The Science of Ketamine: What’s Really Going on in Your Brain?


Episode 128

Jeffrey Becker, M.D.

As one of the earliest researchers and advocates for ketamine’s use in healing pain, depression, and addiction, Jeffrey Becker, M.D., is on the forefront of harnessing ketamine’s massive untapped potential. In addition to his personal functional psychiatry practice, Jeff is the co-founder and CSO of Bexson Biomedical, which has created a subcutaneous ketamine infusion pump for safe, at-home pain management. In this episode, Jeff and Paul enjoy a wide-ranging discussion about responsible use of psychedelics, the connections between mysticism and science, and the fragile future of these powerful substances.

Jeffrey Becker, M.D., has over 20 years of research and clinical experience in NMDA-receptor pharmacology and clinical use. He was one of the first doctors in the U.S. administering and documenting ketamine for depression, and is a world recognized speaker and expert in the clinical use of ketamine. He maintains a clinical practice focused in Functional Psychiatry and novel treatment approaches to mental health challenges.


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Podcast Highlights

  • How and why Jeff was led to a career in psychedelics.
  • How Jeff’s studies in mysticism influenced his psychedelic research.
  • The neurobiology of ketamine, and how it differs from classical psychedelics.
  • What is “hybrid dosing,” and why is it so effective?
  • Ketamine as a tool in battling the opioid crisis.
  • The science behind ketamine’s healing properties - body, mind, soul, and spirit.
  • Increasing ketamine’s “staying power” through integrating symbolism from the deep self.
  • Psychedelics and the hero’s journey.
  • The goal and vision behind Jeff’s company, Bexson Biomedical.
  • Jeff’s views on the decriminalization movement.
  • The huge importance of preparation and integration to mental stability.
  • Can the ego actually get stronger with psychedelic use?
  • Jeff’s views on patents in the psychedelic space.

Podcast Transcript

0:00:00.3 Jeffrey Becker: Just people, there's a lot of pain out there. So if you're working with people, you hear these stories, and I dived into the pain literature and realized that this looked very much to me like the solution, a solution, a tool to help address the opioid crisis that's killing so many Americans. And here we are, we're about four years in with my company, and we have just moved through a pre-IND meeting with the FDA, and we're doing pre-clinical animal work to kind of show the safety of our formulation, and we're very much hoping we'll be in phase one trials in humans next year. [music]

0:00:47.4 Paul: Hey listeners, welcome back to Third Wave's podcast. Today we have Dr. Jeffrey Becker, who is the Chief Scientific Officer at Bexson Biomedical with us. He has over 20 years of research and clinical experience in NMDA receptor pharmacology in clinical use. He was also one of the first MDs in US administrating and documenting ketamine for depression in clinics and is a world recognized speaker and expert in the clinical use of ketamine. He received his BS from UC Berkeley, an MD from UCLA, and he also maintains a clinical practice focused in functional psychiatry and novel treatment approaches to mental health challenges. Dr. Jeffrey Becker, welcome to the podcast. It's good to have you.

0:01:31.1 JB: Thank you, Paul. It's fun to be here.

0:01:33.6 Paul: So the space that I always like to open up with people on the podcast is first just what brings you to this work? Obviously, psychedelics are such meaningful experiences, ketamine, I would consider when used within a certain setting to be psychedelic in itself, so what has drawn you into this work and specializing in ketamine and having been involved in this space for 15 plus years at this point in time?

0:02:01.8 JB: I found that the psychedelics when I was an undergrad were very important to re-orientating me towards what I had felt like I had been losing, which was kind of a sense of being able to touch deeper aspects of myself and be in touch with really what felt like a connection to God, that felt like it was kind of slipping away in early adulthood. Very interesting to me, it felt very, very specifically neurologic. It felt like I had always been able to just go find it and I was finding that it was harder. And there was this odd kind of cynicism that was setting in, and I didn't really have any way of understanding why that was, where it was coming from. It wasn't like I was traumatized or there was no specific reason for this, and I really set about trying to understand what was happening. I ended up in the Religious Studies department, actually at UC Berkeley. I studied Religious Studies and ended up with Houston Smith in his mysticism class, and he ended up becoming a mentor through the years, and really was someone that I could talk to about this kind of, really that liminal... Lots of that liminality, where I felt like I was overly contained, consciousness was over-contained.

0:03:38.2 JB: Natural psychedelics that I've had a chance to try were extremely helpful to me in re-opening up that space and studying in parallel, the kind of hierarchy of being that is the core aspect of mysticism. Really understanding the planes of existence of body, mind, spirit, soul... Soul, spirit actually, if you follow Smith's kind of paradigm, really felt like a synergy for me. I've been very specific about trying to help pass on these paradigms because I think they're very important. But when I got to medical school, I really wanted to work with consciousness medicine, but these were... These drugs, it's a felony. It still is in a lot of circumstances, and that was not really something available for me as far as the risk was concerned. The amount of time and energy and money and investment of spirit in becoming a doctor was... I just was not... That was too much. I advised a lot, but I've never done underground work or anything in that category, but I had a chance to try ketamine and was profoundly impressed by how gentle it was and also how different it was. What's the word? It's very mysterious, ethereal. It's also very gentle and it's also very, very powerful, which I think is an incredible combination of properties for people that are in pain.

0:05:35.4 JB: And I set out to really understand the neurobiology because it's such a different mechanism of action than the classical psychedelics. That's been a 20-year adventure. We can talk a little bit about that, about the differences in the way that psychedelics work versus the way that ketamine works and its effects upon the inhibitory GABAergic neuron. The kind of inhibitory controlling mechanisms that in many ways kinda control what we think and keep us from thinking this, and keep us from thinking that or make us think this, or make us think that. So the effects upon that relationship between pyramidal cell brain activity in the GABAergic neuron, that was... I would call it an obsession. [chuckle]

0:06:28.0 JB: In the process of doing all of that, I really became an expert in the NMDA receptor and how it works... It's very, very interesting, became an expert also in the chandelier cell, which is kind of the ultimate arbiter of whether a pyramid cell can fire or not, and how those interactions are actuating sub-associative ketamine dosing, which causes this kind of bloom of consciousness and the brain moves up into high gamma and alpha and beta power are actually reduced, Delta power are actually reduced all through the whole brain, really all through the main networks, default mode network and executive network and salience network. So I was able to see through all of that to how effective this would be for depression, and I started doing it, and I started doing it when I talked to a bunch of different anesthesiologists and also some neurologists who were using ketamine for pain, high doses multi-day infusions, and I proposed this kind of low dosing with monitoring, but very kind of careful dosing and was reassured repeatedly about the safety of what I was considering, and I started doing it and here I am...

0:07:54.4 Paul: When was this?

0:07:56.3 JB: This was 2004.

0:07:58.7 Paul: Wow.

0:08:01.5 JB: So it's pretty early and it really had to do with... I understood the neurobiology of this so well, and I also understood the pharmacology of ketamine so well, and then I got enough expert opinion about safety that it felt... It felt definitely reasonable, and I found very quickly that you can attune to the patient, you don't have to go all in, high dose ketamine right off the bat with somebody brand new. A little bit is very different than a lot. And so you can kind of figure out what somebody's sensitivity is to this, and that's... I developed over the years something called hybrid dosing, where you take the target, the theoretical target dose based on your intuition, the patient's sensitivity, their past history, where they're at, whether they're kind of like, Oh, I don't know, or whether they've done a lot of drugs and they're like, Oh, I've done it before, I know what's going on, that kind of thing, and you split your dose and you give them about a third of it and see what happens, and about 12 to 15 minutes you can give the next dose and then you can give the next dose, and so you can kind of meter out the experiences. This is very similar in some ways, curve-wise to IV infusion actually, with a little bit of a... You get these kind of mini-peaks as well, and then you actually get to talk a little bit and grab some of the symbolism when they're coming out for the next shot, and they actually...

0:09:33.8 JB: What's nice about that is that can tell a story. A lot of times you end up capturing stuff in that first experience that you can kind of work in, and there's this kind of evolution of symbolism that if you didn't capture that first part of a triptych, I feel like it's... Sometimes that might be information lost, opportunity lost. So I did that. And then over the years, I cannot tell you how often I've heard from patients that their pain resolved, pain syndromes, fibromyalgia, pain associated with Ehlers-Danlos syndrome, pain associated with slipped discs or failed back syndrome, just people, there's a lot of pain out there, so if you're working with people, you hear these stories, and I've dived into the pain literature and realized that this looked very much to me like the solution, a solution, a tool to help address the opioid crisis that's killing so many Americans and here we are, we're about four years in with my company, and we have just moved through a pre-IND meeting with the FDA, and we're doing pre-clinical animal work to show the safety of our formulation, and we're very much hoping we'll be in phase one trials in humans next year.

0:11:04.1 Paul: And that's so exciting, and it's been such a journey for you and I wanna spend most of the time in our podcast together talking about Bexson Biomedical, which is the company that you started and what you're doing with your innovative technology and patents and that sort of thing. And before we get into that, I'd like to just take a second and acknowledge that you studied under Houston Smith, and that many of the listeners might not know who Houston Smith is, so if you could just provide a little bit of background, Houston Smith and the framework that he had about body, mind, soul, spirit, because I think that'll help really inform the rest of our conversation around healing and pain and ketamine and some of these more granular topics.

0:11:47.4 JB: Thank you. Yeah, it's so dear to me, and I never know if people wanna talk about it, but I think it's one of the more important paradigms that can really ground what people are experiencing and help them understand where the valence of what they're experiencing is located, so that they can figure out how to intervene, and I think we make a lot of mistakes when we don't understand things in this way, but Houston Smith, with PhD Religious Studies professor, he was actually emeritus at UC Berkeley when I was up there at the theological institute and was teaching... He taught, actually... Introduction to religions was where it started with him. He wrote a very appreciated text called The World's Religions that is very honorable as far as the core truths that are in the different religions, how they differ, where they're similar, and his gentle and deep respect for that aching aspect of the human being to try to understand these higher levels I think is... It's very apparent. I think it still stands as one of the most powerful important books in this field.

0:13:11.4 JB: When I moved in to study with him about mysticism, one of the many texts that we read was one of his books, it's called The Forgotten Truth, and in that book, I can bring some of the concepts down into kind of a single concept, but it really comes down to a belief that I actually ascribe to 100%, which is that being is a dimension, and it's a dimension that's as real as time and space, and it's built in layers, layers of being. And you can look at the phenomena that you see in the world, you see in this existence that we're all here in, and kind of see where this comes from.

0:14:13.6 JB: And the idea is that there's body, there's mind, there's soul and there's spirit, and body is really in a lot of ways where western medicine is generally intervening. We think about receptors and metabolism and molecules that are bouncing into each other and things that are going awry. There's stuff happening though, there's being there, there's life, there's some... We don't know why being exists, but it is a thing. We use the word to be all the time, and yet we barely even can say what it is, right? So psychiatry has been kind of located in the level of mind, so what do you think, what do you feel, what is the interaction between these things? There's definitely an interface between the two, but there is something different about thoughts and emotions than there is about molecules and receptors, and yet they're still both aspects of being.

0:15:21.9 JB: And then you've got another layer up, which is kind of soul. These words are interchangeable, and I try to help people not get hung up on a word, like, "Does he mean we have a soul?" I step aside from questions like that because I just think they complicate things, but at the level where we're dealing with archetype, we're dealing with love, we're dealing with things that can't... They really can't be quantified, it's not a quantified thing that you're looking at, you can't say there's X units of love being expressed between this individual and that individual, we can barely even describe what love is, but we do know it's real, we know it's something that we engage, and there are different forms of love as well, so it's an extremely rich, rich landscape, and in some ways, the landscape gets richer and richer the higher you go.

0:16:22.0 JB: And then above this is spirit, which is really, if you look at... I think the best way to think about spirit, it's more thinking more in the Hindu model where God with qualities, so basically the space where God has qualities, like when Krishna is in... When the wars are happening in the Mahabharata, there's qualities, there's stuff happening, but what about nirvana where there is nothing, where God is only what... Is only described in the negative? You can only say that it's not this, right? 'Cause it's not anything, it's all things and it's also nothing at the same time. So that's the highest level.

0:17:07.9 JB: So these four layers are kind of built into the structure of the dimension of being in his thesis, and his thesis is... It's not really even his thesis. I think he did a wonderful job of putting it into words and getting it... It's really very powerful. It's only this big, it's one of the most important things I've ever read. But I think what was profound for me was that as I dived into this, it was so obviously self-apparent that it was almost as if it was something I already knew that was true. It was like, "Oh, of course this is true. It's the only way it could be. It's the only thing that being can be, is a dimension that we're interacting with."

0:18:00.5 JB: And so at the simplest level, we live at the nexus of time, space and being. And I think that's a lot about what's happening right now in the psychedelic kind of renaissance, is that we're really realizing that integration needs to happen. And I'm a big advocate for psychiatry to go both down and up, to think about themselves as also needing to deal with the functional aspects of health, to understand if there are nutrient deficiencies and insufficient glutathione for the brain to quench the free radicals from all that fuel burning in our brain, low B12 levels, things like that that are addressable. But they're in the body, they're in that plane, right? And then the spirit, if somebody's soul sick, is the trauma they experienced when they were in college or childhood, has it caused their... Aspects of their being and their soul to retreat so far that they barely feel its existence, and they have to kinda be in contact with that, I think, to feel well. So that's Smith, and he's a very, very dear, dear human being. He passed a number of years ago.

0:19:15.9 Paul: At quite an old age, I think he was 100 or... He lived a long illustrious life, and was quite close to the psychedelic movement in the '60s, and quite close to Leary and Alpert and Aldous Huxley, and he had a very close relationship with many of those early pioneers. And Huxley in the '40s wrote a book called The Perennial Philosophy, which I think... I can only speculate, but I assume there was a lot of dialogue between him and Huston Smith about that precise topic. And obviously, Huxley was much more of a public figure and literati and Huston was much more of an academic, but the frameworks that they landed on have been even so influential in your journey, in my journey as well when I first started working with psychedelics, acid and psilocybin when I was 19, 20, I had grown up in a fairly traditional household, religious, then started to get into atheism, Dawkins and Christopher Hitchens, and that felt empty, and then finally through psychedelics came to this awakening, and Huxley's Perennial Philosophy helped me to put parameters around that, to understand the relevance of that to religion in my upbringing, and it really is one of those things that brings peace and equanimity on an internal way.

0:20:46.3 JB: That's wonderful. That's a dense text as well.

0:20:50.2 Paul: It is.

0:20:50.9 JB: You have to commit to that one. Huxley is always... He's worth the time and it's always... Sometimes I think people walk away from it being a little bit too much, but no, yeah, I think you described it quite well. And Huston Smith was actually very involved in the beginnings of the Peyote Church, using the Native American church as an actual religion and that was protected under the constitution, and that was really helping with the soul sick natives in this country that were trying to contend with how much loss they've experienced.

0:21:35.2 Paul: And that was really... What many of us don't realize is peyote was really the first psychedelic that was... I don't know if it was legalized necessarily, but even before LSD came on the scene in the '30s and the '40s and the '50s, there was a lot of discussion around peyote and its usefulness, and then we had the mushrooms and the LSD.

0:21:57.5 JB: There are accounts of peyote parties in the roaring '20s in New York.

0:22:03.3 Paul: Oh, that's interesting.

0:22:04.4 JB: Oh yeah. There were psychedelic... There was probably some psychedelic fuel going on at that time too, so.

0:22:14.0 Paul: Absolutely. Well, so one thing that we've learned so far from the conversation is your expertise in ketamine as it relates to functional psychiatry, as it relates to the NMDA receptor site, and one thing you highlighted is that ketamine is actually different, quite a bit different than the classic psychedelics, and yet just as efficacious in many cases for depression and for addiction when it's used within an integrative model. So I'd love if you could tie a couple things together for our audience. One, how is ketamine different than the classic psychedelics? And then two, why then is ketamine, going back to the body, mind, soul, spirit framework, why is ketamine a healing medicine at those different levels, if you will?

0:23:09.8 JB: If I can, I think I should dive a little bit, hopefully in a way that I can translate some of the mechanisms, because it's kind of important to understand how it works. It's different than the psychedelics in that it is what we call a receptor antagonist, which means it blocks a receptor, and all of the classical psychedelics, at least some portion of their activity is through activating the 5-HT2A serotonin receptor. I'll get into where that's located and what that does in a second, but ketamine blocks the NMDA receptor, and it blocks it when it's open, which is important because what that means is that receptor is located in a stretch of neuronal tissue that has been slightly excited, has come up just enough from kind of being asleep or at rest to being like, "Hmm, is something going on?"

0:24:14.5 JB: And what happens is that the receptor opens up and magnesium leaves and ketamine can get in, and what ketamine does when it gets into this receptor is it stops glutamate from attaching. Really, actually, it doesn't stop the glutamate per se, it stops things from being able to flow through the channel. When the channel opens up, it's what we call a coincidence indicator, it's really the key moment when a neuron or the receptor or however you wanna think about it at whatever level, is noting that something important is happening, and calcium fluxes through, it's part of what allows something called long-term potentiation, which is the very single... That's the most important inception unit of forming memory. So it might seem weird to think, "Okay, well, we're giving a drug that blocks the very basis of memory formation. Why would that have an effect like it has?"

0:25:14.6 JB: Well, you have to take a step deeper and understand that that excitation that I was talking about, the fact that it goes to the open pore, we have neurons that live at a slightly more excited state, and actually are less likely to have the magnesium in that pore and so if you give ketamine at just the right dose, at the sub-dissociative kind of dosing range, somewhere like between, depending on the person, 0.3 milligrams per kilogram to maybe 1 milligram per kilogram. Somewhere in that range for any given person, a substantial portion of that ketamine will go to these particular receptors that are on these slightly excited neurons. Well, those slightly excited neurons happen to be the ones that are controlling our thinking. Okay? The chandelier cell or axo-axonic cell is the cell I'm talking about it. It's such an odd neuron that when they found it, it was almost like, "What? This is not real. There're no other neuron that does this." It seemed just far fetched that there would be a brand new neuron that does a complete... It behaves in a completely different way.

0:26:25.5 JB: It has a choke hold around the early axon segment of pyramidal cells, and it has to let go of its inhibitory choke hold. It turns the neurons off with GABA, it says, "Uh-huh, you're not gonna think that. Uh-huh, you're not gonna send that signal on. No, not that, not that, not that." And then finally, it says, "Okay, you can pass that on." These neurons actually live and talk to each other as well, so these inhibitory neurons are... You can pretty much say they are the conductor of thought at a certain level. They're the ultimate arbiter of a given neuron whether it fires, and the fact that they talk with each other and share signaling and share information about what they're doing, and one chandelier cell can actually inhibit many pyramidal cells, you can start to see how powerful the system is. It's part of what we call the GABAergic interneurons net.

0:27:27.5 JB: It comes into being, it's always there, but it becomes very important through adolescents, and it's what allows a young child who's living a little bit in a dream world... I remember when I was little and I was playing on the wall with a light, with a flash light, and for me it was, I think I had two of them even, it was like peanuts cartoon. It was like Linus and Lucy talking to each other and this and that, and I think back to myself, and I think, "I didn't see Linus and Lucy on the wall." I wasn't hallucinating, but it was pretty real. I was like, "This is a thing going on." I mean, what is that, right? It's a dream world in a way, so that all coalesces out and we become much, much more serious when we hit adolescence. And the fine tuning of this system becomes much more granular and much more important all through the 20s. It's kind of like, in some ways we kinda think of it as being done when we're 30.

0:28:31.9 JB: There's a lot, you can still learn new tricks, but the whole old dog thing is, there's some truth in it. So this system can become overwrought. It can become overly constrictive. Remember when I was talking about that thing that was happening to me in college? I was feeling it. I was feeling like where did that sense of things go? It gets really far now. I'm not able to just pull it in and feel it. And I really do really believe like it's really a neurological process. Then when you go up into the level of mind and spirit, we have endless poems and Shakespeare plays, and just the pathos and ethos of this is played out in the humanities as well, where we lose ourselves and we have to find ourselves after individuation, and once we find ourselves after that individuation process then we fully become integrated. We get to receive back what we had, but we lost.

0:29:34.5 JB: So I think that psychedelics and ketamine can really help with this process. Ketamine gets on to the chandelier cell, it looks preferentially. So it turns off this inhibitory tone. Turns it down. You can think of it kind of like a dial. It depends on the dose. You do it enough, you really are, there's so much disinhibition that you don't even know you're human anymore. A little bit, and you still have all of your biographical narrative information available to you, you still knowing who you are, but things open up. Psychedelics work completely differently. In the end, there is an increase in signal with ketamine, but ketamine is like opening up an aperture so more light can come through the aperture, but you're not necessarily strongly increasing the amount of light available. There is a little bit of an increase in the light available, I don't wanna mis-speak. It's a little complicated, there is probably some glutaminergic activity on AMPA receptors on pyramidal cell so I don't wanna mis-speak, but for our purposes, it's about opening the aperture.

0:30:50.8 JB: The psychedelics attached to the 5-H2A receptor, which are very densely located where all the dendrites are coming in to the pyramidal cell, kind of right towards the end, right above the cell body where all the information is starting to just finally coalesce and come into the cell body, tons and tons of these receptors located there. And what happens when a classical psychedelic that attaches this receptor activates the receptor, it causes the neuron to be more likely to fire. It basically, it stimulates the neurons and causes them to push harder on the chandelier cell, on the GABAergic interneuron net. So this model is more like increasing the pressure, but not increasing the aperture. So now you have more light, but you're pushing the light through the same size hole.

0:31:46.4 Paul: So it becomes that much more intense then?

0:31:49.1 JB: Yes, and so you can imagine, if you might, you might conceive of that GABAergic interneuron net as being substantially important in actuating the phenomenon of ego. Ego, super ego, the aspects of, "What I should be. Who am I? What is it that I think and do and feel, and what do I not think and do and feel." Psychedelics push on that system. And the system kind of, in some ways, is intact. We don't get inhibitory activity from the psychedelics in the GABAergic interneuron net. So you are kinda like, you're on your own in terms of letting go. That's why you gotta take a deep breath and strap in and know you asked for this and be as gentle as possible and accept the information as it comes and try not to get caught in Swirling Eddies that aren't taking you... Aren't allowing you to stay in flow.

0:32:49.4 JB: So they're very different. I think that there's something about the way that Ketamine works, and you can imagine this kind of like when the mice were... When the cat's away, the mice will play. So all of these neurons are now getting to talk to each other. There's all these relationships and sharing of information across the brain. And we can see that in functional MRI. This is pretty much factual. It feels like that for patients. They feel like all kinds of aspects of their being are being incorporated in kind of all in one kind of singularity of consciousness. And to some extent, it's kinda what you see in FMRI. But that ego, that interneuron net was not present during all of it. So it comes back online and it's kinda like, "Hey, wait, what? What happened?" It's kinda forgotten what it was trying to do, maybe, but it's also a little bit like, "Hmm." And you kinda feel like you can see that. You see after about a week or two or three, you can start to see people's old patterns start to set back in.

0:33:58.9 JB: And it's a frustration, actually, with ketamine. I wish it had more staying power. That's a lot of what I've been doing over the last 10 years and in my lecturing and teaching is trying to help people and practitioners, just offering tools to help grab as much material as you can and learn how to work with that material, because what you're receiving is symbolism from the deep self. And if you can hold those symbols, work with them, understand what a symbol is, understand that it's a signpost to higher truths, to higher forms of being, it's really the architecture of soul. If you can hold onto that, you can bring that into your life, and you can see amazing things happen. But it does require a little bit more... I don't know, if not intention, education...

0:34:51.8 Paul: Thoughtfulness, in a way, like more of a commitment, because even still today, as ketamine has become... I don't know if I would go so far as to say widespread, but it's definitely hitting mainstream awareness in terms of its efficacy for depression in particular. There's even a pretty strong split between those who believe that ketamine infusions are efficacious, and just the ketamine infusions, and those who believe much more in the CAP model of preparation, experience and integration. And I think what both of us lean more towards is the integration model that the drug itself is useful, and so much of the long-term shifts and change comes from, like you said, the integration of symbolism or the integration of the truth from the deep self, that then becomes... Well, it becomes integrated, it becomes part of that new self that you've unleashed or unfolded or whatever.

0:35:57.5 JB: Yeah. There's that classic hero's journey, where we're kind of lost in the forest and feel forsaken, and then there's usually some kind of interaction with kind of almost magical individual that kind of passes something important to the hero. And there's much of that is what's going on. And if you don't notice those moments, if you don't realize there was a gift offered, then it can be a lost opportunity. I think the psychedelics, because the ego, this interneuron net kind of gets... Is forced, very clearly is forced to submit, in a way, and hopefully it's easier with extra work and preparation and all of that, but you kind of... You're kinda gonna have to go... You're gonna have to let go if you're gonna go in to a solid experience. And so there's something very powerful in that. I think that that's why there can be years and years, a lifetime of learning in a five-hour session. I can remember granular moments from experiences with mushrooms 25 years ago hour by hour, almost minute by minute stuff that happened, and realizations, and I can say astounding. And ketamine is not like that. It's, again, it's a bit frustrating. So I think it's nice that we've got both tools. They both come with their own palette of positives and negatives, just like any tool.

0:37:40.0 Paul: And so part of them... What I'm hearing from you is, part of what Bexson then is doing is saying, Hey, let's make that initial focus on ketamine for pain, which I wanna dive into in terms of why you chose that and what you're doing to address that, but what we've also talked about is that the vision for Bexson is much broader than just ketamine. You're really looking at these various substances and how those can be weaved into the technology and the innovation that you're creating. So I'd love if, just to start with, as a slight shift in our conversation, just what is Bexson, kinda what was the impetus behind Bexson, and what, up to this point in time, has been most interesting about the work that you've been doing with Bexson?

0:38:34.7 JB: My partner and I, Greg Peterson and I was lucky enough to meet him up here where I live in Santa Barbara, and I knew very quickly when we were talking that this was someone who was quite serious and quite disciplined and very, very skilled. Really, a special set of qualities and experience to kind of look at something, look at really... Try to solve big problems. So I was interested in the pharmacokinetic problems that are associated with ketamine, which is that it's got very poor bioavailability. It's very hard to get proper dosing orally. You end up with a lot of extra metabolite that's unnecessary and potential mild to moderate risk if you're using it in pain management in that way. And I also was interested in the problems that are associated with delivery in the mouth health space as well in supervised settings.

0:39:36.1 JB: So we felt that the most... The biggest impact that we could make, and also the most kind of careful and prudent pathway was to go towards pain first. Pain requires, actually, less ketamine than for depression. You're not as concerned with pushing enough drug into the blood stream to get it through the blood-brain barrier and get the effects in the brain and the mind, mind and spirit, that you're looking for in depression. So it's an easier proposition because you can dose at a lower level, you can kind of justify the building of these delivery platforms, which are a lot of work and a lot of expense, and justify it partly because we have a pain problem for treatments, and we've also got one of the worst... It's just unbelievable how bad the opioid crisis is. The number of people that are dying every year is... It's not that far off from being as lethal as World War II for the American... In the American side, in terms of loss of humans per year.

0:40:44.2 JB: So it really is a war, in a way. And we don't have a lot of answers. So that's why we went this direction. In the process of that, we've hacked a lot of the problems that would allow for really quite safe and nuanced and consistent dosing in supervised settings as well. So the same pump system, delivery system, subcutaneous ketamine system that we're using, we're developing for pain at lower doses for at-home use in post-operative pain management is essentially modular. It can be applied for in-office use for the treatment of depression as an alternative to the other routes of delivery that are out there, which I'm not arguing against, I just... I think we are offering a lot of solutions. The interesting thing that has happened is that in the process of solving the problems regarding ketamine's basic chemistry when it's in solution, we were able to raise the pH to... Much closer to the pH of sub-Q tissue, and lower the salt content. Ketamine's a little bit like... You can think of it like salty orange juice. And that's not friendly to that tissue. It basically burns the tissue, you can get a... What we call a sterile abscess. It's not infected, but you damage the tissue enough it hurts. It can hurt for days and weeks.

0:42:14.8 JB: So it's never been a viable path route of administration. So in hacking that, we've created a new pharmaceutical excipient essentially that can be applied to other molecules that have essentially a hanging nitrogen that can be ionized. And that includes, essentially, all of the psychedelics, all of the main psychedelics, definitely the classical psychedelics, and a lot of the research molecules have been developed that are riffs and various substitutions. And also, a lot of the other dissociatives and pathogens. And it's been a bit... Honestly, it's been a bit overwhelming how many ways this technology could get applied. What we are looking at, this... Under Bexson we have a program called Hermes. And what we're doing is applying our formulation technology to multiple different scaffolds to establish whether or not... Do these create formulations that are stable, that are optimized for sub-Q use, and then we are looking at them and figuring out where are the best efforts to... Here.

0:43:30.4 Paul: Is it something we wanna develop in-house, is it something that we're thinking about out-license, and how might it be applied with the different kind of delivery technology solutions that we're developing? Because this pump is one of the things that we're looking at. We're also looking at dose-metered pen injectors as well. And those could be very helpful for reassuring the agency, the FDA, that something like a microdosing model is going to be used properly. And I do... I tend to be... I am very much live and let live. I have zero, very little interest in telling other people what to do. I don't... You can microdose right now if you want to. People are, and there are a lot of experts out there. There's a lot of ways to do this. What we don't have, though, is a way of delivering these molecules in metered dosing that is really quite consistent, straightforward, FDA-approved, and it can protect people both from inadvertent misuse. I think people... I speak with patients and I speak with friends, and microdosing is amazing for many people, and it's a little difficult to figure out, depending on the person. And especially if this is going to go out and be available to people that are not already with one foot in the psychonaut universe, people who really don't know anything about these.

0:45:07.3 JB: Allowing them to use these and making sure that in their first journey or their first experience with maybe microdosing an LSD analog, they're just using 6 micrograms every two or three days, and kinda see what happens. Let them work through the steps like we do with other medications. So, that's what we're doing, and it's been amazing. So far, we haven't found a scaffold that we haven't been able to apply this to, so it's been very heartening and very exciting and a bit overwhelming, but it's a bigger adventure.

0:45:52.0 Paul: And so for the listeners at home, how might this be applicable? How would a Bexson device come into their lives or the lives of their loved ones? Would it be through a psychiatrist? Would it be through a clinic? Is this something that they take home with them? Is this something that's only used within the office, so to say? How are you thinking about the use cases of it?

0:46:16.0 JB: That's a great question, and I think the simplest way to understand the way we're thinking about this is that much of it centers around dosing. I think that microdosing of... There's a lot of different molecules that may be very valuable in mental health treatments, they may be very valuable as anti-inflammatories, they may be very valuable in age-associated memory loss, kind of an anti-aging technique just in general. And when the dosing is low enough that we're talking about sub-threshold, maybe things come up a little bit but it's very, very manageable, it's not a psychedelic trip. At-home use, I think, is very reasonable. I don't know that anybody could really argue against it from the perspective of the actual psychic state. There are some questions about 5-HT2B receptor activation and cardiac risk and all that, and that has to get sorted out. Those are big and important questions. But as far as the psychic space, I don't see why home use would be unreasonable.

0:47:26.0 JB: On the other hand, a full-blown DMT infusion with a subcutaneous pump, that is designed to come on gently but get people into the space without the need for an MAO inhibitor. That's probably most... It's probably very important to have somebody there. I don't think that that... People should be necessarily doing that in their bedroom by themselves. Again, I tend to try to just take a side step to these questions because we're early in feasibility really trying to figure out the way that these things can be gently, effectively, and carefully introduced to society and in an FDA-approved manner to really bring all the institutions and all the institutional wisdom together for the field.

0:48:25.6 JB: I'm not, again, arguing against... There's decrim movement and I am... I have mixed feelings about it, not from the perspective of it being a competitive model at all, it actually comes from a different place. I really hope that we are careful about not turning it into a serious commodity with advertisements and getting people into things that they need to be a little slower about. I've watched what's happened in the Ketamine industry in terms of taking something that is a medicine sometimes, sometimes not, but all the dabbing and the kids that are taking in 400 milligrams of THC a day... I don't think that's good for the brain, I really don't. I think that that's a problem, and we've really enabled an extreme, extreme shift in use. And I do a lot of the work trying to get people off of these molecules when they're really stuck.

0:49:32.9 JB: We see cannabis hyperemesis syndrome where people can't stop vomiting when they're trying to get off of excessive dabbing. There's a lot of fallout, and it's not necessarily being communicated to the public. You can just do a Medline search on that one, if you wanna see. Cannabis hyperemesis syndrome. People are showing up in the ER dehydrated and with bleeding in their stomach 'cause they've been vomiting for so much so long. They're people that can't get out of the shower. There's something about it where when they get out of warm water, all of a sudden it comes back on and they live in the shower. It's weird. Let's avoid that.

0:50:18.8 Paul: Let's definitely avoid that. We'll make that commitment. It's funny, I was talking with someone else in the space who's quite underground but runs a very well-respected place in the middle of the States, and he was expressing a similar concern about the momentum in particular with decriminalization, only because you just need a few horror stories for the media to turn the tide, so to say. And that's always been the concern with this Third Wave, is once this sort of pops out of clinics, how do we actually create a container where it can be intentionally held. I'm curious, from your perspective as a medical doctor and having been in this space for as long as you have, what are some of those downsides that you potentially foresee, and what are you doing with Bexson in particular to help address some of those potential downsides as this becomes more widely used?

0:51:21.9 JB: At first, what we're trying to do about it, I think, the carefulness and the dosing control, that's a big part of things. I think it will be nice when we get into a position where the question isn't, "Should I have three of these caps or five of these caps or two of these stems?" Or, "How strong are these? And what batch do they come from?" They're amazing. Mushrooms have been very, very important in healing aspects of my psyche, but that's not really what you wanna be doing in a medical office. We're just moving into a new phase where the legitimacy of these molecules is becoming established, and if they're going to become tools for the existing medical model, we need delivery solutions that are clean, effective, and consistent, and approved. And then people can also do whatever they want in their homes and on their own time. There's really no... It's not an either/or model. So, that's what we're doing, that's the way we see ourselves as solving those specific problems for this particular arena.

0:52:40.2 JB: I will say that there's... I will point to a cautionary tale of a patient that I have that is something that concerns me, which is that these are extremely powerful molecules, and I don't think that it's always communicated how dark the smoky light of Tibetan Book of the Dead they use a Huxley term from heaven and hell, what that means, and how to handle it, and where to go with it, and how... I have a patient who had had a very, very effective growth phase in his life from ketamine infusions, actually in another clinic, and I was just helping with integration, and he'd had such a good experience that he kind of thought, "Oh, all of these tools are available. I should go and try them out." And he went and did a DMT, inhaled DMT, experience, which can be quite intense. And he had a reasonable first experience, but he came out of it with an enormous amount of material that he didn't know what to do with, he didn't know how to integrate all this new knowledge into his life.

0:54:03.7 JB: Unfortunately, when he talked to the practitioner that was doing the underground work with him, they said, "Oh, what you need to do is do it again." And so he went and did it again, and then he became deeply destabilized. He was this close to suicide for about a week. He felt that everything that was happening around him was not real anymore, that there was... We were living in some kind of simulation. Essentially, it was quasi-psychosis, it was... But he was functional. So that was what was so hard, was he was saying, "I can get up, and I can work, and I can do my homework, and I can get my emails out, and I feel like none of it is real, and I'm never ever going to come back to having my feet on the ground and be able to look my daughter in the eye and know she's real." It's real serious business, it's really, really serious business.

0:55:07.2 JB: He was absolutely, deeply ashamed, ashamed to a level that he could barely look at his wife 'cause he was so embarrassed for bringing this into the family, bringing this level of kind of terror that was oozing out of his pores into the family. And she was wonderful, loving, loving woman, and she was able to give him... It was very important. And he was very lucky that she was like that. It could have been very different at home. So, he's okay. He's re-constituted. We're working through the issues. He's diving into deep spiritual text, he's trying to understand the dark night of the soul, and understand the awfulness of seeing God with unmitigated, unvarnished, unfiltered information. There's a reason we use the word "awful." It's too much sometimes, and so... That's...

0:56:12.7 Paul: Oh. I had never thought of that. Thank you for... Yeah. That's... Wow. Okay.

0:56:19.0 JB: Yeah. It's too much for a lot of us without preparation and without understanding what it is. Anyway, that's one cautionary tale. I have a lot of them, I do a lot of reconstructing and repairing and restoration after excessive psychedelic use. I know, I've seen what happens a lot, and I would just caution everybody to be very respectful of how serious the downsides can be. And they're amazing tools, but like any tool, it's quite sharp and you better know what you're doing.

0:57:02.7 Paul: Yeah. And that's even something that I've spoken to again and again, even just the relevance of microdosing and the concept that I can experience some of these benefits without having to open up myself to everything that is and ever will be. And there's clearly clinical benefit from high doses of psilocybin, and much of that research has been done in a clinical setting, so they've gone to incredible lengths to mitigate a... Not necessarily a challenging experience, but a bad trip, something where something goes awfully wrong. And when we're out in the wild, like the clients that you've worked with, it's hard to know who to trust, it's hard to know which facilitators that you can trust, it's hard to know where they're coming from, how they've trained, and this is a problem and a gap that I've also... We at Third Wave have given significant thought to, we're rolling out a directory now of retreats, clinics, coaches, therapists, we're doing our own training for coaches. This really feels like a huge gap that we have to address if decriminalization and just general sort of the mainstreaming of psychedelics is to be successful, and I feel like the innovation that Bexson is doing is another part of that puzzle, because through the technology that you're innovating, that's just another stop gap to ensure that these are used with intention, with responsibility in a way that creates a sense of longevity with this medicine.

0:58:52.9 JB: Yeah, I think that's really well said. And I do believe that this is actually... Is happening in many ways. I think that there's a lot of awareness of this need and your work and a lot of the work out there of institutes and societies and groups that are very serious about helping make this happen properly. I do a lot of warning to people about some of the rookie errors that happen when people get into the field too quickly and go on the guru trip too quickly. Now they feel like all of this quick... It's a little bit harsh to say, but sometimes unearned knowledge comes and people need to be careful about keeping a very humble ego and not in the words of Edward Edinger and ego, and archetype really being careful about not having their ego identified with the powers of the self. When we do that, when we believe that we've captured all the powers of the self, there are fantasies of omnipotence and omniscience and controlling the universe, and that we can do no wrong because we're so good, it's a type of inflation that can be very risky to people, to individuals directly in their own lives, but it can be very, very risky to people that they work with as well, and it happens a lot, and I would just encourage everybody to watch for that. We need to watch for it in ourselves, everybody needs to be very careful here.

1:00:30.0 Paul: And in some ways, that's... Back to the beginning of the conversation and the religious studies that you entered in Houston Smith, that has been the role of religion for so many years is to help the ego to recognize that it is subservient to something greater and to create rituals and traditions around that very practice. Now, obviously, there's a dark side of religion as well that we're well aware of, but just that container, those rituals, the humility, that comes from... Whether you're a Christian or whether you're a Hindu, or whether you're a Buddhist, or whether you just have a connection to something greater, that is often the reminder because often times with these experiences with psychedelics, we lose in the trip itself, 90% of the ego or 95% of the ego, or it has that ego-dissolving property, and yet what is often the case is, the ego is let's say anti-fragile in a way, so if you keep just five or 10 or a little bit of around it just... It can get stronger and stronger and stronger. And so that is often the case but you'll see people who will work with psychedelics who, like you said, they think they have all this insight and wisdom and awareness, and yet it's actually a form of narcissism or spiritual bypass or something that isn't rooted in humility and true wisdom and honor.

1:02:08.4 JB: Yeah, and this is tough stuff. I don't ever wanna feel like a scold, I think that there's so much excitement and there's so much actual good that's coming as well, so I really don't wanna be the person that's pointing out... Yeah, but don't forget this, but I really think it is important that we don't forget this, it's all on us to do this properly.

1:02:36.8 Paul: One thing that we sort of skirted around, but haven't totally dove into yet, is patents in the psychedelic space, and that's something that I wanted to talk about with you because it's a hot topic, it's one that is incredibly relevant as billions of dollars come into the space, and we've seen a range of patents, and whether or not those patents are tied to innovation is I think a big question, it's a big topic, and I'd love to just hear from your perspective and with what you're building at Bexson, why is it that you think patents are important, and what particular innovation do you hope to bring to the field to grow and build and contribute to this renaissance of responsible use and the clinical use and all that... All that sort of stuff.

1:03:28.3 JB: That's a great... No, this is definitely a hot topic and it's a contentious one, and for understandable reasons. We have an ethic, at Bexson that is... Think, I would wanna be very, very clear about where we live and how we think. We have zero interest in trying to patent something that already exists, we have zero interest in trying to capture space that already exists. I've been in the field for 20 years, really longer, if you think about how long... Going back to undergrad and have deep respect for the work that's been done and the space that's been opened up already, and who did that and how it happened and how important those tools are... And we all own them.

1:04:21.9 JB: What we are interested in doing is protecting our ability to spend really serious money developing things that don't exist yet, that I believe and our company believes will solve a lot of problems for human beings in terms of application of these new tools. We can't accept investment and spend money and spend money at the rate that you spend in pharmaceutical development, without knowing that when we get to the end of our path, if we've invented something that didn't exist before, that we have the ability to make money off of it for enough time, that it's worth the effort, as far as all of that is concerned.

1:05:04.9 JB: I don't have the capacity to raise the money that would be necessary for Bexson to develop all of this through philanthropy. It's just... There's just not enough, or I don't have the gravitas to draw that money in. So that's not something that I could do. We have a lot of patents and patent filings, and we already have a patent on our specific formulation of ketamine for subcutaneous use, but I would be clear, we have a patent on the way that we did that, we don't have a patent on subcutaneous ketamine. We also have patents that we filed on the way that we are producing our pump that has tamper-resistant qualities and has qualities that will allow improvements in delivery and things like that. Those didn't exist, the things that we are patenting and they're part of what makes the whole thing work. So I had an article, I worked with Shelby... Double blind to kind of clarify that, in the patent space... I think everybody needs to remember that patents only last for so long. By the time a pharmaceutical company like us, get's something that we've invented to market, we won't have more than probably anywhere from...

1:06:32.3 JB: We're a little bit lucky actually, 'cause we had a lot of lead time but we won't have more than like 14 years that we would have some protection, and at that point, it becomes part of the common wealth, essentially. Anybody can use that technology for the rest of time. So there's a small little window about 14 years and most drugs, you only have about 11, 10 years, sometimes less. There are some patent life strategies that I would call quasi-shenanigans, there's... Don't get me wrong, there's a lot that's wrong with the pharmaceutical industry, there's a lot. But sometimes people don't really realize where the things are wrong and where they're okay, in my opinion, the patent...

1:07:24.0 Paul: The nuance in a way of...

1:07:26.6 JB: The nuance, yeah, exactly. So I hope that people can see through to our essential ethic, and it feels very clear to me, I really and I don't have any sense of doubt about whether what we're doing is proper, and I would be red in the face and absolutely wouldn't be able to show myself if I was trying to take something that we hadn't invented.

1:07:55.4 Paul: Beautiful. One, I think that's important because, back to the word nuance, if I've learned anything these last few years, there seems to be less and less nuance in conversations, and I think this is just as true when it comes to patents in the psychedelic space, and yet, the number of different companies doing different things, whether it's molecules, whether it's delivery devices, whether it's clinical spaces, whether it's education, training, protecting innovation is important, and it's helpful, and it allows us to spend the time and energy necessary to be inventive.

1:08:35.6 Paul: And I think you and I would both agree that while patents are necessary in the short term, our greater hope for this is for the longevity of this movement, precisely for the reintegration of these substances, and we recognize that this is something that's way beyond Bexson, it's way beyond Anatie, it's way beyond a Third Wave, it's way beyond any of these... It's next 50 to 75 to 100 years. So we look at these from a very small scope because this is what's required on a monthly and yearly basis to create, and I think both of us understand that we wouldn't be doing this work if it wasn't for something much greater. And that's why we continue to show up and why we work the stressful hours that we do, because there's something much deeper there. It goes back to what you were seeking when you were a college student, right? And the fact that you now get to work on a technology that's directly related to that opening, that experience of whatever is beyond is so... It's something that I'm very grateful for in my own work, and I'm sure you are as well.

1:09:57.0 JB: Thank you. I think that's really well said. The safe space that that creates for an inventor and entrepreneur and that kind of creative force to be incubated and to put in... It's really, it's not just money, it's also a huge amount of time in one's life to dedicate to. It could be dedicated in other places, so when you decide you're going to do that, it's nice to know you're safe as you're doing it. It creates a container for creation in some ways. Yeah. Well said.

1:10:32.7 Paul: Beautifully said. So, Dr. Jeffrey Becker, Chief Scientific Officer at Bexson Biomedical. Jeff, just as a last ask, if people wanna find out more about you, about Bexson, about whatever is going on, where can you point them?

1:10:50.5 JB: We have our website, this is... I'm not sure when this will come out, we're doing a bit of rebranding, we've had so much happened in the last year, and our website is so, so far behind in terms of kind of explaining who we are and where we're going. So there will be a new roll out on that front. There's a lot available about me and my orientation towards all of this and other podcasts, and my website has some information, and then there's a lot about Bexson. There have been a lot of articles about us that can get, well, a little deeper on both the science and the technology.

1:11:29.0 Paul: And we'll provide some of those articles like the recent Vice one and any others in the show notes as well. So if folks wanna dive deeper they can do that. So yeah, it was... We've known each other, I think for four years now. We met in late 2017 through a mutual friend, and we had a chance to meet in LA and do a little work together, so it's just an honor to be able to have this conversation in public with you, Jeff, and to learn at length really what Bexson is up to, and how that's been motivated by your own work and everything you've been up to. So thank you.

1:12:06.1 JB: Thank you, Paul. I really, I appreciate your work and that means a lot to me.

1:12:10.1 Paul: Thanks so much for watching. If you wanna stay up-to-date on The Third Wave of psychedelics, subscribe to this channel and visit where you'll find plenty of free resources on intentional and responsible psychedelics.

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