 everyone get into the event. All right, well, good afternoon and welcome to the Health Policy and Bioethics Consortium. My name is Leah Rand and I'm one of the co-conveners along with Dr. Erin Kesselheim and we're delighted to welcome you today to our session on psychedelics and their possibilities as therapeutics. So throughout the consortium, consortium, please feel free to submit any questions that come up using the Q&A feature at the bottom of your screen and you can also tweet about the event or join the conversation on Twitter using the hashtag policy ethics and we'll be using the chat feature for technical questions or discussions among the participants but not for questions. Please use the Q&A feature for that and you can find out about upcoming events at the Center for Bioethics website or at the portal website. So the consortium is a monthly event and our objective is to discuss key issues in healthcare systems and policies and their ethical implications and we do that through bringing together experts with diverse perspectives and different fields of research and interest and we try to stimulate a conversation and think about further opportunities for academic study on the topic. So please mark your calendars for our upcoming events. On November 12th, we will be talking about health misinformation and on December 10th, we'll be discussing gene drives. So for today's topic on psychedelics, I am delighted to welcome Dr. Macy Marks who will be moderating our discussion. Dr. Marks is a senior fellow and the lead of the project on psychedelics law and regulation at the Petring-Flom Center for Health Law Policy, Biotechnology and Bioethics at Harvard Law School. He's an assistant professor of law at the University of New Hampshire, Franklin Pierce School of Law and an affiliated fellow at the Information Society Project at Yale Law School. In 2021, Governor Kate Brown appointed Dr. Marks to the Oregon Silicite Advisory Board, which advises the Oregon Health Authority on the creation of the statewide psilocybin industry. Mason chairs the board's licensing subcommittee. Mason received his BA in biology from Amherst College, his MD from Tufts University School of Medicine and his JD from Vanderbilt Law School. Previously, he practiced intellectual property law in San Francisco where he advised clients on securing and defending padded rights. So thank you for joining us, Mason, and over to you. Thank you so much, Leah. And thank you everyone for joining us. We have two amazing guests with us today, Dr. Sharman Ghaznavi and Dr. Rick Doblin for discussion of turning psychedelics into therapies. If you're not too familiar with psychedelics, they're a very interesting group of compounds, some of which are produced by many species of plants, fungi, and even some animals, and some of which were synthesized by chemists for the first time about 100 years ago or so. They include compounds like LSD, MDMA, DMT, and Ibogaine. And what they share is an ability to change the way that people think, to change the way they see themselves, their relationships with other people, and the world around them. And there are cultures who have used psychedelics for centuries for healing and spiritual purposes, and Western scientists really started using them earnestly in the 1950s and 1960s for research and as therapeutic aids. But something significant happened in the 1970s. There was a sudden shift of policy, and most psychedelics were completely prohibited by the federal government in the early years of the U.S. war on drugs. They became Schedule I controlled substances, the most heavily restricted type of drug, which typically cannot be produced, it can't be sold, can't be researched, and certainly cannot be prescribed. But in the 1990s, after several decades of virtually no scientific progress on these substances, certainly not in the United States, a group of scientists gained permission to study psychedelics again. And thanks to them, 30 years later, we are witnessing a psychedelic renaissance. Substances that were once prohibited have now become the basis for an emerging multi-billion-dollar healthcare industry. And the reason is that there's some very impressive research coming out of this psychedelic renaissance. People who receive inadequate benefit from standard therapies for mental illness, like depression, post-traumatic stress disorder, and anxiety associated with life-threatening illness often benefit from psychedelics. There's something different about these substances. They often act quickly, frequently with few side effects, and they often offer lasting benefits, sometimes lasting several months or longer. But we're really just at the beginning of this psychedelic renaissance. And there are many questions that remain unanswered. For example, when will these therapies become available? Why are they effective? How can they be administered responsibly and safely? And will they be affordable? Will insurance cover them? How should they be regulated? And how might they help us resolve some of the most challenging issues of our time, like rising rates of suicide in some populations, the national drug overdose crisis, and even some of the oldest challenges that have faced all of humanity throughout history, like how to come to terms with our own mortality? Studies on psychedelics are showing benefit in all of these scenarios, and that's why it's so exciting to discuss them. And our two speakers are at the forefront of this psychedelic renaissance. I'll first introduce Dr. Sharman Ghaznavi who will speak for about 20 minutes, and then I'll introduce Dr. Rick Doblin for his presentation, followed by a group discussion. Dr. Sharman Ghaznavi is Associate Director of the Center for the Neuroscience of Psychedelics at Massachusetts General Hospital, and she's the Center's Director of Cognitive Neuroscience. She received her undergraduate degree from MIT, her MD and PhD in Neuroscience from Yale, and completed a residency in adult psychiatry at Mass General and McLean hospitals where she received several awards for research excellence before joining the Harvard Medical School faculty. Dr. Ghaznavi also serves as a psychiatrist at the Dotton Family Center for Bipolar Treatment Innovation, also at Mass General. And her research interests include the cognitive processes underlying mental illness such as rumination, and her work has been published in the American Journal of Psychiatry, Biological Psychiatry and Biology of Mood and Anxiety Disorders. So please help me welcome Dr. Ghaznavi. Welcome. So Mason, thank you for that introduction and good afternoon everyone. So I wanted to begin, let me just share my apologies, it never goes as smooth as I'd hoped. So I wanted to begin by thanking Erin and Leah for inviting me to be part of, to take part in this discussion. You know, when I got their email invitation, I accepted enthusiastically because I think that this conversation is very timely, given the growing enthusiasm around psychedelics, as well as the urgency that some feel given their therapeutic potential. The other reason I agreed was that I saw it as an opportunity to formally reflect on the ethical implications of the work that I'm embarking on. When I was a graduate student at Yale, I had the privilege of knowing Arthur Galston, Art as we knew him, was a botanist and a professor of biology, but he came to be known as a voice for bioethics on campus in his later years. And the reason being that Art's early research was on a compound called tri-iotophenzoic acid, quite a mouthful, and the compound went applied to plants, soybean plants, to cause them to fruit and flower more quickly. However, when applied in excess, they would lead the plants to shed their leaves. Art's research was appropriated by others to develop Agent Orange, which as we all know, was used in Vietnam, and caused untold amounts of destruction to the environment and to humans that were still continuing to appreciate. Art always maintained that it was a misuse of science. He said that science is meant to improve the lot of mankind, not to diminish it. He said the only recourse for a scientist was to be concerned about the social, who's concerned about the social consequences of this work is to remain involved with it to the end. The lesson that he imparted is that scientists need to consider the ethical implications of their work and take part in the important discussions surrounding how their work is interpreted and used. And so I'm hoping that in participating in this discussion today, I'm in small part honoring the lesson that he imparted. So as Nathan said, I'm a psychiatrist and neuroscientist, and I'm in that campus psychiatrist who didn't receive much of an education about psychedelics because they had gone into all of that research and wisdom had gone into hiding. So lo and behold, two years ago, I was looking for ways to treat rumination, which I've been studying for a while. And rumination is the sort of negative, persistent self-focus that plagues so many of us, including those with mental illness. And the chair of our department at the time happened to be at a talk at the Broad Institute. And there, Robin Carr-Harris was presenting his work on psilocybin. Turns out psilocybin affects the very same brain network that is involved in rumination. And so we started to wonder whether or not there might be a role for psilocybin to treat rumination. And what started off is just exploring the research to conduct one study. A year later turned into us founding the Center for the Neuroscience of Psychedelics at MGH. The center is an interdisciplinary center bringing together psychiatrists, neuroscientists, neurologists, radiologists, all working to advance research to transform mental health treatment and innovation using psychedelics. Our mission is to understand how psychedelics promote neuroplasticity and enhance the brain's capacity for change to optimize current treatments, create new treatments, and ultimately make the term treatment-resistant obsolete. Mental illness is the leading cause of disability in developed countries. One in two Americans experience mental illness in their lifetime. One in four Americans struggle with mental illness in a given year. And if clinical experience is any indicator, the past 18 months ensure that number is higher. Every 11 minutes, someone in America dies by suicide. $350 billion. That is the annual direct cost of treating depression in the United States and Europe. Nearly half of that total represents the cost of treating those who have not received relief despite multiple trials, including medication trials and other therapeutic interventions. Patients who are drained, quote unquote, treatment-resistant. In fact, one of the biggest clinical challenges in mental health is treatment-resistance. Those who, patients who have treatment-resistance, those who seek help but don't improve despite multiple medication treatment intervention trials. Who are treatment-resistant patients? It's the patient with depression who has tried multiple antidepressants, maybe a course of TMS, maybe even ACT, and who still struggles to get out of bed and function. The patient with alcohol dependence who's been to inpatient detox several times, residential programs, and is still unable to maintain sobriety for longer than a few months. It's the patient with PTSD who's tried multiple medications, extensive amounts of therapy, but still feels on edge all the time and is unable to function due to flashbacks and nightmares. These are the patients that keep psychiatrists up at night because we desperately want to help them, yet everything we try seems to only help for a little while or not help at all. We recognize that treatment-resistance reflects both the limitations of our currently available treatments, as well as the likelihood that these patients' brains are less capable of change in ways that improve mental health. This brings us to this idea of neuroplasticity. All of the treatments we offer, medication, therapy, ACT, work by bringing about changes in the brain. All healing is manifested through these changes in the brain. Neuroscientists refer to this as neuroplasticity with the thought that just as plastic can be molded, so too can the brain well into old age. Neuroplasticity is seen at the cellular level, at the level of neurons, all the way up to changes in networks of brain regions underlying cognition, emotion, and behavior. From earlier research, we know that some of the factors that help make the brain more receptive to change or treatment are unless there's supply in patients suffering from depression and suicidal ideation. This reduces their brain's capacity to change and adapt to the environment, which makes it harder for our treatments to work. And for our treatments with patient resistance, this problem is magnified. And so the key to solving the biggest challenge in mental health care is to increase the brain's capacity for change in order to promote healing and eventually wellness. The reason we got interested in psychedelic compounds is that psychedelic compounds, and in particular DMT, MDMA, and psilocybin have emerged as treatments which hold the promise of increasing the brain's capacity for change. Work done in animals show that they increase the napdogenesis. So here we have representative images from cortical neurons and rodents. And the spiny processes sort of indicate new synapses where communication happens in the brain. And as you can see, DMT and LSD result in far more napdogenesis than in the control. And so these studies suggest that psychedelics may facilitate neuroplasticity at the cellular level, at the network level, allowing the brain to form and reorganize connections. This creates a unique opportunity to change patterns in brain activity and in turn improve symptoms, behavior and functioning, and we hope ultimately suffering. But one issue is that little is known about how these psychedelic compounds work in the brain to promote neuroplasticity, especially in humans. What we do know is that early clinical trials suggest immediate and sustained relief of symptoms after anywhere from a single dose to up to three doses of a psychedelic compound in a therapeutic setting. Compare this to taking multiple medications daily. That sounds pretty amazing and promising. In fact, early trials show that 68% of patients with treatment-resistant PTSD who received MDMA no longer might criteria for PTSD after 12 months. And in a study of cancer patients, a single psilocybin session led to reduced anxiety and fear of death in 80% of patients, even six months out. The initial results from clinical trials are so promising that they have earned psilocybin breakthrough status for treatment-resistant depression by the FDA as well as MDMA for PTSD. And for those of you who may not know, breakthrough status is awarded to investigative therapies with evidence demonstrating substantial improvement in serious or life-threatening conditions over currently available treatments. It's a pretty high bar. And as of right now, psilocybin and MDMA are in late-stage regulatory trials in 13 countries. Compass Pathways just closed their phase 2B trial for psilocybin for treatment-resistant depression, and MAPS is currently in a phase 3 trial. So at MGH, what we're hoping is that the remarkable advances that have happened in brain imaging since the 1970s, many of them pioneered and developed at MGH will allow us to leverage the ability to see the brain in a way that hasn't been seen before in order to see the neuroplastic effects of psychedelic drugs from the level of neurons all the way up to networks. And our thought is that seeing and understanding these changes in the brain will allow us to transform mental health research and treatment because we believe that we can take the knowledge of how psychedelics promote this sort of change or neuroplasticity, harness it to complement and even enhance current treatments, develop new ones and alleviate the suffering of our patients and greatest need of health and hope. While the center is young and will grow over time and scope and influence, we have three foundational research programs beginning in the next year. All three are in good understanding how psychedelics facilitate and enhance changes in brain structure and function. Although the initial focus is on psilocybin in patients with treatment-resistant depression, our first study, which hopefully will be up soon, is looking at the effects of psilocybin on rumination and treatment-resistant depression. Rumination is this sort of repetitive negative self-focus. You know, why did I do this? Why am I such a failure? Which contributes to depression but also contributes to anxiety and other mental illnesses. And our hope is that by looking also by looking at the effects of psychedelics on what are called trans-diagnostic processes. So these processes that are not demarcated by depression but are seen in multiple types of mental illness will mean that even though we conduct one study in depression we have the ability to affect care for lots of other people. Our second project will look at psilocybin and cognitive and emotional processing. Specifically, salience processing and cognitive reappraisal which are both issues in patients with treatment-resistant depression. And finally, we'll be looking at psilocybin for personality-trade factors that predispose to mental illness. For all of these studies, we will collect a wide array of neuroimaging and electrophysiological data to fully characterize and understand the neural correlates of change with psilocybin. Before I hand things over direct, I wanted to end by sharing another piece of wisdom from someone else I was fortunate to get to know shortly before his death and that was Alvin Novik. And Al was a physician, turned researcher on bats of all things. But in the mid-1980s, as the AIDS epidemic took hold in our country, he turned his attention to research and advocacy for AIDS. One of the things that came out of the AIDS epidemic was that it put a magnifying lens on the drug approval process with the FDA. And it led to a number of important changes, including efforts to shorten the development and review process and also to allow access to promising drugs before FDA approval, the expanded or compassionate access that we talk about now. And Al served on the FDA's antiviral drugs advisory committee. And I remember this account that he gave of coming out of one of these meetings. And he came out to see all these activists with wristwatches held up in the air. And the wristwatches were meant to symbolize the urgent need for drug approval and access. They symbolize the fact that time was ticking and people were suffering and dying. The COVID-19 pandemic of the past 18 months or so was likely given all of us but a taste of that sense of urgency for drug and vaccine development and approval. In fact, those of us who are parents of children under 12 are still anxiously awaiting approval of the vaccine for COVID-19 for children as Delta rages across our country. And I feel like what Al underscored was the importance of considering the human face of suffering and maintaining a compassionate view of the most vulnerable and marginalized populations as we consider difficult ethical issues. In a congressional hearing, he ended with the words that if we can do these rational things by which he meant the research and public policy measures and so on, do them soon, thus implicating urgency of meeting the need and do them with goodwill. We may even achieve a society truly characterized by compassion, love, justice, equality, and respect for others. And the reason Al made mention of goodwill is that he also did an incredible amount of work at the intersection of the body, to discuss the intersection of bias regarding homosexuality and IV drug use that intersected with the AIDS epidemic in a devastating way. And it still remains the case that individuals with mental illness and specifically serious mental illness are marginalized in our society. And what I hope we'll be able to do is keep a focus on those individuals because they have a lot at stake with how the discourse on psychedelics plays out and the history that's about to be written. Thank you. Thank you so much, Dr. Ghaznavi. I will now introduce our second speaker. Rick Doblin, PhD, is the founder and executive director of the Multidisciplinary Association for Psychedelic Studies, or MAPS. He received his doctorate in public policy from Harvard's Kennedy School of Government, where he wrote his dissertation on the regulation of the medical uses of psychedelics and marijuana, and his master's thesis on a survey of oncologists about smoked marijuana versus an oral THC pill for treating nausea in cancer patients. As an undergraduate at New College of Florida, he wrote a 25-year follow-up to the Good Friday experiment, which evaluated the potential of psychedelics to catalyze religious experiences. And if you're not familiar with the Good Friday experiment, it occurred not far from the Center for Bioethics in Marsh Chapel on the Boston University campus in 1962. And there are many other interesting psychedelic landmarks from psychedelic history scattered throughout the Boston area. Rick Doblin's professional goal is to help develop legal context for the beneficial use of psychedelics and marijuana, primarily as prescription medicines, but also for personal growth for otherwise healthy people. He founded MAPS in 1986, shortly after MDMA was prohibited by the Drug Enforcement Administration. And today, MAPS is very close to obtaining FDA approval for MDMA-assisted therapy for treatment for post-traumatic stress disorder. Welcome, Rick Doblin. Great, Mason. Thank you so much for having me. It's fun to comment on how Dr. Gazznauzzi's discussion about Alvin Novick was really interesting for me to hear because based on the pressure from the AIDS community about the need to expedite research, the FDA established what's called the Pilot Drug Evaluation staff. And they were created around 1990. And their goal was to pilot new ways to expedite drug development. And they needed actual drugs to practice on. And so they looked around other areas at the FDA where they could sort of take certain drugs under their purview. And they noticed that the psychedelics in the Schedule 1 drugs, including marijuana, had been basically suppressed for research for over 20 years. And so they went to the group that was regulating psychedelics and said, we'd like to take them on. And what they ended up doing, not because they were pro-psychedelic, but they were pro-science and they were also pro, the need to demonstrate these new approaches that they opened the door to psychedelic research. First in 1990 with Rick Strossman to do a study with psilocybin in a negative frame, in a sense, could DMT, which, excuse me, that psilocybin, DMT. The DMT is the only endogenous psychedelic. And so the thought was maybe too much, but it makes people go schizophrenic. But then in 1992, the FDA opened the door to our own MDMA research. But it's really because of this pilot drug evaluation staff, and apparently it's a lot to do with Alvin Novick and the work that he did to get this started. So I was really glad to hear about that history. All right, so now I'm going to switch to my slideshow. I'll take just a second to set it up. And I'll just say that while we're getting this all set. Okay, there we go. It's just really a pleasure to be here with you today. So I'll talk about some policy and ethical issues. This just speaks to, this was just last week. And this was two emails that I got very close to each other. What was this? This was from a therapist here in Boston that a US Marine pilot. And this pilot's report was about 9 30 a.m. On that morning of this first MDMA experience, I took two bills and began an eight hour long therapy session. I felt hollow and numb for the first 45 minutes of the session. The same as I've been feeling for years of walking skeleton. And about that 45 minute mark, I was in the middle of saying word struggle as I always did. And I burst into tears. It was the first time I cried in about 15 years. It was in that moment that I knew I was going to live. So this is the story of the promise. This was from my assistant. This email that I read just few minutes after the other one. Saying another one of my friends took his life. So I'll be attending his funeral tomorrow. We have our drive and work in reduced hours Monday. So I can drive home. He was a veteran. So this is about the need for urgency. So we've got the promise and the need for urgency. For all the people that are treatment resistant from other available. The purchase. So where are these key issues between public benefit and profit? One of them is where do we set the price of MDMA? I mean, of course, that's constrained by what insurance companies are willing to pay, but that's the real question of do we maximize profits? What do we do with the money once we get it? How do we balance the rate of training therapists with the quality of the training? How do we arrange for therapists in training to receive MDMA a therapeutic setting? So, you know, there's roughly eight to nine million DST patients in America. And it's only going to be an MDMA assisted therapy only by trained therapists. And so that's going to be this big question is how do we properly train these therapists? And I think a key part of it is having the therapist receive MDMA as part of their training. So how do we arrange to do that in an affordable scalable way? We're doing a very poor job of bringing in patients of color. We realize that what we need to do is train therapists of color. So how do we do that? That's going to be a really important issue going forward. Also, we've been entirely funded by donations and grants for our 35 year history. We've raised about 130 million, but now we're at this place where we're projecting a need for 150 million over the next three years, 50 million a year for US commercialization, globalization, including EMA approval and reaching sustainability. The income from sale of MDMA covers operational costs, estimated middle of 2024. So what kind of compromises do we need to make? If any, if we do accept money from investors or partnerships, then can we find the rest through philanthropy? There's now over around 400 for-profit psychedelic companies and so many of our donors were saying, why should I donate? I might as well invest. Another key issue is going to be this issue about drug policy reform. Is it a benefit or a threat to the business model that these drugs are decriminalized and eventually legalized? Or is it nevertheless a moral obligation to work on drug policy reform based on the fact that the drug war has been very ineffective at reducing drug abuse? And then this other key question is, is it important to have bipartisan support from donors and politicians, meaning can we get support from people that we disagree with on many other things? Is that important? How do we do that? So these are some of the ethical issues and ethical issues. Stan has talked about psychedelic, Stan Groff, the world's leading astute researchers, talked about psychedelics are to study the mind that the microscope is to biology and the telescope is to astronomy. And we know that the telescope is controversial for what Galileo was able to see, that the Earth wasn't the center of the universe. It's quite under house arrest because his views challenged what the church thought. Father Bruno, who believed that this was the case, was burned at the stake for saying it. But now the telescope has become a more neutral tool. We use it to explore the universe, to get a better understanding of our place in the universe. We've never seen such a controversial thing anymore. And psychedelics are similarly that way. We hope that we'll be seeing more as neutral tools. And we will just be more open to learning what we can about the mind through the use of psychedelics. This is Alex Gray, an artist, psychedelic artist. This is his interpretation of the maps logo and the emphasis here is that the psychedelic is in the background and human hands. In the foreground, people helping each other. It's about psychotherapy assisted by psychedelics. I think that's a big change from the 60s where the psychedelics were more, at least in the popular culture we're seeing as independent by themselves. But what we're talking about is the context, the set and setting, but it's really the human relationship with the psychedelics. Give you a sense of the psychedelic renaissance. This is over the last 70 years, scientific publications on psychedelics. You can see a peak around 1970. That's the end of the psychedelic 60s. The backlash started coming in the middle of the 60s and then 1970 was a control substances act and then a steady decline in papers over the next 20 years and most of these papers then were about the risks of psychedelics not benefits clinical trials were blocked. And then, right after 1990 is when the paper started increasing. And that's where this pilot drug evaluation staff took over regulating psychedelics and started the opening door and that helped them around the world with regular agencies so now we're in the vast number of papers on psychedelics, more by multiples than where we were in the 60s or 70s. It's an incredible opportunity and we are in the midst of such a great sense. This was just a couple years ago but this was the FDA slide they created the psychedelic slide looking and they're announcing at this conference that they're the FDA is providing a guidance document for sponsors of psychedelic research they're still working on it but that's going to be really helpful. So this is just again to acknowledge that sort of psychedelic reticence is really linked to the FDA and their willingness to entertain research again. So maps is started 1986 35 years. This is our structure maps is the nonprofit. In December 2014 we started the maps public benefit corporation. That's our for profit pharmaceutical arm that will sell MD may for a profit, but then all the profits are going to be allocated according to the mission of maps because maps is the 100% owner of the public benefit book. We have about 130 people now, but a hundred of them work at the benefit for and the rest work that maps the nonprofit. The reason that we can sell MD may for a profit even though we don't have any patents is this policy that Ronald Reagan signed into law 1984 to provide incentives for developing drugs that are off that and it's called data exclusivity. So what that means is that no one can use our data. Unless we give them access to it, the market is generic for in the US over five years. If you do pediatric studies, we've got an extra six months data exclusivity and we are being required by FDA to do pediatric studies if we can succeed in getting FDA approval for MD may assist the therapy for adults, 18 year old or then we already negotiated a study in 12 to 17 year olds with PTSD. Right, so then five and a half years we get data exclusivity and then generic competitors and start applying it takes FDA at least six months to review their application so basically six years data exclusivity. And in Europe. It's essentially 10 years. And they passed their data exclusively after this and they provided more time for that. But our public benefit model makes this difference than for profit companies we maximize therapy outcomes for each patient, not profit. We, for example with s ketamine it's approved for depression but it's administered without therapy. And that means that the results aren't as good. There's not as much integration, people need more s ketamine. It means more money the pharmaceutical company if they would have combined it with therapy the way a lot of the ketamine clinics are now more money goes to the therapists, you don't need as much ketamine that maximizes patient outcomes but not profit so our public benefit model is to maximize patient outcomes and share findings we're not creating IP protection we're just submitted our production. Our process patents are well our information on making GMP MDMA and commercial scale. We're not patenting it we're making a public we want to serve as an ethical model for the for profit industry so they'll adapt some of the policies maybe. We want to become public benefit corporations we're supportive of for profits. It's very important to say the scale of the need is so great. But a key distinction is that we're in favor of drug policy reform, we think that people should be able to have legal access to psychedelics in a pure form in a licensed legalization manner. Where if you misbehave you lose your license to buy them for a while, and you get punished for your misbehavior. A moral imperative and if you can go ahead and buy MDMA for 10 bucks or 20 bucks or whatever and grow your own mushrooms is that going to be bad for the business model for these for profit psychedelics. I think not I think that it will destigmatize and create even more interesting people going to train professionals and psychedelic clinics covered by insurance. But we're not there yet, but regardless of its help or to the business model, there's as I said a moral imperative for us to do that so that's a big issue for us. Drug policy reform is not in and of itself enough we need to build into the culture harm reduction psychedelic pure support we have to train people to learn how to process difficult experiences, and how to work in that way. So we do harm reduction signal peer support what that means of course is that we're supporting personal and spiritual growth, not just treating medical conditions people should be able to access these drugs without medicine without religion. We're also very much using these drugs and kind of conflict situations you could say couples therapy one of the best uses of MDMA is couples therapy but also cultures. And so we're doing projects with Israelis and Palestinians we're doing I was going to be made better. We joke that. Once we've addressed that issue then we'll do the harder case of Democrats. But this is our public benefit model. This is our Zendo psychedelic harm reduction program that we've done all over the world. We have a program with the Denver first responders with the police for doing 100 tests, and we are educating them in a six hour program of what to do if they empower people having difficult trips. So where there is drug policy reform we're trying to come behind and create a community that's likely to be able to support it to minimize problems. And so if this works with the Denver police for 100 or so people then we're going to negotiate to go up to three or 4000 first responders and then. So this is something that we're doing I think it's an ethical imperative this is this idea of license legalization. The example is alcohol if you are a drunk driver you lose your driver's license but you can still buy alcohol really easily. We should make it harder for people to buy alcohol. So I think this license legalization incidentally this idea was Timothy Leary's. So he gets doesn't get a lot of credit for some ideas that he had that were actually rather conservative. And we think that this will happen in 2035 will need a decade of roll out of psychedelic clinics for people to get comfortable with the role of psychedelics and hear a bunch of stories about people who've gotten deal than that will change because attitudes towards legalization, and how we're going to handle adult user use by kids adults of course will have this legal access. But children, I think should have not a complete prohibition should be prohibited for kids, but there should be a parental override. And that is the way it is in indigenous cultures that have successfully integrated psychedelics like the ayahuasca churches the Native American church. And in the US 23 states have parental override so that parents can give alcohol to their kids. This is the way I think it should be done for psychedelics. In our history we've raised over 130 million grants and donations but the for profit people just in the last two years have raised one and a half billion dollars. So that's an important sense of the scale of things. It's been very important for us to get bipartisan support. Rebecca Mercer his family funded Cambridge Analytica owned it. We've heard, you know, very controversial but we came to agreement on a million dollar donation for our PTSD research, which was very important. Elizabeth Koch has now given us this pledge of 2.7 million and since then she's given us another $3 million to move to Europe. And also, but also George Soros. So we span political spectrum and that's been really key. Dan Crenshaw is a member of Congress, a Republican from Houston, and he's a former Navy SEAL. So he's our main ally actually in Congress because in the House because he's heard about so many veterans going down to Mexico for Ibogaine or five MEO or he's heard from our veterans who've been in our study with MDMA. He's very supportive. And so we have much bipartisan support. Just to give you a sense of how this is going amazingly, Texas is anti democracy with voter suppression their anti women's health with trying to end abortion and their anti public health trying to give it mask mandates and yet just recently a few months ago they allocated 1.5 million to the Houston VA to study psilocybin for PTSD and we're working with the same people now will know within a month, but they're considering allocating another 1.5 million for an MDMA arm so it'll be treatment as usual versus psilocybin versus MDMA with veterans inside the VA. And this is so far this has been funded by the Texas Legislature. So we have succeeded in this bipartisan approach. We did get breakthrough therapy. This was in August 2017. Following that was compass got breakthrough therapy for psilocybin for treatment resistant depression then you saw the major aggressive disorder. This is our phase three design that we negotiated in a special protocol assessment. It's 42 hours of therapy. There are three MDMA or inactive placebo eight hour sessions with a male female co therapy team it's not always male female almost always. And it's 12 90 minute non drug preparation sessions as well three before the first one experiment session for preparation three after each one for integration. And people will either get the top row where they get MDMA each time or they got the inactive placebo all three times. There's no good way to do it double blind. That's another issue that we can discuss a little bit later but this was approved by Bob temple the old wise man at the FDA been there since 72 and partner. Office of Science Policy and it's also been approved by the European Medicines Agency. And we do a two month follow up. So that is after the psychedelic after glow. Just to see if it's durable we also do 12 month follow up that's more for the insurance companies. We've got a formal dispute resolution with the FDA. And this was about our protocol to give MDMA the therapist is part of training the FDA has already approved one we enrolled about 95 people we've got 120 total so we can do 25 more there, but we want to do another protocol simpler. And in December 2019 FDA put it on clinical hold said we're never going to give you permission or this it's too risky there's no benefits. And also we don't think you're qualified your proposal we want MD PhD is the lead therapist not licensed to do therapy and we think there should be a physician on the site on the premises for every session, not just on call as we have in phase three. And because we're protected by the special protocol assessment in phase three. They couldn't change that in phase three, but going forward another protocols FDA tried to change it and so we protested and we submitted information. And the FDA just kept ignoring it. And so we eventually appeal in this formal dispute resolution to the Office of Neuroscience process over a quarter million dollars and legal fees and way lots and staff time. And again, we want 100% the Office of Neuroscience overworld the vision of psychiatry and the clinical hold was removed the protocol is active, we're back to license therapist as a lead person not MD PhD and we don't need a physician on site so these were poison pills would have made it way more expensive than necessary. And so this issue is, it's important to challenge the FDA when they think when you may think that they're going off track and this is something they've never done before so this was a terrific resolution of that. We have also negotiated with European Medicines Agency and we've got a Google they are with the same design to go forward with one phase three study in Europe and all except their US data and we're there in nine sites in six countries and we're in the process of training therapists right now in Europe. Our phase three results are pretty incredible published in Nature Medicine, a 10th big articles in the New York Times, they're positive this was the front page of the New York Times a week later, psychedelic revolution is coming psychiatry may never be the same. We've negotiated two 100 person studies, but first one is completed as I said and because of COVID we completed it in last year under COVID and we negotiate with FDA to go forward with just 90 subjects instead of 100. There are a few risks of the fewer subjects you have the less likely you already get statistical significance but we thought that was important. And we're now in the midst of our second phase two study. We've passed the halfway mark for a number of participants enrolled and the interim analysis for this will be in May of next year. We think we'll finish this in October of next year. The results of our first study were tremendous. Two thirds of the people are female one third is male. Most sexual assault or domestic violence. There are armed or unarmed assault combat sudden violence of school or mass shootings these these are the buses and of these 90 people 30th on their primary trauma was from childhood. We had, as you can see more than a third had PCC for 20 or more years. Average was around 14 years. We work with the hardest people this is the graphic results which I'll just the, you can see here that the gap between the people that got therapy versus the people within active receivable versus people that got therapy with MDMA widened after each MDMA session after each experimental session so this helps justify a three session model and our P value was an astonishing point 001 10,000 chance that it's random. We also did great with depression and functional impairment as well. In the two month follow up in our first phase three study 32 people no longer had 32% no longer PTSD and phase two it was 23%. And at the two month follow up in the phase three 67 two thirds no longer PTSD, and it was 56% in phase two, and in phase three of this remaining 33%, but still as PTSD, most of them, 80% of the rest had clinically PTSD symptoms so it doesn't work with everybody, but the results are rather astonishing, and we were still waiting for the 12 month follow up. In terms of the fact sizes is all up to max or the only drugs approved by the FDA for PTSD and they are trivial or small or media low medium maps. So we're presenting it in two different ways the point nine one and the fact size of one is one standard deviation for the more. The normal way you do it is placebo subtract it which means you subtract the placebo effect but in our case the placebo is actually therapy. So we had point nine one which is a large effect size. But that's subtracting the therapy so that's really only the fact of MDMA, but it's 2.1. When you look within subjects for the people that got MDMA plus PTSD. I mean, excuse me, MDMA does there. This just shows that the dissociative subtype which is the hardest group to treat for PTSD did better than the rest on average interface so what this suggests is that MDMA works best even in the hardest cases and we also don't see the attempted suicide which many PTSD studies don't. There was no side effects. We could say that this is meets the. It's not just some highly experienced therapist driving the results it speaks to the quality or training program but we think it really speaks to the incredible for the potential of MDMA in the safety we had more personality in the placebo group than the MDMA group and we had no serious adverse events of suicidal ideation attempt in the MDMA group but two people in the placebo group one attempted suicide twice and one self hospitalized to avoid suicide and so our safety record is great and no party of basketball problems in the MDMA group and no evidence of abuse potential by self report. There are side effects muscle tightness decreased appetite sweating and these are all greater and MDMA them to see both, but they're shortly a very cute they're not that problematic. And so summary, great free value large effect size replicated results from place to no site to site barely good safety profile. And enough meets FDA criteria to get approved on the base of one study. One phase three study instead of two, and we, you know, I'll know about this landmark Alzheimer's drug approval, which confounds research we've been very controversial fks under investigation for this and they failed phase three studies and they added the data. They had significant safety risks and yet this drug was approved. With that kind of data FDA has rejected our request to go ahead with one phase three study so we're in the midst of the second phase three study. This is our timeline we think by the end of 2022 October 2022 will have finished the first phase three study. We have a year to do the reviews by FDA. So we think the third quarter of 2023 will have FDA approval, DA now must reschedule within 30 days. So we think we'll have the for the end of the fourth quarter of 2023. And we think Europe will be about one year behind this. Our goal here is to during this decade to have a million MDMA sessions. We think that if it's an average of two sessions per person, some will need one, some will need three, so we'll need more than three. But we'll just say in the neighborhood of half a million patients, the tan line at the bottom, or is the number of therapists that we want to train. So we're actually talking about training 25,000 therapists. And the tan line at the bottom, at the top is their capacity. So we could, we're assuming that they're not doing just MDMA therapy that they're doing some other things as well but there is more capacity if they want to do that. And we think insurance companies are going to cover it this is been published in plus one this is based on the phase two data we're re interpreting it for phase three data. We're doing research in this Loma Linda VA this month, and in Bronx VA so our use is not assuming massive rollout in the VA but we're trying to make that happen there's over a million vets on disability for PTSD costing the VA around 17 billion a year. Also, our projections don't include group therapy so we're going to be starting a group therapy study early next year at the Portland VA about this training of therapists of color. We had our first training specifically for BIPOC therapists, and we have since given around almost 900,000 in scholarships to 200 BIPOC trainees. So this is our attempt to really move forward in this way. How do we make this legal it's in a way post approval it right now we have two protocols but it's way too expensive to scale. So we're trying to get in the FDA label with MDMA for PTSD is by trained therapists whose training can include one end of the session. And if we can do that, then it's going to be in the label. We're going to need to raise about 150 million as I said to do these different things that I've talked about commercialization US globalization and reaching sustainability. We saw that we're doing some of it with partnerships we've just announced this that they've given us 1.5 million to evaluate a collaboration. And this would be for MDMA for TBI so we're exploring other partnerships like that. This here is a sense from the Boston Consulting Group Revenue potential. They're assuming a wholesale price of $3,500 per MDMA session for the MDMA, not the therapy. And they're assuming in the access of $2 billion of income during this period of data exclusivity which drops dramatically after those junior. But again, as I said it'll be 10 years in Europe. And how will this be regulated the risk evaluation mitigation strategies. It's only going to be prescribed by prescribers that have been specially trained by us it'll be a two to four hour two to six hour training. The therapy itself is only going to be done by people that we've also trained. We are going to, we have 100 hours training to supervise them as they work their first PTSD patient and we have this option now for them to volunteer for protocols. The distribution is only going to be to the prescribers not to the patients it's never a take home drug always administered under supervision and safety screening is required this is what we're going to be negotiating with the FDA. There's going to be psychotherapy clinics like this. This is just to illustrate that the therapist want to be cross trained in the different realities. And this is going to be one of the bigger issues ethically what do we do about a direct consumer ads. It is permissible in the US but not in most countries. And we've prepared some of these for fun, but I think there will be some of these ads and how do we handle them. Based on that. You've now got an overview and I really look forward to our discussions. Thank you both for those excellent presentations it's really interesting to hear about your work. We have many many great questions please continue submitting your questions and I'll do my best to work them in to the conversation. I think I'll start with some questions from the audience. The next question is from Stephanie to Bosch Nick. And Stephanie asks, can you discuss the decreased effectiveness of psychedelics, aside from ketamine. If a patient is also on an SSRI a selective serotonin reuptake inhibitor. So how, how do you handle that how do these substances interact, and how do you address that that potential interaction. And we do feel that, you know, the SSRI is active by some of the same receptor sites and they diminish the effect of NBMA. They also diminish people's emotional range, you know they cut off some of the lows but they also cut off some of the highs. And so we make a requirement that people taper off of all their existing psychiatric medications, including if they're using marijuana. That's very difficult so that has to be a supervised taper under their prescribers review. We prepare people for the fact their symptoms may start getting worse, but that that's part of the therapy that's part of the process so that then they can, instead of learning to work through them. And there is going to be in the future, some studies that we're probably going to want to do that'll be co administration of MDMA with people on SSRIs. There's informal reports that you double the dose of MDMA and people have a full MDMA experience but the concern is about serotonin syndrome. And that a lot of the people don't want to taper off their SSRIs. And that's a real barrier for people to enter the treatment, but it is necessary, or if we can do it safely to double the dose where they can stay on one of the advantages of ketamine is people don't need to get off of their medications, but with MDMA or other psychedelics they do. And as Rick mentioned, you know, the, because of receptor occupancy issues. We also have to taper people off of their SSRIs for the sales lab and trials, again with careful supervision and provided they can tolerate being off of the SSRIs I think that's a major challenge, not only do people maybe not want to grow off of them but can we get them off safely and still conduct the trial in time. Thank you. I have another question from Kyle Ray Patch. What changes to informed informed consent process, if any, do you envision being necessary in these trials, given psychedelics potential to alter decision making and deeper psychological stability of participants. In our very first study with MDMA for PTSD, we had a very difficult time finding an IRB that would work with us. And in the end what we did, I call that there was an IRB called the Copernicus IRB. We figured if any IRB was sympathetic to political pressure from religious or political reasons to suppress scientific research it would be Copernicus and they eventually did take the, did take on for review and they eventually approved it but to make them feel comfortable we had to have the world's longest informed consent form. And in fact it was so long that we had to have a quiz at the end to make sure that people really understood the part of it. And just to avoid the Copernicus being sued by something not being in the informed consent form. So we pretty much had everything in it. However, we have since added some text about how we did have one therapist in our studies engaged in the sexual relationship with a patient after the MDMA therapy was over. And so this idea of how does these drugs affect decision making and stuff. So we talked about this loosening of boundaries and this potential counter transference and transference and so we're doing a little bit better job I think on educating people about you know how it's completely unethical to a therapist they have sexual relationship with their patients but for people to be aware of their, you know, suggestibility and that that's one of the reasons everything's videotaped to therapists. And so I think that just with those little additions to our informed consent form were pretty well set there. Some research studies have gotten around this by actually including people with prior psychedelic experience so they, because the only way to have informed consent about what the experience is actually going to be like is if you've had something like it before or had it before. And I think we, you know, you know, since that time. You know, people have come to appreciate that the reality is we don't, you know, people who sign informed consent for other procedures, don't know exactly what the experience is going to be like and what we have to just pay attention to. This is the suggestibility, the suggestibility piece and I think the ways around it include, you know, having two therapists present recording sessions, emphasizing to the therapists the importance of safeguarding, you know, the patients, because of this aspect of suggestibility. So I'll throw in one of my own questions. Dr. Gosnavi you work with patients with bipolar. And I wonder what you make of the fact that some patient populations have traditionally been excluded from clinical trials for psychedelics so patients with bipolar, schizophrenia or personality disorders for example. What do you think is the potential, if any, for psychedelics to potentially be useful in some of these populations. I think that they've been excluded for good reasons, which is there's a lot that we still need to understand and know, and they're particularly vulnerable populations even among those with psychiatric illness. And there is the risk of predisposing to psychotic experiences beyond lasting beyond the session or precipitating psychotic episodes so even a family history of bipolar disorder or psychotic disorders excludes you from most of the studies. But my hope is that if we understand the mechanisms, we can somehow, you know, use that information to expand some applicability to populations that have until now been excluded from research trials. I mean, as you said I was psychiatrist locations bipolar disorder. So, you know, seeing their suffering firsthand, I want to hope that we'll be able to do something for them. Just later down the road. Yeah, we also just by the way exclude bipolar exclude major psychosis we don't go as far as first degree relatives, we will permit that to take place. I have a question I from Jennifer Chesk, and I'll kind of combine it with one of my questions. She asks, what role could psychedelics potentially have in treating psychiatric symptoms after COVID-19 illness, and I was going to ask a question. Rick you mentioned, or maybe it was Dr. Gosnabi I think you mentioned the AIDS AIDS activism and and compassionate use access to experimental medicines in Canada. The government allows people to access psilocybin through compassionate use and some exceptions, other exceptions to controlled substances laws. I actually I wrote an article about how emergency use authorization could be used for psychedelics, the way that it's used for COVID vaccines and other COVID therapies. I wonder what, what role do you think psychedelics might play in within the context of COVID-19, and do any of these early access programs play a role. Well, we do have permission from the FDA for 50 subjects for expanded access. We also have permission in Israel for what they're calling open access, which is basically the same thing. One of the small phase two pilot studies that we did was MDMA for social anxiety. It was limited to autistic adults, but I think because of COVID there's going to be a lot of people who have social anxiety coming out again. So we can certainly treat, there's more people isolated more people with depression, things like that health care workers burnt out. It's just that COVID has made a lot of mental health crises worse. And so I think we can play a major role there. The one thing that is not going to happen is remote administration of psychedelics. It's something that we've gone to remote administration of some of the prep sessions and some of the integration sessions, but the actual psychedelic sessions are always going to be under direct supervision in person. And so that has slowed down our research a little bit, but you know a lot of treatments have gone online and telemedicine, but I think the actual administration of psychedelics will never go that way. Like, you know, it was just stated that COVID-19 pandemic is only worse than the mental health crisis. I mean, I see it firsthand. You know, you can't even find a bed for a patient that needs it and more patients need it than ever before. So I think that the need is going to only be magnified at the end of the pandemic for because of the isolation because of potential neuropsychiatric sequelae of COVID-19 and so on. And you know, that said, I think that there's a lot that we still need to learn before applying it widely and we have to look at exactly who we're talking about, because all every disorder has increased, you know, worsened and increased over the pandemic. I have another question from Dorothy Doar. Are there data about the use of psychedelics in palliative care and end of life at the end of life? And I think those are some of the most interesting results perhaps. Yeah, there's not in the sense that there is a fair amount of data of psilocybin for people with life threatening illnesses who are anxious or depressed about dying. They can also work with MDMA with people who are dealing with life threatening illnesses. However, at the very end of life, like in the hospice centers or the palliative care, that has not happened yet, that research. One of the challenges is that you've got people that are on multiple medications and it may be completely inappropriate to try to withdraw them from those medications and we don't know all about the drug-drug interactions. I think that psychedelics in particular MDMA at the end of life is great and there are anecdotal reports well documented of people in the last couple weeks of their life taking MDMA in a therapeutic setting. And so MDMA synergizes really well with the opiates and you get better pain control with MDMA and opiates, but the opiates make people sleepy. But they're depressant in that way. So the stimulant aspect of MDMA wakes people up. They get better pain control. They're open-hearted. And I've seen miraculous situations of people days before they die saying goodbye to their loved ones in ways that were just, yeah, miraculous. And so, you know, we already have here in Massachusetts a lot of times ketamine is being used in low doses as a pain med in hospice centers. So one thing that could be done a lot easier would be just use higher doses of ketamine in therapy. They're already getting ketamine. And ketamine blends well pretty much with these other drugs. So I think that it is a very important area of future research, but people have avoided it so far just because of the complexity. I have another question. This is from Nicholas Ludka. Dr. Ghaznavi, you talked a little bit about a rumination and its role underlying mental illness. What is your goal with psychedelics in this context? How might, and you talked a little bit about this with the default mode network, I believe, but maybe you could elaborate a little bit on what the goal is with respect to the potential effect there of psychedelics. Yeah, you know, the hope is that so, you know, Mason just made reference to the default mode network and that is the network of brain regions that are involved in how we process information about ourselves. And so, given that rumination is a form of self focus, it's not surprising that it involves that region as well. And what we know from friends and studies of mindfulness is that it decreases activity and default mode network. And mindfulness helps address rumination in patients with psychiatric illness. And so the hope is that psilocybin could do it and do it more powerfully. So what I've heard from people sometimes is that their experience with psilocybin was like years of meditation in one session. And so the hope is that we can decrease rumination and rumination affects the likelihood to develop a mental illness, the course of the illness, and the likelihood of relapse. So being able to intervene on this process that's a pathological means that there's a role potentially for not only treating and preventing relapse, but maybe even prevent preventing the illness down the road. Someone asked what kind of vital signs you record during clinical trials. Yeah, well, we are MD may increase increases blood pressure and it also increases temperature slightly. So we do periodic blood pressure we used to do it way more frequently than we do it now. We did it several times at baseline. I didn't explain this before but we give an initial dose and then two hours later we give happy initial dose to extend the plateau to make it a longer experience. A lot of these for profit companies are saying they're developing shorter acting psychedelics and we found actually that longer is better in many cases, but we'll see if they can squeeze it into a 50 minute hour or whatever they're trying to do, or two hour session I think that we are basically able to minimize the number of measurements that we're taking we don't see any significant life challenging blood pressure increases we do proper screening ahead of time. We also do temperature so what we're going to be proposing post approval is to eliminate the temperature and the blood pressure readings and just focus again on the screening and you know people sometimes overheat and die from MDMA at raves dancing all night. But we don't see that at all. So we get proper fluids we tend not to give water but stuff with electrolytes, we don't see any real significant increases in temperature and so those are the main vital signs that we're looking at them and based on the data as I said we think that we'll be able to eliminate them post approval. Although if we have to keep baseline before the second supplemental dose and at the end of the session for blood pressure, that wouldn't be a problem to do. But screening seems to be key and through baseline measures to make sure that risk is low, and then there's no actual monitoring during the session with the soul seven session. We have a question from Raquel Sophia Sandoval. I would like to hear more about psychedelics and teams thinking of thinking through regulation and safety for a population with a high need. Rick you mentioned a little bit of regarding regulation. In the context of children. I think some people might find that surprising and there are cultures that get allow children to participate in psychedelic experiences. Can, can either of you comment on the potential therapeutic role in younger people. Yeah, well, all I can say at the moment because we haven't been able to develop any clinical data from that is that will Dolan who was neuroscientists at Hopkins did administration of MD made octopuses. They're very a social but you give them MDMA, and they are pro social to hang out with other octopuses. What that shows is that this pro social effect of MDMA goes deep in our evolutionary history, and is pre verbal. So I think when we start talking about kids, I didn't mention but we do have to do seven to 11 year olds, if 12 to 17 year olds really works. And so I think that it will work with younger kids to because of this sort of deep pro social effect pre verbal. But I also think that when you're thinking about traumatized children, you know, their brains are already worked by the trauma. And the sooner that you can treat them the better and it is actually a requirement by FDA because so many drugs are studied in adults but then they're prescribed off labeling kids without enough information. So that's why we're being required to do these pediatric studies. And that's why we get these incentives for data exclusivity but my sense of it is that it will probably work very very well. You know, and just as a side note I was at a Navajo Native American church ceremony many years ago out on the Navajo reservation and the Navajo man brought his nine year old son into the peyote ceremony and this nine year old son spent up spent the whole night there. He didn't need eat as much peyote as everybody else did, but he did it in this parental support kind of a situation. And so I think we've lost that in our culture by all of this complete prohibitions against you youth use and so I think eventually we need to get back to that and we will hopefully by 2024 2025 start getting data about other pediatric populations but until then it's really just anecdotal. I think we really need the data because not only, you know, Rick's right that we can you know intervening earlier might make a difference but their brains are very much developing and we need to understand how these drugs will affect them in the long run. Yeah, my sense is that the sooner you can layer in like feelings of love and connection. The better, I mean, particularly for traumatized kids, I think that it'll be very interesting once we finally can do these studies and I think people are surprised that the FDA requires it. It's not even optional at this point. We have a comment from Aaron Chironi, just pointing out that some indigenous community communities include their children pets and even pregnant persons in their ayahuasca ceremonies. And I wanted to ask you both about potential state regulation and why perhaps we haven't seen psychedelics so far, with the exception of Oregon, and, and some cities around the country follow this this more local or state level legalization model is that something we might see in the future, or is this just something that's very different. And cannabis for example. Yeah, it's coming a lot. I'm just proud to say that Cambridge was embarrassed that the city of Somerville decriminalized plant medicines before the Republic of Cambridge did. So then Cambridge followed the city of Cambridge followed but we're seeing more and more interest in that there is going to be valid initiatives I think in Colorado and possibly other states to replicate the Oregon psilocybin initiative in 2022. We're trying to create contexts that are providing legal access, not just for people with diagnoses, but for people looking again for personal or spiritual growth or couples therapies things like that. But it's only been a few years since we really had strong data about psilocybin and MDMA and their effectiveness. And so it's a very recent phenomena that that a lot of political activists working against the drug war have moved from medical marijuana to guided sort of either decriminalizing psychedelics. You know the reason I talked about Denver and our work with the police is Denver was the first city to make mushrooms the lowest enforcement priority. And we will see a lot more activity in that regard but when you do this stuff on the state level. There's one fundamental two fundamental things that are missing. First off is that the body of evidence that we're going to get from clinical trials, but then second is insurance coverage. So, our focus is really drug development through the FDA on the federal level and we will support drug policy reform efforts on the state and local left state and local levels but I don't think that that kind of drug policy reform is a substitute or even anywhere near the value that you get from going through the process. We have a great question from an anonymous attendee asking if you could talk a little bit about the process for getting approval for these studies what's involved there. Yeah, well, you know I think the way that chairman talked about, again, albinovic was that there was a period of time there was a subjective element to risk benefit calculations. And those kind of risk benefit calculations were entirely skewed for several decades towards risk and no benefit and therefore no research took place. It was blocked and the US was particularly powerful at that point of time and we exported our drug policy all over the world and we were able to succeed in blocking psychedelic research for decades all over the world. And for reasons other than supporting psychedelics people at the FDA changed. So, their fundamental decision that the FDA made at this 1992 advisory committee meeting was that the psychedelics should be evaluated the way any other drug is evaluating that they didn't need special procedures that they were already FDA was already used to regulating against regulating stimulants right regulating drugs that have significant abuse liability and significant risk profiles and that they had started to have their realms. These opportunities for risk evaluation mitigation, customizing these policies for the particular risks of the specific drug. What we're doing now is basically the same thing as any other big pharma company would do is you do the pre clinical work you do the phase one the phase to the phase three then there may be these, if you get approval and these phase four commitments like our work with the I think we've now reached the point where decisions are based on the basis of science, rather than a lot of public fears. And so it's very rigorous scientific review process by FDA note but it's no different than any other drug. And that's a major accomplishment that we finally got to that point. So that said it is much harder to do a trial of this stuff. You know because of the fact that a schedule one license is necessary. And you have to prove, you know that you can secure the substance. In our particular instance we had to figure out in conversations with the DA how to allow transport of even a single pill from our clinical research pharmacy to the neuroimaging facility in order to be able to scan subjects because we didn't want to transport the subjects after administration so I think it does present additional challenges it does increase the timeline to getting research done. But, you know, the concern that I have is that you know people are going to have access before we know enough. But, you know, it, you know, I think things the tide is changing, you know, and Rick would know that more than anybody else, but it's still very challenging compared to any other drug. Yeah, that's very right. We do have the benefit of senior retired DA official who is now acting as a consultant for us. Chairman I'd be glad to introduce you to him if you haven't worked with him yet but the reason is his son went into the military and got PTSD in Iraq and uses cannabis to help him with his PTSD. He changed the father's mind and so now he's consulting with us with senior DA leadership and it does take more time, but it can be done. And I think we also have the first police officer who's also a psychotherapist who's gone through training in order to give MD may therapy to other police officers with PTSD, they have a high degree of substance abuse I degree of suicide and police force they take in the veterans have preferential high hiring at the police so you get people who are traumatized in their military service and then they get into a highly traumatizing job. I think that it's very early but but what we're trying to say basically is that this therapy is good for the police as well, and that it's in everybody's advantage that the research move forward as quickly as possible. We are approaching the end of our time, but I want to try and ask at least one more question. Nice, and I really liked what you said about training first responders how to how to handle situations involving psychedelics. How might we train them more broadly but also train healthcare providers I could imagine that as these therapy therapies become more common. There's a need for for healthcare providers to really understand them and how to talk about them. In the early days of the LSD research in the state 60s at Johns Hopkins at the Maryland Psychiatric Research Center. They had a policy that everybody that got in touch with the patient even the nurses were offered the opportunity to try LSD. It wasn't just the therapists, it was everybody in that whole milieu that was working with these people. So I think we need to really have a similar kind of an approach to healthcare workers. In general is to offer them their own experiences, so they understand what patients they may be caring for are going through. So, you know, when I talked about what we want to do is train 25,000 therapists. That's not nearly enough to meet the need of all the people that have PTSD and we have roughly 1.3 million more PTSD patients every year. We're going to have to really explore new models I think for both group therapy but also psychiatric nurses or psychiatric social workers or there's a whole lot of training that's going to go on and I think that we can eventually get to this point where healthcare workers if they want to work in this area that they would have this option to have their own personal experiences. Another aspect of this is that, you know, especially with all of the news coverage about psychedelics for mental health and so on, you know, is the fact that people are going out and, you know, gaining access to some of these substances on their own, and not necessarily with a guide on the underground or anything. And so we also have to prepare clinicians to have something of a harm reduction model because if people are going to go use it anyway and show up, how do we, you know, how do we guide them about what the risks are for their particular diagnostic category, what to watch out for because, you know, one of the things you want is a psychiatrist and people have autonomy and if they're going to go out and do things, you know, how to decrease the risk and harm that might that has the potential of coming about and it's going to be important for, you know, psychiatrists and other mental health clinicians to understand more about this and to speak to that need, that use and the possible like, you know, processing that people need to do afterwards. Yeah, I think that over a time, we have a massive public education campaign but we should look at what kids are learning in schools my kids went through the dare program. And it was kind of laughable to read the materials that they weren't supposed to take home and show your parents, you know, and they talked about a lot of things that were not actually the case. So, we have a lot of people that have gotten drug education but they don't know what to believe they know not to believe what they were taught in schools but they don't know what to believe so we really need to get to honest drug education all the way through the school system and also get this training into curriculums for healthcare workers as well so that people can get academic credit while they're getting educated. I think that education is so important and I think that due to the work you're both doing and others in the community there. You're destigmatizing these topics so that people can feel more comfortable discussing them openly which is in everyone's benefit. But thank you so much. I think I'll turn it over to Leah for some concluding remarks. Again, I want to reiterate the thanks and thank you doctors goblin gas Navi marks for this wonderful conversation today. I've certainly learned a lot and the discussion and Q amp a boxes have been busy the whole time so I'm glad that all of you were able to join us. And I hope you will join us next month when we discuss health misinformation so following up on that edge need for education. So thank you all and have a good afternoon.