TrueLife - The Science of Microdosing with Psychedelics - Aleksandra Wingert -Aleksandra Wingert

Episode Date: September 28, 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/An enthusiastic neuroscientist with a particular interest in psychedelic research, neuroplasticity and sexuality. Graduated with an MSc degree in Clinical Neuroscience at King's College London and currently working as a research assistant/clinical coordinator at the Centre for Psychedelic Research at ICL.Also working in a private clinical trial sector to explore the potential of psychedelic trials at the industry level. During my time in academia, I have been extending my skills in both clinical and laboratory research for the past 5 years. I have been actively coordinating the Microdosing 2.0 project and authored two publications in high-impact scientific journals.I was lucky to be awarded the BAP summer project award for my work at the Centre for Psychedelic Research. I am a keen learner, take any chance to grow and to become a better person every day.http://linkedin.com/in/aleksandra-wingert-9301b3174 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 Serafini. Check out the entire song at the end of the cast. Ladies and gentlemen, welcome back to the True Life podcast. I hope everybody's enjoying their Sunday. It's either the first day of the week or the last day of the week. I'm not sure, whatever you want it to be. But I hope it's beautiful for you.

The sun is shining, the birds are singing, and the wind is at your back. I got an incredible show with an incredible guest who's doing some incredible research. I want to introduce to everybody the PhD candidate, Alexandra Wingert. Alexandra is a dedicated and enthusiastic neuroscientist, demonstrating a profound passion for the fascinating realm of psychedelic research, neuroplasticity, and human sexuality. Graduating with distinction from King's College London, where she earned her Master's of Science degree in clinical neuroscience,

Alexander currently stands at the forefront of groundbreaking research as a research assistant and clinical coordinator at the renowned center for psychedelic research at Imperial College London. Alexander's academic journey has been marked by a relentless pursuit of knowledge and a commitment to expanding the boundaries of our understanding of the human mind. With a robust foundation in clinical neuroscience, she has seamlessly transitioned into the dynamic world of psychedelic research. Over the past five years, she has honed her skills in both clinical, and laboratory research, cementing her status as a promising emerging scholar in the field. At the heart of her research portfolio lies the microdosing 2.0 project, a pioneering venture that has captured the imagination of both the scientific community and the general public. Her dedication to pushing boundaries of knowledge and her innovative approach to research

have culminated in the publication of multiple influential articles in high-impact scientific journals. Recognizing her exceptional contributions, Alexander received the prestige. VAP Summer Project Award for her outstanding work at the Center for Psychedelic Research. Her thirst for knowledge knows no bounds, and she seizes every opportunity for growth, embodying the spirit of lifelong learning and personal development. Thank you so much for being here today. How's it going? Thank you so much. Wow, that was such a wonderful introduction. So many positive things. Thank you so much for putting this together.

and thank you so much for inviting me. It's such a privilege being here and having an opportunity to talk about my research interest with you. And as you know, I was a little bit hesitant at first to join the podcast because being in such an exciting place in the field at the Center for Psychedelic Research and working with such a brilliant, brilliant, interesting minds. I thought it's super exciting. It also might make you feel up it self-conscious and I know that I still don't find myself an expert in the field and as I'm trying to grow and learn more every day, it's definitely an exciting opportunity for me to grow as a scientist. But yeah, it's definitely exciting times to be in the field and talking to you right now and I'll try to just show me my perspective of how I see psychedelic research and the research I've done so far, but by no means

I want to say that perhaps I'm not still an expert in the field. Thank you for that. It's interesting to think about the idea of who we are, where we're at, and what we're accomplishing. It seems to me that so many people, regardless of what field you're in, whether you're a mechanic or a researcher or a truck driver, or a swimmer, wherever you are in your life, you're listening to this, you often do some of the greatest work while you're at this stage. A lot of the times you'll hear people in the military talk about being in the trenches. And it seems to me that that is where the war is either won or loss is in the trenches. And I think that people that get up and are in this state of not knowing,

am I an expert, am I a novice, look, you're in the trenches. And we're all here together and we're all you're fighting. So I'm glad that you find yourself in this position. You know, I'm sure that, and I'm hopeful that everybody accomplishes what it is they want to accomplish, but being in the trenches is a badge of honor, and it's something that helps propel the people behind

us into the world of expertise. When they see us fight, when they see us begin to gain knowledge, we are showing them the way forward. So I think it's a beautiful place to be, and I'm excited that you're there. So thanks for that. Maybe we should jump into what are you doing in the trenches these days? What is this microdose 2.0?

project. Do you want to give us a background? How do you want to start? Go ahead. Yeah, of course. Well, thank you so much. So thank you for the brilliant introduction. As you mentioned, I am a PhD candidate at the Center for Psychedelic Research, and my main focus for the PhD is actively coordinating the microdosing 2.0 study. Some of the people in the audience might already be familiar with the first microdosing study that has been done at Empirical College London, which is a citizen science that will blind microdose study. And it was fully online. So we have a few differences and there are a few reasons why we decided to do part 2.0. So let me maybe start explaining the study design and why we design the study in this particular

way. And then I'll give a little bit of kind of differences both with it in the past and what we're going to do now. So as I mentioned, it's a double-blind citizen science study where we're looking for people who are planning to microdose with their own substance, their own initiative, to help with their mood problems and perhaps depression. It might be subclinical levels of depression. They can also have a diagnosis. It's not an exclusion.

However, we do exclude people that are currently on antidepressants or any mental health medication because you know there still might be an issue of the interaction effect we still don't know if it's entirely safe to use psychedelics as well as SSRIs so there is a long debate so to make it as safe as possible we have to have a bit of a stranger inclusion criteria as it is with the majority of psychedelic trials so the tricky part is that we kind of have to rely on people to be kind of honest with us and willing to participate in this research just to contribute to the development of the field and you know kind of follow the procedures we have in a study we have a quite interesting self-blinding procedure where we um when we allocate people

to a certain placebo or microdose condition in a double blind manner so both us nor the people they don't know whether they take the microdose or placebo and we kind of support them on how to allocate those those capsules using little QR codes and it's an interesting concept and it's definitely a lot to explain so i'm not going to go into a lot of detail about it and so we are planning to recruit 60 people at least 60 people to participate in the study which is quite a large number so I hope I'll manage to achieve that in the next two years and we'll be looking into some psychological outcomes like for example depression anxiety as well as physiological outcomes such as heart reverability or changes in sexuality perhaps we also look into sleep we'll be

giving people aurorings during while they participate in the study to look into the hard referability, which is quite interesting to measure because most studies so far only focus on their psychological side of mental health outcomes. But myself, I'm quite curious about how the physiological side will also perhaps change. And as we've been seeing a lot of placebo effect in different various microdosing trials. I would be quite curious to see whether if people do improve potentially in the placebo group, would that psychological improvement also be similar to the physiological improvement? And if yes, then what does it mean?

And perhaps this study might not be able to give us any conclusive evidence. don't know, at least it will give us some sort of more indication of what's going on on both psychological and physiological level. So basically the difference between the first study and this one is that the original microdosing study was only fully online, so people only did psychological surveys and some cognitive testing while we also have a laboratory measure in the lab branch of the study. So we'll be looking into various markers of neuroplasticity using electroencephalography. We'll be looking into BDNF levels in the blood and also some epigenetic markers of immune

response. So I think it's a very exciting study. And something also important to mention is that the reason why we design the study to to be kind of citizen science and do it at home design. It's because we see with those very well controlled clinical trials that people are not necessarily finding a lot of effects with microdosing so far. Like for example, people in anecdotal studies

report a lot of benefits. However, those studies are typically not placebo-contradosing and relied purely on the self-report measure where people have a lot of expectancies. And as you go up into the scientific rigorous hierarchy, the less kind of positive outcomes you find. And we're going to show that in the literature review that will hopefully be submitting quite soon. We're still working on it. It's quite an exciting project. So we postulated that perhaps micro dosing is something that kind of emerged originally on the streets, you know, and perhaps that comfort of doing it at home, but also with a proper placebo measure in place could give us a bit more understanding into the whole microdosing paradigm.

But also because we're going to include a sample that already has some mood effective disorder. orders, hopefully it will give us more indication whether micro dosing has any therapeutic potential or not because so far, most clinical studies that have been done included populations that are extremely healthy. So we might be seeing so-called sealing effect of wellbeing. So it would just be interesting to see whether this will be similar with people that already have some levels of, you know, mental health problems and perhaps have a little bit more room to improve as they would, as they would with antidepressants, you know.

So, yeah. Yeah. It is fascinating on so many levels. And I'm, it seems to me like there's a, there's a lot of things happening with this study. One thing is this introduction of citizen science. I think that not only is the idea of microdosing, pioneering in a way, but so too is this idea of citizen science. Like in some ways, it seems to me that this study and other studies like it are beginning to try to get their hand around other variables.

Like the citizens out here, like how do you measure this other group that's not control? Like I think it speaks volumes of our ingenuity and our curiosity and our ability to thoroughly understand. when we start going out and finding tools to measure that. Like, that's a step up for science. Let's include these people. Let's take it out of the room and put it into the real world. And I realize there's liability for that. But maybe you could talk a little bit more about the citizen science aspect of it.

Like, how did that come to be? We're sitting around on a table with people being like, I think we should move this over here. Or is there anything you can speak to? I know you're limited in some things, however. But maybe you can speak to the idea of citizen science. Yeah, of course. I think it's a very interesting concept.

and quite important for you to mention that. And I have to emphasize that the citizen science concept that will hopefully work in this study might not exactly be applied to using large doses of psychedelics just because of the safety and the preparation to the experience. Like, for example, obviously we wanted to focus on the safety of psychedelic therapies using them in individuals and the elephant in the room is still using it with people with various mental health problems and by introducing the citizen science design

it's great because we definitely limit the cost of the clinical trial and we can include a larger population however we still have quite stringent inclusion criteria for the trial so we do have a psychiatrist working alongside that will make sure that the people we recruit are, you know, it's safe for them to participate in those trials, if that makes sense. So although I think the concept would work for micro-dosing per se, because it's something that kind of emerged from the street, I'm not sure if I would definitely agree that it's something that should definitely be used with trials that use perceptual doses of psychedelics because it's super important to have a good

preparation is super important to have perhaps therapeutic support there it's super important to know how to integrate this experience and I think without previous preparation people that are psychedelic naive that might be quite a scary experience so yeah it's tricky it's very tricky it's but such as the nature of science, you know, and as you were talking about this, I started thinking, how could you possibly come up with a placebo for a medium dose psychedelic? Like, there's just, like, you know, there's no way to not know. I heard people using niacin for maybe a smaller dose where you would get this flush or something like that. But even that, if one is familiar with both substances,

I think it's clearly easy to distinguish between them. But is that a subject that came up when microdose? How do you come up with a presentable placebo? for that? That's a really good question and I'm not sure how much I can reveal about this. Sure, sure. We had a long discussion about how do we do the placebo measure and it's definitely something that is a big issue in psychedelic trials and even last time we submitted a paper with my supervisor to one of the journals, we got a little bit of critic.

It was a paper about using off ceremonial ayahuasca, and it was a data analysis. And one of the reviewers mentioned that it's critical, that it's really difficult to have a proper placebo measure in psychedelics. And of course, it's such a big challenge. But how exactly that will be executed in the future? I'm not sure, perhaps when psychedelics are,

when they are kind of like, you know, approved treatment. Hopefully we won't need that placebo measure anymore. Regarding the microdosing study, yes, it's also tricky because in theory, microdosing should be subperceptual. Whether it's actually subperceptual for most people, it's really hard for me to say about it because everyone has a different experience with microdosing. Everyone has certain expectancies, you know, about participating on the trial.

Some people believe it. Some people think it's a placebo effect. There is a lot of discussion in the topic. Originally, in the first microdosing study, Bala Shiggeti, who kind of designed the study, used for people that use magic mushrooms. The placebo that he suggested using was chaga mushroom powder. Originally, we're supposed to also.

use the chagal mushroom powder in the design of our study. However, because we will be looking into some biological markers like the BDNF levels, we're quite cautious about the choice of the placebo, because there is some limited evidence suggesting that perhaps using those other adaptogens like Lyons, Chagamashemashin powder might be enough to kind of blue boost your genetic and immune system response to a level that might be a confounder in the study. So we really tried to focus and did a bit of research of what substance can we use to make sure that the tablets, that the capsules for placebo and microdose group look and weigh exactly the same for both conditions so people cannot distinguish between them.

but also we have to use something that will not potentially cause any confounder changes. So in the end, we decided to go with vanilla ice protein powder. And for people that are using LSD, they're just going to use a plain blotter paper as a placebo measure just to make sure that the tablets weigh and look exactly the same. So, yeah, it's definitely a tricky concept. And I think for the purpose of scientific research and this study, we wouldn't really be able to use any active placebo because it's such a confounding factor. And if people in the placebo condition improved, then it would be really hard to think, to say what is attributable to this improvement, especially on a molecular level. Wow.

It's fascinating. It's an interesting question to take. in. I'm often, as a non-scientist, it's mind-blowing to me to get to read the research of the mechanism of action and the way, how deep it goes, and what we learn and what we don't learn and stuff, but also as a non-scientist, I begin to wonder, why do we got to know the mechanism of action? Like, if it works, like, why do we got to know if it really connects to that TRKB receptor, you know, or like, what is the, what is the greatness that we, get from really understanding the mechanism of action, do you think?

Hmm. It's definitely a very, very interesting question. Hmm. I do think it's important to understand the mechanism of action because, you know, everyone is different. And can you really say that one substance works the same for all? I wouldn't be so sure, even though, you know, antidepressants have been used for people with, you know, for example, S.R. Ice has been used in people with depression for millennia.

Like, some people are still treatment resistant. They still don't react the same to those antidepressants, you know. So I think it's very important to understand the mechanism of actions because perhaps we can focus on optimizing. And also, there is a matter of side effects. It's really hard to, like, The way our brain is why it is so complex and there are so many interactions and often interactions lead to side effects. So I think the ultimate goal of mental health and any type of drug research is to come out with something that is the most effective as possible and also causes the least side effects as possible. So in order to do it, we constantly evolve, we adapt even throughout life. lifetime our body changes. We have some hormonal changes,

and it's really difficult to find one substance that works for all. So I think that's why it's important to be a bit more creative with how we look at drugs and targets and receptors. So, yeah. It is. It's wonderful to contemplate and think about. It must be rewarding and interesting to be on the forefront of change. In a previous conversation, you and I had spoke about, it's very competitive, but it's also very rewarding to be at the forefront of change and studying this.

How do you navigate this current world of psychedelics that we're in? Yeah, it's definitely exciting to be in the forefront of the change. And, you know, the field is now opening so much. It's constantly evolving. And we have some groundbreaking research going on, large studies investigating the potential of psilocybin for treatment risks and depression. We had some exciting results from, you know, the MDMA trials, which are definitely, definitely such a big revolution.

But there are also challenges coming with it. And it's quite difficult to navigate, especially for scientists that are trying to, you know, pursue it and learn to navigate the field. Like, first of all, academia, it's extremely competitive and a psychedelic research is no exception. So funding sometimes can be limited. So even if you have this wonderful idea of, you know, investigating a concept, you might not have, you know, in practice enough. money to do it. And even if you do find enough money, there are some ethical consideration of how you look into that question, you know, if it's safe to look into it and the methods you use. And also the whole regulatory side is also quite tricky. It's not easy to get, you know,

approval for clinical studies, extremely challenging. And I think it's a good thing because we we need to focus on ethical standards and making sure that it's safe as safe as possible for us to use a certain substance and investigate a specific research question. But at the same time, it's quite challenging because we have those financial, regulatory constraints, and yeah, also the time constraints is like people say that the field is kind of sometimes publish or perish. So like sometimes academics are really pressured to, you know, just publish a lot of research.

And sometimes it's hard, you know, to find enough kind of evidence that could be good for publication. And then you have to find a journal that will accept your publication. So it's definitely challenging. But I think as long as you have your goals in mind and you want to do your research with, you know, a good ethical standard, then it's definitely worth it because it's very rewarding

to do this job and it's definitely very rewarding to see people improve. So yeah, that's the overview, I guess, from my... Yeah. It's wonderful to me. And I see science changing from the idea that we spoke about earlier about citizen science and maybe the move from journals to podcast i'm not saying one replaces the other but it's definitely a new growing platform where you can come on and speak to the current study you're doing without in a way it's publishing like you're getting your information out there but it's it's it's restrictive of some of the regulations like there's things you can't talk about obviously but you can get your knowledge out there and have people reach out to you with more information so in some ways you're reaching an audience

And the other thing I see evolving too, and I'm curious to get maybe some thoughts on this. If there's any studies or just thoughts, but, you know, it seems in the psychedelic community, there's been this sort of wedge between people who administer help. Have you done psychedelics or have you not psychedelics? It's the same problem with language. It's an either or. But what I see evolving is a both-and, like the coming together of both people to sit down and apply the integration. And like, that to me, it kind of gives me goosebumps.

the same way we can look at the liar's paradox and say, oh, both things are true. So too might be the world of science in combining the person with the experience and without experience. Like, yes and, both and, both are true. Let's bring them together. And I think that that's going to give us a more holistic approach in that. What do you think on those thoughts? Is that too far out there?

Or this is something that you kind of see emerging? Yeah, I definitely feel like it's a bit of a controversial discussion. and I don't know myself where I feel about it. And definitely, I'm not an expert, but from my own perspective and how I myself approach psychodetic trials, I feel like there is a little bit of boundaries that it's definitely needed to be put out there. And personally, I think I find it hard to talk about my personal, you know, psychedics. I do understand that it's quite important to talk about it.

And especially when you're a therapist, I'm not a therapist. I'm a scientist, but I can see that it's a quite hot topic right now among, you know, psychedelic therapists, whether it's a good or bad thing for therapists to have previous experience with psychedelics. And I think it's definitely a valid point to discuss. I'm not sure where I personally am on that subject. But I would be curious to see where the field goes and what would be the conclusion of this discussion. Yeah, I'm excited for the future.

I think that there's a lot of cool things happening in the world of psychedelics. Sometimes in psychedelics we think about LSD or mushrooms, but ayahuasca seems to be something that has been at the forefront of for quite some time, both in different cultures and different things like that. And you have done an incredible study with ayahuasca. Maybe you could talk to us about that a little bit. Yeah, of course. It's going to be a little bit of a transition now because I feel like ayahuasca is something

not, you know, it's something that has been published quite well so far, but it's used in slightly different contexts outside of the Western medicine, maybe. And so I've always been kind of interested in that indigenous cultures and use of ayahuasca. And when I first joined Imperial, I have met my supervisor and it happened to be someone that is actually Ayurka researcher himself. So I was extremely excited about finding the right person to do the research with. and it was such a crazy coincidence. So he's a wonderful person. His name is Brandon Wise and it's been such a pleasure

working with him. I've learned so much so far, but to tell you a little bit more about the study with it. So I personally only did the data analysis site because the data has already been collected by Brandon and his supervisors previously in the past, but there's still a little bit of a little bit of bit of data to analyze and I thought it would be a good idea to look into traumatic re-experiencing.

Brandon also happens to be kind of an expert in PTSD and trauma. So it was definitely a good concept to explore. So we had this sample of 306 just people who are non-veterans that went into South America to participate in ayahuasca ceremonies but also 33 Special Operations Forces Veterans that have quite high trauma profile and many of them also have PTSD. So how we approach this topic is first of all to investigate different types of traumatic events within this population and we look at also different sub-populations groups. So for example, what is the difference in a trauma profile of men and women in the population?

What is the difference between veterans and non-veterans? And we also look into traumatic re-experiencing. So the questioners we use, it's called leg five, and it's structured by asking whether you had previous experience and you have a list of traumatic experiences. And then after their experience with ayahuasca, we ask them whether they re-experience. they re-experience certain types of traumatic events they previously reported.

And we found that 59% of veterans and 42 non-veterans were actually experiencing previous adverse life events, which is quite a significant number. And what was also interesting is that females generally experience adverse life events in a higher proportion than males because 57% of females in our population group re-experience a previous adverse events in comparison to 32% of males and just to add the population was kind of proportional regarding the males in females in the situation in the population to start with and it's important to say that women exhibited a greater likelihood of a re-experiencing adverse. life events that men. And it was substantially driven by the differences between

females and re-experiencing sexual assault with four and ten women with previous history of sexual assault. Obviously it's a bit of controversial topic but much more female than male seem to kind of experience. the sexual assault and it's something that has been re-experienced a lot and also regarding the veterans it seems that they exhibited a greater likelihood of re-experiencing certain adverse life events for example experience of disaster loss of significant older and also episodes of harming others so it's kind of it does make sense because they also have a different

trauma profile than people that are not veterans. But what was actually also interesting is that this traumatic re-experiencing was associated with increased discomfort and reappraisal during the ceremony, which might suggest that perhaps it contributes to some therapeutic outcomes, but it's not without challenges during ceremony and I think that should be acknowledged that you know going into this experience might be extremely challenging and and also what

we find as a caveat that there was a small percentage a really small percentage of participants who reported re-experiencing a memory that they did not previously reported experiencing at all, which is quite interesting because you might ask yourself a question whether they just forgot repressed those memories or perhaps these are not their memories and how the hell did they experience them if they haven't experienced them in the first place. So I think it's definitely a very interesting paper to look into for anyone that is interested in you know ceremonies of ayahuasca in relation to Toronto

and it's important to acknowledge that there are differences in populations attending those ceremonies and perhaps, you know, a facilitator might have, you know, a certain approach to accommodate that difficult re-experiencing that might emerge during the ceremony. So yeah, that's the main gist of our first paper. We also have some future papers planned using the same thing. database, but as I am interested in physiological biomarkers, I would really be interesting to investigate the heart rate variability change. And we also happen to have some of this data from wearable devices. And I still don't know whether it's possible to have a good enough signal to kind of stimulate this data and look into it into more detail. But I'll endeavor to try and I will see if we can get some interesting results.

Yeah, I think you'll get a lot of interesting results. It's fascinating to me. Is there any working hypothesis on the, I guess, is there any working hypothesis you know about or scientific studies done that speak to the idea of change coming through confrontation? Because it sounds like in that study, people were revisiting these very challenging traumatic moments. And it sounds like a hypothesis maybe. something along the lines of the path of confrontation is what leads to the change of reorganizing your thoughts which leads to help. I'm not sure. Are you aware of any studies like that or people

that speak about that? Yeah, definitely I'm not an expert in clinical psychology. However, I do believe there are different studies talking about it and also different schools of, you know, therapists say that it's quite important to kind of perhaps re-experience to those memories and kind of shift your focus to that perhaps traumatic event in order to kind of acknowledge it that is there and get better. And I've recently read quite an interesting book or spiritual bypassing which talks about how people will sometimes use spirituality to kind of bypass this traumatic and often, you know, forgotten or trying to desensitize that the emotions they're struggling with and how people can use spirituality to kind of bypass this experience.

And the author of this book, it's definitely an interesting read that I would, comment is kind of, you know, emphasizing that it's very important to kind of try to acknowledge those difficult emotions in order to get better. So I do believe it's definitely a valid point. And it seems that we also looked into adverse life experience and it seemed that, you know, this traumatic re-experiencing was associated with increased discomfort and reappraisal. So yeah, I think there is definitely a lot more research to be done. And I would be curious whether that will be a working hypothesis one day. You had mentioned that perhaps in a future study would like to monitor like the heart rate.

It seems to me like that heart rate would increase with those traumatic experience. And if it did, what would that tell us? Like what would that mean? It's not exactly heart rate that would be, I would like to work. look into, the variable is called heart rate variability. Heart rate variability is kind of reflects a measure of the interbit intervals in your heart right while it's beating. And there is some evidence suggesting that people with depression might have decreased

heart rate variability and that, you know, the more flexible your heart is, the healthier you are and often people that do a lot of physical activity and are generally healthy, they seem to have higher heart rate variability. So I would like to investigate whether, and I know that other my colleagues also investigate hard rate variability. It seems like quite a hot topic now. But yeah, I would just be curious to see whether we could make a similar kind of hypothesize that people with PTSD perhaps have lower heart variability similar to depression because, you know, it's also on the spectrum of psychopathology and probably also suggesting of, of, you know, physical, pathological levels, like, you know, the way your heart works, the health of your heart.

So I would be curious to see whether perhaps there is any change we're going to see after the ayahuasca trip or perhaps during the trip. And yeah, similar to what we're going to do in the microdosing project who will also look into heart rate variability because we expect our population to have some levels of subclinical mood problems. So we hypothesize that those people will have a lower heart rate variability than healthy people. And we're going to look into potential improvements while they're on microdose. And also on the follow-up, which happens after the microdosing period.

So four weeks after they complete the microdosing period. So we're not only going to look into whether there is any potential change in heart rate variability, but also whether this change can be a long term. And yeah, I think it's quite interesting. It's fascinating to think about it. So you would get the results back from that and then measure it against. What would you measure it against? Like healthy peeings in different studies?

What would you measure that results against? Yeah, that's a good question. So firstly, we could just simply focus on pre-and-post changes. And also, as you know, we're going to have the placebo group in the study. So we can also compare if people in the placebo condition could also improve in heart rate variability. But it would be also difficult to say whether this change, if there is any change, if it could be attributable to just the track, because there is evidence suggesting that even improvement in your lifestyle, in a level of physical exercise can also contribute.

to that positive change. So whether we can hypothesize that this change is definitely attributable to psychedelic or not, it's really hard for me to say, but maybe we could look at heart rate variability as a potential biomarker of, you know, mental health and also physiological health change. And if yes, I think it's definitely a great and interesting biomarker to have because it's completely non-invasive how we measure it. But I'm not sure whether wearable devices will be good enough to,

and accurate enough to show this change on a clinical level. But, yeah, it's something that we're still investigating. Yeah. On the topic of a lot of the times in the literature, when we talk about psychedelics or in theogens, in the literature you seem that you, you hear this term set and setting. And I'm curious in the ayahuasca,

in the ayahuasca paper that was published, they measure the setting. Like it was in a ceremonial setting, we heard. But was it done in South America? Was it done like on a reservation somewhere? Like where was the location of that? And did they incorporate the set and setting in that particular paper? Yeah.

So that particular data, I should have mentioned it. It's data from ceremonial ayahuasca. in South America and I believe the data is coming from five different retreats in South America. I'm not entirely sure what retreats because I didn't actively participate in collecting this data. But yes, it's been done in ceremonial settings in South America with a proper, you know, shaman or Korean Dero and yeah, whether the set and setting is a moderator of the experience and perhaps mental health outcomes, it's very difficult for me to say. And I think the research is currently being done about set and setting.

And also, you know, it's so much different to how we conduct trials in the UK or in academia where set and setting is completely different, you know. But if you can picture yourself as a, for example, if I can picture myself, as someone that is coming from, you know, Western world with some, with some, you know, significant traumas going to the jungle and going through the whole experience. I'm not entirely sure whether this experience being so different from the idea of the world I currently have, which is, you know, in the jungle, would be extremely helpful in me integrating this experience. But again, I'm not definitely an expert on that matter, and my research is many, you know, clinical.

So I could tell you a lot more about the settings we have in our clinical trials in London. But it seems that, you know, those people seem to improve. So, yeah, I'm not entirely sure how the set and setting in Amazon moderates the outcomes, the mental health outcomes people have, but it's definitely interesting to look into. Yeah, it would be a cool study. You know, when you look at a lot of talk therapy or when I read some biographies of people

from some of the things that I have read, getting leverage on yourself is like a big step in changing. And I would imagine that gearing up for a trip to a different country to experience a whole new culture is a giant step in getting leverage on yourself. It's really saying, yourself, I want change, I'm taking this next step, which is a big part of any sort of healthy

dynamic of whether it's relationships or family or friends. And it's really a fascinating concept to think about. And I'm all for people finding ways to take that next step or harness the courage it takes to become their authentic self. It's really wonderful to think about that aspect of it. And you know, yeah, I'm sorry. No, no, absolutely. I agree with you. And I think like even taking this big step and going for a trip to, you know, Amazon, it's kind of an intervention itself. So it might be a significant confounder, but as long as, you know, we don't cause harm and there are some benefits, I think I don't necessarily think it's a bad thing. If I were to wave a magic wand and be able to fund any project you wanted,

like what are some projects? Like if you had the ability to have, if I was a giant backer and I had tons of money and I could fund whatever project you wanted to, would there be a set of projects? Would there be one in particular? What would it be? Wow. First of all, if you do have those magical skills, please do. Please.

It would be absolutely amazing if you could. It's an interesting question. It's hard for me to kind of choose, just like focus on one project. There are so many interesting research question in my opinion. And I think if I were to choose, I would probably focus on kind of, you know, finding the right biomarkers of mental health and physical health, because I don't think we currently have enough reliable biomarkers to kind of investigate the improvements in plasticity

and, you know, in the physiological and psychological well-being. So I think it's quite important to mention there is also a huge translational gap between, you know, animal models and human clinical research. As you know, the mechanism of action papers are mainly focused on animal models or cellular models. However, the methods we currently have are not entirely translational to humans. And also, sadly, it's really hard for us to investigate what's going on in a human brain on a very kind of molecular level, because the only way we can do it is using brain imaging, which is, which is, which is, is typically quite expensive if you want to use pet imaging that gives you an indication on,

you know, the receptor level, the cost associated with investigating any working hypotheses are just humongous. And I think that's a big limitation because, as you know, everyone is different. So to kind of really have a good understanding and prove your hypothesis, you need a large sample, but you cannot enroll too many subjects on a study that is extremely expensive because you have those financial constraints. So it's definitely a very tricky field to kind of operate, to try to be as translatable as you can, but also focus on the high cost of the methods.

And yeah, I think it's definitely good to investigate. When you say biomarkers, you know, I'm familiar with the loss in translation from, like, rats to humans. Like they have like the head twitch and they cut off their heads and they look at all that kind of stuff. Obviously can't do that with the human. But when you say biomarkers, I don't know what that means exactly. Is that like different levels of serotonin or is that different? Like what does it mean biomarkers? Like what specifically would you be looking for?

Yeah. I mean, it really depends. So biomarker as a variable that you can. you can use as a working hypothesis to test a certain, for example, trade or to test a certain kind of improvement in physical or mental health. For example, we could say that BDNF is kind of the biomarker we use to test a neuroplasticity. However, there are also limitations surrounding this biomarker. So I think the field is still constantly developing, and I think we need to test more of those biomarkers, not only of neuroplasticity, but just as an example, BDNF is a biomarker that we can test both in animals and in humans. However, the way we tested in humans is typically from your peripheral system. So like by taking the blood side, samples because it's not extremely expensive to do.

It's kind of doable to kind of take a blood sample from participants and test the levels of BDNF in periphery. However, neuroplasticity is a process that occurs centrally in your brain. So if it's a good enough biomarker to test from periphery for a process that happens in central nervous system, it's a bit of an overstatement in my opinion and also different interact with may also affect the circulating levels of BDNF in your plasma. So it's extremely tricky to find the right ways to measure our working hypothesis still. So I think there needs to be a lot more research done in humans. And yes, sadly, to do it, it's quite expensive.

So for example, focusing on heart rate variability as a biomarker of perhaps improvement in depression, which we still don't know if it's an actually good biomarker, it would be great because it's completely non-invasive. It's not expensive to test it. You can either test it using the Overeign as we do or any sort of wearable seems to measure heart rate variability with enough accuracy

to kind of see a difference within you as, you know, know, perhaps non-clinical subject. So it would be good to find more of those kind of cheap and reliable, you know, biomarkers that could help us assess the improvements on both mental and physical health. It's fascinating to think about it. In a previous published paper, I think you spoke about the geometric shapes of plaque in a while back. And I only scanned through that paper a little bit. But what does that geometric shape of that plaque tell us?

Like, why is that important? Wow. So it's something that I did so much earlier in my career. So basically maybe to give a bit of context because it's a bit of context to talk about plaques that happen in that cardiovascular system. after talking so much about psychedelics. So before working in a psychedelic field during my undergraduate studies,

I came across that research group that does a lot of bioengineering and working with, you know, cardiovascular system. And my supervisor was kind of investigating he wanted to focus on investigating potential risk of people having an acute cardiovascular events in a non-invasive way. So what we did is using a 3D modeling software applied on some cardiac computed tomography of the heart to first of all extract. the vasculature of the heart. So it's called coronary arteries, like all of our hearts have some arteries and little veins around them. And what happens in people that have a coronary artery

disease is that some plaques are forming in those arteries. So for some people, it might be stenotic plaques. That means they are mainly form of fatty tissue. For other people, it might be more of a calcified plaques. So typically to investigate in the clinical population if someone has a potentially coronary artery disease, the methods that are being used are kindly kind of invasive and involve putting a catarer inside of your artery, which again has a higher cause because you need a qualified clinician. Again, it's invasive. It's not a very nice procedure.

So we thought maybe we can approach it in a different way and use this 3D modeling software to kind of extract the arteries. And so the first step was to extract the models of the coronary artery trees of, I think it was 27 images I had at the time. And then the next step was to extract those plaques from those arteries. So it's a bit of a challenge because how we see it

on the computed tomography might not be extremely, you know, accurate as you would see it with the contrast inside of your vein. So I try to develop a method on how to kind of visualize those plaques in a non-invasive way in people. So then the next step would involve to kind of extract the plaque itself and measure the geometric properties of this plaque. And my supervisor, who's also a brilliant scientist,

has a lot of computational background. So he applied his knowledge to kind of develop an algorithm that would help us perhaps predict a chance in the future of someone having an acute cardiac event based on the geometric properties of the plaque. And he does similar research in people that might have a risk of stroke. So also by measuring the angles and the geometric properties

of the vasculature in the brain, you might be able to predict a risk of stroke in the future. So again, I think it leans nicely into the conversation about trying to find non-invasive biomarkers, to kind of perhaps diagnose people and help people because it's such a in-med knit and now we have such a sophisticated, you know, computerized technologies that might help us

to diagnose those people much earlier because if you have a method that is definitely much cheaper and non-evasive, there is a greater chance of getting someone tested a bit earlier than after it actually happens when typically it might be too late to, you know, improve in general health outcomes than if it would be when you, if you were tested much earlier. So, yeah. It's so fascinating to me.

Might it be possible to use that algorithm or that research in some of the things you're doing? Now, it sounds like he has found a way to take this 2D model on screen and verify it by all the research. You know what I mean? Like, in some ways he's, okay, here's what it looks like on the screen, and here's the tools we're going to measure it. You know, it, I don't know, it just seems to me like he's figured out a way to translate this two-dimensional object into reality. That probably has a lot of repercussions in other research and stuff like that. It's fascinating to think about it. I'm so stoked to hear people talk about it. Is it, it seems like it's going to be, in those findings, did they match you up? Do the computer model that you saw on the 2D screen? When you measured it

afterwards, were they similar? Was the geometric shape the same? So there are definitely some limitations with this research. First of all, the models I've done were only based on the CCTV images and we didn't like, we didn't come back to those patients and actually measure the properties of those, you know, plaques using different methods. It's something we postulated as a potential tool that might be used in the future if we do much more research. But it was not exactly verified in that population sample we tested. It was more of a retrospective assessment and trying to come up with a method that might be potentially used. And it's also important to mention that most of this research is happening in Asia.

I believe I think it's China. So I'm not entirely sure whether the clinicians did any follow up with those patients and what would be the long-term outcomes of those patients that we measured. However, I do think that there is a potential trend of moving, the paradigm to more personalized and perhaps cheaper diagnostic medicine that I think would definitely be very interesting to investigate more and we just have to be creative and we have to be kind of you know adventurous and open-minded so I quite like taking that direction of making something accessible to as many people as you possibly can,

if that can potentially help those people and it's accurate enough. But again, it takes a lot of time and it takes a lot of funding. So sometimes we start doing those things and this research, but never end up having any conclusive findings because the sample is not big enough to show statistical difference or it's too hard to come back or, you know, the grant is ended. Yeah, it's just really tricky to navigate academia. That's a lot. I don't, I didn't know that. And I'm willing to bet most people don't ever see that side. Like there's all this promise of a study that gets done, but then it never gets revisited. But that's kind of heartbreaking in some ways. It must be difficult to look at that

from that perspective. Yeah, absolutely. Man. I think creative, adventurous, and open-minded are all three great words that describe you and the work you're doing. I'm super thankful for all your time today. And I really enjoyed it. I'm really excited that people are out there looking for answers to problems and questions and are excited to do it and are at the forefront of it. But before I let you go, maybe you can talk about where people can find you, what you have coming up and anything else about the microdosing study that we didn't touch on. on. Okay. Well, I'm not a huge social media person. So I do use LinkedIn quite a lot. I think that really good platform because it's professional enough and there are still some, you know,

boundaries. So I quite like to use LinkedIn and I'm open to anyone who's interested to have a conversation about microdosing or psychedelic research to reach out. So please do if you are interested or would like to ask me any questions. For people that might potentially be interested participating in our microdosing study, we do have a sign-up link on the Imperial College website. So if you simply type in microdosing 2.0 Imperial College London, you will come up with the website on Google,

and then you can read all the information you need. And I would strongly recommend reading the participant information sheet and the inclusion criteria. before you decide, you know, starting the trial. And what else I have coming up? So mainly the coordination of the trial, which I hope will be fruitful. And also hopefully some workshops soon, I might do some presentations about microdosing again

and some of the sexuality and female targeted research. So I would definitely let you know if there is something coming up in the near future. Yeah, we didn't really touch on that. Is that something you want to talk about, the female targeted research? I think we might be running out the time right now. Me too. I would definitely love to talk about it more in the future. Absolutely.

Well, everyone listening, go check out the show notes, check out the work she's doing. doing. It's really incredible. And I had a fantastic time talking to you. Thank you very much for your time. Ladies and gentlemen, hang on, Alexander. I'm going to talk to you briefly afterwards, but I'm going to hang up with the people. Ladies and gentlemen, thank you so much for spending a little bit of your Sunday with us. I hope the rest of your Sunday is beautiful. And that's all we got for today. Aloha. Thank you.