Psychedelics, Spirituality, and What You Need to Know About Depression – Dr. Charles Raison – HPP 57

SPEAKERS

Dr. Charles Raison, Dr. Will Van Derveer, Keith Kurlander

 

Dr. Charles Raison 00:00

It tends to increase with modernization in general. And it, of course, increases with societal stress. There’s no doubt that it has a huge effect. In our lives, both depression and suicide have been increasing. I mean, there’s some evidence depression has been increasing for 60-70 years now. It certainly seems to be increasing in the last 20 years in the United States.

 

Dr. Will Van Derveer 00:22

Thank you for joining us for The Higher Practice podcast. I’m Dr. Will Van Derveer, with Keith Kurlander and this is the podcast where we explore what it takes to achieve optimal mental health. Hello, everyone, and welcome back for another episode of The Higher Practice podcast. We’re very excited about this episode, because our guest is so illustrious, he is for sure one of the big minds behind in the research space, the new definitions of mental health and the root causes of mental illness. He’s had his hand and a huge array of different aspects of trying to understand what’s really happening, particularly in depression, a far ranging and really bright creative mind, Dr. Charles Raison. I really enjoyed this conversation. We covered a lot of different areas, and in particular, the connection between the immune system and the functioning of the brain, which is a really hot frontier and understanding what can go wrong and how that can present with symptoms of depression, anxiety, insomnia, etc. Dr. Charles Raison is the Mary Sue and Mike Shanin chair for Healthy Minds, children and families and Professor of Human Development and Family Studies, the School of Human Ecology and Professor Department of Psychiatry School of Medicine and Public Health, University of Wisconsin at Madison. The Web of Science named him one of the world’s most influential researchers, with nearly 11,000 citations in the decade proceeding to 2019 and 137 publications. Dr. Raison serves as the founding director of the Center for compassion studies in the College of Social and Behavioral Sciences at the University of Arizona, and is on the Scientific Advisory Board of the US Sona Institute, which is a notable psychedelic Institute. Dr. Raison is internationally recognized for his studies examining novel mechanisms involved in the development and treatment of major depression and other stress related emotional and physical conditions, as well as for his work examining the physical and behavioral effects of compassion training. Let’s welcome Dr. Charles Raison to the show.

 

Keith Kurlander 02:53

Thanks so much, Chuck, for being on the show.

 

Dr. Charles Raison 02:55

My pleasure, man.

 

Keith Kurlander 02:57

Yeah, it’s great to have you and Will and I have both obviously been following your work for a long time. We really appreciate getting to talk to you here. I thought a really good kind of jump off point is just to find out a little bit more about you. You’ve really dabbled in a lot of different areas of research and psychiatry and I know you’re researching psilocybin now about heat and gut brain connection stuff and just so many different really cutting edge areas. I’m really curious to hear a little bit about your personal story of what’s going on and how this all happened. How is it for you?

 

Dr. Charles Raison 03:33

Yeah, well, so you know, people come to me for advice. A lot of people that are like docs, because I’m a doctor, I’m an MD and a psychiatrist. And so people come sort of wanting to know how they can get into research and the first thing I tell them is, don’t ever do what I did. It was this crazy combination of mostly luck and timing. And, you know, because I’ve been in a bunch of different academic sort of locations in my life. And sometimes I’ve really prospered and sometimes I haven’t prospered. And that’s a testimony to the fact that I’ve had this very odd sort of path through things. That is not something that you’d ever want to try to repeat. So, I was a journalist. Initially, I wanted to be a novelist, and I actually packed up and moved to Denver. So I was in you guy’s neck of the woods in the early 80s. I discovered that I had no talent for writing novels whatsoever, and sort of had this revelatory experience. Literally, one day it was Christmas Eve in 1984. I was on a road down in Texas. I had been going through really tough times in my personal life, a breakup of a marriage and had gone into psychotherapy for the first time and I really was impacted by it. And I had just like flash, I could be a psychiatrist. I could go to medical school and become a psychoanalyst, you know, and I made this absolutely spur of the moment decision, that’s what I’m gonna do. And then I had to figure out how to go back and take my science classes and I ended up having to do a postback program and barely got into medical school because people thought I was crazy. Because I was a journalist, I didn’t have any science background, but, you know, I did well and ended up at UCLA still sort of thinking I wanted to be a therapist. Then I went through residency and discovered I didn’t like therapy. Actually, I don’t have the patience for it. I ran the emergency service at UCLA. So I was seeing all really, really severely psychotic, mentally ill people. And that’s where it was. But I had always had this sort of underground interest in spiritual stuff. I’m not particularly religious, but you know, I guess I’m not a lot of people. I have the urge and not the certainty, but I had the sort of long connection with Buddhist thought. And in the mid 90s, I’d finally gotten old enough for some of these core very straightforward Buddhist ideas about the mind that really struck me. I saw it myself. So I started hanging out at a Tibetan Buddhist monastery down in Southern California just casually, and through a long series of crazy things they asked me eventually. I ended up hosting a big fundraising dinner for the Dalai Lama’s sister at UCLA. So I got to know the Dalai Lama’s sister. And we kind of hit it off. And she introduced me to these Tibetan Buddhist monks that were working in western environments. So I began to sort of Crash Course, just sort of hanging out at dinner with these guys. They taught me a lot of stuff about esoteric Tibetan, Buddhist, especially tantric practices. And I became kind of oddly obsessed with some of the practices that manipulated thermal regulatory pathways in the body to produce these profound sort of euphoric mental states. Don’t ask me why. I don’t know but there was one particular tuma that I became so obsessed with that I said, I want to study this from a Western perspective. These guys are onto something. They’re doing something to manipulate their body to produce these changes in their brain and my buddy in those years, Lipson Robgave, a brilliant Tibetan philosopher and doctor and Western psychologist made a comment that really was the launch of my career. He said, you know, Chuck, the reason that sutra mindfulness practices take like trillions of years to produce enlightenment in our system is because the mind is so insubstantial and flighty, good luck trying to control it, right. On the other hand, tantric practices harness bodily energies. Now they had a very different idea of what bodily energies are, but very clearly these sort of bodily energies, you can manipulate them. And when you do that, you can drive the mind into these sort of fixed states that are hard to asail, either with mental activity or things happening in the world that basically produce, in this case, sort of blissful euphoric state. And I was seeing a lot of very sick manic patients at the time. And so my initial interest was like, Whoa, these guys figured out a way to make people manic. If we can understand how you use the body to produce these states, maybe we’d learned something about that. But over time, it morphed into this idea that perhaps bodily processes represented something akin to deep brain stimulators. Things that might be harnessed to put the brain in more stable positive mood states. That one sentence launched a thousand ships for me so I said I gotta do this. UCLA was not a conducive environment in those years for that kind of work for a guy like me, who had no particular training in research. So I packed up and moved to Emory University in Atlanta, and was fortunate to fall in with, I think, really the world’s leader in the secondary mineralogy world, certainly in a psychiatrist’s perspective, Andrew Miller, and remarkable Tibetan Buddhist studies program led by my very close friend and colleague, Lobsang Tenzin Nagy, and I retrained. I became a scientist of sorts. I really only was able to do that because I’d been a journalist, I think I knew how to write. And so I know how to write up other people’s ideas in particular, Andy Miller’s, you know, which I shamelessly stole, and that was it so then I began to do this research, begin to get grants, but always you’re right that I’ve done all this stuff but there’s always been this sort of theme behind it. A couple of themes. One is sort of what is the role of consciousness in human well being and how do mind body or brain body interactions—how do they play into that and how can bodily processes be accessed to sort of change conscious experience? Really, if you look at my work, almost all of it circulates around just those couple of ideas.

 

Keith Kurlander 09:11

That’s a great story. I love your story.

 

Dr. Charles Raison 09:13

Great strange story, yeah.

 

Keith Kurlander 09:18

You know, I’m going to ask a different question. I always love where these things go. I’d love to hear your thoughts with everything you have studied and where you started on – What is consciousness? What is your take on that with everything, you know, at this point?

 

Dr. Charles Raison 09:34

Well, okay, so this is really interesting. I have gotten more and more interested in that question over the last five years. And the reason being, of course, is because well, let me back if you’ll bear with me, I’ll back up for a sec. So I started my career because I was interested in trying to study these esoteric Tibetan practices from a Western perspective. So I always had this bias that people had discovered these potential things a long time ago, that sort of low hanging fruit. Things you could do to produce these very powerful, sort of psychological states. And so, as I did all these psychoneuroimmunology and all this, I began to realize that a lot of these ancient practices tapped into these things we’ve been talking about, so I began to study them, like you mentioned, heat, hypothermia and, you know, about five years ago, I fell into an opportunity to get involved with the psilocybin work. And of course, although that’s not a bodily practice, per se, it’s definitely an ancient practice, right? People have been doing this for thousands of years. So that’s how I kind of morphed into the psilocybin work was this interesting sort of recuperating or retooling ancient practices for the treatment of depression. But psilocybin, it seems very clear from the data we have thus far that it works by inducing these really shocking, surprising, powerful, immediate psychological experiences then there’s something about the experiencing of those experiences that often change people. And so, of course, this gets really interesting then because these are conscious experiences and so we should already know that consciousness might have relevance to mental illness or mental health because, I mean, posttraumatic stress disorder, clearly is a disorder where something happens to you. You have a conscious, horrible, surprising, uncontrollable experience, and then you’re different afterwards. And there’s some data to suggest that if you block sort of conscious awareness of the trauma, you reduce the risk of PTSD. So it shouldn’t be surprising that psychedelics produce sort of the same thing in reverse, you know, shocking, powerful, surprising, out of your control, in this case positive. So I and my colleagues in the University Wisconsin have gotten really interested in this question of; wow, so psychedelics might serve as a probe to understand the reliable induction of conscious states that might have these real therapeutic potentials. And also a way to see maybe consciousness, whatever we mean by that, has the ability to actually interact with matter in a reentrant way and change people. So this is an ancient philosophical problem in question but we decided, we were working on a study, which we haven’t started yet, but we’re pretty far along in getting set up, especially before COVID, where we’re going to actually try to take people that are depressed and give them psilocybin and see if we remove the conscious experience, Does it still work because of an antidepressant? So when we started working on this study that we call the recap study, we realized that we didn’t quite know what we meant by consciousness. So right now, you’re conscious, you have a sense, right? I mean, people are gonna say, nobody knows what consciousness is. But the definition is often something like what it feels like to be something to be somewhere. You have a sense that there’s an awareness here. You know, when we’re awake or in dreams, that sense is always with us. Interestingly, though, we don’t remember most of what we’ve experienced in our lives, but there is another aspect of consciousness which is memory and narrative reconstruction. So a lot of who we think we are and a lot of how we interpret the world at this moment has to do with what we’ve experienced in the past and some of that is programmed unconsciously. But a lot of it is conscious. I see a certain thing and I go “Oh that reminds me of when”, and it changes presently. So consciousness has these two aspects, what they call phenomenal consciousness, which is just a simple sense that you have a sense of awareness at the moment, and Access Consciousness, which is the consciousness that you can consciously Access Memories and those sorts of things. So, I think that whatever it is, consciousness is some combination of those things. And so we’re going to basically, first we’re going to remove the memories and see whether it still works if people can’t remember their psychedelic experience around this idea of literally testing. If you cannot remember it, and it works, it suggests either that that raw basic consciousness at the time is doing the trick, or that it’s just basically a sort of deeper level biological thing, the consciousness gets thrown off like smoke at the back of a car. On the other hand, if you can’t remember your psychedelic experience and you say I don’t feel any different. I don’t know what you did to me. That would really suggest that there’s something about the memory, that part of sort of access consciousness that is key for this particular therapeutic intervention, but also perhaps for certain types of transformation. Now, there’s a complexity though, which is, as we started working on this, it’s very, very difficult to say. So let’s say that just the conscious experience that you have during a psychedelic experience is enough. You don’t have to remember. Is it the awareness? Is it this immaterial factor that’s doing it? Or is it the brain changes that produce that factor? And trying to figure that out is very difficult. So it’s really interesting when you try to test consciousness. It’s very hard to separate neurobiology from phenomenology. So, really all I think we are trying to do at this point is say, there may be a neurobiology that is mandatory that manifests as consciousness, but you start getting into these circles that are really complicated but really cool. long answer to your questions.

 

Keith Kurlander 15:07

No, I think that’s a great place to go. I’m sure Will, you have some burning questions from this. I love this rabbit hole. I mean I’m all going well, how do we even know just because we’ve moved memory that we’re removing the phenomenological experience.

 

Dr. Charles Raison 15:21

You’re not. Well, we don’t know. You’re not removing the experience as it happened at the time. And you may not be removing unconscious elements of it. Of course, but if we’re interested in consciousness, you’ve at least removed some of that but you see, you begin to think about it. I mean, I came into this. It’s a really simple, straightforward idea. People go, “Oh, that’s interesting”. But you start digging, and it gets complicated really fast. I mean, it’s really interesting. Consciousness is sort of, the more I’ve read about it, the more I’m just befuddled by the mystery of it. Descartes was probably right about this, It’s the one thing we know for sure. The one thing you can claim to know for sure, is your conscious experience just by tautology, because you’re having that conscious experience. Now, the experience is almost certainly not what you think it is. It’s not continuous. It’s not as solid. But there’s something there and past that everything else is supposition. I mean, this is the old phenomenologist argument that you may exist, I guess, you know, I mean, I’m talking to you. But I act like you exist. But I’m not really sure about that. And you act like you’re conscious, but you could be a really super smart bot. Right? So on the one hand consciousness seems unfindable by science, and it’s been often relegated to being the sort of worthless epi phenomenon. And on the other, when you get down to it from a certain angle, it’s the only thing that is actually real that we can know. And by the way, since we’re talking about this, I have a colleague at University of Wisconsin named Julio Tunoni who is probably the world’s most important consciousness researcher right now. He’s the originator of something called integrated information theory. And the reason I’m thinking of him is the work is very mathematical way beyond me. But he starts with this idea. It’s really interesting, you know, so most scientists say, well, let’s understand the structure of the brain and maybe that’ll tell us something about consciousness. He reversed it. He said let’s start with the structure of consciousness, and see if we can identify structures in the brain that would be able to manifest that phenomenon. Fascinating, right? It totally turns it on its head. And it’s gotten a lot of traction, I mean, Templeton has put in $10 million to test the theory versus in much more sort of, you know, started with biology based theory. So it’s really interesting stuff.

 

Dr. Will Van Derveer 17:49

Wow. There’s so many different rabbit holes, we could go down.

 

Dr. Charles Raison 17:51

I know many, many.

 

Dr. Will Van Derveer 17:52

It’s wonderful to have you. You’ve been one of my idols for a long time, Chuck and it’s just wonderful to get to share some time and pick your brain here. To hear a little bit about how things work. One question that comes up for me, sort of like the issue, I guess this leads into, for me the issue of healing, depression and the role of consciousness or maybe, and this might be a separate phenomenon, but the role of remodeling thinking patterns. And then this other area of your research in the past anyway of looking at the role of inflammation, the role of supporting cells in the brain, astrocytes and microglia and how it all fits together. I guess I’m wondering if you could speak to that, in terms of your current perspective about that.

 

Dr. Charles Raison 18:49

Yeah, sure. So, the microglia, the question of neurons and microglia, I try to stay out of the brain to the best of my ability. So unfortunately, that also means that I have a lot less expertise in those areas, although certainly I think one of the surprising things in affective neuroscience over the last 15-20 years has been this sort of realization that the abnormalities, the generalized abnormalities you see in the brains of depressed people tend to cluster more around glial cells than neurons. We always thought glial is glue that these were just sort of supportive structure cells. I mean, that’s clearly not true now. I love this idea that neurons are essentially digital, which allows them to send messages rapidly and with fidelity over longer distances, but that more localized information processing in the brain, a lot of that stuff is done by astrocytes, which are sort of analog in their information processing. So you get the sort of cool mixture of analog and digital which if artificial intelligence ever produced this sort of Cyborgian things that are part human part machine, they will build upon some idea like that right? It may be that the analog nature of the brain is part of what contributes to its ability, the human ability to have consciousness. You know, I mean, it’s beyond us not to digress on this, but real quickly, I’ve kind of got a hobbyist interest in artificial intelligence. And there’s this assumption that consciousness and intelligence are inextricably linked, but it’s clearly not true. Right? When Tunoni and I talked about this, one of the things we talked about is the very real potential future of super super intelligent creatures, but nothing home. There’s no lights on anymore. No felt sense of what it’s like to be that but way smarter than we are way better to solve problems, which to me is one of the scariest of all future scenarios, kind of the AI zombie world. But he said it may be actually that the glial cells and that sort of analog nature of things is doing something contributing to the fact that evolved nervous systems have the sort of quality of theirness that purely digital things don’t have. So interesting and of course, there’s a real link between glial cells and inflammation. So, microglial cells are sort of the macrophages of the brain, but they are their immune cell lineages. They play an essential role in the development of the brain in utero. We think of them as supporting brain health. When things are quiescent, when inflammation occurs in the body, they can be activated, there’s still a lot of debate though about whether that activation, whether they’re the real bad guys, or whether it has to do with signals coming in from immune cells in the periphery or immune cells that actually cross the blood brain barrier. But the tie with inflammation and glial cells is really tight. So for instance, we know that one of the things in animal models at least that inflammation in the body does is that it signals astrocytes to sort of reverse their glutamate reuptake pump, you know, the sort of cycling of glutamate and GABA, and generally, astrocytes sort of seem to function like like vacuum cleaners. They surround synapses and they keep the glutamatergic signaling within the synapse, regulated they don’t let it spill around because glutamate is hot and toxic, but inflammation actually reverses that reuptake pump so that the astrocytes will actually spew glutamate out into the extracellular space. And one of the really intriguing findings and ideas is that when that happens, there’s actually NMDA receptors not just within the synapse, but extrasynaptic. So NMDA receptors within the synapse when they’re stimulated they do these things through ampa. But they basically sort of drive BDNF production and sort of that’s how long term potentiation happens. But when the astrocytes reverse their polarity. Spew the stuff out and the glutamate interacts with these extra synaptic NMDA receptors. They have the opposite effect, they actually turn off BDNF. So the end result of that is that things get taken offline. And this has never been proven, but my little evolutionary theory is that they do that as a way to avoid pathogen manipulation. So if you look at the areas of the brain that are most susceptible to sort of changes with inflammation, there are areas that have a lot to do with decision making and behavior. And one of the greatly underestimated sort of things that goes on in this interconnected world is that pathogens can drive host behavior for their own benefit. Certainly toxo is a classic example where it seems to change human behavior. That’s sort of an evolutionary dead end kind of a spandrel. But you see that, and I think one of the things we’ll find over the next 50 years is that some of the things we think we’re doing are not us, it’s our central nervous system. It’s us. We’re like the big taxi cab being driven around by the microorganisms. So there’s that. And then, of course, it’s interesting, we’re still working. Your buddy and mine, Chris Lowry and I continue to work on looking at sort of the impact of some of these ancient practices or some of these bodily based things on immune signaling. And, in particular, we’re working, we’re gonna submit a paper pretty quickly, looking at the effects of heat hypothermia in depressed people on immune functioning. It’s really interesting. One of the things that’s emerging from that work is that some things that we think of as being beneficial for health actually seem to acutely activate inflammation, or at least activate aspects of inflammation that we generally think of as harmful, which is really interesting. So one of the things that I’ve sort of fixated on recently in the world of sort of secondary menology is this idea that inflammation may not be all bad, especially phasic inflammation may actually do things that are beneficial, and that some of these ancient practices that involve sort of adaptive stressors, like exercise, like heat, like fasting, but especially like heat and exercise may actually sort of physically activate parts of inflammation that may then have beneficial effects. So this idea that inflammation is always bad, that depression is an inflammatory state, that we should be giving people anti inflammatories is something I’ve really moved away from pretty strongly.

 

Dr. Will Van Derveer 24:54

That really resonates over here with kind of the perspective about resilience and how to build resilience. I’ve treated patients who were exercise addicts and they were tearing down their resilience. There’s kind of acute episodic challenges to the entire system. Not just on glial cells or the microscopic pathways of inflammation level, but also on the consciousness level on the existential level. I think it really brings more resilience and more pathway.

 

Dr. Charles Raison 25:30

This is really interesting, Wil. So usually you see people in Boulder, so no surprise, because you see people that are exercising so much that it’s damaging them basically. Right, exactly. So this is something I’ve gotten really fascinated by. I’ve really come to believe in the U shaped curve. That is, if you asked me to toss out a couple of slogans that mental health would benefit from the U shaped curve would be right up there. Because many of these things, maybe everything in life, but many things, if it’s too low, it’s a problem. If it’s too high it’s a problem. Exercise is a classic example. Right? You’re right. I mean, you know, elite athletes, man, they are right on the edge of going south. I mean a little bit more exercise and they get sick. I mean, the reason we talk about exercise is this unqualified good is only because we don’t exercise enough. You know, we’re all down on this side of the curve. And a lot of things are like that. You can see psychological stress, right? So I’ve gotten interested in this idea of hormesis that certain time limited measured challenges that are really detrimental at higher levels but at lower levels essentially can build up resilience, build up strength. We generally think of it as in relationship to that toxin or that stressor. But exercise, it’s just beautiful in so many ways as an exemplar of that where if you’re really sedentary, you go to part of the psychologically and physically, and if you overdo it, you go to pod and then somewhere in there, there’s this sort of level where you’re getting enough to maximally function and what treats me is that from an evolutionary perspective, that level is probably fairly consistent with what most humans did across most of evolution, not because how they live before was perfect, but because organisms that were genetically able to sort of optimize that niche, that opportunity, procreate, reproduce. So you know, over time that the organism begins to match the environment if you’re having to be active and chase down prey and all this sort of stuff. But then if you undershoot it, you fail. And if you overshoot it, you fail. So it’s interesting.

 

Keith Kurlander 27:30

I like the evolutionary conversation and maybe expanding on that a little around depression. So, as we’re seeing depression is, if not already going to be the largest global burden of disease on the planet. And really interested since you’ve studied a lot about depression, in your research, a couple questions. Is depression increasing over time? Is that what we’re seeing?

 

Dr. Charles Raison 27:54

Seems to be. Seems to be in some places in America for sure. Right in many parts of the Western World. There’s other places, there was just a large sort of study that came out. And I wish I could remember where it sort of wasn’t increasing. But it tends to increase with modernization in general. And it, of course, increases with societal stress. There’s no doubt that’s a huge effect. But yes, in our lives, both depression and suicide have been increasing for, I mean, there’s some evidence depression has been increasing for 60-70 years now. It certainly seems to be increasing in the last 20 years in the United States.

 

Keith Kurlander 28:28

And you’ve obviously delved pretty deep into biological aspects of depression. And I’m curious about your thoughts on whether we are facing a major sociological issue? Are we facing an ecological issue here? Is it all of the above or sociological issues?

 

Dr. Charles Raison 28:45

Yeah, it’s all like a kind of weird, perfect storm of things. Right? There’s probably 100 but you know, it’s interesting. COVID has reminded me of data showing that people that are sort of taking a pick out what I mean by this with people that are sort of lowered down, but think that they’re looking up are much more satisfied and happy than people that are up looking down. Right. And so, you know, one of the problems with being on top of the world is that it’s like being on the North Pole, every direction goes south, right? You know, if you’re on top of the world, there’s like many, many pathways down and not really many pathways up, which is sort of like a governor on human happiness. You know, I think, in general, many people in our world have this feeling that the best times have passed or the future is going to be frightening and uncertain, and that we’re sort of here looking down, right. And all of us, regardless of our political stripes, whether we embrace it or deny it are aware of things like climate change. And now COVID, of course, has really screwed things up because our entire world and everything we took to be solid has been shaken apart by something we can’t even see. This is going to cause a deluge of mental health problems. So on a sociological level, there’s this sort of that sense of, you know, are things going up or are things going down? If we, as a society, as a culture, think that things are going down in some way, generally, that’s going to in itself produce hopelessness and depression and fear. And then of course, there’s a lot of aspects of the modern world that are useful for commerce, but are sort of depressive. A lot of the ways we structure our social support systems, we can talk about that. There’s also biological things that I’m really interested in. So one of the things again that Chris Lowry and I’ve written a lot about is the fact that over the last 60 or 70 years, we’ve hugely disrupted our relationships with the microbial world. And overall, much to the good because prior to the early 20th century, about half the people born were dead of infection by the age of 17. And we now can feel that terror of infection in our life so it’s an evolved horror right? So the fact that we managed to develop antibiotics, especially, you know, sort of this liberating thing. But along with that, we kind of tossed the baby out with the bathwater. And we have so altered the microbial environment that we’ve also gotten rid of a lot of things that we co evolved with, and we need to function optimally. So this has to do with what the bugs that are beside us, but also the things in the environment around us. You know, we evolved in a world where a lot of microorganisms kind of modulated our immune functioning to reduce inflammation for their own purposes, not because they were trying to be nice to us, they needed to survive in our bodies, and they didn’t harm us or they helped us. We’ve disrupted so much especially on a society wide level. There’s ample evidence that this has produced a rash of autoimmune conditions, allergic conditions, asthmatic conditions, all of which are highly associated with depression, and probably with depression. So there’s, for instance, there’s data that C sections which totally changed the infant microbiota are respected. For things like depression and behavioral problems, we’ve not only disrupted our relationship with each other or radically changed them in the modern world, but we’ve radically changed our relationships with the microbial world. And really, I always say, to be human is essentially, that the essence of human life is to be in relationship with other humans and the bugs and microorganisms, that almost everything in our life boils down to those two, to managing those relationships. And we’ve so altered all those relationships that were really showing the wear and tear we’re beginning to get so far away from from the inputs that we’ve evolved to need to feel kind of normal and balanced and you know, satisfied that it’s set up this kind of whirlwind of sort of psychological problems,

 

Dr. Will Van Derveer 32:48

Thinking of our friends in the microbiome, I remember reading, I was fascinated when the book epidemic of absence came out by Moises Velasquez. He was talking about some of the things Dr. Lowery talks about which is, in particular, this is such a microscopic question, but I’m fascinated to ask you this about H. pylori, and I think the guy who got the Nobel Prize who discovered the pathogenesis of it, in terms of ulcers. But then we know that the timing at least there’s a strong association between this massive logarithmic increase in autoimmune asthma and autoimmune disease in the 70s around the time H. pylori was just eradicated and there’s some theory of allowing the human immune system to develop along with H. pylori up to a certain point where the risk of ulcers and stomach cancer increases and then maybe at that point, we should be eradicating H. pylori. Just curious your thoughts about allowing these old friends to exist up to a certain level and then the ones who are going to cause us trouble maybe we eradicate them later.

 

Dr. Charles Raison 33:59

Yeah, exactly. So, you know, before you had you to ask like, what are studies that I’d love to see done? A hugely important study in terms of mental health is looking at just this question, if we’re not going to live in a natural world, and the natural world kind of sucked too, to say people are sick or died, you know, it was good, but it was bad, it could be improved upon. But the way to improve upon it is not to just wipe everything clean. The way to improve upon it is to do exactly what you’ve suggested to literally test. Oh, you know, maybe children need H. pylori until the age of on average 12 and it should be removed, right? Overall, that trying to understand what the developing human organism needs in terms of microbial support and interactions from conception into adulthood is one of the great unanswered questions. I think because, you know, a lot of us throw probiotics down ourselves as adults, but it’s probably kind of a day late and a dollar short. The clear real permissive periods in human microbial interactions that occur earlier in life and that nobody really understands. Nobody has really studied their heart studies. Duke is yet to follow people for a long time yet to watch kids grow up. But this is one of the core questions in my mind is, if we’re going to live in an unnatural world, how do we intelligently and artificially, how do we intelligently but artificially increase the richness. Don’t just do something stupid, like kill all bugs, but do this and then switch it out? You know, hepatitis A same thing, right? So hepatitis A, in traditional times, was a childhood infection that was pretty mild. And it had really, you know, sort of seemed to have these immunomodulatory benefits. But God helped you get hypnotized as an older person in the modern world. It doesn’t kill you. It makes you wish you were dead, right. So, again, evolution is an imperfect beast. It never produces perfection. That’s why we don’t live in a perfect world. But it’s pretty smart. And it’s pretty wise, and it has a lot of these interesting redundancies, which make trying to understand how it’s working very, very difficult. But if you’re in a situation that you find pretty nice, throwing in odd things, and disrupting evolutionary sort of coevolved sort of interactions is a very dangerous thing to do. There’s a lot of roads down, right? If you like the forest, don’t go plant a tree from Asia, because, you know, if it’s got some nasty sort of invasive species in it, there’s a lot of ways to kill the forest. And so, we humans had evolved into a space. We were really nicely evolved and regulated into this sort of open space, but it was a space that had a certain kind of lifestyle and had a certain kind of societal, generally social organizations and certain types of relationships with the microbial world. And it could definitely be improved upon and we have improved upon it. But all those improvements often come with hidden risk, you see the immediate benefit, you don’t see the hidden risk, you know, COVID being the classic example, right? So we think that human interdependencies are a great thing in the world, culture is a great thing, and it is. But if you don’t think about the fact that we’re not the only beings in the universe, and if we don’t bring microorganisms to the table, we’re not gonna be able to do it right, because we did not evolve to exist, these massive sort of conglomerates that are at high risk from giant collapses from things like this. So again, it is directly relevant to what you’re saying. The real answer is it’s like a version, that U shaped curve. You know, it may be that h. pylori is really useful at some points, and then you pay a price for that usefulness that evolution was willing to accept. Maybe we can shave that price off and keep the benefit. That’s really what science should be trying to do in general.

 

Keith Kurlander 37:41

Yeah. I love that sort of symbiotic relationship you’re describing, of really working with everything around us, but trying to understand the ecology of the human being so that we can obviously tailor our existence in the most efficient way is what I think I hear you talking about. I’m curious about this, and you mentioned it, if you were able to fast track a handful research projects, like what are the handful or burning questions you feel like would really propel us forward in the mental health field right now that we getting those answers would really give us some significant headway here.

 

Dr. Charles Raison 38:28

Yeah. Well, okay. So let me narrow it down. Let’s just take depression as an example, because that’s really kind of what I understand. Or let’s say the type of emotional misery that when it reaches a certain level really impedes people’s ability to function, ability to find satisfaction in life. So I’m going to set aside things that look more like real illnesses like bad schizophrenia, a bad bipolar disorder but if we go up all the way up to bad depression, there are a number of things we really need to understand. Nothing is more important than trying to figure out what we might be able to do early in life to build resilience in adulthood. My chairman of Psychiatry at UW Madison, sort of sometimes, we’ll say that we’re like in college, is trying to treat everybody we’re treating has got stage four cancer, they are going to die, you know, you want to treat cancer. You want to prevent it first, and then you want to treat it really early on. We don’t have any early treatments yet. That’s a whole other story, meaning that just puts people on antidepressants early on is not necessarily going to help them. But what we do need is the ability to prevent these things or deal with them early in development so that people come into adulthood with sort of maximal resilience. That’s number one. And so, you know, trying to understand how we can optimize microbial environments is a classic example of that. And then of course, there’s all the human social environment. I am not a fan of genetic manipulations strictly because what we’re talking about, you think you’re changing one thing and changing something else. So you know, I mean, these forced evolution studies show that you think you’re trying to breed for one thing and you change the way the ears work and with Facebook and everything’s connected so much better to sort of build upon Evolved Human strength I think, try to just willy nilly rebuild human beings. And then I think on the other hand, trying to understand how to treat depression, once it starts is the other great thing. Now that sounds like you’re gonna like everything in the world. But I say this because one of the really distressing things that I’ve experienced professionally in the last five, seven years is the growing realization that, although people benefit from our treatments, and thank God, we haven’t had a depressant, they come with costs and risk that I had not appreciated, which we could talk about for hours, but basically, the data that if you come to see me as a young man, and you’re depressed, and I put you on antidepressant, and you actually feel a lot better, let’s say it actually works. The data that I now have provided you with something that’s going to really benefit you across your lifespan is really disappointing. And there’s increasing counter evidence that what may be happening is that once you start down that path, you kind of have to stay on it if you want to avoid being depressed again so that you end up sort of becoming this Cyborgian creature, it’s you and the antidepressant. And every time you try to stop the depressant, you get depressed again, the data for that is really distressing to me. And this idea, so you know, you think about depression is like this. It’s caused by stress, and it is a stressor. And so people come in, and they’re at a point in their life where they’re being pushed. And what we do as doctors is, you know, it’s the equivalent if you’re hot, cool it down. If it’s cold, warm it up. We say how can we make that pressure go? We’re going to take away that pressure with an antidepressant. A lot of times it doesn’t work. And that’s another problem. But what got me really interested in a distressing sort of way is what happens when it does work. So now I’ve put you on an SSRI, and all the things that really bothered you before then you go, I feel much better now. It’s all worked up. I wouldn’t get long in my relationship, but I’ve got other things in my life, whatever, you know. And so, many people find that depressing problems either vanish or mitigate. And then you go along, and everything is beautiful until either the antidepressant stops working, or you kind of flatten out Phil Dahl or you decide you don’t want to be on a pill for the rest of your life and you stop the antidepressant, and people have a high rate of depressive relapse. And you know, Peter Cramer to his credit with listening to Prozac back in the 90s. He recognized that the things only work when you’re on them. What he didn’t know was that stopping them may be a huge risk factor for worsening your depression. So this idea that the way to deal with things is always just to soften it up in mental health may have some real limits, it may have some real applicability just like antibiotics have costs. Nonetheless, if you’re dealing with a bacterial infection, by God, you better have an added biotic, but maybe you don’t want to put them in your meat supply in the same way. There’s times you just want to take the heat off people, right? But I’ve gotten hugely interested, like we’ve been talking about in this other approach, which is actually adaptive stressors. Are there ways that we can take these episodes and somehow, instead of taking it away in a very intelligent, cautious, safeway, push it to the point where there’s some sort of breakthrough, some sort of change, and we talk about perception and how people look at things in the beginning, you know, some way of changing people’s perception or their emotional state, that combination of things changing in ways that then make them more adaptive, more resilient, so that they don’t need some sort of outside stimulus from something that can add a depressant but you’ve done something pharmacological. Your behaviors are physiologically that sort of pushes the system and causes a reset. And now they’re in a different state. And now, they’re able to be undepressed based solely on the functioning of their brain body system. They don’t need continuing external input to maintain that new kind of homeostasis, if you want to call it that. Trying to understand whether that’s possible, how to do that, and better understanding when and how the costs of just medicating people and calming down for the rest of their lives, trying to understand those costs and ways to do the opposite and how to combine them I think is really going to those are the studies if I had like 100 million dollars, I would strategically fund those lines of research to try to help us build up our capacity to use these adaptive stressor based approaches that then are time limited and set in motion longer term resilient responses. Try to understand what are the risks and limitations of just medicating symptoms away and then just like with your pylori thing. Are there ways that we can best understand when to just medicate things away for at least a while and when to use these more adaptive stressor based approaches? Really, at the end of the day, if I live long enough and have enough money, that’s what I’ll spend my life doing.

 

Dr. Will Van Derveer 45:16

Thank you. Well, it feels like this adaptive stressor model really, really resonates, Keith, with how we’re educating people and the fellowship, and really inviting people to look at this bigger picture. And, and that leads me to the question of whether you feel, Chuck, like taking this approach of this more, maybe more informed or more sober approach around psychopharmacology and with the cognizance that there is a cost. Is this something that clinicians need to already be incorporating into their way of working with people at this point in time?

 

Dr. Charles Raison 45:56

Oh, yeah. Absolutely. So you know, we started this conversation with stories about my personal life. So I’ll tell you a story from my personal life in this regard. So I think all psychiatrists, well, not all but like many of us have struggled with depression. And one of the ironies of my life is that I spent my professional life in the last 20 years at least trying to find ways to replace antidepressants, while at the same time, personally, I’m like a poster child for these things, man. I mean, if I take an antidepressant, as long as it’s got a certain logic, we have to take components. I’m exactly what I described as me, all the things that are sort of subtle and all this comes like, oh, man, I just want to do my work and everything’s fine. And you know, it takes me back to a prepubescent mind state where I’m just excited about projects. And it’s great. And I lose these levels of emotional depth, which really sort of bugged me after a while, but I get side effects. I get sleepy sexual side effects, but it really is just a thing to experience this. And now about 6, 7 or 8 years ago, I was giving a talk in Colorado. With one of the great psychiatrists at the interface of Big Pharma and psychiatry getting requests, Jim, who is probably one of the most remarkable humans I’ve ever known. He’s like a legend. And the more you know, the more you realize the dude’s just a legend. We were walking around the Capitol in Denver, and I started telling him about, you know, I was taking this antidepressant. And he turned to me, he said, Chuck, that is a bad idea. And I said, What are you talking about? He said, should you know about Tardive dysphoria? I said, I have no idea what you’re talking about. And he said, there’s evidence that the prolonged use of antidepressants is not good for you, you shouldn’t be doing this. And it distressed me, man. It was one of the, you know, like one of these transformative experiences where we were talking about consciousness. We’ll see. I could see exactly where I was in front of the state capitol. I said, What are you talking about? He said, there’s increasing evidence that when you take these agents long term, it’s not good for your brain. You don’t want to do that. Well, you know if this guy had been a psychotherapist or if he was the sort of, you know, sort of anti med guy, whatever I would have been like, Yeah, but this guy, this guy is the probably the most prominent psychiatrist and champion of big time pharmacology. And so it was really impactful. And so thank you, Rakesh, for setting me off on this pathway where I began to really dig into the literature and begin to find this stuff. So, yes, based on that, and Rakesh would tell you the same that would when dealing with depression, what I said I think really should be now what we do. You don’t want to be stupid and withhold added depressants, but this idea of reaching for them always in a casual way, just to shut up the symptoms is probably a mistake. Again, I think antibiotics and there are some things like vaccines, which there are pharmacologic intervention, but they work by strengthening and already evolved protective mechanism, this case your immune system, right so you know, vaccines don’t go and kill or organisms, they’re cooler the organisms in your immune systems co evolved together. So there’s a strength there. The vaccine works within that co evolved system to strengthen it. So you don’t use resistance. You don’t blow things up because you’re, you’re not going outside the system. If I could say it was antibiotics, they evolved, you know, for fungus to try to fight off bacteria, they had their own place, we yank them out. And now we use them. And because we’ve taken them out of their evolutionary context, they’re awesomely powerful and they rapidly screw up your environment and they drive all these problems because they drive resistance they set up, they set up compensatory evolutionary boosts against themselves, right. antibiotics and antidepressants I think are similar in that way that their overuse sets up systems where they become perhaps resistance resistant to their effects, and produce long term changes in the ecology that are probably bad with antibiotics more generally, with antidepressants, perhaps in the ecology of the person’s brain body continuum. So it’s not. You shouldn’t use them. It’s the overuse that is a problem. So I think, you know, anything we can begin to do to think to help people try these more adaptive stressor type approaches, that don’t induce that are more like vaccines, you know, why does Why does running make you feel good running makes you feel good, because of course, human evolution probably had to run to chase down your food, you chase down your food, you get to eat it survive, you impress the other tribe members, you get to know that beast on your back. And if you have a genetic makeup that gives you a hedonic reward from running, you’re more likely to run therefore, you’re more likely to eat right? So these are codes. So you take that you don’t need to throw something new into the system, you just can intelligently kind of push that system, and it’s already there for you and you don’t set up these opposing evolutionary forces that build the resistance to the degree that we can do these sorts of adaptive stressor interventions, I think they hold real promise. And then I think just like the antibiotics, you hold the other things in your hand when people really need it because the system is being overwhelmed. You have to basically kill some bacteria for the immune system to handle things, you have to kill some of the stress for the people for the system to be able to handle it. But it would have radically different implications. So for instance, you might try to treat people’s added depressants at lower doses for a minimal period of time. Something that you know, when I was trained, that was like, unethical, you do not do that. That’s like satanic evil stuff, right? Well, these are studies, they should be done, right? They would never be adequately done, we don’t know. But this would be the implication of these ideas. And ideas are often wrong. So I’m not, but these are just things we should think about as clinicians. Definitely, we should try to foreground wellness based, adaptive stressor type practices, into our treatment of patients, and do it seriously enough that it doesn’t seem like oh, by the way, if you just exercise a little on the side, that’d be good, right?

 

Keith Kurlander 51:51

Yeah, as we wrap up, I would love to hear your thoughts on ketamine for depression. And, you know, I think anyone that’s ever done ketamine knows that there’s work involved. If you’re going to take ketamine there’s essentially a psychedelic experience that happens. And I’m curious about your thoughts on would you frame that as sort of an adaptive stressor intervention in a short term model that can reset? Going back to what you were saying earlier, and get people prepared to do some of the more long term work?

 

Dr. Charles Raison 52:21

Yeah. So let me say first, that I think psychedelics in general are adaptive stressors. For many people. That’s exactly what they are. They’re there psychological adaptive stressors, right? Robin Card Harris, who’s the kind of wounded kid of the psychedelic world has written just brilliant essays on added presence that operate primarily perhaps you search on a five HD one a receptors that did just have sort of produced adaptation to current conditions versus psychedelics and other five AC to a receptor agonist, which induce intense experiences produce behavioral change, right? Instead of just saying, What’s the problem? You go, there is a problem and I’m going to deal with it right, that experience is usually stressful for people and I don’t need to tell you that a lot of people do psychedelics for surprise. Even when they do it in a very therapeutic context, they have very difficult experiences that they say thank you that was what really helped me it was horrible. It really helped me, you know, ketamine, you’re right, has that potential, I think, especially at higher doses, especially when taken in a therapeutic setting. And there’s a lot of this going on in your town, as you know, and many people are now repurposing ketamine as a sort of available psychedelic modality. Because the others are not legally available right now. Ketamine, though, is interesting, because I think, very credible data obviously led to FDA approval, that for many people that don’t respond to either headed depressants, you can give ketamine at lower doses. People have a little bit of dissociative funkiness, but you can do it with a blend and a gurney and not talking to them and telling them hey, well, you know, if you feel weird, just try to ignore it. It’ll pass right? People still get these effects. I think ketamine is oddly dual. I can’t prove this to you. But I think that at lower doses, it’s just an antidepressant basically, right. And it produces a rapid effect. So it’s different from SSRIs. But that’s probably purely biological meaning it probably has to do with differential rates of driving synaptic genesis and neurogenesis and this sort of stuff. You can see it in the signal, right? So you do ketamine on average, one dose like that, and people feel better for about a week. You do psilocybin at a psychedelic dose one time and people feel better, depending on a condition for weeks or months suggesting that there’s sort of a different mechanism. So ketamine, I think, can be either used as just a regular old fast antidepressant or in a more psychedelic like way. And of course, obviously, unless the higher dose would block the direct biologic effects and there’s no evidence for that. There’s much to be said for trying to do it as a psychotherapeutic enhancer. I personally suspect that classic psychedelics like LSD, psilocybin, mescaline, do not have direct edit present effects. I agree with Robert Cart Harris, I think we’re going to turn out that this could turn out to turn neuroplastic agents that make the brain remarkably sensitive to internal external context. And that is that they produce experiences. And the experiences are what drive the changes. We talked about it, we’re actually trying to directly study that. But that’s what the data right now is. It’s suggested that the day may not be direct, you know, you do so you just do suicide, but it’s not going to just make you feel happier because of what it does to your brain. It needs to be paired, what it does to the brain, maybe permissive and maybe necessary for the therapeutic benefits but not sufficient. And I’ve got some colleagues from early animal work to suggest that both ketamine and psilocybin produce very rapid synaptic genesis, neurogenesis spine, you know, the brain, in the animals to ketamine has an antidepressant effect the psilocybin doesn’t. And that would be consistent with this idea that there’s something about classic psychedelics that needs perhaps some level of cortical complexity to be used as an antidepressant, you know?

 

Keith Kurlander 56:04

Yeah, thank you. That’s super informative. Well, as we wrap up, I’m really curious. The last question, you know, this conversation for me this, most of this podcast audience are providers. And then there’s some people interested, obviously, just for the things they’re dealing with. There’s the back group, too. And this conversation for a lot of providers is sort of like mind blowing, like, Oh, my gosh, I wasn’t thinking about any of this stuff before this moment. And what I’m curious about is for that person that this is really like mind blowing, like, there’s all these different ways, like, where did they get started? In terms of okay, either they’re a medical provider or a therapist or whatever, like, where would you recommend people get started to start, you know, dealing with this kind of new innovative way of thinking about a patient in relationship to their environment and how to help them in that process.

 

Dr. Charles Raison 57:00

Right. So this is really a challenge, right? I mean, we, you know, there’s not, this may just be my ignorance, but there’s certainly not very many kinds of fully packaged, sort of this is how you do. If you’re interested in this idea, this is how you do it. You know, we’ve been talking about Rakesh Jen, he and his wife, Sandra have produced an online wellness platform called the wild five, if you just Google wild five, it’s free. It’s available. And it combines sort of exercises with physical exercise, mindfulness, sleep, hygiene, social connectivity and mindfulness into a package that is really pretty user friendly. And that gets at some of these ideas around you know, like exercise and stuff. short of that, that this is where I always get kind of embarrassed because I wish I had something that I could pull out a drawer and say, you know, here’s a potential package for doing this. But you know, all these things are available. There’s a lot of information available about them. In terms of exercise, psychedelics, I caution people, I go around talking about them as if they’re God’s gift to mankind. These studies that need to be done to really assure that they work for depression have not been done yet. And so we’re always cautious and say that this developing thing on the other hand, ketamine is available, it’s legal. And it has antidepressant effects and exploring the use of ketamine as an intervention in a psychotherapeutic setting is something that people can examine now, and it for some people might enrich their practice, and a lot of people feel that way. You know, I think if one made a list of things, you know, another thing obviously, we’re still very actively involved in hypothermic work. And you know, we use the super fancy expensive machine in our studies, but I have colleagues that are looking at sort of more widely available modalities, and frankly, there’s some data showing the hot baths added present effects, try to incorporate phasic hyperthermia into how people treat things, is this going to solve all their problems? No, it’s not. But we and others have shown it has a clear antidepressant effect. We haven’t talked about it, but I’m very interested in intermittent fasting. And there is now some data, especially in older adults showing that it does have a depressant effect, you know, it’s something people can try. You don’t want to go overboard on it. It’s just like the exercise we’re talking about, but don’t go anorexic. But there’s a lot of convergent data that episodic sort of food deprivation has immediate mood elevating effects for many people, and also may have some longer term antidepressant effects. So all these things, you know, one time I did this 16 hour seminar for a bunch of huge mental health program systems in Southern California. And when I was done, I guess the states got storm people a little bit pissed off at me. They said lots of really interesting details, but you mean 16 hours at the end of the day, all you have to say is what our grandmother told us. And it’s a problem with all this. Yeah, it’s kind of a version of what your grandma told you. But it’s how it’s implemented and packaged. You know? People want to feel for clinicians, for your patients, you know, they don’t want to feel like you say once you go try to exercise, they want to feel like, here’s an exercise program, I’m writing a prescription, this is what I expect. So we’re gonna hold you responsible, if you want to do treatment with me use expectations, and, you know, intention, and placebo and all these things, to try to make these these interventions to honor the fact that they really are powerful, they do have effects and they can be implemented in ways that feel like you’ve gone to a doctor, I think finding ways to do that is really key for bringing this into a practice.

 

Keith Kurlander 60:34

Thank you for everything and that’s been really helpful. And I just want to thank you for everything you’ve focused on so diligently in your career, your research, and you’re just making such huge, huge impact on a massive, massive ongoing question and problem around you know, if we even just focus on depression, like the impact you’re bringing that conversation is just so large. I just really want to thank you for that.

 

Dr. Charles Raison 61:04

Thank you. I appreciate the kind words and great questions, guys. You know, we’ve probably said everything I pretty much know about but I’m happy to come back some time. If we can reiterate something. I’d be happy to get back. This was a great conversation. Really good idea.

 

Dr. Will Van Derveer 61:23

Well, what a rich conversation and exploration with Dr. Chuck Raison, one of the world’s foremost explorers and researchers and brightest minds and really pushing the field to understand what is happening under the hood of a mood disorder. How do things emerge from the biological, the psychological, the spiritual and symptoms of depression and how we can, as clinicians do a better job of resolving these complex issues. Thank you, Chuck Raison for your commitment and dedication. If you enjoy learning about the lesser known root causes of mental illness and listening to this podcast, please leave us a review. This is how others will hear about this podcast and you can join our community by going to email dot psychiatry institute dot com that’s E M A I L dot psychiatry Institute, all one word dot com (email.psychiatryinstitute.com) and enter your email there and we’ll be able to send you newsletters and videos to keep you up to date on this rapidly emerging field. We look forward to connecting with you again on the next episode of The Higher Practice podcast where we explore what it takes to achieve optimal mental health.