Psychedelics: Latest Research & Clinical Applications with Dr. Anthony Bossis

Interest in therapeutic use of psychedelics has grown exponentially in recent years. And with recent studies showing these miraculous molecules help with depression, anxiety, and substance abuse, is it any wonder the p-word is on everyone’s lips? In this unique episode of New Frontiers, the fantastic Dr. Austin Perlmutter guest hosts and interviews renowned psychedelics researcher Dr. Anthony Bossis, clinical assistant professor of psychiatry at NYU and the NYU Center for Psychedelic Medicine. With decades of experience in psychedelic and palliative care research, Dr. Bossis shares an evidence-based deep dialogue on meaning-making, spirituality, and end-of-life care. Tune in to learn how psilocybin can lower depression, anxiety, and end-of-life suffering, the appropriate intervention steps to avoid “bad trips,” what cancer patients define as their most meaningful experiences – and so, so much more. It’s a podcast packed with powerful insights on the human race’s quest for meaning and finding our true selves in a world full of distractions. Can’t wait to hear what you think! ~DrKF

Psychedelics: Latest Research & Clinical Applications with Dr. Anthony Bossis

What do love, meaning-making, and psychedelics have in common? And why is research on psychedelics coming back after a decade-long hiatus from its heyday in the 50s and 60s? In this episode of New Frontiers, guest host Dr. Austin Perlmutter talks with Dr. Anthony Bossis, clinical psychologist and clinical assistant professor of psychiatry at NYU, about his seminal work on psilocybin’s positive effects on mental and emotional wellbeing in cancer patients. With mental health issues worsening in the context of the global pandemic, interest in psychedelics as a promising solution has skyrocketed. As a leading researcher in this field, Dr. Bossis shares the remarkable findings of his clinical trials including psilocybin’s ability to dramatically improve quality of life and reduce hopelessness and depression, the importance of preparatory work prior to psychedelic therapy, how mystical experiences can help us connect and find meaning in life, psychedelic applications in treating end-of-life distress, alcoholism, addiction, smoking cessation, depression, eating disorders and much more.

In this episode of New Frontiers, learn about:

Dr. Austin Perlmutter: Well, hello everybody. This is Dr. Austin Perlmutter. I am honored to get to guest host this podcast today, and I’m doubly excited because my guest today is no other than Dr. Anthony Bossis. And he is a remarkable individual that I’ve had the opportunity to hear lecture multiple times and had a chance to speak with after some recent conferences. He’s a clinical psychologist and clinical assistant professor of psychiatry at NYU and the NYU Center for Psychedelic Medicine. His work is some of the seminal work looking at specifically psilocybin and how psilocybin influenced emotional distress and changed existential wellbeing scores after a single dose of psilocybin in people with cancer. He is a supervisor of psychotherapy at the Bellevue Hospital, and he is a co-founder and former co-director of the Bellevue Hospital Palliative Care Service. So for many reasons, I am thrilled to be welcoming Dr. Bossis to The New Frontiers in Functional Medicine podcast. So Dr. Bossis, thank you so much for joining me today.

Dr. Anthony Bossis: Austin, so great to be here. Great to be here. Thank you.

Dr. Austin Perlmutter: Fantastic. Well, I have so many questions for you, and I think you are an amazing person to be having this conversation with because obviously we’re all interested in learning about opportunities to improve mental health these days. The mental health issues seem only to have worsened in the context of the pandemic. And many people, myself included, have been very interested in how psychedelics might play a role in mental health. So I’d love to just start with hearing a bit about how you came to be interested in the concepts of psychedelics and end of life care and their intersection.

Dr. Anthony Bossis: Yeah. Thank you. And thank you for, I think the greatest introduction here to the topic is unfortunately the pandemic, and it reminds us both to address it for a moment and how that dovetails so well with this conversation. This pandemic has been just years of unspeakable suffering, but what it has done, and I hope this isn’t lost on all of us, is pulled the curtain back on what’s always been there, which of course is this isn’t permanent, death and suffering are always right there with us and how do we cope and navigate suffering. And clearly this pandemic has reminded us of this, it’s been like one global existential  dharma lesson or something for all of us. And hopefully there are lessons being learned and it does dovetail well with today’s topic that I know we’re going to touch on, which is how do we help mitigate the anguish and the suffering that can accompany the end of life, the end of each individual life.And this pandemic has certainly amplified that in this globally existential way.

My own background, I’ve had a fascination with these medicines going back really about 40 years to my early twenties, giving my age away there. And as a kid, like so many of us, I just was plagued a bit by existential distress. And we all wondered as kids what happens after we die and that clearly, if I look back, led to an interest in comparative religion. And I came across in my early twenties, maybe a little before, the whole literature and mystical experience through Huxley and of course like so many of us back then, Alan Watts, reading these incredible writings of so many people. They really spoke to my own personal longing for understanding what is death and what happens to consciousness. And I came across all this first psychedelic wave of research that was really done in the 1950s and 60s.

And these are the days before internet for the listeners when we used to go to public libraries and look at microfiche and look at books. But the body of literature was there. And it’s an incredible body of literature, that first wave of research, where they used LSD and a little bit of psilocybin, mostly LSD, we’ll define these medicines in a little bit, I know, to alleviate end of life suffering in cancer patients, and also to help explore what is spirituality, what is consciousness, which we don’t know. And that just gripped me. And ever since, I’ve been fascinated by mystical experience, comparative religion, and psychedelics, and always hoped one day I would do this. And sometimes in life things come out the way you might want and dream. And here I am many years later grateful to be participating in this reemergence of psychedelic research in America.

Dr. Austin Perlmutter: That’s an amazing answer. So many of the things that you’ve described resonate for me in my personal exploration of these topics, but I would like to come back to something that I feel is often missed in the conversation, because as many listeners know, there’s been an explosion in interest around the topic of psychedelics, both in the consumer space, as well as in the academic space. And so looking at Google trends or looking at PubMed trends, there’s just much more going on with relation to these molecules, but you mentioned that first wave of psychedelic study.

And I think it’s an area that many people don’t know is that tons of research was done in those early decades after, I guess, after the initial synthesis of LSD, looking at the effect of these molecules on a variety of different outcomes. And then there was a pretty substantial dip in the subsequent decades, which relates in part to the government regulation of the access to these molecules, both in the research and the non-research settings, but any thoughts on the value looking back at of all that initial research as it pertains to do we think that research was conducted in a way that we can draw conclusions from it? Does it have to be redone and in a way that can be looked at through the rigor of current trial standards?

Dr. Anthony Bossis: It’s a great question. And I appreciate you started off with that because there isn’t a researcher today who doesn’t really admire and respect and I think most of us should admit we stand upon the shoulders of these great pioneers from over a half a century ago. So yeah, just for a few minutes, it’s a great way to start. And two quick caveats. One is the experience itself that we’re going to talk about today, this mystical experience that we call it, we still call it that even within the scientific realm, is not unique to psychedelics. I believe we’re wired for meaning, humans are wired for these transcendent experiences. And they’re found that the mystical core of the great religions and traditions and been written about for millennia, Pew studies show everyday people have glimpses of these transcendent peak states.

The great Aldous Huxley, who was a great supporter of psychedelic work and had it himself and it changed his life, spoke often about this mysticore of human experience, and how in those days LSD could generate that experience as well as similar to the kinds that occurred naturally throughout the ages. So that research era is just a very rich period of time. And I remained fascinated by it. Albert Hoffman invented, discovered accidentally LSD in 1938, than in 1943 stumbled across having the experience accidentally initially then intentionally. And it was quickly looked into as a scientific tool to understand consciousness. Quickly, LSD was used in the first wave of research for two primary clinical indications. One was for alcoholism and many listeners may not know Bill Wilson, the founder of Alcoholics Anonymous had an LSD experience a number of times. And through that spiritual, powerful epiphany he had, that led him to the insight that the spiritual realm could serve as an ablation to want to have alcohol, to try to transcend this body we live in and the other arm was through cancer distress.

People like Stan Grof, Bill Richards, the great Walter Pahnke who died very young tragically back then, began to look at how one LSD experience, and more importantly, this generated peak mystical experience that we’ll define clearly today, could reduce, dramatically reduce, the suffering in cancer patients. And it did that in a very different way than other medications do. Most medications people take, and took back then, work as you take the medication every day. You take it every day to achieve a desired effect. And typically medicines quiet down unpleasant symptoms in terms of antidepressants or anxiolytics and anxiety agents. This medicine provided this incredible transcendent altered state of consciousness and the insights cultivated within that experience dramatically changed their perspectives on life, death, consciousness. And we saw these great results. That went on for a number of years into the mid 70s.

And as you implied or said, in 1970 President Nixon, the Substance Abuse Act was signed. And these medicines that were at one time legal for the culture itself, became out the reach of the public and incredibly out of the reach of researchers. And this promising paradigm of research came to a close in the mid 70s and 30 years went by or so before this current reemerging phase we find ourselves in. And a quick historical note that’s fascinating, not only was the research interesting, but they were culturally legal. So people like Cary Grant, the biggest star of his time, and others were having LSD or psychedelics in their psychoanalytic experiences, in their psychotherapy to facilitate growth and transformative experiences. So it’s incredible that there was such a cutting edge then, and then it came to a grinding halt, and we lost really decades of promising understanding about these medicines. And here we are now. So to go back to your question, really picking up where they left off, the study’s the same, we’ll talk about the trials today, how we do this. We do it in the same way they described – preparation, medication session, integration. The way it’s done is the same. And so we really, hats off to the pioneers who really began this incredible treatment model.

Dr. Austin Perlmutter: An amazing answer. I’m glad we went there because I think that the past is so important in understanding the present as it relates to why psychedelics are perhaps viewed in the way that many see them, which is as drugs of only abuse and as hallucinogens with no actual benefit to human health, which designates the schedule one. One of the things I’m hoping we get into a bit here is thinking about the difference between the experience itself, or maybe not the difference, but just this idea that there’s more to it than the experience itself, that is the drug experience, which is the altered state of consciousness induced by a chemical signal within the brain and the fact that there are lasting effects. And I think probably you and the group you’ve worked with are one of the premier study groups in the world as far as showing duration of some of these effects.

And so hopefully we can talk specifically about your recent publication in 2020 looking at some of the results of your 2016 trial. But I guess before we get there, I would love to see your take on, here we start out 1950s or so with so much work being done. From some of the papers I’ve read, there were over a thousand studies, there were over 40,000 participants in these studies, just a lot of work that was done. And then again, a fall off. And I think it’s clear or objective to say that in that period, it’s not like human mental health has improved all that dramatically. It’s something I talk about a lot is, despite the fact that we’ve had so much progress and in so many aspects of human civilization, I guess, and human society, innovation, it’s not like we’ve seen the prevalence of mental health conditions like anxiety, PTSD, depression, end of life distress, really drop off.

And in many studies it would actually be the opposite. Again, I think pretty clear to see that it is increasing, at least rates of anxiety and depressive type symptoms, general stress as a result of the pandemic. So I’m wondering if you feel like humans have lost touch a bit with some of that depth that was provided by psychedelics, but just by the types of relationships, connections, conversations that might have been more prevalent prior to the modern technological age, and whether, I know this wasn’t something that we planned to talk about, but whether the short term interactions or instant gratification interactions that many of us participate in through social media, through scrolling through content has changed our ability to tap into that.

Dr. Anthony Bossis: Boy, what a great question. That’s kind of the topic for our times, isn’t it? Yeah. That’s a very big conversation. We could sit here all day and try to pick that apart. What a zeitgeist we find ourselves in, not only within this pandemic, but modern life and of course since the birth of the internet and this way we live today. I think it as a connection and I think that’s what you’re getting at. Part of the research, we think part of the efficacy of these experiences is the meaning, is the personal sense of meaning that’s cultivated, senses of, I mean, people speak very often about the feelings of love toward self, towards others, meaning about their personal life. Why am I here? What is life? What happens after death? What do I do here in the face of suffering? Big questions, particularly for those who are in the cancer trial and who are at the end of life. And it does seem Austin, that this current zeitgeist with these quick digital interactions and the loss of maybe conversation and maybe religion has changed.

Religion initially were these, a means to define, to link back, to bind back to a source. And they were built around communities and conversation, meaning-making rituals. And it does seem that’s receded a bit in this current time and there’s no shortage of suffering going on. We all know the data on anxiety, depression, and PTSD and suicide is up tragically. And so it’s a very difficult time. It’s interesting that these medicines come back because there’s some talk and we’ll address this today as well. We want to keep things in perspective. There’s an impulse to offer maybe a promise, but there is talk that these medicines, and more importantly these experiences they generate, may revolutionize how we treat suffering. Again, Zoloft, Prozac, you take every day to quiet down a symptom.

These experiences literally bring the patient into the suffering through this three to four hour, five hour experience in this dramatically altered state into the suffering itself and ideally transform it, or understand it, at least in a better way. So I think in many ways what these medicines do or the experiences do, is to redefine and recalibrate our relationship to suffering. But suffering is, it’s above my pay grade, but suffering does appear to be the design of human experience. There is suffering in life. And there’s no way around that. And these experiences and what the participants tell us is that it changes that relationship to suffering and that through that suffering comes, and that’s the part people do hear about in the press, these incredible transcendent, joyful, loving insights into what this life might be about, but it takes first moving through some very challenging experiences.

Dr. Austin Perlmutter: It is powerful stuff just to, I guess, show my cards here. I think we’re a generation distracting ourselves from looking at the important stuff and for better or worse, I would argue for worse, the tools for distraction have become so good that it’s really difficult to stand in anything or to want to stay in anything uncomfortable. I know in my medical training and in palliative care and otherwise, it was pretty clear that people had disconnected themselves from the experience of death and didn’t want to think about it until it was absolutely unavoidable. And we’d have families coming into the ICU with one of their loved ones at the end, and they just have no infrastructure as to how to process it. And we’d have maybe the chaplain came in, somebody else and there would be a bit of a connection there, but as you’ve mentioned, people have lost connection with religion, and I’m not arguing that’s good or bad, but the rituals and the experience of death and what that represents has just been pushed to the fringe where everything is centered on the moment.

And it does seem like there is an intrinsic depth to talking about those types of things, but it is also intrinsically uncomfortable because it is the opposite of everything we’ve been hoping to optimize in the modern day. So I just think, especially now, it is something we’re being exposed to with a lot of death and dying as reflection of COVID and we don’t have the tools to manage that. So beyond, I think even the psychedelic work, your work with helping people make meaning about that end of life and I know you’ve worked in palliative care, it seems so important.

So I would like to, I guess, make sure we have time to adequately cover your work. I think that this is what makes this conversation, one of the things that makes this conversation with you so exciting for me is that you’ve actually done this research where you’ve shown some of the most remarkable effects from psychedelics used in a very specific context. And so I’d love to start around the 2016 publication and then transition to some of the work you published in 2020 showing the long lasting effects of some of the initial work.

Dr. Anthony Bossis: That’s great. Thank you. Yeah. And to dovetail with what you just said regarding death and dying, fortunately, there is some improvement I have to say. Palliative care and hospice movements have really helped increase the awareness of the conversation in our culture. Every year we see New York Times best sellers around death and dying, and we see end of life doulas and death over dinner. And so we’re seeing the conversation a little better. You think of Ernest Becker’s The Denial of Death, it really was the final taboo. It is advancing. However, we’re still far from it being fully integrated into life. And the people often ask, “Well, isn’t it depressing to think about death all the time?” And as you know, paradoxically, it’s not. I think to accompany us that that’s always there and this life does have an end, actually in its best, liberates one to live more fully versus this kind of pushing it off to the end, which we don’t know when it’s going to come.

George Harrison famously said as he was approaching death to his wife that you can’t wait till the end to prepare for this. It’s a lifelong journey to prepare for the end and the end of life is part of life. So hats off to the palliative care movement that’s really done so much good work and increasingly to help educate the public. Yeah, our study at NYU and John Hopkins were published together in 2016. And again, stands upon the shoulders of the great pioneers of the 1960s who published some papers that one LSD generated experience could dramatically reduce depression, anxiety, and just the attitude about death and the important thing that came out of their research that we really continue today and is an important part of our conversation is, it seems to, and about two thirds of the people, maybe a little more, to generate what we call a mystical experience, Abraham Maslow called it a peak experience.

There’s many names, there’s no one name and it’s not one thing per se, but Carl Jung called it the luminosity, Rudolph Otto, and we actually define that. There’s a clinical measure, research measure, that began, was developed back in the 1960s that we still use in the modern research. And there’s only a few brief features. One is that, in this experience, the person of the subjective experience that all things are connected, unity, literally all people and things are connected, that it’s one unfolding essence. The other feature is the noetic quality, a term coined by the great William James that as if one is encountering ultimate reality. Austin, I’ve never heard, rarely ever heard in the sessions I’ve guided, a person come out of it and say, at the end of the day, when they’re back in ordinary consciousness, “Oh, that was a temporary drug effect and that’s all it was.”

It’s more like, that was ultimate reality, or that was more real than this or that part of whatever this all is. And that’s remarkable to hear. A sense of sacredness is often within the experience, deeply felt positive moods, ineffability, impossible to describe, which of course we read about in all the great mystics as well. And what I think one of the most important features is this what we call transcendence. Transcendence of time space, as we know, which I know sounds very out there for a listener, but people report and all these research trials going back half a century and in naturally occurring experiences, transcending this body that we have, time and space as we know it, as if pulling the lens back on experience and seeing ourselves in a much larger panoramic field. And that really recalibrates our perspectives on life, death, what is the body?What is consciousness, which we don’t know, what is death?

And for the person who is dying and whose body will soon stop working, as we’re approaching death, there’s the knowledge that this body will soon stop functioning. And if we associate who we are with the body, then I stop. And maybe that’s the case. But when many people have insights of is that there’s something more enduring about who I am, whatever soul or spirit or self is that consciousness, my continuance in some ways, something much more mysterious and grand. And that insight is a gift for people who are approaching the end of life. So picking up with the first wave of research, we did a trial at NYU and Hopkins looking at one dose of psilocybin, a high dose, a moderate to high dose to generate this powerful experience inpeople with cancer, many with very advanced cancers.

And we published in 2016, as you mentioned, and the results were quite remarkable to us and those who are aware of this. It generated a rapid, next day and sustained decrease in depression, which is hard to treat, anxiety, hopelessness, it improves spiritual wellbeing, existential wellbeing, quality of life. Up to 90% of the participants reported improvement and quality of life. And the one thing it treated, which is interesting, is something we call demoralization, which is becoming a very important construct or experience in palliative care is a sense of meaninglessness, existential distress, hopelessness. And it’s hard to treat with medication like you would with depression, it doesn’t overlap with major depression in the same way. It’s very unique. And this changed that. It reduced the demoralized state, and we’re going to have a new trial this year looking at demoralization as the primary variable, actually in a psilocybin multi-site trial.

So that was really fortunate for these patients and these findings, and they were published together and the features lasted, the relief lasted to the end of the trial, nine month marker, up to 80% continued to report less depression, less anxiety, and a dramatic reduction, not might have been, but a very dramatic drop. And you mentioned the 2020 trial paper. So the surviving members, we contacted 3.2 and four and a half years later and readministered these measures, many had since passed away, but for those who were living, they continued to report these effects, these reduced experience of depression, anxiety, demoralization, which again is really interesting. So a lot of questions here. We want to do larger scale studies, more people. We’re still in clinical trials. People often write and say, how do I get this medicine?

I want to be clear that we’re still in FDA approved clinical trials, that psilocybin is not available yet legally in America. But we hope within the five years or so with more trials and more continuation of these findings, that it will be rescheduled, meaning available prescription for those at the end life. And quickly, qualitatively, what was remarkable, more remarkable than talking about data and reduction and symptoms was their experience, Austin. Talking about that, even if this is the only life, the appreciation for every minute they had. We saw our greatest sense of equanimity. We heard a lot about love, and it’s always curious to hear scientists talk about love, but they spoke about love and forgiveness towards themselves, for others, of a greater love that maybe the energy or the force of whatever this all is like the Greek word agape.

And so you have scientists and clinical researchers talking this language, but this is what they were telling us. And so that’s where we stand with those papers. We’re looking forward to the next series of trials. And hopefully in a few years, this will be available at a larger scale. We don’t die well in America. We’re getting better at it, but there’s, as you know so well in your work, there’s improvement in chemotherapies and in pain management. But boy oh boy, we really have a hard time kind of addressing the emotional and existential distress that can often accompany us as this fleeting life winds down.

Dr. Austin Perlmutter: That was just, it’s incredible to hear. What it brings to mind for me is a number of things, but there are so many of us who are seeking to practice evidence-based medicine, where we’re looking at all of these papers, we’re reviewing the sample sizes, we’re looking for sources of bias and then we’re intervening and saying, oh, well the ace inhibitor pass for somebody with this diabetic complication based on these data points, and all of this to me collapses at some point to what are the outputs or what are the outcomes we really care about? And it strikes me that hearing those outcomes that you just described, those are the ones that actually matter and everything else is a surrogate. So we get people’s blood pressure down. We work on their hearts.

We bring people’s blood sugar down. Sure, all of that is important. But I think we can agree that what really matters is what you’ve described. And so it’s certainly looking at things like objective markers of quality of life, but it’s also just asking people about it and hearing from people that this was one of the most meaningful experiences they have had, that they felt connected to the whole. I guess at some point it comes down to personal philosophy, but it just seems really, really important to spend extra time thinking about studies, interventions that get us to those outcomes. And I would love to try to put this into context. Do you know of any other interventional trials that show these types of results as it relates to mental health as far as the timeline, as far as the rates of side effects?

Dr. Anthony Bossis: Yeah, no, we don’t. This is again one day. The very next day, these symptoms of depression, anxiety drop off and are sustained. We don’t. It really is a paradigm shift in medicine. And you mentioned the value, how they report the experiences, around 67%, somewhere in the high 60% range of people report this experience being the single most, or top five most meaningful and/or spiritual experience of their lifetime. And you think about that. So that includes getting married, having children, all the things that life delivers, all the good things and all the tough things, death of loved ones, but those experiences are just imprinted in our consciousness. And this experience is among those. And here’s where we get a bit philosophical and maybe leave, change gears a bit, but what I’m often left asking, why would that be? Why are we wired for meaning? What’s the function?

Why are humans wired for these experiences? These are not unique just to this medicine. They’ve occurred naturally throughout history. They seem to form the foundations of the great wisdom traditions. A recent Pew study showed 49% of Americans report having some glimpse of a religious type experience, although it doesn’t get talked about a lot. It isn’t part of our cultural lexicon in a way. Astronauts have these. It’s called the overview effect. I invite the listener to Google “overview effect” and astronauts, when they see the pale blue dot as Carl Sagan affectionately called our home Earth, floating there in this black abyss, they’re catapulted into these experiences. The astronaut Edgar Mitchell in 1971, coming back from the moon on an Apollo mission, had a naturally occurring mystical experience in the spaceship looking out the window at all of that, and came back and spoke about it and dedicated his life, the rest of his life to understanding these transpersonal experiences.

So it leaves us with the question why? Why are we wired for meaning? And isn’t that something? And these medicines can generate that experience. They also generate other experiences too, not just this one, but autobiographical kind of psychodynamically-oriented experiences. They can revisit earlier traumas, unresolved relationships. They could also be very difficult. And I want to make sure we get that in. The encounter with the self, to paraphrase Jung, particularly if you’re approaching death can be profoundly difficult and there are tough stretches in these experiences.

This is why we have this treatment model that again was developed in 1960s, weeks of preparation, getting to know the person, preparing them for how to navigate this experience, getting to trust, have a sense of trust and rapport with the two therapists who were present the entire time. And the day of the session, lie on a couch with headphones and eyeshades to block out distractibility and attention to the surrounding environment and to go inward, into the unfolding changes in consciousness. And it lasts a few hours. The peak part of the experience could last three or four hours, and they come back into ordinary consciousness.

Then there’s weeks of addressing and therapeutically integrating the experience. So it isn’t a one off, which in cultural terms, people would call the bad trip. It’s not a great term, but it’s the preparation. It’s the screening carefully. It’s the consent. It’s the support. It’s trained guides there, they’re really embedded within this model that has been shown to be very effective and not have serious adverse effects, but again, Austin, why would that be? Why is consciousness, why does it take us in that direction?

And people often ask, why are these studies so ideal for psychedelics? And I think the answer is psychedelic experience, not just for the dying patient, but for so many people who have it, even other indications, healthier people, it seems to draw them into suffering and often the question of death. People actually have what we call a death, re-birth experience in consciousness in these trials, kind of remarkable to talk about, but why would I do that? And it’s a question above my pay grade and I guess any of ours, but it just fuels us to really, huh, isn’t that interesting? Consciousness seems to have almost this self-healing mechanism at times, and these medicines seem to generate it sometimes in the right setting. And isn’t that something? To be involved in this research is a great gift.

Dr. Austin Perlmutter: So a couple of points I’d love to pull out here. One being, and I know I mentioned this before, but I think it’s important, is that the effects of these molecules, even a one-time dose have been shown to endure in some cases for years after. And I think that that is really important because there’s still, I think a misconception, that psychedelics are the drug experience, that they are a chemical experience in the brain. And first that might not have any positive benefit. I think you’ve clearly shown that’s not the case. But secondly, that they only last as long as that molecule remains in the brain. And I think a difference here between conventional antidepressants, which are predicated on the idea of just raising or lowering a certain neurotransmitter for a certain period of time. And when people stop them, those effects tend to go away.

So I think that’s really important. The other piece here I just bring up is there’s a concept called hormesis, which I don’t know how well it translates over into your work Dr. Bossis, but probably listeners of this podcast will recognize hormesis as a term talking about a positive stressor, a short term stressor that actually makes the body stronger. And it’s often described in the context of things like exercise, which is actually a stress on muscles that breaks them down, but it builds them back stronger.

And from what I’ve seen so far, it does look like, if you are to measure levels of stress hormones in the body when a person is having a psychedelic experience that they do go up relative to baseline. So I think it is really key to understand number one, not all psychedelic trips, I guess, are this massively positive experience, that there is a lot of stress involved with it. And that stress is reflected both in the psychology, as well as in the biology of how that works. So I just wanted to reinforce the point that you made about the need to do preparatory work to ensure that these things actually go in the right type of direction because they do seem to be a pretty tremendous stress on the psyche if they are, well, perhaps always, but if, especially if they go in the wrong direction and-

Dr. Anthony Bossis: Yeah, that can be, go ahead. I’m sorry.

Dr. Austin Perlmutter: I think that one thing I would just like us to address is I see a lot of conversation about just saying psychedelics are always good, always positive, and therefore there should be no limitations on how they’re used. And I guess part of what I take from conversations with you and other people who are doing the actual research is there is a huge difference between just assuming that the ingestion of this molecule will solve all of our problems and the planning intervention that includes really the integration on the front and back end of the experience to plug it into a person’s life, as opposed to just the molecular experience of taking a drug and expecting it to solve our problems.

Dr. Anthony Bossis: Certainly. And that can’t be overstated and the context matters. The set matters. The setting matters. This is not for everyone. It’s not going to heal. We impress so many promising hopes of all this, and hopefully it is a relief, a tool to relieve suffering, but we’re still in early research and context matters. We certainly can point to many experiences that are not so wonderful in the ways we’re talking about. So that matters a lot. And it’s not about the drug experience. Again, I don’t think these are drug studies, per se.

I think they’re experience studies. And this medicine, for reasons we can’t figure out, does trigger. We know a bit of the neuroscience, but it triggers this altered state that’s remarkable, but that seems to be part of the human experience. And when it’s happened, when that occurs, it could provide insight into who we are and in this case how we die, but it’s also being shown to relieve depression, anxiety, helping with smoking cessation. And there’s a trial about to come out with alcoholism, but yeah, it’s a paradigm shift in how it’s taken and set and setting matters. And I think there’s a tendency in the press or the sensationalistic part of this to just chalk it up to it’s all peaches and cream, and these can be very difficult emotions, very difficult experiences. The encounter with self, as Jung would tell you, is not always an easy one.

Dr. Austin Perlmutter: Yeah, very important context. I think, always important to couch whatever is said about psychedelics in the idea that these aren’t the panacea that some people are pointing them out to be. I guess that’s my opinion. I don’t mean to impose that on you. But obviously we’re seeing a lot of news outlets reporting on these as the solution to what ails society.

I guess, to that end, I would love to talk about your thoughts on where psychedelics fit into the larger conversation around ways to connect to that more meaningful state of things. There’s been conversation about meditation being one of these types of opportunities, not for everyone, I guess, but I feel like for most people that is obviously more readily available, as well as perhaps lower concern for things going south. I was in an interesting conversation one day with a group of people describing the potential negative outcomes of 10 day silent retreats in that some people do have breakdowns from that. And there did seem to be the overlap with meeting yourself and that can be a relatively challenging experience. So I’d love to hear your take on that if you have one.

Dr. Anthony Bossis: Yeah, well, that’s certainly a true. We know from in Zen, they call them sesshin, these longer 10 day or longer retreats and plenty of stories of people not doing so well in the depth of those incredible experiences. And then similar to this, people do have very difficult times during these psilocybin generated experiences, but in terms of the larger question, it’s interesting, we began talking about the pandemic and this incredible time we find ourselves in. We began by talking about the pandemic and it’s such an incredible zeitgeist we find ourselves in, but hopefully it’s also an inflection point for some change in the direction of things. And you mentioned meditation and could a different kind of a greater awareness of spirituality be cultivated during these interesting times? There’s certainly talk about that. Religion is going down in many polls in terms of attendance, but the experience about religious experience is going up. In Pew studies, more people speak about having transcendent experiences. More people are seeking ways of finding meaning. And that was the container that religion would fill. So hopefully that could be revisited in terms of its earliest intentions.

But yeah, it’s an incredible time and we’ll see, and it’s interesting psychedelics are back now in this way. And within the next couple of years, we’ll have to see, it’s unknown. No one really has an answer for this, how this is going to unfold. We do hope these medicines are available within five years or so for treating things like PTSD, which NDMA treats, a different molecule, end of life distress, alcoholism, addiction, smoking cessation, depression, eating disorders. So there’s that aspect of it. And then people ask, “Well, how can these meaning-making experiences be used in other ways?” To cultivate spirituality, to cultivate meaning-making among ourselves and big questions. I have no answer for how this is going to unfold, but it’s certainly, it’s really interesting to be part of that conversation.

Dr. Austin Perlmutter: I feel like you have a very unique sense of these things given your work and beyond, I guess, the psychedelic work, just your interaction with palliative care on the whole. As we’re closing things out here, one of the things that I see come up a lot is this idea that a person’s opinions at the end of life are more valuable than their opinions at other times. It’s well, at the end of the day, what people really care about when they’re laying there in their deathbed that that supersedes their opinions of the last however many decades. But I feel like not only do you have insight into that, but you have insight into how you can change that for the better. And so I guess just in closing, any thoughts as to insights you would have gleaned from interacting with these people at these points and what you could bring back to the rest of us who are trying to better understand these things that allude us up until the very end.

Dr. Anthony Bossis: Yeah, what a great question. And of course that’s fun for all of us to hopefully meditate upon. I bear witness to these experiences people have on the psilocybin which of course dovetails well with how people talk at the end of life as well. And it’s no surprise, right? You know what they’re saying at the end of life and you know what you see what people in these trials were saying that in the end it was about relationships. It was about love. Those are the values that mattered. What’s the old, there’s no pockets in coffins. The things that drive us humans so often and so frequently throughout the arc of life cease to be so important at the end. And we hear that you hear it firsthand with people who are dying and you hear it often in these psilocybin trials, people really come out changed. And it recalibrates the hierarchy of what’s important. Viktor Frankl, the great, he was a Holocaust survivor and wrote Man’s Search for Meaning, he developed a meaning-making psychotherapy as well.

He often speaks about that, how meaning matters and meaning matters now, by the way, in research outside of our trials, we’re showing people in these studies come out with a more enhanced sense of a personal meaning, but we know through other research now that meaning seems to be a buffer against end of life, and throughout the lifespan, distress and depression anxiety. It seems, as Yalom would say, we’re wired for meaning. I think we’re wired for meaning-making. That seems to be the design of who we are. And it’s hard to do in a culture where sometimes meaning is not on the front burner. You said earlier, what a distractible world this is. And there was a recent book that just came out, I was watching an author speak about this, like we’re so distracted.

Our brains are broken, our capacity to even get through a book now seems difficult and that’s really unfortunate. And so in the end, we hear about the things that we know that matter. And these experiences do seem to reinforce that in these patients and I just want to go back and hats off and just such respect for the people in our trials. People come in these trials Austin without knowing what might happen. We prepare them and we educate them as to how this might work and how to go into the experience and go into the unfolding changes and you’ll be safe and trust the unfolding changes, trust us. And it’s a whole medical preparatory thing we do. But their courage to do this. And they’re really the pioneers. So hopefully in 10, 20, 30, 50 years, if these medicines are being utilized in a way to really, being used in a way to alleviate suffering, these early patients will have been pioneers in creating some of the first evidence. So, yeah.

Dr. Austin Perlmutter: Yeah, I love it. I think to try to close things out here a little bit, if we’re thinking about the primary endpoint as far as what matters, and this is a podcast geared towards both medical practitioners and to members of the public. I think hopefully we can agree this is a shared endpoint that we all care about, which is to make meaning, to have more meaning in life. And it, I guess double meaning here, the primary endpoint or the endpoint we all face at some point is death. And to be able to actually enjoy life before that and to have integration at the end seems so important. And so, Dr. Bossis, I just want to thank you so much for your time and for this really illuminating conversation.

I would love to get a chance to catch up with you maybe in a couple of years when things have gone a little bit further. We didn’t get a chance to talk about it, but there are things happening in Oregon with decriminalization and implementation psilocybin use. And so there are a lot of things happening right now, hopefully which will move things towards more equitable access to these medications for the people who need them. But again, just so grateful for your time and for your wisdom. And I know our audience will appreciate it as well.

Dr. Anthony Bossis: Well, thank you. Thank you for that wonderful closing. And I hope to see you before a few years for sure. And thank you very much. And this finally, I think, yes, making meaning and what these medicines seem to do now is also ask us what is consciousness? What is all this? It’s easy to think that the brain generates this remarkable thing we have, but we’re a question, what is that? It’s called a heart problem, right? What is consciousness? So, so fascinating. Thank you so much. And just a treat speaking with you, Austin.

Dr. Austin Perlmutter: Fantastic. Thanks again.

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Anthony P. Bossis, Ph.D. is a clinical psychologist and clinical assistant professor of psychiatry at NYU School of Medicine, an adjunct professor of classics and religious studies at the University of Ottawa, and an Investigator at The Lundquist Institute for Biomedical Innovation. For over 15 years, he has been conducting FDA-approved clinical and mystical experience research with the psychedelic compound psilocybin. Dr. Bossis was director of palliative care research and co-principal investigator on the 2016 clinical trial demonstrating a significant reduction in emotional distress from a single psilocybin session in persons with cancer, specifically, a rapid decrease in depression, anxiety, hopelessness, and demoralization along with improvements in spiritual well-being and quality of life. He is the study director and lead therapist on a clinical trial investigating a psilocybin-generated mystical experience upon religious leaders. Subjective features of mystical experience include unity, awe, sacredness, transcendence, and a greater connection to deeply felt emotions including that of love. His primary research interests in the study of psychedelics are the treatment of end-of-life existential distress and advancing our understanding of consciousness, meaning, and spirituality. Dr. Bossis is a training supervisor of psychotherapy at NYU-Bellevue Hospital Center and a faculty member at The Center for Psychedelic Therapies at the California Institute of Integral Studies. Dr. Bossis is on the editorial board of the Journal of Humanistic Psychology and a guest editor (with Charles Grob, M.D.) for the journal’s Special Series on Psychedelics. He has a long-standing interest in comparative religion and mystical experience and in the interface of psychology and spirituality. He maintains a private psychotherapy and consulting practice in NYC.

Austin Perlmutter, M.D., is a board-certified internal medicine physician, New York Times bestselling author, educator and consultant. He received his medical degree from the University of Miami and completed his internal medicine residency at Oregon Health and Science University in Portland Oregon. His focus is on helping identify and resolve the biological basis for “stuckness” in the body and brain, especially around decision-making. He hosts the Get The STUCK OUT podcast and is a co-producer of the Alzheimer’s, the Science of Prevention Docu-series. His writing is featured online on MedPage Today, Doximity, KevinMD, Medium, Psychology Today, MindBodyGreen, and DrPerlmutter.com, and his work connecting COVID-19 with immune-related depression appears in the peer-reviewed scientific literature.

Website: austinperlmutter.com
Podcast: Get the STUCK Out
IG: austinperlmutter
Twitter: austinperlmd

Bossis studies:

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial (2016)

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer (2020)

Psilocybin, Spirituality, and Palliative Care: Research and Implications, Feb 2021

PSYCHEDELICS AND PSYCHOLOGY: Modern Medicine Meets Ancient Medicine | Anthony P. Bossis | TEDxMarin

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