Episode Transcript
[00:00:12] Speaker A: Welcome to brain Forest Cafe with Dennis McKenna.
[00:00:19] Speaker B: Dr. David E. Nichols, known as Dr. Dave to his friends, is one of the world's foremost authorities on the chemistry and pharmacology of psychedelic substances.
Prior to his retirement in June 2012, he was the Robert C. And Charlote P. Anderson Distinguished Chair in Pharmacology at the Purdue University College of Pharmacy and also was adjunct professor of pharmacology at the Indiana University School of Medicine.
The focus of his graduate training beginning in 1969 and of much of his research subsequent to receiving his doctorate in 1973, has been the investigation of the relationship between molecular structure and the action of psychedelic agents and other substances that modify behavioral states.
His research has been continuously funded by government agencies for more than three decades, widely published in the scientific literature, and internationally recognized for his research on centrally active drugs. He has studied all of the major classes of psychedelic agents, including LSD and other lysurgic acid derivatives, psilocybin and the tryptamines and phinephylamines related to mescaline.
His decades of experience and wide respect within the research community, combined with his insistence on rigorous methods and quality science, have set a high bar for contemporary psychedelic research.
In 1993, with the collaboration of colleagues, Dr. Nichols founded the Hefter Research Institute. Realizing his vision of a privately funded institute as the most effective mechanism for bringing research on psychedelic agents into the modern era of neuroscience, that vision was more than prescient. Since its founding, the Hefter Institute has emerged as a leading force advancing psychedelic research in numerous institutions. Since its founding in 1993, Hefter affiliated researchers have accounted for 63% of top cited articles on classic psychedelics.
I was proud to be among those scientists originally invited to join the board of the Hefter Research Institute in 1993.
And today I'm equally proud to invite Dr. Dave, my colleague and good friend, to share his wisdom with us.
[00:03:17] Speaker C: So Dr. Dave, welcome to the brain forest cafe.
[00:03:23] Speaker A: Great to see you again Dennis.
[00:03:25] Speaker C: Great to see you as always.
So I really appreciate your taking time to talk to us about this. Obviously we share a long history. We've been in this game for longer than most people, actually. And maybe we've learned a bit about psychedelics, but your achievements in the field are just staggering. I don't have to be the one to tell you that. I was just looking at your publication record at Pubmed. How many papers with Nichols de as an author were on them? Nearly 400 papers.
That's pretty impressive.
[00:04:12] Speaker A: Yeah, well, got to do something, I guess so.
[00:04:19] Speaker C: Well, that's one way to look at it. But you didn't get into this because you had to do something. You got into it because you were passionately interested in psychedelics and how they worked and some of these other mind altering substances. But psychedelics was your main focus. Would you say that's accurate?
[00:04:45] Speaker A: Yeah, I was very lucky. In the right place at the right time as well.
[00:04:50] Speaker C: Yeah, I think many people weren't. I feel the same way. I mean, we had different tracks. I never became a successful academic, and I sort of lost interest in really becoming that. But I was able to work within institutions that gave me chances to work on things I was interested in. But I was never on a track to become a prominent tenured professor as you somehow managed to do probably production.
[00:05:26] Speaker A: I'm writing my memoirs and the title is the accidental professor.
[00:05:32] Speaker C: There you go. That's a good one. So you're writing a memoir?
[00:05:38] Speaker A: Yeah.
[00:05:44] Speaker C: When is that going to be published?
[00:05:47] Speaker A: Oh, I don't know. I have to find somebody that wants to publish it first. I'm going through doing final edits. The beginning is boring. It's about my early life. And then I get into sort of my sociopathic behavior as a teenager, making explosives and tear gas and blowing things up, and then got into graduate school and somehow managed to end up working on psychedelics. And from there on it was like in my groove.
[00:06:17] Speaker C: Yeah, that was the groove. And you stayed in it from 1969 to the present, and you're still in it. So what do you look at about all that's happened in psychedelic research in the last decades and particularly the last couple of decades? What rises to the top? What impresses you most?
Are you happy that psychedelics are now almost respectable? Lots of people are wanting to investigate them, or what's your about where they're at right now? Because it's a long way from the founding of the Hefter institute 30 years ago.
[00:07:04] Speaker A: Yeah. I never imagined really we'd get here.
It was at a hefter meeting and some woman asked me, where do you see the future of this field is going? And this is probably 20 years ago. And I said, I don't know. Someday, probably long after I'm dead, someone will be having midlife crisis and they'll go and see their primary care physician and they'll send them dead onto a chauvin psychiatrist and they'll give them a sexual psychedelics and they'll get a new perspective. And she says, oh my God, do you think I'll be dead by then? I said, probably, but if the vector is pointing in the right direction, that'll be okay, right?
[00:07:46] Speaker C: Well you can mess.
One doesn't know how long we're going to stick around, but certainly you've been a pioneer and I think founding the Hefter institute was probably in retrospect it seems like a great idea and it was. The hefter has been a beacon of sort of leading the way. And in terms of fostering good research and all that, much more low key I think than maps. I mean maps has made many contributions but in a lot of ways they're in some ways a pr campaign and that's good, that's probably needed. Hefter kept the focus on research and worked with so many investigators and fostered so many young and old investigators in this field. And I think it shows in some ways that work has had an impact, obviously, particularly when it comes to psilocybin.
We didn't stake out psilocybin as our exclusive interest, but as it turned out we ended up, we, I mean the Hefter institute turned out kind of supporting a lot of that seminal research that's lent to the place we are today where psilocybin is kind of being recognized as the primary therapeutic.
You know, the hefter can take a lot of credit for that. And of course Roland was on our board for a long time and the man's a saint and hopefully I hope he's in heaven with the saints now because he know an incredible horse to move this work know as well as being a wonderful human being. And I think that's important too. I think it was Stan Groff who said the reason that the new wave of psychedelic research is being respected is because of the character of the people that are doing know. And I think he's definitely right about that. And Roland is one of the prime examples.
[00:10:23] Speaker A: Yeah, I was really happy to be able to recruit Roland for the, you know, I had made DMT for Rick Strassman and then he wanted to move ahead and use psilocybin. So he had a small grant and he said ok, why don't you make some psilocybin? And we started working on it and it turned out that the way Hoffman had made it originally was with a reagent. It was called benzo phosphorl chloride, but that reagent was said to be unstable and bottles of the reagent sitting around could spontaneously detonate. Well my technician Stuart came to me and he said I'd rather not work with that. And after we had a discussion I said we're not going to work with anything that can spontaneously.
So we spent out Rick's money. Rick and Straussman. He got really upset with me because he thought we had a know in the contract, you agree to make something for a certain amount of money. But with a research grant, which I saw, we had you say, we're going to propose to try to do this. And we just couldn't find a way to do it. So we worked and worked and worked for a long time. And then Bob Jesse came to me. He started working with Roland to do his study of psilocybin in normal people.
And we had figured out a reagent we could use. It wasn't a great reagent. It was a derivative of penafluorothenol. And you could put a phosphate on that and it would transfer onto silos and make psilocybin. But then you had the byproduct, you had this pedophlophenol. And because it was so electron deficient, it stuck to the endle ring, which was electron excessive. And so you get this complex. It was very hard to break up. So we made initially about 4 grams, I think somewhere around 4 grams of Roland. And that was for that study that he published 2006. That was the first study in normals. And then we went back and I looked at Alkman's patent, and Stewart hadn't looked at the patent. I looked at the patent, and he had in there tetrabenzalpyrophosphate as an alternative to what he was using. So then we started using that, and then we made 24 grams or so of psilocybin for Roland to use at Johns Hopkins. But I don't know if you were in the board meeting then or not, but Charlie Grove was supposed to do a study with MDMA and cancer patients.
And he met with the board and he says, I don't want to give cancer patients MDMA. It's a psychosimulate, stimulate their heart rate and blood pressure, and they're already really compromised. And I really don't want to give them that. What do you think we could give them? So we looked at the possibilities. I don't know if you remember this discussion or not, but we said, well, there's LSD. Of course, that was used widely in the LSD. We thought there would be immediate feeding frenzy, immediate be going, you're giving LSD to dying patients. This is horrible. This is terrible. Again, this is back in the was mescaline. We knew it was in aoticactus and native american sacrament.
And it lasts a long time. Like LSD, they both last eight to 10 hours. So if you were going to use ordinance therapy, you'd have to keep some patients overnight and release them the next day. So that would add cost to the clinical component. And mescaline made a lot of people nauseous and actually vomit. And so we said, we don't want to give sick people something makes them feel sicker. And the other possibility really was psilocybin. And people had been eating magic mushrooms for millennia, and it only lasted four to 6 hours, which means we could do it in one day, bring them in the morning, give the treatment, and then they could be discharged the end of the day. And it was fairly benign. We knew we probably wouldn't have to do a lot of toxicology tests because so many people had been eating magic mushrooms. I think it was generally recognized as safe, although some of the studies have had to do some preclinical talks, but really not a lot. And that really was the key. And then being able to make it. And now the synthesis has been improved a couple of times since my synthesis. So now it can be made in multi kilogram quantities pretty easily. And of course, Usona has made one and a half kilos by the syphilis method, probably. But I think we were very prescient in choosing psilocybin. It had been used in the Good Friday experiment that Walter Paykey had done back in, what, 62, I think.
But nobody had really talked about it. The magic mushroom story came out of Life magazine with the New York baker and Valentina, his. And so people knew of it. But I remember when I rode a plane early on after we started after night, I was sitting next to a psychiatrist and I said we were using psilocybin, planning psilocybin studies. And he said, psilocybin? What's that?
Did you ever hear of magic mushrooms? He said, yeah. I said, well, that's the active component in them. And then he was baffled that we were planning to do a study where we were going to give those to humans. You're going to give these drugs to humans? Because there was so much media, negative media coverage, really, back in those days.
Nowadays we look back and think, well, starting the hefter institute, it was a lot of fun, and we got a lot of comradeship, and we started a lot of interesting stuff. I never really thought about the fact of how banned and how negative it was, but we were really swimming upstream with respect to a lot of the media. As you know, nobody was talking about eating magic mushrooms and giving lsd to dying people and things like that back in those days. And really, I think you're right that the seminal studies that we respond to were Charlie Grove study of cancer patients in UCLA, which he published in 2011, but it wasn't really definitive because his doses had been too small. But he got it published in a top journal. And then the two studies that Johns Hopkins and New York University with psilocybin cancer patients that were both published in the same issue of journal Psychopharmacology in 2016, I really think those kind of the seminal studies that got people thinking, because now you could get approval to do the studies, you wouldn't get money to support them, but the FDA would approve the studies. And people are starting to say, oh, yeah, you can use these. And there was more media attention on what these were, and books were starting to come out. So I think if Hefner hadn't been know, you have to give credit to Rick Dobbin. He is quite a dog and pony show and raised millions of dollars to get MDMA off the ground. But in the beginning, I think he planned to look at a lot of different know. He paid for the psilocybin in the Francisco Marina study of psilocybin and OCD at University of Arizona back when. And I think Rick thought he was going to expand and cover lots of psychedelics. Well, a multidisciplinary association of psychedelic Studies, MDMA, I don't even consider as axia. It's not a classic psychedelic, but I think he had much more ambition than just doing MDMA. But once he got into the meat of the thing and realized that was going to cost him tens and tens of millions of dollars, most drug companies find this out. Most startup biotechs find out. You can't get unfocused. You have to say, okay, this is what we're going to do, and that's where we're going to put our resources and put our attention. So Rick focused on MDMA, God bless him, and it looks like it might be approved next year. And we really focused on psilocybin, which has been used widely now for lots of different indications. And I think psilocybin won't be too much farther out than the MDMA as far as getting approval from the FDA.
[00:18:35] Speaker C: So you think that psilocybin is not going to be approved within the next couple of years? I mean, it seems like there's a huge body of data now that shows it's efficacious and it's safe, and in some ways, it's almost the ideal classic psychedelic for clinical use.
What are the barriers to approval? How come it's not getting fast, not enough publicity?
[00:19:04] Speaker A: It has been fast track for dream resistant depression.
[00:19:07] Speaker C: Right.
[00:19:08] Speaker A: Like MDMA group. So I think it will come, but there are a lot of little studies, whereas Rick's focus was totally on MDMA for PTSD. So what you're seeing is small studies for OCD, small studies for smoking cessation, relatively small studies for alcohol use disorder, studies planned for eating disorders. So there's a lot of little ones, but you basically get it approved for a single indication, and I don't know if there's any. I think compass maybe is closest to being sort of the drug paradigm to getting approval for psilocybin in major depressive disorder. But all these little studies, I mean, it's certainly demonstrating the possible value psilocybin for lots of different things, but the FDA wants a single indication, and nobody is focusing all their attention on getting large enough clinical studies for single indication. So that's probably a little bit of the problem. The other problem is nobody wants to spend a whole day in a clinic. When I asked Steve Ross at New York University what he estimated the cost was per patient in their study of cancer patients, and he said when he added it all together with the clinical rental time, and that's the therapist, and the whole bed, he thought, was about $25,000 per patient, you're not going to get insurance companies to reimburse $25,000 per patient. So scalability is a big issue. MDMA.
MDMA, you have two or three sessions, and the sessions last, what, three to 4 hours?
And it's recognized that PTSD is a real serious problem, especially with veterans, and there isn't anything.
So I think with psilocybin, it's going to take longer.
It would be nice to shorten it. There are attempts to shorten its duration of action. A company that I was associated with before, Lucius Therapeutics, which was bought by beckleysidek, we developed an intravenous infusion method that looked like we could achieve therapeutic levels and get back out in two to 3 hours.
But if you get beyond that, if you look at some of the other things, like, I know there were people that were thinking of developing a molecule called two cb. You know what that is?
But there's no preclinical toxicology. And if you go with diisopropyl tryptamine, a four hydroxy dipt, which is a very short acting tryptamine, it lasts, I think, two to 3 hours there's no preclinical toxicology on that. So I think with anything else people come up with, if it does have a history of use, I think they're going to have to spend the money to do preclinical talks on it, and that's going to take a lot of time and money, and investors, they want a quick return, a quick return on their money.
[00:22:09] Speaker C: And it's difficult to make a profit on psilocybin because it's been in the public domain, and all this effort to find derivatives and so on, that could be patentable. They may be, but they're not necessarily better than psilocybin. I mean, Terrence said a lot of things, but one thing he said that I think stuck, that I think there's true is truth to he said, psilocybin is made for man.
And of course, he said it back in the made for humans. I mean, it is kind of uniquely compatible with human physiology. It's nontoxic.
Maybe the length of duration is a little bit too much. But actually, I kind of feel, for instance, these extended DMT states that people are working with, or even ketamine, there's sort of a feeling, maybe it's a characteristic of our rushed culture, but it's like there's a feeling like if you can't do it in under 2 hours, then it's not good. Anything beyond that. But I think you have to spend time in these states. You actually have to change the paradigm so that therapists are able to spend more time in the therapeutic space with their patients, because it takes time to work through this stuff and work it out. So the current therapeutic, it seems like they're attempting to devise the medicine to fit into the existing protocols. What they need to do is change the protocols to fit the medicine is sort of my feeling about it, and especially with things like psilocybin, or even that demands a completely different approach. But actually, I don't think ayahuasca is ever going to become an FDA approved drug. And I don't think it should mean, you know, back earlier in this century, we were talking about getting an IND for ayahuasca, and there was a lot of discussion. Well, subsequently, some people have done that.
They don't have any funding to support the research, but they do have the IND.
But I'm sort of leaning toward the idea that these plant medicines shouldn't be. With the exception of mushrooms, which you can grow by the taught, there is no shortage issue with something like ayahuasca or iboga.
These have been turned into endangered species basically because they've gotten so popular. So we have to think about that.
If you couldn't make enough ayahuasca to serve everybody's needs, there are billions of people who could benefit from it, but that's impossible to produce that much.
[00:25:30] Speaker A: Always considered ayahuasca to actually be very similar to psilocybin in terms of its effects. I'm not sure. I mean, it was attractive because it was a planned medicine and people could go to Peru or other places and have the sessions, but I was never convinced that it was superior to psilocybin. A duration of action is about the, you know, you know yourself. A lot of people know, they consider the purging as part of the process. The times I've taken and I didn't vomit and I didn't feel like I wanted to purge, I always thought it was because the ayahuasca had not been properly prepared and had a lot of byproducts in there that were emetic.
But anyway, a question I've gotten asked a lot is about this move to develop non psychedelic psychedelics, so to speak. And you've probably heard this.
[00:26:26] Speaker C: Yes. I wanted to ask you what your perspective on that is.
[00:26:31] Speaker A: So I think for major depressive disorder, just garden variety depression that people are treated with ssris, with, I think a pill is fine.
But if you talk to people that have been given, especially psilocybin in cancer patients or even in substance use disorders, alcoholics, there's a cognitive component.
I think you've watched some of the videos that, I also watched some of the studies of people that were cancer patients that were given psilocybin assistant therapy. And there's a process there going back and reexamining your past, reexamining your relationship with your siblings and your parents, looking at your life as a whole, and you really get a different perspective, and there's something that changes about your perspective on your view on life and death, your view on death. It's not so frightening for those people anymore. Whatever has happened, the parallels to the near death experience. A lot of people have a near death experience from an accident or something like that. They come back with it, from it with a new jua de viva. They're excited, they're not afraid of anything. They're much more risk taking, much more open in their personality. Same kind of thing happens to cancer patients when they have that transcendent experience. And I think that's really an important component, to be able to think about death, think about your life. Think about the things you've done, and that doesn't happen with the pill. That's not going to happen with the pill. And then, of course, the follow up integration where you can actually talk about, what do you think that meant? How did it make you feel?
We saw one of the guys in one of these studies who had become estranged from his brother for ten years. And after the session, he called his brother up and said, we need to connect again. You're my brother. I love you. Let's not let things happen like this. Those kinds of changes in perception don't occur with a pill. You need that, whatever that cognitive component is. Psychedelic does. I think the same thing is true for alcohol use disorder, substance use disorders, even perhaps for smoking.
We saw the interview at one of the after meetings from one of the alcohol use disorder patients that have been treated in a New York University study by Michael Boganshuz. And he this. I took this medicine. I went back and I looked at when I first started drinking and why I started drinking and why I kept drinking, and it completely changed his life. He'd been little with his parents, and he said every time he went someplace, he'd look to find out where were all the alcohol stores. So when he needed to drink, he knew where to go, and his life was all focused on getting alcohol. Where was he going to get his next drink of alcohol? And he said this medicine changed him completely. And I don't think that happens with pill. We've never had a pill that did in any way.
And one of the first things that the afternoon wanted to do, but we never could get any interest was treating eating disorders. That is the most lethal psychiatric disorder, and it primarily strikes young women, adolescent and young women.
And what is it about an eating a? It's a dysmorphic body image.
Always. Mark Geyer and I talked to Franz Olundweiter years and years ago about, you could take somebody with anorexia, give them psilocybin, and have them stand in front of a mirror, say, what do you see? And I don't need to tell you what the consequence of that would be, because you can imagine with what psychedelics they see, probably this ignaciated young woman that was killing herself, and that would be powerful, that psychedelics really have the ability to enhance those perceptions. So those kinds of things I don't think you get with a pill.
[00:30:17] Speaker C: Yeah, I think that's exactly right. I don't think you can separate the cathartic, ognitive experience that is intrinsic to the therapeutic effect, maybe with major depressive disorder it's an exception because maybe there's just some kind of a long term shift in the receptor ohm in some ways that chemical imbalance or something you can restore, but it's a difference in perception. I mean, on one hand, the school of thought that says we can design non psychedelic psychedelics, I mean, by definition that's an oxymoron. There is no such thing as a non psychedelic psychedelic because it's not a psychedelic, but it's this perception that it stems from this perception that people are just molecular machines.
And if we use the right monkey winch and we tweak the machine a certain way, we can be fixed. And what that does is it takes the soul out of the process. And I think a major thing, my own personal feeling is that with the reintegration, re acceptance of psychedelics into medicine, effectively you're bringing the soul back into medicine. You have to acknowledge that there's something called the soul, the spirit, whatever you want to term it, that really responds to these kinds of things. And medicine has been trying to exorcise spirit out of medicine for 150 years to say, well, we're just complex machines and that's all there is to it, and you can use these molecules and make changes. And I think psychedelics are the strongest argument, illustration, really, that that's not the case. There's more to it.
What do you make of these extended state DMT protocols that people are working with now? Apparently in an effort to, well, in some ways to have a powerful experience that's shorter but not too short, less long than psilocybin. I mean, what's your perspective on all that?
[00:32:57] Speaker A: The, I thought one of the motivations for that you, if you read this stuff from Rick Strawson's DMT studies or you watch the movie, these people thought there were aliens that they could communicate with, but they didn't have a long enough time to communicate with them.
[00:33:16] Speaker C: Right.
[00:33:17] Speaker A: I think part of motivation of these extended DMT trips was to see if they could make it long enough that they could communicate with these apparent alien entities.
I never saw anybody say, oh, well, therapeutic effect is going to be improved if we just extend the duration of DMT. Now, maybe some people have said that, but in the beginning with Strassman, Andrew Gallimore, they said, well, you don't get tolerance to the effects of DMT like you do with mehclin or LSD. So if you don't get tolerance, we can give it repeatedly or we can give it our extended period of time where we can extend that out.
I never saw anybody say, we think that will improve therapeutic efficacy. I've never heard anybody actually say that. Then that may be part of the rationale. But in the beginning I heard people say, yeah, maybe if we could extend that, we could communicate with these alien entities.
I think it's more something they're doing more for curiosity than for any real medical reason. That's just my perception.
[00:34:29] Speaker C: This was very much from the psychonautic perspective. Exactly. Yeah. These protocols were developed because of people that wanted to contact the entities. So let's get into that. What do you think about the entities?
I put you on the spot, but what do you think about these entities? I'm not sure I've ever encountered an elf machine in my DMT experiences, but many people.
What's going on there?
[00:35:06] Speaker A: I don't really know if these things are coming out of the subconscious or know we really don't understand the mind. But I had a friend, two friends that, they moved to Tampa, Florida. And he called me up one day and said, we just had the strangest experience.
My friend and I took some LSD. And in the middle of that trip, I was projected on board some kind of flying saucer. And it was this, like, reddish reptilian guy who was there. And he looked at me, saw I was there, and he was really freaked out because I wasn't supposed to be there. And I was freaked out because I didn't know who he was. And I looked at my friend that was tripping with me and I said, do you see what I see? And he was freaking out too. And he said, yeah, that reptilian thing. So I'm going. Two people share hallucination. So I'm not sure.
I suggested this to someone, and it was just pure speculation. But is it possible that more advanced civilizations communicate through some form of telepathy? And that when you take a psychedelic, it breaks down your conscious inhibitions and you're more open to that? If you read some of the books about people have taken trips to LSD, it almost sounds like some of them have had telepathic experiences that they then verified. Seeing somebody that had died, they'd come to visit them and stuff like that. So I don't know. When you open up those realms of the mind, is it possible you actually can communicate with alien beings from other dimensions or whatever?
I really don't know. It's not very scientific to think things like that. But having seen people that had paranormal experiences that I could verify in my own life.
There are things that I can't explain. And so maybe psychedelics open people up to that more so that they're more susceptible to, say, alien influences of one kind or another.
Just total speculation. I have no basis for really believing any of that.
[00:37:24] Speaker C: Right.
It's a tough area because there are so many assumptions that you have to make to talk about it like they are in other dimensions or they're extraterrestrial.
And all of this is sort of the presupposition is that they are outside of ourselves.
I haven't seen anything that in science.
There's the Occam's razor, there's the idea that the explanation that is the most elegant, that explains all the data is probably the correct one. It doesn't need all this embellishment. I haven't seen anything yet that would demonstrate that these entities are not basically products of the imagination, products of the mind in some ways. If you look at different religious traditions or shamanic traditions and so on, they're crawling with these kind of entities. They're all over the place. They're in every religious tradition. They're in shamanic experiences.
And there was this interesting book recently published on the field guide to the DMT entities. I don't know if you happen to get copy of that.
Well, they asked me to write a blurb for it, so they sent me copies, and I'm going through it. And it pretty well covers many of the categories of different categories of these entities. But what struck me is so many of them look basically like we do. They're humanoid in construction. So to me, they don't look like you and I look like normal humans, but they definitely have that same body type and that sort of thing. The vast majority of them would suggest to me that, again, these are based on inner experiences, and that does not devalue them as experiences.
You can learn from these encounters. But I don't think it proves that there is a realm of other dimensions that know you can pop open that portal and transport yourself to that dimension. That was the Terry and Denny model when we went to. And we were totally convinced of exactly that, that these things were essentially a way to visit another dimension. Well, we all know how that turned out.
Reality had a way of sort of crushing those crazy ideas because it just didn't work. And then at the end of the day, we had to say, or at least some of us had to say. I had to say most of the insights that we thought we got at La Charrero were gibberish, and they had no, meaning they were interesting as ideas, but they really have no explanatory power.
[00:40:50] Speaker A: Yeah, the most logical thing would be is that they're inventions from your unconscious. They're representations of something that theoretically, I guess if you took a psychedelic and you queried one of these entities, you could say, who are you to it? Or what do you want? And they might just dissolve, or they might say. Might tell you something about yourself that you had been wondering. But I think you're right. I mean, the most logical scientific explanation is that they're products of your unconscious that are popped up by these amazing effects of psychedelics.
[00:41:24] Speaker C: Right.
I'm basically a Jungian. I'm comfortable with the idea of the collective unconscious, and I think that's a reasonable supposition. The idea that on some bedrock level, we're all connected and individuals are like islands in the sea, we're sticking up out of the sea, but underneath everything is connected. And that may be the genetic evolutionary repository of these ideas and these notions of entities, because they're so similar in these different traditions. So I think they may represent just the particular instantiation of something that's universal in the collective unconscious.
[00:42:19] Speaker A: Yeah, I had a friend tell me who had spoke some fibroflexy DMT, that he had this vision, and it was like a big pipe that had this intense light inside, and the pipe had little holes poked in it, and the holes were people's souls were shining through. We were all part of this light inside that was shining through, but we were all coming out as representations, but everything was all one. So those kind of little pokes in the pipe that were letting the light true, I guess they could be distorted all kinds of ways, right?
[00:42:59] Speaker C: Yeah. It seems that these are common motifs. So there's something about the way these things are structured, and maybe there are commonalities in the dying process.
I think it's pretty clear that Rick Strassman's notion about the activation of pineal, you pretty much put that to know. You've demolished that idea. But some of recent researchers from, I think, the University of Michigan that John Chavez is showing have that DMT is in the brain. It's not concentrated in the pineal, it's actually in the cortex and in various parts of the brain at concentrations that are comparable to serotonin and dopamine and these other neurotransmitters. What's your perspective on those? Why isn't there more research on this cortical, the role of DMT in the cortex or in general on the brain? Forget the pineal. It's not about the pineal. The pineal is some kind of romantic, mythical construct. But the fact that DMT is in the brain is pretty well established now.
[00:44:20] Speaker A: So what's it doing?
I don't know if it's established in there that is physiologically relevant concentrations. The papers I've seen, I think it's really a long shot. I don't know if you need to invent DMT to talk about changes in cortical function because normally serotonin activates the serotonin two a receptors of the cortical prevail cells, which are the major computational units in the cortex. So when you meditate or fast or do a the kinds of ancient traditions that produce changes in consciousness, I don't think you need to invoke an exogenous or I guess if you argue that it's there, I don't think you need to invoke that because you get serotonin there already. Serotonin and norepinephrine both activate cortical primal cells. So just a change in the electrical conductivity of those cell membranes in the cortical cells is enough to do it. So I don't think you need to invoke another agency just because we know it's a psychedelic.
[00:45:32] Speaker C: You're saying that serotonin is the main endogenous psychedelic?
[00:45:39] Speaker A: Yeah, that's the main neurotransmitter that regulates tone in the cortical primal cells. So you can change the release of serotonin, shut it down and increase it, and you're going to change the conductivity of the premonal cells, which is what's essentially at the heart of the psychedelic experience, I think. So you don't need to invoke another drug. The only reason they bring it out is because they know that if people smoke in or injected, it produces these powerful changes in consciousness because it acts at the same receptor and serotonin accent, but in somewhat different way.
[00:46:16] Speaker C: Right.
So perhaps through meditation or other techniques, you could actually activate this serotonin circuit, and that would be the basis of the endogenously induced mystical experiences. In effect, it's really a serotonin trip in sort of like we're on a serotonin trip all the time in the sense that serotonin, all these neurotransmitters help synthesize this reality hallucination that we inhabit.
[00:46:56] Speaker A: Yeah, I think that's true.
You've got serotonin tone there all the time. It changes when you go to sleep and go into REM sleep.
I would be willing to bet if you got somebody who is doing a long term meditator, if you could take a sample of his cerebral spinal fluid while he's meditating, I don't think you'd find any DNT there. I just told him I think the natural transmitters you modulate those to just any variety of tried and true methods that have been used by vestics through the years, and even a spontaneous vesticle experience. I don't think you need to invoke DMT. You can change the electronic electrical potential those cells just with your ordinary physiology.
So that's what I would say. I don't think you need to invoke another substance. And the only reason they do is because they know it's a powerful psychonote. So they fought really hard to show that it occurs in the brain and it occurs in the pineal gland, and it's really powerful when it stimulates serotonin two a receptors and sigma one receptors. But they've worked to try to show that, and I don't think it would be that hard to show. If it was really that important.
[00:48:21] Speaker C: Well, that work should be done then that would be very interesting to do that.
[00:48:27] Speaker A: But you won't get anybody to fund it.
So that's the problem.
[00:48:31] Speaker C: That's a problem. Well, funding psychedelic research is sexy.
Funding serotonin research and ordinary physiology, even extraordinary physiology doesn't have quite the cachet. But, well, research, the decision studies, not based on science, but other factors.
[00:48:57] Speaker A: The studies that were done essentially strangulating rats and showing that they had this massive increase in neurotransmitter release in the brain, well, dopamine was released, serotonin was released, and maybe some DMT was there, but it was a massive release of norepinephrine, dopamine, serotonin and all kinds of things, as well as endogenous opioids, endorphins, and that's endorphins are produced under times of stress. So I think there's a whole soup of things that are dumped into the brain if you're near death. And I don't think you need to invoke DMT. In fact, I would say the endorphins are probably more powerful in inducing all good states of consciousness under stress than some of the neurotransmitters are.
[00:49:47] Speaker C: Right? Well, this is probably closer to the truth. It's not what people want to hear, but there's something.
Basically what I'm taking away from this is the process of dying is almost by definition a stressful process, and you're going to get a cocktail of things that are released into the brain. DMT may be one of them, but certainly that's not the whole picture. And yeah, the endorphins and those sort of things, but they don't induce psychedelic experiences. Exactly.
Endorphins.
[00:50:31] Speaker A: Well, they produce altered states of consciousness. Right, right.
We haven't had anybody who actually has died and come back from the dead to tell us that the experience was not like endorphins.
[00:50:49] Speaker C: Yeah, that's the conundrum. We've have lots of reports of near death experience, but those are not death experiences.
So they're a reflection of your neurochemistry and state of mind while you're. Then, you know, then you come back. You don't cross the threshold.
Nobody comes back to tell the story of what it's really like after you cross the threshold. Which makes me wonder, Dave, what do you think happens when you cross the threshold? Or do you want to, as a scientist, chemist, and pharmacologist, what's going on? Is there life after death?
[00:51:41] Speaker A: Because of the things that I've seen and heard from other people, I think that our spirit survives death.
That's my personal opinion. And one of the reasons my first wife had all kinds of weird experiences, and she would see things that were going to happen before they happened and before I went to grad school, she described the apartment we were going to live in, and it was to a t. And she was always saying things like, and if she'd get a headache and she'd say, oh, somebody's going to die. I've got this terrible headache. And the next day her mother would call and say, uncle, such and such died. And the thing that I remember the most was her father had developed cancer and he had been in remission for a while, but then started going downhill, and this was in the summer, and she woke me. And I was very interested whenever she had a dream, because her dreams are always so vivid. What was your dream about? When is your dream? She woke me up and she said, I had a dream last night. It was really vivid. And what was it? Well, my father's mother, her paternal grandmother, had come to her in a dream, and she said she died when I was four years old. If you'd asked me to describe her, I couldn't tell you. But in the dream I knew it was her. She said, I'm coming on the 16th at 06:00 a.m.
The 16th at 06:00 a.m. This is like August what does that mean?
So time went on, and it was October 15, and he had been going downhill.
His cancer had started in his prostate, and it had spread into his liver, and he was jaundiced and emaciated.
Anyway, she called and told Maxine. She said, I'm afraid it's close. Your father is refusing to rest. And he had said, when his mother died, she came to him in a vision and said, someday I'm going to come back for you. And he remembered that. So he said, I don't want to be asleep when I die. I want to be awake when.
So she called her daughter, my wife, and said, he's refusing to sleep. I'm saying, Mac, get some rest. Just get some rest. He said, no. He refused to go to sleep. So we hung up the phone and she said, well, now we'll see. It's tomorrow at 06:00 a.m. I looked at my watch, and it was the 15th. I said, oh, your dream. 16th at 06:00 a.m. And he died the next morning at 06:00 a.m. On the 16th, which is what she had seen in that dream.
Now, my son maintains that maybe people from the future can go back to the past or whatever, but for me, the simplest explanation was that his mother, Eric, had lived on. Come and told Maxine this when I'm going to come to get him. So there was a date and time that I could verify personally, and that's actually what happened. So when I look at things, like then I had a wife named Barb, who had a number of wives, actually, but her son, her brother Sonny, had been in a wreck in Florida. He'd run away from home because their father was so brutal. He'd run away. He was 15 and had been in a wreck in Florida, a car wreck, a fairly serious wreck. And she was asleep and she said she woke up and Sonny was standing at the bottom of her bed. He walked over, kissed her on the forehead, and then just sort of shrunk down and shot out on top of the ceiling. And she couldn't move. She was paralyzed. And then when he shot out, she jumped up and ran out of the hall. And her mother came out and said, were you just in our room? Someone was just in our room. She said, no.
And so that apparently was a point in time at which he had actually died. He had been injured so seriously that he died. And she was able to connect that to his time of death that he'd shown. He'd come to tell her that he'd loved her and he missed her. Now, it could have just been a hallucination, but I don't know how she would have known he would have been dying at that exact moment.
And I used to read a lot of paranormal literature, and people would say, I saw such and such was on an ocean voyage in the days when they had wooden ships. And he came to me and stood to fill the bed and told me that he was all right and he was going to be fine, and he loved me and he missed me. And then, of course, back then, it would take two weeks before you'd get a message. So then two weeks later, she messaged that the ship was lost at sea. And that was exactly when it was. So I read a lot of that stuff, and I think there's some art of us that survives, and I don't have any clue what's afterward, but I think there is some part of us, some energy part of us that survives. That's my person.
[00:57:02] Speaker C: Coming from you, that is pretty reassuring, because you, as kind of a very reductionist, hard science kind of guy, of course, I know you have a lot of funny ideas that you don't talk about publicly.
You're deeply interested in aliens and that kind of thing.
Well, we won't go there.
Keep that off. But that's very interesting that you say that. I'm reassured by that. I've been sort of leaning toward the idea that there isn't. It's hard for me to understand how you can.
You need a brain to support these processes. You need some kind of a physical substrate to support consciousness. And how can it exist without that infrastructure or that underlying physiological structure? And when that's not working, then I think consciousness maybe can't exist without that framework. At the same time, keep in mind that we don't know very much. We have to keep an open mind.
[00:58:22] Speaker A: Someone asked me once about that, that's sort of the same question. I said, suppose that we have this life force, a field of consciousness, and the brain is just simply a transducer that brings that information into a three dimensional body.
[00:58:39] Speaker C: Well, it's possible, yeah. So the brain is more of a receptor for some kind of psychic field. I mean, I'm okay with that. I think the brain is definitely a processor of this information, this idea that you receive information through your sensory neural interface portals, and then the brain kind of takes that information and associates it with memories and other kinds of random thing and kind of extrudes this reality hallucination that we inhabit, which is ordinary consciousness. I guess what they call it now is the default mode network. But I prefer reality hallucination in the sense that we inhabit a model of reality. We don't inhabit reality itself. We never see that, but we see our model. That's the bubble that we live inside.
And that is like a waking dream in some ways.
So anyway, I don't know if we'll ever.
[00:59:56] Speaker A: You realize, of course, you're just a figment of my imagination.
[00:59:59] Speaker C: Yeah, and you're a figment of mine, too. But we got to agree that there's something out there. Yeah, exactly.
[01:00:07] Speaker A: That's the thing when you get into matters of philosophy. And so, of course my wife thinks, when you die, that's it. But yet she had a paranormal admit that she can't explain. How do you explain that? Well, it just happened.
I think there's more going on than what we understand.
[01:00:31] Speaker C: Yeah.
Well, it's been a very interesting conversation. Thank you for. I have one last question.
Maybe you can answer it and maybe you can't. But when you see where we were 30 years ago with the Hefter institute, when the Hefter institute was founded, we're now in this place with psychedelics where they're being accepted into medicine and everyone.
It's always a two edged sword. Where do you think it'll be in 20 years?
Or do you even think about that? You and I will be long gone.
[01:01:09] Speaker A: But 20 years, I have no expectation of living to be 98 years old.
I'm hoping that it continues on and we figure out how to make it scalable. And I think that mental health of western civilization will be vastly improved. One of the things know they found with psychedelics and the studies that Roland did at Jaws Hawkins was that psychedelics increase the personality trait of openness.
You're more open to new ideas, you're less biased in your beliefs, which means less bigoted, less racially bigoted.
I think it will be good. And I think the shaman, when they were using these in ancient societies, they were curing all kinds of people, but probably they were also curing bullies and mean people and trying to make them more acceptable to the rest of the tribe. So I think in 20 years, if these can be scaled up and people start using them routinely, and I think they'll be used for things that we can't even anticipate now, I think we'll be much better off as a species and as a society. In fact, if you look at what we're doing, people that take psychedelics, they look at the air pollution or water pollution. And many of those people get really cranked up about what we're doing. And in the were taking LST, they were the ones that really shocked at what we're doing in the planet. They were anti war, things like that. They're all good perspectives. So I think more proliferation of that. In fact, I could see in the future that you could even have sort of not a barn mitzvah, but something comparable where you get to be 15 or 16 and you would have a psychedelic session just to get the crap out of you that had been put into you by propaganda and dysfunctional parenting, et cetera. So I think the world would be a better place if psychedelics took their.
[01:03:18] Speaker C: I agree.
It's interesting that effectively, I think what you're saying is they can be catalysts for opening our minds, increasing tolerance, helping us be better, more compassionate people. And right now in our society, the trends all seem to be in the opposite direction. It's all about ardulizing, pointing at different groups and saying, you're not like me, and you must be suppressed, or you must be.
I've sometimes said psychedelics are potentially catalysts, or they're medicines for the soul, and I mean the individual soul, but also the collective soul. If we could find a way to integrate these into society in a way that respects what they really are without stuffing them into necessarily a clinical context or some kind of way to deliver them to people, that emphasizes their ability to open people up, to basically educate people on the moral level, to really internalize these ideas that psychedelics bring to the front, bring to the forefront, that we enunciate, but don't always interiorize the idea that we are all one.
That's the basic thing, that we're not separate from each other or nature, any of it. We're all part of this matrix. And the perception we have that we're separate is an illusion. It's part of this reality hallucination that we construct, and it's important to disrupt that. And that's what psychedelics do very well. But, yeah, I hope that they'll still be around and we'll figure out how to use them a better way.
[01:05:29] Speaker A: I think sense studying is crucially important because you and I both have known so many people that use recreational psychedelics who are just assholes, and they have to be used in the proper context, where the set and setting the goal has to be to really look around you, look at the humanity around you, look at the way the world is structured and how you fit into it, and your place as part of the whole and perspective that allows them to be the kind of catalyst that they can be and not just used kind of willy nilly. And I think that's important that they be used in the proper context.
[01:06:09] Speaker C: Right, exactly. And it doesn't have to be clinical.
In some ways the ceremonial context is somewhat better, but I often say with ayahuasca. Ayahuasca is a liquid, it will fill whatever vessel you create for it, but it needs to have a vessel. There needs to be a container for the experience, and I think that's true of all the psychedelics. So that's the challenge, to create those containers that enable them to work rather than waste our time trying to make non psychedelic psychedelics. Maybe it's worthwhile from a science point of view, but I don't think it's going to improve the use of psychedelics.
Anyway, it's been a great conversation.
[01:07:05] Speaker A: What a long, strange trip been, Dennis.
[01:07:08] Speaker C: What's that?
[01:07:10] Speaker A: What a long, strange trip it's been.
[01:07:12] Speaker C: Well, it's been a long, strange trip, that's for sure. And it's not over yet and it's still plenty strange.
So thanks very much, Dave, it's been a wonderful conversation and appreciate it. Well, I'll see you on the Zoom call on Sunday, I guess. But I hope to see you in person one of these days.
[01:07:37] Speaker A: Yeah, I miss you.
Hefter board meeting is Sunday, right?
[01:07:42] Speaker C: Yes.
Didn't even get into the hefter much, but it is what it is.
It's amazing that it's lasted this long and it's still a.
So that's good. It's very different from what it started out, but it's still doing good things. And you started it, Dave.
You deserve credit for that.
[01:08:11] Speaker A: Well, I hope I get some good karma and if we live multiple lives in Debuke the next summer and I'll get some of that karma back.
[01:08:20] Speaker C: Right.
All right, well, we'll end it here and have a great day.
[01:08:27] Speaker A: Thanks, Gwell.
[01:08:30] Speaker C: Take care.
[01:08:45] Speaker B: Thank you for listening to brain Forest.
[01:08:47] Speaker A: Cafe with Dennis McKenna. Find us online at McKenna academy.
