Making Sense with Sam Harris - #377 — The Future of Psychedelic Medicine 2

Episode Date: July 26, 2024

Sam Harris speaks with Dr. Jennifer Mitchell and Dr. Sarah Abedi about recent developments in research on psychedelics. They discuss the history of this research and the war on drugs, recent setbacks in the FDA approval process, MDMA as a treatment for post-traumatic stress disorder (PTSD), the challenges of conducting this research, allegations of therapist misconduct, new therapeutic models for mental health treatment, psychoneuroimmunology, "non-psychedelic" psychedelics, good and bad trips, the FDA's coming decision on MDMA-assisted therapy, "right-to-try" policies for pharmaceuticals, the role of psychedelic therapists, the problem of having all this therapeutic work being done underground, and other topics. Petition to approve MDMA-assisted therapy for PTSD: https://www.approvemdmatherapy.com/ If the Making Sense podcast logo in your player is BLACK, you can SUBSCRIBE to gain access to all full-length episodes at samharris.org/subscribe.   Learning how to train your mind is the single greatest investment you can make in life. That’s why Sam Harris created the Waking Up app. From rational mindfulness practice to lessons on some of life’s most important topics, join Sam as he demystifies the practice of meditation and explores the theory behind it.  

Welcome to the Making Sense Podcast. This is Sam Harris. Today I'm speaking with Drs. Jennifer Mitchell and Sarah Betty. Jennifer Mitchell is a professor in the UCSF Department of Neurology and Associate Chief of Staff for Research and Development at the San Francisco VA. Her research is focused on identifying and developing novel therapeutics for drug and alcohol abuse, PTSD, stress, anxiety, and depression, and on understanding the neural mechanisms responsible for these disorders. Dr. Mitchell has extensive and diverse experience with human and animal pharmacology, hypothesis-driven neuroscience, human proof-of-concept studies, and clinical trials. neuroscience, human proof-of-concept studies, and clinical trials. For the past few years,

her work has centered around the development of psychedelic medicines for a broad range of mental health conditions, including PTSD, which we will discuss. Dr. Sarah Abedi is a board-certified emergency medicine physician and psychedelic facilitator for clinical trials. She has worked as a psychedelic facilitator at Pacific Neuroscience Institute and is set to join the Psilocybin and Mindfulness Study at the USC Center for Mindfulness Science, which I think my friend Jonas Kaplan is also associated with. She works on policy change to expand funding for mental health research. She has served as chief medical officer and deputy campaign manager for the Treat California initiative, which I discussed on a previous podcast. This was a citizen-driven initiative aimed at establishing a $5 billion funding agency to explore novel therapeutics, including psychedelics, and that will be coming back around, I trust. Currently, Sarah is the Chief Medical Officer

at Treat Humanity, an organization dedicated to advancing the research of medical health therapeutics, including psychedelics. And we've posted the relevant links for Jenny and Sarah in the show notes, as well as one that gives more information about the upcoming decision that the FDA is making with respect to MDMA-assisted psychotherapy for PTSD, which is pretty much the focus of today's discussion. We talk about recent developments in research on psychedelics and related compounds, MDMA especially. We discuss the history of this research and the war on drugs, a recent setback in the FDA approval process, MDMA as a promising treatment for PTSD, the challenges of conducting this research, allegations of therapist misconduct, new therapeutic models for mental health treatment, psychoneuroimmunology, the so-called non-psychedelic psychedelics, good and bad trips, the FDA's coming decision

on MDMA-assisted therapy, right-to-try policies for pharmaceuticals, the role of psychedelic therapists, the problem of having this work being done underground, and other topics. And now I bring you Dr. Jennifer Mitchell and Dr. Sarah Betty. I am here with Dr. Jennifer Mitchell and Dr. Sarah Betty. Jenny, Sarah, thanks for joining me. Thank you. Absolutely. Thanks for having us. So we're going to talk about the state of research into psychedelics. This is a topic I've covered a few times on the podcast. I have an interest in this that I have not made a secret, but we seem to be approaching a kind of critical moment here

in the progress in this research, so I want to cover that. And perhaps we can just start with each of you briefly describing your backgrounds in science and medicine and how you came to take an interest in this topic. Jenny, let's start with you. Sure. So I am a neuroscientist by training. I'm a professor at UCSF in the Departments of Neurology and Psychiatry and Behavioral Science at UCSF, and I'm also the Associate Chief of Staff for Research at the San Francisco VA Medical Center. And I've been studying psychedelics in clinical populations for the past approximately seven years now, primarily work with psilocybin and MDMA for PTSD. And in terms of how I came about it, I'm a native San Franciscan. I got to see a thing or two as a kid. that was very proactive when it came to psychedelic use and got to see a thing or two there as well and thought that these could potentially be intriguing compounds to study and develop as

therapeutics. And so that's me. Nice. Yes. So I'm an emergency medicine doctor. And what actually really led me down this path was probably what I saw in more in the emergency room. And so before I actually started, even in the field of ER, I really thought most of what I would be seeing would be acute emergencies. And that was actually could not be farther from reality. And so a lot of what I would actually see were chronic medical problems with really

an emphasis, I would say, on untreated mental health issues. And it felt like this revolving door in my ER. And I can't tell you how much as a clinician, it was difficult day in, day out to see patients coming in, asking for treatment and help. And there was really nothing I could offer them. And so that's when I really got curious, you know, is there something else that we're missing? And so that's what really began my exploration. And I actually started doing research in the field. So I've worked as a facilitator, a psychedelic facilitator at Pacific Neuroscience Institute, studying various effects of psilocybin and LSD on mental health issues, as well as I will be joining the team at USC Center of Mindfulness Science, looking at psilocybin's effects on mindfulness.

And separate, even anecdotally, as I was understanding more about these compounds, I found countless people whose lives, in their words, were saved by psychedelics. And they ranged from everyone, moms, first responders, students, Navy SEALs. ranged from everyone, moms, first responders, students, Navy SEALs. And they would report that they had tried every conventional medical treatment available and it didn't work. And so usually they saw psychedelics as this last ditch effort, this Hail Mary. And so many would report having been on countless pharmaceuticals and they felt like it would numb or blunt their symptoms. And then they emphasized how important it was to do blunt their symptoms. And then they emphasized how important it was to do it therapeutically. And so what I was curious about is what is the

hurdle? What's that roadblock that is not allowing us to explore this as a treatment or understand it further? And so what it always came down to me was funding. There's an issue with funding here. And so for many reasons, including the war on drugs, the stigmatization of these medicines, it's been really hard to get government funding to fund this work. And so for the past few decades, philanthropists have really had to foot that bill. And so that's actually where I got involved more in the policy space with psychedelics. And so I was involved with the Treat California Ballot Initiative. And I'm not sure if your listeners remember the prior podcast, you had interviewed Jeannie Fontana, where she was

Dr. Jeannie Fontana, where she was discussing this project. And so just as a reminder, it was a citizen-driven ballot initiative in California that would have created a $5 billion funding agency to research and support this field of psychedelic medicine. As many, I think, who understand the complexity of this field recognize that this is a completely new paradigm and it doesn't really fit in the structures and frameworks that we currently have. And so that initiative would have allowed us to do research and to understand the risks. It would have helped us provide education and access. And so, you know, maybe a little bit of an explanation of what happened. We had built a

very powerful coalition and there was this incredible movement. And when we pulled on the language that we actually had received from the attorney general, this would be actually the language you'd see on the ballot. We found that while Californians really believed in psychedelic medicine and researching it and understanding it, they actually did not have confidence that a government agency could uphold its promise. And there's this growing distrust in the government to get anything done. And so educating the public on why the TREAT initiative stands apart, it was difficult. So we didn't, yeah, we had to unfortunately stop and we've shifted now

to treat humanity. So that's what I'm doing now is I'm the chief medical officer at Treat Humanity, where we're looking at the same issue, how to unlock the necessary capital to fund this research and build the infrastructure, which I actually would argue would help address a lot of the issues that we're seeing come up with the FDA committee and MDMA. And so some of the things we're looking at is possibly a campaign in 26 in California, federal options, global options, and it's a joint effort. So we need the best and brightest on this. So that's a little bit of what I'm doing right now. Nice. Yeah, maybe I should just take a moment to review some of the history here because it will remind people of why the involvement of government and the attitude of government is

so complicating and why we're at some risk of losing the hard-won progress that many people had begun to take for granted in recent years. So just to quickly run through this, many of the compounds we would talk about, I think we're going to focus on MDMA because of the recent study and FDA advisory ruling. And MDMA is not technically a psychedelic. We might add a footnote there later. But most of these drugs, MDMA, LSD, psilocybin, have been around for quite some time. You discovered in the 20s, 30s, 40s, I mean, psilocybin goes obviously way back in native medicine in the form of mushrooms. But the interest of Western science is, for the most part,

an early and mid-20th century project. And much of this was bearing fruit in scientific research and seeming to hold great promise. And then the 60s came around, and Timothy Leary, who was one of the PhDs at Harvard who was doing this research, also became a great proselytizer of the countercultural potential of these drugs, LSD in particular. And in, I think it was about 1966 or thereabouts, he told a generation to turn on, tune in, and drop out.

And we had a great counterreaction to this-cultural moment, which culminated in the war on drugs in 1971, when more or less all of the most promising compounds were officially ruled Schedule 1 and therefore declared dangerous and worthless. And so a full generation of research on psychedelics and other therapeutics just went into eclipse. Actually, MDMA is a bit of a, once again, an outlier here in that people really didn't rediscover it and begin taking it until the 80s. And so it wasn't covered by that initial schedule in 1971, but then it was quickly ruled to be, you know, at the moment it became popular, it was ruled to be Schedule 1 and therefore forbidden and illegal. And then, if memory serves, I think in more or less in response

to that, I mean, many people in the therapeutic community recognized at the time that MDMA held immense promise for healing of various kinds. And when it was ruled illegal, Rick Doblin formed MAPS, the Multidisciplinary Association for Psychedelic Studies, and began working to change our drug laws and to restart research. And he was working, you know, by definition on the fringes of society for quite some time. And then there was this quiet resurgence in research. I think Roland Griffiths started at Johns Hopkins in 1999, and he published a paper on psilocybin that got a lot of attention in 2006. And then the floodgates really opened when Michael Pollan, the journalist, published his New Yorker piece in 2015 and his

book, How to Change Your Mind, in 2018. And this is, you know, it's in these last six to ten years that we have been talking more or less as though it were a fait accompli that the psychedelics were coming back and that we were simply going to not make the mistakes that had been made in the 60s, you know, so floridly by Timothy Leary in particular, so as to create a counter-reaction from the government and some understandable paranoia that, you know, handing these powerful compounds to everyone in sight could create a lot of unintended harm, which I think we would agree is quite possible. So here we are, more or less in the present. MAPS and the spinoff pharmaceutical company Lycos has brought research through, now I'm coming to you, Jenny,

through stage three clinical trials. And this is where, Jenny, you, to my understanding, join the story explicitly. Tell me about your involvement with MAPS and Lycos and the study you have done and where we are, because there was recently a fair amount of press attention about the FDA's advisory panel reaction to the study that you ran for Lycos. And so talk us through that and complete my sentence for me. Sure. I think my original interaction with what was then MAPS-PBC was accidental. I was accidentally invited to their phase three planning meeting. I didn't know it was a phase three planning meeting. I myself had never done what we call phase three. So phase three is like

the last step in the FDA clinical development pipeline. It's a multi-site study. Typically, it involves a high number of subjects. You're sort of already past your dose finding stage and your safety stage. And so I went to this phase three meeting and I met some of the people that were MAPS PBC at the time and accidentally participated in this day with them. And then by the end of the day, it was very clear that there was great opportunity to work together. And so at that point, I agreed to join their phase three program and investigate the efficacy and safety of MDMA for PTSD. And so we started with a study that involved participants that had severe PTSD, and then the replication phase involved a slightly

broader study population that had either moderate or severe PTSD. But remarkably, the outcomes of both studies were very similar. And I didn't know this at the time myself, having been sort of new to phase three studies, but that's, I guess, kind of unheard of for the results to be so similar, especially as you brought in your study population a bit. But in short, approximately, what, 70% of the participants over the course of the two studies lost their diagnosis of PTSD. And that is a remarkable outcome when compared to our current gold standard treatments for PTSD. And I think that's why it raised so much interest and garnered so much hope for those. Jenny, I assume everyone believes they understand what PTSD is, but you might take a moment to just talk about how we think about it and why it has been so difficult to find therapy for and just how much suffering is under that acronym. Right.

Okay. So that's a very good point. I think that post-traumatic stress disorder is PTSD. And we have a book called The DSM that tells us sort of how to define PTSD. And that book says that PTSD has to occur in response to experiencing or witnessing a traumatic event. And that traumatic event must often involve death or serious injury. So you can imagine, first of all, that there are a lot of people that say, I have PTSD. We throw the term around kind of colloquially at this point, but

a lot of the time we don't have people that meet that diagnostic criteria. When they do, unfortunately, PTSD is particularly hard to treat. It also often occurs, it's not like a standalone diagnosis, which would be really convenient. It often occurs with other comorbid diagnoses, such as depression, anxiety, TBIs, drug and alcohol use disorder. And unfortunately, those comorbidities make it much more treatment intractable, much more difficult to treat PTSD. And so one of the issues that we've had, of course, then, is that we don't have any great pharmacological therapeutics for PTSD. We have two FDA-approved SSRIs, so the selective serotonin reuptake inhibitors that were developed for depression, sertraline and paroxetine.

Those two SSRIs are often prescribed for people that are suffering from PTSD. They don't work for a majority of the subjects that have PTSD, but I think that the hope has always long been that because depression and PTSD are so often comorbid that perhaps you're tamping down the depression and that helps the PTSD more generally in a subset of subjects. I don't know. So that's one problem is that we don't have good pharmacological agents for it. We have these two talk therapies, right? Cognitive behavior therapy, prolonged exposure therapy. And the problem with those, and those are typically considered gold standard therapies for treatment

of PTSD, especially in veterans. But the problem there is that you're asked to live and relive and re-relive your trauma until you sort of, it doesn't have the same impact that it had originally is the idea. But you can imagine that that process is extremely painful. Most people don't complete a full course of treatment because it actually sort of stirs the pot and generates even more symptoms as you're reliving that trauma.

So that's why we really needed a new therapeutic for PTSD. There's a huge unmet need. PTSD often, especially in our veteran population, triggers suicidality. And so we lose almost a veteran an hour to suicide. And my personal belief is that better therapeutics could improve those numbers. Yeah. Yeah. So in that context, hearing rumors of a 70% response rate, that's fairly thrilling data, right? People seemed thrilled. I mean, I was, I myself was genuinely surprised at the remarkable efficacy that the compound demonstrated. I mean, I did think that there'd be a signal there. I didn't think it would be that robust. I didn't think it would be that durable,

but it has shown to be. So I think that that's all great news. And I think that it originally generated a lot of enthusiasm. And then more recently, there's been this pushback, right? The pendulum's been swinging. Can you say something about the pushback? Sure. I mean, I think as many people know, there was an advisory committee meeting that was held by the FDA recently, and that advisory committee believes that there isn't enough evidence of efficacy and safety to move forward on approval of MDMA for PTSD. And this advisory committee is not the FDA itself, right? So I think it's important to remember it's not that the FDA ruled that MDMA was not approvable as a therapy for, in conjunction with therapy for PTSD,

it was the advisory committee. But still, that seemed like a setback and suggested that there's some confusion in the field exactly about how MDMA-assisted therapy works and about how safe and efficacious it actually is. Well, what were the actual, and Sarah, feel free to chime in here at any point, but just sticking with you, Jenny, what were the actual criticisms? I mean, there were criticisms about unblinding with respect to, you know, what was the active agent and what was the control. I mean, this is kind of a comical problem that one runs into, and this goes all the way back to the original

research in the 50s and 60s. And the problem is these, in most medical research, when you want to do a double-blind control study, you can effectively do that because it remains a mystery to the participants who's taken the active compound and who hasn't. But when you're giving people drugs like MDMA or psilocybin or LSD, the effects of these drugs are so powerful and so unignorable that in its most comical variant, there was the study, I think it was run by Leary and Albert back in the early 60s, usually described as the Good Friday experiments, where they gave a bunch of seminarians, you know, they gave half placebos and half, I think it was synthetic psilocybin, might have been LSD. And, you know, half of the room within the hour was having the beatific vision, and the other half was, you know, looking over their shoulders, wondering why they weren't seeing God. And it was just absolutely clear to everyone, although I think one of the controls also had a mystical experience, if I'm not mistaken.

But in any case, it's very hard to keep these blind experiments blind. Was that the problem that you had with the study? I myself didn't think it was a problem with the study. It was definitely something that the adcom brought up as a problem for them. So I think you've raised a couple of interesting points. I mean, the first one is that it's very hard to blind psychedelics trials. Most people know that they've taken the active drug. Some people don't. So we had people in phase three that guessed wrong in both directions, which I still find

kind of fascinating. There were people that received MDMA and they were like, nope, I got the placebo. And there were people, but still got better, mind you. And then there were people that received the placebo and thought that they'd received MDMA. it's an eight-hour talk therapy session, and you're typically wrapped in a nice warm blanket, and you're reclined, and you've got headphones on, and you've got eye shades on, and you've got two therapists at your elbow. And so, you know, not so surprising that some people felt that they still had a remarkable therapeutic and transcendental experience. So there's that, yes, it's hard to blind these trials. But also, it's hard to blind mental health treatment trials in general because what you

want is for your drug to work. And if your drug does, people typically know it, right? In other words, if you're giving a drug for depression and people come in and say, my depression's gone, typically they also know that they're on the active drug because their depression's gone. So in general, when you're asking, if you're looking at like what, rheumatoid arthritis and you're looking at inflammatory markers

or swelling or whatever, you're not asking someone how they feel as much. In a mental health trial, you're typically asking them if they feel better. And if that's the end point, then it's often going to be tainted by the efficacy of the drug. So this wasn't a surprise, I think, to anyone

as the FDA and at that time MAPS-PBC sat down and discussed the study design. And what they decided was that this would be, you know, relatively impossible to blind completely. And it took them many years of, as I understand it, this was before I was involved, but as I understand it, it took like 13 years to decide on the study design and the study design ultimately involved telemedicine. And so I guess, you know, it was sort of fortuitous that it happened when it did 13 years prior, we didn't have the telemedicine platforms that we have today. So we have Zoom now. And that means that instead of determining at the study site, if someone looks like they're doing better, you instead have them call in to a completely anonymous person that they haven't ever

interacted with before far away via telemedicine, and that person assesses these outcome measures with them. And that way, this assessor doesn't know where this person's calling from, if they thought they received placebo or active drug, if, you know, they're at the beginning of the trial or the middle or the end or in follow-up. And that was the study design that the FDA and the sponsor agreed on together to ensure that this lack of blinding was minimized as much as possible when it came to assessing and evaluating the drug efficacy. So there's that. And I think that was oddly lost in the ad comp. And I didn't hear the FDA say very much about it at the time, even though, again, they had agreed to this study methodology years before with what is now Lycos Therapeutics. So that was a surprise, that was a surprise to me. Yeah, that people had so much issue with the blinding. I also thought it was kind of a surprise because, I mean, if we were talking about a cancer drug, those studies don't typically have a comparator arm anymore.

And so you don't need the comparator arm to receive FDA approval for a novel therapeutic. And what about allegations of therapist misconduct? And what about allegations of therapist misconduct? Yeah, right. So I think that's one of the things that most plagues, MAPS, PBC, and Lycos Therapeutics are these claims, this one in particular from a phase two study that happened many years ago in which a therapist inappropriately began a relationship with somebody that had been involved in one of the trials. And obviously, that's

horrific. It's inappropriate. It's malpractice. That was not somebody that was involved with phase three. That was not a therapist that was allowed to continue after these allegations came to light. And also, perhaps most importantly, the therapy component of the treatment is not under the purview of the FDA. Like the FDA doesn't talk about the therapy in general because they have no control, no say over therapy, right? We have state boards and licensing boards and accredition boards that keep track of therapists and their practices. And that's what would happen if MDMA-assisted therapy were to be FDA approved. So it was odd to hear the ADCOM sort of go down that rabbit hole and talk so much about therapy and previous behavior of therapists and how the therapy

would be monitored when none of that really was supposed to, as I understand it, be part of the ADCOM meeting. It's definitely not part of what the FDA will evaluate during the approval process. Sarah, do you want to jump in here on any side of this? Sure. Yeah, yeah, yeah. I actually think there are a few things that are important to touch on. One being that psychedelics really offer a completely new therapeutic model. And I think it's important to talk about how different that is from our current existing model. And I think it's important to talk about how different that is from our current existing model. And I really do think it's important that we talk about what can go wrong so that we

can create structures to prevent it from happening as best as we can. And lastly, I think it's important to look at how we may need to evolve our current institutions to meet the demands of the people. And so what I mean by that is, you know, we would not be here having this conversation if our current medicines worked for everyone. There's, I believe, nearly a billion, according to World Health Organization, of people suffering from some sort of mental health condition, one billion. And if we look at Americans in particular, one in five, right, are living with some sort of mental health illness. So that's about 50 million people in the United States. So if we hone in on PTSD in particular, I believe

it's somewhere around 13 million. And MDMA would be one of the first to offer a new treatment, I think in around 25 years. And so I think it's just important to note that there is this desire to find something else because the current conventional medicines work well for some, really well, and for others, they're failing them. And so I think there's a lot to touch on here. You know, some of the critics of the vote for the committee actually had mentioned that there was just one member of the FDA advisory committee that had had expertise in psychedelics, saying that the committee may not, as Jenny was talking about, have a full understanding of all aspects of the treatment. And he actually did vote in favor of the treatment's efficacy. And as Jenny was touching on this, the FDA does, you know, regulates medications, but they never regulate psychotherapy

or a medication whose effects are really closely tied to therapy. And so this really raises the question about, you know, is there a belief that they need to standardize and create protocols for some sort of therapeutic aspect of psychedelic treatment? And I think that really gives us an opportunity to see where there's room for growing in our current medical model. And so a lot of researchers, I think, believe that because of, as you were mentioning, Sam, the really complex history of these classes of medicines, we're seeing the data face significant scrutiny, probably more so, I would say actually definitely more so than any other drug class, any new drug discovery. And so I think it's important to note that some people see these

medicines as a movement, right? And not a scientific endeavor. And so scientists want to be careful to say, you know, if there's a preconceived notion within an organization that these medicines are effective, and all we need to do is substantiate that belief, then where is the confirmation bias here? And how is it going to have us maybe overlook some blind spots? And, you know, as? And as Jenny was saying, researchers in the field might actually see this as some sort of period of recalibration. So maybe we're moving initially past that hype and really thoughtfully considering any potential risk.

And I think they're emphasizing that we want to know when they can go wrong before we bring them to the market. And so I feel as we embrace all the aspects of this field, it really shows the maturity of it. And I think it's really important to discuss that, as we're talking about this challenge of double-blinding, right? So in evidence-based medicine, you have these placebo-controlled double-blind clinical trials. They're gold standard. Patient doesn't know, experimenter doesn't know. We were talking about how that's really difficult. When someone is taken as psychedelic, they usually know.

So I think for me, what has been really helpful to break this down is to really reflect on the type of research model we're using and understanding how this new paradigm, maybe it does not fit really well with this research model and what are the limitations of our current method so that we can develop and evolve to other methods that would actually capture this work? And so I may actually touch a little bit, if it's okay, Sam, about what I feel like is the groundwork for modern biomedical science. And I really feel like it's actually predicated on mechanistic reductionism. So this concept was born in the scientific revolution around the 17th century. Thinkers like Newton and Descartes would apply really mechanistic and reductionistic approaches to understand the natural world. So I think Descartes

especially really saw the body as a machine. He thought that all physiological processes could be really explained in terms of a mechanical principle. And they wanted to try to explain really complex biological systems in terms of their simplest components. So in this model, you're looking at linear cause and effect relationship. You're going to simplify the system to isolate the variable. And that approach helps us understand specific mechanisms of action

of a drug at a molecular level, which I think is really important. And it's been highly successful in treating a lot of things in human biology with targeted interventions, pathogen recognition, genetic mutations. But on the other hand, I think what we are feeling right now with psychedelics is that it takes a bit more of a systems thinking approach. So it's actually viewing the entire system. It's emphasizing the interactions and interconnectedness of its parts. So this model actually really operates on the premise that the human ecosystem is more dynamic.

It's more nonlinear. It embraces that there's a lot of complexity here. And I think a lot of people will argue that this approach is actually much better suited for chronic diseases and mental health issues. And just to point out that that's actually what we're seeing an exponential rise of in this country and around the world is chronic diseases and mental health issues. So when we're taking that reductionistic approach, it's targeting specific components or drugs that target a molecular pathway, whereas complex systems thinking is looking at multifaceted strategies, right? We're looking at the social implications, environmental, behavioral.

And so while I think that mechanistic reductionism can really provide powerful tools to understand these systems, and I think we can absolutely use them to understand the pathways in psychedelics, there's something about complex systems thinking that offers more comprehensive framework to understand the interconnectedness of human health and ecosystem. And, you know, as I'm speaking, I want to share an example because this can sometimes be a little bit elusive. So an example of systems thinking in my eyes is this field, and it's fairly new, of psychoneuroimmunology. So this is a prime example of systems thinking in medicine as it's looking at the effects

of psychology on the nervous system and the immune system. And so if we're using this field to understand, for example, trauma's effects on the body, we actually see that trauma can lead to a dysregulation of the hypothalamic pituitary adrenal axis that will spike up your cortisol, your stress hormones. It will increase inflammation in the body. That chronic inflammation we're actually seeing is linked to a lot of different diseases. And so we see this actually with people with PTSD, they have higher rates of cardiovascular disease, diabetes, we're actually seeing is linked to a lot of different diseases. And so we see this actually with people with PTSD, they have higher rates of cardiovascular disease, diabetes, autoimmune conditions. And we actually think that's probably from a dysregulation of their immune system.

And to tie this in further, there's another study in this field and it's around the childhood, adverse childhood experiences. So this study actually looked at individuals with a really high number of adverse childhood experiences, and they actually found that numerous health problems were associated in adulthood. So children that had higher numbers of trauma linked to physical disease as an adult, so heart disease, diabetes, really illustrating this long-term impact of trauma on health. You can find this questionnaire on the CDC website. So why I bring this up is that this is where I feel that the FDA can continue to evolve, right? I believe, think we need to take a little bit more of a systems-based approach. And so when I think

about that therapy component of psychedelic medicine, which is really tied in right now to the medicine. So, you know, the medicine and the therapy that is, it's almost really, you know, we don't think we can do one without the other in this trial, right? So it's really emphasizing this, this integrative approach that I don't know aligns really well with traditional rigid protocols of clinical trials, right? That are designed for conventional pharmaceuticals. And anyone that's been to therapy can really attest to that nonlinear framework. Yeah. And I think another thing I actually want to touch on that I always think is so fascinating is this exploration of when we see this complexity here and we want to move to maybe

finding something that fits better in our model. And that actually, I think, is the exploration of quote-unquote these non-psychedelic psychedelic compounds. You know, the term is psychoplastogen, right? So, you know, many participants feel that that non-ordinary state is at the cornerstone of this healing. But scientists want to see, is that true? And so they want to understand, is that psychedelic experience itself essential, or is there some sort of underlying neuromodulation that's responsible for this shift? And there's a lot of contention in the field about this. And I think proponents of the psychedelic experience report that they feel some of the most meaningful experiences of their life, right?

So they've gained this insight that they felt would be otherwise inaccessible, shifts their perspective on how they see the world. And it actually reminds me of what an astronaut would feel, right? When they go to Earth, they call this the overview effect, this state of incredible awe and overwhelming emotion and this connectedness to other people. And so when people have these experiences, they feel that this hasn't just helped them with their objective depression, PTSD. They feel that another layer has been added on. So they're now learning, reported by them, that they are living with purpose, a more

meaningful life. They feel like they're part of something, part of a community, really part of earth, which I actually think some would argue is a central tenant to being a human being that need to belong. And so again, this is where I think we can evolve our research methods, right? To encapsulate the entirety of this and not just an objective decrease on a measurement scale. So for some people, it might not be enough to live PTSD free or depression free. That's great. But surviving, you know, maybe the goal should be more a deep sense of thriving and optimal success. So that makes me have to reflect on what are the scales that we use to capture success,

you know, in our current model? Do these assessment scales fail to address some of the more complex whole person dynamics? And does this suggest that we may need more validated scales to capture this? And the last thing I'll touch on is, I think this is why it's so complicated, is that we also need to talk about the cost-benefit analysis that insurance companies will complete. So an insurance company will probably prioritize a treatment, actually definitely will, that addresses medically recognized conditions, right? With a measurable outcome that are clear, quantifiable, and that align with most importantly, traditional medical criteria.

So an insurance company, when they assess whether the benefits of a treatment justify its cost, if a treatment significantly improves overall well-being, but it's expensive or lacks robust evidence of cost-effectiveness, insurers actually may be hesitant to cover it. So that's why I think it's important to really look at our current model and see what parts are begging for some evolution. Yeah, all of that's very interesting. I think it's, I mean, to, I guess, make contact with a few of the points you made there. One reason why the therapy seems like it needs to be an integral part of this and why it's unsurprising that it would be, is that here, when you're talking about a few treatments with MDMA or psilocybin being efficacious, you're not talking about

taking a drug for the rest of your life. And therefore, you're not talking about the ongoing pharmacological consequences of being on this drug, and that's simply having some neurophysiological effect that improves your condition. Just of necessity, you're talking about a very punctate experience in your life. And from the first-person side of this, or for one who has had these experiences, it seems quite obvious that it's a matter of, in the end, it seems quite obvious that it's a matter of, in the end, thinking and feeling differently about yourself and your place in the world and your past experiences. I mean, this is why I would be willing to bet that the phenomenological component of the psychedelic experience rather than merely the pharmacological one is going to prove necessary. Right? So I'll be fascinated to see where that research goes with the so-called non-psychedelic psychedelics. But the idea that you could

unconsciously have all of the benefits, that will be surprising because from the first person side, it really does seem to be that it's a matter of using these compounds to get tremendous leverage over one's mind based on the power of ideas and insights and changes in perception and feeling that if they're not actually truly durable, I mean, every experience comes and eventually goes, but what you have at a minimum is the new reference point that such an experience is possible, right? You know what it was like to have felt that way yesterday, and so it's by definition opened a door in the architecture of your mind, which you, again, even as a mere memory, it

reframes your sense of what is possible for you as just as a person, you know, living a life of painful ups and downs, perhaps still. It potentially changes everything, even if the ongoing character of your experience hasn't changed all that much. And that's even, that's probably the least successful case we're talking about. So, you know, leaving aside the real downsides and dangers, which, you know, we should probably address because obviously there are some people who shouldn't take these compounds. And as there are, you know, for every great experience one can have on many of these drugs, there are equally awful and harrowing experiences one can have. I hesitate to say that in the context of talking about MDMA because I'm not aware of the liability for bad trips being quite as obvious as with LSD or psilocybin. But still, nonetheless, I'm sure there are people who take the drug and have a bad time. Jenny, would you like to jump in here? Sure. I think you're absolutely right. I think it's rare,

but that there are people that take MDMA and they feel that it opens a door to bad and dark things that they don't have an opportunity to address and that leaves them feeling worse instead of better. I think that in general, we probably all agree psychedelics don't work well for everyone, maybe shouldn't be given to everyone. There may be a number of comorbidities that should limit one's access to a psychedelic, at least at these early stages of development of some of the drugs. So I agree with all of that. Yeah. And I actually think that's probably why, you know, that's the argument of exploring these non-psychedelic psychedelics. So these psychoplastogens and Sam, as you were talking

about it, I felt like it's important to also note that let's say, you know, we are actually opening a window of neuroplasticity, we should probably also consider what new tools we'd want to add during that time. So not keeping it as the strict pharmacological intervention that it possibly could be, where it's similar to taking an antidepressant every day or for a period of time. And so, you know, without maybe integration, you know, this class of medicine might really miss a crucial opportunity for an added benefit. And as you were touching on, you know, how we can speak a little bit about, you know, some more of the controversy that is, has been coming up around this study, I think one important one to touch on is that, you know, this new paradigm, this framework is

using a system to understand the system of a more of an intrinsic healing capacity that I think is really important to touch on because I feel like that's the one of the cornerstones of this work. So if you're okay with that, I'd like to discuss that, that how this concept compares actually to our current conventional model of medicine, you know, where it can aid and actually where there could be harm in this model. And I think it's really interesting to note that there's this discussion that psychedelics can have this intrinsically regenerative action. And researchers want to explore that and they want to see that. We have seen a lot of people

report that and they have had a lot of success, but can it also elicit something false, like a false insight, a belief? And how do we support a participant through that process? So again, to me, when I see when something might be going wrong, I want to know so that we can start building those structures and frameworks to really understand it. And so similar to, you know, like thinking about how psychedelics could have this ability to have this intrinsically regenerative action on the mind and brain, you know, there's a similar thought of the intrinsic

healing mechanism of let's say the physical body. So after an injury or sickness. So I think it's important to, to break down this concept, you know, is it myth-making? Is it centered on this role of priming and expectation after being shaped in therapy? Or is there really some sort of legitimate mechanism that exists in a self-regulating living system? It's interesting that there are some scientists that are actually studying this. And there was something that was released a few months ago looking at this where patients had received a placebo versus psilocybin, and they both had psychological support, and they were both given a scale to assess this concept of this intrinsically regenerative action.

And they found that the scores on that assessment were actually significantly higher for those that received psilocybin than placebo. And I think to me, this really warrants, let's investigate this more. Let's understand this new paradigm that we're bringing forth. And so I think another part of it that feels really central and different than what our current conventional model offers is that it's somewhat more involving the individual to have agency in their own mental health. So I think this approach is enabling participants to examine those core beliefs themselves, to be able to go in, look at them,

see how it governs their lives, identify which ones could be maladaptive and no longer serves them. And so it's important to recognize, I think, these maladaptive mechanisms, they were once evolutionary responses. They helped us survive at a particular point in life. But now we have the ability, I think, with these medicines to become consciously aware of them, to become aware of maybe the long-term imprint that these survival mechanisms have had, and maybe see how we can transition from a state of mere survival to one that's more thriving.

And so I think this is about teaching people to have more adaptive coping skills and how they can actually be more aligned with who they are. And so when I look at this paradigm of psychedelics, we've actually seen, as you had mentioned in the beginning of this podcast, that this is a cornerstone of health for many cultures. We've seen it in a lot of indigenous communities around the world, and it really differs from our current pathology-based medical system. So, you know, this biomedical model. And I think it's important to touch on because, you know, when I think of the pathology-based system, it's really focused on diagnosing. It's focused on treating disease, isolating symptoms, and really treating specific conditions, as I was discussing before. But this model is different, right? So

it's really emphasizing that interconnectedness of it all, the physical, the emotional, the mental, and that it's really the whole person and not just the disease. And so, you know what I... Sorry, go ahead. No, I was going to say you're raising some really great points and implications, I think, for clinical use of these compounds, because let's say that they are neuroplastic, right? And let's say that they open up a window of opportunity that lasts longer than an eight-hour treatment session, right? Which is basically what you're suggesting here, I believe. And that you're sending a participant home at the end of that eight hours and you're hoping for the best. And perhaps that window is open for another

14 days. I think it raises a bunch of issues around clinical care and around disparities in access to drug treatment. Because if you've got somebody that has PTSD and they're from a marginalized place and they don't have a lot of money and they don't have a really healthy community to go back into and you've put them back in that community after that eight-hour treatment session, I wonder what happens over the next 13 and a half days and whether or not that negates some of the effects, the efficacy of the drug in treating whatever you were trying to treat, right? And so what you're talking about too is how we'd sort of bolster that with a lot of integration work and a lot of care and a lot of attention. And it's unfortunate, but as you've already said, our current manner of clinical practice doesn't typically allow for that or have ways to easily enable it. And so I think that's something that we also have to talk about as a group. And I think it's something that managed care and insurance providers and everybody else are particularly worried about is this is a potentially great therapeutic or series of therapeutics for

somebody that has means to engage in a lot of integration work, perhaps for days, months, you know, years into the future. But if somebody doesn't have access to those additional resources, are we potentially opening them up to fail or to get worse in some way? I think that's just something that we really have to address before these therapeutics move much farther forward.

You nailed it, Jenny. I think that's such an important part that we need to be able to hold it all. And that's why I think the systems thinking actually helps understand this more because it's not just a biological mechanism that's causing this PTSD. There's a lot of other interconnected issues at play. What is going on societally? What is going on in the family dynamics? What is going on, et cetera, et cetera. on societally, what is going on in the family dynamics, what is going on, et cetera, et cetera. So looking at that entire picture is crucial. And I think that's actually a big reason why I really was a proponent of the TREAT initiative is because we were looking at that, that you cannot

have someone take a psychedelic medicine and then put them back into what some might call a toxic environment after they've had these profound insights. People, they need childcare, they need time to actually process and integrate, they need time off of work, they need a very comprehensive space to be able to do this work upfront, to actually be able to see the benefits. I really appreciate that you touched on that. Yeah. these compounds tend to be so powerful and so reshaping of a person's sense of what life is good for in the end that it sounds like we could be in danger of deciding, well, it's just too potent, right? It's just you're pulling at the threads of a person's life, but here you've got

some kind of central thread that can unravel everything. You know, we've given someone an experience for five hours in the case of MDMA or 12 hours in the case of LSD, after which they may decide they're in the wrong job. They may decide they're married to the wrong person. They may decide that they really, that everything needs to change in their lives. And there's going to be a vast difference in people's ability to respond to that 20 megaton upheaval in their lives. And again, we're stipulating that in many cases, these upheavals are very, very good. But again, it can take the form of now all of a sudden they believe in God when they didn't, or they no longer believe in the religion of their parents. A sea change

in who they are and how they want to live is possible in a way that it's not when you're approving how to repair an ACL tear in a person's knee. But admitting all of that and admitting that there are very wide disparities in how lucky people are, right? So there are two people with PTSD coming in for the now approved MDMA treatment for it, but one will be returning to a life of affluence and a happy marriage and healthy kids, and one will be returning to a life of chaos, right? And we can't fix all those problems, but the question is, can we put enough in place so that it will be unambiguously good most of the time for the person to have had this intrusion into their lives for 12 hours or 24 hours or 36 hours or whatever the protocol is that has to at some point be bounded

by the sheer limitation of what any clinical practice can deliver to any person. Right. I really think we can. I think we just have to be particularly thoughtful about the guardrails that we put in place and how we do them. And I think sort of that's what came up during the ADCOM FDA meeting, but it's just not the purview of the FDA to come up with those, right? It's, you know, as Sarah probably would suggest, it may be the purview of the states that states need to come up with a system for psychedelic facilitation and oversight of the facilitators and sort of determine how much of that facilitation is a standard of care so that you don't sort of high-five somebody at the end of a six- or an eight-hour session and tuck them back in their car and wave goodbye,

but that you know that if they need that integration work and if they need a safe environment, that you've got one available for them so that they can make the most of their therapy. Yeah, and I think just to touch on what you were saying, Sam, you know, a big part of this, again, to me is just what a new paradigm this is, right? So, you know, as we were touching on looking at this pathology-based model that we are very familiar with, the FDA has been, it's a huge part of something that FDA is very comfortable with. But, you know, the participant is very passive, right? As they receive this care, there's that heavy reliance on pharmaceuticals, medical interventions when necessary, standardized protocols.

So one size fits all. And right now we are trying to move and evolve and offer this new paradigm that is completely different, right? So the patient is really active in that process. You know, there is a deep connection between the mind and body. We feel like the mental and emotional state can significantly impact physical health. And, you know, there's really personalized care for each person. So I think even one thing to touch on is, you know, one of the criticisms was that there was not adequate possible reporting

of some adverse events, including increased suicidality. So irrespective of it not being okay to have inadequately documented that, I think the more we explore what is that telling us, this is how we can learn, as you were saying, to create the frameworks and the safeguards. So if I hear that increased suicidality, kind of as Jenny was mentioning, what's going on? Is this a biological issue of MDMA? Is it the nonlinear nature of healing? You know, when some individuals will initially experience, you know, exacerbated symptoms before improvement, is this a very emotionally taxing process, you know, of any type of new therapy where you're recalling these distressing events?

And the last part is, do we need for some people, maybe a smaller portion, more comprehensive support? And what does that look like? Would that be something, as Jenny was saying, as the states or other places think about that therapy component, do some people just need more integration? And so I think the last thing I want to touch on in this part is, you know, some people would may have reported that, you know, they're feeling better, right? Or sorry, no, they're not feeling better, but the actual measurements that we're using show that they're getting better. And I think this is again, another moment to examine the current, you know, scales and methods that we're using to see

if quote unquote, someone is getting better and really noting that this is a completely nonlinear process. So for example, you know, one of the primary instruments that was used in this MAPS study, which is, you know, the gold standard is the CAHPS-5, right? So it's the clinician administered PTSD scale. It's given by a clinician and a patient is there to identify trauma or traumas that they feel like are the source of their symptoms. And so, you know, in psychedelic therapy, we often see that there can be previously unconscious memories that can arise. And that newfound awareness might have a patient initially seem to be approving on the CAP scale in relation

to that known trauma, but they're simultaneously experiencing new distress from this. So I think it's really important to look again at how nonlinear and dynamic this work is and create systems that actually really can understand that. Okay, so let's talk about the moment we're in with respect to the FDA's deliberations and what, if anything, is at stake here and what would be useful for anyone who's in a position to make policy on this topic to hear at this moment? I mean, if you could imagine that the people in charge were listening to this conversation or people poised to influence the people in charge were listening, what would be useful for them to hear and think about that we haven't touched on already? I mean, from my perspective, I think part of it is that there's this plan

called a risk evaluation and mitigation strategy that the FDA can ask Lycos, the sponsor, to provide to show that they've established these guardrails around some of the concerns that the ADCOM brought up. And that would be a way to enable regulatory approval of MDMA-assisted therapy and ensure that data were still being collected to look at adverse events, side effects, et cetera, in what we'd call phase four testing, so post-approval testing of the compound. And I think this would be particularly useful for MDMA-assisted therapy in part because once it's out of phase three testing, as Sarah sort of suggested, there is probably going to be a lot more, you know, variability in terms of how it's administered

and to who. And so we'd want to know if it really does need to follow this sort of strict methodology that's been enacted for phase three or whether it's actually much more effective in a different, under a different set of circumstances, different set of procedures. And I think that it would be useful for people to know what a REMS plan is and that it could be enacted here and it could allow for this therapeutic, but also psychedelics in general, to move forward with additional oversight post-approval. Yeah, I agree very much, Jenny. I feel like it's also important. We've spoken a lot about the details of this, and I think it's important to look at it from a patient perspective. And part of the committee, when there were actual just public criticism, there were a

lot of veterans that actually spoke about looking at the risk reward of potentially saving millions of lives. You know, when, you know, you had alluded to Jenny, there are nearly 20 veterans suicides a day. The current treatments aren't working. There are countless veterans that are saying that they're healing with this after having given up hope. And they feel this frustration with these continued obstacles and roadblocks and this anger and that we're not actually even caring about. What about the over-medicalization of the veterans? What are the limitations of the current treatments? And really feeling frustrated that they've served in this country, they've suffered subsequent mental ailments from this, but they have to seek these therapies elsewhere.

And so as Jenny was saying, this really begs the question, how can we address maybe some of the pitfalls in this research while still making it available to people who arguably maybe could be on the brink of death? And I see an importance in really including subject matter experts on the review committee that can really understand this completely new paradigm, you know, encouraging a collaborative and interdisciplinary research model where psychiatry, psychology, neuroscience, pharmacology, all of them are there. And there's a discussion with academia, industry, and government that can really facilitate a different way to look at this. And we can consider the expanded access programs and making them more accessible,

allowing patients that really have these conditions, that they've exhausted all other treatments, access these investigational drugs out of clinical trials, but we're still collecting additional safety and efficacy data. I think that's totally right. I don't think we talk enough about right to try, especially with respect to our veteran population, right? We talk a lot about that for other end-of-life conditions, right? If you've got cancer and you don't have a lot of time left, there are a lot of therapeutics that are available to you that have a very complicated risk-benefit profile, but you're still allowed, once you've administered the education around that compound, to try it if you feel like that compound is something that you want to try. And we don't treat PTSD, in my opinion, as dire and life-threatening a condition as we do

typically cancer. And so there are a lot of veterans that, as per Sarah's comments, would say, look, I've tried everything else. I've put a gun in my mouth. I've done all these other things, and I'm going to kill myself if somebody doesn't give me another idea, another opportunity to try something different. And for them, I think that they definitely deserve right to try and that there must be a way, if we're all clever and we put our heads together, to figure out how to allow veteran access to these populations, to these substances, and maybe even that could be a way to allow for FDA approval of MDMA-assisted therapy, as an example. Like, within the VA system, that might be a way to start the ball rolling and acquire data

in a population that really, I think, in my particular opinion, needs access to the drug the most. Yeah, I must say, the fact that we're focused in the research on veterans gives me some hope that we're not going to see just a simple reboot of the war on drugs and the same kind of political all that we do and don't do for them and are in many cases scandalous failure to take care of them, that concern cuts against the grain politically that, you know, frame the war on drugs as we came to know it, right? I mean, this is, you know, if you're going to generalize, as you move right of center politically, you get greater and greater squeamishness and concern around the, certainly the off-label and extracurricular use of drugs, but you get more and more concern about our nation's veterans. And so I just think it's, for just purely pragmatic political reasons, starting here makes a lot of sense to say nothing of the fact that so much of the need is here as well, therapeutically. Jenny, you also mentioned end-of-life care and the right to try compounds. I think end-of-life care is also one of these areas where it's just so obvious, ethically speaking, that the censorious logic of the war on drugs just is not making contact with the reality of

human suffering and is compounding it pointlessly. And so, you know, getting people who are terminally ill the right to take, you know, any compound they want in the end is just so easily defended. Okay, so the FDA has to make some kind of ruling in, is it the middle of August, correct? And I guess there's some fear that they may just decide to close the door to this research and not give approval. Why might they do that? And what are the, we've flagged some of the issues here, but can one of you tell me more about what really could actually present a real impediment to this research moving forward? Yeah, something that was touched upon in the committee meeting was some of the boundary violations and sexual abuse that had come up. And so, you know, I think when any sexual abuse arises, you know, whether it's in the underground, whether it's above ground psychedelic community, whether it's in any other field, we really need to talk about it. We don't want to sweep it under the rug. A therapist having

sex with patient is unethical, full stop. So let's bring that common sense into the room. The more we understand, I think the dynamics at play, the more I think we can educate and prevent while continuing to create mechanisms of safety for the field. And I just want to point that we've seen similar issues in other fields, and it doesn't stop their progress. I think instead, a mature response would be to put significant effort to prevent such harms. Get curious about what's going on. Is there increased suggestibility? Is there increased vulnerability? You know, we see that increased vulnerability in normal talk therapy, right? When patients are sharing very deeply personal and sensitive information, it's placing a lot of trust in the therapist. And so this vulnerable psychological state, you know, can make them more susceptible to manipulation. And, you know, we can take this

further that, you know, this dissolution of personal boundaries with psychedelics in these non-ordinary states can be exploited by untrained or unethical practitioners, you know, and this deep connection that's fostered by psychedelics can exacerbate. So, you know, the way I look at it is this vulnerability that's created in any therapy space is essential for, I think, the healing work. And the space allows for deeply held emotions and thoughts, and I see this in normal talk therapy as well, that will allow for an exploration of defense mechanisms. So how have they been there to protect us?

You're being seen and heard in these therapy sessions. And so I think because of the power of that human connection, there's a closeness that develops and that can become confused with romantic or sexual intimacy. So I think it's just really important to note that these emotions come up and the lines can get blurred and you can set a boundary and you don't act on them. And so it's just important to note that sexual abuse, power dynamics, they're inherently and unfortunately seen in human nature. We see them in all fields, in all walks of life.

And we really need to hold that these abuses can happen in this context. And so what could we do to prevent it? So, you know, the reason why I think this work is so important to come above ground is this is what will allow us to establish very clear ethical guidelines and protocols that we can continue iterating on. So there will be very clear comprehensive ethical guidelines in my eyes that will address boundaries, consent, appropriate behavior. It will make sure that the participant really understands this and what the safeguards are and that consent is ongoing and that you're aware that an emotion

like this can come up and you don't act on it. And furthermore, this is again, the need for having more rigorous training that includes therapists understanding their own boundaries, educating on sexual abuse and trauma-informed care and ethical conduct. And the most important part of this coming above ground is the accountability and reporting mechanisms, which I think are essential. Because when we don't have them, what I worry about is the underground psychedelic community is flourishing because people are desperate for treatment. And so it will become very difficult for a sexually abused patient to come forward. Not only do they have shame around this, but they feel that they might even get in trouble for

having taken an illicit substance. So can they even report this? So it just feels even more essential to bring this above ground and start creating those structures and frameworks now. I completely agree with Sarah. I think one of the best things that could happen with approval of these substances is bringing it all into the light and allowing for additional accountability. There's so much responsibility involved in being a therapist and any therapeutic alliance can be abused. And so there needs to be additional oversight for psychedelic therapy and approval, I firmly believe, is one way forward to enabling that. Yeah. I mean, the fact that the current therapeutic work that is happening all over the place is, by definition, illegal and could land its practitioners in prison makes any reporting of anything incredibly fraught,

you know, whether it's just the pressure applied to somebody to, you know, not report the bad experience they had with a therapist could be coming from the place of, listen, not only do you not want this person to go to prison for the thing you didn't like that they did, but you stand a chance of setting back this whole area because you're going to reboot the war on drugs for everybody. I'm not saying that's an ethical pressure to be brought to bear on somebody who had a bad experience with a therapist, but you can see the social dynamics of it happening because this whole thing is underground and by definition unregulated. Exactly. As Sarah knows, that's what wakes me up at night, is the inbox full of people that did

something in the underground that destabilized them, and then they got ghosted by their therapy team. And now they're looking for help, and they don't even know where to go. Okay. Well, it should be obvious, if it were not obvious already, that therapists, facilitators, caregivers should have something like a Hippocratic Oath that they follow, right? needs to be training to put people in these roles who are qualified to serve in them. I don't know if there are any other possible pitfalls and downsides we want to talk about. I mean, perhaps there's something we can say about what this training could look like and the opportunity it actually offers for a, I mean, it's hard to imagine a career that could be more fulfilling than this.

When you think about what it looks like when it actually works, right? I mean, it's just, this is the very picture of compassion. I mean, it's just the role of a psychedelic therapist, again, is happening underground in a way that is far from ideal. But if you could imagine the true professionalization of this and, you know, all the appropriate guardrails and the academic study that would facilitate, you know, a selection process and the generation of expertise, you know, relevant to deliver this care, it would just be an amazing thing for people to be able to do. And, you know, along with, you know, plumbers, massage therapists and nurses, it will probably be one of the last things that AI will capture. There will be no radiologists, but there will be psychedelic therapists if we play our cards right. What, if anything, can we say about the training of these therapists?

about the training of these therapists? Well, I can say that one of the nice things about the phase three clinical trials was that it was an opportunity for what is now Lycos Therapeutics to stand up their own training program and to sort of cherry pick providers that already had a background in PTSD and trauma treatment and then administer these additional trainings to them to get them up to speed with a psychedelic facilitation. And so that could be added into their REMS plan as an example, so that they had oversight over the first generation of therapists that would deliver this cutting edge care. And that would also give all of our states a chance to enact their own training and credentialing programs, oversight, maybe even insurance for psychedelic providers so that they were all very

well trained and monitored and that there was a system of recourse for reporting or addressing misconduct. Yeah. And to further touch on that, I think that's why it's essential to have really comprehensive training programs because as we were touching on it, you know, when it goes right, it's beautiful. But what I'm really interested in is when the psychedelic or the paradigm of psychedelics can show some challenge. And so one of the things that I think could be addressed well in psychedelic programs is people can have false insights in psychedelics, right? And so having a comprehensive training program that includes a lot of this information, includes the potential of false insights, and really how to incorporate that knowledge, you know, using case studies, role play, where you can simulate these scenarios and understand how, you know, when they're coming up, how to hold it in a non-directed way instead of actually maybe adding more fuel to the fire.

in a non-directed way instead of actually maybe adding more fuel to the fire. And I just think it's just important, you know, there's going to be a lot of critical thinking necessary. You know, you're not going to be dismissing some of these beliefs outright, but how can you foster, you know, an environment of open inquiry? And I think the most important part for me is supervision, right? And continued education, just like, you know, when I finished medical school, you know, and I was training to become an ER doc, like residency to me was where I learned everything. And so I thought I knew how to interact with patients. And there's a lot that I learned on myself, but to reflect that back to someone that has, you know, understood this space and can help me glean some insight, I think that is very important.

So I think some of those would be high on my list and why I'm really looking forward to having this come above ground so we can really start iterating and improving upon these models. Well, Jenny, Sarah, it's been an education and fascinating. Is there anything that either of you want to say in closing that might be relevant for someone to hear in the, again, now I'm focused on the decision that the FDA has to make next month? I mean, I personally truly believe there's still a path forward and I hope the FDA follows the data and feels likewise. Yeah, I agree. And I think one step further is, you know, as we're continuing to explore how to really elevate and understand this field, again, to me, it still comes back to funding. And so, you know, what we're trying to do

with Treat Humanity is to access more capital to be able to answer these questions. And so I would really encourage anyone in your audience, Sam, because some of the most intelligent people in the world that listen, join us on that mission to explore the different ways that we can bring these things. I don't think we have to move slowly. I think we can actually, with the proper funding, move quite efficiently and get the help needed to people that desperately need it. Well, there'll be links to whatever websites you guys want me to link to in the show notes. And

again, Jenny, Sarah, thank you so much for your time. Absolutely. Thank you for doing this. Thank you, Sam. Thanks, Jenny. Thanks, Sarah.