able to relax them initially and so how do we do that? Well like I said at the beginning, we now know with confidence that the serotonin 2A receptor is key to the characteristic, the signature effects of psychedelics. It's the initiating event. But then there's this is other curious question. What goes on afterward? Now some people will tell you that it's mystery, perhaps we'll never know. I tend not to agree with that. I don't think psychedelics work in any supernatural way. I don't think they work by magic. I think they work based on the laws of nature and that we can naturalize this phenomenon, we can demystify this phenomenon and because of that make the best use of these compounds. And so what happens when you stimulate the 2A receptor? Well I said it induces this window of plasticity, I've described it elsewhere as an entropic state. You can think of this in relation to temperature, how you can heat up a substance and make it more dispersive then the the phenomenon becomes harder to predict, it becomes more chaotic. And so if we come to sample that phenomenon, we experience uncertainty because it's chaotic. We don't know what it's going to do. And so this is a really quite a natural mapping between what's going on at the physical level in terms of an induced chaos that we can see in the brain. We see brain activity becoming more complex more entropic harder to predict and people have this, they embody a state in which their ordinary assumptions start to kind of disperse and they feel a very acute uncertainty and lack 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 in terms of the acronym but it stands for Relaxed Beliefs Under Psychedelics. And I think this is the kind of foundational phenomenon. So if we can relax our high-level beliefs, beliefs in ourselves, our ego for example, then we can be more sensitive to both what's within our 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 and it has to be emphasized, it is a process that perhaps doesn't end during the acute psychedelic experience itself but starts bleeding into the integration work as well. But how can we experience insight if we don't first relax the way the system may be including our clear vision. And so that's really critical that there be a relaxation even a collapse of these including factors like our ethos and then in those conditions have the possibility to see 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 emphasize there's initially a relaxation of these high-level beliefs in a hierarchical sense. Remember I emphasized that these 2A receptors are in the highest aspect of the cortex. There are other 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 pyramidal neurons, very important brain cells, very key computational units in the brain. Also important 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 can recalibrate them, we can have beliefs that are more in tune with data. Data that can be within us, our emotions, our bodies proprioception, interception, but also more connected and in tune with of course the world out there, other people and perhaps even some philosophies and perspectives on the world beyond just person-to-person interaction. So this is where I'm working towards a conclusion that there is, its initial relaxation working towards the revision of beliefs. It very much resonates as what our patients and I think others say in the context of psychedelic treatment that it feels like a kind of rebooting, a resetting of a system that's being in a sense malfunctioning, becoming stuck in it's functioning. You have a 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 network associated 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 look after people have come down from a psychedelic, here we're looking the next day after treatment with 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 the experience but ethically could you really do that when you're trying to treat people with depression with psilocybin. You know you don't really want to shove them in an fMRI scanner. But here we're doing our scanning one day after the treatment and we've seen this reintegration of the very same network that disintegrates acutely. We also see that those who responded back to the treatment were those who show this reintegration effect most markedly. Now this is something that's also been seen with electroconvulsive therapy and granted this is a very different treatment model from that but ECT is, if we just look at efficacy, does have a particularly you know high efficacy for at least dropping depressive symptoms. That's not a defense of ECT, it's just to say that that's what the evidence tells us. It is effective at reducing depressive symptoms. So it's interesting, I think, that there are overlaps there. But of course there's much more to psychedelic and what is it that is more. Well by definition these compounds are mind revealing. That's what first drew me to this work, reading Stan Grof's book Realms of the Human Unconscious. Just being absolutely 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 had to 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 relaxation of that conclusion. And this term epistemic transformation that now after the experience and perhaps also during although things can be quite chaotic. But there's a kind of realization of revelation, there's been a shift in perspective and ability to see the bigger picture. Now something's known and it can't really be unknown. The mind is unfurled, it's opened up and we've been able to see more of it. And so here just showing that insight scores are correlating with 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 energy landscape 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 into the depression right and it's gonna be hard for that ball to get out and so how could we change the landscape so that there could be greater freedom and the ball if we think of the ball as where the mind is at any particular moment, how could we change this landscape so that it can move around more freely. Well we can pull it tighter, we could flatten the attractor landscape and so we're developing based on our brain imaging work now, results that'll soon be published that actually show this a flattening of the attractor landscape that systems configurations in the brain that are ordinarily dominant become less dominant under a psychedelic. So that the mind can wander more freely under these compounds and again this may well account for the ability to have spontaneous insight that appears to mediate 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 to this. It's a team effort here, I say here, back in London with the wonderful group that I work with. It's a real pleasure to work in this domain and it's a pleasure to contribute to 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 gonna bid you adieu now and get our panel rolling. Thanks so much for your time and we'll see you again soon. - Thank you, all the best. - Cheers. So I think to all our panelists will invite you all up with Julie moderating. As they're coming up just want to mention again 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 psychiatrist in New York City and I've edited a book on MDMA and a book on cannabis which I do consider to be a psychedelic and I'm the medical monitor as Delara said of some MDMA PTSD studies and cannabis PTSD studies. How I thought we would start is for everybody just very quickly say lookin' at a you Rick. Say a little bit about what you're doing now but then what drew you to 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 working in Mexico and we are bridging the traditional indigenous medicine with psychedelic medicines and 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 and all the contribution that could be made if we take a closer look of the wisdom that is still alive in those traditions. - And maybe a word or two about what drew you to this field 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 got introduced to the ayahuasca so this was really life-changing for me and so I got engaged of trying to bridge this with Western psychology in psychotherapy and exploring more the potentials of this medicines. - [Julie] Can you explain ayahuasca for people who may not know what it is? - Yeah ayahuasca is a plant compound from Amazonian medicines which is a mixture of two plants vine Banisteriopsis caapi and leafs from the chacruna. There's up to 80 other 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 at Johns Hopkins since 2004, conducting research with psilocybin and some other psychedelics studying things like mystical experiences and healthy normals, cancer patients with existential distress, depression, anxiety, smoking cessation as was mentioned. That's some work we're continuing with, had some very promising results, hoping to expand that to some other addictions. We've started some work on anorexia, hopefully very soon. So we're moving in a number of directions. And in terms of what got me interested, I'd say I 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 interested in psychedelics or you don't know anything about psychedelics you don't know anything about the history, the indigenous use, you haven't talked to anyone who lived through the 60s. So my interest is in psychedelics as behavior change agents. Which I really see 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 and drugs were just all around and I too was very interested in drugs and behavior and I remember sort of seeing how oddly people would act or behave if they had had LSD or PCP and these were things that were sort of somewhat common in the 70s in suburbia. So I sort of feel like that's how I came to it is that I was sort of somewhat surrounded by drugs and it may have been a little bit self-selected. And then I went to University of Pennsylvania where they had a major called the Biological Basis of Behavior where I learned psychopharmacology and more about behavior change with drugs. But while I was an undergrad there was a new drug on the scene which I was very excited about. I didn't think there would ever be a new drug in my lifetime, I mean I, you know, there seemed like there was already enough with LSD and mushrooms and cannabis and I thought that was plenty but while I was an undergrad 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 catalyst to make the therapy go deeper and be more efficient. And that was around the time that I met Rick Doblin and he will speak soon with you. I'm gonna let Michael speak now because I think we're having some technical difficulties with my microphone. See if they're having them with yours. - Thank You Julie. - Thank you is that you? - Wait, it's more me. - That's ghost Julie. Well I've had a long-standing interest as a writer in altered states of consciousness which grows out of my interest in our relationship to other species and plants and in particular and I've been struck by the fact that one of the things we use plants for and have for thousands and thousands of years, has been to change consciousness. And this is common among virtually all cultures. And that struck me as a very curious human desire. What is it good for? What's the value of changing consciousness? So that was in the background when I touched on that in a book called Botany of Desire in a chapter on cannabis. And then I started learning about the research that Matt and Roland Griffiths were doing at Hopkins and specifically about the study of cancer patients which is a mind-blowing piece of work. And I wrote an article about that for The New Yorker and I interviewed a great number of people who were really right up against death, against their mortality and on a single psilocybin trip they had experiences of such power and transformative power that they had completely reset their understanding of their own mortality and were able to in many cases diminish or even eliminate their fear. And this struck me is so improbable and so important that I became intensely curious about the process. What was the science behind it? How could we possibly account for these changes? And that led me down the path that became my recent book, How to Change Your Mind. But it really began with those cancer patients and my interviews with them as well as the researchers at Hopkins in NYU. - Well I got into this field primarily because of fear and politics. Growing up in the 60s I was educated about the Holocaust, I was scared I would be a victim, I was a young boy during the Cuban Missile Crisis and then also in the tail end of Vietnam. And so I just felt like the murderous nature of the human species was potentially gonna make me a victim and all of us victims and we see what's happening with the environment. And I stumbled on psychedelics and felt that they were tools that could promote a sense of identification beyond all the ways in which we defined ourselves through our religion, through our country, through our gender, through our class, all the different ways that we separate ourselves from each other and define ourselves. That this sort of psychedelic mystical experience, the sense of unity and connection had profound political implications that would be in the direction of compassion. And I felt that these tools when I first woke up to them in the early 70s 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 this area and that was really through reading Stan Grof and the work that he pioneered with psychedelics and transpersonal psychology. And so he really inspired me and was someone who would like to be here. He had a mild stroke. He's doing really well now but still learning about reading and talking so he couldn't be where here with us today and just said that if anybody wants to 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. And what I ended up doing and what I'm doing now is started basically a nonprofit pharmaceutical company because these drugs were abandoned by government, pharmaceutical companies, major funding organizations and so MAPS is on the verge of starting phase 3 for MDMA-assisted psychotherapy for PTSD. We've raised $27 million all in donations and we're starting phase 3 and we're moving to work in Europe as well. And just to give you a sense of how things are changing on Monday I was in Orlando and I gave a talk at the International Association of Chiefs of Police and it was about MDMA for trauma among police officers. And the same strategic sense I have also President Trump, he was there as well and for different kind of reasons and so I think that we're on the verge really of medicalizing these drugs and I think that that's the doorway into reducing the fear that people have about them and to show that we can create contexts where the benefits outweigh the risks and hopefully it'll lead to a reintroduction of these tools into our society for therapeutic uses 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 of those right now is sort of at the interface of medicine and psychiatry. I completed a fellowship that really looks at how people respond to medical illness from a psychiatric perspective and the manifestation of psychiatric medical symptoms, medical symptoms as a response to stress, depression, anxiety. What I'm working on for next year is my first study in psychedelics working on an imaging pilot at MGH, hopefully involving some of the study subjects for MAPS so we'll see how that goes. But as far as psychedelics and why I've been interested in this, this is something I've been following with a lot of interest since medical school and 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, the substance of the mind to heal people and I think if you learn about what psychedelics seem to offer for promise for healing people there's a great deal of potential there. So that's really what I've been seeing and I'm really happy to be here and excited to see the progress over the past few years. Research is just exploding in this area. It's really cool. - So Franklin when you look to the future and like what's your dream job? What's your absolute fantasy dream for what kind of research you could be doing if Mass General was like what do you want to do? Just tell us what you want to do and you can do it. What would you choose? - Yeah sure. So part of what I really like, I spent a lot of time in residency focusing on psychotherapy so that's actually a big component of what I'm interested in and at the totally opposite end of the spectrum, I'm also interested in the neuroscience and what we can learn about consciousness. So my dream job would really be working in a translational research center where I could be both working as a psychedelic psychotherapist for patients but also working on research initiatives to really understand. I think these medicines not only are treatments but as Dr. Carhart-Harris was talking about, they offer 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 things but what they actually are from a phenomenological level. - So speaking of phenomenology, I actually want Michael to explain a little bit about default mode network and your understanding of it because you go in depth in the book talking about default mode network and maybe just this idea of like shaking up the snow globe and what that would mean. - Yeah picking up on what Franklin just said and referring back to Stan Grof who I think we need to thank for, with Leo's help, bringing us all together. One of the things that got me started on these kind of questions as to what psychedelics reveals about the mind beyond the therapeutic applications is a line of Stan Grof's that I think has influenced all us. And I forget when he wrote it, I think in the 70s, but he said that psychedelics would be for the study 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 when I first heard it but I increasingly don't think it's so overstated. And that these substances have the potential to open a very interesting window. When you disturb a system as with a particle collider, you can force it to reveal its secrets very often and I think that that's something that is happening. And I think that Robin, who you just had the privilege of hearing lecture, is making really profound strides in. One of the areas that he only touched on briefly is when he began imaging the minds of people on psilocybin, using at first fMRI and then some other modalities. He was surprised actually, the field was surprised, to discover that contrary to the expectation that psychedelics would simply boost mental activity across the board, psilocybin, and this proved to be true for LSD as well, diminished it, quieted action, 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 the cortex, prefrontal cortex with older systems involved in memory and emotion. And it seems to 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 autobiographical memory, the way we construct stories about who we are and fit information from our lives into that story. It's also a sort of bestrides the mind in kind of the top of the hierarchy and seems to be kind of a very important traffic hub and when that network is silenced or at least quieted very interesting things happen. When you see that happening on an fMRI what the patient is reporting phenomenologically is a dissolution of the sense of self to a greater or lesser extent. So that seems to kind of support the idea that that's what's going 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 exchange information in a way they don't normally which might explain the prevalence of things like synesthesia where one sense is cross-wired with another or hallucination. So that was a very important insight I think into consciousness and in our sense of self that already psychedelics have helped us to see and no doubt there will be a lot more like that. - So Matt I kind of want you to pick up a little bit on this idea of ego disintegration and default mode network, 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 a little bit about the mystical experience. - I think it's taking that hub off line as Michael said. You know it's like this, a bus driver that doesn't allow anyone else on the bus to talk to each other. They have to relay messages to the bus driver and without that bus driver you know everyone else is not allowed to communicate. And so you're kind of kicking that bus driver off for a second then people can start chatting and getting rowdy. So I think that that more has been looked at on the the positive side. The sense of unity which is a core feature of the mystical experience which is a construct we've looked at in a number of studies now. But this is more speculation here, I think that disintegration is also an inherent part of the so called bad trip. The challenging experiences which is something we've more recently started to focus on, we've developed a validated scale to assess the nature 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 sense of self that seems to be the biological correlate of it is the default mode network functioning it seems. That's kind of the ultimate carpet that's pulled out from somebody. That's where our minds are full of models of heuristics and the self is the ultimate model at the center of everything and it's key probably. And to be clear this is part speculation based on the research but so many of our human problems, so many of our psychiatric disorders that don't have a really great correlate in nonhumans, you know really have to do with sort of the necessary evil of that very strong sense of self. It's very useful but it has, gosh it can be full of kinks. And so when you acutely disintegrate it, you could have this oceanic boundless 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 incompletely jarring experience. We found that on the positive side when the sense of unity or the the fuller construct of mystical experience is endorsed with unity, transcending time and space, it's a sense of paradoxicality, ineffability, positive mood. When someone rates those qualities as very strong after their psychedelic experience we see that healthy normals, people without a diagnosable problem, they and the people around them are saying that they are better functioning over a year later. They're easier going, they handle problems better. We see that cigarette smokers are more likely to be biologically confirmed as abstinent from smoking. We see that cancer patients are more likely to have less depression symptoms and anxiety symptoms and other studies there seems to be that trend for the alcoholism work that Michael Bogenschutz has done as well. So there's something very special about this sense of unity. about this acute experience and that's really the, I see that as the paradigm shift that 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 as a medication facilitated learning experience. This state of plasticity very much in line with what Robin was describing where, yeah, under the right circumstances it could be dangerous for things to go a little bit more into chaos but in the right conditions pushing things towards the right direction with the right safeguards in place, you can drop that sense of self acutely in the right way and that can lead to some wonderful outcomes and some of those kinks tend to be kind of taken out of the system. - So I know with the Hopkins research, they really showed definitively that the more intense of a mystical experience you had the better the outcome. Whether you're quitting smoking or whether with Bogenschutz you're quitting alcohol or you're quitting being afraid of dying. But if you have this sort of ego disintegration and the sense of unity and connection that you come away feeling better. And a couple of things I mean one is that you know at the peak of a psychedelic experience for some people they feel like everything is connected and they are part of that connection and that's a blissful feeling. And one thing that you see in surveys of people who use psychedelics is that they feel more connected to the environment and they are more sort of eco conscious and I know that MAPS is looking at using MDMA in a conflict resolution. But this idea that if you sort of quiet the self and the sense of self and you're more committed to everything being connected you may be a better citizen. An interesting research showing that when you present people with their own political views that they agree with, their default mode network kind of lights up and they're like that's me and that's what I believe in. And it may be that if we can bring that down a little bit and bring some of the beliefs down and have people be more open to some other political ideas that that may also be better for us. But I want to ask you Anja, if you're comfortable speaking about ayahuasca in ritual context and some religions using ayahuasca as a sacrament and this idea of unity and connection not just to the universe when somebody is peaking on psychedelics but also just connected to the clan, to the tribe, to the group that's having the ayahuasca and social cohesion. I was wondering if you're comfortable talking about any of that? - Yes, sure. - Okay. - Yeah, I think this is one of the contributions actually that traditional medicine can make to modern psychedelic medicine is the group part. Ayahuasca and as other psychedelic plants that are used in indigenous people are used a lot also for socio-therapeutic processes. Oftentimes the family is present too, of a patient and then there's a lot of group dynamics that happen in ayahuasca ceremonies which I do believe they have a big therapeutic value. Interestingly in such groups where ayahuasca is administered it happens very frequently that an experience of one member of the group is complementary to the experience of another member of the group. So in a group integration process this can be used therapeutically to enhance the individual therapeutic experience. I think also the fact that as human beings we are social beings like this group container speaks to the social part of the soul and that indigenous people have intuitively just very subtly developed techniques to create a group consciousness within a ritual. So you wanted me to speak about the ayahuasca religions. There is syncretic ayahuasca religions where ayahuasca is used in a very structured context in very huge groups and it's really impressive to see how well-structured those religions can contain the collective non-ordinary state of consciousness and directed into in this time like collective blissful states of religious ecstasy. But also if there's individuals that having a difficult time that go and touch dark inner spaces, they are very carefully taking they took a part in a special therapy room where they accompanied in a very centered and individualed way to pass those difficult spaces they may experience. So those models I think they could be adapted into modern psychedelic therapy in a way that could reduce costs for those application because it's very costly to have two therapists for one patients. And I do believe a lot also of the therapeutic value of the group as such if this is really taking care of in the appropriate way. This is like the most important factors because on the other hand groups that are too big and that are 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 and politics and I wanted you to talk a little bit about this conflict resolution and also the the couples PTSD work. I know this is MDMA and not psilocybin or LSD and I think officially MDMA is not a classical psychedelic but I think if you're using the definition of mind manifesting then I think that MDMA is a psychedelic. It certainly works on the serotonergic 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 resolution studies. - Yeah, you know part of the work that we're doing to help mainstream psychedelics and MDMA in particular is reaching out to various therapists who work for the Veterans Administration who have developed different non-drug therapies for treating post-traumatic stress disorder. And there's one particular approach called cognitive behavioral conjoint therapy. Conjoint meaning couples. And it's where one member of the couple has PTSD but it affects the relationship. And so through the work of Richard Rockefeller and his cousin Senator Jay Rockefeller who was on the Senate Veterans Affairs Committee, we got to open up some doors for us at the Department of Defense and that the VA and they suggested that the first study that they would permit their researchers to do was to blend MDMA with this cognitive behavioral conjoint therapy. We had to pay for it. The vets had to come or the subjects had to come from outside the VA and the people had to use their academic affiliations not their VA affiliations but we were able to get permission to give both members of the couple MDMA. So this was the first move from individual psychotherapy with two therapists a male-female team for one patient to moving into at least two people getting 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 to diminish the PTSD symptoms in a substantial way from the person that has PTSD and also increase the couple's relationship. And we're starting to sort of back our way into couples therapy. You can't medicalize psychedelics for couples therapy because it's not traditionally a disease. They have a difficult relationship we can, feels that way sometimes but we can only medicalize for you know major diagnoses. But that was a step towards understanding how this drug can be used, MDMA, in both couples therapy and PTSD but also in furthering conflict resolution ideas. And so you know one of the clues that came to us about this was when MDMA was first developed as a therapeutic drug in the middle 70s to the early 80s and then it sort of escaped from that and became a party drug Ecstasy and then got criminalized in the U.S. in '85 and I was involved trying to protect the therapeutic use of it at that time. Then it started moving to Europe and particularly to England and it was being used in a lot of clubs and bars in England in particular and what people noticed was that the soccer fans 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 and Protestants would get together in certain areas and do MDMA together. And right now there's groups, small groups of Israeli Arabs and Israelis Jew's doing ayahuasca together and doing MDMA together. And so MDMA diminishes fear about difficult emotions. It makes people better listeners. It's make them more empathic. It releases oxytocin and prolactin that promotes a certain kind of bonding and so the idea that we can use MDMA and potentially other psychedelics as well in conflict resolution context is something that we're very much interested in exploring. And I think it's at the very early stages. Again it's very difficult to medicalize that but it's something that we can do experiments with and we're hoping 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 each other so much that are unwilling to even talk. It'll be kind of the people that are closest to the people on the other side and want to learn more about them. So in a sense we're gonna be training the trainers. We're gonna be working with peace activists from both sides and trying to help them realize their own biases and their own fears and help them become 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 for a whole lot of other things. But I think this idealistic vision is not completely ungrounded or fantastical. I think there's a lot of evidence to suggest that these drugs can be used in conflict resolution situations and I would say just one thing about the difference between the way you described about the mystical experience being the key to therapeutic outcomes. That the depth of the mystical experience with classic psychedelics correlating with therapeutic outcomes and that's a fundamental difference between the research that's been done with psilocybin and the early work with LSD and the work with MDMA. And so what we found is that there is no correlation between the depth of the mystical experience and people do have quite profound experiences in that nature and using the same measures as is used in psilocybin. People score pretty high on this dimension of mystical experiences but there's no correlation between that and therapeutic outcomes from PTSD. What it really involves is taking people's memories of their trauma and helping them confront them in a different way where they're not so terrified and they could process them. So I think that in a conflict resolution situation, you're not losing your sense of self, you're not immediately going to 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 resolution and then eventually what we'll do is administer other drugs as well. And so I think that's really the direction that we're hoping to go in. - I want to touch on a couple of things you said. I mean you mentioned oxytocin and my little ears go bling. I'm very interested in oxytocin and I know that with ayahuasca or with psilocybin or LSD at the peak when you feel like everything is connected and you're connected with the universe and that kind of feeling of connection that is a high oxytocin state. With MDMA which is also a high oxytocin state, it's a little bit more grounded and less out there and more like you're connected with your partner if you're doing conjoint therapy or you feel very connected to the therapist and this enhances the therapeutic alliance. And that is one of the outcome markers for how well people do is if there's an enhanced therapeutic alliance between a clinician and a client, you're gonna have a better outcome. And one of the things that MDMA seems to particularly get at because the oxytocin sort of dampens the fear response and the amygdala is less fear and more love and more openness basically and more trusting and more bonding which does sort of again get us back to this kind of us and them mentality. And if we're all on the same team we can work together but I did I wanted to talk to you Franklin about you're interested in psychotherapy and you're interested in psychedelics. I'm wondering if you feel as I do that MDMA is particularly well-suited to be a catalyst to make psychotherapy go deeper and go faster be more efficient. Do you have any sense of that? - I mean I think it depends on what you're trying to treat and what you're trying to accomplish. One thing that seems clear though is that the outcomes that we're seeing from all of these studies that are coming out are really major changes in response to depression, to end of 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 it often takes time. It takes multiple trials particularly from psychotherapy alone in order to sort of get to these states. You know I did the Part B MAPS training and part of that was really just watching a lot of the therapy sessions with these veterans with PTSD and they were really sort of having revelations about their trauma that you would be overjoyed to see in the clinic but you would spend two years of intensive weekly therapy and this was happening in a single session. So I certainly think from the realm of trauma and sort of getting someone into a state where they feel comfortable processing some really difficult experience that they've had that really has kind of left an imprint on the way they think about their world. And that sort of goes to what Robin was talking about, about altering beliefs, traumas, you know more than probably anything else. Stamp they're, sort of, they leave 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 trauma but in terms of perhaps things like anxiety, particularly end-of-life fears about destruction of the self that may be why psilocybin perhaps is more well suited. Something that's a little bit more introspective that lets people get a little bit deeper not into trusting but into meaning and sort of more existential aspects of existence, so. - Katherine MacLean refers to psychedelics as sort of like death rehearsal because when you have that ego disintegration and you don't exist anymore it's very frightening and uncomfortable. Maybe Michael you want to talk about being in the void and what that feels like. But after that sort of not existing and being in the void, optimally you have the bliss of the light and things coming together and sort of feeling that and I forgot where I was going with this actually. - You want to report from the void? - But if you want to talk about, I got lost in the void which sometimes 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 transformative experiences on psychedelics, I became naturally intensely curious to try it myself. I had had 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 of how I work. You know when I wrote about the cattle industry, I bought a cow. So writing about 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 with underground guides and there is a extensive community of very serious therapists who were working underground illegally and I found my way into this community and worked with several different people, using several different medicines. The relevant case though that I'll share with you, is a guided psilocybin experience that I tried to make as much like what was going on at Hopkins as I could in terms of dose and setting and everything. And you should know I was terrified before every one of these trips, I had a sleepless night, I argued with myself was this a crazy thing to do, I went to my cardiologist before I made a move. I was a very reluctant psychonaut and I would I realized every time this happened that it was my ego actually trying to stop me from this assault on my ego. But fortunately for me it failed and I managed to go ahead and have the kind of experience that I was hoping to have and on a high dose psilocybin trip, I'm gonna cut to the chase. But I did have this kind of shocking experience well into the trip of feeling my sense of self go up in a puff of little Post-it Notes. And I and well for a writer I guess it was. But there was another but there was a perceiving eye nevertheless. Even though I saw my sense of self fall apart, somebody there was another first person that had opened up and it was the first person that I had never had any acquaintance with that was completely fine with what was happening, felt no sense of panic, no desire to pile those little slips of paper into a you know pull them back together and then I looked out again and I saw myself spread 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 environment with a guy that I trusted. I mean without question this very risky letting yourself disintegrate but and I think that that's a key to psychedelic therapy, is creating a container where you feel safe enough to let go and that's a fundamental difference between the so-called recreational use of these drugs and the therapeutic or spiritual use of these drugs. And I remember afterwards I came back for an integration session with my guide and she said what happened that was note worthy and I told her about this dissolution of self and the surprise of it was that I said I found there was another ground on which to stand that wasn't my ego. I don't know what it was. Aldous Huxley would have said it was the mind at 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's gone, my ego is back in charge, in uniform, on patrol. And she said, "Well you've had a 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 these substances that you know if you're involved in psychotherapy or psychiatry and in any way there are many things that are anomalous about this. One is you're essentially prescribing not a drug exactly but an experience of a certain kind. So how you use that experience going forward becomes very important. For me I asked her how could I cultivate this and she said meditation. And it's no accident I think that a lot of people who experiment with psychedelics find their way into meditation as a way, a non-pharmacological way, to connect with a kind of consciousness that is less egocentric. And I have, you know I think someday we'll look at psychedelics is a very good way to kickstart a meditation practice. I was 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 ego dissolution as sort of like death practice. You, Hopkins specifically, work with people who are anxious about their death and the psilocybin isn't necessarily gonna change the course of their medical illness but it is gonna change the course of how they deal with it, how they respond to it. - Yeah I was telling Michael earlier, I think the cancer patients are really sort of give me participants for this stuff because they have been dealing with 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 but it would be easy to see where they think that would be the goal. You lay, it's really heavy like, you can have the most terrifying experience of your life, you could you know you name it subjectively and it could be happen to your heart pulled out of your chest, you feel like your body is just being torn apart, you name it it can happen. But you know those so often with the cancer patients, you know like yeah right you're just describing my life for the last you know whatever X number of years with these issues they've been dealing with. 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 creating a safe container, the solid rapport but nonetheless about a 1/3 of the folks on a high dose will have what people could call a bad trip. We frame it in this context as challenging. It could 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 saw their own destruction and they came through went out the other side. It's sort of the ultimate catharsis in dealing with a potentially terminal illness. So I think we have and we've since conducted research in many people in the broader population who have had so-called bad trips and in part to develop our scales but we found that it's very common for people to hold their most difficult psychedelic experiences as amongst the most meaningful experiences of their life and among the the greatest learning experiences of their life. So yeah they can be, we have a lot to figure out, you know we're not at that you know some work that actually went on in New Mexico years ago actually, tried to target difficult experiences for this purpose. I don't think we're there yet. I'm not sure if that would be the, you know there's a lot of ethical questions surrounding that. We try to minimize it but if you give high enough dose, you're gonna have these very difficult experiences where you can have call it what you will, ego death. - And I think some people have on the other hand like really 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's one or the other. These are five, six hour sessions. - Right, usually get a little taste of everything. - Right. - My sense is, please correct me if I'm wrong but certainly from my patients reporting to me that in general psilocybin may offer sort of fewer challenging experiences than something like ayahuasca. Is that your sense of it at all or not necessarily Anja, 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 think it's not like substance specific but I do want to echo what Matthew just said about this characteristic of difficult psychedelic experience that are passed through in a contained way that they really help people to become more resilient to difficult life experiences because it's like they get the self efficacy, I can deal with difficult emotional spaces and there's another way through. That's what I have observed a lot with my patients. And in this way I do believe that psychedelics prefer to death because that's a very difficult life experience in this way and but also even for births. Like I've witnessed other women who had psychedelic experiences before giving birth that they had much easier births processes like really letting go in this way. So I think there's also this other spectrum of life that psychedelic can expand our consciousness to spaces that we have not experienced. And another benefit I see in the contained use of psychedelics is for people with difficult grief, especially ayahuasca in the sense, I think ayahuasca has this characteristic, indigenous people refer to ayahuasca liturgy as the refine of the soul or the wine of that. That many people have this experience, they get in contact with a beloved one that has passed away and find 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 mentioned birth. It didn't occur to me but I mean that is another very high oxytocin state and if you have natural childbirth you can see all the sort of special drugs that your brain leaves set aside just for that, just for being in labor and it may be that the experience of really letting go and learning how to let go and learning how to not exist and sort of 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 neuroplasticity and 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 all and MDMA turns out, are capable of sort of stimulating the growth of either new neural connections or actual nerve cells, neurogenesis. So we're talking about psychedelic assisted neurogenesis, neuroplasticity, I think this is gonna be a very big deal and I don't think that there are too many other treatments in psychiatry where you're actually seeing new neural connections and new sort of circuitry and networks formed. Did I leave anything for you to say? - Yeah I'm very interested in it too. Although I something I think I can add to it is that neuroplasticity can take so many different forms and neurogenesis the growth of new neurons or a specific type of brain cell is just one of those ways. There's branching, there's new connections being formed then we kind of go up an order of kind of a layer of analysis then we could talk about new networks being formed. So I was I think the paper published on psilocybin at least the in vivo paper in rodents on psilocybin neurogenesis wasn't convincing. But I you know it would be great to see more work along those lines. But we do know that neurogenesis is not always a good thing. I mean the growth of cells isn't always what you want. I mean cancer. So I guess I just want to kind of in 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's it, 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 different by a number of different mechanisms. Clearly there's learning going on. - I'm glad you mentioned learning because I think we should circle back and maybe Rick you can talk about this sort of re-consolidation of memory idea that some of what, keep in mind that most of the psychedelic research that's going on it's in the context of ongoing therapy. There are multiple sessions where you're preparing somebody for the experience, then they have the experience and then there are multiple sessions where you are processing everything that they learned or that they experienced. But I think unique to MDMA-assisted psychotherapy is this opportunity to go back to the trauma and sort of debrief the trauma but reconsolidate and Rick I want you to talk about that a little bit. - I don't think that that's necessarily unique to MDMA though. I think that probably happens in these other drugs too and what we're really talking about is psychedelic medicine where people could get different drugs at different times in the course of therapy. It's not like this drug is perfect for this and should only be use for that and these drugs shouldn't be used for this or that. 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 basically we have these traumatic memories, people with PTSD have them and they can't really escape from them and these memories are linked to very painful emotions. And under the influence of MDMA the painful emotions, the experience of them is diminished. People can remember the trauma and actually memory is enhanced for the trauma so a lot of parts of the traumatic experience that people didn't have consciously available. And then you're looking at them from 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 you would look at it and you would just put the book back. And what actually is happening is you're sort of taking to book off, consolidating it from different parts of your brain, and then 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 the trauma, but then the fear that's attached to that is replaced by this sense that the memory is from the past. It's not happening at the moment. It's not always about to re happen, 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 back that memory, you're able to not react to it in such a way that it's re traumatizing again constantly, but it's changed and it's in the past. So, I think that's the process and that's why that process requires people to be grounded in their biography and that's where I think that the mystical experience is not correlated to outcome because it's about this episodic memory and replacing the emotional tone to it. I just wanted to add one thing about the ego death 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 these terms 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 Copernican revolution where people thought the Earth was the center of the universe and then it turns out, actually, you know, the Earth is not the center of the universe and we rotate around the Sun and the Sun rotates in the universe as well. I think that's the switch that we need to make from our egos: that we as our own individual love's are the center of the universe and the most important thing and we're sort of disconnected from history, and you become part 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 still some part of us that's still watching, that's still paying attention, and I think that makes it less scary a little bit. If you think about it not as ego death and who I am is gonna go away completely, but it's more this transparent to the transcendent. Michael, I just want to ask you a little about the 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 I was sort of curious who, what was the most fun interview you had where you just really enjoyed yourself and it was fun? And then, who was, and I think I may know the answer to 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 were following 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're like, 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 group of 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 believing in a transpersonal idea of consciousness and others who, Robin used the word, denaturalized the experience and really want to ground it in biology, and I think that's one interesting split. And so, God, I mean I interviewed a lot of the people we're sitting with. Rick was enormously helpful to me and I've described hi as a journalist's dream. He'll say anything and he never goes off the record. But also, Matt helped me enormously in 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 generosity in this community, of transparency in this community. So, yeah, I mean ... I just, I learned so much and I knew nothing about these issues. I had never written about mental health or the brain, and so I relied on a lot of people to give me an education. I mean, a key interview for me was Allison Gobnick, 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 consciousness of children which she regards as another altered state, and indeed it certainly is if you've had kids. And that she really believes that there's a dialectic between using the mind to explore the environment or exploit it, and kids are wired for exploration and not the kind of purposefulness, directed thinking; attentive, focused thinking that you need to exploit the world. And that the mind of the child is very psychedelic in her view. She really thinks four year olds are just tripping all the time, and she's very convincing about that and it's a very good model for the kind of thinking which is much more experimental, many fewer priors ... very, you know, less predictive. 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 environment and 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 outside of the box. So that's the ... just to give you an idea of 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 Griffiths to 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's really, he picks his words very carefully, he's gonna - Bob Jesse. Bob Jesse, who is probably watching this, is an unsung, behind the ... I mean, Rick is a very well known, key figure in the renaissance of psychedelics. Without him, I don't think it would have happened, and he's been knocking his head against the same wall since 1986 and finally it is yielding and his head is still intact. But another figure you probably have not heard of is Bob Jesse who is a former computer engineer who had some really powerful psychedelic experiences in 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 drug researcher at Johns Hopkins, but I actually found both of them ... you know, they were harder interviews than this guy, but eventually fascinating. Roland got into this work because he had had a mystical experience of his own. Not through psychedelics, which as far as I know he's never tried, but through his practice of meditation, so very interesting biography that 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 his words with tweezers. Right. And in fact chooses your words, too. If you use 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'd you use the word recreation in a negative context? The word recreation is a very positive word, and so on. So, it was just a wonderful cast of characters, and I've met two new ones today and so I feel like I profited enormously from the people I met in this world. You talked about children sort of seeming like 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 like guiding someone that was tripping down the streets of New York City. Like, you cannot be in a hurry cause she just wants to look at everything. But you know, that reminded me ... Oh, and also I remember talking to my husband Jeremy about this, that we, you could also make the case that a toddler, maybe instead of tripping, they're just kind of stoned where they have fresh eyes and everything is sort of interesting and, you know, as if they've never seen it before 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 interesting paper that a psychedelic researcher named Peter Hendricks just published - I saw that, yeah. Where rather than talking about the mystical experience, which is off-putting to many scientists, he argues that the key mechanism is awe. The experience of awe gives us a sense of ... it's a human emotion. I didn't realize that it's one 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 paper and then show them images of Yosemite or some, you know, awe-inspiring scene and ask them to draw themselves again, they'll get a lot smaller, and that ... It's also a very pro social 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 think we're groping for words to describe a phenomenology that I think is across the board. Right. So, Peter Hendricks, who wrote this paper on awe and I think it's like the International Journal of Psychiatry, it was a journal I was 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 wanted to ask you, Anja, because we're talking about children and I know that in a lot of these ayahuasca based religions that children are allowed and invited to participate. They drink a little bit of the ayahuasca. I was wondering could you talk about this a little bit? I know it's a little taboo in our culture but in other cultures, it's not. Yeah, I think the important part is that there's a cultural difference. It's not ayahuasca only. Also, the Huichol people give a little bit of peyote to the children in the indigenous cultures where ayahuasca is still part of indigenous medicine. They also hive a little bit of ayahuasca to the children in the ayahuasca religions. Brazilian ayahuasca religions have adapted this and they do the same. Those are very small micro doses only, but they are believed to enhance this intuitive part of the brain in the children in this way. They're really small doses and controlled group ceremonies where they ingest it. I know from a few studies who have followed up 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 adolescents and they have found that they are more resilient to those troubles that adolescents, those challenges that they are facing and they are more resilient to drug abuse, also. So, that's maybe something interesting to rethink. Obviously, it's ... it's beyond our current Western paradigm to practice ayahuasca or other psychedelics with children, but I think it's important to observe what other cultures do and just see what we can learn from this. I also wanted to add on the question you asked me previously and those difficult experience with ayahuasca in comparison to difficult experience with psilocybin. There is one important aspect that ayahuasca is very physical and there is this strong body-oriented aspect, I call them, from a more psychotherapeutic perspective, because it's not only on the body; it's really like if you would do a body-oriented psychotherapy that there's many emotions that are processed through the body. And these physical processes that ayahuasca can induce, they really bring people to the state of surrendering easier 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 absolutely need to talk about micro dosing, but I know that Rick wants to speak a little bit about adolescence and ritual. Am I right? Yeah. Go right ahead. Well, it's just that when you try to make a 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 called phase 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. And so, if that works, if we can prove it in adults, then we need to prove it in 13 to 17 year olds. 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 it is 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's surprising to some people, even in our Western cultural context, the FDA is actually requiring us to administer MDMA to adolescents. I wanna just quickly, sort of, tackle this adolescent ritual. Michael, I know you talked about this in your book a little bit, this idea that in our Western culture, we really don't ... maybe we have Bar Mitzvahs or Bat Mitzvahs but in general we don't really have this, a ritual where, you know, now you are an adult and now you are in the community. And sometimes what ends up happening, certainly in 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 micro dosing perhaps with Matt and you also, if we can? Yeah, I think that for many young people in America, psychedelics have been one of the most important rites of passage, although we 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 in the 1960's. We had a very unusual situation for a moment there where you had young people experimenting with psychedelics, having these powerful rites of passage that put them in a place that adults didn't really know. You know, the traditional rite of passage, whether it's the Bar Mitzvah or the vision quest, is usually organized by the adults in a community and they bring the adolescent, after passing through these various obstacles, to the adult world. In the case of psychedelics, you had a rite of passage organized by the kids that landed them in a country that the mind of the adults didn't understand and was very frightening to them. So, I think we had a very ... and that's why we had so much conversation about the generation gap. I mean, the youth in that period 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 think now you've got, and one of the reasons that we are having this renaissance, is that many of 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 ... I mean, Timothy Leary had a lot to do with inciting the backlash in various ways. On the other hand, as Rick points out, he had a lot to do with creating a world in which psychedelics could be possibly normalized by turning on as many people as he did. I still think, though, that this research has to proceed with enormous care. I think that there are risks. They're not so much in the toxicity of the drug, but in the fact that there is ... you have patients who are vulnerable 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 the drugs in an uncontained way. So, the risks are still there. I think that they've changed a good bit, so I'm optimistic and more optimistic all the time that our culture may be ready to integrate these medicines into its mental health care and ... for one very key reason we haven't talked about, which is that we have a mental health crisis. Today is 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 the part of psychiatry and psychology to look at some new tools right now because of the crisis. 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 in psychiatry now where, all of a sudden, we have all of these other tools at our disposal that we didn't before, including micro dosing. I definitely have patients who have gone off their ADD meds or off their antidepressants and they are just micro dosing. And, I don't know Franklin if you're comfortable talking about microdosage, if you have any thoughts about it, but I feel like we should cover it a little. Yeah, I think that we need to have more studies on micro dosing - There are none, so yeah. There's none. I think somebody is doing something, right? Right, The Beckley Foundation in London is starting to organize, I think, an LSD micro doing study. Yeah. Do it yourself, yeah. But I think the most interesting aspect of micro 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 integral to the effects of what psychedelics can do, and that a lot of people, really we're seeing it more in the media now, who practice micro dosing and seem to be talking about how it has a great benefit for them for a variety of issues. And that just sort of leads me to wonder, you know, when we start talking about ego disillusion and ego death, do we actually need to have that? And I think, you know, the drug companies are gonna be one industry that's gonna be very curious to know this because when we start thinking about can we develop analogs of psychedelics that actually don't have a very potent psychoactive effect, but may actually achieve similar rates of remission in depression and anxiety? I think that's a very interesting question. Just to define micro dose, I mean, traditionally it's about a tenth, would you say? Yeah. A tenth or even a twentieth of, sort of, a macro dose. Are there any, Mike, are you, is Hopkins planning on doing any micro dosing research? Oh we plan on doing everything. What's next for Hopkins? We haven't started it yet but it's definitely on 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's article about using psilocybin in smoking cessation. These are people who couldn't quit for 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 addictions is these aren't, you know, we aren't thinking ... unlike the rest of most psychiatric medications and addictions, we're not talking about quelling the response to the nicotine receptor, mediating reinforcement or craving, and there's not similar hypotheses about alcohol. These are general mechanisms with no doubt a biological basis that probably have to do with the changes in brain network dynamics that we've heard about today, default mode network. Potentially long term changes. Maybe other types of biological correlates, gene expression. Who knows? But everything, and particularly a psychological description of what's going on, everything is pointing towards general mechanism: behavior that is stuck. A mental repertoire that is stuck and in that sense, I even think of depression and these other disorders as addiction broadly defined. OCD? OCD. Anorexia? Anorexia. There's lots of times when my patients are stuck - Right. And I want a jackhammer, so ... and this could be that? Yeah, and this is like, you wanna be careful with that jackhammer and you can't use the jackhammer - Like any jackhammer. Right, but in the right container with the right 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't started 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 well spent to try to find it, but they have spent hundreds of millions of dollars since the 80's in trying to find - Without much ... right. A medication. With no approval. I mean ... you know ... I mean literally about 100 compounds have been worked up into clinical, into human clinical trials. Right. I mean, if this stuff holds up with cocaine addiction, I mean, it's ... I often say in comparison to ketamine, like it's rightfully considered 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, you know, six months. This is what's the crucial difference between ketamine and the classical psychedelics is with ketamine people do get better. They feel better right away. It doesn't last. They need more. But with some off these other studies with psilocybin or LSD or ayahuasca, people are getting better and staying better. Yeah and in fact, you know, we don't know that they get worse at six months; we've just only looked out that long in the cancer work with our trial and the NYU trial. So, you know - And the smoking cessation, right? You're looking at 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 test their urine, we have them blow into a machine - And with MDMA PTSD, you're getting somewhere between 60% or 80% of people at six months or one year out that don't meet criteria for PTSD 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 sort of an ongoing ... No one's every cured in psychiatry, you're just a little better. You still have to come every week. We did a three and a half year follow up with some of our people. Some of them are ten years now. Talk about the follow up to the Good Friday experiments that were here in this neighborhood. Can you talk about that? Yeah, yeah. And also, Michael, if we have a minute to just maybe ... a minute? I know, I'm asking Rick a question. Careful. A few minutes to talk about Harvard's history in all this. We should, it's probably the elephant in the room. We should get to it before we open up to Q & A, which we will. Well the first ... in the 80's when I wanted to do research, I had to do a senior thesis at college and I wanted to focus on psychedelics and at that time the FDA was not permitting any research at all. And I realized that there was 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 Andover Newton Theological Seminary students and there was an attempt to learn whether psilocybin could produce mystical experiences by people who were religiously inclined in a religious setting. 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 Johns Hopkins and was working there with the LSD research. And so, I realized that he would have done, if he was alive, a long term follow up and when it comes to this question about mystical experience, the traditional literature on this says that the most important aspect of it is what is called the fruits test: what is the fruits of the experience? You can describe what happens but what aspect, what impact does it have on your life, and then really what impact does it have long-term? So, this was in the middle 80's so I decided to do a 25 year follow up to the Good Friday experiment and I went to Andover Newton to see if they would help put a little announcement in their alumni newsletter so I could contact the students that were participating, and they refused to do that. They didn't want to have anything to do with it and I thought okay, I'll go to their library and see what papers they have and anything like that. They didn't even have a copy of the dissertation and out of desperation I just wandered in the library and I found a list of the alumni as of 1973 and their addresses. So, I wrote a letter to 350 people and eventually I was able to identify 19 or the 20 people and track them down all over the country and went to interview them - And this was before the internet. This was like letters and stamps, right? This was hard work, right. But you find a few 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 remembered parts of the experience extremely vividly, also they validated the fact that this was a genuine experience. So this was in the Nancy Reagan, "Just Say No" escalation of the drug war in the 80's, and if there ever was a time where people would have been culturally motivated to disavow the validity of that experience, that was then. And yet, they could remember it and they also could say that it was valid and many of them had had non-drug mystical experiences afterwards that they could compare. They generally said that they preferred the non-drug mystical experience cause they were more positive but that they felt that the drug experience was sort of oscillating between this fear of letting go and also this sneeze of connection. But I think one of the things that I learned that was most important was it validated the theory of change, for why I devoted my life to this. And it's a little bit what you said, Michael, about how part of the backlash was because of when psychedelics went wrong or people had difficult experiences that they couldn't handle. But all of the people that I talked to that had the mystical experience from psilocybin talked about how that sense of unity motivated them to get involved in the struggles of the day. They became more involved in the Civil Rights 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 these people having these experiences of connection, getting involved in challenging the status quo, and then having that become a problem. Now, I think Leary and others made the problem worse 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 so we know more. But I think really the essence of it was that there are ways in which these experiences as used ... Now, this was again used by religiously inclined people during a Good Friday service at Boston University Chapel, and the person that was doing this was 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 in starting to do psychedelic research, because legally you can ask people about what they thought without having to get permission from anybody but an IRB, and it validated both the 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 the audience briefly at the end. Okay. But people have been submitting questions online, both from the live audience and from the webcast. So what do we have, DeLara? So, the first question is: do the scientists and doctors observing the initial therapeutic effects of psychedelic substances have a duty to advocate for changes to current drug laws? Yes. Next question. I work in drug policy reform. Rick works in drug policy reform - Yeah we just published that paper that we mentioned, or yeah, I think DeLara mentioned that it, you know, should this be approved for 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 is saying that there is no medical use. So, when you have psychedelics in schedule I, when you have cannabis in schedule I, it's illogical. So, I think many of us would like all drugs rescheduled with more science, less politics. Or, perhaps, not scheduled. But the current scheduling does not make any scientific or medical sense. It is much more about politics and fear and xenophobia and, sort of, pharmaceutical company greed and things like that. You know, I mean take this new CBD medicine which is being scheduled all on its own in one little schedule, but if it's not an FDA-approved CBD medicine, then it's still schedule I. Illogical. Not, it doesn't make any sense medically. Prescription THC, pure THC; schedule III. A plant that contains THC and CBD? Schedule I. Doesn't make any sense. So, does anybody else wanna talk about drug policy? I could go on and on. Well they're two, I mean they're two separate issues. One is the, you know, incorporating psychedelics in medicine where there would be a prescription, and the other is an effort, and perhaps the question was referring to this, whether these drugs should be legalized, which I think is a much harder question. It seems to me important that there be a way for people who are not sick to have access. What Bob Jesse memorably called the betterment of 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 very hard question. The drugs are very powerful. I do think that they need the kind of container that Anja was talking about. The virtue of legalization is you can regulate, whereas if you don't legalize, anything goes - Right. But then how do you regulate? And I think those are hard questions and not as obvious as the rescheduling question. I just wanna add, I think another aspect of this ... and this could open up a whole nother can of worms, but who are these medicines going to benefit? And I completely agree with you Michael, I think everyone who works in this field would advocate for some kind of container. On the other hand, you know, assuming that the container is some sort of structured therapy, I think at least in the beginning there's gonna be a great deal of difficulty getting insurance to pay for this. I think that's gonna bring up issues of access and social justice in terms of who is actually going to be able to get into psychedelic assisted psychotherapy, and I think that's really important for 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 lobbying for in all of this, too. That's really important. Last weekend I was at a psychedelic conference called Horizons and a women spoke there. Her name is Monica Williams and she specifically spoke about marginalized people not really having access to these trials. And so, Maps is sort of enabling a group of people in Connecticut to focus om MDMA in the treatment of racial based trauma or racist based trauma, and having people of color and marginalized people come in and be research subjects because if you look at the 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, or volunteers? Yeah. Pretty even though. But I would ... just offer that 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 be unavoidable. 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 conversations within conversations. In the broader aspect, yeah I think it's very clear that the criminalization of 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 been minimized and the devil is always in the details, because I think when you make something a controlled 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 legalization mean? It could mean many things in terms of how ... are these clinics one can show up to for the betterment of the well, or does this mean you could sell it, you know, at the 7-11. So, the devil is in the details, but it kind of just touches on that bigger question of, you know, the unintended consequences of criminalizing drug use and basically criminalizing addiction, 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 and politically between cannabis and psychedelics? Well, I'll just say that I think cannabis is 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 that sense of ... just, you know, the interruption of your chain of thought, the new material coming to the surface. But I would say politically, it's astonishing for people to realize that we have an open door at the regulatory agencies for research with psychedelics, but there is 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 and federally regulated research. So, we've been trying for the last 20 years to break the monopoly held by the National Institute on Drug Abuse, and they can only provide 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 wanna market, and so as long as there is this government monopoly, the plant will never be able to be made into a medicine and what we hear about the CBD from Epidiolex, that's imported from England. So, we have no domestic production, no domestic supplies, and we're getting ready to sue Attorney General Sessions and the DEA to try to force them to respond to roughly 26 applications from people around the country for people to grow marijuana for license. Obama permitted the DEA, two years ago, to say they would end the monopoly and then when President Trump got elected and Sessions got the head of Attorney General, he's blocked the DEA from ruling on that. So, ironically it's easier to do research with psychedelics than with marijuana. Maybe we should have said at the beginning that people may wanna silence their cell phones. What sort of education options or career tracks exist for those who are interested in pursuing a path that incorporates psychedelics? Are you ... I imagine you're navigating this to 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 or track. But I think what I would suggest to anybody who is interested in this, given that this 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 so people aren't blindsided by what you're trying to do. Lobby your supervisors, lobby your department chairs, and talk to them and be open. I think having a rational, science-based approach, a clinical-based approach; these are the reasons that you are interested in this - You know, one of the things I encourage people to do is to have, host a journal club. Get a bunch of articles showing these amazingly huge Cohen's effect sizes; show them the numbers, show them the data. You know, people understand journal clubs, they understand statistics. Show them that this research is already going on at some of the top institutions not only in America but around the world. I would just add that, I don't know if you would call it a career path but maybe it is, but there's now a certificate program in California at 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 ... there are going to be many phase three and phase two trials coming up, both in this country and 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 are taking this class. I met several oncologists who want to incorporate it in their practice and therefore wanna learn how to be guides. But if this research continues on the present course, you know, within five years or so there will be a career. Yeah, I'll just say that it's actually coming sooner than that in the sense that the FDA and the DEA permit a program called expanded access and President Trump just signed a law called Right To Try. And so what that means is that if you have a disease that nothing has worked for and there's a drug that's being studies 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 discussions with FDA and DEA about this and so next summer, the end of next summer, we're going to be opening up expanded access where people can pay for their treatment. We have over 5000 therapists who want to be part of our training program, and unlike other drugs that, many of them once they're approved by the FDA, anybody can prescribe them, any doctor can prescribe them; that's not gonna be the way for psilocybin or MDMA. The only people that will be able to prescribe them and the only people that will be able to work with patients are 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 that we've been, so far, trained almost 200 people in how to work with MDMA and there's different parts of it and we're training now. We've trained everybody we need for phase three for the US. We're in the midst of training people for Europe and we're gonna start in March to train people for expanded access. And so I think really, the first time in 50 years 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 a different angle. On the education side, too really establish yourself ... and maybe this is ... Well, this is true if you're gonna be a therapist too, I guess. Establish yourself in the areas outside of psychedelics as firmly as you can. If you wanna be a therapist, learn to 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 with the best addiction experts. If you're going into grad school and you have a choice to work with this person who just started some psilocybin research and you're interested in 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 to do anything with psychedelics. Next question: is any of the research of psychedelics and neuroplasticity, excuse me ... neuroplasticity and neurogenesis focused on treatment of Alzheimer's or other types of memory loss? We have that, we're planning on doing work with Alzheimer's patients with the primary focus looking at those sort of existential questions more so than the actual direct disease state, such as memory. But those will be secondary measures. But in terms of this, if you're seeing this pattern of an existential crisis that 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 die you're going to lose everything that you know while your spouse is having to wipe your rear end. I mean ... that is a heavy, heavy thing to deal with and so we're kind of hoping that general mechanism might be at play and we'll see improvements in quality of life. Especially cause we know that coping with how one handles that diagnosis early on can have some effect in progression of that disease state. Just to bring it back to the question around the idea that the ... the ideas of neuroplasticity and neurogenesis; this actually might provide some relief from Alzheimer's? Is there any indication of hope or anything there? Yeah. I mean, we couldn't say anything beyond what you just said that sounds plausible, but we don't know ... you know, we don't know whether that would scale up to be at play in Alzheimer's. I think the kind of, the best thing to do is look at those softer measures which are, we call them soft but they're in fact very important. You know, quality of life, how you're living on a day to day basis which we ... there's probably abetter bet that you're gonna see some movement there and 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 everything that you've heard of today has been privately funded. There's not yet been major, or even significant 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 not currently being followed up on. Will double blind randomization ever be possible for this research? Can patients be blind to their treatments? If not, what alternatives can eliminate study bias? So, that's a really important question. It's very hard to do a blinded study with psychedelics because ... for most people at some point it becomes pretty clear whether somebody has had psilocybin or placebo. One of my ideas that 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 use sort 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 sort of ... Sorry, that's a medical term. So, it somewhat resembles. But Rick, wanna talk about the whole blinding problem? And I know, Michael, you mentioned it too and I was glad that you covered it. Well, a lot of my dissertation at The Kennedy School was on how to address the methodological challenges of dealing with the double blind issue. And so, I thought I solved the problem and I thought it would be low doses of the test drug versus full doses, and you wanted ... that would increase the blinding, but the challenge was gonna be to find a low dose that wasn't so low, like a micro dose that you didn't even know you took it; but that wasn't too high that you got so much therapeutic benefit 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 the proper control, and when we met with the FDA I started out by saying that there was an early Harvard president that had a saying: he said, never forget, there's always a Harvard man that's on the wrong side of every issue. And I said, in this case, it was me. I thought I solved the problem but we found that the low doses of MDMA actually had an anti-therapeutic effect 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 activates them in the low dose but doesn't give enough of the fear reduction. So I said, both to the FDA and to the European Medicines Agency, that there is no solution to the double blind problem. And what you could do is you either can let us have blinding and use low dose MDMA, but you're gonna make it easier for us to show a difference between the therapy and the therapy plus MDMA. The best solution, I thought, was inactive placebo with full dose, with therapy versus full dose MDMA with therapy. And so, what the FDA said is that the way to reduce bias in those circumstances is, the first point is random assignment: that you get everybody similarly motivated and willing to go through either the placebo or the MDMA, and that once you have random assignment, that solves a lot of the issues of bias. And then the other part is how do you do the outcome measures? Who says whether they got better or not? It can't be the therapists that are doing the measures themselves. So, we've worked with the Boston VA that developed the CAPS, the Clinician-Administered PTSD Scale, which is the recognized outcome measure, and so we have a group of around 20 CAPS raters that are gonna do the ratings on telemedicine and they will be randomly assigned to whoever is the next person to get the rating so that we're breaking the connection between the rater following the person through the study and knowing where they are in the study, and also the therapists aren't gonna be the raters. So, under those conditions the FDA said go ahead and use an inactive placebo. They felt it was more important to see what the therapy does by itself and see what you do when you add a drug, and they surrendered the fact that the double blind isn't gonna work. But I will share the one thing in our training of therapists we actually got a protocol where we can give MDMA to therapists as part of their training. And so we've had 60 people who have gone through that and they either get, they get two experimental days, two days apart, with a day of integration after. They either get inactive placebo or full dose MDMA. And we have had two circumstances, both with psychiatrists, where they were randomized to the ... The 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 they had watched a week of videotapes about what MDMA is like. It's like they had these incredibly productive sessions. They actually had pupil dilation as well. Did they? And they had some blood pressure stuff going and they convinced not only themselves, but experienced MDMA therapists were 100% sure that they had the MDMA. And that happened twice. So, both times with psychiatrists. So, the double blind is a powerful methodology even with drugs like MDMA, but these were people that really wanted so much to have the MDMA that they convinced themselves and they had really ... The one psychiatrist that convinced, one of them, when he got the crossover and he was convinced that it was gonna be an easy day because it was gonna be the inactive placebo, after about an hour when he started feeling the MDMA, he couldn't talk for several hours after that. He was so stunned by what happened and at one point he was pointing to the books on the shelf there and he was saying, he was like going like ... like it's all in the heart, and it's like the books are nothing and it's all in the feelings, and he couldn't talk for hours and everything flowed more easily and deeper. But double blind is amazing. Boston VA that developed the CAPS, the clinician administered PTSD scale which is the recognized outcome measure and so we have a group of around 20 CAPS raters that are going to do the ratings on telemedicine. And they will be randomly assigned whoever is the next person to get the rating, so that we're breaking the the connection between the rater following the person through the study and knowing where they are in the study and also the therapists aren't gonna be the raters. So under those conditions the FDA said go ahead and use an inactive placebo. They felt that it was more important to see what the therapy does by itself and see what you do when you add a drug and they surrendered the fact that the double-blind isn't gonna work. But I will share that one thing in our training of therapists, we actually got a protocol where we can give MDMA to therapists as part of their training. And so we've had 60 people have gone through that. And they either get, they get two experimental days, two days apart with a day of integration after. They either get inactive placebo or full dose MDMA and we have had two circumstances both 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 they had watched a week of videotapes of what MDMA is like, is that they had these incredibly productive sessions. They actually had pupil dilation as well and they had some blood pressure stuff 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 psychiatrists so that the double-blind is a powerful methodology even with drugs like MDMA. But these were people that really wanted so much to have the MDMA that they convinced themselves and they hadn't really. The one psychiatrist that, one of them when he got the the crossover and he was convinced that it was gonna be an easy day because it was gonna be the inactive placebo. After about an hour when he started feeling the MDMA, he couldn't talk for several hours after that. He was so stunned by what happened. And at one point he was pointing to the books on the shelf there and he was saying he was like going like. Like it's all in the heart it's like the books are nothing and it's all in the feelings and he couldn't talk for hours and everything flowed more easily and deeper. But the double-blind is amazing. - You know, I mean we could spend a long time talking about placebo response and how amazing it is and how sort of underutilized and underappreciated the placebo response is. In psychiatry it's a real problem because people you know if you're looking at like an antidepressant and placebo like sometimes as many as 30 or 40% of people get better on placebo. Placebo's a big deal and you know how what is the mechanism of that? How do we get better just thinking we're taking something that's gonna make us better? What's doing that? - Another question and I think after this last question from this app here we'll pass the mic around, see if anybody has a question they want to voice. As psychedelic medicine becomes more common, what kind of effects might we expect on recreational use? - [Matthew] I don't. - [Anja] I think that Rick. - [Computer] Goodbye. - Recreational use will get more structured because I do think that recreational use is also inspired by what happens in psychedelic medicines. And people who take psychedelics don't want to have a bad experience. So if they have more access to models of how to have a good experience and what is needed to have a good experience, I think recreational use will become safer. Speaking about ayahuasca rituals for instance like unfortunately there's many ayahuasca ritual spreading with facilitators that are not adequately trained to contain such deep non-ordinary states of consciousness and if people would have a model of how well trained facilitator guides group, they have better criterias to choose where in which hands they give their mind. Because that's what they do, participating in a ritual is like you give your mind in the hand of a facilitator. You better choose and know how to choose who's gonna take care of this vulnerable states you might cross in an appropriate way. So I do think there is a retro alimentation that it's gonna happen hopefully. - I think well also we need to define recreational. I mean there's so many non-medical uses. There's the spiritual context or the religious context that you've talked about, that is one. There is the underground which has its own codes of conduct. And I have some concern that as demand for these therapies increases and curiosity about them increases that there'll be lots of people just hanging out a shingle saying, I'm an underground guide who don't know what they're doing. I mean similar to the ayahuasca-ers that are around. And then there are people taking psychedelics and going to a concert. So it's not one thing recreation. There's kind of a serious intentional non-legal use of these drugs and then there's a playful use 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 psychedelic harm reduction. So I think recreational use as it is currently practiced, will be accompanied more by a group of people at these settings that are trained to help people who have difficult experiences to turn them more into productive experiences. So for example we do this at Burning Man and festivals all over the world and this particular Burning Man we had 900 people apply for 260 spots that we chose to help out. We had over 330 people come to us for assistance. So I think once psychedelic medicine gets more established and the laws change 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 of just having a good time and when stuff difficult comes up rather than welcoming it, I think that's Anja what you're talking about. If people have a model this can be therapeutic when difficult stuff comes up they'll work on that instead of saying, oh my friends don't want me to talk about this, I'm gonna stuff the feelings and people can end up being worse off for long periods of time afterwards. But I think this model of psychedelic harm reduction will become more established over time. - I just want to say one quick thing. As a psychiatrist I know that these are very different models of use and that one is safer and one is less structured but recreation is therapeutic and I think that for instance if you go to a rave and a bunch of people are taking MDMA and you feel very connected to the group and you have this sort of collective effervescence and you feel joy and you feel connected to people and you don't feel isolated that's therapeutic. And I think that it's even medically therapeutic. So you know it's a spectrum. And there are things I think anytime that we are relaxed or resilient or handling stress, the sort of anti-inflammatory and just like soothing ourselves, calming ourselves, that's the potential to be therapeutic even though it's in a recreational context. Did we want to see if any people have a question? - So we could take two questions. If you could line up at the microphone over there. I'm going to ask one more question okay then we'll take two from the audience. Is there anyone who should not try psychedelics? - People with psychotic disorders. And here's the rub though '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 psychiatric screenings where you can identify people with even the predisposition. So I would say if anyone has a question, I mean of course the advice is that there are risk and we're not encouraging anyone to use but whether it's in you know we know something about how the human animal responds to these compounds and so whatever setting it is in, people with that psychotic predisposition those tend to be the people with the prolonged psychiatric reactions. It's also the case that anybody at a high enough dose can have a difficult experience that can be destabilizing where they have to drop out of college where they either kind of life is taking a kind of a turn for the worst. And we've done some survey work suggesting that is related to the degree to which this they had a sitter present and also related to pre-existing, even non-psychotic psychiatric symptoms. So people coming in with anxiety type issues tend to have an exacerbation if they have some lasting issue, an exacerbation of anxiety type issues or same thing for depression. So it's hard to tell. - Right. The safe, you know, 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, if you'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 are really dangerous to mix with MAOIs like antidepressants and with MDMA there are certain medicines that are very dangerous to mix with MDMA that you may not think of like cough syrup dextromethorphan or decongestants. So there are risks in terms of medication interactions and the thing to keep in mind with all the research that goes on here is that these people are heavily screened to 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 really great robust responses. And when it's sort of unleashed on the general population and there 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 pressure or cardiovascular diseases or in the case of ayahuasca, gastrointestinal lesions like this. And so it's important to watch out for those things too. - So what's your question sir? - Yes it seems like we're in a wave now of increasing acceptance of the value of non-ordinary states of consciousness, provided that they are induced by drugs and I'm curious if there's any, this leads to any new thinking about the value of spontaneous non-ordinary states of consciousness that would ordinarily be diagnosed as psychosis or other forms of just madness. - That's a heavy and complicated question. I know sometimes people talk about things like Kundalini explosions or things that feel natural and physiologic but they're leading to intense altered states. It would be lovely if we had more, if we gave people more latitude about non-ordinary states of consciousness and accepted that there's a lot to be gained in these states. I do think there's a lot of stigma and sort of labeling and 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 I had people come in who were in a manic episode who were really blissed-out and felt amazing and had things to teach me and I was ready to learn and they seemed like they were tripping but they weren't tripping they were manic. But I definitely approached them that they you know were having a non-ordinary state of consciousness that they could learn from and that I could learn from. It would be great if we had more of that in our culture. Right now we really don't. So maybe this will help show people that there are other ways of being that 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's watch says that it is six o'clock because mine's at home. - Hi so you mentioned the word meditation a couple of times through the panel and I was just wondering if there is any current crossover in either studies or treatment that combines meditation and psychedelics. - 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 adopting a 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 adjusted and then we had that same high dose group with a really extra layer of support with going from like six extra drug sessions to 26, including group discussions with other participants which people really valued and which we hadn't done before, is normally not part of this stuff. Essentially the short answer is in terms of the session itself and this gets to the fruits kind of test that Rick was mentioning, the terms of the session itself rates of mystical experience squarely dependent on the psilocybin. I mean now keeping everyone had the same sort of minimal safe preparation for the experience and the safeguards but in terms of, so under those conditions its the psilocybin dose that led, to having high-dose, led to the full-blown mystical experience. But in terms of a number of pro-social outcomes, quality of life, altruistic behavior, the types of stuff a lot of people hope to get 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 that they definitely combined in terms of those long-term fruits and people often said that they're different ways of accessing the same type of thing and so we're still sort of dealing with the long term meditator data but people definitely claimed even after you know five or 10,000 hours sometimes lifetime annotation that there was some profound value in having these these experiences. - One small point I'll add to that is one of the interesting findings after Robin Carhart-Harris did his fMRI scans of people on psilocybin, a researcher at 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 in the default mode network looked remarkably similar. So that there's some reason to suggest that they're similar states at that level as well. - There's another study that was conducted in the Zurich University by Martin Heidegger and his team with long term zen meditators. And they found that the psilocybin deepened the meditation practice. So this might 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 use psychedelics have lower rates of intimate partner violence and another that there's less recidivism and those people in terms of being imprisoned. - Yeah parolees are less likely to re-commit crimes. - Right, like a parolee is less to commit crimes or end up back in prison if they have psychedelic experience. So weird, interesting sort of societal ramifications from these non-ordinary states of consciousness. I want to thank all of our sponsors, the Broad Institute and MAPS and Harvard an Mass General and Gift and Leo and I'm sorry but I'm totally, Delara sorry I just really had a brain fart there but don't blame the drugs it's just gas in my brain. That's okay I'm smiling. And I would like to thank all of our participants, Franklin and Rick and Michael and Matt and Anja and I'm Julie and we're gonna go have a little reception I believe all of us, yes all of us will go so we'll have a chance to chat more and talk more and thanks everybody for coming. Thank you.
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Channel: Harvard Medical School
Views: 330,684
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Id: SwMHr43fTqE
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Length: 176min 44sec (10604 seconds)
Published: Fri Nov 09 2018
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