TrueLife - AI- Driven Psychedelic Drug Discovery

Episode Date: February 6, 2023

One on One Video Call W/George https://tidycal.com/georgepmonty/60-minute-meetingSupport the show:https://www.paypal.me/Truelifepodcast?locale.x=en_US🚨🚨Curious about the future of psychedelics? Imagine if Alan Watts started a secret society with Ram Dass and Hunter S. Thompson… now open the door. Use Promocode TRUELIFE for Get 25% off monthly or 30% off the annual plan For the first yearhttps://www.district216.com/AI-driven psychedelic drug discoverybeyond mental healthToday we speak with Jachym Fibir Co-Founder At April19, they use innovative AI coupled with state-of-the-art computational chemistry to design and develop the next generation of psychedelic-inspired compounds, expanding the utility of psychedelics beyond mental health into neurodegenerative indications and longevity.The mission:Classical psychedelics are showing breakthrough therapeutic potential in mental health, but their use is currently limited to certain patients and indications. We deeply respect these compounds and the legacy of indigenous people and research pioneers who discovered the amazing healing power of the psychedelic state.Standing on the shoulders of these giants, we have identified a unique opportunity to use basic principles of psychedelic action to heal not only mental health, but also to prevent and restore age-related neurodegeneration. Combining together the latest in AI-powered computational chemistry and psychedelic drug design, we are developing a unique class of compounds, which may provide a much-needed answer to the ever-rising threat of cognitive decline and dementia in our constantly aging population.We have an incredible discussion, that dives deep into the world of psychedelics. We go deep into the objective, subjective, and …….wait for it…..the philosophical nature of it all…imagine that! I really enjoyed this conversation. It exceeded all of my expectations. If you want to know what the next generation of psychedelics may be then check out the company’s website below. If your an investor NOW is the time!!!!!!!https://www.april19.ai One on One Video call W/George https://tidycal.com/georgepmonty/60-minute-meetingSupport the show:https://www.paypal.me/Truelifepodcast?locale.x=en_USCheck out our YouTube:https://youtube.com/playlist?list=PLPzfOaFtA1hF8UhnuvOQnTgKcIYPI9Ni9&si=Jgg9ATGwzhzdmjkg

Darkness struck, a gut-punched theft, Sun ripped away, her health bereft. I roar at the void. This ain't just fate, a cosmic scam I spit my hate. The games rigged tight, shadows deal, blood on their hands, I'll never kneel. Yet in the rage, a crack ignites, occulted sparks cut through the nights. The scars my key, hermetic and stark. To see, to rise, I hunt in the dark, fumbling, fear. Hears through ruins maze, lights my war cry, born from the blaze.

The poem is Angels with Rifles. The track, I Am Sorrow, I Am Lust by Codex Seraphini. Check out the entire song at the end of the cast. I can't feel it inside. Ladies and gentlemen, welcome back to the True Life podcast. We are here with Yahim. Am I pronouncing it right, Yahim? Yeah, it's Yahim.

Okay, nice. He's an, he, I should have the bio written down right here. Yeah, and would you be so kind as to maybe give people a short introduction into who you are, what you're passionate about, and maybe April 19th, what you've been working on? All right. So, I am originally a medicinal chemist. So that's how I started my academic career. The University of Chemistry and Technique. in Prague and I studied drug production and synthesis. So it's really kind of building on my interest in chemistry throughout my life and this vision that I want to, you know, discover, invent a new drug that's going to help a lot of people. And I started working in the forensic laboratory of biologically active substances at my uni. And this is really a laboratory focused on various psychoactive substances and studying them, analyzing them, and synthesizing them for different purposes for research. and I initially worked on cannabinoids when I was in my undergrad and that didn't turn out to be a really fruitful line of research that I was doing

and I wanted to do psychedelics because I was really interested in them and there was this really amazing new research about the mechanisms of action coming out just at the time And my supervisors and the laboratory were so kind to give me the option to come up with my own topic for my diploma thesis if it's any good. And so I was looking through these different papers that were coming out and I formed a hypothesis about a really cool kind of compounds that could have even higher. better way of increasing neuroplasticity within the brain while also having neuroprotective effects. And I decided to really pursue that, so really design the compounds so that this profile of the hypothesis. And that's what got me into drug design. I studied drug design at UCLA in London also and then went on to try and synthesize the compounds that I've designed.

And it really is this now hypothesis about this pharmacologically unique kind of compounds that I'm trying to basically develop and to a new kind of psychedelic therapy, psychedelic-like therapy. And the focus is now that these could be perfect for indications in neurodegeneration and traumatic brain injuries because they would allow even, you know, better protection of the brain and better prevent neurodegeneration and aid the restoration of damaged neurons and things like that. Yes, so that's about me and how that really vision and research project basically turned

into a company is when I, after doing UCL, I met my two other co-founders, Richard and Surin. And these guys are really into AI and have been doing AI and machine learning for decades. I don't know how long. And we kind of, they were looking into how to apply AI in the field of psychedelic drug development. And that's how we got together that they would provide the expertise to develop the best AI drug discovery tools that would enable the development of the compounds that I've been working on. And that's what we've been doing for the past two years. So, yeah.

It's such a fascinating story. There's so much in there. But before we can get into the idea of what a novel psychedelic looks like, we should probably back up and begin closer to your thesis. So what was the thesis that you wrote when you were beginning your work at uni when you were finishing up? Yeah. Yes. So this is about.

basically looking into the mechanisms how psychedelics act on the basically biochemical level and they bind to different receptors within the brain and the main saccadolic receptor for the classical psychedelics is a 5HG2A receptor And if you activate it in a certain way, then that somehow leads to psychedelic effects. And there are also other receptors that these compounds may bind to. And that also affects the overall effects they will have. And I have been, so basically if a drug targets more receptors at the same time, this is called polypharmacology. And it's usually these different polypharmacologies that make up these specific properties of a drug within a series.

and I have decided that there was this one specific receptor that some psychedelics were binding to. And that's what I studied trying to understand what is the role of the second receptor for these unique cause of compounds. And currently I can't talk about the second receptor yet. And that's because I have now really am in the mission to get patent protection around this. As unfortunately, there is no way to get a drug to market without patenting it in this time and place. And this is something that we need to work around with when really going for this very, very ambitious goal of getting a truck actually approved through all the critical trials and so on. So in order to secure that money, you need to play the patent game. Yeah, that's the hard truth.

Yeah, it is. It's super exciting to hear, though. like I'd speak to a lot of different people in the world of psychedelics. And you know, you're the only person I've ever talked to who has, who has explored this idea or this discovery of a second receptor that something can be binding to. Is there, can you, and if you can't answer any of these,

just let me know. Does it seem as if there's a firing pattern that leads to the psychedelic experience? Or, you know, like sometimes like a spark plug would hit like the one, two, four, three plug. So is there something in a firing range that leads to the experiment, or is it just the attachment to the receptors? So from the scientific evidence on the very much lowest level, there seems to be a pattern that you can have a drug binding to this 5HT2A receptor that's associated with the sacrileg effects. and you need to you need the receptor to change its confirmation to a different one,

which is a process called activation. The activation actually is like a very much a spectrum of things. So normally this is a receptor for serotonin, and if that binds to it, that would be called the classical response and the natural response. But if you have slightly different compounds of serotonin that put the receptor in a slightly different shape, that still can lead to the organism to think, okay, this receptor is activated, but it looks kind of different. So the response is also different from the body.

and saccadelics are this weird class of compounds that produce a specific shape of that receptor that leads to these effects. But this is just the beginning, right? When that happens, it basically kind of, how I see it is that this new shape of the receptor, upon binding to psychedelic. It's interpreted by the body that it really doesn't know what to make of it. And it introduces a bit of a noise within the signaling pathways. Basically, like, it can't read, is it a zero or one? Is it zero or one?

I'm not sure. And each of the neurons maybe reacts in a different way. And it just introduces noise within the system. It's like there's the some of the signals are sent to, you know, wrong areas and there's just a bit of a mess. And that probably is a very simple explanation of how these effects come together. And yeah, it's basically that the noise means to more firing of the neurons. and the signals getting to places where they wouldn't have normally traveled to, which is basically, you know, this, you get new perspectives, new associations,

while at the same time the brain feels more connected overall, because, you know, there's connections where there haven't previously been any. And from that on arise, this psychedelic phenomena that we experience. Man, it's so fascinating. Okay, so when we talk about the actual receptor site changing shape, is that confirmation that psychedelics do in fact change the structure of the brain? This is very dynamic space. Okay, okay.

And at this level, where there's just molecules, and molecules change shape all the time within a cell. When we talk about changing the structure of the brain, more often that is talking about the neurons, the cells that are bound together in some such ways. And essentially how I imagine when we talk about brain circuits, for example, which is the brain structure, it's um these neurons have uh axons and dendrites which are the connections to others and along

those connections they sent their signals and when you are sending a signal somewhere the um more you send it through the same connection the connection grows and become stronger And that is the process of learning. And that is just completely normal. But it can happen that we create a connection that is not working out for us. That is some kind of toxic loop or negative follow-up, whatever. And when we use it often and often enough, it becomes so strong that we cannot really fire the neuron anywhere else. but in this direction of the negative thought, right?

And here, psychedelics and help by temporarily allowing the neuron to brain anywhere, to fire in other directions as well. And when it does, it actually creates new, tiny connections to different places, which is a process called NURBUS. or more technically it's dentitogenesis and synaptogenesis so that there are tendrils growing and then the tendrils connect to a different neuron which is the synapse so these new connections are made and this allows effectively a novel area novel avenue for thought which is great but obviously these are up to one trip kind of very small and if we don't use them they're gonna you know disappear again so that's why all of this integration process is super critical for retaining the benefits of psychedelics and you need to send the signal through that new connection that you've made uh while tripping uh to make it grow and

and uh be a constant option that you can use with your brain later on It's really well said. And as you were, as you were explaining that in my mind, like, I'm a huge fan of maps. I love maps. And like, if you look at a big map and you look at a river system, you can see the main artery of the river going down. And there's all these little tributaries off there. And the way you were explaining that, it seems to me that that's almost like a good metaphor

for what's happening because you're starting to see these little things going. If you just said, okay, I'm going to dam the water up and shoot it down this bypass over here. You know, the same way people who are stroke victims learn to walk again, they got to teach themselves to do it again. And the way you describe the integration with psychedelics, it's so moving to me because I know it's not a panacea, but I really am excited to hear about the research you're doing and hear that explain that way. If I may for a moment ask you this question, which is relevant, you know, Pete, is it, it seems to me that long-term psychedelic use, like if you get on a program of using psychedelics, maybe you microdose, you know, three weeks

in a row, and then on the fourth week you do like a six or seven gram dose, you know, it seems to me that you're also becoming familiar with the psychedelic environment, like just like any environment that you explore, the more you explore that environment, the more you become aware of your surroundings in that environment. So my question is, do you think that there is something beneficial about getting to understand the psychedelic environment, not only for you, but for helping other people who may visit that environment later? Yes, I think you are getting into the realm of how do we work with the experience while we are in this. Yes.

So I have this other metaphor that I'm sometimes using. And it's often when I'm talking about the concept of cognitive liberty, is that you have this basic sober mind state, and that is essentially one reality. And you can change their reality by walking. over to a different place within the physical world, which changes where you are. But you can also change the way, the place, the reality by modifying the way your brain processes, the signals from where you are. And each drug basically elicits this unique change in the way

your brain processes information and that in itself could in some sense called be a new place and each of this drug now has a new place and it's about yes if you're new there you're probably going to be a bit lost you know like what what's what's going on where am i what's this and you will need to familiarize yourself with all the ways how what you're normally used to gets processed in this new mind state because it's unexpected you don't know how it's going to change it it's it's not it's natural so in this sense you can learn and you can see okay like if I look at this white wall I'm going to see patterns it's just you know simple simple as that or but There's a lot of these things that people who have never been in this state will not be familiar with.

And if you, so if I go to the fact that it can help someone to familiar themselves with it, I think it's important for this therapeutic aspect. because when you initially have this experience and you're in this new place, you're mostly going to be filled with wonder and awe and these philosophical questions, what about the nature of the reality and so on? And this is kind of good to think about, but there's usually no real answers to that. You could be good thinking about your whole life.

not get anywhere. So in that sense, it's good if you pass that point, you get familiar with it, and then you actually use it for more immediate needs of the therapy that you want to focus on or something. I see it especially often with DMT where people report the first experiences like, wow, how is this possible? You know, my brain cannot do that. That's not possible. My brain has generated these crazy, you know, 3D, full HD patterns or visions.

And then only after a while you can get to notice that there's some things from your subconsciousness appearing within the vortex of visuals that can give you clues on what you are not focusing your attention enough on or what you should be doing and things like that, you kind of only get to pick out when it's your, I don't know, third, fourth, fifth session. Yeah, it's, you got to be careful or there's death by astonishment. You know, you just like, I can't, wah! And then it's gone. Yeah.

Yeah, yeah, yeah, exactly. So fast also that you don't even have time to think about it. All that, it's just, it's. So that is an incredible way to, that I think about that a lot. I think about the landscape. I think about the intention of going to that space and being, doing my best to be present there. However, I juxtapose that with this other idea. of the, and this is, I've heard it explained in a different way.

And I think that they're kind of at odds. And this other way that's explained is that psychedelics, they decouple memory from experience. And so it's almost this other idea is that, you know, maybe it's not so much novel as it is erasing the current layer of memory that you've tied to that thing to the last. 30 years. I don't know if those are at odds or if they work together, but what do you think? This is super interesting. I believe that a lot of therapeutic value that we can get is exactly,

as you say, take our memories and reevaluate them in a different light. And that's definitely what psychedelics allow you to do. And I think it's because you have your, so I don't know if it starts for me when you're four years old, but you create this operating system within your brain. And that really, people don't realize how many things are encoded in that system. What are all the minute things that you learn when you're growing up,

be it in the speech and interactions with other people, in how you tie your shoelaces and all of that? And this is really, and when you process new information, you really always check with the settings of your operating system, whether that fits in or not. and you always see them in the perspective of what you've learned before. And you can have some, for example, memories of trauma that you were looking with one perspective that you had at that point when you experienced that. and that was like really really horrible and you you cannot really solve that with the mindset that

you had before but it's encoded in the language of the mindset and even if you grow older and your mindset's overall changes you still have this old memory there that's you know a part of a old software that's not been updated for for years and years and you You need to take that out and kind of convert it into the new one and see it from the new perspectives of the person that you are now, where you have ideally the input of a therapist who are the best source of, how to call it, functional and efficient operating systems of the brain

where they can actually kind of fix the bucks that you might have by having to this line of metaphor. I think it's a great metaphor. You know, it's difficult to try and describe

a landscape where words fail. And I think in the psychedelic experience, words begin to fail. You know, so many people find, you find yourself deep in this trip, experience, alternative realm, however you want to explain it. And while we can use words to describe it, it's very difficult to explain it. I can say that there's this alien that is coming and talking to me, you know, but that doesn't really describe what's actually happening. You can just get as close as you can to it. And it may be possible that metaphors, analogies, even poetry is in fact the proper way to speak. That may be the only way we can really connect to each other is to use that type of language.

And I'm wondering, what do you think is the connection? It seems to me that there is a really big connection between psychedelics and language. In your ideas, what do you think is the connection between psychedelics and language? So you've actually said it very well, that language is essential for communication between two people. So one person has this experience that is, you know, multi-dimensional and super, super complex. But even without any psychedelics, yes. So, so like what you feel and what you perceive, you know, that is, that is like, like way, way, way more data than what, and you cannot directly transfer it to another person.

So you need to compress it within language symbols. And the other person has to read these symbols and extrapolate from that something that you've, you know, try to get across. And it's obviously not going to be perfect. It's basically a compression where a lot of the information is lost. And I think we've done a pretty good job developing our own language systems as humans and it allows us to work together. It's what connects us.

But when, so I guess there's two aspects. First, this under psychedelics in the acute experience, the words break down because of the chaos within the brain. And then when we are, you know, sober and can integrate it, we still don't find the words, but that's because we cannot find the words to describe that. So I guess there's two aspects how language fails here. And I think this is a very,

tricky in terms of how to convey to people that there's actual value in these compounds. And I think that this plays a massive role in terms of prohibition and how to approach that is that the inability to come close to a description using words for the people that are the decision-makers, but have not had the experience themselves. And really, there's this other world where you're not even barely aware of what's there. And yeah, so I see a problem there. And another problem with being unable to use good language

to express it is in terms of the, development of compounds that are supposed to have a certain effect, therapeutic effect. And when you cannot even describe that well in words what the compounds should do, then it's very difficult to try and develop something like that. So it's definitely in the early basis, it's more of a trial and error. an error following some more basic information you know about these compounds, but the way how they interact with the human brain and what are the nuances of the experience that we cannot really well describe words, even though we're trying that is a long way to go, you know, from chemical structures and molecule to these nuances in the trip.

or like what kind of colors are present within the trip or things like that. That's just such a long way. Yeah. It's, it's, there's so much there. I love the way you explained it. I, I do think that this issue of language is something that human kind of struggled with since the Tower of Babel.

However, you know, it's so fascinating to see it come to a head right now where in the world of clinical trials, scientists want to see objective results, but so much of the therapy is subjective, so much is trying to explain an experience. And there's almost no way to quantify it. So, you know, even when you can show results and show a patient who may have gotten over PTSD in one or two sessions, you know, how do you measure that? Like, it's, it's all. almost to a point where the people writing the check don't have anything to go on except the words of the therapist and the patient. You know, it's a conundrum, right? Yes. So there is, I guess, I'm not sure that I completely agree with you that it's impossible in the sense that this is,

true also for other forms of psychotherapy and interventions in the mental health sector. So this is something that we're struggling with on other fronts as well, not only in the psychedelic world. I think that what the psychedelics bring in in terms of uncertainty is one, of course, the placebo effect that you cannot call. control within the properly within clinical trials using psychedelics. And I think we're trying to get. So, okay, we don't really care that the patient has to self-report what has happened to him because that's what we do and all the other indications.

normal. But in terms of what we ask the patient going through that therapy is really important. And the question is whether we are asking the right things so that the person, maybe having his experience for the first time, can understand what we mean. For example, like what happened within the sessions and I think that we don't have the language developed for the individual things that happen when we are within the change state of mind and I really like some of the efforts. So, for example, people from psychonautifici, they're developing this subjective effects index, which is a collection of all the different phenomena of someone is experiencing and under the effects of cyclic drugs and categorizing them and naming them, basically.

And I think there have also been some on DMT nexus and some forums, and really it's super important that we go to this place of changed, of altered state of consciousness often, so that we, you know, familiarize ourselves with it. And once we start to develop language for things that happen to all the people, in common, we can have much more meaningful discussions or we can begin to talk about these things. And I think that we're a long way of before we can really have, I don't know, meaningful discussions about close-eye visual experiences of like high-dose, South Sidebin, where we see,

you know, I've seen this phenomenon. that one and yeah yeah i've seen that you know last week and that that's that's kind of quite out there people are usually just describing it in their own words and then it's like you get the feeling that it was something amazing but i don't think we're able to share the content of these experiences effectively yet i think we can improve to what level, I don't know. It's brilliant. It's brilliant to think.

It's almost like we're building a new alphabet so that we can have a conversation. We're seeing these things for the first time. It's really fun and interesting to get to talk to someone who is so knowledgeable and is creating, in some ways, a roadmap for people to follow. And in other ways, which we should maybe can shift gears and talk about. what does it mean to begin drug designing a new novel compound? Perhaps a new type of psychedelic. Can you run us do that? So now the drug design process is mostly done in silico and computers.

And it's about describing the relationship between the relationship between the chemical structure of a molecule and its biological activity or its effect when administered to humans. So as you imagine, this is like really, really complex equation with a lot of variables coming into that. and you need to take into account. So the most crucial things that are driving the activity of a compound is, as I described previously, how it binds to the receptor and what kind of confirmation of the receptor it creates. and given the fact that there's, you know, tens of thousands of different receptors within the body and all the other things that,

all the different systems that we have, then, yeah, you need to take all of that into account. But how we simplify things is that we just focus or firstly focus on the receptor or receptors that we want to be the drivers of that biological activity and we model how these compounds bind to those receptors. And that can be done either through learning the patterns of previous drugs or actually modeling the structures of the receptor and trying to fit the compounds within the receptor

and see how well they fit. And this is the early design stage where you're really trying to look for what possible molecules might have that activity. And then it's the much more tedious, longer, and cost-efficient or cost-intensive process of actually testing whether that compound works. And we need to go very small in small like in vitro essays to see really whether there's an affinity

between those two compounds, what is the pathway that it gets activated when these compounds bind, then does it have effects on larger structures like cell? cultures, then organs or smaller animals, and then eventually humans. And that's also a long process before we can proclaim, okay, this is safe and effective to be used for treatment. So that's just the general overview. Obviously, there are so many parts that go into that that probably would be best if there's something within that process that you're most interested in that I can talk in more

detail about. Yeah. It's such a giant thing. And as you're explaining it, I'm thinking, wow, how would you even form a model? I know, like, on mice, you could crack their heads open and, like, look in there and stuff, you know, but obviously for human beings, that's a little bit unethical. And so, you know, I guess maybe, I'm not even sure what to take it from. there. But I, you know, I guess I'm wondering, like, in today's world, we can use EEGs or EKGs to kind of

see a little bit what's happening there. But where are we right now in the ability to monitor what's actually happening in the brain on a psychedelic? You are hitting the later stages of. what we would normally consider to be the drug development process. So I know that you have spoken to Nick Murray. Yes. I love that guy. Who is much, much more knowledgeable in this than I am.

It's about, I suppose, monitoring as much as we can throughout the throughout the entire body and for brain you have functional magnetic resonance imaging which is super expensive and you have to you know be inside of a huge magnet to get the readings out which is I guess the most sophisticated way of looking to within the human brain in real time. And but I've heard in our accelerator that we were part of that there was a startup trying to get fMRI working

even with much smaller magnets than are usually required. And really, I think that is a very, that it will be possible through new technology to make functional magnetic resonance imaging much smaller, much more compatible and accessible. So I think there's still a long way to go. But right now, as you said, we can do EEG, then fMRI, and then what Kernel is doing is monitoring the flow of oxygenated blood, basically, within the brain. And I see this as not how traditional drug development process usually goes. or for whatever people may say,

it's very much about trial and errors still. And we, a lot of drugs, and you may be surprised, we just don't know really how they work, what kind of effect they have. But if you design clinical trial that looks at some outcome that might be very, very abstract, as you said, in mental health treatment, we're just asking people a bunch of questions and depending on what they say, we determine, okay, that was a success, that wasn't. And, you know,

what happens within the body to cause this response, we often do not know and in much simpler drugs. So it doesn't have to be psychedelics to be appropriate. but we still don't know actually how it works. And I think that, yeah, the sacadalic research is mostly within that phase that we're, or if I'm talking about novel saccadalic research, we're just trying out. And this is also because this is a chicken and egg problem. you would ideally want to run all these different brain scans under the influence of a certain new molecule before even, you know, spending a lot of time of developing it and proving that it is safe and effective. But in the current environment, you would anyway still need to, you know, bet on some drug and put a lot of money into it to develop into its stage before the,

Regulators even allow you to give it to humans to actually make that brain recording. Unless you're Alexander Shulgin, of course, then you... Yeah, yeah. Beautiful. You know, when I think of novel drug design, I think that almost the entirety, with the exception of Shogun, with, you know, almost the entirety of drug design is an exercise in like confirmation bias. You know, like this drug does this. How do you know?

Because I, it seems to do it. You know, like the best guess, it's just the best guess. But I here's what. And tell me if you think this is crazy. I think that the, okay, it's tough to get this out. I think that you can theorize what's happening in the brain better than you can demonstrate it on any kind of machine, E, E, G, EK, and even your, when you use those machines, all you're doing is measuring confirmation bias. But I truly think, you know, you can go back, okay, you can go back to like, if you, if you read Plato's works,

and you read Socrates and Tamaeus. There's this one scene where Socrates goes into the dirt and he takes this slave boy who doesn't speak, they call him a barbarian because he's not a barbarian, but it's Babel, right? And he takes this young boy over here and he draws like a square. And then that guy draws a line through it.

And he's showing everyone like, look, here's a guy who thoroughly understands the dimension of this cube right here. I don't have to tell him anything. He just drew the line there because he knows what I'm talking about. And when you see this, things, when you read language like that, when you read stories from the past, when you take a psychedelic and you see a 3D object spinning in front of you, like I think that what we're

seeing are the solutions to the problems. Like if you can see the same, you know, tetrahedrigon moving in front of you right there and you see it and I see it, like maybe what we're seeing is the activity in the brain right in front of us. And if you can go into the psychedelic world realm with the intention of understanding neuroplasticity, I think you can see what's happening in the brain. And I think that's just as good of a drug design as measuring it through waves or measuring it through, you know, some sort of EEG or oxygen in the brain. Like I know I'm kind of way out. I'm just way out on the field right now talking about this. But, But it's plausible, right?

Yeah, yeah, yeah. I think I understand what you mean. And the thing that is, the thing why people are not using that more is, I think just because this is unique to psychedelics. as if you were to use this in the design of for example I don't know cholesterol reducing drug

you know you're not you're not going to see the cholesterol being broken down by some process within your body when you take that and this manifestation of the effects of a drug that we can directly perceive, as you said, in front of us, is something very, very unique in the sense we, of course, we have that with, I guess other drugs also have very tangible effects and that would be possible to use your own

let's say organism to try and you know see whether it is active and what effects there are but why that and i'm getting to the main reason why this is not used then is because essentially you are without proper understanding of the molecule on other levels, you cannot really predict what is going to do because even tiny changes to the molecular structure can have really dramatic effects on the activity of the molecule. And so, for example, you have a series of compounds and you know, anecdotally, some of them are psychedelic. So you just assume that a okay, this drug is also going to be a psychedelic in a similar way, and it's not going to be a neurotoxin

that's going to, you know, kill my brain cells. Right. And this is the fact that it is inherently risky to do this self-assessment of a drug, and that's why the regulating process doesn't want people to. you know do that it is I think there are different rules for actual self-audid administration I think in some ways the in some countries it was accepted I think there are even some articles beside Shilgen's work where people have experimented with new new drugs on them and reported that in the scientific literature I think in Germany it's

you know, allowed epically as long as it's the, but I mean, I might be, I might be lying there, but I think I've, I remember something like that, that as long as it's yourself, as the researcher, you can do it on yourself, on your own responsibility. But in this world, it will still not give you enough data anyway because for anything to be reliable, you need more measurements, more people to do that. And it is inherently, you know, taking on the risk of trying a new drug onto the humans. And it's probably difficult to make sure that the people you give it to, fully understand the extent of the risk that they would be undertaking. So that's why these mechanisms are in place that when clinical trials for any drug are done,

that it's, first of all, there's enough preclinical evidence that there shouldn't be any kind of toxic effects. And then that, you know, all of the people within the trial are unbiased and know what the risks are and so on. But there's this question that is really something to think about, and that is we have basically outsourced the risk from humans to other animals, and that's what makes up the most part of the pre-comitlimate asset, or not the most part, but historically it has been an inseparable or necessary part. is that you test these compounds on a lot of different animals,

a smaller first and even larger ones to observe the toxicity and kind of judge whether or extrapolate whether a vaccine in the animals might not translate to some toxicity in humans. And obviously there's people who are rightly concerned that we are just taking the risk and suffering onto animals and so that we can be safe and this is this is like a very very difficult topic for basically ethics and philosophy right and I like that we are now moving towards through technology. We are able to actually do a lot of advanced systems in vitro.

So, for example, we can grow organoids, which are like tiny organs in the testing tube or wherever. where you can even so how does it work is that you basically take a human cell and you can even take it from the specific human that you want to treat but usually from the person that maybe has the disease and you can reprogram it to revert back to you know this state where it can change into any kind of cell

and then you can tell it, okay, now grow me neurons. And it starts to grow neurons. And if you provide the correct growth factors, it will continue to grow into a neural culture that is going to differentiate within into, basically it's all an entire miniature of a brain. And these are called serenial. organoids. And this is a much better model of actual stuff that's going on within a human body.

And it's also much better translatable to humans because it's actually human cells and human receptors. Because you have this problem when you test some toxicity of a compound on mice, it might be toxic there, but not toxic in humans and vice versa. So there's a because, we have different structures of the receptors, different sequences, different sets of genes, and so on. So these advances in Organized have actually resulted in, I think, it was NDA or some of the regulatory authority, accepting basically an investigational new drug applications, which is an application for whether you can administer that to humans. And you can now get that without any animal studies just by doing that. And it's also sometimes supported by microdosing, which is actually an equivalent of what

Rishulgin was doing. But you can usually use, you need like a body of preclinical evidence on these in vitro maloes and organoids. Then you can get a microdose. study approved, where you put like very, very tiny amount of compound to humans. And then you can actually, if nothing happens, nothing bad, then you can go on to face one trials with the full dose of the drug. Man, that makes up so many questions in my mind.

Have you talked to the Shulgen Institute? Have you talked to those guys over there? Yes, yes. We've had, we've had one call with them sometime back. Man, he's got books and I got the p-cal and the teacot. He just has books of molecules that he's made and like, okay, but this brings up another question. Why do we need novel psychedelics? Like, why do we need them?

Like, maybe we just play around with the dose of the ones we already have and maybe different doses of psilocybin cure different types of mental illness. Maybe we already have it. Yeah, yeah. That's a very good question. And I think that the drugs that we have are super valuable, the classical psychedelics that we have now. And their value is really in the mental health world, where we have found very efficient ways how to do the psychedelic-assisted psychotherapy

and get meaningful results using that. And it's also very safe. But you have to, from the perspective of general direct design, you usually how it goes is that you have these initial lead compounds that are sometimes called first in class that are oftentimes. derived from nature or their, with the case of psychedelics, you have some certain deputies like LSD. And this is just something that we have, like, found, and we applied the therapeutic process onto that. And in that sense, the therapeutic process and the therapy has to

adapt to the properties of the compounds that initially we found that has these effects. And when we see that this is working, and this is called like validation process, basically, we see that happening with psilocybin for depression, for example. And this tells us that, okay, we can use drugs that bind to this 5HG2A target to use as a basis of a treatment for mental health disorders. But then you ask yourselves, okay, and if we want to treat that, could there be a different drug that would in turn be optimized specifically to be used in this treatment? And then you have the option to mess around with the properties of the drug to better actually fit the needs of the treatment. And I think that is always the base in drug discovery and development. For example, with penicillin.

So you have this and it's antibiotic properties. It's awesome. But, you know, okay, it doesn't work on these guys. And it doesn't wear these organisms. So, okay, we're going to tweak the structure and now we're getting, you know, the better antibiotics. And, you know, penicillin itself is hardly ever used now after all those years because we have all these other range of options that turned out to be. And statistically, it's very likely because the possible space of molecules is so vast that, you know, you're probably not going to get the perfect thing for specific treatment in one shot.

And when I come back to psychedelics and the first generation of them, there are several ways how these could be improved. So one of the limitations is that the treatment of high-dose psychedelic is that the treatment of high-dose psychedelic is demanding and is contraindicated for a lot of patients and it might actually be also a bit of risk to individuals, for example, that are old and have some comorbid diseases and so on. it's a question how to make it available for people that, you know, could not, they would not pass the requirements to be accepted into psychedicist psychotherapy. And then also, for example, where we're focusing on is that there is possibility of using psychedelics for neurodegeneration and traumatic brain injuries.

But this, as you said, is very much a different paradigm than the psychotherapy where to take one big dose once in a couple months. You need to regularly dose that so that you continually have the effect of these drugs. And that is very difficult with their tolerance buildup. And there is also a risk of cardio toxicity because these drugs bind to 5H2B receptor that has been associated previously. with cardiothiopathy and development of hard problems when administered regularly. And so we are aiming with April 19 to actually solve all of these problems at once.

And it's actually by introducing this novel target, we have compounds that are inducing neuroplasticity and additionally also are neuroprotective and still have the same mechanism of action but supplemented by a different pathway also. And this removes the reliance for the effects on neuroplasticity to be tied with this 5HC2A target and that allows even in lower doses to still have a potent neuroplastic effect. And there is space for actually looking at different compounds and seeing whether their combination of duration of effect and the tolerance that they induce and the, you know, I want to say cognitive impairment, but this is something that we cannot really model now is obviously going

to come in to play a later stages. But we and also 5H2B binding, which is corresponded to that cardio toxicity and those are just the main parameters of a drug that we can fine tune early in the process and we can find a compound that would be safe and effective even while you would be regularly dosing these elderly and comorbid patients that have you know neurodegeneration or that have gone through a stroke or some other brain injury, traumatic brain injury. And I think that is something that the first generation of psychedelics does not address well. And really, if there was a drug that I'm describing and we think we can make that, then this would really open up the possibility of applying psychedelics also in other areas.

such as mental health. And yes, I think that there might even be improvements in mental health in, you know, making some drugs more safer, last for a shorter time to afford, you know, get more affordable therapies. But I think that the possible for innovation is, as you mentioned, kind of small, because we already have super powerful drugs that are super effective in mental health. health and that's why we as a company are not focused that much into that space, even though there might be applications of our compounds within mental health also down the line. But what I really

would want to do is that, okay, we have discovered this amazing mechanism that produces, you know, higher neuroplasticity in the brain and this allows for the neurons to you know, as you mentioned in stroke, some parts of your brain die out. And you can, by inducing greater neuroplasticity, tell the surviving neurons to, you know, connect in such ways that they actually replace and restore the loss functions of those neurons that have died. and this is very much what psychedelics do. This is what I talked about earlier,

creating more connections within the brain, more synapses. And we have very limited data to support that psychedelics will be effective in neurodegeneration. But I think it's a lot because people have been mostly focused on really proving to all those politicians and decision makers that these, you know, compounds have value, and the best way is to do that in mental health. And that's why, you know, and the research was limited and kind of hard to get approved. So that's why not many people were really ventured into the neurodifference to an alternative area,

but I am super convinced that it's going to have a great, great effect. Not that it would be disease-modifying that it would cure, you know, Alzheimer's or things like that. That's not really very likely, honestly. But we don't have cures for neurodegenerative disorders of this magnitude. And what we do anyway is symptomatic treatment, which has a lot of side effects. And then we have supportive treatments of some sorts that some look kind of promising. but for a long time, I believe the best thing we can get is focus on supportive treatments and saclidates are perfect for that, also because they approach the problem,

even though they might not cure the cause of the problem, they approach it holistically. So when you have a patient with neurodictive disorder, they will be freaked out. They will have anxiety, depression, and all these other associated. of mental health issues. And if you can, you know, have a compound that will address both your mental state and the state of your brain, the neurology, I think that's going to be a very powerful tool in helping these patients to, yeah, keep their, keep their dignity and within this, you know, very, very horrible state that is neurodegeneration and dementia. That is, that's so awesome, man.

I love every part of it. And there's a few things that I would like to address. Number one, I think you could say that depression and anxiety may be the warning signs of Alzheimer's before it happens. The same way someone loses movement in their arms when they have a stroke or that they're, you know, there's telltale signs of things that happen before the actual big event happens, whether it's on the planet or whether it's in your body. maybe if we can use the psychedelics to address the anxiety, the depression, maybe it's like getting to the Alzheimer's before it happens. Maybe that's where the magic is. I couldn't agree more that they are going to see psychedelics. And there's just an opinion. I'm not a doctor. I'm a truck driver. But it's I wholeheartedly believe that you're going to see the use of psychedelics

in treating neurogenerative diseases. Where I think there is going to be an issue. And DARPA is actually doing a study on this right now where they anesthetize people and then give them the psychedelic to see if it has the same kind of effects. I'm of the opinion that you have to be conscious. You're going to have to do the work. You need to see the plants breathing. You need to face the demon. Whatever the demon is, maybe that demon manifests as you thinking you're an alien. But whatever is going on in there, I think there's a component of consciousness that needs.

needs to be active while it's happening. I could be wrong. And maybe that's why DARPA's pumping $30 million into this study. And it didn't even make sense to me until you started bringing up the idea of traumatic brain problems or neurogenitive diseases. And like all of a sudden I was like, oh, on the battlefield, Alzheimer's disease. What's the biggest play coming our way with all these baby boomers retiring? Like, you know, there's, they're really, even though when you talk to people like Rick Strassman or all these geniuses that came before us and they say, listen, we've been here before. It's not a panacea.

It's so easy to start to see what it could be used for. And I'm just so thankful that we're at a time where we can begin to do it. And I'm so excited to talk to you, man. This is amazing. Yeah, yeah. And you touched up on a very important issue that a lot of people are warning about and they're finding very, I would say, controversial ways how to deal with that,

and that's the aging of the population. Yes. Right. So our birth rates are dropping, and this might be maybe a bit of a conspirational theory, but we've actually seen a lot of this pro-life and anti-apportion movements. And, I mean, I can't help do things.

associated with the drive of the governments to, you know, get people to make more babies so that they're not, but because they see that we're dangerously approaching the point when people are just going to be aging and there's going to be a lot of old people and the demographics are going to be maybe unable to support the entire civilization. because those old people are going to require all this kind of care. And now you have also longevity companies and researchers trying to, you know, extend the human lifespan even more. And what I think should be done in this longevity is really, really to focus more on the health span,

on actually making sure that the people are healthy when they age, not how long they will live per se. I mean, that might be as an afterthought or, you know, just a secondary thing that you want to solve. And for example, dementia, a case caused by neurodegeneration or other means, is really at this point, once you're older than 60, your risk of dementia exponentially increases. And there's been studies that it actually continues well.

If you get worse and worse and so there was this study of people aged over 90 years and about 42% of them already had dementia in some form. And then the incidence was still rising exponentially of your risk to get dementia. So if we don't solve that, we're going to have a lot of old people and they're going to require a lot of care because this is so intensive to care about someone who has dementia. They're slowly losing touch with the reality, losing their independence. And it's actually horrible. So I have also a bit more personal experience seeing how the people are slowly, you know, losing. it and it's very scary and not only for the person themselves which i cannot even imagine but for all the

people around them that need to you know be with them in their difficult states and you know help them do basic things uh yeah so that is something that i really want to address and i see a big potential in in um using sacrilylex for this and you you said that yes um there is an approach in trying to say, okay, like, we don't need this sacriolic effects for this class of compounds at all. And I also disagree with that. I think that, yes, there would be an effect. But what is this, you know, selling point of the cyclic drugs is that they actually do this chaos within the brain. that causes, inspires the brain to find other ways of connecting together and start this rehealing process.

And I've also used this metaphor about psychedelics, macro dose of psilocybin. It's okay, like you're exploding the house that is your brain. and then you know you're slowly you know building it up again throughout that experience and that is most effective you know because then you would have the non-halocinogenic or non-psychedelic psychedelic psychedelic psychedelics that you know you still have the brain but you're just trying to build some things on top of it you know so that's obviously not as effective to there's a broken house trying to just build over it and what we will be aiming for and this is obviously very abstract is to retain that element of breakdown of this entropy in Greece but do the demolishing

of that in a more controlled way that the people could actually really be in control but see that you know the there that there is some way of and this corresponds to the visions that you said that is the chaos and you know kind of destabilizing of those previous neural circuits but you ideally would want to have it in a way that is not preventing you from functioning in if you want to use that in this neurodegeneration traumatic brain injury treatment and so that's why what we are aiming for is I would call non-intoxicating effects of these psychedelics as opposed to you know non-psychedelic or non-holicinogenic and I think that there there is a there is a way there's a threshold even when doing psychobilic

as a microdose, the current psychedelics. But I think that it's not enough that you're just taking a microdose because there's this rapid onset of thorins. You cannot take it continually. And there really is not enough of an effect as we're getting from various studies to actually have a therapeutic. really significant benefit. It can have effects on people's, you know, creativity and ways of thinking and there's definitely a fact for that. But if you're, if you consider that your brain is degrading at a rate that no other drugs that we try to develop over, you know, 100 years is able to stop that. The results that we're getting for microdosing with the current drugs, it's very

unlikely that it could affect that to a significant degree, in my opinion. I might be wrong, but we don't have that data for humans yet. It's fascinating to me. I did a self-experimentation where I did like between a half a gram and a gram a day for 30. days. And I was surprised, and this is just my own subjective results, but I was surprised at how little tolerance that I actually felt. You know, if you read James Fateman or, you know, you do your research online, you can see that the average microdosing procedure is probably like, you know, three days off and one day on or two days off and one day on. But I found it, I did find the realm of creativity was easily accessible. I did find that the colors and everything was turned on

if that kind of makes sense. And it seemed to me depending on how much sleep I got and my diet, but the feeling was always there. But I want to shift gears and talk about go back to the idea of getting the neuroplasticity and potentially having good or dramatic effects when you're in an unconscious state. So you would said that like at the high doses of psilocybin, like there's the explosion, the chaos happens in your brain. And then earlier in our conversation, we had talked about making sense of the environment. Isn't the making sense of the chaos where the actual integration is? And if you are unable to be conscious, if you're unable to make sense of the chaos, then you're not getting the benefits. If you just have the chaos in your brain, maybe you have the

those tributaries or the neurons firing off and making new paths. But is that enough to get the changes you need for neurogenitive disease? Like I think I was trying to make the case again for you have to have, you have to be in the realm of the big explosions and make sense of it in order to do the learning. Yes. Very, very interesting thing to think about. I believe that on some level, it's going to be slightly effective, even if you don't, even if you are unconscious. When you say slightly, I'm sorry, when you say slightly, what, what person, is that like a 5% or I mean, I know we're just kind of guesstimating?

Well, well, so, so that's actually why. we are introducing this other target into the equation because there are other ways how to affect the unconscious pathways that are contributing to the survival of neurons, the neuroprotection and neuroplasticity. And so there are other drugs that induce neuroplasticity. For example, a range of antidepressants, but other drug classes as well that help this process. So definitely there are ways how to, if we're talking about the neurodegenerative indications, then this would have some effect.

I don't know about the percentage. I can't, can't guess. But what is, I think, shouldn't be lost, is that as your brain degrades in that state, you will lose some of the neurons that have been doing some functions, right? And that's why you're like stopping to function properly in some aspects. And one thing is to just slow down the data. degradation process and that that that that that that that that you can do and that that that's okay but um even you know subcont on subconscious levels and subconscious mechanisms if if you want to call it that

but uh i think there is a lot of benefit if you were to be in this neuroplastic state induced by sacadilics that introduce a little of chaos and but you can still function where you can find more efficient ways of performing the functions that you need to perform even with the limited amount of brain cells remaining. And that is very much about actually learning. So you are, when, you know, some connection in your brain, you know, dies out. You will need to find a way how to work around that. Yeah. And psychedelics, if you know, you have that state of the neuroplasticity can allow you to or maybe also work with input from some therapist or a doctor to find a different way and maintain the functioning through alternative

neural pathways. And I think that this, you know, this is the restoration of function. of the brain, basically. So that I think is very crucial and very beneficial to have what you're talking about, this sense of the psychedelic state that is giving you new ideas, new associations, new perspectives on how things could be done. So yes, I think that if you separate it

into this neuroprotective part, and then the neuroror restorative part or function restoring property, then you probably needed for the function restoration to work to its maximum. But I'm talking here, I'm not talking about mental health. It's different in mental health. I think mental health treatments without this effect would be much, much less useful. and I just compare to taking normal antidepressants is like, yes, you're feeling a bit better and you might be able to find ways of thinking differently, but there's no assistance in that. And it will be pretty much the same doing any kind of other talk therapy to change that because your brain is neuroplastic on its own, right?

but this saccharactera effects of actual you know chaos within the brain that is what's you know the main driver allowing much more profound change and it's about i think this very important aspect is that once you are if you're in a normal state you can only make such changes to your thinking that you can imagine imagine. You need to, you need to, you know, imagine that a different way of thinking is possible. And it is very hard job of a psychotherapist to explain to a person that they can think in a different way. They don't see it. They have a wall in there, right? And then you take a psychedelic and it shows you that there's actually, you know, 10 different paths that way. And you can have chosen. And you can,

you can choose that part during that experience and find that it's there. And then you can kind of, you know, integrate that and really, you know, change your way of thinking. And if you if you don't have that, you know, those random associations running through a brain in that state, or you're not aware of them because you're a drugged under an anesthetic, then there's no way to see those hidden doors that are aware there in your mind. man I'm you know it seems that at least in the west like when I think of the drug companies like Pfizer or all the drug companies over here you know for so long we've used medicine as a coping strategy like okay I know you hate your life I know you're depressed I know your anxiety but just take this pill and now you can continue to do the shitty life that you're doing and you'll feel better but psychedelics seems to offer a new method of like yeah this is not a coping strategy this is you realizing that you have a real problem. and you can fix it. And here's how you do it. Like that's that's real medicine. That's real work. And like I'm so excited for the future. I'm so excited for what you guys are doing. This conversation is blown my mind. I am thankful. I know you're getting close on time. But I wanted to touch really quick on this idea that we may,

we may not even be able to get into it. But you know, you guys are working a lot with artificial intelligence. And in the world today, we see things like chat GPT and automation, yada, yada, yada, and brain chips. But it seems to me there's a race between biology and technology. And on one level, you have the Elon Musk brain chip. But on another level, you know, you guys are building cerebral organoids, which you can test natural compounds on. So it seems to me, like we're using AI to further the biological natural processes of healing. So it's just weird that, like, you know, it's, it's weird and it's beautiful, but it seems like there's a race between biology and technology on some levels, but maybe it doesn't have to be. What do you think? Yeah, so I think that

this AI that we're developing is actually our attempt to mimic the biology. because that is so much older than us, so much more advanced, we don't understand what it is. But we have picked up pieces of how nature does things and how they work. And we have transformed them into this world of silicon. And virtually we can replicate them. And if you look at concepts such as evolution that has lived, you know, generated super complex things. We can kind of, you know, do that in a computer and also generate, you know,

all this various things through the process of crossover and mutation and selection of fittest. And so that's some part we're doing evolution machines. And then another thing we've borrowed from nature is the structure of the brain. And those are the neural networks that are changing the world right now. And it's just a simple concept in it that you just have, you know, various notes that each, you know, processes information from notes passing it to it, which is like a neuron sending a signal to another neuron. And it just does some operation on it and then sends it onward. And this kind of mechanism allows you to learn things, to remember things, to generate new things. And so we're kind of building essentially another brain for ourselves to think within these computers.

And that's how it complements the biology. research is that, you know, we can outsource some parts of our thinking because it's getting so complex, like people are looking at it's crazy. And by building, you know, okay, some helpers that can do that for us. That's great. And we can outsource, you know, various tasks for remembering and recalling things and in the sense of looking for actual new molecules this has been used for a long time because it's much more closer to molecular structure is much more closer to kind of encodable language that you can feed into these machines as are other things so you can actually teach them all

predict some structures, some properties of a structure without doing all these real-word essays. So it's the predictive AI. You can also train a model to generate a set of molecules that have a set of properties and that's the generative AI. And this is really like so efficient now that, you know, medicinal chemists are slowly, you know, just losing the, I guess, edge of being able to perform better than machines at this drug design. And actually, the best way as it was designed to get a medicinal chemist and give him a couple of other brains. that he can work with and some of them, you know, could be his lab assistant, but some of them

are just computer brains and and by using them in smart ways, we can get so much more done, so much more quickly. And that's what we're working on. But yeah, there's no time to get into the details, but maybe maybe in a other chat. Of course. Of course, where can people find you? And you got anything coming up and where can people find you? Okay, so you can find us on April 19.AI. That's our website. But we're active on LinkedIn,

April 19 Discovery on Twitter as well, April 19 Discovery. And we are now trying to get money to run the next stage of our research. So to run all those real world experiments with the compounds that I've been designing and synthesizing and those that are coming out of the AI tools and models that we've designed. We just now need to actually go to the lab and do the experiments. So definitely if anyone wants to help us with that, they can reach out. And we're also open to collaborations.

We're working with some universities and research institutions and other companies. So yes, we're open to discussions to push this thing forward. That's beautiful. If you're listening to this and you are a fan of psychedelics, Tim Ferriss, if you listen into this, this is the guy right here, Tim Ferriss. This is the next John Hopkins right here. If you're listening to this, reach out to them. Check them out.

These guys are on fire. It's such a fascinating conversation. I'm excited you guys are out there. And we'll get together again soon and we'll have some more chats. I really enjoyed this. I enjoyed it as well. It was great. It was great.

We got into some very deep and interesting stuff. Yeah. So it's fascinating. I'll let you go. I know you got to leave. I would talk to another two hours if I could, but we'll be in touch, man. Ladies and gentlemen, thanks for listening. All right.

Thank you. Thank you. Bye. Aloha.