(From YouTube)

Dan Riley [00:00:23]:
John Dean, real pleasure to have you on the show. I've been interested in the subject we're going to be talking about for a long time. Welcome, man. It's great to meet you.

Jon Dean [00:00:31]:
Yeah, same.

Dan Riley [00:00:34]:
I would love to start with a basic question to you. I know you're a scientist, a former musician, maybe a current musician as well. Still, how in the hell did you get interested in the subject of what we're going to talk about today, which is DMT?

Jon Dean [00:00:51]:
Yeah, it's pretty straightforward. I have always been really keen on science in grade school and high school and whatnot. I didn't really, when I started college, think that it never occurred to me, hey, go be a major in chemistry, which I was. Yes, I tell the story pretty much the same way every time, but it really kind of boiled down to a little bit of an existential crisis early on in life. I had a close friend that died out of nowhere young. We were like 19. And yeah, for whatever reason, that just kind of hit me, hit me pretty hard. And it was also like right around the time where you're experimenting with consciousness, it all factored into one another.

Jon Dean [00:01:54]:
And I just became fascinated by the idea that the brain is complicated to the point where you can take a compound that'll completely change consciousness and change reality, and that there has to be some sort of neurological at least correlate of that. And there wasn't a whole lot of research on that. That kind of sent me down the path of changing a major to chemistry. Well, I didn't really have a major at that point, so I started taking psychology courses, and I was playing music, playing in bands along that time as well. So then I kind of got through all the psychology courses that were interesting to me, which most of them had abnormal or biological correlate to them or underpinning to the curriculum, and then started taking chemistry and really enjoyed that a lot. Always liked organic chemistry. And then through my reading and through my studying, came to find that DMt is present in bodily fluids in humans and in other mammals, and that it's literally like the same molecule that when you take it exogenously, you have these very powerful, bizarre experiences. And no one was really at least contemporarily investigating why DMT is present in the body from a scientific perspective.

Jon Dean [00:03:26]:
And I mean, it fascinated me one and then two. It just seemed like you could do these types of studies, right, if you're able to quantify DMT, which it was clear that you could, even if it was kind of crude, and the studies never really hammered it down, so to speak. But it was a starting point. So that kind of got me into what I did for my master's in PhD, which was look at rodent models for quantifying endogenously generated DMT within the living rat brain, specifically. And we use that approach because we would be able to compare it to known neurotransmitters using these, like, bread and butter analytical chemistry techniques. So able to sample the fluid right out of the living brain of a rat, which circumvented sort of all of the literature that said, oh, well, DMT gets broken down really quick, which it does, it seems, in the blood and the periphery, and nothing was really known about the brain because there weren't really any studies, like directly looking at a living brain, because in the. Couldn't really do that. There's like a lot of post mortem stuff and radio labeling precursors and tossing it into tissues and things of this nature, and then, say, in the molecular biology sort of caught up, you could clone the enzymes that have been shown to be able to biosynthesize it.

Jon Dean [00:05:00]:
So we kind of took a multimodal approach to understanding the distribution of those enzymes in the rat brain and sampling living brain fluid. So that's kind of what brought me to my PhD, at least. And then now I'm doing human clinical trials, like we talked about a little bit on psilocybin or chronic phantom limb pain, and then soon to be doing continuously infused DMT studies as well. So those will be launching within a couple of months, if we're really lucky with the regulatory stuff, but we're getting closer to getting that off of the ground here, too.

Dan Riley [00:05:44]:
At UCSB, I want to clarify a couple of things for the audience. When you say no, that was great. I think just to define terms, when you say endogenous DMT, you mean it's naturally created in the human animal and in other mammals as well, if I understand that correctly, that it's found throughout the human body. This is a lot of what I think your 2019 study indicated. And I also wanted to dig into the story you started with, which was your friend dying at 19. How do you think that that influenced the trajectory of your life from then to now?

Jon Dean [00:06:29]:
Yeah, the first part is correct. Right. So endogenous DMT, it means it's naturally occurring. So it's not like you smoke it. It's what you can measure without doing the drug like it's already being produced. It seems like in the body by, by some sort of, sort of known mechanism but not really known that well. Yeah, so yeah, that, and then it's just kind of, well, I mean it made me question reality, honestly, it made me say well we don't really have a clue what's going on with reality, with the brain, with life, with death. No one really knows what that is.

Jon Dean [00:07:13]:
And there's so much research on, in science, there's so much research on keeping people alive, which is fantastic research. It's very valuable to be alive and very grateful for that. But yeah, I was just like, wow, no one really knows too much about what happens when you die, at least from a scientific perspective obviously, because when you die materialism sort of goes out the window for what we know, right. So it's kind of hard to measure that but you can measure the process and things that are related to just. It's hard to fund those types of studies. So there isn't a ton out there on that.

Dan Riley [00:07:59]:
There's a great Carl Jung line which I love about this which I heard a couple of years ago, which is life is a short pause between two great mysteries which I think is maybe related to some degree to your curiosity, especially in the face of someone close to you dying. I want to go into a little bit of the chronology of know knowledge about DMT. And in preparation for this interview I was rereading Rick Strassman's book DMT the Spirit Molecule and just getting more familiar with some of the specifics of what happened when that people began to learn about DMT as a molecule. And just to set the table with some of the history, I'll give a couple of points and you're welcome to correct me if any of this is wrong, but my understanding is that the canadian chemist Richard Mansky synthesized DMT for the first time in 1931. In June 1965 a german research, german research discovered and quantified DMT in human blood and urine. I think you were referencing that a little bit earlier about DMT being known to be a part of human bodily fluids. Strassman it seems like really, and I think I've heard you use this phrase about his work, ripped the door off of psychedelic research or reopened the door for psychedelic research with his DMT research at the University of New Mexico in the 90s. Maybe I can just give this to you.

Dan Riley [00:09:30]:
And I'm assuming in your journey to where you are now. That man, and potentially that book had an influence on you. What do you remember resonating about Strassman and his work know interested you in general?

Jon Dean [00:09:46]:
Yeah. So that book definitely was huge in my trajectory. Rick's book, DMT, Spirit Molecule. So right around that time, that's how I found out about DMT. I read that book. I don't remember how I found the book, to be honest. I might have just been like serendipity at a bookstore. I can't even remember.

Jon Dean [00:10:07]:
Or maybe I saw it in like irrowit or something because this is close to when it came out. It would have been the early 2000s when I read it. But anyhow, yeah, that book, it was just communicated very well. The concepts. Rick writes very succinct and communicates very complicated concepts well, in my opinion, scientifically, but then also isn't afraid to speculate a little bit and be very clear that hey, I'm speculating here, but this is an interesting avenue that a scientist could venture down if they are ready for the long. So his book was definitely big in my trajectory.

Dan Riley [00:10:57]:
And to be clear, Rick Strassman is a doctor, a psychiatrist, and a professor, as I understand it. I mean, a pretty well credentialed man. I want to read a couple of quotes from him and you talked about speculation. The book details his experience of injecting DMT. This is all above board. This was all authorized to, I think, 50 or so subjects, 400 times. So 400 doses into roughly five dozen volunteers and recording basic biological responses like their heart rate, their blood pressure, but also anecdotal feedback from these people who are reporting what it's like to get a certain quantity of DMT injected into their veins. And maybe before I read some of Rick's speculation, I'd be curious to know if the stories from the people in the book still resonate with you as being noteworthy or just extremely interesting.

Dan Riley [00:12:06]:
I will just say personally, what got me interested in DMT is having friends. Having had this experience of smoking DMT and listening to what they said they experienced, it is just damn peculiar. I don't know how you could listen to some of these stories from otherwise extraordinarily intelligent and sober minded, rational people and come away from hearing some of these stories not scratching your head a little bit. Maybe I'll just give that to you and ask if there are any stories from the book or even in your personal life of either your own experiences or friends doing DMT and sparking an incredible amount of wonder and curiosity.

Jon Dean [00:12:51]:
Yeah, I think you summarize it pretty spot on. That's what attracted me to the study of it in particular, because it's found naturally, and it doesn't necessarily mean that because it's found naturally that it's involved in near death experiences and dreaming and some of the more out there theories of what it's doing in the body and in the brain, because we haven't really established that scientifically, just because it's so hard to really quantify that the molecule itself, in the body, particularly in humans, which is something that we're working toward assays that would be more reliable in humans. So that kind of would be the gold standard to establish any physiological role for DMT, let alone some of the more speculative and admittedly a little bit sexier hypotheses for it. But since the overlap is there, since there are dreamlike qualities to a DMT trip, or there are overlaps with some near death experience reports with DMT, and since it's found naturally, it's not exactly non scientific to make that connection. That's how science works, in my opinion. That's how it works for me, anyways. I think that the psychology and the experiential component of any type of neuroscience is particularly important to understanding how a certain area of the brain works. Because otherwise, it's just a lump of flesh, right? Depending on if you're talking about psychology and experiential content, it's not really known what endogenous DMT is doing.

Jon Dean [00:14:50]:
But those reports certainly are enticing to think that something that's so similar to serotonin, which is a major neurotransmitter, and this is also one of the findings in our 2019 paper, was that when we measured and compared DMT in the rap brain, in the living rap brain, with these microdialysis probes, they're called, we were kind of surprised, too, to see that it was in concentrations comparable to serotonin, about half of serotonin. There's more to it than that. Obviously. You got to zoom in a little bit to look at the pharmacology. And those were, some of the discussions that stemmed from the paper were, well, is this actually a concentration that would necessitate any physiological function? I'm not a pharmacologist, but I would say that if it's their half a serotonin, it's likely doing something in the brain, whether that's related to processing any sort of information or consciousness, who knows? It could be an anti inflammatory role. There's been studies that have shown that it's helpful for stroke, at least in rotom models. And then people are carrying out clinical trials right now, early phases of administering DMT to people that have had a stroke to try to expedite recovery. So it's really not known what's going on there.

Jon Dean [00:16:30]:
But to go back to the original question, it's very peculiar that you can increase the amount of DMT in the brain to a large level and have such strange effects. More so than if you increase the amount of serotonin with something like MDMA or something like that.

Dan Riley [00:16:56]:
What do people. And again, I know you're a scientist, and part of that ethos is not overstating what you have high confidence in believing and can show evidence for. But just anecdotally from the stories that you've heard in books and in your own life, perhaps. What do people report from? I think it was Terrence McKenna. I was listening to an interviewer, Dennis McKenna, who mentioned that part of what appeals to him about DMT is its simplicity as a molecule, and that you just noted how common and the level at which it seems to be endogenous in the brain. People who get a spike of DMT inserted into their bodies, what kind of stories do they tend to report in your experience, when they seem to go somewhere else?

Jon Dean [00:17:58]:
Yeah, I mean, they're pretty variable stories, right? I mean, they're out there. So we haven't started to do our studies yet, but the reports are fairly. There's a lot of commonalities. And something that pops up a lot in the literature on high doses is having some sort of contact with what seems to be an entity that is potentially freestanding and autonomous in its own right in a different dimension or something like that. That's pretty common. It pops up a lot. There's some debate whether that's potentially a cultural thing. That's a very interesting question in and of itself.

Jon Dean [00:18:52]:
I remember I did a talk not too long ago in Arizona, I think it was in Phoenix, and somebody asked a really good question. I think I gave some smart ass answer because I was like, man, I don't have an answer to that. But it was regarding, with people that speak different languages, has it ever been kind of investigated what the sort of link, like what language was being communicated by? Because two way communication with entities is very common in the DMT experience. So something like that, I think would be an interesting question that would kind of hint at the cultural significance of it. But yeah, bizarre stories. But I think a pretty common thread seems to be entity phenomena. I'm just kind of dipping my feet in that world now and starting to understand more of the literature on the experiential components because I was living in the molecular biology world for so long with the endogenous stuff. And now that we're ramping up to be administering DMT in humans, yeah, we want to understand everything related to safety and proper dosing.

Jon Dean [00:20:16]:
And then also the experiential component is going to be huge in the investigation. So we're very interested in the types of experiences that people have, particularly in the domain of entity contact and things of this nature. Just really basic science questions. We have the potential to really change the visual system, right, with DMT and at a basic level, understanding what happens in the brain to juxtapose that with just like normal visual processing is something that we're interested in doing. And then of course a lot of the studies we do at UCSD are geared toward alleviating chronic pain. We have a very large pain research community here, so we're particularly interested in things like I was saying earlier, like DMT for stroke and other pain conditions that don't have a lot of options. It's a pretty big study and out of the gate it'll be in healthy individuals. But yeah, we hope that it can help some people for sure.

Jon Dean [00:21:32]:
That's the main goal. And then to do the cute neuroscience in tandem.

Dan Riley [00:21:38]:
Yeah, I didn't know this before preparing for this conversation that apparently there is some evidence, or a significant amount of evidence that subconscious quantities of DMT also seem to have potentially some antidepressant characteristics or effects on people similar to what many people report on psilocybin, which I wasn't aware of. And I want to get into your research at Michigan and some other subjects as well. But just to pause for a second and think about a person who has never heard about this subject or knows very little about DMT or the psychedelic world in general. I have to imagine for someone who is leading these studies, it's probably a delicate dance to speak cautiously so that you can back up what you are claiming with evidence while not sounding crazy. Because so much of what I came across in the last few days in preparation for this, if I were to, I think, tell an average american or average person what these people claim to be experiencing and what some of the more speculative theories are about DMT in particular, these people are crazy could be a common reaction that a lot of people would have. How have you dealt with that for yourself? I mean, obviously Rick, just in reading his book, he clearly was extremely interested in learning about the anecdotes of what people were experiencing under the influence of DMT, but he had to get funding and do this legally. So I'd love to put that to you to speak to a general public or a general population audience about how you think about that.

Jon Dean [00:23:35]:
Yeah, okay. That's a lot. Well, I watched the Super bowl, and I feel crazy. It's a very relative thing. Right?

Dan Riley [00:23:45]:
Fair enough.

Jon Dean [00:23:50]:
We just want to do it, right? We want to do it, and by right, I mean, most importantly, safe. So that's what keeps me up at night and has over the past several nights, I'm sure, is just making sure that we're doing this safely across the map. We understand the responsibility of keeping the people that are participating in all of our studies with psychedelics, making sure that they're coming out of the study benefiting in some way, shape, or form. So that includes having a team of monitors, like therapists on hand that work with our participants from the beginning, all the way through the end of the study, whether it's for the clinical outcomes or in the case of the DMT work initially, just not for a clinical indication, just otherwise healthy individuals that are participating. So that's number two. We're geeks. We want to know how the brain works. Also, neuroscience in general, no matter what question I feel like in neuroscience, you're asking, I mean, yeah, we ask these crazy questions about consciousness, but even if you dive down the periscope of any kind of isolated neuroscience question, like, how does vision work, or how does hearing work? Or isolating the different sensory systems, you get into some pretty crazy stuff.

Jon Dean [00:25:31]:
It's fascinating, right, that this lump of flesh can do all these wild things and generate these amazing experiences in animals in general. Right? Not to just take it to the human level. Yeah. Let's see, where am I going with this? So, step one, right? Safety. And then step two, just try to have a question that's just very grounded. I mean, we just want to do, like, concrete stuff. We don't want to jump ahead too far, you know what I mean? We're interested, like Rick Strassman and these less mundane questions because it's kind of hard not to be when you're talking psychedelics, especially DMT, since it is endogenous and you take a big bolus of it, and you have these wild, wild experiences. What does that say about how the brain works to generate consciousness, but you can't jump too far ahead, right? Because we have no idea how consciousness really works.

Jon Dean [00:26:44]:
We try to stay grounded in the types of questions that we're asking. So, for our DMT study, we just want to ask some fundamental questions about how vision works and how the brain produces vision, and how a visual perception differs from something like imagination. So things like that. So these questions that you can actually kind of get at the grounded materialist root of the question, and that's like a springboard to ask some wild or some crazier questions. And for things like endogenous DMT, there's ways that you can ask those wild questions, too. So if there's a way to measure DMT, particularly in a human brain or in the body, non invasively, and get a good read on it, so that you can reliably say, like, concentrations were at this before some intervention, and concentrations were at this after some intervention, if you had a decent temporal resolution, you could start to do simple things like track it across the sleep wake cycle. And this is something, even in rodents, that can be done right now with the right funding and the right study. So, if you want to ask the question, is DMT potentially involved in dreaming? Which is an interesting question, seeing as we do know that it's very similar to melatonin, which is kind of involved in the sleep wake cycle.

Jon Dean [00:28:25]:
It precursors, tryptophan. So all that funnels into pineal regulation of melatonin and circadian rhythms and whatnot, serotonin, even. So, you could just track DMT across the sleep wake cycle in rodents or in humans, particularly in humans. It would be interesting if you were able to correlate different aspects of someone's dreaming and rem sleep with DMT release. So things like that. I mean, most of neuroscience, I think, is pretty correlational, at least with fMRI, like in the brain, you're just saying, how do these voxels and how does this blood flow, or veg, how do these frequencies correlate with behaviors? But it's a start. I mean, it's kind of the best that we can do right now. And I think things are getting a little more sophisticated with some of the rock star like computational neuroscientists out there are able to develop these pretty wild models of vision, things like that.

Jon Dean [00:29:34]:
It's a pretty exciting time to be doing neuroscience, let alone psychedelic neuroscience. So, safety being grounded, being concrete. Personally, I got out of animal research, rodent research, to try to make more of a direct impact in people's lives, if possible, only here for so long. So if we can do some studies that can be incredibly beneficial to somebody that maybe doesn't have a lot of options, like in our phantom one pain study. It's an exciting burden to take that on and to make sure that we pull it off in all the ways that I just described, and then too, being respectful of the historical roots of the medicines that we're utilizing and hopefully integrating into western culture in the clinic. So that's something that I myself have very little knowledge of and trying to work at when I can and be conscious of that. In our newly launched, soon to be launched psychedelic center at UCSD, we really hope to, we have a director for anthropology that is leading up that charge of respecting indigenous cultures. And yeah, not just saying that, like actually trying to work with organizations like Shakruna and Swan that has contacted us, that we hope to keep trying to form some collaborations with.

Jon Dean [00:31:15]:
So it's a lot of different angles, lots in slots out.

Dan Riley [00:31:22]:
A lot of what have yous. I want to read out. What I have gleaned are the three primary kind of takeaways from your 2019 study. And I think universally among the people that were interviewed in a documentary that I was watching a couple of days ago about DMT, were remarking about that study being a landmark study or a landmark paper, and I want to read out what I believe those three takeaways are and put these three to you and have you edit or add anything that you think might be relevant. This is a 2019 paper from the University of Michigan which found, one, that DMT's level in humans is comparable to serotonin and dopamine. Two, the two enzymes that are responsible for DMT synthesis occur in the same nerve cell and three, cardiac arrest was induced in rodents in the study, which led to a 600% increase in DMT in the visual cortex of the brain. And the question there being could this explain the near death experiences that many people report? And I believe you mentioned that somewhere upwards of 20% of people who have cardiac arrest report a near death experience. I don't know if that's a reasonable summary to you of that paper, but I'd love to get any additional thoughts or clarifications you might want to give on what that paper really showed.

Jon Dean [00:32:59]:
Sure. So let me try to go one through three. We didn't actually measure DMT in humans. In the study, we measured enzymatic expression. Well, the mrna, so it goes from the mrna to the protein. We did see pretty high expression for the first time in human tissues, human brain tissues, in the frontal cortex, I think in human brain we found, and in the pineal gland, also of the enzyme that takes tryptamine to dimethyl tryptamine. Okay, so that was one and then two. I think you said the colocalization.

Jon Dean [00:33:59]:
So there's two enzymes, and one of them is an enzyme that takes tryptophan into tryptamine. It's like a decarboxylase enzyme, and it's AEDC for short. And that enzyme has been known to be present in brain tissue for a long time. And then the other one, inft, is the one that we saw in the human brain tissue. So in the rat tissue, this is all post mortem, by the way. So there are tissue samples that have been preserved after death. And then we're able to do some molecular biology techniques to amplify the mrna that's in the tissues. So what's cool about that approach that we took is called NCT hybridization.

Jon Dean [00:34:57]:
You're able to go by like a cell by cell level, so you could look within individual tissues and individual cells within those tissues. And so that's what we did. So in the humans, we are a little more limited on the samples that we had. And we also, unfortunately, didn't have the two probes for the human tissues. So we only looked for the INMT and then in the rodent. This is 0.2 that you were alluding to in the rodent study. In the rodent tissues, we found in the same cells in the brain, presumably neurons, we didn't have neuronal markers, but they looked pretty neuronal in their architecture. And we saw in the same cells we found INFt and ADC, which would increase the likelihood that that cell would be able to make DMT.

Jon Dean [00:35:54]:
So that's 0.2 and then three is the increase at cardiac arrest. Yeah. Unfortunately, when you're doing animal research, at the end, you euthanize the animals. We were given permission to keep monitoring and measuring throughout the death process. And we did see, following cardiac arrest for upwards of 60 minutes later, that the DMT levels increased upwards of like eleven fold, actually. So even more than what we reported, because we had a bunch of different strains of rats and we wanted to keep it as apples to apples as possible and look at just within one strain of rat, because we did see some differences in different strains in terms of neurochemistry, which is a completely another thing, but interesting. But anyhow, yeah, we don't know though what that means because it's just a fold increase. So you have to keep in mind, like baseline, just because something goes up eleven fold doesn't necessarily mean that so much.

Jon Dean [00:37:12]:
If it started out low. So the nanomolar concentrations that we reported, that was kind of like, novel for the study, because, again, no one thought that it was in the same animal or range as serotonin. And in the dying brain, serotonin increases big time at death, at least in rodent models, way more than DMT. But it's interesting. So, like, there's a couple of papers from the same group that were actually like, before we put out the 2019 study. So the Borges again, lab GMO borges again, at edumesh, where they looked at neurotransmitter changes and electrical changes in the dying brain. And we did too, with the DMT study. But one of the take homes, I think, is that it wasn't just like everything increased, right? So we monitored a whole slew of different neurotransmitters and neuromodulators and neurocompounds, and it wasn't just like everything.

Jon Dean [00:38:25]:
Just like the cell dumped everything out, right? So it seems like it's a crude speculation based on not a lot of data, but it seems like that it's like a regulated process dying. Right? But, yeah, point being, with the fold increases for DMT, I think it was upwards of like, man, I have to go back and look. I think the highest we saw was maybe like around like 40, 50 nanomal or something like that. But we didn't report all that data. Some of the big questions, discussions stemming from that study was if it would actually activate the receptors, right? Because there's like a functional level that a neurotransmitter, a neuro compound, or any substance would have to meet to be able to activate. There's certain assays, like EC 50, I think it's called, where you would basically see a reaction whether you're measuring calcium changes or there's a couple of different ways of doing it. The DMT to be functionally selective or activate the five h t two a receptor. I forget.

Jon Dean [00:39:44]:
I think it's something. I haven't thought about this stuff in a while. I'm living in human fMRI world now, but I think it's like the lowest is in the range of like 32 nanomolar or something like that. And what we reported was only like a couple of nanomolar increase, I think the highest. And the study that was published was like, I don't even remember my own study, man. It's been so long. Like ten animal or something like that. So it's really not known.

Jon Dean [00:40:12]:
Is that in a psychedelic amount just because it went up 600%. Because when you hear that, you're like, oh my God, 600%. That's like everybody's tripping, right? No idea.

Dan Riley [00:40:26]:
This was a point I wanted to clarify, and I believe this is right, but I would love to get your confirmation or not on this, that my understanding is that one of the things that's remarkable about the knowledge that DMT is within the human animal is that that is unlike any other known psychedelic, that psilocybin, for example, or LSD. These are exogenous, not endogenous. They're not in our systems by default. Is that correct?

Jon Dean [00:40:59]:
Yeah, to the best of my knowledge it is, yes. Even things like the endocannabinoid system and endogenous opioid system, which we do a little bit of human research on the endogenous opioid system at UCSD, we actually block it while people are meditating. And we want to understand if the pain relief that we would see during meditation, particularly our recent study in people with chronic low back pain, if the meditation is engaging the opioid system, then the idea is if you administer naloxone and block the opioid system, you should be able to turn off that pain relief effect from meditation, which wasn't what we saw in the recent study, suggesting that mindfulness is engaging something else to relieve pain. But, yeah, in terms of DMT, the brain is like a soup, right? So it seems like there's other, if not psychedelic molecules. Well, I mean, five MeO DMT has also been reported in bodily fluids. So it could be that that is also in the brain and in the body naturally. No one's really doing these studies for whatever reason, it's pretty bizarre that even if it doesn't turn out to be what people think it is in terms of oh my God, it's why we have near death experiences, it's still pretty fascinating that a molecule that is such a powerful psychedelic is naturally in our bodies. And understanding why that's the case, I think would really help us understand the brain a lot better.

Dan Riley [00:42:51]:
Yeah, I want to go into some of the. You used this word sexy earlier, sexier, some of the more interesting, some of the wilder speculations about what might be going on during these experiences. And I referenced this earlier in the conversation about a couple of lines from Rick Strassman that I wanted to read out, who arguably has more experience with scientific studies of DMT than anyone, at least in modern times in America. And I want to read a couple of a quote from him and then a comment with a partial quote in it. And this is one from him. This is Rick Strassman. Quote, the chemistry of the research subject's brain. This is in reference to the studies that he was doing at the University of New Mexico.

Dan Riley [00:43:43]:
Quote, the chemistry of the research subjects brains, which is the organ of consciousness, was being changed by DMT in such a way that they could then receive information that we weren't able to receive normally then. This is another comment from Rick. If one wanted to speculate wildly, one could argue DMT neurotransmitter system, quote, mediates our sense of reality. I've heard similar comments like that. Obviously, I think you would probably agree that there is a lot of speculation in these kind of comments, but I want to maybe move us from the known scientific studies to some of the wilder speculation that I'm sure you've given a lot of thought to. I remember learning this about Darwin, that when he was developing his theory of evolution, that one of the reasons that he was so reluctant to come forward with it is that it felt like he was confessing a murder. I think that's a direct quote. And his original plan was to wait until his death to release this because it flied in the face of contemporary knowledge and understanding about the way that the world worked.

Dan Riley [00:45:10]:
And obviously, I don't think we're at a level, we probably both would agree, or we're not at a level at this point to make those sorts of claims necessarily about DMT, but to put on the speculation hat for a minute, what is your potential hypotheses here about what this molecule really is or might be? And that perhaps with the studies that you're doing right now or about to do, could begin to peel back a little bit and increase our knowledge about what might be going on here.

Jon Dean [00:45:50]:
Yeah. So, Rick, I think he lays it out pretty clear that he's speculating, right? Yeah, he shows if one were to wildly speculate, and then he proceeds to be the one to wildly speculate. It's very hunter Thompson of. I mean, I don't, it's, I think it's important to think big like that and to have some theories that are exciting and they could potentially be dead wrong. But it inspires people to have imagination, imagination and creativity. It's so lacking in science, kind of because everybody thinks it has to be rigid and mechanical and materialistic, which, I mean, are sort of important qualities for science also kind of keeps things grounded a little bit. So we're not there yet, clearly, and we're not there in terms of being able to answer those questions. I think that it's an interesting hypothesis, and Rick and I have talked about this to a pretty large degree, that there could be much like we talked about the endogenous opioid system, the endogenous cannabinoid system.

Jon Dean [00:47:26]:
There could be a system that isn't necessarily the serotonin system that is engaged by psychedelics. And a prime candidate for that system would be an endogenous DMT system, right? Because it's a molecule that has psychedelic properties that exist naturally. So if we understood more about how that compound exists in our bodies and what its physiological role is in our bodies, that's kind of step one before asking the bigger questions. But cannabis is psychoactive, opioids are psychoactive, and no one disputes the presence of those systems in our body. So I don't think we should write off the potential for DMT to be involved in the response of. So say you administer, and this is an easy study too, what can be done in rodents right now, if you had the funding, if you have a way to measure DMT reliably, which in rats we do, especially at the University of Michigan where we conducted those studies, and my friend Nick Glenos, who took over a lot of that with my old PhD advisor Dinesh Paul and Jimo Borgain, he has some pretty exciting data that you can pull it up now from his thesis, where he replicated the findings that we found with DMT, with that measurement system of the probes right in the brain. And he took it to a slightly higher degree of specificity too. We just did HPLC.

Jon Dean [00:49:06]:
So high performance liquid chromatography, and it's just an analytical chemistry technique of a way that it's like bread and butter, to measure a compound like the purity of it or the concentrations of it. And then he coupled it to an additional technique that literally looks at a much more particle level, so to speak. So it's like HPLCms is what it's called, it's more sensitive. And what he saw was they found very similar to what we found, concentrations of DMT in the living ronant brain, very similar to the couple of nanomores that we saw. And we were looking in the visual cortex and he looked in the frontal and in the parietal cortex and saw. And you could pull up his thesis online, you could find the PDF somewhere, found DMT levels higher than dopamine in those brain areas. So having the ability to have that assay, you could do the study where you just administer psychedelics, like say you give a rat psilocybin and then measure changes in DMT. It's a scratch the surface type of way of understanding.

Jon Dean [00:50:30]:
Step one is do DMT levels change? Are they modulated by administration of an exogenous psychedelic? So it's not really like super mechanistic, but at least it's like you're moving the needle. And that's kind of the first step in my eyes. And similar things could be done in humans if we had a way to reliably image in a living human brain, like with pet imaging or something like that, which we are slowly chipping at here at UCFB. So that'd be kind of like the gold standard, but from Rick. And that's kind of the Strassman quote that when you said that, it made me think of our conversations about an endogenous psychedelic system. Kind of like the endocannabinoid system or the endogenous opioid system. But it's even more intriguing in this case because the molecule is the same molecule that's psychedelic. Whereas to my knowledge, the synthetic opioids that are administered and the cannabinoid, the endocannabinoids aren't the same as what's in the plant.

Jon Dean [00:51:41]:
You know what I mean? So rather intriguing, but I don't know. I mean, yeah, imagine, speculate and keep it grounded. Step one is to do the really foundational stuff, but if that research doesn't take place and then you can't push it forward anymore. So it would be very unfortunate if more groups weren't looking into why the body makes molecules that have psychedelic properties, at least in large amounts of exogenous administration. It's a very fascinating question, for sure.

Dan Riley [00:52:25]:
We started this conversation with you talking about how, as I understand it, at least part of your interest in all of this came from knowing someone who died young. And probably in addition to the pain, I'm sure, of losing your friend. Just looking for answers as to like a child would, trying to wonder what it means to be human, what happens after we die? And I'd be remiss if I didn't ask you, I mean, in all of your years of working in this field, and I'm sure you have conversations like this all the time, how has your work in this field, and I guess with DMT specifically influenced your current understanding of how to answer a question like that?

Jon Dean [00:53:18]:
I don't know. I don't think it really has all that much. But I think for me personally, it's made me kind of. And this is pretty common theme to other people that have had powerful psychedelic experiences, like something that comes up in the Hopkins studies, right, or has come up all the time. This, from the participants, is this experience of taking a hero dose of psilocybin in a clinic was in the top five most memorable experiences, comparable to a birth of a child or the death of a parent or something. My mother just died not too long ago, a couple of months ago, and it was very sudden. Thanks. Yeah, it was very sudden and unexpected, so we thought relatively healthy.

Jon Dean [00:54:16]:
So I was there when it happened and was able to also go into the emergency room and just be present, like at her death. And I think that my experiences with psychedelics, my personal experiences, much better prepared me to be there for that moment, to understand that moment a little bit better. Or I guess I could say to at least understand the importance of that moment. I mean, I know that everybody that has lost somebody would say, well, that's an important moment, but I wasn't afraid to be there, basically, is what I'm saying. You know what I mean? It was just something that was very natural. It was very psychedelic experience, not quite in the classical sense of taking a psychedelic, but the effective qualities and overtones were there. So I just was kind of there meditating and trying to be as present as I could possibly be for that moment. That's the best I can answer your question, because I think that's kind of like the experience that has kind of come full circle for me, losing a friend at an early age and then having all these other experiences, researching the brain, et cetera, et cetera, because we just don't know.

Jon Dean [00:55:40]:
We could do all this neuroscience and be all smart like, and at the end of the day, it's a mystery, right? Yes, it's still a mystery. Don't understand it much better, but I think maybe don't understand the whole thing, so to speak, but just have that perspective of maybe being a little more appreciative of it all.

Dan Riley [00:56:13]:
Do you think that in heart comes from an increase for yourself in being comfortable with not knowing the answer? I will just say personally that that used to really bother me, and I think the older I've gotten, the more I've realized how little I know about almost anything. And part of, I think, the joy of accepting that is not needing to pretend that I know more than I do and being hopefully a little bit more comfortable with the unknown. I don't know if that's part of what has made some of these accepting moments easier for you or not.

Jon Dean [00:56:53]:
Yeah, that definitely resonates with me. For sure. I've kind of just learned, right? Okay. Yeah. It's okay to not know. It's just like, turn the ego off a little bit, right? Turn it down, tune it down a little bit and just kind of go with it and just be in the moment, man. For sure.

Dan Riley [00:57:23]:
I love that. Maybe we can close. I know we're getting close to the end of our time together, but I know you have a lot of work ahead of you, and I'm sure studies that you're excited about. Hopefully not today, but coming up here.

Jon Dean [00:57:37]:
It looks like it. Yeah.

Dan Riley [00:57:40]:
Where do you think we are right now? You mentioned that the psychedelic study. I'm in Austin.

Jon Dean [00:57:50]:

Dan Riley [00:57:51]:
But in history. Where do you think we are in where this increasing understanding might go in? Know. I know a lot of universities are opening up psychedelic centers. UT Austin just opened one down the road from here. Maybe we could close on kind of your hopes for the future. What do you want to study? What's really exciting you about this field in general?

Jon Dean [00:58:21]:
Yeah. I think that in terms of neuroscience, one of our collaborators the other day when we were talking about the DMT study had mentioned. He's like, you're at the perfect time in neuroscience to be asking some of these wild questions about how the brain works and how we could develop these computational models to understand it a little bit better and to understand how psychedelics perturb that and potentially elicit some of the health outcomes, et cetera. Yes, I think you're always going to say that contemporarily, we're at the best point, if you know as much as we ever have known now. But I think from a neuroscience standpoint, that's pretty true. My approach, man, is always to just stay in my lane and do what I'm good at. Don't try to oversell it, don't take too much out of it. We're just trying to do some rock solid science, help some people out if we can, and do it all as safe as possible and set it up so that tradition can continue for 100 years, 200 years, whatever.

Jon Dean [00:59:45]:
And I'm sure it'll evolve into other things. But obviously, right now, the psychedelic science is a fairly hot topic, and we just want to make sure that we're doing the research in a rigorous and reproducible way so that we can figure out what's going on with it and how to maximize the payoff for everybody involved, especially in our clinical trials.

Dan Riley [01:00:15]:
For sure. I think that's a good place to stop. I really appreciate you coming on the show and giving me the time. This was fascinating to research and a great conversation. So thanks so much.

Jon Dean [01:00:26]:
Appreciate the invite and always down to chat.

Dan Riley [01:00:30]:
Thanks, man.

Jon Dean [01:00:32]:
Take it easy.