Telemedicine, Ketamine Lozenges, and Healing Depression


Episode 101

Dr. Casey Paleos

Dr. Casey Paleos is among the earliest researchers in the third wave of psychedelic study, both in ketamine and other psychedelics. In this episode, he and Paul discuss the use of ketamine in telemedicine, early psilocybin and ketamine trials, effective ketamine protocols, and re-forming the grooves in our brains.

Dr. Casey Paleos is a board certified psychiatrist with over a decade of experience working with ketamine and other psychedelic medicines in both research and clinical settings. A Co-Principal Investigator for the NYU-Bellevue Ketamine for Depression Study, Dr. Paleos was one of the early researchers to identify ketamine as a breakthrough treatment for depression. As a clinician, he has been treating patients for depression and anxiety using ketamine therapy in his New York private practice since 2016. He is the scientific director at Mindbloom, which provides ketamine therapy via telemedicine.

This episode is brought to you by Mindbloom, a mental health and wellbeing company on a mission to help people expand their human potential by increasing access to effective science-backed treatments for anxiety and depression, starting with guided ketamine therapy. Mindbloom partners with licensed psychiatric clinicians to help their clients get the most out of treatment through technology, content, and hospitality-inspired client experiences. Third Wave's viewers can get $50 off with the code "thirdwave is here."

This episode is brought to you by Mindleap, which connects you with trained psychedelic specialists, who help you to prepare and integrate your microdose and high-dose experiences. You can download the Mindleap app today on iOS or Android and start working with any of Mindleap's 40 specialists. Just use the code ‘THIRDWAVE’ for $25 off your first session.

Podcast Highlights

  • The ins and outs of telemedicine ketamine therapy.
  • The history of ketamine, from battlefield anesthetic to sedative to psychedelic treatment.
  • Psycholytic vs. psychedelic therapy.
  • What is the Wolfson Protocol and how does it work?
  • Does real growth require the use of psychedelics therapeutically, rather than  recreationally?
  • How Casey’s early psychedelic experiences influenced his career path.
  • From drugs of abuse to profoundly impactful psychological treatments: tracing the history of psychedelics.
  • Inside the first psychedelic research studies in 50 years, and the challenges of being on the forefront of the third wave.
  • Paul’s own experience with ketamine lozenges, and his upcoming intramuscular injection session.
  • From the vicious cycle of ruminative thinking to quieting the default mode network, enhancing neuroplasticity, and forming healthier brain patterns.

Podcast Transcript

0:00:00 Paul Austin: This episode, we have Dr. Casey Paleos, the former medical director and now scientific director at Mindbloom. He was a board-certified psychiatrist with over a decade of experience in working with Ketamine and other psychedelic medicines in both research and clinical settings.


0:00:16 PA: Welcome to the Third Wave Podcast. I'm your host, Paul Austin, here to bring you cutting edge interviews with leading scientists, entrepreneurs, and medical professionals who are exploring how we can integrate psychedelics in an intentional and responsible way for both healing and transformation. It is my honour and privilege to bring you these episodes as you get deeper and deeper into why these medicines are so critical to the future of humanity. Let's go and let's see what we can explore and learn together in this incredibly important time.


0:00:55 PA: One of the biggest challenges that people face with psychedelics still being illegal is finding a reputable coach, therapist, provider, practitioner who can hold space for them, both in the preparation and integration process. And that's why we're so excited to partner with Mindleap Health, which has built an application that connects you with trained psychedelic integration specialists. These specialists can work with you to unpack the complexity of your psychedelic experiences and help you to derive greater meaning from either a therapeutic or just a recreational psychedelic experience.

0:01:30 PA: So if you're interested in learning more information about Mindleap Health, you can download their app today on iOS or Android and start working with any of their 40 psychedelic specialists. I will be featured as a coach on the platform as well as our other microdosing coaches here at Third Wave. And if you want to work with anyone on the platform, again, to either prepare or integrate your psychedelic experience, you can use the code "THIRDWAVE" to get $25 off your first session. That's code "THIRDWAVE", to get $25 off your first session.

0:02:05 PA: And this podcast is sponsored by Mindbloom. Legal psychedelic medicine is here and it's available through Mindbloom. Mindbloom helps you transform your life with safe science-backed psychedelic therapy. If you're looking for your depression or anxiety breakthrough, Mindbloom provides a fully guided and clinician-monitored experience tailored just for you. Some clients see results as soon as 24 hours after their first session. Mindbloom is in fact, our first official partner here at Third Wave, and a company and organisation that we support.

0:02:40 PA: In fact, I'm going to start my own Mindbloom experience in the coming weeks, and will write about my experience going through Ketamine therapy to address both Cannabis addiction and general anxiety. The Cannabis was to cover up the anxiety and I can't wait to share my own transformation with you.

0:03:07 PA: Hey, listeners. And welcome back to another episode of Third Wave's Podcast. Today, there were a few surprises. I will say there were a few surprises in the episode. We sat down with Casey Paleos, a board-certified psychiatrist, and it turns out, I had no idea prior to the conversation, but Casey was involved in the first ever Psilocybin for end-of-life anxiety research trial, NYU. So he is basically one of the OG OGs, has been involved since the very early days. I think it was 2009 or 2010, was when he was a medical student at NYU and then was involved in some of the clinical trials that were going on.

0:04:00 PA: And we get into that context and that history in today's episode. We also get into Mindbloom's programme. Mindbloom is an official partner of Third Wave, so as part of our intention to create a trusted ecosystem for our community, like listeners like you, we're starting to develop strategic partnerships with companies in the emerging psychedelic space. And what I love about Mindbloom's model is they do telemedicine Ketamine therapies. You can actually get Ketamine sent to your home and you can go through their guided experiences through an app, and then they will also plug you into a guide or a facilitator who will be there to help hold space for you.

0:04:42 PA: And they have a four-step process treatment protocol, and we just get into some of those specifics in this call. What Ketamine does is they use, or, I'm sorry, what Mindbloom does is they use Ketamine lozenges, so we talk about the difference between Ketamine lozenges and IV Ketamine, which is much more... Or, I'm sorry, IM Ketamine, there's all these different ways to do Ketamine. So IM Ketamine is more of a full-on psychedelic trip, Ketamine lozenges are much more like a psycholytic therapy, which is why it's very useful to root things up, to look at them, and then process them as needed.

0:05:16 PA: Casey is quite voracious in his vocabulary, so we had a few little fun moments where he had some really interesting play on words as well, so these are just fun dynamic things that emerged in the conversation, but genuinely, it was a pleasure to talk with Casey. We hadn't really connected at length before. I'd never met him at a conference. We had done one webinar in the early days of COVID. And so to have a chance to sit down with him for over an hour and to dive into all things Ketamine, psychedelic therapy, his personal experiences with psychedelics, he was very open about them, which not all professionals in the space are. And then going and diving into Mindbloom's approach, why it's effective, and what we can learn from it.

0:05:56 PA: And I'm recording this intro on November 2nd and I will be going through the Ketamine treatment, the Mindbloom Ketamine treatment myself fairly soon to help address some issues with anxiety, so that's something that I'll also be writing about publicly in the near future. So keep an eye on Third Wave's blog and my Medium page. If you wanna follow me on Medium or on social, I'm @PaulAustin3w, PaulAustin3w, and yeah. So Casey Paleos, MD, board-certified psychiatrist and scientific director at Mindbloom.

0:06:41 PA: You've been on the NYU studies, and those were for Ketamine, or you were on... Looks like you were also on the Psilocybin for Cancer Anxiety.

0:06:50 Casey Paleos M.D: Yeah, yeah. Started out, cut my teeth in the field of psychedelic medicine while I was actually still in residency at NYU. Was a study therapist in the Psilocybin Cancer Anxiety trial there. And then after I graduated residency, I stayed on as an attending in the Emergency Department at NYU in Bellevue for about five years. And during that period of time, Steve Ross and I... Steve was the PI, one of the PIs on the cancer anxiety study. He and I co-designed and led Ketamine for depression trial that took place in the ED at NYU in Bellevue, and that was my first first-hand exposure to using Ketamine clinically.

0:07:32 PA: Was that one of the first studies that was done? Because I know, it's a little bit hard to say.

0:07:37 CP: Well, no... Yeah. No, it had been done... We were actually... This was back when I was doing that Ketamine study. This is probably around 2013 or so, 2013, '14. So, yeah, it'd been going on for a good 10 years. It'd been maybe five or six or seven years since the Zarate study from NIMH, that was published in 2006. That's the one that replicated the John Krystal study from Yale in 2000, but it was in 2006 that the field at large really started paying attention to Ketamine.

0:08:08 PA: So what is that timeline for Ketamine? Because I'm familiar enough with the psychedelic research. Johns Hopkins published the mystical experience in 2006, the Psilocybin occasioned mystical type experiences. And then we have the one that was published in 2000, I think '11 with Katherine MacLean about openness. And then the NYU one. What is it then... 'Cause Ketamine's been in use since the '50s or '60s, since an anaesthetic or whatever.

0:08:29 CP: Early '70s. Yeah, it was synthesised in 1962. In 1966, it started being used in Vietnam, became very widely used as a battlefield anaesthetic there amongst soldiers. And then in 1970, it was approved for civilian use by the FDA as a surgical anaesthetic and a procedural sedative. So that's its official, to this day, its official FDA indication, is for those things. And it was in practice, and it became hugely, widely used, especially in third world countries, developing nations, and even to this day, it's probably the most widely used anaesthetic because of its wide safety margin. And you don't need a lot of high-end monitoring devices or a lot of staffing the way you do with more conventional anaesthetics.

0:09:17 CP: Because uniquely amongst injectable anaesthetics, it doesn't suppress respiratory drive, it doesn't drop blood pressure. Which is another reason why it's really useful in the battlefield if you're exsanguinating from a gunshot wound, you don't wanna be giving something that's gonna lower your blood pressure. Ketamine actually preserves blood pressure and allows interventions to happen in the field that aren't gonna be dangerous from the anaesthetic itself. And it's not as favoured in anaesthesia, in the United States at least, but it is very commonly used in emergency medicine, especially in paediatrics. Because, again, of its safety profile and because it has, at least when given intravenously, it has a very rapid onset and offset, lasts pretty briefly, probably around 10-15 minutes from a single dose of full dissociative anaesthesia or procedural sedation.

0:10:06 CP: So that's really useful if you have a six-year-old that comes in with a laceration on their scalp or something, and they need a suture, very easy for an emergency medicine physician to give Ketamine, have them anaesthetised just long enough to put the sutures in, so the kid isn't even more terrified and in pain than he is. So it's been widely used in those contexts for, at this point, 50 years. But it wasn't until studies done at Yale, mainly in the late '90s, that the mainstream psychiatric fields really took notice of Ketamine. And it had actually been used as a psychedelic, dating almost at the very beginning of its history in the early '70s. There were some studies done... There was one done in Iran, another one done in Argentina. There was a guy in Mexico, Salvador Roquet, who was a fascinating psychedelic researcher who would use Ketamine in these... To the modern mind, really insane 24-hour protocols where he was using LSD and Datura and...

0:11:08 PA: Whoa. [laughter]

0:11:08 CP: Yes, yes, yes, and morning glory seeds, and crazy 24-hour sessions where the... The therapist would be there the whole time and they're projecting these crazy videos and photos from the person's life, childhood photos, and juxtaposing that with really horrific images from, I don't know, movies and strobing lights and intense music. This really crazy protocol that he claimed to have really good success with, and this was actually a sanctioned research in Mexico in the mid-'60s, and he was a guy who was in communication with a number of the researchers at Spring Grove and Stan Grof and Bill Richards, and that really seminal old school coterie of psychedelic therapists, at the tail of the second wave. He was known to them.

0:11:55 CP: So he was using Ketamine in that context, but then there were also some other more sedate researchers using Ketamine as more of a Ketamine-Assisted Psychotherapy model/psychedelic model, but that didn't go... Wasn't very well known, I don't think, to the field, at least in the States. There was a Russian researcher who was using it starting, throughout the '80s and '90s up until the early 2000s, who's used it in thousands of patients, largely actually in addiction, alcohol and opiate, but other types of psychiatric conditions, too. His name is Evgeny Krupitsky.

0:12:32 CP: He did a lot of seminal work using Ketamine, which has since, the Russian government shut it down in 2002, because after the fall of the Iron Curtain, there was a lot of abuse of Ketamine amongst teenagers. It became an epidemic there, and so the government cracked down and said, "Nobody except for anaesthesiologists basically can use Ketamine anymore. So he wasn't... Even though he's obviously an MD and still practicing psychiatry and doing research, he wasn't allowed to use Ketamine in his research anymore.

0:12:58 CP: There's a guy named Eli Kolp who was one of his proteges who came over to the US and still practices using that model in a place in Florida called The Kolp Institute. Its use in psychiatry actually goes back quite a bit longer or further back than 2000, but 2000 is when, what's now known as the NIMH protocol was born, which was half a milligram per kilogram intravenous over 40 minute in a drip by an anaesthesia model, where you're giving... Generally, now it's four to six infusions over a course of two to three weeks, and it's a very...

0:13:34 CP: I would say, it really highlights a very interesting split in the field, in the medical field, particularly in the psychiatric field. There's the camp that is very reductionist and wants to distil all of mental illness or cognitive and emotional phenomena to simple brain function, and wants to conceptualise the efficacy of Ketamine, in this case, as a strictly biologic-pharmacologic one, and I certainly won't argue against the fact that it very clearly does have very potent neurophysiologic effects that are involved in its efficacy, but most of the Ketamine infusion clinics that exist currently in the States are run not... By practitioners who have no mental healthcare background, they're largely anaesthesiologists or nurse anaesthetists.

0:14:21 CP: There's some emergency medicine doctors doing it, and a very proportionally small number of actual psychiatrists using Ketamine in that way. But then you have, I think, an increasing number of psychiatrists and psychologists who are using more of a Ketamine-Assisted Psychotherapy model. So there's the KIT, Ketamine Infusion Therapy, that's more of like the NIMH anaesthesia type of administration, and then there's KAP, or Ketamine-Assisted Psychotherapy, which is trying to leverage the state induced by Ketamine as a tool for psychological exploration.

0:14:55 CP: And I think the real difference and the crux there of the difference is, on the one hand, the medical reductionist model really discards the subjective contents of the Ketamine experience as pathological at worst, trivial at best. It's seen as a nuisance, something to be reduced, like the dissociative and psychedelic effects are seen as problematic, whereas the more, I think, enlightened holistic view actually does perceive the actual value of the subjective contents of the experience and is really trying to work with that and work with the information that is being furnished thereby by the patient's unconscious to understand where healing needs to go for a given person.

0:15:39 PA: For some of that research so far, Phil Wolfson has written The Ketamine Papers and helped to pioneer the Ketamine-Assisted Psychotherapy model. How does that compare to psychedelic-assisted psychotherapy, in terms of efficacy and what's going on there?

0:15:55 CP: Yeah, the Wolfson model's interesting. He published... He did, yeah, The Ketamine Papers, which was great, a great contribution to the field, for sure, he edited, but he also published a paper along with a number of his colleagues. I think it was three different clinics around the country had been using both sublingual and intramuscular administration of Ketamine and a Ketamine-Assisted Psychotherapy model. And in that paper, which was published, I think in March of last year, they talk about two different forms, which they refer to as trance and transformation.

0:16:33 CP: So the trance is, I think, more akin to what we might call the psycholytic approach, psycholytic versus psychedelic psychotherapy, where you're inducing a state of relatively mild dissociation that is preserving a person's narrative sense of themselves as an individual person in the world, preserving the subject-object, I-thou normal constituents of ordinary consciousness, but using the sort of dissociation that Ketamine induces in that dose range as a way... So in that dose range, it definitely diminishes activity in the default mode network and helps soften, I think, thereby the habitual defenses that people use against unconscious material that, for one reason or another, the psyche is trying to keep sequestered out of the waking state, largely usually because there's negative emotional affect or that is attached or confected to that material.

0:17:33 CP: It's kept out of conscious awareness because we need to get groceries and we need to drive to work, and we need to function, and we're being flooded with these really painful memories or experiences, functioning isn't really possible. So it's a short-term solution that the psyche uses just to promote functioning in the world, but over the long term is deleterious to the person because those experiences, unless they are processed and metabolised properly, do not heal, and they become these psychic abscesses that are constantly leaching toxins into the whole system in various ways.

0:18:11 CP: And what Ketamine does, I think, is, or can do, in the trance or psycholytic dose range, is soften the walls around that abscess and allow more direct access to the material, which in the presence of a skillful therapist can be really conducive to powerful healing experiences, versus the higher dose intramuscular Ketamine that they were using. So the way that they described their protocol, Wolfson described the protocol that he was using, along with these other clinics, is that they would generally start people with sublingual in the office and see how they tolerated it; do some work in that state, engage with some of this material.

0:18:56 CP: And then, presuming they tolerated it okay and made a certain amount of progress, at some stage, they would say, "Okay, now it's maybe time to go into a deeper experience," and they would offer an intramuscular Ketamine experience, which he describes as transformative, and that would be more of the psychedelic type of experience. And these are experiences that can be really profoundly psychedelic and shading all the way into the full-blown mystical experiences where people are losing that sense of I-thou, the subject-object distinction, and having experiences of oceanic boundlessness and bliss and noetic certainties about certain things, and obviously those can be...

0:19:35 PA: Ineffability, right, the William James sort of...

0:19:36 CP: Yes, exactly.

0:19:37 PA: Five characteristics.

0:19:39 CP: Yes, yes. Positive mood, ineffability, loss of ego boundaries, and sense of oceanic boundlessness, yeah, all that stuff, which is what, as you mentioned earlier, Roland Griffiths and his team at Hopkins published about, years ago, back in 2006. So, yeah, you can get that with Ketamine too, for sure, and for reasons that remain a bit mysterious, that, in and of itself, can be really potently transformative. But I think in all cases with... Which was, whichever method you're using, to induce the mystical experience, the integration obviously is a hugely important piece, and how are you translating this really information-dense packet of psycho-spiritual material that you're encountering in this psychedelic experience and unravelling that and weaving it into this tapestry of how you're living your life from day to day?

0:20:32 CP: That is really the work, and which is why people can go to a rave or a club, or some place where they're doing psychedelics recreationally and have really powerful experiences; when they get back to their job on Monday morning, it's back to the same rut in a lot of cases. So I think... Not to say that recreational use is necessarily always bad. If you're trying to leverage the effect of these medicines in a way that promotes healing, it does need to be used in a more systematic context and a much more thoughtful context than just like an isolated excursion into some psychonautic amusement park and then back to work on Monday morning.

0:21:14 PA: Right, like Burning Man.

0:21:15 CP: Yes, exactly.

0:21:16 PA: Pretty much Burning Man is what you're talking about.

0:21:17 CP: It's pretty much Burning Man. [laughter] Yeah, yeah, yeah.

0:21:21 PA: The psychonautic theme park, I like that, that's probably gonna be the quote. Hear Casey Paleos talk about the psychonautic theme park. [laughter] And this is all great, Casey, 'cause it helps our listeners have a fairly good understanding, just to summarise, and come back to a point in the centre, a fairly good understanding of the lozenge approach which is a more psycholitic approach, from what I understand, compared to an intramuscular approach, and just putting them into that mystical experience, oceanic boundlessness. And what I wanna do is I wanna return to, specifically how Mindbloom, where you are the science director, you've helped develop the protocols and programmes, how Mindbloom is doing that.

0:22:02 PA: But before we get into that, I think what a lot of our listeners definitely love to hear is just how you started to get involved in this work in the first place, because you've been, like you said, back in 2000, I think '12, '13, '14, you've been involved in this space really since the very early days, I would go so far to say. So coming from a board-certified psychiatrist perspective, you're really one of the early pioneers in this survey of the psychedelics. So before we get back into the programmes and the efficacy of Ketamine therapy, just a little bit more context around, how did you get involved in this work? How did you get involved in these studies? Why do you care about this so much? I'd love just a little bit of a perspective or insight into that, into your own world.

0:22:45 CP: Sure, yeah. I'm happy to elaborate on that. I guess it goes back to my own irresponsible recreational use of psychedelics in my late teens, and I'm 44 now, so I'm pretty sure the statute of limitations has expired on that. But, yeah, at age 18, 19, my first couple of years of college, I had some really powerful experiences with LSD and Psilocybin, changed my life completely. And it was shortly after that I discovered the work of Carl Jung, and so did really seriously, just developing my own internal spiritual life, it just evolved into a kind of... I wouldn't say it was super systematic, I didn't join an ashram or anything, but it definitely woke something really powerful in me that remains very powerful to this day, this sort of inner internal seeker and it just awakened this gnostic thirst that I've had really since that time.

0:23:42 CP: And maybe even before then, if I were to reflect back into my early childhood, I think it's all contiguous on some level, but had those experiences early on. Some of them were amazing, accidental epiphanies that really changed my life and I was using them in the spirit of that most adolescents, I think, do stupid things which is, 'cause it's there and it's fun, it seems fun. And your friends are doing it and it seems like something fun to explore. But it became a lot more profound than that for me. And I stopped using it for many years, followed Alan Watts's advice and hung up the phone after I got the message. But the insights and inner transformation that occurred has really stuck with me.

0:24:21 CP: And so that happened a long time before psychiatry was even on my radar or mental health, and I went... I was an undergraduate at Cornell. I graduated 1998, but I had majored in Film Studies, thought maybe I wanted to be a filmmaker, realised that I don't have anywhere close to the level of self-discipline that would be necessary to actually make a career in doing something creative. And so decided to go back and fulfill the prerequisites for medical school. Long story short, ended up going to University of Pittsburgh for med school in 2003. And didn't go there thinking I wanted to go into psychiatry, I didn't know... Carl Jung was one of my heroes, but I hadn't... My impression of psychiatry at that time was that it was a lot of pill-pushing and not a lot of psychotherapy, and I wasn't... It didn't really interest me to just do that.

0:25:09 CP: I thought maybe I would be an emergency medicine doctor or a surgeon, or something along those lines, but during med school, you do all your [unclear speech] rotations and in different fields to figure out what your aptitudes are, and during my psychiatry rotation, it was just... I actually realised that my very rudimentary conception of it was not accurate, and that you can actually really do meaningful and powerful work with people even in the modern rubric of psychiatry. And it was also just where my tribe was. You find in med school who your tribe is, and for me, it was people practicing psychiatry, interested in it, were people who still preserved a huge, in many cases, interest in humanities and art, and I didn't wanna lose, that has always been a very important piece of my life.

0:25:58 CP: Literature and film and music to this day remain very important parts of my life. And a lot of other fields of medicine, it selects or breeds for a more... Mindset that isn't as appreciative of that stuff. Which just seemed really amazing to me that I can practice some branch of medicine and still have the content of a film or a book be actually relevant to the treatment I was doing, which you can't really say for any other field of medicine besides psychiatry, so... And I was also really fascinated with just the narratives of people's lives and how people make meanings of their lives. And so that's what led me into psychiatry ultimately. But when I graduated med school in 2007, first of all, the research at NYU still was a year or more away from starting, and I was totally unaware of the second wave of psychedelic research at that time.

0:26:47 CP: I had known and read about the stuff that was going on in the '40s and '50s and '60s. I knew about that history, but was totally unaware of Rick Strassman's work, or maybe I'd heard something about the DMT, The Spirit Molecule, but didn't know that there was anything happening at Hopkins, didn't know about Charlie Grob at UCLA, and those are the only two things that were actually happening, I think at that point. Not on my radar when I started residency. And then in 2009. I was, I think, a third year resident, I attended a lecture by Steve Ross, who was... I had known because he was one of my professors in the substance abuse module of our didactics as a resident. We would take classes and he was one of our teachers, and so I knew him from that. But he was giving a talk.

0:27:32 CP: I remember sitting down for this grand rounds presentation, which is this thing where, as a resident, you go because basically they give you free lunch, [chuckle] and then you sit down and sit, and listen to somebody lecture on something for an hour, and often they're informative and interesting. But he goes up to know what he was talking about, and he starts presenting on the very early, maybe for six patients or so, that... In the Psilocybin Cancer Anxiety trial, and I was totally blown away. Up until that point in my life, as I mentioned, this sort of gnostic flame had been lit for me 20 years previous, almost, but maybe at that stage, it was more like 10 or 15 years, but I had no inkling whatsoever that could ever be woven into what actually, my day job, so to speak, or what I could actually make a career out of.

0:28:16 CP: And so this, sitting in this lecture and hearing him talk about this research that was happening, not only did I learn for the first time that it was actually happening in clinical research and the psychedelics, but that it was happening at the actual institution where I was training, literally in my backyard. It just felt almost too serendipitous or synchronistic to be an accident. And I don't know, everything's crystallised for me in that moment, and I knew this is what I was... Why I'm in residency here, it just made everything for me, and I'm not... Certainly, this isn't a novel insight, the ancient Greeks talked about this, but life really only makes sense in retrospect, and it's amazing how it does.

0:28:56 CP: It's amazing how you can look back over the course of your life and these seemingly totally disconnected phenomena weave this really beautiful, meaningful tapestry when looked at in hindsight, and this was one of those moments for me, was like, "Oh, that's why this happened, and that happened, and this happened, and I'm now sitting in this lecture hall at NYU as a resident." And so, anyway, I approached him after the talk, was gushing about how excited I was, and he was really gracious and said, "Yeah." I asked him, "How do I get involved in this work? How can I do this?" And he was like, "Send me an email and we'll make it happen." And long story short, I became the first psychiatric resident to conduct psychedelic psychotherapy in 50 years, within a few months of that. [chuckle] Yeah. So it was really just remarkable, and I was just in the right place at the right time, very lucky in that respect.

0:29:46 PA: And Carl Jung has a term for this.

0:29:48 CP: Synchronicity, yes. Synchronicity, yeah, yeah. Yeah, I don't really believe in accidents, not where this type of... And it's interesting, the more you do... I found that the more in tune you are with just your inner truth, just what really resonates with you as a person, the more you get to know yourself and who you are, and what purpose you have. 'Cause I do believe that everybody in life has a purpose. The more you can align your activities, your outer activities with that inner reality, that inner truth, the more you can actually allow the outer to resonate with the inner. It really, I think, enhances the frequency and the profundity of these synchronicities. That's been my objective, observed experience in life. I don't know if that...

0:30:35 CP: And there are plenty of reductionist arguments as to why that is not... Maybe it's apophenia or pareidolia, or I'm just trying to see patterns where there aren't any. But, that's not real, those explanations are not sufficient for me. It's just too profound to dismiss. But, anyway, so that's how I got into the Psilocybin Cancer Anxiety trial, and that was life-changing for me. It was really profound work, just the clinical and just the richness of the clinical work. And I had already, even in my third year residency, started to become a little bit disillusioned with this mainstream psychiatric model, I think... I don't know if we wanna get too deep into the weeds of [unclear speech] psychiatry, [chuckle] but I don't know how much time you have, but I don't know how long...

0:31:22 PA: There's a really good book, there's a really good book called the Anatomy of an Epidemic...

0:31:27 CP: Yes.

0:31:27 PA: Which... There are probably many good books, but I read that one back in 2016 on a recommendation from a close friend, because I was... Third Wave started in 2015, I was starting to get into this space, and she's, "You really need to read this book." And what they talk about in that, as you had referenced earlier, is this biological model that was actually built off of the penicillin model...

0:31:48 CP: Yes, exactly.

0:31:48 PA: Of what was effective from an antibiotic perspective, and they try to approach brain health...

0:31:53 CP: Right.

0:31:53 PA: As they did with the antibiotic method, and that was the underlying framework for antidepressants and anti-anxiety medications and some... Adderall and Ritalin and some of these...

0:32:03 CP: And that legacy is still reverberating very powerfully in modern psychiatry today, and you can achieve partial efficacy with that, but to me, it's... You're pruning the branches where, in a situation where the disease is actually in the roots, and yes, maybe you can make their branches look a little better and functioning can improve somewhat, but if you're not addressing the roots, what are we actually doing? And what is the meaning or the purpose of the work that we're doing? I'm not interested in making people more efficient cogs in this sick machine that we live in; I'm interested in actually promoting genuine healing, and I don't think you can accomplish that with an SSRI. In fact, I know that you can't really accomplish that with an SSRI. An SSRI can maybe help people function, and this isn't to knock SSRI.

0:32:54 CP: Years ago, I was depressed and diagnosed with depression and went on an SSRI during medical school, probably saved my life, but it's... So it's not to dismiss the utility of that, but to get deeper, you can engage in psychotherapy, and I think SSRIs can make psychotherapy easy enough or can make a person who's functioning poorly, function well enough to then engage in psychotherapy, and you can... I think genuine transformation and healing can happen in psychotherapy, but too often, it's really... People are so defended around, especially with trauma, significant trauma, developmental trauma, that talking about it, the talking cure, so to speak, is just not enough. And this is what we... Why I think psychedelics are important to the field because... So I should say that since, after I left NYU back in 2017, I took on a job as a co-principal investigator alongside Ingmar Gorman, who I know is, you've talked to a couple of times.

0:33:56 PA: Yeah, I love Ingmar.

0:33:56 CP: Yeah, he's great. Yeah, he and I have been Co-PIs on the MDMA-assisted psychotherapy study in New York City for three-plus years now. And so I've continued the research with using MDMA, and with these substances, you can create the conditions for really profound healing experiences that are just not possible with conventional means. And so my point is, I was... Even as a resident, I was starting to come up against this frustration of just the limitations of conventional methods, and seeing first-hand through the Psilocybin Cancer Anxiety Study what is possible using these agents, it's not even a question to me that this is the future of the field, and it's something that preserves the meaningfulness of what we would call symptoms in a way that eludes the reduction as sort of penicillin-based model of psychiatry that still unfortunately predominates the field.

0:35:00 CP: When I was in training, psychedelics were... We certainly didn't learn anything about the history of psychedelic research or psychedelic medicine at all. And when we were taught about "psychedelics," we were just told that they were drugs of abuse and drugs that should be avoided, and the drugs that can induce psychotic disorder. And with Ketamine, Ketamine also, even though it's legal, has been legal all this time, was only ever talked to us as a drug of abuse. Even back then, I think I'm sure the curricula now are probably quite a bit different, just given all the research has come out. But when I was in residency from '07 to 2011, it was still barely a blip at that point. And again, I think it just really underscores this bias, this implicit bias that exists in psychiatry and in the culture at large, against the usefulness of altered states of consciousness. If you're in a state of consciousness that isn't either totally ordinary or maybe a little bit hyped up on caffeine and/or a stimulant, you're not useful...

0:36:03 PA: Or alcohol.

0:36:04 CP: Or alcohol. Alcohol is different. Alcohol, I think, is just a way to, I don't know, let people blow off steam, and if you're drunk, that's a trivial altered state of consciousness. "Oh, he's just drunk." But if you're on psychedelics, there are really profound experiences that can happen and profound truths that can be hit upon, that the mainstream, conventional psychiatric view would tell you are just pathological or trivial, and this is simply false. I think, gradually, the field at large is starting to come around to this idea, but these prejudices 10 years ago were even much more pronounced. Anyway...

0:36:41 PA: I wanna get into two things now. The first thing I just wanna hear about, 'cause it's such an interesting tidbit in this conversation, is the fact that you were the first psychiatrist in residence to be part of a clinical trial with psychedelics in 50 years, and Michael Pollan wrote a fantastic article in 2015 for The New Yorker...

0:36:58 CP: Yes, I remember.

0:36:58 PA: Called Trip Treatment, which was about these studies. So I'd love if you could just bring us into that time period. It's 2012 or 2013, right?

0:37:08 CP: No, earlier than that actually. This was 2010. I was, I think...

0:37:12 PA: It was 2010? Okay.

0:37:13 CP: Yeah, yeah. That was in 2010.

0:37:14 PA: And the people who were coming and enrolling in these studies, what are their perspectives on psychedelics? Obviously, it's end-of-life anxiety, they may have been diagnosed with terminal cancer. What's the vibe, so to say? What's the mindset, the mentality of the patients that you're working with, and the people that you're seeing, and it's just like, what's going on in those rooms that...

0:37:34 CP: Yeah, I think in those early days, NYU used to... They had a lot of trouble recruiting in the early days, a ton of trouble recruiting. It took a lot of legwork on the part of Steve and Jeff and Tony, the three PIs, and Gabby, Gabrielle Agin-Liebes, who was the study coordinator, played a huge role in this to build bridges to the cancer... What is it? I forget the name, the Perlmutter Cancer Center, which I think that's the name of the cancer specialty centre at NYU. First of all, they wouldn't even allow this study to take place, the institution wouldn't allow the study to take place on the grounds of the medical school or the hospital. We were operating out of the dental school across the street for the first number of years of that study.

0:38:16 CP: That has since changed, but we were in this back... And that was only because the dean of the dental school happened to have some kind of sympathy to psychedelics and had his own cancer experience, and it's only because of his personal largesse were we allowed to do any of the work there. But, yeah, we were like this dirty secret that the university didn't want anyone to really know about, so we're operating out of the dental school, which was fine, it was a nice facility, but a little weird. So we were... It was difficult to make inroads to other areas of the university, in the oncology department for patient recruitment. So I think the earliest cohort of people, I think, were people who had... By and large, most of them had their own experiences, so I think...

0:39:00 CP: This is cancer, right, so the demographic is a bit older, so although certainly there were people in their 20s or 30s who had young, very young for younger forms of cancer, let's say, or forms of cancer that are autistic, where cancer and things like that can present in earlier age groups. But by and large, people were probably, I would say, on average, average age of, say, 55 to 65 or something like that, something in that range, and certainly, from 40 to 60, I think would probably be, or 65, would capture the majority of the people in the early cohort. And the reason I'm bringing that up is to say that a lot of them were people who had experiences with psychedelics in the '60s, like recreational in the '60s and '70s, and had good experiences with them in their own personal history, just in a recreational context, and thought that maybe...

0:39:50 CP: And maybe they had some powerful or profound experiences that didn't end up getting really integrated into their life that they thought back on fondly. That certainly was the case where the patients I had direct contact with, but they were self-referred or they would find out, and a lot of these people are really desperate and really struggling and had failed so many other treatments that it was like a last ditch, sort of treatment of last resort. And I think because it was cancer patients, I think the optics of that helped maybe, even though it was kept on the periphery of the medical centre or the medical academy there, it was I think allowed to happen in part because of just the sympathy that somebody in late stage cancer generates. It's somebody who's really suffering, we don't really have anything else that can help alleviate their suffering, maybe you might as well try this seemingly crazy experimental treatment to see if that would help.

0:40:44 CP: I think that was part of how we got it, how Steve and Jeff and Tony got it by the IRB when they first initiated the study, but... So, yeah, so they were people who were really suffering, crippled in many or most cases by their anxiety. And they underwent two treatments each, one was placebo and one was Psilocybin, and I'm sure you've read the stories. Michael Pollan talks about it in that New Yorker article that you mentioned, and elaborated on them in the How To Change Your Mind book. But life-changing, totally transformative experiences that would put them into sustained long-term remission from symptoms that were previously crippling them. From a single experience, which that's not how psychiatric meds conventionally work.

0:41:34 CP: So there's, already there, there's something really profound happening that the current paradigm can't well account for, which is part of what made it so exciting for me. But, yeah, that initial cohort of end of patients. A lot of them ended up surviving their cancer diagnoses because initially, it had to be terminal the way that the protocol was written, but because of just the length of the protocol and the delays involved, it was felt that would become prohibitive to recruitment because people had to have a life expectancy long enough to realistically engage in a relatively long-term clinical trial. It was changed to... It had to have been a terminal diagnosis, but they could be in remission from that diagnosis, as long as they were still having a lot of anxiety about recurrence, then they would...

0:42:25 CP: So there were people who were in remission but still dealing with the spectre of recurrence and crippling anxiety around, what if it comes back? But then there were also some people who died very shortly after their engagement in the study, but died in ways that they would not have been capable of, previous to their enrolment in the study. And I think Michael Pollan writes really beautifully about one particular case like that in his book. There's the story of the gentleman who was basically on his deathbed, but was just beaming this beatific tranquility that was a magnet to people, other people, other staff in the hospital floor, totally at peace with his death, his transcendence into death. And it's really... To see that type of outcome is really humbling and profound, and makes this work super meaningful.

0:43:17 PA: And we're now seeing the fruition of that in Canada recently, the nonprofit TheraPsil just got the first four Canadians to be legally approved for Psilocybin treatment for end-of-life anxiety.

0:43:30 CP: Oh. I didn't know that, I didn't know that.

0:43:31 PA: You didn't?

0:43:32 CP: No, no.

0:43:33 PA: Oh, yeah, yeah, so it's finally come around. So, that initial groundbreaking research that you carried out 10 years later...

0:43:40 CP: Wow!

0:43:40 PA: Which is an interesting trajectory, is now medically available to Canadians. And talking with a friend recently who's a CEO of one of the public companies in Canada, he said that Health Canada is now being flooded with applications for Psilocybin because these first four were approved, so they've inadvertently opened up Pandora's box, in a way. So it could act as an incredible ledge, so more and more people have access to these medicines.

0:44:07 CP: Is this purified Psilocybin or Psilocybin mushrooms that were approved?

0:44:11 PA: Psilocybin mushrooms.

0:44:12 CP: Wow.

0:44:12 PA: So they get actual mushrooms that are sent to them, or they're able... Or I think it's something like they have to figure out how to get the mushrooms themselves maybe, but then they can legally do them, I don't know, it's one of those weird sort of in-between areas and a company called Numinus is now cultivating Psilocybin mushrooms, they just actually finished the first cultivation. There was an article, I think, published in Forbes today or yesterday...

0:44:39 CP: Wow.

0:44:39 PA: Where they're cultivating the actual mushrooms and their intention is to begin distribution to these end-of-life anxiety patients in Canada who are getting approved for Psilocybin treatment.

0:44:49 CP: Wow, I'm embarrassed, I didn't even know that it happened. I knew that was in the works, but I didn't... I haven't been keeping up to speed with... I gotta... I don't know, do something about my RSS feed or something...


0:45:01 PA: Let's do that, yeah. Well, so we've focused a lot so far on... We initially were talking about the history of Ketamine and it going from an anaesthetic to being used as an infusion, to being used from a psycholytic to a psychedelic perspective. So we have the full range of that. We talked a lot about your personal journey, in terms of your own personal experiences becoming a psychiatrist, being at NYU, becoming the first in-resident psychiatrist to be involved with these psychedelic clinical trials in 50 years. And one of the main reasons we're connected today is because of the groundbreaking work that you're involved with when it comes to being the scientific director at Mindbloom. We had Dylan on the show previously. I think we published his episode in August at some point, and Dylan and I have become quite close, I would say, over the past year, as we're both running businesses in this space.

0:45:51 PA: And when I first read about Mindbloom or heard about Mindbloom, it was probably a-year-and-a-half ago, and it was that they're opening up a clinic and they'll have a clinic in New York, and they're doing lozenge treatment. I thought, "Oh, this is really interesting." And then COVID hit. And then all of a sudden, the model that Dylan was creating, which was like, we both have the clinic and we have the tele-app, became so much more relevant because people weren't going into clinics anymore. So I'd love if at the final wave of this conversation, just loop us into your experience with Mindbloom. It sounds like you left NYU in 2017, I think is what you said. You've been co-principal investigator. Where does Mindbloom come into this picture and what in particular have you been creating with Mindbloom to ensure the experiences are as efficacious as possible?

0:46:39 CP: Sure. Yeah, backing up a little bit, as I mentioned, that I was part of running the Ketamine study at NYU in Bellevue with Steve back around 2013-2014. And then it was... I started up my private practice as I was gearing up to leave my faculty position at NYU, opened up my private practice in 2016, and pretty shortly thereafter, started using Ketamine in my own private practice just because I had been able to see first-hand how well it works and gained some proficiency in administering it and how to use it, and so I started using it in my own practice. I had been using it for probably two, three years when Dylan first approached me. He had found me, so I used to... I was, before COVID, for a few years, I was practicing once a week out of Julie Holland's office. Julie Holland's another guest I know that you guys have had on this podcast, which she's a great woman, a friend of...

0:47:36 PA: Julie's great.

0:47:36 CP: Yeah, she's awesome. She's awesome, and a real powerful ally and advocate for this work. Yeah, she was letting me use her office once a week to do Ketamine infusions, and so that's what I was doing there. And Dylan, I think, reached out to her and asked her basically if she knew anybody using Ketamine, and she referred him to me. And Dylan and I had a... Started up a conversation, we met a few times. Long story short, I became the first medical director of Mindbloom back in... When the company launched. That's in, I think it was June of 2019. And shortly after that, Dylan hired on Jack Swain as a management like COO type. Jack was a good friend of Dylan's from high school, but he had spent a number of years working in consulting for healthcare organisations, hospitals and other organisations, and so had brought a lot of experience just in terms of medical operations, like how you build a clinic and all the stuff, the logistics, the nuts and bolts stuff goes into that, which not really my bailiwick.

0:48:38 CP: And so, Jack and I worked pretty intensely for a few months coming up with the protocol that was obviously predicated on this idea that we would have a brick and mortar clinic in New York City where people would come in and do treatments, and if their first in-clinic treatments went well, then they could be transitioned to at-home remote treatments. And so, that was one of the ways of making the treatment more accessible because the... By and large, in this type of treatment, the largest overhead cost, because the Ketamine itself at this point is very inexpensive, it's been generic for 40 years, and is very cheap, the drug itself is cheap. What isn't always inexpensive is the clinician's time.

0:49:20 CP: So for example, the rules and protocol we were talking about before, you're looking at treatment sessions that are two to three hours long, and in private practice, at least in New York City, it's very customary for people to be getting paid $300 or more an hour for that, and as you can imagine, that cost racks up pretty quickly if you're doing multiple sessions. One of the ways to make the treatment more accessible and the rationale for going down the remote route initially was to essentially try and create a treatment model that really focuses on empowering people themselves to engage with the work, engage with the states of consciousness that are facilitated by the Ketamine sublingually at low doses with guidance and training from our clinicians, be able to... I would describe it as, if you're familiar with mindfulness-based stress reduction type of therapy, I would describe it as a Ketamine-assisted mindfulness-based stress reduction or mindfulness-based...

0:50:23 PA: That's Jon Kabat-Zinn's programme that you put together?

0:50:25 CP: Yes, yeah, yes. It's not formally, we're not like... It's not following the manualised MBSR protocol, but it's definitely strongly informed by similar principles. And so we... I think we launched in October of 2019, was when we first started seeing patients, and then obviously by March, COVID hit and we were really only operating at full steam for two or three months by the time that happened. But as you've mentioned, we were uniquely suited to filling in this kind of void that occured when everything started shifting to remote treatment because of COVID, because we had already thought through and designed an entire protocol based around remote treatment. The thing that we did need to figure out is how were we going to replicate the experience of the first, which is really mandatory, of having somebody do their first treatment session under close clinical supervision or scrutiny.

0:51:19 CP: And so we figured out a way around that, having the clinician available, or presence by telemedicine during the actual first dosing experience. We figured out a way to replicate that observational requirement, and it seemed to work really well. The one thing that has... I'm no longer the medical director, but to my knowledge, I don't think we've resumed any in-person treatments yet, and without the benefit of an in-person treatment environment, you can't really do intramuscular, and we were doing intramuscular injections in the early... Earliest days before COVID, some people would come in and we had just started to do that, similar to this idea, the trance versus transformation idea that Wolfson wrote about in his paper. We were employing at Mindbloom, but we weren't basically... Didn't have very long to refine that.

0:52:09 CP: Right now, the treatment is still limited to sublingual, 'cause it's the only form that, in my opinion, is really safe to use at home for the general population, but still even with that, the effects have been really great. We're getting... And certainly, none of these drugs are a panacea, Ketamine's no exception, but we've had people saying that they've gone through the treatment that we facilitate through Mindbloom and achieved effects that they weren't able to achieve through five, 10 years of psychotherapy and conventional psych meds, which is something you hear routinely from patients who undergo psychedelic-assisted psychotherapy of all kinds. I think it really just speaks to something huge that the conventional reductionist model is missing... Missing out on a huge lacuna and understanding that characterises the reductionist model. So, anyways...

0:53:01 PA: Well, and I've gone through... I haven't yet gone through the Mindbloom experience, so we're recording this, I think it's the 23rd or the 24th of October today. I will be going through it, I think, next month or end of next month. I've done the lozenges personally a couple of times, and have never done intramuscular. I have an intramuscular appointment set up for next week, but...

0:53:22 CP: So they are doing intramuscular injections back in the clinic?

0:53:24 PA: Not with Mindbloom, sorry. This is with just a local facilitator in Florida that I'm trying the intramuscular, but...

0:53:30 CP: Oh, you're in Florida.

0:53:31 PA: Yeah. Yeah, yeah. But with the lozenges, what I found to be most interesting about them is I did them with a playlist, like... I would call it a ketatation. It was a few other people, we had a playlist on in the background, and it was... Especially as someone who's... I work quite a bit, and I would say I'm a little more heady than the average person, so I have a lot of mind chatter, and it gets to your point about the mindfulness-based stress reduction. It's like when you go into that Ketamine lozenge experience, it's almost like the mind just totally quiets down, all the chatter just evaporates, and there's just a sense of being able to touch in to that essence of self that normally you're distracted to or distracted by something else, you're not really in touch with it.

0:54:25 PA: And it's just, it's a much... Or it feels like a much softer landing than maybe a classic psychedelic like Psilocybin or Ayahuasca, which can be quite... There's visuals and there's a lot of emotional up and downs, and there's a lot of purging sometimes, whereas I felt, at least from my experience, Ketamine felt just very, the lozenge, felt very smooth. And it felt especially... I didn't have... I prepared a little bit and integrated a little bit, but I didn't have the whole protocol preparation and integration, and it feels, like you were saying with the psycholytic approach, when it comes to the lozenge, there were just things that came up, like insights that I would normally repress or not allow myself to witness or feel that were just like, "Oh, that's true, and that's true, and that's true." It just created a spaciousness for those things to come up and be seen and be heard and be witnessed, which I normally wouldn't have allowed those to do, and because of that then, for the week after, my anxiety was way lower 'cause that's mostly what I've been struggling with, has been anxiety, as many of us during COVID, and it just was like, everything was just... Felt way more smooth, way slower, it didn't feel like I had to be in a rush anymore, and it was really healing in that way.

0:55:40 CP: That's wonderful. Yeah, what you're talking about really speaks to one of the prime neurophysiologic effects of Ketamine and many psychedelics, or all of them, which is their capacity to suppress or diminish the activity of the default mode network, which probably, I'm guessing a lot of your audience is familiar with, but just in brief, the default mode network is essentially the... It's a finding, a neurophysiologic finding that we see on functional brain imaging that essentially correlates very strongly with the mental chatter. It's associated with when the person is engaged in activities of mind-wandering or self-reflection or rumination, or essentially whatever your brain is doing on default, hence the name, that's the default mode network.

0:56:32 CP: So, as opposed to the task-positive network, when you're really richly engaged in some kind of outwardly focused task, then the default mode network is suppressed because your brain resources are being used up in, I don't know, some... If you're trying to put a puzzle together or do a math problem or something, or working on your car or whatever, when you're doing something that really requires a lot of active real-time attention, then the task-positive network takes over and the default mode network diminishes. But when you're not doing that, your mind is left to its own devices, so to speak, then the default mode network takes over. And for people who suffer from a lot of chronic stress, anxiety, depression, the content of that chatter can be really obviously painful or counterproductive and can lead to thought processes that exacerbate stress.

0:57:25 CP: And you become your own worst enemy in a lot of ways when your default mode network is really caught up in a lot of negative or stressful or depressive rumination. And that becomes a vicious cycle, because one of the things that happens to the brain under chronic states of stress is an impairment of neuroplasticity, which is the brain's ability to form new connections, and because any time you're using your brain for something, what's actually happening, fascinatingly, on a microscopic level, is that synapses are forming and unforming between brain cells, so the little connections, connection points that happen between brain cells, and they're up to 10,000 per brain cell in the brain, and in the human brain there's like 100 billion brain cells in a healthy adult brain, and we're talking about trillions of connections that are happening that are really in the state of dynamic equilibrium.

0:58:17 CP: And the more you use a particular brain circuit, the stronger the connections between those synapses become. And so there's actually an increase in the density, the quantity of synaptic connections between two nerve cells to brain cells in a circuit that's used very often. So the reason why it becomes easier to play an instrument, for example, with practice, is that you're physically strengthening the connections between the brain cells that are involved in that activity. So there are actual structural changes that are happening in the brain depending on how the brain is used. So, that phenomenon is as true for things like language acquisition or learning how to play an instrument or things like that, as it is for anything you're using your brain for.

0:59:01 CP: If you're using your brain to ruminate negatively on things, then the circuits underpinning that brain activity are going to become strengthened, and you couple that with the state of impaired neuroplasticity that occurs under stress, you basically have a smaller level of freedom, or there are fewer degrees of freedom for any particular nerve impulse to travel down when you start thinking. And so you can think of it as like you're just digging the grooves, so to speak, almost literally digging structural grooves in your brain deeper and deeper in these ruminative circuits, and that becomes a vicious cycle, because the ruminative circuits induce more stress, and more stress impairs neuroplasticity even further, and so you can see how it becomes a really rapid... It can become a rapidly vicious cycle that get people stuck.

0:59:49 CP: And people can lose functioning altogether, people can stay in bed for weeks on end, because they can't stop ruminating on this horrible thought process, or they become so anxious that they can't leave their house, they're having panic attacks just at the thought of leaving their house. And so this is the extremes to which the brain can get out of whack because of those factors. And what Ketamine does is two things. It diminishes the activity of the default mode network for the time that it's actively present in the brain, and it even does that for a period of a few days after the Ketamine itself is out of your system. There's still a relative diminution of DMN, default mode network activity, and that lasts for up to 36 hours, I believe, post-dosing. And the Ketamine itself is out of your system within 24 hours, so there's something... There's some long-term potentiation that's happening or intermediate term potentiation that's happening with the DMN.

1:00:42 CP: And then in conjunction with that, there's also, through a separate neurophysiologic means, an enhancement of neuroplasticity, which means those deep grooves aren't removed, but the brain has a greater capacity to form alternative grooves. And so, if you're using your mind in ways that are healthy and... If you're engaged in some kind of psychotherapy or other kind of self-cultivation, in the window of neuroplasticity that happens after a Ketamine dosing, which is again, is around something on the order of 36-72 hours, then you're allowing your brain to form essentially healthier patterns of activity, and if you focus on that... So the adage that is used in neuroscience often is this truism, neurons that wire together... Sorry, neurons that fire together, wire together.

1:01:32 CP: Which means, what I was saying before, this idea that if you're, let's say, using as neural circuit underpinning some repetitive activity, like practicing a musical instrument, the more you get those neurons to fire together, the stronger they wire together, the stronger the connection between them become. And so, if your neurons that are firing together are ones that are underpinning healthier thought habits, they're going to wire together more strongly, and therefore make it easier for you to have essentially a healthier... Hopefully, ruminate less, but if you're ruminating at all, it's hopefully not in... As despondent a way as you're... The rumination, I think is more, probably, more of an artefact of this just impaired neuroplastic state.

1:02:16 CP: Your brain doesn't have so many available paths to offer a neural impulse, and so the ruminations are just like the deepest groove that is available, but when you are... And one nice metaphor, I think Mendel Kaelen is the one who came up with this, this idea of psychedelic treatments and/or Ketamine treatment acting as like a fresh coat of snow on a ski slope that has a lot of deep grooves carved into it. The treatment gives a fresh coat of snow and allows for different grooves to be formed. Anyway, that's, I think from a neurophysiologic standpoint, what's happening. And from which you can see that if you couple it with things like mindfulness-based stress reduction or cognitive behavioral therapy, or really any kind of therapy...

1:03:02 CP: And I've had patients spontaneously report to me that their EMDR treatments, Eye Movement Desensitization and Reprogramming or Reprocessing, which is a type of... Special type of treatment used in PTSD, they spontaneously reported to me that those treatments were more effective when they happen around the time of their Ketamine treatments. So again, the brain is in this neuroplastic, state of enhanced neuroplasticity. The chatter is muted to a large extent, especially during the infusion or during the dosing, sublingual dosing in your case, which is why you're experiencing that chatter to be much less prominent or absent altogether. And your brain is also now in a state where alternative forms of chatter can have a greater probability of taking hold, if you choose to use your mind in that way.

1:03:48 CP: And so, it really does matter what you're doing with that window of opportunity. But even just from a straight pharmacologic standpoint, those changes can be really salutary for people, which is why the reductionist KIT, Ketamine Infusion Therapy model works, even in the absence of psychotherapy. Because presumably as long as people aren't going to some horribly re-traumatising experience in their normal daily life, they are given an opportunity to just benefit from a somewhat healthier brain. And it's not perfectly understood what... How all of this translates into such a rapid and robust antidepressant effect, but it certainly has a lot to do with neuroplasticity. All of the nuances really have yet to be figured out. That's a large question.

1:04:35 PA: Which is... And that's a hugely exciting thing about this space, is it's still in its infancy to some degree.

1:04:41 CP: Oh, absolutely.

1:04:43 PA: And even Aldous Huxley talked about this when he wrote about psychedelics in the 1960s that we've pioneered externally, at least on Earth, about as far as we can, we've crossed all the oceans, and the [unclear speech] gloves, and the new frontiers or the antipodes of the mind...

1:04:55 CP: Right, yeah. Yeah, I love that. I love that, yeah.

1:05:00 PA: Casey, I just wanna thank you for coming on the podcast for... I had no idea that you were in that first early study at NYU, so that was just a beautiful nugget that came out of our conversation together and...

1:05:13 CP: Sure.

1:05:14 PA: For all the work that you're doing... As there's a lot more that we could talk about, obviously, but even as the space grows, and more and more investment is coming in, the fact that we at Third Wave have partnered with Mindbloom, just to help people find efficacious treatment when it comes to Ketamine, we owe a debt of gratitude to you for the work that you've done. Not only prior to coming to Mindbloom with all the research and the MAPS-sponsored stuff, but also now the programmes that you're putting together that are reaching thousands of people outside of regular clinical trials as well. So I just appreciate all your insight and knowledge. I won't forget the quote that you had earlier, which was, I think, something about psychonautics amusement park?

1:05:53 CP: Right. Uh-huh.

1:05:54 PA: Yeah, so there are just a few really golden gems in our conversation today. And if listeners wanna find out more about your work, if they wanna find out more about Mindbloom, the URL is, and we'll include more details about that in the show notes as well. Casey, I just appreciate you coming on and sharing all of your wisdom and your knowledge and your expertise with our audience.

1:06:18 CP: Sure. And if I may, if I'm not overstepping, I also want to really make people aware of another project that I'm working on. I'm still staying... I'm still working with Mindbloom as their Science Director, but some of my colleagues from the MDMA-assisted psychotherapy trial and I are also launching, hopefully, in the next month or two, a nonprofit psychedelic medicine clinic and centre for training and research called Nautilus Sanctuary, which is going to be, hopefully, able to offer scholarships for people who can't necessarily afford the out-of-pocket cost.

1:06:52 CP: Because right now, because Ketamine is off-label, a lot of insurance companies to this day are still not really reimbursing or paying for it. These treatments are really exciting, and as we've talked extensively about, can be really powerful and effective for people who aren't deriving benefit from other methods. But as of right now, they're still very expensive because of how labour-intensive they are on the therapist side, and we're trying to find ways to solve for that problem, and the Nautilus Sanctuary, using a nonprofit model, is one attempt at doing that. So I just wanted to put that out there, too.

1:07:23 PA: Beautiful. And so... And we'll include that in the show notes as well, Nautilus Sanctuary. Will that be in New York City then?

1:07:28 CP: Yes, the first... Yeah, we're starting in New York City, on Bleecker Street right now, is where we're starting. We're actually cohabiting space where we're doing the MDMA-assisted psychotherapy trial, down on Bleecker. But, yes, But, yeah, thank you for having me on, Paul. Really appreciate it. This was a fun conversation.

1:07:49 PA: This was fun. Yeah, it is really good. Thanks, Casey.

1:07:51 CP: Alright, take care. Have a great weekend.

1:07:53 PA: You too.

1:07:53 CP: Bye-bye.

1:07:54 PA: You too. Bye-bye.

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