Peeking Into the Brain: How Psychedelics Are Redefining Neurology

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Episode 203

Evan Cole Lewis, M.D.

Dr. Evan Cole Lewis, VP of Psychedelic Neurology at Numinus, joins The Psychedelic Podcast to delve into the world of psychedelic neurology and its potential to revolutionize medicine.

Dr. Lewis & Paul F. Austin take us deeper into the underlying mechanisms of psychedelics and their impact on neurological networks. The conversation explores how psychedelics like MDMA, ketamine, psilocybin, and LSD can manipulate and reorganize those networks, leading to tailored treatment approaches for people with neurological conditions. From Dr. Lewis’s perspective, precision psychedelic medicine is poised to provide breakthrough treatments for traumatic brain injuries, concussions, functional seizures, cluster headaches, migraines, and mental illnesses.

With cautious optimism, Dr. Lewis and Paul envision a future where psychedelics offer transformative solutions for today’s most challenging conditions.

Evan Cole Lewis, M.D.:

Dr. Evan Cole Lewis is a neurologist and clinical neurophysiologist with expertise in pediatric neurology and epilepsy. He is an Assistant Professor with the Department of Pediatrics at the Hospital for Sick Children and the University of Toronto.

Dr. Lewis is the founder and medical director of the Neurology Centre of Toronto (NCT), Chief Medical Advisor for the Jamaican Medical Cannabis Corporation and VP of Psychedelic Neurology at Numinus, a Canadian company focused on research and therapeutics with psychedelic medicines.

Dr. Lewis has extensive clinical experience in the utilization of medical cannabis for the treatment of neurologic conditions in both adults and children. His practice focuses on brain network disorders, including concussion/persistent post-concussive symptoms, headache and migraine, and functional seizures.

He has a special interest in treating brain network disorders with psychedelic therapy. He has delivered many national and international educational seminars, talks, and lectures on brain network disorders, medical cannabis, psychedelic therapy, and the intersection of psychedelics and neurology.

Podcast Highlights

  • Why Dr. Lewis chose to work at Numinus.
  • Exploring how psychedelics bridge the gap between psychiatry and neurology.
  • Why psychedelics challenge neurology to adopt a complex-systems approach.
  • How psychedelics counterbalance neural rigidity with harmony & flexibility.
  • Psychedelics’ potential to treat traumatic brain injuries (TBIs).
  • Ketamine’s role in activating & strengthening dormant neural pathways.
  • How plant medicine helps people unlearn old habits & experience child-like awareness.
  • The mystery of functional seizures.
  • Dr. Lewis’ belief that psychedelics will enhance neuroscience & precision medicine.

This episode is brought to you by Numinus, a mental health company bringing safe, evidence-based psychedelic-assisted therapies to people in need. They have clinics in the US and Canada, providing mental health treatments such as: ketamine-assisted therapy, talk therapy and virtual mindfulness programs and practitioner training. Numinus is a leader in psychedelic-assisted therapy, both through research and in practice where approved by governing bodies. Learn more at www.numinus.com.

Podcast Transcript

0:00:00.1 Paul F. Austin: Welcome back to the Psychedelic Podcast by Third Wave. Today I'm speaking with Dr. Evan Lewis, Medical Director of Numinus Toronto, and the VP of Psychedelic Neurology at Numinus.

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0:00:12.8 Evan Cole Lewis: Unless you going to therapy every single day, listening to everything your therapist is saying, doing all the work in between, not feeding this with all of the crap that goes on in your life and the relationship you're not happy with and all this other stuff, you have to create such a artificial environment for therapy to work quickly. This is why therapy takes a long time. If you work at it, eventually you will unlearn these things, perhaps. So what psychedelics do is they are able to reduce that energetic state by the mechanism and function that they act on in the brain. They provide the catalyst that can break that energy down. It's difficult to do on your own, and this is why you can then unlearn and remove that brain state and shift into another one.

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0:01:02.3 Paul F. Austin: Welcome to the Psychedelic Podcast by Third Wave. Audio Mycelium, connecting you to the luminaries and thought leaders of the psychedelic renaissance. We bring you illuminating conversations with scientists, therapists, entrepreneurs, coaches, doctors, and shamanic practitioners, exploring how we can best use psychedelic medicine to accelerate personal healing, peak performance and collective transformation.

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0:01:40.1 Paul F. Austin: Third Wave is grateful to Numinus, a mental health company, bringing safe evidence-based psychedelic assisted therapies to people in need. Numinus has joined us as a partner. They have clinics in the US and Canada where they provide mental health treatments such as ketamine assisted therapy, talk therapy, as well as virtual mindfulness programs and practitioner training. Numinus is a leader in psychedelic assisted therapy, both through research and in practice where approved by governing bodies. They've also created a music as medicine program, where they partner with leading ambient musicians to foster a community of individuals seeking mindfulness and alignment. Numinus has been advocating for greater access to psychedelic therapy for years, and we're proud to partner with them as they continue to push the envelope. You can learn more at numinus.com.

0:02:30.9 Paul F. Austin: Hey, listeners. This is Paul Austin, founder and CEO at Third Wave. Today I'm excited to have Dr. Evan Lewis on the show. We go deep into the topics of psychedelics, neurology, and how psychedelics can help us to heal what have been thought to be intractable conditions like cluster headaches, epileptic seizures, concussions, and brain injuries. So we go deep into the neurology behind it, we talk a little bit about the metaphysics of neurology as well. A little bit more background on Dr. Evan Lewis.

0:03:04.0 Paul F. Austin:  Dr. Lewis is a neurologist and clinical neurophysiologist with expertise in pediatric neurology and epilepsy. He's the founder and Medical Director of Numinus Toronto, the Chief Medical Advisor for the Jamaican Medical Cannabis Corporation, and VP of Psychedelic Neurology at Numinus. Dr. Lewis has extensive clinical experience in the utilization of medical cannabis for the treatment of neurological conditions in both adults and children, and his practice focuses on brain network disorders, including concussion, persistent post-concussive symptoms, headaches, migraines, and functional seizures. He has a special interest in the treatment of brain network disorders with psychedelic therapy, and it really was a pleasure to have him on the podcast today.

0:03:50.2 Paul F. Austin: Some key highlights and takeaways. We're gonna talk a lot about networks, the default mode network, salience networks, complexity networks. We're gonna talk about the relationship between those networks and how psychedelics can help to heal certain dysfunctions and disorders of the brain. And you're also gonna hear a little bit about Dr. Lewis's background, what brought him into the space, and why he believes psychedelic medicines can help us to unlock a lot of these previously intractable conditions. All right, that's it for now. I hope you enjoy my conversation today with Dr. Evan Lewis.

0:04:26.2 Paul F. Austin: Hey, listeners, welcome back to the Psychedelic Podcast. Today we have Dr. Evan Lewis, the Medical Director of Numinus Toronto, and the VP of Psychedelic Neurology at Numinus. Evan, it's good to be chatting once again. Thanks for joining us.

0:04:41.2 Evan Cole Lewis: Yeah, thanks Paul. Thanks for having me.

0:04:44.1 Paul F. Austin: Yeah. We had a chance to connect at the first Wonderland Conference in 2021 in Miami. I think first at the conference itself, and then at a little after party. I remember this conversation between you, myself, and Alli Schaper, who is one of the co-founders of Microdosing Collective. I believe at that point in time, you had recently started with Numinus, maybe in the prior three to six months. You were starting to get a handle on the role that neurology would play in the larger Numinus ecosystem. And I'd love just to set the frame and the stage for the rest of this conversation. I'd love to tell us a little bit about why you chose to work for Numinus. What inspired that decision, why'd you make that decision.

0:05:33.7 Evan Cole Lewis: Yeah, sure. I can't believe it was that long ago, so it seems like so much has happened since then, [chuckle] eons ago. So, why Numinus? It stems from early on, I got involved in pediatric, well, I'm a pediatric epilepsy specialist by training, and was involved early with medical cannabis for the treatment of pediatric epilepsy, and then kind of naturally made a foray into psychedelics. So a lot of the work in psychedelics was inspired by my work in cannabis. I really wanted to find a way in which to introduce psychedelics into the field of neurology and where it could help my patients. And the way to do that was to find partners that were of like mind. And I knew Payton a little bit before that, and then began to talk to him about where psychedelics would fit within neurology. And it seemed like it made a lot of sense as our conversations extended that we could really find areas within neurology that could accommodate psychedelics. And the way to do it was to look at the clinic that I established in Toronto and start looking at some of the important patient populations that I had at the clinic here, and find ways in which utilizing psychedelics as a tool in our toolkit could support their healing.

0:06:57.8 Paul F. Austin: So probably the most famous neurologist is Oliver Sacks, and you, I'm sure, know of Oliver Sacks. Many of our listeners may have heard of Oliver Sacks. He was both a neurologist, but more prominently a writer, and he wrote an entire book about his psychedelic experiences. I'd love for you to talk a little bit about why you chose neurology and if you studied or read about Oliver Sacks when diving into this overlap between psychedelics and neurology.

0:07:32.4 Evan Cole Lewis: Yeah. For neurology, it always seemed to me to be the natural next step for where psychedelics were gonna go. And a lot of the basic understanding of neurology, you can... If one has that, you can naturally see where psychedelics come in, presuming you've got the understanding of how psychedelics operate as well. And Oliver Sacks was quite inspirational for me, more than I would say, kind of like my prepsychedelic neurology life, with his stories. And outside of the books, his descriptions of his psychedelic experiences, his just descriptions of neurologic phenomenon in patients always fascinated me. He has multiple books where he describes these bizarre syndromes and bizarre perceptual experiences people can have with distortions of time, distortions of space, distortions of body image. So fascinating, these little vignettes that he describes. That to me, was much more fodder for my role in segue into psychedelics, because I was very fascinated during my time in training trying to figure out how your little tiny areas of the brain could result in such profound perceptual disorders for patients.

0:08:55.9 Evan Cole Lewis: And then large areas of brain injury could result in a whole host of different types of perceptual disorders. And really, when it comes down to psychedelics and what the effects of psychedelics are doing, that's exactly what they're doing, they're altering perception, they're affecting these areas of the brain which he described with such beautiful language, those same areas and what they would produce when those areas weren't working, were defective, or there were deficits in those areas. So psychedelics were kind of a way that I thought, "This is a tool to study those phenomenon. If we could understand where psychedelics are acting in the brain, do they line up with some of these other syndromes?" And if you can then overlap these things, it gives you a such an insight. It's like Stanislav Grof's quote where he talks about how psychedelics are to psychiatry like the microscope is to biology and the telescope is to astronomy. I say this, I always quote him and then say, "But it's also to neurology as well. Psychedelics are to neurology and psychiatry." We can't exclude neurology there.

0:10:05.8 Paul F. Austin: What's the difference between neurology and psychiatry?

0:10:09.3 Evan Cole Lewis: Good question. I'm gonna say no difference. I'm gonna say it is a difference of language. I've had this conversation with somebody else...

0:10:17.1 Paul F. Austin: Semantics.

0:10:17.8 Evan Cole Lewis: Right. It's totally semantics. For me, it really is. And I think it's semantics and it's a way to separate two kind of ideas or concepts that really required separation some time ago to understand the brain in its structure and its real physical matter, and then to understand the brain in ways that weren't... Back in the day people weren't able to describe it physically. And that was the realm of psychiatry. And these things split in the 1800s. Actually the famous case of Phineas Gage, I don't know if you've heard of him. He's... Your listeners may not have, yeah, he had a bar... He was a railway worker and he had a bar that went through his face and up through his brain, he survived.

0:11:10.2 Evan Cole Lewis: And then he had particular deficits, and they studied him because they knew exactly in the brain where these deficits were happening, and they were able to then describe how he was. And by doing that, they were able to localize that area of the brain, subserve the functions that he no longer had. And this was really the birth of neurology. And then they started... This kind of doctors broke off and started to explore different areas of the brain that would 'cause different deficits in people if they were damaged, and this became neurology. And then the more elusive things that we have in psychiatry, which didn't really make sense 'cause the brain appeared normal, but were more large scale brain problems, this became the field of psychiatry and they separated out.

0:12:00.7 Evan Cole Lewis: And the beautiful thing, I'll just finish with, is that what I think psychedelics are doing is bringing these two fields back together and letting us understand that there really is no difference. They're both are physical based processes, they're both complex, physical based processes that have an interlink. And I said to my friend the other day, I was like, "Where do you draw the line? Where do you draw the line between neurology and psychiatry? Where is that line and who made that line?"

0:12:28.9 Paul F. Austin: Well, and what's coming up for me a little bit is psychiatrists will often do, let's say, talk therapy. So they'll both be in sort of the emotional narrative or story of the individual, as well as be maybe prescribing them a drug or a medication that they think will help based on that story and narrative. Whereas I see neurology as being a bit more particularly focused on the physiology or the brain, less so the sort of maybe trauma or emotional story, even though that plays a role as we will explore through this conversation, especially with psychedelics. That feels like maybe the slightly nuanced difference between... Although I would ask you, do you... I sense you see patients, you probably talk with patients, you have... But maybe it's not an hour long session where they're telling you about their relationship with their mom, necessarily. I don't know.

0:13:26.2 Evan Cole Lewis: Interesting. So I think your conception of it is correct, especially when you see it on TV, and especially when you are a student of neurology and you're in a classroom learning neurology versus that in psychiatry, that's how you're taught. And then you go off out into the world with all this great neurology knowledge. I joke with people I finished I think grade 28 or grade 29, something like that. And I go out into the world and I start seeing patients on my own, and it's almost like nothing I learned actually translates into practice. Because people come in with horrible epilepsy or a bad stroke, that's just one small part of their story. Nevermind the fact that they had... They have to deal with having seizures and... For years.

0:14:20.9 Evan Cole Lewis: And the impact that that has on them as a person, the impact that it has on their family, the impact that it has on their partner. And then all of that gets wrapped up into this whole thing we call epilepsy. And it's just... It doesn't... It starts to not work, the basic tools I was given don't apply. I can give a medicine and hopefully the medicine works for the seizures, the person comes back they don't have epilepsy, but their quality of life is still terrible and they're struggling. A lot happens with this in brain injury, you see it a lot in brain injury, concussion, long-term concussion symptoms. So it's like... This is why I say it's a function of language. It's a function of language to create experts, but we lose the other piece to the puzzle. And then... And we become very siloed in what we can do. And you come out and practice, and you start to help people and you're not helping them the way that you thought you were going to. It's really challenging. It really is... It is a challenge. And that's the piece, the piece is we lose that psychological psychiatric aspect to all conditions, which is taught really poorly in general in medical education, especially when you become uber-subspecialized into a field like neurology or elsewhere.

0:15:37.6 Paul F. Austin: So it's almost like the map is much different than the terrain. You can learn about the different potential indications, but at the end of the day, when you're in the complexity of life, the actual experience is going to be unique and personal and complex, and there's no necessarily one prescription fits all.

0:16:01.4 Evan Cole Lewis: I love that. That's just it. You see, you can study the picture of these hills and the way they appear, but then you go walk on them and it's an entirely different experience. It's somewhat, it's an approximation of what you learned.

0:16:15.2 Paul F. Austin: It's an approximation.

0:16:16.6 Evan Cole Lewis: That's really what it is. It's somewhat of an approximation. And then it's almost like you have to figure out what it is that you're missing here, that's not completing the puzzle.

0:16:26.9 Paul F. Austin: Yeah. It's like with a map, you know, "Oh, topography, there's probably gonna be a mountain over here, or there's gonna be this stream over here. There's gonna be a lake over here." But once you actually get up to it, and once you confront it, once you're actually walking the terrain, you're not gonna know... There could be a wild animal or a rattlesnake or a fucking lion that pops outta nowhere and eats your head. So you just got to... You got to be willing to adapt and learn. And I picked that up from this guy, Tucker Max, who wrote about how he did, I think, 10 years of talk therapy before working with MDMA to heal his trauma. And he said, "The talk therapy was to help me get the map of my psyche and my story, but the MDMA brought me into the somatic experience of catharsis release, being able to actually move through it rather than just intellectualizing it." And I feel like that's been a core challenge with our western medical model, is we've separated the mind and the body, and what psychedelics are doing is bringing those back together.

0:17:29.2 Evan Cole Lewis: Yeah. I agree. And you can even go further and apply that to anywhere. So the other piece of the conversation I had with my friend was about... I said, "Well, what's the difference between neurology and gastroenterology? The study of the gut. What's the difference? Is the gut separate from the brain? And if it is, where's that separation? There's a whole nervous system in the gut that attaches to the brain, that sends signals up there, that gets integrated in our brain, that sends signals back into the gut that tells the gut how it has to move, which then has a gross effect on the other organs, etcetera, etcetera. So at what point does a gastroenterologist stop becoming a gastroenterologist and a neurologist? And what point does a neurologist stop becoming neurologist and... Or stops becoming neurologist and you flip that over the gastroenterologist when these things are intimately connected?"

0:18:17.8 Evan Cole Lewis: So it really is... It's like one of those things that technology advanced to a point that allowed us to get really specific. And so everything got separated and fragmented, and we all went off and really studied those separate areas. And now that we understood them to some degree, now our technology has shifted to show us that these things are also very integrated. So it's almost like there's a coming back to the pendulum swung on one side, and now the pendulum's coming back towards the middle. Because prior to things being siloed, you go back in time to medicine and how medicine was viewed, and it was very much a holistic type of approach. You had all these things that were interconnected and then they got all separated and fragmented. And it's almost like we're coming back. And I really do think psychedelics is the thing that will bridge this idea of separateness, and we'll start to realize that we need both separateness and non-separateness.

0:19:21.1 Paul F. Austin: Duality and non-duality, right?

0:19:22.6 Evan Cole Lewis: Yeah.

0:19:22.7 Paul F. Austin: That's sort of living in the paradox of our absurd existence, as Camus would say.

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0:19:30.6 Paul F. Austin: Hey listeners, Paul Austin here. We'll be right back to this conversation with Dr. Lewis after a brief word.

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0:21:21.9 Paul F. Austin: Let's move into some technical things.

0:21:23.5 Evan Cole Lewis: Sure.

0:21:23.6 Paul F. Austin: Tell us a little bit about the brain, neurology... From a neurological perspective, what are different parts of the brain and what parts of the brain are psychedelics most active in supporting or tying together? Tell us a little bit, and it's probably... Maybe ketamine may be different than psilocybin, may be different than MDMA, but just give us a little bit of taste of what's going on there.

0:21:46.4 Evan Cole Lewis: Not a hard question to respond to.

[laughter]

0:21:49.1 Evan Cole Lewis: How much time we have though. So there's so many ways you can tackle this. One neat way, I'm thinking about a couple ways to answer this question, one neat way I've been playing with lately is looking at classical neurology versus modernizing neurology. So and that plays on some of the stuff we've been talking about already. So classical neurology is very much what we call a locationist type of neurology, that there are areas, very specific areas, of the brain that subserve very specific functions. So as an example, we know we have an area in the brain that's on the left front part in most people, most right-handed people, and that's where your ability to express language comes from, to write, to express. This is famous as Broca's area.

0:22:35.7 Evan Cole Lewis: Then we have, at the back of our brain, we have our occipital lobe, and this is where all of our visual representations get... Our vision comes in from our vision... Visual system goes back there, and the initial processing of how we see the world is back there. So that subserves a very specific location. So you can do that and you can... And the entire brain has been mapped. It was very famously mapped actually in Montreal in Canada by a neurosurgeon, who did... Yeah. They...

0:23:04.8 Paul F. Austin: At McGill or?

0:23:05.8 Evan Cole Lewis: At McGill. Yeah, exactly. Yeah, Wilder Penfield. And what they did there was they did awake brain surgery on people, and stimulated parts of the brain, and had them report what they were feeling or watch what happened, like did their hand open and close, or did their fingers move. And they mapped this all out. So we have a map of the brain that says very specifically where all things are. Okay. So that's great and that really worked and has worked for a long time. Now, as we've advanced forward, well, there's discrepancies. That model doesn't totally work. It makes sense in some cases, but there's a lot of inconsistencies. That's the classical neurology piece, that there's parts of the brain and if those parts of the brain are damaged or affected, certain things will happen. The entire body's been mapped out there. But now as we've moved forward into more modern neurology with more modern technology, we're finding that there are regions of the brain that are connected and these larger regions can connect all throughout the brain and they're very specific.

0:24:04.4 Evan Cole Lewis: So it might be very particular parts of the brain that connect, and these parts of the brain as a connected network have a certain function. So famously, in the psychedelic spaces, the default mode network, so that's an example. These are separate brain regions which have an interconnectedness. So what does the default mode network do? It's very much this network that when you are inwardly focusing on yourself, concepts of yourself, things that have to do with yourself, this network seems to be active, versus other networks that we're finding. So one is the salience network, this is another set of networks that direct our attention outward into the world. So if you are walking down the street and suddenly somebody runs quickly past you, and you direct your attention out to that person, that's something that's an important piece of information. That network becomes active and it moves... And then another network moves your eyes over and you see this person who's running by you.

0:25:10.9 Evan Cole Lewis: So there's a whole host of these networks. And this is really cool 'cause this is... We didn't really know this before. This stuff became discovered in the early 2000s with functional imaging, and this now has given us a whole new way of looking at the brain that might reconcile some of these inconsistencies that we have. Now coming to psychedelics, so these network ideas are really important, because this is something we didn't know about before and we're now able to see this in modern neurology. So it's almost like prior to that we had this classical neurology, and this is the idea I'm starting to play on. It's like classical physics, it's like we had Newtonian physics. And Newtonian physics are great. Newtonian physics can... That got us to the moon, and you can use that to approximate the way the planets move around the sun. You can even use Newtonian physics in a lot of other ways, and it gives you a gross calculation of things.

0:25:57.5 Evan Cole Lewis: But then when you wanna get really specific, like you wanna make sure GPS satellites are properly orbiting around Earth and staying aligned, you got to start employing different types of physics in that case, and start to move away into modernized physics. It's almost like with neurology, it's kind of the same idea. It explains so much, but we have to now move into this modern conception of how the brain's working. And it's very much at a network level. And this is where psychedelics act. So this is why I come back to the idea that psychedelics are really gonna offer us a window into the brain. 'Cause psychedelics don't work at very particular locations in the brain; they do, but these particular locations they work at tend to be ones that are the networks of the brain. So psychedelics work at the level of networks.

0:26:48.6 Evan Cole Lewis: And so this is allowing us to really understand these brain networks, 'cause if we give psychedelics to somebody, we can analyze these brain networks, we can see how these networks change. And then if we look at these networks in certain conditions that psychedelics tend to help, like depression or PTSD, OCD, substance use disorder, etcetera, etcetera, going on, and some conditions in neurology, and that overlap is there, then maybe we're sort of starting to understand these disease processes. And now the last leap going forward is, this is where psychedelics is even more interesting, and this is the most recent stuff that's coming out in understanding psychedelic neuroscience, is that even when we analyze the network effects with psychedelics, there's still inconsistencies even there.

0:27:50.1 Evan Cole Lewis: So a real good paper just came out by Manesh Girn, Carhart-Harris, a group there that talked about utilizing this idea of complexity science to look at brain networks. And what that means is it's not just the networks, it's even a level above that. It's how these networks interact with each other and change over time. So they posited a theory that psychedelics not only affect networks, but they affect the whole brain in such a way that the brain can move more easily between network states from one to another to another, and this is the idea of cognitive flexibility. And they're using this idea to reconcile all the differences. Really technical, I know that's a big explanation for a lot of people, but it's a really important point. And I think the takeaway point from what I just said is that it looks like psychedelics were operating at a very large map, like high level scale, to put the brain into states where it can move between brain states more flexibly.

0:28:41.2 Evan Cole Lewis: It interconnects the entire brain. So it's not just a default mode network picture that's been played up a lot. And it's not just the default mode network being more interconnected under psychedelics. It's a much more difficult complex, actually, picture that's arising from this, that's gonna require really advanced neuroscience techniques and technology, that we don't have just yet, to understand. So you got to stay tuned, there's more to come for this. And it's fascinating, interesting, and again, this is why psychedelics are really gonna advance the field of neurology. So last thing I'll say here is I tell all the young neuroscientist, that I've taught in the university and new neurologist, this field is wide open. Nobody's doing this stuff. There's so much to learn here, and it's so fascinating. If you truly are a brain scientist or a brain clinician at your basis, why aren't are you doing this stuff? This is where the gold is right now.

0:29:37.2 Paul F. Austin: I want to come back to that, because I want to talk a little bit more about what psychedelics have taught and are teaching us about neuroscience, and how they're helping to pave a path, actually, for the future of neuroscience. But before I wanted to draw a little bit of a parallel, which is when you talk about network, the network level, what we know about psychedelics, when we work with these medicines subjectively, they often connect us to nature. I even use this sort of metaphor of the mycelial network. Timothy Leary would call it, "Finding the others." People often talk about how they feel so connected and interconnected. So what I also love about this is psychedelics open up this capacity for fractals and holons, where when it works inside the brain, it's helping the network to sink in more, to become more adaptable, that then is actually helping to heal the gut.

0:30:32.0 Paul F. Austin: Because the vagus nerve facilitates this gut-brain access. That gut health is then helping us to be more disease free or healthier in the way that we are. And then we have more energy to show up and connect with others, to build sort of this new vision of a world that is in tune with nature and that has educational systems that are actually relevant for the 21st century, and has healthcare systems that look at the entire individual and not just the biology of their brain necessarily. So I love this sense of tying it into complexity science. We did a podcast with Manesh. It hasn't been published as...

0:31:14.2 Evan Cole Lewis: Oh, cool.

0:31:14.4 Paul F. Austin: As of this date, and when we're recording. It may be published before we record this, but we got pretty deep into that complexity science. And even I talk a lot about psychedelics and leadership, and what we know about leadership is; you have to be adaptable, you have to be able to shift, you have to be able to learn quickly, you have to be able to pivot, you have to be able to make decisions when you don't have everything at your disposal. And that's why I often talk about how psychedelics are great tools at adaptability. And that's true for the leader, the self, and it's also true for the brain.

0:31:52.6 Evan Cole Lewis: Yeah. No, it's definitely the case. And it's all... And the neat thing about that is the opposite is where you can find the pathology. So the opposite is if you were too networked, if your networks are too ordered, too structured. So if... You could start as a great leader and what got you there perhaps was your ability to be flexible, to be adaptable, to listen to the people. And then what happens with leaders when they stay in power for too long is they ossify, and they get stuck in their ways. They get... They become too rigid, I.e., they're... And it's almost like that's what's going on in their brain, their networks are becoming too rigid, too stuck.

0:32:36.6 Evan Cole Lewis: And this is what happens to all of us, and then their leadership then fails. So it's almost like this happens at the level of the individual brain cells, which scale up to the brain networks, and then the networks get too rigid. And then the result of the networks is these brain states, if you look at a complex system, they can't move that well. And if they're not moving that well, that gets expressed as your behavior. And your behavior is only a function of what's going on inside.

0:33:07.2 Evan Cole Lewis: So this is where, if psychedelics reverse that process temporarily and give you access to a more connected whole of the brain temporarily, and give you some insight there, you can maybe modify, update your system, have some perspective that you're too ordered, too rigid. And that's actually a very highly energetic state. So this actually lowers the energy of the brain when you move away from too much order and allow that flexibility to come back. And so, yeah, you can scale this up in the examples of leadership, you can scale it up everywhere. And same with... Come to your example of nature, too ordered, too structure of a forest, it will eventually destroy itself or lose all of its richness and its properties.

0:34:00.4 Paul F. Austin: And this even, not to get too philosophical, [chuckle] but part of what I think we as a human species are rediscovering is this sort of wild, primal, archaic side. Because we've been over domesticated, we live in boxes, we live in very ordered, overly ordered. Environments which has led to a lot of disease and dysfunction that is presented around too much constriction, too orderly. All of these states that psychedelics help to heal, depression, OCD, addiction, anxiety are typically... And this is sort of the basis of the default mode network, and some of these other neurological things, are typically because of an ossification or there's too much rigidity. And then the psychedelics act as sort of this counterbalance. It's also why psychedelics are not great for schizophrenics because they're all the way on the other side where there's just too much chaos. Right?

0:34:55.1 Evan Cole Lewis: Yeah.

0:34:55.6 Paul F. Austin: And so I think considering that, it's as with in, so with out, psychedelics help us to deossify, to de-order, to come back to balance. And I think what's really interesting then, is how do we start to create, and this is probably gonna happen in the next 10 to 15 to 20 years, how do we start to create external environments that actually represent that place of balance and harmony with the true self or with nature.

0:35:18.4 Evan Cole Lewis: Yeah. That's true. And it's gonna have to complement the people living within those environments for sure, because that is part of the problem. And the external order allows the brain to make more accurate predictions. So for... I don't know if that's the conversation you got into before, but that's how the brain operates. The brain operates by making predictions and it wants to make the next best possible prediction. If your environment is very consistent and ordered, then it's easy for your brain to make the next possible prediction. The better your brain predicts, the more structure develops in your brain, the more ordered the networks become in your brain. So an overly predictive brain is actually not good, it leads to too much order. And we all know what psychedelics do.

0:36:16.3 Evan Cole Lewis: One thing psychedelics do, from a neuroscientific point of view, is they reduce your high, top-down high-level predictions. And this is, again, intermixed with all of this. And this is how the environment also can feed that as well. So it's good to be in different environments, the brain loves novelty. A cool example of this is, I did a deep dive for a while into isolation. It's not so self-evident why, if I say to you, "I'm gonna lock you in a white room with a toilet and you're gonna eat the same thing every day in that time I lock you in there," all of a sudden that sounds really frightening. But it's not so obvious why that's frightening. Why is that inherently frightening to all of us, to most humans, if you tell them you're gonna do that to them?

0:37:02.9 Paul F. Austin: Lack of novelty, maybe?

0:37:04.4 Evan Cole Lewis: It's the lack of novelty, exactly. And so the brain just easily can predict its environment at all times. And the brain wants novelty, it wants it. There's almost like a desire for the chaos. There's a desire for the disorder because that allows the brain to learn. It's really... It's interesting if you think about it that way.

0:37:25.7 Paul F. Austin: Oh, it's super interesting 'cause now I've been thinking about neuroplasticity. We hear about how learning music, about learning new languages, about keeping the brain active and alive is so necessary to not only help heal dysfunction, but also potentially mitigate the chances of Alzheimer's and dementia. So in other words, if you don't use it, you lose it. And so that novelty is important. At the same time, I'm a week away from going into a dieta in Costa Rica. So 12 days of silence. I'll be mostly in one little hut for about 18 hours a day or something like that. I can bring an instrument, I can bring a couple of books, I can write poetry, but I can't talk with anyone, I can't look at anyone, I eat very little. And it's interesting 'cause I have been nervous, and yet I'm also surprisingly excited. And I think, in just within the sort of context of this conversation, it's because I have so much novelty all the time and I'm always out and talking and doing things to actually have, even just for 12 days, that rebalancing of quiet stillness, equanimity, peace, nothingness, feels like it'll act as a great sort of counterweight to how I normally exist and live.

0:38:39.2 Evan Cole Lewis: Yeah. And then very easily understand this point is, "All right, well we're gonna extend that to 90 days." All of a sudden that maybe doesn't sound so appealing anymore, or maybe it does? This is where it's really cool. It's like this, the brain, needs the balancing. That balancing is so inherent to the way the brain functions. And I really think this is where it gets really neat. And I think Manesh and the group have really touched on something important; that we were all new with the psychedelics when Robin Carhart-Harris was developing the idea of the REBUS model and the brain network kind of increased integration and decreased diversity was appearing. And now with this other layer of complexity science, I really, really think it's such a smart perspective and one that is gonna open up a lot for this field in terms of what happens in the next five to 10 years.

0:39:37.1 Paul F. Austin: Let's talk a little bit about neurological disorders. And there were five that we talked about before going live; cluster headaches, migraines, functional seizures, concussions, and traumatic brain injuries. And just a brief anecdote before you dive in. I was recently on an ayahuasca retreat, and there was a man who was on the land there, he had been there for several months. 14 years ago he had a traumatic brain injury, he couldn't talk for six years, and then he started working with cannabis. It started to bring back a lot of things. And then he started working with ayahuasca and psilocybin, and now he can walk, he can talk. It's slow, but he's experienced significant healing from working with psychedelics, from a point where he couldn't talk, a doctor said, "You would never talk again," and now he can at least interact and have conversations and communicate.

0:40:29.3 Paul F. Austin: And I've heard anecdotes like this time and time again, about how someone has a traumatic brain injury in particular, and they start to work with micro doses of psychedelics, or they start to work with higher doses of psychedelics and it actually starts to repair the brain. And I'd love for you to talk a little bit about, just sticking with traumatic brain injury, and then I think we can find our way into some of these others. Why is that? Why are we hearing all these anecdotes of psychedelics helping with traumatic brain injury? What's going on from a neurological perspective?

0:41:03.4 Evan Cole Lewis: Yeah. Sure. I think I'm gonna preface it all by this field is wide open and we don't really know. And a lot of what of what I'm getting...

0:41:10.9 Paul F. Austin: Some of this is speculation.

0:41:11.4 Evan Cole Lewis: Yeah. A lot of what I'm gonna say is, well, it's speculative, but it's grounded in some understanding of concussion, TBI, and also the mechanisms of psychedelics, and some we've touched on already. The first, I think, really important thing is... Two billion important things I think to consider, is there are different degrees of traumatic brain injury. So when we say mild traumatic brain injury, we're talking about concussion. And concussion means that there's been no clear structural damage to the brain. Meaning if someone gets diagnosed with concussion, one of the key features is that if I do an MRI or a CT scan and I look at their brain there's no bruising, no bleeding, no tears. They look essentially normal.

0:42:00.8 Evan Cole Lewis: Moderate to severe traumatic brain injury is different. That is when you do get bleeding in the brain and cell loss and things. So that's a different kind of area. And then the other piece to separate out is acute versus long-term. So acute concussion or acute injury is what happens within the first days to a couple weeks. And then there's beyond that, and those are also two different viewpoints that you have to consider. So when we have this conversation, it's very important to pinpoint which one we're talking about. I would select mild traumatic brain injury, concussion and long term, because that's where I think psychedelics have actual action. On the moderate to severe side, you can have action as well, but if you have a severe brain injury and you have a bleed in a certain part of the brain, the cells die, those cells are not coming back. Especially if you're an older adult, the function there is probably lost and probably lost long term.

0:43:02.4 Evan Cole Lewis: So the last piece I'll say is when I hear a story like this, the devil's in the details. You got to know what the history was with this patient, this individual. What is the actual brain injury? Is there... Was it concussion? Was it... So this is all important. So it'd be hard to comment specifically about this, but I can infer one of these groups. I can infer that this one individual may have had mild or moderate TBI and this is now long term. So that's where we're at. All right. So, I guess I'll take it back to a mild concussion, because what you're hearing a lot of is you're hearing a lot about athletes who have these concussions or multiple concussions, and then long term are having a lot of symptoms, a range of symptoms. And these symptoms can range from cognitive problems, sleep problems, emotional behavioral problems and physical problems. And the physical problems are really interesting. They have light sensitivity, sound sensitivity, pain sensitivity touch sensitivity. They have positional sensitivity that's manifested as dizziness, feelings of dizziness, inability to walk, stand up straight. And I've probably seen over 2000 of these patients in my practice, maybe more long-term concussion, not athletes, but mixture of athletes, people in motor vehicle accidents, slip and falls, and they have a range of all these symptoms.

0:44:25.6 Evan Cole Lewis: And this is the... Probably some of the most interesting people, because it doesn't... It sometimes doesn't really matter what happened, what kind of injury it was, but months, years down the road, they have these range of symptoms that are all kind of similar but a little bit different in the domains I just described. And very little therapy works. You've got to put... These individuals need physiotherapy, functional therapy, they need vision therapy, speech therapy, like this individual you're talking about had speech difficulties, and any range of therapies. And they don't really work that well. Okay. So what's going on? So here's where we start looking at those individuals. You put them in functional brain scanning images and their networks are altered. They have abnormally connected networks, and they usually have normally connected networks a lot in the areas that they're complaining about, and also in some other areas, meaning that the way information is getting integrated into their brain, it's not happening properly. Such that, "What is the problem here?" The problem is they're suffering from a disorder of perception.

0:45:38.7 Evan Cole Lewis: So when... So I say, I often say this to patients, so light sensitivity is a really common experience of people with chronic concussion. Light is too bright. And I always say to people, "Well, the sun didn't get brighter and the lights in your office didn't get brighter. Your eyes are fine. The nerves going back to your occipital lobe, we talked before, are fine. So there's only one thing that could have happened. And that one thing is your perception of the brightness of the light is disordered." And how does that happen? Well, let's take us back to the conversation we had before with the brain predicting the world. So the brain predicts the sun is a certain brightness and it's predicted that your whole life. So the brain makes a prediction of the sun, the sun comes into your eyes in a normal situation and your prediction is pretty close to where things are.

0:46:36.3 Evan Cole Lewis: So the sun has normal brightness. You don't squint, you don't need glasses, it doesn't bother you. If you are over predicting the brain, the sun's not changing, you make this over prediction, well, you have this big difference here in what your brain is expecting the brightness of the sun to be and what it actually is. That difference is your experience of discomfort in the sun being too bright. And if you take that idea and you expand it out to all the symptoms people have in TBI, long-term concussion, that is the underlying problem. The problem of how the brain is perceiving the world, it's over predicting. It's too ordered. Its networks are too structured, too rigid, they're abnormally connected. So what happens there in the concussion is; the brain gets shaken up, it absorbs a lot of energy, the cells get stretched, you have this acute response where the brain networks break down. And these are the initial symptoms of concussion.

0:47:38.8 Evan Cole Lewis: The brain doesn't like that. So what it does, it reflexively tries to repair itself. 80 to 90% of people, this works. 10% of people, the brain over corrects, it gets into this state of overcorrection and it tries to overcorrect the network, and repairs the networks too well and continues to do this in a runaway process such that you now have really strong, rigid connected networks that are over predicting everything and they're giving you an abnormal sense of perception. So someone who can't talk, the only reason I can make words and talk right now is because the next word that I wanna say, that my brain is setting my mouth up and all my muscles and everything in order to tell you, it's already decided all that and it's predicting exactly how all of the stuff should go. So it comes out well and you hear my language.

0:48:26.3 Evan Cole Lewis: If I'm over predicting those things, I'm gonna overshoot everything and I'm not gonna be able to formulate the muscles and coordinate all the muscles in a way that it's gonna formulate language like I used to. So that is an example to explain maybe this individual, and how things went there. Say he didn't have some area specifically structurally damaged in the brain, so it's a network phenomenal. It's a hyperpredictive network due to the networks being too rigid. What does psychedelics do? Integrate networks, break them down. Then you get in there with therapy and you can restore the networks. So this is one way that we're working with our patients at our clinic, and this is the hypothesis and the idea that we're running on why psychedelics might work now, whether it's ketamine or the serotonergic psychedelics, I have some thoughts there, but so far we're using ketamine and we're seeing some results with our patients here.

0:49:19.4 Paul F. Austin: Okay. I have a clarifying question. So what is the role then of dendritic sprouting? So we've heard recently that both ketamine and psilocybin helped with dendritic sprouting, which can help to create new neuronal connections in depressed brains, for example. Does that have any role in terms of helping to heal TBIs, or what does that look like?

0:49:37.5 Evan Cole Lewis: Yeah. Good point. So I left that out. Okay. So one key point here is you used the word new neuronal connections. So that's kinda a bit of a misnomer too, 'cause you don't really want new connections, because new connections implies new pathways and new connections, those are disease states. New connections are tumors, new connections are epilepsy, new connections... You don't really want new connections. The way to think about it is you've got overused connections and kinda dormant connections, because prior to the brain injury you were seeing light fine. So you have the connections to perceive light totally fine. What happens in the brain injury is one pathway gets overused and that's the rigid network. The energy gets kinda flowing down that pathway, the electrical energy. So what happens in psychedelics is when you have the two pathways, and I guess viewers are gonna have to see what I'm doing I'm kind of, one pipe is larger and one pipe is smaller, that's the more dormant pipe.

0:50:42.3 Evan Cole Lewis: Under the influence of psychedelics, the pipes become a little bit normalized in size, and then you begin to feed that dormant pipe. So it's not a new connection, it's just an older connection. And once you feed that a little bit... And this is where the dendritic growth happens, the dendritic growth goes and starts to feed that pathway, you start to reinforce new dendritic growth around that pathway that previously wasn't there. And this is where the old adage comes from, "The neurons that fire together wire together." So you start to fire more down one pathway, and as you fire that the psychedelics promote dendritic growth and synaptogenesis through the pathways where BDNF is signaled and mTOR is being on those... If you kinda dig into the mechanisms and that starts to develop and reinforce the old dormant pathways.

0:51:39.4 Evan Cole Lewis: So now the old dormant pathways start to become revitalized. So it's almost like it's not a new neuro growth, it's a real nuanced idea. But you have... But it's important to understand. And it's really important to understand, 'cause I tell this to patients, why it's so important to understand, it's so important to understand is because you can get better. Everyone can get better, everyone can improve. So you don't need to make new things, you just have to activate the old things that are not working there anymore. And the psychedelics helped to reinforce it through the dendritic growth and synaptogenesis. I'm hoping that makes sense.

0:52:11.9 Paul F. Austin: That's helpful. No. It's super helpful. It's almost... What I'm thinking of is, we often talk about how psychedelics return us to a childlike state. And when we are young children, we are much more spontaneous, we are much more open, we are much more free flow, we are much more connected, in a way. And then we learn, often through school and through church and through parents, to shut off certain parts of ourselves. It also shuts off certain parts of our brain. So this idea that these aren't new, but it's just opening up old channels that have been just not used makes total sense. Super helpful.

0:52:50.5 Evan Cole Lewis: So this is where the concept of unlearning is so important. It's not learn... So that's what... That new pathway is learning, but it's also unlearning the dominant pathway. And it's much, much more difficult to unlearn than it is to learn. Much more different. It's much more energetically unfavorable to unlearn than it is to learn I.e., getting rid of old habits, shedding old habits. And that's expressed as that, it's really hard to kick habits. Why? It's easy to gain a new habit, just do it for 6 weeks straight.

0:53:28.5 Paul F. Austin: Why do psychedelics help so much with the unlearning process then?

0:53:30.8 Evan Cole Lewis: So doing it on your own is so energetically unfavorable. Your brain is in a state, locked into that state, a high energy state that's stabilized. It's stabilized at a high energy state because it's serving some function for you. When you do therapy or you try to get to break down this high energy, you ought to give it a lot of energy. You're giving it energy with therapy, but unless you going to therapy every single day, listening to everything your therapist is saying, doing all the work in between, not feeding this with all of the crap that goes on in your life and the relationship you're not happy with and all this other stuff, you have to create such a artificial environment for therapy to work quickly. This is why therapy takes a long time. If you work at it, eventually you will unlearn these things, perhaps, presuming your life stays stable, it doesn't change, and something tragic doesn't happen, or bad. So what psychedelics do is they are able to reduce that energetic state by the mechanism and function that they act on in the brain. They provide the catalyst that can break that energy down. It's difficult to do on your own, and this is why you can then unlearn and remove that brain state and shift into another one. Hope that...

0:54:50.3 Paul F. Austin: This is helpful. Yeah. This is good. This is really good. Okay. Next question.

0:54:53.8 Evan Cole Lewis: We're getting pretty complex here. It's...

0:54:55.9 Paul F. Austin: This is good. Next question I wanna get into, I wanna talk about functional seizures. You had sent me a preprint of a paper prior that outline some thoughts, I briefly reviewed it, but it was a little over my head. [chuckle] And functional seizures are different than epileptic seizures.

0:55:14.7 Evan Cole Lewis: Yeah.

0:55:15.2 Paul F. Austin: Yeah. Tell us a little bit, what are functional seizures?

0:55:17.8 Evan Cole Lewis: Sure.

0:55:19.0 Paul F. Austin: How do they defer from epileptic seizures? And what does it look... What does the early research look like when it comes to ketamine use to help with functional seizures, and why is this important?

0:55:26.4 Evan Cole Lewis: Cool. Okay. Yeah. I'm going to walk you through an example that will solidify this concept for you and the people listening, because it's fascinating if you look at it from purely neurologic point of view, but it's really terrifying for those that have it. And it's a really difficult treatment resistant condition that affects a lot of people and causes a lot of disability and impacts those who suffer from it quite significantly. So, yeah, you've got epileptic seizures. So epileptic seizures, first off, are your classical seizures that we know of. They're expressions of motor movements that are due to abnormal electricity in the brain. So if I use what's called an EEG that measures electricity from the scalp, and I attach that to a person who's having an epileptic seizure, I'm gonna see a bunch of abnormal electrical activity that's consistent with the seizure at the time of the seizure. Functional seizures look a lot like epileptic seizures, and... But when I put an EEG on someone who's having a functional seizure, the electrical activity is totally normal.

0:56:38.0 Evan Cole Lewis: So the problem is not with the way the neurons are sending electricity back and forth, the problem is the way in which the brain is functioning, hence why we call them functional seizures. So they're these repetitive stereotyped movements that people can have, where they lose consciousness. They may or may not lose, or partially lose consciousness, looks exactly like a seizure, but not due to electrical activity. So then that begs the question, what are they? Because they often get confused. And you need expertise in epilepsy really to distinguish these, either by looking at them or by doing the proper tests. So a lot of these people go undiagnosed for many years, they get treated like epileptic seizures. So they're on medication for several years before they encounter a specialist who identifies them or does the proper testing. And in addition to that, they're very debilitating because you're having these episodes out of nowhere, difficult to work. Often it comes along with challenging mental health issues because it really sucks to have these for a long time. They can be very challenging, really not a great state. So what are they? Okay.

0:57:51.0 Paul F. Austin: Maybe even from a neurological perspective, what are they? What's happening?

0:57:53.7 Evan Cole Lewis: Yeah. So it's not entirely clear. There's a lot of models, but what you can think of them as, they're spells of dissociation. They take people out of themselves. So a way to think about this is... And I'll frame a model of kind of one model for this, to give an example. 'Cause 70... Or roughly, it can range up to about 70% of people, have challenging childhood experiences and/or trauma and/or abuse that subsequently develop functional seizures, in their either teenage years or early adulthood, more or less. So you can imagine this, you were a child growing up in a very challenging environment. Now a challenging environment is stressful at most times, so the brain starts, in its predictive ways, starts to try to remove you from the stress. It feels the stress a lot, tries to remove from the stress.

0:58:48.4 Evan Cole Lewis: And so it starts to realize that these series of events are not favorable to the brain. So it tries to find ways to remove you, and it'll make you do things, and it'll make you go to your room and avoid, and all of these things. But if you're just bombarded by this all the time, eventually over time you sensitize the sympathetic nervous system to the point where compared to someone else who's not exposed to this, you're operating at a slightly higher own time of your sympathetic nervous system at all time. So on average, your sympathetic nervous system is getting driven up, and it's getting driven up and driven up. So you're sensitizing the system, it's easily activated. Okay? Now, all people, all brains have a fail safe switch. If you are encountered by something that's too anxiety provoking, too stressful, your brain almost shuts you off.

0:59:42.5 Evan Cole Lewis: And this is... We know this from people who have really, single event traumas. What happens? They often say, "I dissociated, I wasn't there. I don't remember any of this." Your brain is saving you from that really high intense level of stress and energy, this really revved up sympathetic system. So it dissociates you, and then you come back into yourself, and you're almost transported into the future and the event is over. 'Cause your brain can't be so highly energetic, so this is what happens. So this is like this fail safe switch. Okay. So as you are growing up in a childhood that's very challenging, you have this sensitized sympathetic system that's just operating at a higher level, and your fail safe switch is more easily activated.

1:00:21.3 Evan Cole Lewis: So then when less stresses are encountered, bigger stresses, you might then dissociate, and that's really good. Once you've dissociate, it removes you from the stress, your brain decompresses, and your brain feels better after it decompresses all of this energy. Now your brain learns that that's a really good way to get you out of stressful situations. So it does it again, and then it does it again, and it does it again. And now you've sensitized your threshold to dissociate to the point that eventually in time you don't even know you do it and you just dissociate. Almost like you are listening to me now, and all of you listening, and you Paul, you're just understanding me talk, how are you doing that? At one point in time, you didn't understand how I'm giving you language and giving you ideas, you had to learn that, it took a long time, it took like three to five years of living around language as a little baby until you could understand language.

1:01:25.4 Evan Cole Lewis: So this is the same thing. It just happens to you. You just hear me and listen and process and it all makes sense. You just walk and you don't even know how you walk, you just walk. So the thing with this, you just dissociate, when you get into this state, you just dissociate. You don't even know. So any little stress that hits you, now you just dissociate and you disappear. So this sensitized threshold. So now the question is, "Well, why do people shake?" And this is really... There's a lot of complex reasons why, but one way to think about this, which might be an interesting model, is if you ever watch a documentary and you watch a gazelle getting chased by a lion across the plains of Africa and it's gets away...

1:02:07.1 Paul F. Austin: To release the trauma of the disassociation.

1:02:09.3 Evan Cole Lewis: Well, when it gets away, what does it do? Do you ever notice?

1:02:10.9 Paul F. Austin: It shakes.

1:02:11.1 Evan Cole Lewis: It shakes. It's shaking out this highly... It's high sympathetic state is so highly energetic that once it's stopped, the brain can't decompress the energy fast enough, it actually has to decompress it through muscle movement and allow it to go. So what functional seizures are, are hypersensitized dissociative spells that at one time was adaptive when you were a little kid because, or a younger person, it got you away from the stress. But then the brain learned and liked it so much, it just does it all the time. And there is... And the last thing I'll say about this is there is some interesting studies, if you attach people to of measures of your sympathetic nervous system, like heart rate variability and other measures, and what you can see is, as you're talking to these people who suffer from functional seizures, their heart rate starts to become quite variable.

1:03:06.5 Evan Cole Lewis: That's a sign of high sympathetic stress. If you or I felt that, we would feel that and we'd start to feel anxious and we'd be like, "Oh, this is a bad situation. I got to get out of here. I don't like this. I'm not feeling good." When people have the same types of heart rate variability and you ask them, "How are you feeling?" They'll say, "Fine." And so it's called panic without panic. Their inside sympathetic nervous system is going, but they have no conscious awareness that it's going. So they're separated from their fight-and-flight response, such that the next little stress that comes on, the brain just associates and moves them forward in the future. So these are functional seizures, totally difficult to treat.

1:03:43.1 Evan Cole Lewis: Now what do they do to? Overall, what I'll say, the brain's predictive capacity has done this therefore, it's rigid networks. And we know this, there's a lot of network signs, underlying functional seizures that shows abnormally connected networks, some that are too interconnected. And so our hypothesis, and a lot of people within this field or some a... Set of people within this field, for these types of disorders have queried whether psychedelics can work.

1:04:10.8 Paul F. Austin: Ketamine in particular.

1:04:12.2 Evan Cole Lewis: So ketamine, there's one case report out there about someone who had a arm paralyzed because of this, very similar kind of mechanism, and ketamine worked for this individual. So we posited that this might be the case with ketamine for functional seizures. And there's a case report that's in review right now, and it should be out for publication, hopefully, within the next month or two, from our group here, where that we met a woman who was having two to three seizures a day, two to three functional seizures a day, not epileptic seizures, for five years. A whole host of a lot of other difficulties, challenging childhood, drug dependent, suicidal, suicide attempts, a really challenging life. And we brought her in for ketamine-assisted therapy, and after three sessions of having... After having two to three seizures a day for five years, three ketamine sessions, three weeks apart with therapy, after the third session, she went seizure free for nine days.

1:05:14.8 Evan Cole Lewis: Eight months later, we did some maintenance ketamine after the therapy, eight months later, she's having two to four seizures a month that are mild that she can stop most of them, most of the time. She's back at work, she's functioning, she feels amazing, her depression scores are down. It is, from a person who's dealt with functional seizures for a long time and has felt really challenged by this and disheartened, because you can't really help these people and it's really, this is almost...

1:05:45.3 Paul F. Austin: It's a breakthrough, potentially.

1:05:46.7 Evan Cole Lewis: It's a breakthrough. It's amazing. Yeah.

1:05:49.7 Paul F. Austin: And I think that's a great place to land. We're almost up against the hour mark here, but what breakthroughs are you learning about through psychedelics as it relates to neurology? What are you most excited about the next three to five years in terms of how psychedelics will change the neurological landscape?

1:06:07.8 Evan Cole Lewis: Yeah. I think it's going to inform us about network neuroscience and how to manipulate networks very precisely. So ultimately, I think we're gonna learn that... Someone will come in and after processing their history, doing some functional imaging, maybe doing some testing of their genetics markers, you're gonna have a panel of an individual, you're gonna be able to realize that, "This person needs this type of setting. We're gonna start with MDMA, and then we're gonna do two weeks of ketamine, and then we're gonna use psilocybin, and then six months later LSD." And we're gonna have this very tailored type of approach to people, 'cause we're going to try to reorganize their networks. And I think that's where this medicine... We're gonna... It's gonna move into kinda like precision psychedelic medicine in shifting networks and really getting at conditions and disease states that we really don't have answers to right now.

1:07:14.8 Paul F. Austin: Including what we talked about today, TBI, concussions, functional seizures, also something we didn't get to touch on too much, cluster headaches, migraines, right?

1:07:22.7 Evan Cole Lewis: Yep.

1:07:23.2 Paul F. Austin: There looks to be a lot of promising treatment potential with psychedelics. And, of course, the biggest block is prohibition, funding. And so I think that just speaks to the importance of what Numinus is up to with all of the clinics that you now have and are working on with legal ketamine, as well as many other modalities. And it's hopeful when places like Colorado legalize and California has it on the ballot, and MDMA and psilocybin will soon be here. But that is a... It's like a goldmine that we're just so close to tapping. And I think so many of us are not only enthusiastic, but just optimistic about how psychedelics can really help to treat very difficult neurological diseases and disorders.

1:08:19.0 Evan Cole Lewis: Yeah. Agreed. Totally optimistic, excited, recognize, though, we have to be patient in a couple of ways. We have to be patient so we're safe on the neurology side, but I think we also have to be patient with the neurologists. Of all the specialties, neurologists are probably [chuckle] a group that are quite embedded in a dichotomy of A, B, yes, no. This is the field of neurology, and the field of neurology is going to have to undergo, itself, it's gonna have to undergo a renaissance of its own to really accept this. And it's a function of all the things we've talked about. If we wanna really come full circle with the analogies and metaphors you've been using, neurology is the ordered, rigid brain network, and psychiatry and psychology is the more entropic type of brain. So there needs to be a merit there too.

1:09:17.5 Paul F. Austin: Which is saying something...

1:09:18.9 Evan Cole Lewis: Yeah. Yeah.

[chuckle]

1:09:20.1 Paul F. Austin: If we're referring to psychiatry and psychology as that. Dr. Evan Lewis, Medical Director at Numinous Toronto and VP of Psychedelic Neurology at Numinous. Evan, it's been a pleasure. We get to have a lot of private conversations, it's nice to have a public one for all of our listeners. You're incredibly informative and knowledgeable and thoughtful, and thank you for all the work that you're doing around psychedelics in neurology. It's super pioneering and it's really been fun to chat with you today.

1:09:48.1 Evan Cole Lewis: Same, Paul. Appreciate it.

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1:09:56.1 Paul F. Austin: Hey folks. This conversation is bigger than just you or me, so please leave a review or comment so others can find the podcast. This small action matters way more than you can even imagine. You can also go deeper into this episode at thethirdwave.co/podcast, where you'll find full show notes, transcripts, and all the links that were mentioned in this conversation. To get weekly updates from the leading edge of this Third Wave of psychedelics, sign up for our newsletter at thethirdwave.co/newsletter. You can also find us on Instagram @thirdwaveishere, or subscribe to our YouTube channel at youtube.com/thethirdwave.

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