Hello everyone and welcome back to Adventures Through the Mind. This is a podcast that explores topics relevant and related to psychedelic culture, medicine, and research. I'm your host, as always, James W. Jesso. This episode is going to explore some of the groundbreaking research that has come out recently around the use of the psychedelic compound ibogaine in the treatment of mild traumatic brain injury, also called concussions. Our guest is Dr. Nolan Williams. [Music]
Nolan Williams, MD, is an associate professor within the Department of Psychiatry and Behavioral Science and director of the Stanford Brain Stimulation Lab. He has a broad background in clinical neuroscience and is triple board certified in general neurology, general psychiatry,
and behavioral neurology, and neuropsychiatry. Themes of Dr. Nolan's work include examining the use of spaced learning theory in the application of neurostimulation techniques, development, and mechanistic understanding of rapid acting, antidepressants, and identifying objective biomarkers that predict neural modulation responses in treatment-resistant
neuropsychiatric conditions. His work resulted in an FDA clearance for the world's first non-evasive rapid acting neuromodulation approach for treatment-resistant depression. He has published papers in high-impact peer-reviewed journals including Nature Medicine, Nature Mental Health, Brain, American Journal of Psychiatry, and the Proceedings
of the National Academy of Science. Further, Dr. Williams also has an expertise in psychedelic medicines for neuropsychiatric illnesses and is the first investigator to conduct mechanistic clinical trials exploring the neurobiological effects of ibogaine. Specific to that last point, Dr. Williams was the head of a study run at the AmbioLife Sciences Center in Mexico where he evaluated the effects of ibogaine on veterans with brain injury, particularly
mild traumatic brain injury also called concussion. The first paper released from these results is titled Magnesium Ibogaine Therapy in Veterans with Traumatic Brain Injuries and was published in the journal Nature in 2024. He joins us on the show today to talk about brain injuries, generally ibogaine, and the treatment of brain injuries with
ibogaine. We also talk about ibogaine as an anaerogen, the cardiac risks of ibogaine, and how to mitigate them, how ibogaine compares to other treatment methods for brain injuries, including other psychedelic molecules, microdosing ibogaine for traumatic brain injury, and that ibogaine can seemingly de-age the brain.
Additionally, we also talk about pharmacology versus context in the healing benefits of psychedelics, separating high technology from time, and how and why using the vehicle of capitalism to fund psychedelic research may be a good thing. Okay, so that's the interview you're about to hear before we get into it. Two things. Number one, this interview isn't two
parts. It's one episode, but it's two parts. I had to get on two separate calls with Dr. Williams in order to get the entirety of this interview, and you'll notice the bandwidth isn't super great in the first one, but it's quite clear in the second one. You might not notice a difference at all, but if you're watching the video feed, you'll definitely notice a difference, so a bit of a heads up there. The second thing is that this podcast is brought to you by listeners like yourself via Patreon.
If it wasn't for my patrons on Patreon and their ongoing continuous contributions to the production of the show and the various costs, time-wise and material-wise, in its production, I wouldn't be able to do it, and I love doing this, and I love the larger body of work that supports it. So, thank you patrons. An extra thank you goes to those who have been giving quite significantly, and in doing so, their names are presented on the screen here on YouTube or in the description to
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advance. Without much further ado, here is my interview with Dr. Nolan Williams on Adventures Through the Mind, episode 188, Treating Traumatic Brain Injury with Ibogaine. Enjoy. Dr. Nolan Williams, welcome to Adventures Through the Mind. Yeah, thanks for having me. Appreciate it. I am interested and excited for this interview because, I mean, psychedelics generally, psychedelic medicine is a topic that I'm very curious about, have a lot of excitement for.
Sometimes I've got an edge for the movement of the culture, but that's an aside. But, specifically, the excitement is pertaining to where this particular psychedelic medicine or what it's treating, which is essentially traumatic brain injury. And what makes me excited about that is that I
found out that you were doing this research. She's from a friend of mine and also a colleague for many years, Trevor Miller, who works at Ambio, which is the same center that you did the research we're going to be talking about today at. And I've also known Jonathan Dickinson for quite a while as well, one of the other members of Ambio. In fact, he was, I think, the third person I ever had on this show, which is back
several years ago. And I got a message from Trevor explicitly telling me about this research because he had learned that I had incurred a head injury from a car accident now a little over two years ago. And he was like, "Hey, you might find this personally interesting and professionally interesting." And I was like, "You know what, Trevor? You are absolutely correct. Fast forward some amount of time. Your paper has been released and here we are talking
about it." So the paper is about the efficacy of using Ibogaine in a combination with magnesium in a structured setting, that structure being Ambio's sort of clinic or center there and the effects that it had on veterans that had traumatic brain injuries. Now, I want to explore that piece by piece throughout the course of the interview and starting with specifically, maybe seems like an obvious question, but it's quite a complex question, which is what is a traumatic brain injury?
And you could tackle this and/or the causes, symptoms, prevalent impact on persons in society, however you want to tackle the question. Yeah, that's a good question. So whenever the head gets accelerated and kind of immediately stops, what happens is that the components that had the brain, the skull, all that stuff, the cerebral spinal fluid decelerates at different speeds, and the brain decelerates slower than the skull. And what that does essentially is it allows for the brain to
impact the skull and effectively hit the skull. And that's what you see, whether it be football, TBI, or even a blast injury or whatever, that the brain moves in a different way than the skull moves, since the brain effectively hits a part of the skull and causes injury to the brain, because obviously the brain is less hard and less dense than the skull. And so there are kind of standard ways in which that happens. And that's kind of the frame that this kind of falls under.
So in the case of military TBI, a lot of it ends up being blast injuries and whatnot, where people get thrown back and their brain actually accelerates quite quicker than their skull. Their brain effectively smashes into a part of the skull and causes a dysfunction. And that can produce a whole host of symptoms that for some people persist ongoing. Can you give us a sense? I guess any kind of injury can
take a number of forms. If I think about injuring my knee, I could tweak it a little bit and it hurts for a little while and I cause minor damage, but it's whatever. Or I could have a minor strain or I could fully tear my ACL. I could shatter my part of the bone or something. There's like a wide range of potential injuries that can occur when I say fall on my knee. What's the sort of range for the kind of what will
qualify as a traumatic brain injury? You don't have to go into every single one, but at its least extreme, it might be like this. At its most extreme, what has happened to the brain would be diagnosed as this. Just give us a sense of the range. Yeah, I mean, so there's mild, moderate, and severe traumatic brain injury. Severe traumatic brain injury is seen on structural MRI. It usually takes the form of a kind of a traumatic subarachnoid hemorrhage or a contusion of
the brain. So basically there's some bruising bleeding that happens alongside structural injury. You can have people get in car accidents and they can have the orbit fracture backwards and hit the orbitofrontal cortex and cause contusions and whatnot. So that's all kind of within the range of possible kind of severe TBI, whereas mild range of what we think about as a concussion, really, there's nothing on brain MRI. There's nothing on CT,
standard MRI and structural MRI and CT. So you're really just seeing a kind of functional impairment and then a headache, nausea, vomiting, that sort of thing. And so there's a big range
of what you can experience from the severity. And then because the brain has different functions in the place in which the brain accelerates and hits has a different function, you can have a host of symptomatology that presents as a result of where on the head you were hit or which direction the blast injury happened.
Yeah, like say theoretically, I could hit my head in a part that is like that area of the brain is more involved with, say, emotional regulation or I could have the trauma happen somewhere that's more involved in sort of like neuro-optical function. So on one end, I could have a lot of emotional dysregulation, on another end, it might present as like difficulties and sort of like managing my I function. Is that kind of what you're speaking to?
Yeah, yeah. So it's anatomically specific, as is everything with the brain, right? If you have a stroke in one region, you have one set of symptoms, you have a stroke in another region, you have another set of symptoms, you have a, you know, whatever other, you have a seizure in one part of the brain, you're gonna have a set of symptoms, you have a seizure in another part of
the brain, you have a different set of symptoms. So that's the complexity of the heart is that the trauma inflicted has a gradation of severity, as well as a location specific symptomatology that coincides. So that's the, does it make sense?
Yeah. And so like TBI as a term refers to like a possibly quite a huge range of both sort of like, what's injured, how it's injured, and are like what part of the brain, but like what's injured, how it's injured, the severity of that injury, and it's sort of like, its symptom expression. Yeah. And I'm wondering what, like, if you could give us a sense of what the impact that would have on a person and then maybe
expand that out into society as well. Because, you know, even if you said, you know, they could have headaches or, you know, dizziness, etc. But there's a whole range of other symptoms that people with head injuries tend to have going all the way into increased sort of anxiety symptoms that present as post traumatic stress disorder, depression, like ongoing sort of like energy, crisis, these kinds of things.
What would you describe as the sort of impact a head injury could have on a person's life? Yeah. So, you know, any neuro dysfunction, whether it be head injury or stroke or whatever it is, can have profound impact on quality of life and ability to perform activities of daily living, right? Those are the two things that people think about as a kind of general metric that's not neuro atomically
specific, right? You know, my ability to get everything done I need to get done my ability to be happy with my own life, right? And traumatic brain injury symptoms that are chronic affect both of those things, right? They reduce your quality of life and they increase they reduce the, you know, the amount of activities of daily living that you can be involved in, that you can perform yourself, right? And, you know, that's a huge personal cost and it's a huge societal
cost, right? The personal cost is the personal cost is that, you know, quality of life years are reduced, you know, so it's not just, you know, you can think about the number of years you live, you can also think about the number of years that you live well, right? And you want, from my vantage point, you want to live a long life and you want to live a healthy life, right? If not all of it, right? And traumatic brain injury, you know, at minimum reduces for some people the number of
quality years they have. And then depending upon the interaction between that and other factors, it can even reduce, you know, lifespan, you know, if it's associated with other medical comorbidities. And so I think, I think that coming up with ways of reversing disability related to anything, including traumatic brain injury is super important. I think that the promise of neuroplasticity psychedelics are the ability to potentially have a restorative effect beyond just a symptomatic
improvement. Symptomatic improvement is great. Restoration, neuro-restoration is the name of the game, right? If you can restore function to pre-morbid levels, that's super important. And just to clarify, because you cut out there for a second, you were, you had said that the potentials of like neuroplastic effects of psychedelics can have like long standing positive effects on like brain injury, not just in reducing symptoms, but even just like bringing back a more sort
of like functional brain. Is that what you're saying there? Yeah, I mean, in the like, kind of sci-fi range of the possibilities of what this is doing, right, if you can, you know, if you can restore function to pre-morbid levels by having a neurotrophic effect, having an effect where you're effectively, at least in kind of mild cases, as we saw in this study, like, seemingly restoring function, you know, restoring function is different than symptomatically improving
something, right? I can have heart failure and have a terrible heart and give drugs that restore my heart's ability to might that can, can reduce the symptoms of congestive heart failure, such that while my heart's the same, I'm not having shortness of breath and water in my lungs and stuff like that. But my heart's the still the same, right? If you do an echocardiogram, that drug really hasn't, in some cases, hasn't
changed the nature of my heart. It's just like, change the physiology such that like my bad heart works okay, you know, for symptom, you know, symptomatically. That's very different than saying, you know, I've got a drug that can effectively reverse congestive heart failure, we don't have drugs that can totally reverse congestive heart failure to a point where people don't meet criteria for congestive heart
failure, right? And so even in the heart, which we know a lot more about, we don't have like, completely restorative technologies. So the idea that, again, and they're kind of, I don't, we don't totally know, right, but in the kind of sci-fi range of what this could do, you know, and what, you know, some people are hoping it can do, we have a lot more work to do to figure out if that's true, is that you could have some restorative function, right? You're bringing the brain back
to some place that it was at pre injury. And that's the part that I don't know, but it seems to me like, if there is a drug that could do it right now, that Ibogaine has, you know, is one of the best candidates for that, given what we've seen. But we just don't know, we have a lot more work to do to really figure that out. I want to dive specifically into Ibogaine, and then the results
that you got out of your study in a minute. But I think I want to really like double down for listeners who, like even myself as somebody who is still in the sort of long running effects of what, you know, post concussion syndrome, the amount of sort of misunderstanding I had about the, about the condition and about its impact and the amount of misunderstanding and misperception that the sort of like, larger society has on on how this would impact a person, I want to kind of like, really
help accentuate that. It's I've heard it described oftentimes as like an invisible injury. Like if you see somebody walking on crutches, you know, right away, oh, they have some sort of, you know, orthopedic condition that means that they
need to rely on this thing to walk. But you don't generally see and be like, Oh, that person has a brain injury, you just perceive their behavior, or they're sort of, you perceive their behavior in a particular way, and not recognizing that sometimes both as a consequence of the symptom, and as a direct symptom, their ability to function cognitively, emotionally, relationally, socially has all been compromised to a point that makes it extremely difficult
and sometimes problematic for not just the person, but their relationships. For example, from what I understand, there's a not insignificant sort of observation that emotional destabilization and of course, from that problems in relating even as far as like intimate partner violence could be a direct consequence of changes that happen to the brain from brain injury or repeated concussions. I think I just
want to make that clear for listeners by saying it. But if you'd like to comment or sort of like expand on any that I welcome you to do so. I mean, there's, you know, there's a huge, like I said, it's much more about the neuroanatomy and the severity than it is like that it's TBI per se, right? You have the same symptoms of somebody has a stroke in the same region, right? It's not a, it's not like, hyper specific to TBI. The problem with TBI and constructing therapeutics for TBI is that
there's no symptom, there's no good symptom scale, right? If you have a visual cortex hit, you're going to have a very
different set of symptoms. And if you have a prefrontal cortex hit, or primary auditory cortex, or whatever it is, right, like there's, there's just like a whole host of potential symptomatology that aligns much more with the anatomy than it in the severity than it does the specifics of TBI per se, but the idea that brain injured persistent brain injuries can manifest in a huge range of symptomatology makes sense because the brain can manifest its behavior in a whole huge
host of potential behaviors that you see for people walking around in the streets today, you know, and so it just falls within that same big range. I want to before I specifically move on to Ibogaine, this is the last question I have about TBI specifically, which is, you know, you spoke to like the huge implications this could have on compromising someone's quality of life and ability to function
in life. I'm wondering what kind of metrics there are with respect to the amount of TBI that is happening broad scale, say in the United States, I believe that's where you're located. And what the sort of proposed impact of this sort of amount of TBI is is having on society as a whole, as we understand like the necessities of a person's function within our socio economic system.
Yeah, I mean, that's probably pretty hard to quantify just because, you know, we don't even know, a lot of people have had at least a concussion at some point, right? And we don't even know the the, the scale of that the implications of that, it's probably super under diagnosed, because a lot of people just shake it off. You know, are there persistent symptomatology related to that? It is some of the risk of what we think about
as idiopathic psychiatric illness. So the things that we think are just spontaneous or happen as a result of like, stress within one's life, how much of that is actually post traumatic mild traumatic brain injury, we just don't even register that, right? So I think the question is a good one. The answer is completely unclear, you know, it's it's seemingly very
broad. You know, from from what you can kind of read in the tea leaves of how many people have had a concussion in their life, you know, and how many of those percentage of those people have had, you know, a subsequent psychiatric illness, you know, it could be a fair amount of those that at least that was a risk factor for but we don't we don't really we don't really know, you know, I think what we do know is the folks that have had a reasonably pretty least reasonably significant, let's
say sports related concussion that everybody on the field visit, you know, can kind of visualize as it happens, or people that are in blast injuries in the military that have some set of symptomatology that their fellow military kind of acknowledge is a change. But you know, even with, you know, the sort of thing, the were, were folks have, you know, ex football players or boxers or whatever, like 20 years later, start having these cognitive problems. Even in some of those
cases, it's not a direct head injury, right? It's, it's repeated body injury, like body pressure injuries where people get hit in their stomach, and then there's a force transmitted up to the head, for instance, right, and there's repeated body hits that happen over and over again. And that seems to have a negative, you know, negative impact on the brain, because you're transmitting high amounts of force up to the head, you know, we just don't, we don't have a good handle on
this, because none of it's being measured. You know, nobody's really going around and kind of measuring other than some of these, like football helmets that people have made and that sort of thing. But, you know, there's probably there's, there's a paucity of kind of brain measurements at, you know, at large in society that can answer that question. I hope in 20 years, we, we, we have metrics and measurements that are continuous measurements that can tell us some of this.
But from your, if you were to, if you were to make a sort of educated guess from the data that you do have, you do feel like it would be fair to say whatever that effect is, it's likely substantial? Yeah, I think so. I mean, it's, you know, anything that crosses the 1% mark in culture and society has a huge impact, right? I mean, we know that, you know, and so just by the scale of things. And so in that way, absolutely.
So let's move in directly into Ibogaine. So I kind of wanted to structure it like, okay, this is traumatic brain injury, that's its own little island, you know, this is Ibogaine, that's its own little island. Now let's, you know, explore the waters around these two things where that where they sort of meet in the in the tidal flow. So with that, what what is Ibogaine? Can you give me a little sense of what this molecule is and how it affects the brain?
Yeah, it's a it's an alkaloid of the the Iboga root bark, which is the Iboga tree is a central West African tree. The root bark is contains a host of alkaloids, including Ibogaine. But there are others, Ibogalein, Ibogamine, you know, on and on. So it's not the only alkaloid. The buliti have used Iboga root bark ceremonially for for millennia. The French discovered this in 1899. And by 1930, isolated Ibogaine and turned it into a drug that was used in France until 1966. Then that
went on the Controlled Substances Act in France. And, you know, as a Controlled Substance Act in the US and other places that that limited use of these these compounds. Every country, not Canada, not Mexico, not Australia, not New Zealand. And so Ibogaine is kind of unique in the sense that it didn't get
kind of worldwide band, it got banned in certain places. And, you know, it's been used kind of in these underground clinics since the 70s to try to treat folks with with a variety of symptomatology, but primarily in the addiction range, you know, and the kind of opiate use disorder and related addictions in it. For some reasons, we understand for some reasons, we
don't seems to interrupt addiction. And then, you know, much more recently, there's, there's been an interest in in utilizing this as a neuroplastic agent to try to treat people with brain injury, as you noted earlier. What do we know about about the direct pharmacological effects of Ibogaine unrelated to, you know, treating a particular condition or disability or injury? What do we know about just broad scale Ibogaine goes in, this seems to happen in the
brain? Yeah. So it upregulates neurotrophic factors like glial derived neurotrophic factor, brain derived neurotrophic factor, and produces, you know, a whole host of interactions with the serotonin receptor with with the opioid receptors with glutamate receptors. And so it works kind of like ketamine, it works kind of like MDMA, it works kind of like classic
psychedelics, it has this really broad effect. And the kind of synthesis of all that is that it produces this very stereotype psychological phenomenon in which people have a earlier life reevaluation of memories that primarily were emotionally
salient. And for a lot of people end up being traumatic in which they reevaluate the memory in a neutral third party stance, and they're able to re contextualize it and then seemingly reintegrate the new context into their memory system such that the traumatic aspects of it change and people have a better understanding of what it is. And so that's, that's the, you know, that's the drug both phenomenologically and pharmacology pharmacologically.
Now I, I did, you did refer to it as a psychedelic, I understand that to be a very fair characterization, although, and you'll have to forgive me if I'm kind of like confusing this because I read a couple of papers on the effect of ibogaine including including yours to prepare for this interview. So it might not have been used specifically. But the referencing ibogaine, not just as a psychedelic, but also as an onyrogen, which is like a substance or chemical that
generates dreams or dreamlike states. Can you just let me know if I'm just like misattributing that to you? But if so, can you outline a little bit why it would sort of fit as an onyrogen as well as a psychedelic in contrast to say, no one's calling psilocybin an onyrogen? Yeah, so the reason why people think about as an onyrogen is that it produces a dreamlike phenomenon in which that
reevaluation occurs, right? And it's all like, you know, primarily closed eye reevaluation, it's not an open eye, kind of visual distortion, visual, you know, hallucination, visual, perceptual change that happens with say, LSD or psilocybin, right? And so, you know, it's these things are
imperfect, right? You know, the psychedelic terminology you talk to, a really strict folks who have this kind of very a psychedelic, a receptor agonist in order for them to accept it as a psychedelic and only classic psychedelics like psilocybin else to really fit into that bucket, you know, and then that's kind of the splitters and the lumpers will think about ketamine, even in MDMA is psychedelics, and the splitters are going to say that, you know, that's the ketamine
is a dissociative anesthetic and MDMA is an intactogen or an empathogen, right? So it's, these are splitter, lumper problems, it's not really like, you know, and so, you know, you can call it an erogen, I think it's totally fair to call it a psychedelic in the paper, we call it an atypical psychedelic.
I think the nice thing about referring to it as an erogen, which is how we primarily referred to it in the paper is, you know, there's there's baggage on LSD, you know, and that baggage is going to stick around for a while until the boomers are, you know, until it's 2060 or something, you know, to be in and so it's one of these things where, you know, from from that standpoint, you know, there's there's some baggage around the term psychedelic, there's some baggage
around some of the psychedelics, that's going to take some time to shake, I think. The nice thing about Ibogaine as a therapeutic agent is that Ibogaine does it is not, you know, is not a recreational substance in any form or
fashion, right? You can make an argument and a pretty strong one that MDMA can be a therapeutic MDMA can be a recreational substance, you know, as we all know, right, people were using MDMA and raves, they probably continue to do so, you know, we're going to see an FDA approval for this hopefully, in the summer, you know, I don't think that that's the that's going to be a fair characterization of Ibogaine at all, right? It's not recreational, people don't
particularly enjoy it, for the most part. And, and because of that, it's not, you know, it's not something that I think we're going to have as much of an abuse liability risk on. And in fact, like people, you know, the stories of Howard Lotsoff and others were, they ordered this because they wanted to have a therapeutic, a recreational effect when nobody knew what it would really do. And they had a therapeutic effect, but not a
recreational one, right? And a lot of what you hear about with Ibogaine too, is that people are not, if you, if somebody takes Ibogaine, you have a conversation with me, so it really helped me, I was like, Oh, when are you gonna do it again? Like, I don't know. I'm not really sure. I'm gonna do that again. You know, I don't know if I'm gonna go through
that again. You know, and so it's one of these things where, you know, and that's not everybody, you know, I'm sure Trevor and Jonathan have some friends or whatnot that that I've done it multiple times, but as a generality, it's not, it's not something that like people are like jumping to do the next week, right? You got to be really intentional about it. And it's not a frequent use thing. So it doesn't really fall into
the abuse liability tolerance kind of story. Whereas ketamine certainly does, you know, and some, for some folks, you know, MDMA does, you know, and then I think like the classic psychedelics, it's more, more in the middle, right? People will take those a burning man or whatever people will not take them in a, you know, an abuse liability sort of way, generally, so it's kind of pretty low risk, but but also, you know, reasonably recreational.
Yeah, it's exciting to see the sort of, you know, medical potential or like just even the research potential of ibogaine because of what you just described there with a kind of like not necessarily having that same baggage and not necessarily having that same abuse liability, sort of potential. And also to its, its, its regulatory status makes my assumption is it makes it perhaps easier to do research on it than it would if it had no.
No, and that's because of the cardiac risk, right? And so it's probably the hardest to get through the FDA, because of the risk of having an arrhythmia, but it's not really the psychedelic effects as much as it is the cardiac risk and it's kind of long tail of drug, you know, in system, you know, it lasts for a while. And so that's really the issue from regulatory standpoint is that there's been deaths, right? Primarily in people with opiate use disorder and addiction and
whatnot. But even in the absence of that, there have been, you know, a couple of cases of people that didn't have that. And so studying this is very hard. You know, we did this study with
Ambio for that reason. You know, our plan is to, you know, to look into trying to do a US based trial or trial in, you know, a country that is accepting to do a trial, you know, normal healthy control trial in this, but it's now going to be under a regulatory auspice, you know, under, you know, kind of the monitored settings that regulatory bodies would want. And that's not straightforward, it's going to take some time, it's going to take some work to get that done. But it's worthwhile to do.
Yeah, I appreciate that clarification. And also it speaks to another aspect of Ibogaine that is unique under the the Lumber's categorization of psychedelics, which is that, you know, you could, you could effectively die as a direct result of what Ibogaine does when you put it in the body, like, you could theoretically die under LSD or psilocybin, but this is usually as a consequence of, you know, with the dose that you would have to take to directly kill you, the LD50 of
psilocybin is massive. But you could theoretically die as a consequence of choices that you make when under the influence, but with Ibogaine, you could directly die as a consequence of its effect on the heart. And I understand that and I'm going to ask you about the study, just this next questions about the study, so don't go too much into it yet. But I understand you attempted to compensate for this potential risk with an aspect of
variable that you put into your study design. But can you tell us what that risk is? Like, from what I understand, it's, it has something to do with the interval between heartbeats, that in some people, the interval can get so wide that the heart just stops beating completely. Yeah, yeah, you're very close. Yeah, that's a great, great understanding. So essentially, there's a there's a receptor, a potassium channel receptor in the heart called the HERG Herg
potassium channel. It's very well characterized. There are drugs that are FDA approved that have an impact on her and so chemo drugs, actually some anti rhythmics can be anti rhythmic and pro rhythmic rarely. So they're anti rhythmic, almost
everybody and then pro rhythmic and a small group of people. And in that group of people where they're pro rhythmic, I mean, you know, the in this case, tikka send is the drug where it's pro rhythmic, it can cause a widening of the q t interval, the interval you're talking about and the q t interval widening past a certain number of milliseconds increases your risk of going into another rhythm called torsades de pointe, which is a an arrhythmia that is not I became specific, again,
it can be induced by a whole host of things. And it's a fatal arrhythmia, meaning that if you don't get somebody out of that rhythm, they're going to die. Right. And so, so, you know, torsades is a is a risk that that, you know, you don't want to have with any drug, I being has that risk. It's somewhere in the one in 300 range, the risk with tikka send is closer to one in 100 range. You know, there are other chemo drugs that have a risk there too. The way to deal with it is a combination of,
as we see it prophylaxis plus monitoring, right. And the prophylaxis piece is utilizing a range of compounds that have been shown to shorten q t interval and reduce, reduce risk of, of torsades and other arrhythmias and q t prolongation. And so, you know, like, you know, IV magnesium is one of those potassium is another calcium is another. So we know those three, you know, elements can do it. oral
lidocaine can actually do this. So there's a host of cardiac agents that have been shown in various experimental manipulations to do this. And so what's novel about this kind of vantage point is this idea that that essentially we can modulate this, this risk by, you know, by pre administering it in everyone. So the next question I had for you is now that we've talked about TBI generally and Ibogaine generally, specifically, I want
to go into the study that you ran with Ibogaine. Tell me, tell us about your study, the design, and I guess, in some sense, what drew you to investigate the potential of Ibogaine for this purpose? Yeah, you know, I guess your last question first, I've, I've always been very interested in Ibogaine since I came across it, you know, more than a decade ago. You know, I was in a in the airport in a pretty much Central American country and, and was in
a books, like a bookstore in that airport. And there was not a whole lot of English books, but for whatever reason, Breaking Open the Head was one of the classic Daniel, like, yeah, so I read that, that book, got it really interesting. And obviously, he has a part in there where he went and had an Iboga ceremony and then read a lot about it, you know, from the experiences that folks had written up around opiate use
disorder. Got pretty convinced that it was a useful compound for that, but then thought it was reasonably unstudiable, right, because of the regulatory hurdles, one would have to get over to do something in the US, given that it's a psychedelic, which is kind of problem for FDA number one, especially back in
2010 or 2012, or whenever that was. And then on top of that, the issue of the cardiac risk, right, and the fact that, you know, folks had a cardiac, there's, you know, one in 300 roughly risk of torsades and death in the opiate use disorder population, which I think is in part more specific to that opiate
use disorder population, but this is a generality. And so, you know, you're kind of thinking in those those terms kept it on the radar, you know, but didn't think it was kind of immediately actionable, got out to Stanford working on other things, and then had heard about some early veterans that had been, you know, treated with with IBM for for PTSD, TBI related symptomatology depression, and kind of reengaged into the idea, connected with a number of folks
that you probably aware of, you know, the vets, co founders, Martin Polanco, others, and talked to everybody and kind of came out of that conversation with a, you know, conviction that this was something that would, you know, would be helpful, you know, to folks and one needed to construct a study
around that. So we went to the Stanford IRB and developed a trial that would let us, you know, evaluate veterans before they went to went down to Mexico to participate in this sort of in this sort of a study where essentially they would be evaluated by us, they'd go down there, receive treatment and then come back and be reevaluated at multiple time
points. So and the retreats that they were going on, like your study team wasn't adding anything in particular, or was there anything specific that your study team was adding to what otherwise would have been or subtracting, perhaps of what otherwise would have been the standard sort of retreat experience for people before and after your testing?
That's a great question. Yeah, you know, I mean, one of the things that normally happens is there's normally a five m e o DMT administration that that happens right after the Ibogaine and we delayed that past our one month follow up very intentionally to see an Ibogaine only effect, you know, and so in some ways that was specific to the study, in the sense that these individuals signed up to know that they weren't going to get the five m e o. You know, in addition to the Ibogaine, it
really made it for a much more pure Ibogaine question. But you know, but we didn't, we didn't have an effect on the, you know, some of the other kind of sweat lodge stuff and that sort of stuff still happened, but was, you know, limitation in the right up of the trial. And what kind of things were you testing? Like what what measures were you getting before and afterwards that we're allowing you to track changes? Yeah, and so, you know, there's multiple layers and levels of,
of kind of assessments, right? But there's like gold standard FDA level assessments that that, that folks use to get drugs approved by the FDA, right. And so, you know, there'd been a couple of studies out there, where folks had used kind of not FDA compliant sort of measures, and they saw some
effects, and that's great. Mostly patient subjective scales, which have a lot of, you know, confounds because it's not, it's not as objective as, as a clinician rated scale, clinician rated scales aren't completely objective, but they're better than the self report scales. And so we put together like, like an FDA, you know, gold standard kind of level of clinician rated scales that we did with with everybody before after one month, and then we have followed it out to a year, as well as
neurocognitive evaluations, right. And so the idea of being able to get a neuro behavioral readout of what various executive functioning scales read out to look like, as well as biological measures. So EEG MRI, both functional MRI, structural
MRI. And the goal there was to get, you know, a really, really complete data set that captured, you know, what is the kind of the most comprehensive, I began related neurobiology study that's been conducted, right, nobody's really looked at the effects of Ibogaine on on the brain, and as well as kind of the most comprehensive clinical evaluation of what Ibogaine is doing, from a cognitive psychiatric neurological standpoint. So pretty exciting to be able to do that.
And you measured things that had to do with their sort of the, like you said, so objective pictures, MRI, fMRI, EEG, this kind of thing. But then also, you were measuring their level of like how they qualify for degree of post traumatic stress disorder, depression, I'm not sure what else. And then the neurocognitive testing was because TBI, one of one of its primary consequences is, you know, compromised, cognitive function, working memory function, executive function.
And so that's why you included those tests as well. Yeah, that's right. Yep. And now I understand that you there was something and I'm not sure if this is normally a part of the program, that's at Ambio, the center that you that you were doing this research with. But you added something else, you added magnesium to the treatment protocol. Can you explain what that was all about? And why you chose to include that?
Yeah, so magnesium is a is the treatment for torsades to point the arrhythmia that that can happen with Ibogaine, it can happen with other drugs, actually. So anything that's a QT prolonging agent. And we've known for some time, and it's actually part of the American Heart Association guidelines to provide Ibogaine, I'm sorry, to provide magnesium in the setting of torsades. And, and so that's kind of the known treatment for
for torsades. But there hasn't really ever been any descriptions of using magnesium or any other any other element, you know, for prevention of a drug induced torsades or QT prolongation. There's some studies around cardiac surgery related QT prolongation. And some studies around using oral lidocaine for for drug induced QT prolongation. But that's the general idea is that, you know, this, this is one of a host of potential cardiac protectant sort of drugs that
could could have an effect. And so, so that's, that's the general idea of why that combination makes sense for that purpose. And was there a particular particular reason why you focused on a veteran population for this initial trial, or this particular trial, rather than sort of larger subset of TBI people, like why you went specifically to veterans? That's, you know, that's who's at this stage of the game, who's going down there, who's willing to go down there, you know, and
so there've been a couple of NFL players. And, you know, there's some interest, you know, with with professional sports, but not at the level of the of the military, it makes some level of sense, like in retrospect, why, why that group would be willing to do it, right? If you think about it, they're the ones that are tolerant of one in 300 death risks all the time, right? I
mean, I don't think that's what the risk is here. But that's, that's the kind of reported risk in the literature with an opiate used to sort of population. And so, you know, they before the, you know, before this is at scale, well, there's still, you know, a handful of folks, every single one of those veterans was pretty much accepting the assumption that they were
accepting a one in 300 death risk. And it inherent in that, which is, which is pretty interesting is, you know, the calculation that maybe their death risk is higher with not doing it. Because of the suicide risks that these guys encounter and to my knowledge, there hasn't been a single fatality from Ibogaine, you know, in these individuals, but there's plenty of fatalities from suicide of folks that didn't get it. So I think, on balance, you know, we're gonna have to see how
the data plays out. But, you know, it's, it's probably true that the risk is higher in the untreated groups than in the treated groups. But, but that's the thing that's kind of a speculation at this point, not something that we have any real super hard data on, we have like 1000, 1000 veterans that have gone down there, but we need to be able to do this at scale to
really know that but it's an interesting problem, right? That that's hard to kind of deal with from a regulatory standpoint, point and like a societal standpoint, when the risk of not taking a drug is higher than the risk of the drug itself, or an intervention, it's higher than not having the intervention itself. And that's certainly where the state of everything is,
right? The oral antidepressants that are out there don't have a particularly good anti suicide effect, you know, they don't really seem to have one much at all from from the, you know, the
studies have been done. There are a handful of drugs that do, you know, it, you know, at scale societal levels, but in individual studies, don't, it doesn't play out like lithium, you know, and so it's one of these things where, you know, it'll be interesting to see is there's more work done in this space, if we can, you know, have a really substantial reduction
in suicide risk. And if we do, then that's a that's kind of a big deal for for this group in particular, and then for society more generally. So with the group of veterans that you had going down there, did every one of them qualify as having, like evidence of a TBI either sort of report it reported evidence or something visible on a scan somewhere? Or were there was there possibly a mix? Yeah.
Yeah, mild TBI. So mild TBI and concussion are reasonably interchangeable terms, you know, in the sense that they both refer to a traumatic brain injury that does not yield a structural abnormality on a standard MRI or CT scan. Right. So when you go and look at their brain, in the kind of normal
scans, you don't see anything. If you look at their brain, you know, there's this kind of DTI diffusion tensor imaging work that people have done in various ways of analyzing that, where you can see that they're what they call pot holing and various things where there's small tears in the white matter tracts from the sharing effects of the, you know, this acceleration deceleration, which is effectively what you're dealing
with, right? You know, with a TBI, I think I said this last time, too, that your brain is just decelerating at different rates, so that the, you know, essentially the brain itself is accelerating and stopping at a different time than the skull. So if you hit your, if you're, you know, if you're riding your bike, and you slam your head into a concrete wall, the first thing that's going to hit is your skull, and it'll stop. But
your brain isn't going to stop quite yet. Right? Your skull stops, and then, you know, almost, you know, whatever, milliseconds later, seconds later, whatever it is, the, the brain will hit the skull and then stop. And so it actually decelerates on a different time scale. And when that happens, then you can imagine there's sharing effects on the white matter tracts that are in the middle of the brain,
particularly around the thalamus. And so, you know, there are experimental imaging modalities that can show what we think are abnormalities in mild TBI, but we don't see it with normal structural scans. There's only one or two people that actually had abnormalities on a structural scan. Now, the reason to do that is, you know, you always kind of want to start in these sorts of studies with a kind of milder folks and see if you get an effect because if you don't see an effect there, then
it doesn't make sense to go to more severe populations. If you get an effect there, then you march it up to a more severe cohort. And that's really, that's really what we did. So so everyone in your study classified under like a mild TBI or concussion, you didn't have anyone that had any like obvious brain damage or or anything like that, we had like one or two that had had obvious structural scan kind of moderate TBI. But but the vast majority of people it was it was, it was mild. Yeah.
Okay, so then what did you what did you observe? Like on the on the other side, where you've analyzed the data now you've put out the paper like, with respect to Ibogaine, I guess, in addition to magnesium, it seems like magnesium was less about adding to the Ibogaine effect than taking away from the from the risk. Yeah, that's right. Exactly. What did you see? Were the like, what did you observe is the effects Ibogaine had on these veterans with TBI and the variety of their symptoms?
Yes, so we saw a reversal of traumatic brain injury disability. We saw a improvement across a broad range of idiopathic psychiatric illness or depression, PTSD, anxiety, and reduction in suicidal ideation, and that, you know, reversal of disability on the hudas. And so it's, you know, that was the particularly robust finding was seeing that, you know, one month, most of these folks had gone into no disability from mild to moderate disability, which is pretty striking.
And what about the cognitive function? Like, was there a notable change in people's cognitive functioning as well? Yeah, the cognition improved across the board as well. Yeah, so it was pretty great. How, how significant are these results in the sort of like, larger field of TBI treatment? Well, there's no, there's no kind of biological therapeutic
for TBI. And so everybody is always looking for TBI therapeutics that would be of interest, you know, and this is definitely, you know, one that that's promising, you know, there was a an editorial that accompanying editorial written by Dave Brody and Sean Siddiqui or TBI researchers, and they, you know, they felt that the study was compelling and worthwhile
pursuing more, you know, data on. And that's important, you know, because they've been really the only ones, you know, that have had recent signals of effect with transcranial magnetic stimulation, you know, and so they kind of leaned in on this too. So I think the idea that, you know, more studies need to be done, we need to do a controlled trial, you know, it needs to go through the standard, you know, science
process to kind of move it forward. So I guess like, I, I have the question of something like, because your response was very tempered there, and the sort of reporting around it, which I don't expect you to take the same raw raw that sort of reporting on science as a scientist, I imagine you don't want to sound like a science reporter, those
are different roles. But my sense was that, that these results are, they're really substantial in the sort of in in the sort of, oh, yeah, we sent people down for this singular treatment. And it had these these seemingly massive changes in an area of medicine and therapy, that at best is incremental, and slow over time, if not a lot of the time, almost entirely ineffective to get people out of a disability state.
Yeah, you know, there's levels of knowing, right. And the greatest level of knowing in this case would be a multi site trial that other people conduct that follow, you know, this protocol and find the same thing with a blind in place. And you'll see me out saying a bunch of really compelling things that are definitive. If I if I sit on the show, and I tell you, yeah, this is definitely a treatment. And this is, you know, and my colleagues that do this sort of work would, would, you know,
would have me at the stake or whatever. Because we don't, we don't really know, you know, we, I mean, in theory, and that's why nature medicine, you know, had us put all this extra stuff in there, you know, we, you know, we had to list the sweat lodges and the this and the that that were going on down there. Now, we know in isolation, that none of that actually produces like robust changes in their own right. I think the reason why MBO does that is very good. I'm not trying to detract from that.
But it's, it's likely, it's likely not the primary mechanism of improvement here. It's likely that the the drug itself was but without having like a really sterile, non therapeutic environment with no activities, they're therapeutic, you know, you're, you're basically pulling all that out of it and creating an environment which everything's neutral other than the treatment itself, then you, you don't, you can't make the same level of claims. But on the flip side, you know, nature medicine
was willing to publish it. And so everybody believes the signal is really there. But, you know, to really know, you gotta, you gotta jump through all the hoops. And it's, you know, the funny thing about that is that it's, it's just this is a modern day convention. That's not necessarily how things got into, you know, into the pharmacist closet forever, right? It's just
more of a, you know, modern thing. So, you know, I did a TEDx talk recently, I may have talked to you about this in the earlier half of the show, but looking at thinking about how to really think about these results in the context of history. And so talked a lot about scurvy and how we knew, you know, that vitamin C and, I mean, eventually vitamin C, what was vitamin C containing fruits were necessary for treating scurvy.
And, yeah, there was there's levels of knowing, right? And that's, that's definitely, you know, that's definitely there embedded in history. But like needing a fully blinded study to know isn't necessarily the way we've always done it. But it's certainly modern convention. And in order to get things through and not have people point to something and say, yeah, that's you don't know, really, you have to do it that way. Now, it's interesting, like, of course, I can appreciate that. I
understand that. And it's also interesting to consider that in the context of a psychedelic molecule, we'll say, you know, obviously, Ibogaine doesn't fit the classical group, but it fits at least loosely into the psychedelic category. Because so
much of because psychedelics are not like an aspirin, right? I take an aspirin, it's got a pretty dedicated result, I take it, and it's gonna do what it's supposed to do, it's going to have that pharmacological effect where with psychedelics, the medicine of the psychedelics, so much of it is influenced by context, like somebody could take five grams of mushrooms in one context, and it can heal their depression, maybe they
could take it in another context. And they've got depression plus post traumatic stress disorder from being an absolute terror
for whatever, six hours. And so it I guess I was going to save this question a bit more for later, but I guess I'll kind of like weave it in now, which is that, you know, like, how much do you think the the the benefits that you're seeing, the changes that you're seeing are purely because of the molecule itself, physical molecule, physical brain, physical change, and how much of it might be influenced by the sort of like larger therapeutic container that allows for those changes to
take place, or the larger therapeutic container that allows for these experiences not to be troubling so that they're more, you know, inclined towards like a like a positive valence. Definitely. Yeah, I mean, I think that, you know, we society and Western culture and kind of the scientific method and kind of how the medical establishment sees how to deal with things. It's all like centered around certain assumptions about
reality, and about what's therapeutic. And if you're talking about a knee infection or skin infection, or, you know, osteoarthritis, or whatever it is, you know, I think you can be reasonably sure that, although some people may disagree with me on this, but reasonably sure that those assumptions are are pretty valid, you know, that, you know, you've got this infection, you take this antibiotic, the antibiotic has an effect on the bacteria that kills the bacteria that ends up
you know, resolving your, your, you know, bacterial infection, your skin or whatever it is, right? You know, and that's, there's, there's good evidence that, at minimum, that particular approach is one effective way of taking care of that problem, right? With, with psychedelics, the problem is, is that it kind of gets in the way of assumptions and, and philosophical kind of framework of Western medicine, right?
Because we should just be able to give the pill. And it doesn't matter what the person's thinking or doing that the pill just kind of works, right? And that's how like, you know, heart pills work, antibiotics work, and blah, blah, blah. The problem with, with the psychedelics is that this is, this is something that's a nonspecific enhancer of certain experiences, particularly MDMA, I would say that one. In particular, it's important. And I'd argue that classic psychedelics are
somewhere in the middle. And I think I began to is very important that people feel safe and in a container, but it's not as much psychedelic assisted psychotherapy, and it's more its own, its own kind of framework. And so that's the, that is the,
the kind of thinking behind that. And because of that, I think that, you know, we're gonna have to really grapple with this idea that even more so than the normal with a vulnerable patient, this is kind of an extreme of a vulnerable patient, and we have to really set a framework up for those extreme, you know, vulnerabilities that all patients taking these compounds are in. And, you know, people try to tackle this with a male and female therapist and in all of these kind of settings
to be able to try to safeguard against it. But I think we're gonna have to really think really deeply about what interactions and what words are spoken and all of that in a highly plastic state. You know, the the area where this has been solved out at some level, which is really interesting, is in therapeutic hypnosis. Right, every word that's spoken by the hypnotherapist is intentional, the person is in an altered
state, very vulnerable in that altered state. And the hypnotherapist is very clear about what they're saying and not saying to the patient, and the setting in which they're producing for the patient. And there's a long, you know, and that's the first conception of Western psychotherapy, and it's effectively inducing an altered state. And so that's why I've been pretty interested. We've done some hypnosis studies, we've actually been able through neurostimulation to change the
trait, make people transiently more hypnotizable. And the goal of all that is really to understand how do you access that altered other place, and what's in there? And what are the the bounds of it? What are the contexts of it? And so in some ways, that's very similar to what you're talking about.
Do you think that it's possible that if in a future study, people with similar sort of clinical diagnoses and set of symptoms, etc, are brought into a, you know, very clinical space, and are just given the Ibogaine with somebody there to just track them from like a pretty standard place, nothing special, nothing extra therapeutic, just safety protocol, trying to sort of like, eliminate the humanity as much as possible to create this kind of objective, drug only measure.
If it turns out that those people aren't getting as much benefits, you know, according to your study, or in a larger therapeutic container, like was present at the at the Ambio Center, that that suggests that do you feel like that would be like a cue to reconsider Ibogaine? Or would that be a cue to sort of even further consider facilitation context to support the positive outcomes?
I think the latter, I mean, I think the thing about Ibogaine is really interesting is this life review slideshow that people talk about seems to happen, irrespective of any
sort of psychotherapeutic interactions, right? And so Howard Lotsoff, who was a poly substance user, who was, you know, the first person in the US that really kind of tried to champion Ibogaine, ordered online for the purposes of recreation, and found quite quickly that this is not a recreational compound and came out of that, no longer desiring to use any sort of, you know, substances and to my knowledge
never really did after that point. And, and he, I think he like ordered it, man order or something and didn't have a, didn't have a container. And so I think, I'm not suggesting that people do that. But it's, it's, it's probably the case that some people need more support. It's probably the case that some people need less support. And the question is, how many people, what percentage of people need more support? What does that support look like? Or, you know, vice versa? I have, I'm a
scientist, I have no opinions on this. I run a clinic and all, you know, I don't have any agenda around saying, my way is the way, you know, I don't have, I don't have any beliefs about that. I think that, you know, where I sit, there's a signal there that's really robust, that we have to figure out what's driving it could be all a host of things. I'm totally open to the idea that the therapeutic environment is mandatory for its effect. I'm open to the therapeutic environment being
less mandatory for its effect. I don't, I don't have an agenda there. I, I think it's always best to have a safer environment. And then you scale down the acuity of that safe environment. And that's what we're going to have to do in order to be sure that we don't cause harm, which is one of my like, Hippocratic Oath things is to, to not cause harm, right? So I have to do that. But the idea that, you know, there's more or less necessity for this, it's just, it's very unclear, because
people haven't done the work to figure that out. I think Robin Cart Harris, up at UCSF is, is looking at this question as it relates to psilocybin assisted, you know, psychotherapy, whether the, you know, the actual psychotherapy, you know, set and setting pieces, important or not, I think he's gonna, he's gonna help to try to sort that out for psilocybin. But it's one of these things where you have to almost do that trial. And the problem is these, I mean, trials gonna be really hard to do, you
know, and so it's gonna be a while till we answer that. So I think whatever ultimate design comes up from just the base trial, it will be scrutinized, and then we'll have to kind of figure it out from there. So let's take a couple steps back to a to the question we were on there about, you know, how your results compare to other TBI
treatments. I mean, pharmacologically, from what I understand, we don't have any drugs that that fix the damage that, you know, the symptoms of TBI come from mostly we have drugs that mask symptoms or support people through their symptoms long enough that the brain can hopefully heal itself, various non pharmacological treatments that could support things. You have drugs that like treat like, say, you know, spasticity
and things like that from traumatic brain injuries. So there's not nothing but but it's, you know, they're daily drugs, it's Botox or something. But there's nothing that certainly is helped with reversing any of the major cognitive deficits in any robust way, people use stimulants and stuff like that. But it's not, you know, not at the level that it's certainly not a single administration that lasts for a
long time. That's what's really striking about this. So I think, you know, it's very compelling, because it looks like it's a neurotrophic, you know, factor up regulator, it's, it's, it's not like you have to keep taking this every day, it's like you do it, and then it persists for, you know, we have day, you know, your one year data, it's persist forever. Really, one year, it's still persisting the benefits people
had in your wow. Yeah, that's very promising. Or like, I feel it feels very promising, because I myself am living with post concussion syndrome. And I felt the sort of yo yo of trying to find the right treatments and so on and so forth. So yeah. Yeah, it's, it's, it is, it is very compelling. And you know, placebo degrades quite quickly, right? And so you can have a in treatment naive people, you can have a pretty robust placebo effect, but the placebo effect generally degrades quickly over
time. And so the idea that this didn't degrade over time makes it more probable that there's something real about it. While it's not a controlled trial, at least, you know, that's, that's a compelling feature. So that's, yeah, we're trying to, we're trying to, you know, sort a lot of that stuff out and kind of move forward on some of that. So yeah.
Now, how do you think I began? Okay, so there was a, a paper that came out, I think within the last two or three years, specifically looking at psychedelics, you know, writ large as possible agents for treating brain injury, because of their sort of neuroplastic effects, neutrophic effects, etc, ranging everything from including MDMA and the classical psychedelics, as well as ketamine, I myself have received ketamine as a as a TBI treatment. Do you think that the
same principles? Maybe that's not the question. It's more like, how do you think or what's your thoughts on how your observations with Ibogaine, do you think that they're also going to apply to other psychedelics as well? Or is there something special about Ibogaine you think that's having such a seemingly robust effect? I mean, it seems to be a longer acting drug, it seems to have a
broader pharmacology. I mean, it doesn't seem it does have a broader pharmacology that affects more neurotransmitter systems. And so we, you know, we think that's probably a big piece of what's playing into what's driving that, you know, that range of effects. So yeah, it's, it's, but it's early days, you know, the basic science hasn't even been really well worked out on this yet. So
so I think you've maybe alluded to it generally. But is there like, do you have any sense of or theories as to why the Ibogaine itself has this effect on participants, sort of like underlying TBI issues and their symptoms? Like you did mention, it has this neutrophic effect, you mentioned this life review effect, based on the pharmacology of Ibogaine, do you have a sense or a theory as to like why it is that it seems to be having these robust, these robust effects on the brain specifically?
Yeah, I mean, there's, you know, like one way of dealing with that question, which is to say, Oh, it's just this broad acting kind of dirty drug. And that's way like most people would, what most people would say to you. And they say the same thing about ketamine. Oh, it's just this dirty drug that has these broad effects or whatever. And to be clear, dirty just means that it's sort of like, it's it's promiscuous with how much effect it has. Yeah.
Promiscuous. Yeah, it dances with everyone or whatever. Right. You know, the reality is, is that dirty also implies random. Random effects, and it just kind of randomly does x, y and z that it does. You know, things in nature aren't that random. They may seem random. But, you know, evolutionary pressures create solutions for problems, you know, based off of the pressure that's exerted being exerted on that plant or
animal or whatever it is, right. And in that way, in kind of in the microwave, that is random, too, in the sense that like, you know, bird number one is got a yellow or beak because that helps them, you know, ward off this that or the other. And so on this island, that's the case, you know, that's kind of random in some sense. But, you know, but in some ways, it's not random, right? Like, you know, force one exerted pressure on on
on animal or plant to and something happened. So the question is, how random is these very specific, very interesting, seemingly quite therapeutic, sort of psychological effects of Ibogaine, you know, is it really, like, just completely random, that all just played out, you know, or not. And most people
would say yes, I'm just not sure. I think saying yes, and, you know, assumes a level of understanding that we don't actually have, you know, about what, why that really remarkable compound sitting in a rainforest shrub in the middle of Central West Africa and, and why we were drawn to use it and continue to use it, right. I think I think that it's probably not as random as people would assume. What about pharmacologically? Like, what do you think there
might? Do you have a sense of what it might be about Ibogaine as a compound and its effects on the brain that allow it to, like, my assumption is that, is that and maybe this was supported in your in your fMRI or your your, you know, the scans and
something that you took. But my assumption is that the resolution of these TBI symptoms after the Ibogaine is likely correlated with some sort of physical change to the structure of the brain, some repair of the sheared, I can't remember, he's a dendrites or something, but basically, like repairing some damage. And that it's not just like, oh, it's not just up in my mind, I'm thinking differently now, but there was some sort of structural change to the brain that would allow for the
resolution of these symptoms. Is that correct? And if so, or if not, why do you think that might be the case? Well, I think that Ibogaine certainly has this neurotrophic effect that's probably driving some of the biology just described if that's in fact, we need to do a lot more work to
prove that out. But but, you know, like I said, I mean, I think the way that I think about Ibogaine, which is really interesting, almost counterintuitive is, you know, we have this psychopharmacology, psychopharmacological kind of way of thinking about drugs right now, that's like a 15th century key, you know, talking about like the single tooth on
the metal rod, right? That's right. The modern day key is much more complicated than that it interdigitates with, you know, a whole host of pins that ultimately causes for the door to be unlocked. Right. And, you know, I think the human brain is a lot more like the modern day key, and a lot less like the 15th century key. So we've been trying to jam a 15th century key into a modern day keyhole. And I think Ibogaine is a lot more like a modern day key. It it it interdigitates with a whole host
neurotransmitter systems. And it does so in a very sophisticated way. And because we don't have tools to understand the concert level effects, and we're still stuck on trying to understand what the violin is doing, we don't really have a way of answering your question. Right. I hope that's helpful metaphorically. No, it is very helpful metaphorically. So I appreciate that. I got two final sort of larger questions and then one sort of closing question. Now, I've heard some reports. This,
you know, I don't know where it came from. I can't remember if I read it in your study. I don't think I did. But I've heard other people report on this idea that Ibogaine can de age the brain. What do you have any knowledge of that of that proposition and what your thoughts are on it? Yeah, so Ibogaine can can reverse brain age estimations by AI algorithms per our data. It's unpublished, but everybody and
their brothers talking about this. My talk in Denver, I it makes me a little bit nervous, because I think we need to do a lot more before we actually really know that, you know, but but you know, that's a signal that that's there that may be true. And, and why it does that again is, is kind of unknown to me. But I think it's important if that's true, because, you know, people probably would want that to be something that that we know. So that's that one. And then, yeah, what was your second
question? I mean, I think that that was the question around, oh, like, essentially, like, is, is that the case? And if so, what your thoughts were around why or how, but I imagine that the the wire how is goes back to that, that metaphor about the modern key versus the 15th century key. Yeah, I mean, if you think about it, like, if we are 15th century key makers, and you give, if you go back to the 15th century, and you give a key maker, a modern day lock, and
they look at that, their mind's gonna blow up, right? And so you're asking a 15th century key maker to understand your modern lock, or your modern key or whatever. And the idea, now, if you gave that to them, and had them take it all apart and take a look at it, and then go and try to build a new one, would we have had modern day keys earlier in time? Absolutely. Right? It would have sped up the key and lock technology, maybe by 100 years or whatever, because they'd have been able to inspect
and look at this. And that's the value of psychedelic research, right? Is this ability to, you know, we've been muddling around with 15th century keys, we've been trying to optimize a 15th and a half century key or something. And now all of a sudden, we've got this modern day key and lock in front of us, we're able to use it again. And we're looking at it and going, well, gosh, you know, that 15th century keys, not very good. And this one's really good. But God, I don't even know how to begin
to understand how this works. Because it's so many pins, it's so many interactions of the key with the thing. And we're just so used to this one tooth with variable heights. And that's it, right? Like, that's really like the simplistic way we've been dealing with pharmacology. And so to, you know, to, to kind of go, go into that and try to have any explanation, real explanation, I mean, give you hand waving, but any real explanation about what is going on there would be me making up a
story for you. And people like to make up these stories and say things. But I don't, you know, I just acknowledge the fact that we don't have the tools.
One thing that was interesting when you when you use this, oh, now we have this new modern day key as 15th century key makers, I, you know, I couldn't help but think about sort of, well, I'll just leave this as just like a throwaway reference or whatever, but just kind of like in our modern kind of so much research is being led by profit agenda, especially in pharmacology, from
what I understand is like, can we make a marketable drug? If not, like, let's not fund this research, or so on and so forth.
But when I think about it, this very reductionist, like bringing it down to the basic single thing, you know, single pin, single key, so on and so forth, and when you're talking about bringing in this advanced modern day key, it's also interesting because it's you're also saying, well, well, actually, we're bringing back this other thing that existed for 1000s of years, in other cultures before we developed the single key and now wondering how to sort of like, up level our whole key
process now that we're sort of analyzing based on the reference of these like ancient tools. I've again, obviously being used for a very long time, from what I understand, or the plant Ebola likely longer than, you know, we're making keys. Yeah, you have to separate high technology from time. That that TED talk that I just gave the whole like, essentially set of assumptions that was in there was that it's about separating time from technology and that we have linked the future with high
technology. And in the pharmacological space is not true, in my view, right? And some I mean, some drugs that we made that are outside of the CNS, that's, it's probably true, some new chemo drugs or whatever. But, but as far as like, what do you do with somebody with depression? You know, I think the SSR eyes that humans have made are very impressive, right?
They're kind of like old tech in many ways. And psychedelics are more high tech, you know, and so this idea that you can separate time, linear time from technological sophistication. Right. And I think that that's where people get really stuck. The idea of getting drug companies to get, you know, psychedelics through and having a profitable drug to me is unrelated, relate, right? Like, you know, let them do that.
Because that's the only way you're going to get this out to people, you know, people have this, especially the psychedelics, basically, well, that shouldn't happen. And all this reality is those people live in Northern California, have the financial means to go buy their psychedelics from wherever and get to go on an ayahuasca retreat, because they
have the money to go down to Peru. The, you know, what these companies are doing is they're really getting access for people to get this through Medicare that are on disability that don't have access. Right? Like, in some ways, I find it'd be kind of counterproductive to think about things like that. So I think that's that, which I think is really just about getting psychedelics to the masses when you threw a vehicle of capitalism, right? You can have a view of that or not have
a view of that. And then there's a separate agenda around using and understanding these drugs to either make new drugs, or to refine how the drug is administered, or what it's doing, or to understand something about the brain. And I think they're,
they touch each other. But they're, they're, they're really separate issues, you know, and they're probably gonna be companies that do the second thing too, which is going to be ultimately more important, but to get this thing done to normalize this whole space, and to be able to say this is actually a treatment, you know, that's actually a policy importance. Yeah, and the policy follows. Well, hopefully it follows research, usually, a decade behind from what I understand.
But yeah, this is good. I'd like to I'd like your comments there. I, I've heard Dennis McKenna talk often around like trying to nudge big pharma companies and big otherwise, like massive thing, massive corporations, or just basically like economic super forces to be like, hey, you should save the rainforest because your next billion dollar drug might be in there. And if you plow it down, you're never going to find it. And I think he's spot on with that. Right? I think he's 100%
that is 100% true. And that's absolutely what they should be doing. You know, and I think that's 100% right. And I think that's the value of those entities, right? It's, you know, if Pfizer could go in and buy, you know, 5000 acres of the rainforest and preserve, you know, all that vegetation and study it, it would it would behoove them to do that. That's 1000% true. And it's the right thing to do for the world, you
know, and I think I think he's he's spot on about that. So yeah, it's, if there was some big, you know, some big pharma company that grew out of doing psychedelic, you know, approvals and that one went in and was able to, you know, preserve, preserve the rainforest or preserve Gabon's, you know, I boga tree supply and give back to the people or something like that. I think that's a huge win. You know, I think that you know
what I mean? I think, but it's got to be that right. It's, it's got to be this kind of hand in hand dance between how do you give? How do you get everybody access? How do you give back? And I think if we can figure out a good way of doing that, then you can use capitalism as a vehicle for good. Giving back and hopefully over time taking less, but that taps into the larger sort of force of the consumption machine that capitalism is presently sort of, you know, banking on. But that
was kind of intended as a throwaway reference. I really appreciate that you brought your mind to it. I want to ask you this, this sort of final larger question before I kind of ask you what's next and yada, yada. So based on what you so I'm going to ask you to speculate something based on what you know now about Ibogaine, what you know and don't know about Ibogaine, Ibogaine treatment, TBI, etc. Could you speculate on what the potential efficacy might be for smaller long duration
administration of Ibogaine for TBI? Of course, I'm talking about micro dosing here. But I do understand that there's a, there's some relationship to the neurotrophic effects between the immediate action of Ibogaine and the longer, you know, impact of nor Ibogaine is one of its metabolites and so on and so forth. Maybe that's a part of it, maybe not. But yeah, anything that you'd be able to offer on that. Yeah, but we just don't I mean, the big thing is we just don't
know, because we know even less about that. But I would say that you know, the French were using low doses of Ibogaine from 1930 to 1966. And while there's not really the, you know, the data back then is, you know, very scant is like a, is like a, you know, a positive spin on, you know, maybe non existent on what, you know, what that was. I think it's important to kind of understand that, you know, that that that drug was was around at
micro dose levels for a time. And the reality is, is that if people didn't didn't have benefit for doing that, then it wouldn't have been a product, right? And so, you know, there are plenty of things that that were offered up as potential cures for various things, and probably had a similar sort of placebo effect possibility and didn't stick around for 36
years. You know, but low doses of Ibogaine did. And so as a base case, I'd argue that just the sheer fact that it was around for multiple decades and utilized, you know, suggest there was something there. Now what, beyond that, I can't really talk much about the data. But I but my, my suspicion is that that's going to be an area that's going to be really studied over the course of the next couple of years, the decade to really sort that out.
Yeah, it is it is very, it's very interesting to me, I think explicitly because, you know, if I consume psilocybin, it metabolizes and is like out of my system in a very short amount of time, the metabolize from what I understand have little to
no sort of ongoing effect. But with Ibogaine, nor Ibogaine has several other like clinically relevant effects, and it will build over time because it's fast soluble, it can build up in your neural tissue over time where you take small amounts every day, eventually you get to the place that you've built up enough nor Ibogaine in your system that might mimic what
would have been there after a single flood dose. Now, that's based on what I understand, which is, excuse me, you know, clearly, clearly less than the data set that you're working with. But I do find it something as something uniquely something unique in the micro dosing space that it might have to offer. Mind you, and maybe you could answer this is, you know, Ibogaine still has this cardiac risk. And my assumption is that perhaps, you know, micro dosing it over a month long
might introduce that risk, it might not. I don't know. Again, I assume we don't have this data. Yeah, I mean, we, we don't have a sense that I mean, it's scant.
So you don't know, we don't really know this. But I didn't get the sense that the really low dose Ibogaine in the French population, you know, had any, there's, there's nothing in the literature to suggest that that had, you know, a cardiac risk that was, that was written down, you know, and so, you know, whether it did or not, I bet, I bet you couldn't really know
that. But it, I would think that you'd have some sense that that could have been present, really, a lot of this stuff ends up being, you know, dose related anyways, that was several orders of magnitude less than a flood dose. And so, so my suspicion is, is that I'm not gonna sit here and tell you there's no risk. But my suspicion is that there's less risk, if you look at the information that we have available to us. But still, again, a lot of work to be done.
You know, you don't, you're not gonna really know that until you do the trials. Okay, this has been excellent two part, two part interview. Before we close out, and I get sort of whatever final information you want to share us with, what's, what's next for you? What are you working on now? Like, what has you excited as a scientist right now? Okay, yeah, yes, we're developing. We're working on a drug delivery system with a guy who kind of invented this in
radiology here at Stanford, Rage, Iran. It's this idea of that we can package drug and nanoparticles, and use ultrasound to release it into specific brain regions and deliver drug just to that brain region. So it'll help us to understand kind of brain behavior relationships. Cool. And, and what's, what's next for, for people who are interested in your, your stuff with Ibogaine here? Should they be waiting expecting follow up reports at any time or follow up papers?
Yeah, we have a ton of papers coming out on the neuroimaging in the EEG and the long term follow up and then looking into other ways to do this in the US. So a lot of Ibogaine work, you know, is coming that paper was just the first one. Yeah, excellent. So obviously, you're a scientist, not a social media influencer. But if you have any sort of social media channels or somewhere that you would suggest people that they would follow you to stay up to date on your research, or, or, or, or, or
or, or you know, get in contact with you in some way. Yeah, the X, Twitter, whatever, handles Nolan, RY, Williams. And, and so people can see me there, Nolan R Williams.com is the website. Happy for anybody to kind of check in with us around studies and papers and all that good stuff. So thank you, sir. Appreciate the time. Thank you so much, Dr. Nolan Williams, been a excellent conversation, and I appreciate you offering your time today. Thanks, man. Take it easy. Goodbye.
Okay, thank you so much for tuning into this episode, listening all the way to the end. If you're like me, you're probably really excited about the work that Dr. Williams is achieving here with Ibogaine with traumatic brain injury in connection with MBO. And you want to really stay up to date with what's coming out with respect to that. And so definitely follow Dr. Williams at his X handle, the platform
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telegram. Links to all of that are in the description to this episode, wherever you're checking out. I appreciate that very much. If you're interested in psychedelic mushrooms, I have a couple of books that I've written on them. I'm in
production on the third. My second book, it's a storytelling narrative, the true light of darkness, my first one, more academic scholarly style, decomposing the shadow, both of which are available on Amazon, or, you know, somewhere that isn't Amazon if supporting Jeff Bezos is not your highest highest desire. And they're also available at ebook, or you could get signed copies from me directly from my site. And yeah, that's it for this episode. Thank you so much for tuning in
all the way to the end. And until the next one, take care.