EP 211: Austin Perlmutter | Nature, Psychedelics, and Epigenetics

Welcome to Radical Responsibility, the podcast dedicated to ridding the world of blame and shame, where we explore the issues you care about from a unique perspective. 100% ownership for each and every circumstance we face in life, day in and day out. Hi. Welcome to another episode of the Radical Responsibility podcast. This is your host, Dr. Fleet Maul. And in this episode, I'm really happy to be joined by Dr. Austin Perlmutter, a board certified insurance internal medicine physician and New York Times best selling author, to explore the profound connection between nature, psychedelics and our health. We're going to discuss the fascinating role of plant compounds in influencing our well being and the potential of psychedelics like psilocybin in enhancing mental health. We also explore how these experiences can induce lasting changes in DNA expression through epigenetics, as well as help heal intergenerational trauma. So tune in and learn how the body mind connection can be unlocked through nature and cutting edge science. And I'm very happy to be here this Morning with Dr. Perlmutter. Dr. Austin Perlmutter. Welcome, Austin.

Hey, thanks so much for having me.

Oh, it's great to have you. And we're really, I've really been looking forward to this conversation. I'm going to share a bit of your bio with our audience and then we'll jump right in. Sound good?

Sounds good.

All right, so Austin Promoter, M.D. is a board certified internal medicine physician, New York Times bestselling author, published researcher and international educator. His mission is to help people improve their health by targeting the biological basis of stuckness in our brains and bodies.

He's writing presentations, podcasts and online education programs explore how environmental factors influence our cognitive and mental state and have reached millions of. Dr. Perlmutter currently serves as the Managing director at Big Bold Health, a food as medicine company focused on helping people rejuvenate health through better immune function, where he's running a first of its kind study exploring effects of plant nutrients on human aging through epigenetics.

So you've been working on the front lines of research looking at how environmental factors influence our mental states. And I wonder if you could shed a little bit of light on how nature can help heal our brains and what the data says about the mechanisms of this. And in your bio, as I read your bio, I'm also curious about this notion, the biological basis of stuckness. I found that an interesting phrase. And then of course, food is medicine. So maybe we'll, maybe we'll just start there generally before we move into talking about psychedelics and psychedelic assisted therapy.

For sure. Well, let's start with just a sense of where we are today. So 2023, 2024, we're in a place where despite the fact that in theory we have access to all the things that should make us healthier and happier, we see that in countries like the United States, people are dying earlier. For the last several years, we see that mental health conditions like depression and anxiety have been on the rise, especially in young people. And so we're really not getting that much healthier as a kind of aggregate, especially in the United States. And we're certainly not getting any happier. And I would argue that the majority of, kind of the basis of what is going wrong is brain related. And why do I say that? It's because if you think about the principal drivers of our behavior, what we do, as well as the principal drivers of how we feel, these are brain related systems. And as much as there are so many things that matter in health, whether it's blood pressure or heart disease or diabetes, the truth of it is that the most important variable that we have is our brain state, specifically our ability to enjoy our lives. That is a mental health outcome. So with this in mind, that's why I've been so focused on trying to help people understand what is getting their brains stuck and how they can get this stuckness out of their brains. As it relates to variables that either get us stuck or get us unstuck. One area I think we have hugely undervalued is the power of nature. And that's kind of a big topic because, you know, nature, some people say, oh well, I want natural medicines. I think that's part of, but certainly not the entirety of what I'm describing here. What research shows us is that nature has a number of pathways by which it can help to heal us and specifically heal our brains. So that range from the food that we eat. There's a huge difference between eating foods that are close to what occurs naturally versus foods that have been ultra processed to things like psychedelics which are kind of at their, their basis derived from nature, natural elements to just being outside. A large body of research now demonstrates that being in nature, even if you're not doing anything, but just simply being outside has healing, restorative benefits. So all of this is to say that I think that the mental health of the United States and the planet is really the most important thing that we all need to focus on. And as we're looking at variables that impact it, we absolutely have to be thinking about how the natural world can impact and positively improve Our brain health and our mental health outcomes.

So we know that, you know, that the healthy functioning of our brain affects every dimension of our lives clearly. And, and there's a lot of lifestyle elements of our lifestyle that can really support brain health, from exercise to getting enough rest to, to eating well, all of these things and continuing to learn. And as you. Well, you talked about being outside in nature and you know, there's a movement in the original, I think in Japan called forest bathing. Of just being, especially being out in the forest and out in nature for periods of time has all kind of beneficial impacts. So I'm wondering if you would also.

You know, from a Western point of view, perhaps especially a more reductionist view of the brain and mind. Mind arises from the brain. A more Eastern view would be that, you know, it's at least a symbiotic relationship, if not consciousness being the original source of the material world. And at the very least, although certainly the healthy function of our brain is affecting our mental health and our mind states, the mind states that we cultivate can very much affect our brain health and be reshaping our brain. So I'm wondering if how that plays into your view of, of how we work with our, our, our mind states moment to moment.

It's an interesting question and it kind of verges on the topic of spirituality and certainly philosophy, which I would say are slightly outside the bounds of internal medicine, where I got my basic training. But there are a number of important conversations around this idea where you at some point realize that you can lock in every physical variable there is. You can get good sleep, you can eat a healthy diet, you can go outside. There's more to life than that. There has to be more to life than that. And if you really think about what it is that seems like the principal driver of happiness, of long term satisfaction in life. It isn't the people who necessarily get great sleep every night. It isn't the people who exercise every day. It's the people who are connected. And I think, let's just stick with that term here as a larger question of what it means to be connected.

We've seen around the world rates of disconnection rampant. And what I mean by that is that people feel disconnected from the people around them, from their environments, from themselves. And that isn't something that you can simply solve, certainly not with, in my opinion, a drug. And also not just with dialing in your lifestyle variables, because the connection is something deeper. It speaks to what it means to be human, to have a meaningful existence. And so to that end, I think there's something to be said for where can we find that connection? Again, some of that can be through spirituality, some of that can be through nature. Some of that can be through, and very consistently has been shown in the research to be significant through reconnecting with important relationships in our lives. But again, there's more to this than simply dialing in the neurotransmitters and rewiring the brain networks. Right? That kind of takes, as you said, a reductionist approach to assuming that the brain is simply a computer and that if you plug in the right variables, then you'll get the right outcome, in this case, happiness. And I think one of the things that helps me to appreciate that being a human is more than just having X levels of norepinephrine and dopamine and serotonin, is that there does seem to be something transcendent about certain states that are independent, perhaps of being able to measure, at least based on the tools that we have right now. So not to jump ahead, but when you think about some of these states that come along with psychedelics and how, for example, that one of the best predictors of whether somebody gets a significant positive outcome isn't the level of something like psilocybin in their bloodstream, but rather whether they have experienced that transcendent space or that transcendent brain state, it does get to the point of kind of questioning as we look at health outcomes, how do you build in some of what you've described, how do you build in some of the magic, some of the awe, some of this connection to something beyond ourselves? I think nature is one of the portals to that. Research has shown that being exposed to awe inspiring nature does some really interesting things to our brain state, does some really interesting things to our mental state. And so I think finding ways to reconnect with things, things like that, to things beyond ourselves, beyond this kind of small ego that builds to be so big and colors so much of our days. It's a really important part of the conversation and definitely not something that I think conventional medicine does a great job of building into a care plan.

And that's kind of why I invited that, you know, opening into that territory a little bit, because I think it really will come into play as we discuss further the role of psychedelic, the potential role of psychedelic medicines. You know, we were talking a little bit before we started about the work I do in the, in the criminal justice and public safety world. And I have a colleague who's a New York police Department detective. He's also a professor at Columbia University and a psychologist. And he did a small conference in New York on the value of awe. And really it was focused in the public safety. Very unlikely thing, but here was gathering together law enforcement and talking about the value of awe for health and well being. So quite amazing. So before we move into talking more about the role that psychedelic medicines could play in all this, maybe talk just a little bit more about some of the strategies that you offer for people to leverage nature for both healthy brain functioning and overall well being and happiness.

Sure. So let's talk about nature exposure, just as a theme. You've already alluded to this, but Basically since the 1980s there's been a movement that started in Japan called Shinrin Yoku, which translates into forest bathing, which is the idea that simply being in nature without an agenda, just spending time outside in natural settings, has a healing property. And this is one of these scenarios where we do all these studies, we do these reviews, these meta analyses. Does nature have a beneficial effect on us? I think we kind of know intrinsically it, it's different if you spend the day outside walking on a trail, under beautiful trees, next to a river, so on and so forth, compared to spending that day indoors, watching tv, on your phone. It's, it's pretty straightforward that you feel differently in those two scenarios. What the science is showing us though is kind of more, in a more nuance response way. What are some of the pathways that exposure to nature appeared to activate? And a lot of this has been around stress. So there are, there are some very clear statistics around this. But the bottom line is that people are feeling incredibly stressed. And so if you have this continuum of what stress represents, I think it's important to note that we want a little bit of stress, what we call eustress. It's what makes us stronger, more resilient, allows for our brains to make new connections in the absence of stress. We're kind of in this stasis where we're not feeling motivated or any sort of desire to do anything differently. Which I guess depending on how you approach life, doesn't seem to me to be the best strategy. But we all know that in the modern day, the type of stress that most people tend to experience is really not this positive stress, but rather is distress. That is this chronic grading feeling of I'm not quite able to resolve my problems. Relationships work, the general stress of where the world is heading. And so it's thought that there are aspects of that that can be exacerbated based on the amount of time that we spend in non natural or kind of urban types of environments. So stress can come from our screens, watching the news, playing on your phone, engaging in stressful conversations at work. These are things that are major contributors. We know that based on a recent publication by the APA that watching the news or engaging with the news is a major driver of stress in the American brain, not surpr. So there's two things about nature I think that are relevant as it relates to the stress topic. One is simply unplugging and not taking in what is kind of intrinsically stressful. Content by being outside is important and maybe that's enough. It's you're unplugging and you're doing something else. But there's also data suggesting that nature may actually kind of activate anti stress pathways itself. So what some of the studies have shown is that exposure to nature is linked to a number of variables associated with decreased stress. So we're looking at a decrease in sympathetic tone, a relative increase in parasympathetic tone. We're looking at a lower blood pressure. So systolic diastolic blood pressure, we're looking at lower heart rate, we're looking at lower cortisol levels, we're looking at lower perceived levels of stress. So if you're going to ask somebody subjectively, do you feel less stressed when you go out into nature? And there's some, some really interesting kind of correlates to this that relate to brain function. So exposure to nature correlates with better focus and that's in adults as well as in children with conditions like adhd. So we know from research that when we are stressed, we don't have to get into too much of the neurobiology here, but it tends to shift us from a more reflective state to a more reactive state. It kind of closes out our peripheral vision and gives us that tunnel vision, which can be really helpful if we need to stay focused on the predator in front of of us. But not super helpful if our goal is to be taking in additional data and to be reflecting on our decision. So if stress narrows our focus, then having anti stress interventions can widen our focus again. And we know that again, if we want to be able to be focused on a number of things, be reflective, that anti stress interventions seem helpful. So this helps to explain why in people who are exposed to nature, even virtual nature, which is really interesting, there appears to be a better focus. Coming back to kind of the general theme here, nature exposure is linked to anti stress Benefits. There's research showing that in as little as 15 minutes of even an urban natural environment, so this is in Ann Arbor, Michigan, being around urban nature, that there were decreased levels of salivary cortisol. So we're not talking about you need to spend five days on an Outward Bound trip in order to get some stress reduction benefits. That's one part of it. There's also data showing that nature exposure is linked to improvements in immune markers, specifically natural killer cells, as well as a number of other variables. But I'd say the main thing would be the stress reducing benefits as well as some of these other brain specific benefits like improved focus, restoration of focus is the way it's been described.

Well, I have no doubt that that's the case from my own anecdotal experience. Interestingly, you live in the Pacific Northwest and in Oregon there's a, in eastern Oregon there's a state prison in the Oregon Department of Corrections where they have something called the blue Room. I don't know if you've heard of it. I don't know why it's not the green room. I think it maybe is painted blue. I haven't had a chance to visit it.

But prisoners can ask to go into the blue room and they sit in there by themselves and they basically watch nature films. And it just really brings their stress level and their anxiety levels down. And they found that, you know, prisoners who are dealing and often prisoners who are in isolated, you know, high security cells and so forth, they can get pretty agitated and so they request to go into the blue room and they, they spend some time in there and even staff have been using it. And we, we brought some.

A group of sheriff deputies from Los Angeles up there to see that because they were interested in possibly duplicating that in, in Los Angeles. So you kind of mentioned a little bit about the time required, the dosage, the level of exposure. From what I remember about the Japanese forest bathing tradition, I think they talk about three hours being out there. Now many of us don't have three hours. I know myself.

We have a retreat center where when I'm there doing leading retreats, we have a screened in ports on the second floor and great place to have breakfast because it kind of sticks out into the forest and it's surrounded by. You sit out that screen, you feel like you're literally surrounded by forest and having breakfast out there. I just feel my whole nervous system just start to, you know, just settle down. And all my cells are doing their happy dance. Right. And here at home The Connecticut river out at my back door. And I try to get out there for even five minutes. I mean, I walk the dog a couple times a day, longer, it's more up and down the sidewalk. But I love just to walk out to the river and just stand there and absorb.

That quality of the natural world. The Connecticut river and the eagles flying and things like that. And even being out there five minutes seems to do a wonder. So I'm wondering if research has shown anything about, since we're kind of in a clinical conference here, what's the minimal effective dosage?

It's a great question, right? Yeah. So I wrote an article a while back basically talking about how do you dose vitamin N? And I love kind of that idea, that concept of this is a nutrient, if you will, that you can look at how to get the right amount for what you need. And what I'd say is a lot of the research comes from larger scale epidemiologic data where it's looking at while people who were exposed to natural places for several hours a week or people who live in greener spaces and so on and so forth have the following health outcomes. But what I will say is I don't think there's a, a bad amount of time to be in nature. As much as we want to tether this to a specific numeric outcome. If you're getting outside for five minutes as opposed to zero minutes, that's amazing. If you're looking to really dial in based on the research, what you need, I'd say it starts at around 15 minutes. There's data at 15 minutes, 20 minutes. And then you start to look at some of the interventional studies. There was one that was done at Stanford where it's looking at longer walks. So I think it's around 90 minutes. That seems to decre rumination, change brain patterns.

I think in some worlds we get to a place of actually prescribing a specific dose of nature based on interventional trials. But where I am concerned, we might get to is kind of the idea that unless you're doing whatever it is, let's say it's 90 minutes for mental health, that it doesn't make sense. And it reminds me a lot of the conversation around exercise. So we would say that you need to do 30 minutes for five days a week. Right? That's kind of the general recommendation is to get to that 150 minutes of moderate intensity exercise per week. But does that mean that the person who goes out and exercises three days a week for 20 minutes there's no benefit to that. I definitely don't think that's the case. So I'm always cautious of trying to say here's the minimal dose, because there is no bad scenario in which you're getting a dose of nature exposure. Just like there's no bad scenario if you're going for walk but you're not quite getting to your high intensity interval training level of exercise or your heart rate quite high enough. There's still beneficial things. So I always start with people and kind of get a sense as to do you spend time in nature, do you prioritize nature exposure? And if the answer is no, it's far more important to find a way for a person to get a dose of vitamin N than it is to nail down the exact amount of vitamin N that they're getting. And to that end, one of the kind of of dominant themes for me in the more recent years is the understanding that so many of the recommendations that we make as doctors or that people tend to make as those in a position of knowledge are not taking into account habit change and the way that brain change actually works. Because the truth of it is the majority of recommendations that doctors make are very hard for patients to follow through on. What we're talking about here are terms like compliance. And we would typically say that a patient is non compliant if they don't follow through with their recommendations. Right? We'd say, oh, you were prescribed these blood pressure medications, you didn't take them the way you were supposed to. You're non compliant. You could maybe talk through with the patient and say, well, why didn't you do that? You know, did you just not remember? Did you not care enough? You really need to do this, it's really important. But the truth of it is that our brains work in kind of very clear and reliably specific patterns that relate to our habit change. And what we know about habit change is that we tend to do do the things that we enjoy more than we tend to do the things that we do not enjoy. We tend to do the things that are easier rather than the things that are more difficult. So that was a long winded way of basically getting to this point. If the goal is to change your health with regard to any sort of intervention, in this case we're using the example of nature. It is so much more important to find a way that you can make it sustainable than it is to do it for a few days and then forget about it for the rest of the year. That's the new year's resolution version of this. It's why most people do not follow through on their New Year's resolutions. They go very hard at the start and then it falls apart because they didn't use habit change neuroscience. So again, long winded way of saying this. If your goal is to change your behavior, in this case we're recommending that you use some nature exposure as a way to improve your brain health, your mental health. Find a way to make it easy, find a way to make it enjoyable. So in your case, if you're getting outside for five minutes a day with your dog or going down by the river, that's something that is reliable. I mean, if you have a dog, your dog's going to tell you you need to go outside now. So tether your experience to that and find a way to make that fun. So don't, you know, force yourself to walk three miles a day if that's going to make you miserable. Just find a way that you can get outside and enjoy some of that nature. And some examples that I would give finding a local park on the way back to your from work, spending 20 minutes there after work, you could exercise, you could draw, you could meditate, you could just walk through the park. It's basically finding a way to enjoy that experience. Because what happens is that embeds in your brain a habit loop that makes it more likely that you will continue to engage in that behavior. So rather than fighting yourself to make that possible each day, your brain is actually on your team. And you as far as what the self you want to become and the brain that you already have are both on the same page. I know that was maybe a little bit more than you were looking for there, but I think it's so important to emphasize that because almost all the time I find that other doctors, even myself, were making these recommendations without actually taking into account the way that the brain works. And so they fall flat. So whatever it is you're trying to do, these are some of the core strategies that I would say are important.

Absolutely. And you know, the idea of minimal effective dosage, I mean, if the bar is too high, that could be counterproductive. But I know Amishi Ja's research on mindfulness and a lot of her research with mindfulness and first responders and military, she came up with the minimal effective dosage for mindfulness to improve brain health and focus was 12 minutes a day. It was pretty low. When I first Learned to meditate 50 years ago, if you didn't do 45 minutes, you weren't meditating. Right, right. Of course, everybody has changed that. Even five minutes a day can be very beneficial. I think it's really important message that a little bit of any of these things goes a long way. I'm also curious, you know, when I do get out there, even for a few minutes, and take a moment to just look at the river in the sky and breathe and, you know, even if I only have a few minutes to do that.

It. It triggers memories of. Of being in nature for more extended periods of time. And it kind of connects with. It feels to me, anyway, this is purely anecdotal, but it feels to me like it connects with a set of.

Possibly a neural map and a neurochemical.

Kind of landscape that I have a memory for and allows me to reconnect with that and sort of almost connect back with the longer periods of time I've spent nature, but also bring that with me a little bit. I mean, there's something. Once we have a connection to the natural world, it's kind of like you talked before about connection, right? The importance of being, you know, connected with ourselves, connected with others and connected with the natural world and connected with some other, you know, some dimensions of life that give our life meaning and purpose. So there's something about that relation, maintaining that relationship with the natural world. Once you've established it, I'm curious about your thoughts on that.

Well, I think that's true. And I would start from the perspective of we may have our own internal memories as far as. Well, I remember a few years ago and so on and so forth. But if you consider kind of the aggregate memory of humanity, we realized that this idea of spending time indoors is a relatively new kind of development, especially the amount of time. So the average human in the United States is spending upward of 90% of their day indoors, either in their office, in their home, or in an enclosed vehicle. That is so out of sync with the way that our genes have developed over the last hundreds of thousands, if not millions of years. So when we talk about kind of our default state as humans, it is in nature rather than indoors. And I think it's absolutely true that, you know, there are aspects of us that are. Are deeply hidden, but are in our genes and in our epigenome that are going to feel more at home, more comfortable in a natural environment. There's another correlate of this, which is this. This really strange concept that has seemingly come up more recently, which is that we have humanity and what we do. And then there's nature. Nature as though those are separate topics. As though humans are not part of the natural world. And that doesn't make any sense, other than humans have this big ego and we want to think that we're super special. I mean, we are special, but just like every animal is special, you know, we have certain aspects of us that are unique. It doesn't mean, though, that we have to create this artificial divide between humans and the natural world. And there are a number of ways in which this can be represented. You know, there's some people will feel an intense sense of calm when they're in a big open space where they can see long distances away. And maybe that's because, you know, there's no predators on the horizon. Some people, like me, will experience an intense sense of calm when you're out camping. And maybe that's because I don't. I know I'm off the grid. I don't have the other obligations. But maybe there's something that is very kind of primitive within us, that feels this sense of contentment, knowing that we're in the place where, in essence, our genes had developed. There are all sorts of considerations around ways in which the modern world will make us feel sick, will make us feel unhappy, make us feel unhealthy. There's an entire branch of research around something called sick building syndrome, which is the idea that being indoors and especially in buildings that are constructed from the wrong types of materials can make us feel sick. Whether it's the off gassing from the construction materials, other air pollutants, other things that are in that natural environment or in that artificial environment that make us feel unwell. These are things that are real for many people, that when you're in nature, you are kind of receiving the opposite of it. It's also notable that when we're in nature, it's not just what we see and hear that matters. And I think that's really interesting. So there are molecules produced by trees, by plants, that we inhale. And these molecules may activate kind of ancient loops in our brains that make us feel in different ways. So when you're really immersed in a natural.

Yes, you might be hearing birdsong. Yes, you might be seeing the green or the blue. And we know kind of those are things that have been studied. So exposure to green space, exposure to blue space, as far as the benefits, referring back to what you described, as far as what's happening in that Oregon prison, but we're also inhaling molecules, and these are things that are speaking to very deep programming. So I think, again, there's so much that can be said and you can jump into some of the really, really fascinating science around epigenetics and how basically our genome evolved to be outside or at least to be exposed to those natural elements. And what is nature speaking to? And that also gets to another topic around, you know, if you're thinking about the benefits of nature for your health, for your brain health, it's not just the time spent outdoors, but rather in aggregate, it's asking what, what data is being transferred from the natural environment to us? And how is there this continuum between our surround, between the plants and animals that are outside the air that we breathe, outside our own outside, in which in this case would be the microbiome that's technically outside of us, but in some ways is an extension of the nature around us. And what we would say is, well, this is where we begin, which is our own cells that we know are dramatically impacted by our environment. So when you, when you look at that continuum, you realize that it's not like nature's outside and we're inside. This is all part of one perpetual motion machine. And so, so, you know, you get to this place of saying, well, this is incredible, this is amazing. But you can also get to the place of saying, my goal is to really care for the entire system, which means not only caring for your own health, but paying attention to the health of the nature around you as a reflection of your own wellness. Which, you know, is again, a little bit of philosophy here, but I think becomes so relevant when you see what's going on in the world today and how we've generated this, this artificial disconnect between the health of humans and the health of the planet.

Well, there's growing, that's kind of a bridge into.

Continuing the conversation here because there's a growing interest in molecules that have been derived from plants and the natural world. Polyphenols and psychedelics and traditional plant medicines and so forth, as well as those that have been synthesized originally from plants. And so I'm wondering, what are you seeing in the research and the patterns with our relationship to these molecules? And also, I can't help but, as you were speaking, brought to mind Paul Stamets work, who's on our summit as well, and he speaks about the importance that fungi have co evolved with humanity and the importance of the mycelium to the whole natural world and the correlate between our nervous system and the mycelium, between our microbiome and the mycelium. And then of course, course, one form of fungi is psilocybin, which is one of the major psychedelics being researched right now for psychiatric assisted therapy. So I don't know where you want to go with that, but maybe we can start talking about these molecules and maybe move into how our relationship with these molecules and with various plant medicines could be another way to optimize our health and well being.

Well, I would start with the idea that if you think about the ecosystem that we live in as humans, it's really the dynamic is data transfer. That's really what's happening. If you think about what's happening all around you, why things are the way they are, it's all data transfer. So whether that's photons from the sun that are transferring data and energy into plants, or the food that we eat, which is transferring carbohydrates and other macronutrients into our cells, it's energy and it's data transfer. And so I think it's an interesting question to ask what data, what signals are we picking up from our environment? That's a big. You can basically apply that to anything that you do in a given day. The conversations, the news that you consume, the food that you consume. But as it relates to this specific topic, which is thinking about human brain health and things that we can do to improve it, and specifically mental health, I think that there is this question of what data are we receiving from plants or from the natural world that's worth paying extra attention to. And so usually these topics don't necessarily come together in these conversations. You have conversations around psychedelics, then you have conversations around nutrition. In the conversation around nutrition, most of it goes around. Well, it's calories, it's carbs, it's fats, it's proteins. We know that in plants there are thousands of extra molecules. Maybe extra isn't the right word, but there are thousands of molecules that are not carbs, they're not fats, they're not proteins, they're not vitamins and minerals. They're a group of molecules called.

They're basically two ways to look at it. Phytonutrients or phytochemicals, depending on if you're looking at kind of a journal article or just talking about it. But they're the same thing. Phytonutrients or phytochemicals are a group of thousands of molecules in plants that act to help a plant kind of adapt to its environment. So these are immune signaling molecules for plants. They fight off bacterial infections. These are resilience molecules for plants. They help to fight off UV light or excessive heat stress or salt stress. And they have a number of different names, a number of different functions. But within this group, the best characterized subgroup are polyphenols. Most people have heard maybe not the term polyphenol, but they've heard of a term called antioxidants. And for a long time, and I'd say even for most of the instances where we hear this term, people are describing polyphenols as antioxidants because in test tubes they have an antioxidant effect. So the idea here is, well, you should drink some red wine because it has the polyphenol antioxidants. You should eat some blueberries because it's got polyphenol antioxidants. The reality of it is polyphenols are a form of data transfer and a form of signaling that exists within plants as well as fungi. I will say that when transferred to humans appear to have a number of signaling pathways, whether it's immune signaling, epigenetic signaling, metabolic signaling, that do a number of things to our health. And what's super, super interesting here is it is very likely that the story of polyphenols as antioxidants is either wrong or not the important part of this conversation, even though that's the one people have heard. Instead, what's far more likely is that polyphenols in our diet are poorly absorbed, but they are acted upon by our gut microbiome to form secondary metabolites which are then absorbed by us and have immune active effects, have brain active effects that can pass through the blood brain barrier, have epigenetic effects, meaning they change the way our DNA is used and that they transfer data, data between our environment to ourselves in a way that is only now being discovered. So we think about how do we learn about the environment, what's going on around us? Well, of course, it's what you see and what you hear, right? Well, yes, and it's what we eat. The food that we eat, the food we consume is transferred into data that is incredibly specific to the place in which that food comes from. You know, it's not just about, about the carbs in that bite of broccoli. There's all this giant family of nutrients that is teaching our microbiome and by extension our own cells, about what was the soil quality in which that broccoli was grown, what was the heat exposure that broccoli was exposed to, what maybe is that broccoli predicting for next year's weather pattern? So there's A ton of data that's being transferred there. We also know that people who eat diets richer in polyphenols tend to be the ones who live longer, tend to be ones who have less depression, 10 to be those who may have protection against conditions like Alzheimer's disease. So there's a lot to be said as it relates to specific brain related outcomes that speaks to the fact that it's more than just an antioxidant mechanism. So that's polyphenols, phytochemicals or phytonutrients. This is how plants are able to transfer data to us in ways that we're only now understanding the other part of this psychedelics. So you'll have many speakers talk about psychedelics, kind of what they are and their potential uses. You know usually we talk about psychedelics these days as mental health kind of pharmaceutical level potency interventions that happen to come from natural sources. Now there are a number of synthetic psychedelics that have been investigated. But when you think about the classic psychedelics, the triptamines, those that are based kind of on a serotonin back backbone, so these are things like psilocybin, dmt, lsd, they come from natural sources. So psilocybin as you've already mentioned, comes from a number of different mushrooms when you think about dmt. So that can be found in certain plants. There's also an MEO DMT which occurs naturally in a toad of all things. LSD was initially synthesized from a fungus. So these are things that occur in the natural world, not to mention things like peyote, so ayahuasca, which as I've kind of said part of that is the DMT component. So they occur in the, in the natural world. And there might be this question of why are they there in the first place. So are they just chemicals that a plant or a fungus created to try to ensure that an animal that ate it would not come back? Well, didn't really work out or is there something more to this? And if you look at this from the perspective of saying this is all just a web of interconnected data transfer, it's really interesting to qu question what is the data that is being transferred to us? So there are all these hypotheses of course, around psychedelics, the stone date, whether it is somehow instrumental in our development as a human species. What I can say is if you take the larger picture and you ask how are we doing? How are we doing as a human species? I would say the answer is not great. Given all the resources and intelligence and everything else. And then you say, well, is part of that due to a lack of connection with something bigger than ourselves? And if the answer to that is yes, then you have ask, well, how do we reconnect to that? And psychedelics are one of the most powerful ways that we're able to connect to something larger than ourselves, larger than our ego, larger than the idea of an individual, something bigger. It is so interesting to note that people who consume psychedelics on average feel more connected to nature and that the experience of psychedelics, especially the research I've seen is around psilocybin, seems to itself reconnect people with nature. So there's some really interesting webs, networks here that tie all of these things together. What I would say is if we're just curious about this question of what can the natural world teach us, how can it, how can it change our bodies, change our brains? Then you look at all of these things that I've just described, whether it's just being outside in nature, whether it's consuming plants that are containing data like polyphenols that appear to influence our brains and bodies, or psychedelics, which again, again, largely derive these classic psychedelics from natural sources that appear to change our bodies, change our brains in a way that connects us to nature, connect us to other people. It's at least an interesting thing to consider, which is how do interventions that connect us back with the natural world and connect us with each other by the way of nature, play a role in where humanity has to go in the coming decades? Because the last thing I'll just say here is if you consider the existential threats to basically this planet's ongoing existence in a way that allows for the support of diversity. Animal life, human life, what are the things that are most likely to take humans kind of off the grid? They're largely self inflicted wounds, whether it's climate change, nuclear war. These are things that are a direct reflection of humanity's kind of lack of empathy for each other and for the planet. So it's super interesting to think about, about when you look at what happens when people either consume molecules like psychedelics or there's a really interesting study that I was looking at that basically compared dietary intake of a diet that was rich in polyphenols with trait openness. And it showed that people who consumed more of these molecules in this diet were more open, were more willing to look at different information. There's some deep and very important things here because really what it gets us back to is the central theme of connection. If we feel connected to the natural world and people, people around us, it seems really hard that we would allow for things to continue on in the way that they are, which is killing other people unnecessarily, destroying the planet and the environment unnecessarily. So, again, gets us to a little bit of the philosophy of what's it all about. But I think that there are some biochemistry, and then there's the bigger picture of what seems to happen when people are more dialed in on receiving these messages from the natural environment. Environment.

Well, I just love the way you're opening up the conversation. This is incredibly helpful because as you pointed out, you know, part of the, the. The hubris, and I'm sure it was a natural part of our evolution. We developed these supercomputers that we carry around on our shoulders, and so we developed a lot of hubris, and we imagined ourselves to be separate from and to dominate the natural world. And so there's so many different ways in which we're learning the untruth of that these days. And I love what you talked about, data and energy transfer, that all these things, that's really what we're talking about here. And a colleague, Dr. Dan Siegel, who's also on our summit, who, in his work in the field of interpersonal neurobiology, talks about science, doesn't really have an accepted definition of mind, but the one that he proposes is a flow of energy and information within and between, so between with others in a natural world. And that what we really are and who we really are is in that matrix. And it's a matrix of the continual flow of energy and information or data. Right. And so it's really fascinating and it can really enlarge our thoughts about what we're really involved, because there's a danger of kind of conventional world of science and medicine taking the whole psychedelic thing and converting it into just pharmaceuticals and pharmacology. Right. And not having this broader view. And there may be benefits from that approach, but I think it's really interesting to open up the conversation in this way. Andrew Weil, who's also on our summit, who's very famous integrative physician.

Has spoken about how what hasn't been researched at all really is a potential physical health benefit. Benefits of psychedelics and plant medicines. There's been, you know, the focus now is currently on mental health and, you know, the tremendous promise that some of these plant medicines combined with psychotherapy offer for treating very difficult to treat human forms of suffering and mental disorders. And so Forth but he was pointing out that he feels there are tremendous potential benefits for dealing with chronic pain, for dealing with physical ailments and just for enhancing health and well being. And of course there's that whole world of, you know, where there is a dearth of research and there needs to be a lot more research the world of.

Supplements that may involve microdosing of plant medicines and so forth that could be more about wellness than about curative in terms of.

People who are dealing with physical or mental illness. So it's just really fascinating to open up the conversation as well way. And I'm wondering if you could talk about.

A little more about.

You know, on the surface of it. I mean often like we're a lot of the conversations, you know, in the summer we're trying to understand, well, it looks like these psychedelic medicines are really helping people, especially combined with psychotherapy. So how does it work? You know, we're, we're trying to understand the neurobiology of it. And you know, there's some, there seems to be some commonality between various non psychoactive or methods like meditation and breath work as well as psychedelics seem to take the default mode network offline to a degree. And so our constant self referencing and discursiveness goes down and we get opened up to other experiences. But you know, in talking with Bessel Vaniculk he says, well we don't really know that could be a bunch of neurobabble. You know, I mean it's, there is some sense to that, but it's like there's really a tremendous amount of mystery and complexity. So I'm wondering if you can speak to sort of embracing that complexity and embracing that from a research perspective of not jumping to try to oversimplify this whole thing. Okay, you have this chemical and affects that molecule in the brain and it's got a serotonin receptor and boom, you know, this happens. But to more embrace the complexity of kind of what you were referencing.

Right. Well, I think this gets back to kind of a principal question of, you know, what are we doing here? What is valuable to us? And there's a theme that I see come up a lot which was incredibly pervasive in my medical training. And it's kind of, it's necessary for conventional medicine to work, which is the best thing to do to solve for a health issue is to target a receptor and suppress, usually suppress, sometimes activate whatever pathway has gone awry. And you know, so we think about this in the context of let's say a person has High blood pressure pressure. So we say, well, your blood pressure is high. We have a, a drug that can act on calcium channel or ACE inhibition or a beta blockade and that'll lower your blood pressure and check the box and send you out. We know that that is effective because it's such a. It's a sledgehammer, right? It goes in there and it basically binds to and changes these receptors around the body. And it does work. I mean, if you've been in the ICU and you've pushed some of these drugs, you'll see instant effects on our physiology. And that's great. That's what you should do. In the scenarios in which things get extreme, where I think it gets a little bit more complicated is in the state of mental health. And the reason for that is we kind of operate in this western version of diagnostic codes. And so we'd say, well, this person has been feeling sad for the last two weeks. They've had a loss of interest in their usual activities. They're feeling guilty, they're not eating as much, they've slowed down, they meet the criteria for a major depressive episode. So that means that I can give them that diagnosis. I can put them in the diagnostic code in the computer, and then I can put them in the treatment algorithm that includes psychotherapy and basically psychiatric medication like an ssri, and that's depression. Now, over here, this person's been feeling a bit more concerned about the state of the world. They haven't been able to accomplish the things they've wanted to because they've been so nervous about stuff. This person over here has generalized anxiety. So I know their algorithm is a little bit different. And then there are, you know, a whole bunch of different kind of in betweeners. But thinking about those as kind of two of the major mental health conditions, there's no scenario in which going through those questions can in any way approximate what is happening in the human brain. And something we've seen recently is this destruction of the idea that serotonin issues explain depression. There was a recent umbrella paper that was published last year that kind of looked at the available data as to whether serotonin and serotonergic hypotheses were basically the idea that serotonin receptors and changes therein could explain depression and said, no, there's just not good data for this. Now, that challenges a model in which we want to treat mental health conditions like we would something like a blood pressure problem, which is, this person has high blood pressure. We know that there is this receptor when we Target the receptor, the blood pressure comes down. Because if you think about the drugs we have for depression right now, in theory, a SSRI selective serotonin reuptake inhibitor is supposed to target the receptor for serotonin. It is supposed to increase bioavailable serotonin, basically in this synapse, so that the postsynaptic receptor can pick up more serotonin and therefore a person feel less depressed. But when you look at the data, doesn't seem like that's what they do, and it doesn't seem like that's the mechanism of depression. So they may do a number of things. It's interesting, SSRIs may have an anti inflammatory effect, they may have a metabolic effect, they may have a neuroplastic effect, may upregulate bdnf, so on and so forth. But the point I'm making here is we can't assume that mental health issues or brain issues are anywhere near as straightforward as something like blood pressure. And even blood pressure is really complicated. So as much as we want to find a receptor or find a pathway that explains depression anxiety that we can target with anything, whether it's a psychedelic or a conventional pharmaceutical or mindfulness or whatever, it kind of dilutes the truth of it, which is our mental state, our brain state is an incredibly complex thing that is super dynamic. And it also takes away from this idea that the optimal state of brain function and mental health is not one in which, which you're just solving for one variable. Right? So to be human, to have a life experience is not to be fully happy all the time. It's to have diversity of how we feel, it's to experience sadness, but not let that sadness pull us down to where we're there every day, all the time. There are absolutely instances where I think it is the correct next thing to get somebody on a pharmaceutical as soon as possible. So especially something like suicidality, you know, you don't want to be messing around and saying, look, you should be more mindful when a person is actively suicidal. But I think as we look at, you know, what it is that allows us to really flourish, to have satisfaction in life, it isn't just pure happiness and bliss. That doesn't make any sense. And it's also not just amping up the levels of a neurotransmitter to the point where, you know, we would say, well, you're taking care of. So I think it is simultaneously important for us to investigate the pathways that are involved in molecules like psychedelics, because in order to gain more widespread acceptance and availability, it's necessary for doctors like me to say, well, you know, at first I thought that these were just drugs that people used at raves and that they had all these crazy, terrible brain effects. But now I understand that psilocybin has a 5HT2A receptor agonistic role. And I know that that is a receptor that is tethered to a molecule, serotonin, that I know has something to do with mental health. So I could see the utility in prescribing this. Oh, and by the way, Jeremiah, New England Journal, Lancet have all published papers to show that this is an efficacious therapy.

But and I think this is an important point here, is you have to save room for the magic, because at the end of the day, we are not just the composite of neurotransmitters. You have to be part of something bigger than yourself. And so simultaneously, I think it's important to do the investigation. But I'm scared about a scenario in which psychedelics become purely medicalized, where you go into the clinic and you're given a dose of a chemical and then you're basically told, go on with your life. Because I think we would all agree, and this is in the context of kind of the setting for psychedelics being so important. If the setting that you're returning to in the modern world is a toxic one in which every environmental factor is setting you up for worse mental health, you know, all the agonism at A2A receptor is not going to matter in that larger toxic load. So I think it's important then that we have still have these conversations about how do you connect people with something bigger than themselves. And psychedelics do provide a gateway for that that can happen inside the bounds of one's own mind, which is really interesting, right? So usually to kind of have these awe inducing experiences, to have these moments where you appreciate our small role in the overall universe, you need to be out doing something and taking in new data. You might be looking in a telescope, you might be at an amazing concert, you might be looking at the sequoias, redwood trees that are so big, or you might be looking out over the Pacific Ocean. But psychedelics let you have that experience in your own mind and provide people with the understanding that there is more to this whole thing than, you know, social media likes and the specifics of whether your boss likes you and all these other things, things that are real concerns for many of us, but that get put a little bit in their place when we Connect to something bigger than ourselves. So again, kind of a more, maybe a more comprehensive answer than what you were looking for. But I think, yes, we need to be looking into the mechanisms. When I get up on stage and talk at a conference and I'm talking about glutamate and serotonin and neuroplasticity, I think that's the message that many academics need to hear to understand, understand it through the language that they speak, which is peer reviewed science. But when I'm talking to a friend or family member and they're saying, what interests you about psychedelics? I'm not talking about that, you know, I'm not talking about inhibitory GABA neurons. I'm talking about there are very few things in life that right now seem to provide an opportunity for us to understand what it means to be human and have meaning in life.

That are so reliably available in, in the context of a, as in the context of a psychedelic experience. And I'm talking about the fact that we cannot go on just saying it's okay for so many people to be suffering for so much of their lives and restricting access to potential life saving medications simply because we're uncomfortable with the idea that something alters our mental state. Like how can we allow for alcohol to continue to be legal when we know that it contributes to hundreds of thousands of deaths each year?

But where psychedelic use to date, when you look at these severe negative outcomes from studies, we're talking about the level of case reports when we know that hundreds of thousands of people are using these medications in the United States each year.

Well, I really just appreciate, again enlarging the conversation. And you know, interestingly, personally, I've had some very profound psychedelic journeys with the eye mask on the music, so very much an internal journey of the mind. But I think some of my most powerful psychedelic journeys have been out in nature. And you know, and I think that connect coming back, that connection with the natural world, that's one of the things that so many people report that has shifted their perspective on who they are and their sense of well being and their sense of okayness and safety and so forth forth is feeling more connected to that, to the natural world. And that seems to be a theme running through our conversation. We're towards the end of our time here, Austin, but I wanted to. You mentioned epigenetics before and the epigenome. And you know, this is a field of science that's so enlarged our understanding of human health and both mental health and physical health, longevity, so many different Things. And so I wonder if you could talk about the relationship between epigenome and psychedelic. And my understanding, you know, we tend to want to think of things that, you know, have analogies and metaphors. And so with the computer is. Is a, you know, great metaphor for the brain and the mind. And we maybe even think of the genes that are, you know, there in our genetic code, in the DNA in the cell, that they have these little switches on them that are the epigenetic switches or something that. But I. My understanding of the epigenome is more of a field of energy that's impacting the gene expression within the cells of our body. And. And so again, coming back to this transfer of data and energy, I wonder if you could talk about psychedelics in the epigenome.

Right. Just as a quick background here, because this is a relatively.

Poorly known topic. So epigenetics is kind of the idea that our DNA use is driven by things that happen on top of the DNA. So even if your DNA is relatively fixed, meaning you have 20,000 or so genes, and those genes are more or less in the same places, we know that those genes expression, meaning taking the data from our DNA and converting it into proteins, converting it into pathways that affect our bodies, are largely flexible based on how we interact with the world. An epigenome is basically the idea of all the things that go on top of the DNA that can modify the way that it's being used. Epigenetics is the idea of. Of, you know, you can change the way your DNA is being used based on basically lifestyle and other environmental variables. So data on epigenetics is still pretty new, but we have seen from a number of studies that people's epigenome changes based on environmental effects. One of the areas that is probably most relevant to this conversation is adverse early life events or adverse childhood events. And heavy stressors seem to change our epigenetics such that they can impact our health later in life. And importantly, epigenetics kind of by definition means these are inherited changes. So it's not just the DNA has changed for a day, and then it goes back to the. Or the DNA use or the way it's being used. It's changed for a day and then goes back. It means that these are changes that either exist after a cell divides, so it creates the same changes in a new cell or even transgenerational, meaning a mom could pass on epigenetic changes to her kids. So really interesting stuff. And it's. It's definitely revolutionizing the way that we look at health, medicine and environment as far as how a person can change over their lifespan. Because it has been the case and basically was the case even when I was in training, which was not too long ago, that we looked at nature and nurture as kind of two different things and there were relative contributions to each of those things. But now we understand, understand that the genes that we're born with, the DNA that we are born with, as much as that isn't necessarily being changed. It almost doesn't matter because what we are doing is changing the way it's being used. And that's more important. Real quick point here. There are still a number of diseases that are genetic diseases that we haven't necessarily solved for. And we can't just say, well you can epigenome your way out of blankety blank, it's a genetic disease. But it is the case for most conditions that have a genetic component. We believe that epigenetics can change aspects of that. So this is changing, it's revolutionizing kind of the domain of health. Where I think there's some really, really interesting kind of tie ins to our discussion here is if you think about how psychedelics seem to work, we'll just cover here a couple of the mechanisms. So we said that basically the 2A receptor for serotonin we see said there are perhaps some additional changes to neuroplasticity. We know that maybe the sigma 1 receptor is involved, we know that maybe there's some immune effects, but these are all kind of more short lived effects. Meaning if you were to look at levels of psilocybin in a person's bloodstream, a person would have a psychedelic experience and then maybe we'd say there's some changes in serotonin binding receptors and so on and so forth. We wouldn't necessarily expect for that to persevere for years. And yet what we've seen pretty consistently, consistently across domains like ayahuasca and psilocybin is that a single dose of a psychoactive medication may have mental health benefits that last four years after the experience. So there's kind of this question about, you know, as much as it's nice to think about serotonin is serotonin are changes in serotonin and receptors that happen after a single dose of a psychedelic sufficient to explain why somebody years later will still be experiencing ongoing mental health benefits from one dose of psilocybin. And I kind of feel like the answer is no. Right. So there's probably more going on now what that more is, but we don't know. But one of the potential explanations is epigenetic change. Because if you think about what would happen if you modify the epigenome, basically, if you change the way that the DNA is being used, used, then you could set up a change that lasts for an indefinite amount of time because you've kind of gone to the source. Right. You've said, we are going to change the way that your DNA is being transcribed, translated and used in the body. So that's some really, really interesting mechanistic idea. Now, what do we know about psychedelics today? It's still pretty limited as far as human data showing that psychedelic use impacts epigenetics. There have been a couple of studies that have kind of questioned how this may be possible. And there was one study that was recently published looking at whether certain epigenetic regions might predict people who got benefits from mdma. What I do think is the case, or what is the case, is that there are a number of pathways that psychedelics can activate that we know are involved in epigenetic modification. So. So immune pathways, serotonin pathways, metabolic pathways, these are all ways in which the epigenome can be activated and modified. So I think we have some mechanistic evidence there. It's also the case, and I'll just bring this up, which is if you think about what a psychedelic is when it comes in its more kind of natural state, let's use ayahuasca as an example. So an ayahuasca beverage is not just the kind of MAO inhibitor and the dmt, which we would think of as the psychoactive components. So the DMT is the piece that's psychoactive of the MAO inhibitor is what makes it last longer. But it's also filled with polyphenols of all things. So polyphenols. We have better data than we do for psychedelics that appear to impact a number of pathways involved in epigenetic expression. So kind of the idea that I would float out here, and this is an area of active research, I'm actually involved with a team that's trying to look into this right now, is this question of if we're curious about how a single dose of a molecule can have effects that last for years, we have to be curious about how that happens. Now, you could go to the psychological aspect of it and say, well, when that person had this profound transcendent experience, we know that that tends to predict the people who get remission of their depression, let's say for a few years. This isn't Necessarily the case based on the data. But let's say that you could make the psychological correlate, which is you really need to have that deep kind of imprint from that meaningful transcendent experience to have the highest benefit as far as a 2, 4 year time frame. What is the biological correlate of that psychological experience? What is being changed in your body that basically relates to the intensity of that? And it may be epigenetics, which is really, really interesting. So the epigenetic imprint here may be the physiological or biochemical core correlate of that intense, meaningful, transcendent experience, which I think really just kind of is, is a beautiful way to describe this. Because in essence, what we're saying here is that your DNA expression is, is plastic, that you're actually changing kind of the core aspect of what we thought was the.

Unmodifiable aspect of humanity, which is you have your genes, you have your DNA, that is what you are, and there's nothing more that you can do. So I think it's kind of a beautiful thing. The one other thing I would just put forth, there was a opinion paper that was written that I thought was really interesting, which was specifically looking at trauma and mdma. And so where we started this conversation was the idea that epigenetics are correlated with trauma. We think that severe trauma may have an epigenetic imprint that lasts for years, potentially decades, potentially transgenerational. Is it possible that the way that certain psychedelics work is by removing the unhealthy epigenetic marks? And that's a really, really interesting question. Is it possible that how MDMA is able to create enduring effects is that it goes in and removes these epigenetic trauma marks on our DNA and in doing so kind of changes the way that our brains work. At least it's something to chew on for the moment. I don't think, as you already said, we don't know. We don't have the answers as to how exactly psychedelics work. But I think being curious about it and as somebody who does research and is generally curious about science, this stuff is fascinating. So you'll hear more about this in the years to come. Maybe this is the first time people who are listening have heard of the term epigenetics. Probably the first time they've heard of the term epigenetics in the context of psychedelics and polyphenols. You're going to hear more about that.

Wow, this has been so incredibly rich and so incredibly helpful. We could do a whole nother interview. We could do a whole nother conference on epigenetics and psychedelics. And there's so much, you know, our awareness around traumas increased so much in the recent decades. And now our understandings of intergenerational trauma and the possible one of the transmissions of that being possibly epigenetically. And of course, now a lot of the mental health situations that are being addressed with psychedelics, the underlying root causes often have to do with trauma. And of course, there can be all kinds of issues around intergenerational trauma that is racially based and around marginalization and the impacts of various kinds of oppression. So this is an incredibly rich area of exploration and would love to have another conversation, go further with you about this. We'll have to create that opportunity. But thank you so much for everything you've shared today, Austin. And how can people find out more about your work?

Yeah, my website is a very original name. It's austinpromotor.com and I have a newsletter there if people want free information on some of the things that we've been talking about today. I do some kind of, I guess, independent research, so you can look for me in PubMed if you want. And I am working on this study with Big Bold Health is the immunity company that I work with right now. So Bigbold Health.com is where you can find out more about the research that we're doing specific to how polyphenols may regulate our epigenetics. And so we're preparing that for public health location now.

Wonderful. Dr. Austin Promier, thank you so much and please be well and we'll. I look forward to our next conversation.

Me too. Thanks for having me step into the.

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