Beyond the Mainstream: Insights from Psychedelic Chemistry, Culture, & Consciousness

Podcast Highlights

• The history of psilomethoxin and Hamilton’s own experience with it.
• The limitations of reductionist approaches to understanding psychedelics.
• Exploring the well-documented history of bufotenine and its subjective effects.
• Hamilton’s takeaways from working on Hamilton's Pharmacopeia.
• Hamilton on maintaining a balanced perspective in psychedelic journalism.

Show Links

1. Hamilton’s podcast
2. Hamilton on Instagram
3. Hamilton on Twitter
4. Hamilton's Pharmacopeia
5. Alexander Sherwood, Ph.D.’s paper on psilomethoxin
6. “Lysergic” by Krystle Cole
7. “Pharmako Gnosis: Plant Teachers and the Poison Path” by Dale Pendell
8. (podcast) Episode 120: Brian Muraresku - Psychedelic Sacraments and the Roots of Modern Religion
9. (list) Psychedelic Films and Videos

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Podcast Transcript

0:00:00.0 Paul F. Austin: Welcome back to the Psychedelic Podcast by Third Wave, connecting you to the leaders and pioneers of the psychedelic renaissance. My name is Paul F. Austin, and today I am speaking with chemist, journalist and celebrity documentarian, Hamilton Morris.

0:00:18.7 Hamilton Morris: These neuroscientific frameworks for conceptualizing the action of drugs are almost like personal mythologies that they create that have nothing to do with neuroscience. There's this kind of strange way of talking about it that has, if anything, just increased my appreciation of Alexander Shulgin and how much emphasis he put on the value of experience, as did Terence McKenna, the supreme value of direct experience as the ultimate measure and the most sophisticated high resolution tool for the analysis of these drugs.

0:01:01.7 Paul F. Austin: Welcome to The Psychedelic Podcast by Third Wave, audio mycelium connecting you to the luminaries and thought leaders of the psychedelic renaissance. We bring you illuminating conversations with scientists, therapists, entrepreneurs, coaches, doctors and shamanic practitioners, exploring how we can best use psychedelic medicine to accelerate personal healing, peak performance and collective transformation.

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0:04:56.9 Paul F. Austin: Welcome back, listeners. This is Paul F. Austin, Founder and CEO at Third Wave, and today I'm thrilled to bring you a conversation with the one and only Hamilton Morris, the psychedelic chemist and researcher who's best known for his docu-series Hamilton's Pharmacopeia, released by Vice TV. By the way, if you haven't watched any of his episodes, you're in for a real treat. It's a fascinating exploration into various psychoactive substances and the science and lore behind them. Hamilton and I had a chance to connect in person at the 2023 Wonderland Conference in Miami. Our conversation begins with a deep dive into the scientific and historical perspectives of some lesser known compounds like bufotenine and psilomethoxin, unraveling the intriguing history around psilomethoxin including Hamilton's own experience with this interesting compound.

0:05:52.9 Paul F. Austin: Hamilton also guides us through the nuanced world of psychoactive substances, drawing from his extensive background as a psychedelic chemist who offer insights that go beyond the mainstream narrative. Along the way, we confront the limitations of reductionist approaches to understanding psychedelics and dive deep into the subjective experiences that these substances offer. Hamilton also shares some profound takeaways from his work producing Hamilton's Pharmacopeia. And we navigate the complex terrain of psychedelic journalism, discussing the challenges of maintaining a balanced perspective in a rapidly evolving field.

0:06:32.5 Paul F. Austin: This episode is a rich and nuanced conversation on psychedelics drawing from the insights of legends like Alexander Shulgin, Terrence McKenna, and many others who have paved the way for us as a culture to have a deeper understanding of the psychedelic experience. I hope you enjoy the episode, I'm sure you will. But before we dive in, a quick reminder to follow The Psychedelic Podcast wherever you listen to podcasts. And if you haven't yet, you can help more people find this show by leaving a review. It's a simple and small action that only takes a minute, but it goes a long way in helping us to amplify psychedelic awareness, shifting the cultural conversation around these important medicines. All right, that's it for now. I hope you enjoy my conversation today with Hamilton Morris.

0:07:20.0 Paul F. Austin: All right. Tell us about psilomethoxin. I heard you got some psilomethoxin sent to your lab and did some things in it. What's going on with psilomethoxin, Hamilton?

0:07:30.4 Hamilton Morris: Yeah. Yeah. I mean, it's interesting, it's sort of sad I think what happened where, I mean, you know about the background on it. Actually Symposia wrote some good articles about it I thought, they did a very thorough dissection of the matter that listeners can check out if they're curious. But I was interested in this for a while because there was this German mycologist and chemist named Jochen Gartz. And he published a lot of these seminal papers on the chemistry of psilocybin-containing mushrooms that, especially at that time, were very unusual. A lot of basic work on the presence or absence of various tryptamines and different species but also he was interested in how the substrate that mushrooms are growing on can alter the chemical composition of the fungus.

0:08:37.7 Hamilton Morris: And so, I mean, an obvious example would be the presence of tryptophan is the necessary biosynthetic precursor for all of these tryptamines. So his, I believe, first contribution to this area was, well, what if you increase tryptophan? If you have a higher tryptophan substrate, does that result in mushrooms that have a higher concentration of psilocin or psilocybin? And I believe it did. And then he took it a step further and said, okay, well why don't we cut out one of these steps of the biosynthesis and just introduce tryptamine so that there doesn't need to be any enzymatic decarboxylation of the tryptophan.

0:09:14.3 Hamilton Morris: And not only did it work, according to his results, he detected the highest concentration of psilocin ever found in psilocybe cubensis. I think it was at least 2.3% and maybe even higher. So really extraordinary. And then from there, and I think I'm getting the chronology of this right, but it's possible things were happening in a slightly different order. He decided to take it another step and thought, okay, if you can directly modulate the levels of tryptamines present in the fungus by adding these chemicals to the substrate, what happens if you add a completely synthetic material that is not found in nature like DET?

0:10:03.5 Paul F. Austin: What's DET?

0:10:04.1 Hamilton Morris: Diethyltryptamine, a now incredibly obscure psychedelic that at one time was actually one of few psychedelics that were available in the 1960s because nobody was extracting, nobody who wasn't indigenous was extracting DMT from plants. And when I say extract, I'm using the loose definition where a tea would be considered an extraction, but nobody was doing mimosa hostilis root bark extractions in the 1960s. If anybody tried DMT, it was because they were synthesizing it. And if you're synthesizing DMT, you can make anything else with the same synthetic root, any other dialkyltryptamine.

0:10:45.0 Hamilton Morris: If you wanna make DET, you substitute diethylamine for dimethylamine, it's actually easier to handle because dimethylamine is a gas, it has to be transported in cylinders, whereas diethylamine is a liquid at room temperature. So it's a little bit, I mean, it's not hard to bubble dimethylamine through the reaction mix, I've done it many times, but this is a little bit easier. So for them, they thought, why not do this? And on top of that, it's not a substrate for MAO. So it's orally active. And there was even a folk toxicological idea in the 1960s that the metabolic liberation of methanol from the de-alkylation of the basic nitrogen could produce neurotoxic effects after consuming DMT.

0:11:27.5 Paul F. Austin: Really?

0:11:28.3 Hamilton Morris: I mean, this is not true, but this was a concern. Yeah. So much of what we think about these drugs we take for granted now, but in the 1960s, not only was there fundamental uncertainty about the safety of LSD, there was about things like DMT as well. And to them it was like this new dangerous synthetic stuff that people were making. They didn't think of it as so intimately linked to indigenous practices and a long history of use.

0:11:53.5 Hamilton Morris: And it's easy to say something like, oh, those methyl groups are metabolized into methanol, that's a neurotoxin and freak people out. So then the claim was, okay, but DET is safe because that will produce ethanol instead of methanol, which is not as toxic. So DET is the safer alternative to DMT, this is, at least one source was making this claim. So people had access to DET and it is a wonderful substance. It's a Schedule 1 controlled substance now, it's a darn shame that...

0:12:22.5 Paul F. Austin: What is it like?

0:12:24.8 Hamilton Morris: It's sort of like LSD I would say. It's less...

0:12:28.3 Paul F. Austin: So more similar to LSD than DMT?

0:12:31.9 Hamilton Morris: The doses that I've tried, yeah. I've never gotten as prominent visual effects from it. Kary Mullis synthesized DET and erased his own identity completely and went into a sort of almost dissociative fugue state for days and his friends had to reprogram him. He writes about this in his autobiography. Everyone always talks about the connection between LSD and the discovery of PCR, but before that he had synthesized DET and erased his identity.

0:13:01.9 Paul F. Austin: What does that mean to erase your identity?

0:13:03.4 Hamilton Morris: He didn't know who he was.

0:13:04.7 Paul F. Austin: Oh my God.

0:13:05.3 Hamilton Morris: And he doesn't say how much he took either.

0:13:06.6 Paul F. Austin: It's almost like amnesia.

0:13:07.8 Hamilton Morris: Yeah, yeah. I mean, this is what he describes. I've always wanted to track down, 'cause he describes the friends that helped him relearn who he was by reading him poetry that he loved and I've always wanted to hear that story from somebody else's perspective. But, so DET...

0:13:29.8 Paul F. Austin: Inserted into psilocybin.

0:13:31.7 Hamilton Morris: Yeah, so DET, never found in nature, although there is one scientific paper that claims that it was found in the venom of Bufo alvarius, but that is suspect and has never been reproduced. Anyway, and then when I contacted the authors to ask what was going on, they said, "Oh, I think that's a mistake." But other than that, there's no indication whatsoever that this has ever been found in nature. The material is completely synthetic. Jochen Gartz puts it into the substrate of the P. Cubensis that he's growing and finds that these mushrooms, instead of producing psilocin or psilocybin, are producing 4-hydroxy DET, something that had never been found in a fungus previously.

0:14:11.4 Hamilton Morris: And so if his findings were real, this would suggest that you can, that there is a degree of promiscuity in the action of the tryptamine 4-hydroxylase enzyme, and you can put other stuff into the substrate and create all sorts of sort of semi-synthetic tryptamines using mycelium. And this was a really exciting idea that Shulgin speculated about, and it became part of sort of psychedelic forum lore, where everyone would say like, "Yeah, yeah, what about that thing the Jochen Gartz did, though? Someone's got to do that again." And people would kind of have to do it, but no one had access to analytical instruments, so nobody knew if it was really working. And so you'd get these kind of like half reports on the Shroomery of people sort of, they'd take and say, "Yeah, yeah, I think it feels different," or whatever.

0:15:00.1 Hamilton Morris: So you never really knew what was going on. Then this religious group that was founded by a lawyer starts selling a compound that they're calling psilomethoxin that was already a known entity under the name 4-HO-5-MeO-DMT. And this is something that had been synthesized by a French chemist named Marc Julia who is a really, really good chemist. Like one of the highest accomplishments you can have as a chemist is to have a reaction named after you. And Marc Julia has a reaction named after him, the Julia Olefination. So he was no slouch. This is a serious, serious dude, Marc Julia. And he was able to synthesize 4-HO-5-MeO-DMT via an extremely laborious convoluted route that nobody has ever been able to...

0:15:57.7 Paul F. Austin: Recreated.

0:15:58.7 Hamilton Morris: And people have actually now tried, and nobody has ever been able to reproduce it.

0:16:02.0 Paul F. Austin: Successfully.

0:16:03.0 Hamilton Morris: And one of the reasons for that is anytime you have a tryptamine that has a hydroxyl group in the 4 position like psilocin, it promotes polymerization of the molecule. That property that you see where a mushroom bruises blue or black or whatever is a product of psilocin-forming oligomers. And this is not a psilocin-specific phenomenon. In fact, it actually happens more significantly with other 4-hydroxy-tryptamines that only have one substituent on the basic nitrogen or no substituent on the basic nitrogen. So this is just a chemical property. And to even call it degradation is maybe like an anthropocentric interpretation because maybe that's the whole point, is forming these polymers.

0:16:56.2 Hamilton Morris: Maybe that serves some kind of protective effect for the fungus. But, so this is one of many things that made this chemistry daunting and something that not even Shulgin wanted to reproduce. And the idea was kind of like, oh, what if we took advantage of that process that Jochen Gartz described where you dope the substrate with a synthetic material. If you were to follow Gartz's method, you would use 5-Methoxytryptamine but for whatever reason, this group used 5-MeO-DMT. So right off the...

0:17:30.0 Paul F. Austin: Because it's well known and prominent and people know about it and like it creates a buzz.

0:17:36.0 Hamilton Morris: I guess, but you're also using a Schedule 1 controlled substance unnecessarily. It's a very odd choice, especially if it's being done by a lawyer. So that right off the bat was weird, didn't quite make sense, made it more expensive and more dangerous for them to do. But I gave them the benefit of the doubt because as far as I know, it's possible that could work. Like if somebody gets it to work, it wouldn't blow my mind. Maybe there's some slight variation in the tryptamine 4-hydroxylase enzyme in different species, maybe liquid culture, maybe this, maybe that, maybe some kind of conditions could allow that transformation to take place.

0:18:16.6 Hamilton Morris: It seems within the realm of possibility to me that something like that could happen. And so when they reported it, I gave them the benefit of the doubt and I thought, "Huh, all right." And then you have all these reports, people saying it's different. I know it's different. It feels like a microdose at any dose. There's something very, very different about it. So I get the sample, I analyze it, and there's basically nothing in it.

0:18:43.0 Paul F. Austin: Nothing different about it compared to...

0:18:44.8 Hamilton Morris: Well, actually, there kind of was something different about it, which was that there was almost nothing in it. A normal Psilocybe cubensis mushroom would have psilocin and psilocybin in it. This only had trace quantities. So if...

0:18:57.7 Paul F. Austin: Was it because it was just a very old sample? Or could there be...

0:19:02.4 Hamilton Morris: I don't have enough experience with mushroom analysis to say, but I suspect that was not the case. I suspect that if the 5-MeO-DMT was truly being included, and it did exert any effect, it may have even been suppressing biosynthesis of psilocin and psilocybin.

0:19:21.1 Paul F. Austin: Interesting.

0:19:22.4 Hamilton Morris: Maybe. Because I think this was also reported by Alexander Sherwood, that the concentrations were extremely low, if I remember correctly. I'd have to double-check that.

0:19:31.4 Paul F. Austin: And you did this independent from Usona, and Usona also carried out their own research on that.

0:19:34.3 Hamilton Morris: Yeah, and long before and didn't publish it. But what I did instead was I contacted Ian directly and told him what I had found. And I said, "This does not appear to have worked." I could have made a mistake, I don't have an analytical reference of 4-HO-5-MeO-DMT. Maybe the mass spec didn't pick it up, but based on... And I used two different mass specs. Based on the analysis that I did, it did not look like it was there. And I think that maybe there was some wishful thinking at play. Because I know that he then started saying, "Well, nobody has an analytical reference," which was true but I think he...

0:20:25.4 Paul F. Austin: You're a reputable chemist with a pretty solid track record, I mean.

0:20:28.4 Hamilton Morris: Well, I mean, no, I'm not making any kind of claim that what I did was definitive but it should have been taken into account.

0:20:35.6 Paul F. Austin: For sure.

0:20:35.8 Hamilton Morris: Yeah. And yeah, especially because actually extraction of psilocin from anything is non-trivial because it's very... It doesn't like to partition from any aqueous layer into a non-polar solvent because it's almost always charged at any pH. So there actually are complexities with analysis of those sorts of molecules that need to be acknowledged. But yeah. So anyway, and then it kept going. And then Alexander Sherwood actually published. Maybe someone else actually... There may have been some intermediate person that published something, I can't remember. But Alexander Sherwood was the first person to publish a peer-reviewed analysis and found the same thing that I did. And then there was a kind of outcry. And the group was suggesting that Sherwood's affiliation with Usona represented a pharmaceutical company trying to suppress alternative medicine or something like that. And it seemed to...

0:21:44.5 Paul F. Austin: Sort of conspiracy theory.

0:21:45.9 Hamilton Morris: Yeah. It seemed to enter a sort of undignified space pretty quickly. In reality, I don't think any of this is of tremendous consequence. It's more a good story than anything else. Like how many people actually use this? Maybe at absolute most...

0:22:01.4 Paul F. Austin: I tried microdosing it once at what would normally be a dose that would impact me, I would feel it a little bit, I felt nothing, there was really no effect in taking it. And I didn't try anything beyond that because it never really resonated in a way.

0:22:17.6 Hamilton Morris: Yeah. I don't think it represents some kind of a disaster at all. It's kind of funny the way we talk about these things because it's a good story whereas somebody going to prison or something like that, it's not really a good story. It's just taken for granted. But it's actually like a far, far, far worse thing than somebody potentially getting engaged in some unfortunate self-deception.

0:22:35.4 Paul F. Austin: Right, kind of slightly fudging the... Right.

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0:24:17.4 Paul F. Austin: So you've had some transitions in the last probably two, three years. You became well-known for Hamilton's Pharmacopeia on Vice and the last couple of years, you've really turned back to focusing a lot of your time and energy on chemistry. And so I'm curious, what is it that you do in the lab, let's say, that's different from or similar to this process that you just described to us? What are you doing when it comes or how are you inventing these new psychedelic analogs? Why? What does that look like? And in reference to the last story, this was a lot of wishful thinking, what's the test of efficacy you use to figure out if a substance is worthwhile in pursuing or amplifying or understanding more?

0:25:12.1 Hamilton Morris: Well, I think that when it comes to things like depression, there are a number of different tests that exist, but their value in terms of predicting efficacy is pretty limited. I mean, the most well known example is forced swim, where you take a rodent and you drop it into a cylinder of water and you time how long it will tread water before succumbing to exhaustion. And this is used to this day, despite the fact that almost everybody knows that it is at best flawed, if not completely useless, if not worse than useless, actually a source of totally meaningless information that's a distraction. And you've got that. And then you have people debating about various biomarkers and anyone that closely follows the literature on the antidepressant mechanism of ketamine will be aware that it is all the fuck over the place. Like it is just so all over the place that it almost promotes a philosophical question about the validity of these investigations.

0:26:32.5 Paul F. Austin: By all over the place you mean some of the data shows very positive outcomes, some of the data shows very... Like there's a ton of variability in the data that they're finding, or?

0:26:39.5 Hamilton Morris: In everything. I mean, maybe the most prominent example would be that one dominant hypothesis of the mechanism involved ketamine's activation of mTOR signaling. And then it came out that rapamycin, which inhibits mTOR signaling, increased the antidepressant efficacy of ketamine. Like the complete opposite of what would be expected based on all previous work. And what does that say? I don't really know other than take all of this with a grain of salt because it is changing so quickly and is so all over the place, and people always are sort of posturing as if they know what's going on. They're like, "Oh, it opened the critical learning window. It's the default mode network, it's track B, it's mTOR... "

0:27:36.2 Paul F. Austin: I was just gonna ask you about track B because that's the new mechanism of action we're talking about. Right?

0:27:40.3 Hamilton Morris: Yeah, there will always be the new thing.

0:27:42.4 Paul F. Austin: The salience network, yeah, there's...

0:27:45.3 Hamilton Morris: Dendritic remodeling, spinal genesis, whatever. And I'm not to say that these things don't exist or that they don't place some role, but I think that if there's any lesson to be learned from monitoring this literature over the last 50 years is that it's constantly evolving and people don't even really care about this stuff. Like when you actually go to an event like this and you talk to people, you quickly realize that these neuroscientific frameworks for conceptualizing the action of drugs are almost like personal mythologies that they create that have nothing to do with neuroscience.

0:28:25.8 Hamilton Morris: So they're talking about the default mode network. And the default mode network is the ego, and it's about destroying the ego or the critical learning period is you've gotta use this moment, this opportunity that the psychedelic gives you to learn new skills. And like there's this kind of strange way of talking about it that has, if anything, just increased my appreciation of Alexander Shulgin and how much emphasis he put on the value of experience, as did Terence McKenna. The supreme value of direct experience as the ultimate measure and the most sophisticated high resolution tool for the analysis of these drugs. And that's...

0:29:15.7 Paul F. Austin: It's powerful.

0:29:16.5 Hamilton Morris: It's extremely powerful. And at the end of the day, it's the only thing that really matters. I mean, this is something that I talked about today where if I injected five chinchillas with a drug and tabulated how much they twitch their heads, people would say, "That's a very scientific study that you did." But if I were to take that same drug myself, people would say, "Oh, that's not very scientific."

0:29:40.9 Paul F. Austin: Well, our understanding of science is skewed by industrialism in a way, right? And sort of the emphasis on the mechanistic or the emphasis on the, how do we reduce this as much as possible?

0:29:52.2 Hamilton Morris: And ideas of reproducibility and objectivity, both of which are valid. But if you go so far down this road of valuing reproducibility and objectivity over the production of meaningful information, then who cares? Like you have this highly reproducible, highly objective bullshit that...

0:30:13.3 Paul F. Austin: That's irrelevant.

0:30:14.0 Hamilton Morris: That's completely irrelevant. I mean, that's not always the case. It's like some of this animal stuff actually is valuable. Like head twitch really does have very robust predictive value in terms of predicting this psychedelic activity in humans. So it's not all bullshit. And conceivably it could be better. There could be all sorts of weird things that have changed. One example would be the just extreme dominance of mice in scientific research. And that wasn't always the case. There actually used to be more animal diversity in scientific research and that gradually changed. I mean, it used to, if you look at papers from the 50s and 60s, it was not that unusual to see other things, to see chickens occasionally.

0:31:00.3 Paul F. Austin: Monkeys.

0:31:00.7 Hamilton Morris: Monkeys, I mean, you still see monkeys, but that's just, that's more of a price thing. But yeah, I feel like maybe the animal models are not as good as they could be, maybe any number of things. But I can't remember where, how we got on this.

0:31:17.2 Paul F. Austin: So how does this then inform the research that you're carrying out, or the chemistry work that you're carrying out? And maybe as like an add-on to this, I was talking with Dylan DiNardo. You know Dylan?

0:31:27.4 Hamilton Morris: Yeah, yeah, he's a cool guy.

0:31:28.3 Paul F. Austin: Runs Mindstate Design.

0:31:29.4 Hamilton Morris: Yeah.

0:31:29.9 Paul F. Austin: And so we got into this about large language models, how artificial intelligence can potentially help us to better understand through qualitative research the subjective effects of these various substances, which will then help to inform the language that we create around it. So we feel, because part of the limitation with understanding these substances is the language that we use to talk about them and discuss them. It's not, we don't have a vocabulary that's rich enough, which is where the default mode network in these, the neuroscience is making a lot of progress. And what I'm hearing from you is we need a richer vocabulary that speaks from the subjective experience, not just the purely mechanistic objective experience.

0:32:06.4 Hamilton Morris: Yeah, no, I think so. I think that if people took their own experiences a little bit more seriously, it could be tremendously valuable. Like I was interviewing on my podcast a chemist named Thomas Monroe recently, and he has always been a champion of Daniel Siebert. I don't know if you're...

0:32:28.5 Paul F. Austin: I've heard of Daniel Siebert.

0:32:29.4 Hamilton Morris: Yeah. He doesn't really get talked about.

0:32:30.3 Paul F. Austin: Salvia?

0:32:31.2 Hamilton Morris: Yeah. Yeah. He doesn't really get talked about, but he's kind of the guy who definitively established Salvinorin A as the psychoactive principle of Salvia divinorum and established how potent it was and in collaboration with Bryan Roth established that it was...

0:32:45.4 Paul F. Austin: When was this? In the 90s?

0:32:46.0 Hamilton Morris: Yeah. And he did all this by himself as a citizen scientist with no funding, no resources, and did it through careful, simple experimentation that was done thoughtfully. And that is also the case for Jonathan Ott's discovery of the psychoactivity of bufotenine. To this day, to this day, there is debate about the psychoactivity of bufotenine. At the time that Jonathan Ott was doing those experiments, there were many people who genuinely believed that bufotenine was not a psychedelic. They thought it was just a poison. And so he was able to solve that mystery very easily by extracting and purifying bufotenine from Anadenanthera colubrina. And...

0:33:35.4 Paul F. Austin: Is that Yopo or is that the toad venom?

0:33:38.7 Hamilton Morris: It's Cebil.

0:33:40.1 Paul F. Austin: What's that?

0:33:41.4 Hamilton Morris: Anadenanthera colubrina.

0:33:43.5 Paul F. Austin: What's that?

0:33:44.3 Hamilton Morris: It's the seed of a South American tree.

0:33:48.1 Paul F. Austin: And that's what's in Yopo and the...

0:33:50.1 Hamilton Morris: Yopo might be Anadenanthera peregrina. I'm not totally sure.

0:33:53.7 Paul F. Austin: Okay.

0:33:55.1 Hamilton Morris: Which has a little bit... Anadenanthera colubrina is almost pure bufotenine if not pure bufotenine, at very, very high concentrations. Yeah. So it's easy to extract and purify bufotenine from Anadenanthera colubrina.

0:34:08.1 Paul F. Austin: And it's used as a snuff?

0:34:09.2 Hamilton Morris: It's used as a snuff, also in like a traditional chicha drink.

0:34:14.4 Paul F. Austin: Okay.

0:34:14.7 Hamilton Morris: It's also smoked. Yeah.

0:34:17.6 Paul F. Austin: And this is in Colombia, Brazil.

0:34:20.3 Hamilton Morris: Argentina.

0:34:21.2 Paul F. Austin: Argentina?

0:34:21.9 Hamilton Morris: Yeah.

0:34:22.2 Paul F. Austin: Interesting.

0:34:22.8 Hamilton Morris: It's big, and really throughout a lot of South America. And it's funny because everyone is so interested in hallucinogenic mysteries and Mesoamerican mushroom rituals and ancient ayahuasca and morning glories but no one seems to care about bufotenine, which is really firmly established to be, the use of these seeds is in terms of evidence the strongest and oldest evidence of human psychedelic drug use by far, like there is slightly older stuff, but it's more cryptic in its meaning. Like there's peyote effigies that have been found along the Rio Grande that...

0:35:06.4 Paul F. Austin: I think they're 15,000 years old.

0:35:07.7 Hamilton Morris: They're very, very old, but they are not... I mean, I think we probably agree that they're probably an indication that peyote was being used as a drug or a sacrament or whatever, but the evidence for ancient use of bufotenine-containing seeds is pipes that have the residue remaining in them. It's, there's no uncertainty whatsoever. It is completely clear that people were using Anadenanthera seeds in snuffs, in smoking preparations and in enema preparations.

0:35:43.6 Paul F. Austin: Enema preparations?

0:35:44.5 Hamilton Morris: Oh, yes. Oh, yes. Oh, yes. Boofing bufotenine.

0:35:48.4 Paul F. Austin: Have you ever boofed bufotenine?

0:35:50.9 Hamilton Morris: I've never boofed it, no. I've snorted it.

0:35:53.4 Paul F. Austin: What was the experience like?

0:35:55.3 Hamilton Morris: It is both chemically and qualitatively almost perfectly intermediate between 5-Meo-DMT and DMT.

0:36:04.3 Paul F. Austin: Interesting.

0:36:05.3 Hamilton Morris: Yeah. So it's more visual than 5-Meo-DMT, less visual than DMT, more dissociative than DMT, less dissociative than 5-Meo-DMT, more nauseating than either of them.

0:36:18.7 Paul F. Austin: Okay.

0:36:19.4 Hamilton Morris: Has a slightly longer duration than either of them, interestingly, which is sort of unanticipated. It's about the same potency as DMT by weight, maybe slightly less potent, but about the same. And it's kind of interesting that nobody talks about bufotenine because it is not only a classical psychedelic, it is truly the one with the richest history of archaeological evidence for human use. There is a lot of evidence. This is not like one.

0:36:49.9 Paul F. Austin: Interesting. This is something you rarely hear about. This is something I rarely hear about.

0:36:53.5 Hamilton Morris: Yeah, because... Okay. So this all goes back, because there's still, for whatever reason, fundamental debate about whether or not this drug is psychedelic when I can assure you from personal experience, it is psychedelic. And if you look, I'm not the only one. Many other people have tried it, have confirmed that it's psychedelic. And Jonathan Ott wrote this brilliant paper where he carefully conducted a series of bioassays via different routes of administration of bufotenine and definitively established through his own self-experiments using very low-tech techniques that this is a drug. He solved the mystery. All it took was one careful, thoughtful guy extracting and crystallizing an alkaloid and trying it a variety of different ways to establish that it is in fact a psychedelic. And this has enormous ramifications for the discipline of archaeology, for understanding the history of psychoactive plants. And it just took one person doing a study that probably cost like $1000 at most.

0:37:50.5 Paul F. Austin: How is this... What's your take on the immortality key and the sort of Christian Greek lineage? I mean, we know about Kykeon, we know how it was used in the Eleusinian Mysteries. Do you think psychedelic plant medicines were used by early Christians? When that came out, what were some of your thoughts and impressions?

0:38:14.2 Hamilton Morris: I read it. I've hang out with Brian, I think he's smart and interesting.

0:38:17.1 Paul F. Austin: Brian is sharp. Yeah.

0:38:19.3 Hamilton Morris: My take on it is, first of all, I lack sufficient expertise in that area to really definitively have a meaningful take on the matter. But what I do know is that I have spent an enormous portion of my adult life trying to decipher drug practices from the 1970s and 1980s.

0:38:43.1 Paul F. Austin: Interesting.

0:38:44.3 Hamilton Morris: And it is almost impossible to figure out things that people were doing in the 1970s and 1980s in the United States.

0:38:54.7 Paul F. Austin: Interesting.

0:38:56.3 Hamilton Morris: And so when people talk about the practices of long since disappeared cultures thousands of years ago in other parts of the world, I just feel like I have no chance whatsoever of meaningfully interpreting anything about what they were doing. If I can't figure out what somebody was doing in California in 1977, how am I going to know what they were doing in ancient Greece over 2000 years ago?

0:39:32.2 Paul F. Austin: So then what makes the bufotenine archeological evidence that much more compelling?

0:39:36.3 Hamilton Morris: Because if you find a pipe with drug residue in it, that seems... I mean, I don't know. There aren't that many other ways to interpret a pipe with drug residue in the bowl. Maybe the pipe was actually a drug holder and they were just, like to hold it in their hand, but they weren't smoking it. Like, I don't know. It's pretty, the evidence is pretty damn strong.

0:40:08.3 Paul F. Austin: Right.

0:40:08.5 Hamilton Morris: Snuff trays, implements for snorting the powder, ceremonial cloth headbands, it seems. I mean, they're almost certainly snuffing implements. They are often bifurcated so that you can get both nostrils or they have some kind of, it's like...

0:40:26.7 Paul F. Austin: Almost like rapé, like a...

0:40:28.4 Hamilton Morris: Yeah.

0:40:28.9 Paul F. Austin: A rapé or whatever.

0:40:30.0 Hamilton Morris: Yeah. And the enema tubes also.

0:40:32.5 Paul F. Austin: Oh, wow. They found the enema tubes?

0:40:33.8 Hamilton Morris: Oh, yeah. And a lot of them, not like one, but hundreds, yeah. So that is why now...

0:40:43.6 Paul F. Austin: The physical evidence, it's much more significant and sufficient in this case.

0:40:48.0 Hamilton Morris: Yeah. If there were recipes of the Kykeon that showed exactly how it was being prepared with descriptions of the visionary effects or something like that. My main action, my main hesitation with this is that something like what I just described with bufotenine-containing snuffs has never been done with ergot wine preparations. With the exception maybe of the supposed ergot wine preparation made by Gordon Todd Skinner described in Krystle Cole's book, Lysergic.

0:41:25.8 Paul F. Austin: Lysergic?

0:41:27.0 Hamilton Morris: Lysergic. Highly recommend Lysergic.

0:41:28.6 Paul F. Austin: Okay.

0:41:29.3 Hamilton Morris: Yeah.

0:41:29.9 Paul F. Austin: Is it on Amazon or do you have to go on like AbeBooks or one of those sort of...

0:41:32.3 Hamilton Morris: I think you can still grab a copy on Amazon.

0:41:34.3 Paul F. Austin: Okay. All right.

0:41:34.7 Hamilton Morris: That's a real classic.

0:41:36.4 Paul F. Austin: Okay.

0:41:37.1 Hamilton Morris: Yeah. She describes Gordon Todd Skinner making a traditional ergot wine that produced a powerful psychedelic effect. But this was Gordon Todd Skinner who is a compulsive liar and a psychopath who may have just put LSD in some wine and lied to everyone very easily. So who's to say what that was? And he doesn't respond to my messages in prison, so.

0:42:01.5 Paul F. Austin: Wonder why. [laughter] Who was Dale Pendell?

0:42:06.7 Hamilton Morris: He was a guy who wrote these beautiful poetic books. He had amazing eyebrows that were like very sculptural and pointed. And I think he was one of the first people to report on the effect of Xenon, actually. Yeah. I mean, he's famous for these three books that he published that I think they came out in the 90s and had a...

0:42:35.4 Paul F. Austin: Early 2000s as well.

0:42:35.7 Hamilton Morris: Early 2000s, yeah. And they had a real cult following. I never interacted with him but I appreciated what he did.

0:42:44.3 Paul F. Austin: Did you ever read the books?

0:42:45.9 Hamilton Morris: Yeah, I read parts of them. I read his Xenon report and I read his poem about Bufo alvarius venom. I believe, it's been years actually, I haven't cracked those books in a long time.

0:43:01.1 Paul F. Austin: I found out about them seven years ago from your conference nemesis. He used to be a... We used to be close and he gave me a list of books to read and that was one of them. And I didn't read it for years, I just kept it on the shelf. And I opened up, this is Pharmako/Gnosis, the third one. And so I opened it up a couple years ago and read through it and was, I mean, the pros, the balance, the pharmacology, the science, the history, it's a very comprehensive and well written.

0:43:29.5 Paul F. Austin: And there's these beautiful assays as well about like talking sticks and the two dragon problem and a few other things that we have a training program for facilitators, and I'm now requiring that as reading. 'Cause initially it was like, go read... Like, we have these guides on Third Wave about the different substances, LSD and mushrooms and ayahuasca. And a lot of coaches, they like to know about what are the different substances in medicine. So instead of having them read even something like How To Change Your Mind, it felt like Pharmako/Gnosis was still reasonably accessible while having a lot of great contextual information presented in a, I think, beautiful and somewhat compelling way.

0:44:09.3 Hamilton Morris: Yeah. I should read... Check those out again.

0:44:12.4 Paul F. Austin: I think it's kind of like a... Not a lot of people know about it, but it's a really incredible book. I just wanted to get your take on it because you've been around in this space and because of your, especially with what you've done with Hamilton's Pharmacopeia, you've explored so many substances. Okay, so let's go to that. What were your three favorite episodes of Hamilton's Pharmacopeia?

0:44:45.6 Hamilton Morris: Well, I enjoyed different ones for different reasons. The episode with Steve Gill, which was the MDMA episode, has a certain emotional resonance for me because Steve Gill was a, just a kind of forgotten soul who had spent his life making MDMA and doing actual scientific research as well in a sort of Shulgin like lab. He was a lot like Shulgin if Shulgin did things a little differently. If maybe if he didn't stay in school and he sold MDMA and he didn't publish his findings in scientific journals, but the brilliance and the enthusiasm was there every bit as much as it was with Shulgin. And it was people like him, really as much as Shulgin, that allowed our world to appreciate MDMA because a big part of appreciating a drug is having the opportunity to try it. I think maybe one of the reasons nobody's talking about bufotenine is nobody's tried it.

0:45:55.7 Hamilton Morris: And so the fact that so many people got to use MDMA in the 80s and 90s was a product of people like Steve Gill who risked their freedom to make that drug available. And he was somebody that really would have been forgotten, I think, if I didn't have the opportunity to film that episode. And so those were the pieces that felt the best to me where there's lots of things that I really enjoy filming, like it was, I think, very beautiful and amazing going to Gabon and filming the Bwiti Iboga rituals and I would like to think that I had a somewhat novel take on it by integrating this discussion of the natural synthetic dichotomy with the discovery of the supposed tramadol-containing plant. But the reality is that lots of people have filmed Iboga ceremonies and lots of people can bring a camera to an Iboga ceremony and capture beautiful footage of the dancing and the music.

0:47:01.4 Hamilton Morris: And so I'm not the only person that can do that or has done that. Whereas some of these projects, I genuinely feel if I hadn't done them, nobody ever would have and the stories would have been lost completely. And so there's a certain... That was really what my priority was a lot of the time and why I was drawn to a lot of these more obscure subjects. And one reason I also never emphasized medicalization in any major way was I thought, there's a lot of people that are going to do a thing about veterans taking MDMA, I don't need to be that guy. I'll let someone else do that story. I want to tell a story about Darrell Lemaire and him making 5-ethoxyphenethylamines in a volcano. And that's just a...

0:47:49.5 Paul F. Austin: Who was Darrell Lemaire?

0:47:50.3 Hamilton Morris: He was like Shulgin's silent partner, who again, this comes back to this idea that Shulgin invented the drugs, but when it came to distributing them, he didn't want to have anything to do with it, for the most part, with very few exceptions. It just represented too much of a liability. And for him... But someone has to make the drugs. And Darrell Lemaire, like Steve Gill, was another one of these people who was engaged in the large scale manufacture of MDMA, MDA, and some 2C phenethylamines. Yeah. So then that's...

0:48:29.9 Paul F. Austin: Then how did... I mean, what's the volcano story?

0:48:32.7 Hamilton Morris: Well, it was the finale of the first season of my show. They... I had been given... There's this wonderful woman named Tania Manning who lived with the Shulgins throughout their lives and really cared for Anne and Sasha Shulgin and was really vital to their happiness and well-being at the end of both of their lives. And she also developed a really strong understanding of their archives. There's a couple of people that spend a lot of time there and developed an understanding of the archives. The other one, of course, would be Keeper Trout. And they know a lot of things that are not widely known about the Shulgins. And so they were digitizing things and she said, "I've got these letters and I think you'd find them interesting and it would be helpful for us if you digitize them. Are you interested?"

0:49:26.6 Hamilton Morris: And so she, I can't even totally remember why it was that she initially thought that I would be interested, maybe because I was working on a paper about 2C-B or something, I can't remember exactly. But she gives them to me, and it's correspondence between Shulgin and this mysterious chemist named Darrell Lemaire. And I was thinking, "Wow, these letters are incredible. This is a whole chapter of psychedelic history I didn't know anything about. Who is this Darrell Lemaire?" Then I start to realize that Darrell Lemaire, under two tiers of pseudonyms, the first was "Lazar" and then "Hosteen Nez" had written this book about use of various 2C-D variants as nootropics, which I'd read years ago. And I started putting it all together.

0:50:17.3 Hamilton Morris: And I thought, "Oh, wow, Darrell Lemaire is the guy that wrote the 2C-D smart drugs book." And then as I kept looking into him, I started realizing... And his story is really strange, there's this phenomenon where mercury absorbs ultraviolet light. And there is a mineral called Willemite that, actually like a synthetic version of Willemite is used on thin layer chromatography plates, if you've ever seen one, they glow green and it's because they're impregnated with the same type of mineral basically. And Darrell Lemaire had observed that if you look at mercury, it looks like a liquid, but it actually is existing in the vapor phase, but it's invisible.

0:51:06.1 Hamilton Morris: This is the real danger of mercury is inhaling the vapor, which is invisible, just like having it on a tabletop or even touching it with your skin, assuming that you don't have a cut in your skin, is not necessarily so dangerous. And you can visualize that vapor by putting the mercury in front of a Willemite screen and then shining ultraviolet light on it. And then because the vapor is absorbing the ultraviolet light, it creates a black vaporous shadow that you can suddenly see. So Darrell Lemaire saw that mercury would co-occur with gold and created this device for using this UV blocking effect of mercury vapor to help gold prospectors find gold and made a huge amount of money off of this weird device in like the 1950s, retired when he was young, bought a volcano and built a...

0:52:02.6 Paul F. Austin: Where?

0:52:03.1 Hamilton Morris: In Reno.

0:52:04.5 Paul F. Austin: In Reno, Nevada?

0:52:05.5 Hamilton Morris: Yeah.

0:52:06.5 Paul F. Austin: There's a volcano in Reno?

0:52:07.4 Hamilton Morris: Or a, it might technically be like a cinder cone or something like that or some...

0:52:10.8 Paul F. Austin: Okay. Yeah, interesting.

0:52:14.2 Hamilton Morris: That might be like not quite volcanologically accurate, something volcano-like.

0:52:18.4 Paul F. Austin: Yeah, I'm trying to imagine a volcano in Reno. [chuckle]

0:52:23.7 Hamilton Morris: And then blasted out the center of the volcano with dynamite and built a psychedelic drug lab in the center of the volcano. And then on top of that, I had started, I can't even remember how I made this second connection that he had been a sort of mentor to Casey Hardison as well at the end of his life. And then I started thinking, "Wow, this is a crazy story, that nobody knows anything about this guy, Darrell Lemaire. There's barely anything written about him." And so I made a piece about Darrell Lemaire. It was called The Lazy Lizard School of Hedonism. And that was the finale of the first season.

0:53:06.3 Hamilton Morris: And again, this was an example of one of these stories that I feel if I hadn't told it, nobody would have. It would have just been lost. And there's a lot of that in psychedelic history. There's a lot of weirdos that are attracted to this area who do strange and exciting things and a lot of good stories. And that's, for me, that's been one of the major attractions is almost psychedelics aside, there's just some crazy stories.

0:53:31.7 Paul F. Austin: Like the one we started with.

0:53:33.3 Hamilton Morris: Yeah, there's some... Yeah, yeah.

0:53:35.9 Paul F. Austin: Medicalization Is very important. You know, why is FDA approval important? Why is,

0:53:40.3 Hamilton Morris: First and foremost I wish it weren’t important. I wish that FDA approval were not the be-all end-all, but we live in such a complicated society where there's so many different factors that need to be balanced, right? If you say to hell with regulation, this is all benefiting corporate interests. People should be able to do whatever they want, which is certainly a tendency that I have to lean in that direction. But then you still end up with potentially the same problems, but with no safety net in place because anybody can sell anything, with no regulation they can make whatever claims they want. And so total deregulation also introduces certain types of risks.

0:54:29.9 Hamilton Morris: And I think people want a ultra simplistic version of all of this. They want to oversimplify things. And I've, I get it. I've actually contributed to the problem in terms of my own journalism, not my own journalism in terms of my show, but I also was a producer and correspondent on Vice's show on HBO, The News Show. And those were things that I did not write for the most part. I wrote maybe one of them, but they were usually other producers that I was collaborating with. And working on those stories really gave me a inside view of how the news is constructed to promote certain viewpoints that are not necessarily true or that they are oversimplifying very complicated phenomena. Like I was working with this producer who I like a lot and I respect as a person and filmmaker named Eric Weinrib, who had spent a good bit of his career working for Michael Moore. And I think Michael Moore is a brilliant propagandist and I agree with virtually, with most of what he says.

0:55:52.5 Hamilton Morris: So it, for me, it's not so grating to hear somebody who's creating like pro-union propaganda because I'm in favor of unions. I think that's great. Like I agree with pretty much everything that he wants. So it doesn't have the same effect on me, but at the same time you have to recognize these manipulations, even if they're manipulations that you agree with that serve your interests. And so I was working on stories that kind of were like that, where, for example, I worked on this one piece called White Collar Weed. And the story was very simple. You have the sympathetic mom and pop weed growers, they've sacrificed their freedom, they've worked hard for what they believe in. And then you've got these diabolical Yale-educated carpetbaggers who are coming to set up the first cannabis monopoly. And the viewer is sympathetic to the struggling mom and pop growers and they don't like that evil man who studied money at Yale.

0:56:55.4 Hamilton Morris: And so you set up this kind of simple moral dichotomy where there's good guys and bad guys, but that isn't real because the evil Yale businessman who I profiled who was the owner of a company called Tilray wasn't actually evil and Tilray did not become a monopoly. And the problem that the mom and pop growers had was not caused by this Canadian businessman at all. Their problem was prohibition. And so a viewer looks at this and they've been emotionally manipulated to believe that the business of cannabis is bad for the mom and pop grower, but that case has not really been made.

0:57:44.9 Hamilton Morris: It's just a kind of nebulous emotional appeal that can actually distract people from real issues, which in this case is prohibition, which was actually what was threatening the mom and pop growers in addition to more complicated market concerns like the oversaturation of the cannabis market, which resulted in some people just abandoning their crops at some points because they couldn't make any money off of it. That wasn't caused by Canadian businessmen, that was caused by much bigger market factors. Anyway, I've worked on a couple of things like that and I see how it's done and I see how it impacts people. And it, more than anything, concerns me that people can get distracted from what really matters, which is fighting for their own freedom and doing everything in their power to prevent prohibition and the DEA from becoming more powerful than they already are.

0:58:42.3 Paul F. Austin: Yeah, it's like a rising tide lifts all boats. I mean, even one of the teachings of, and I won't get too sort of preaching here, but one of the teachings of psychedelics is interconnectedness, coming together, like working collaboratively, I mean, collaboration is great. And so I think there is something to be said for facilitators who are out of integrity or providers, shamans who are out of integrity. I think the same thing can be said about certain businesses within a hype cycle who are maybe doing things that, let's say Field Trip, for example, who raised a hundred million dollars and kind of went up in smoke. And yet there are people who are doing great and important work that are going to push this forward in a significant way. And I think Atai is one of those companies, I think Compass Pathways is one of those companies, I think Cybin, which I'm an advisor to is one of those companies doing good research and they have good teams. And I think it's going to help with the widespread accessibility of psychedelics for all, whether it's deep room, safe or better ideas.

0:59:47.4 Hamilton Morris: Yeah. I think it's, and we're in a transitional period, a lot is going to change. The current projection is that psilocybin is not going to be approved until 2027. There's going to be a lot of time and a lot of work and a lot of changes that are going to take place in the intervening years. And I think it's important as much as possible for people to try to be constructive and less reactionary because that's what the man wants. The man wants you, they want you fucking attacking each other.

1:00:24.2 Paul F. Austin: Wow. So that was an hour. Thank you. I learned so much from you today. The nuance that you brought to the conversation, the particularity about DET and bufotenine.

1:00:36.4 Hamilton Morris: Bufotenine, yeah.

1:00:38.4 Paul F. Austin: Bufotenine, that's so fascinating. So I just, yeah, I appreciate your commitment and devotion to your work as a chemist and an innovator and an educator. You've educated millions about drugs generally, but also psychedelics. So I just want to share my appreciation for all that, what you've done in the last 10, 12 years in the space. I think it's really moved the space forward in a substantial way and you've made a lot of incredible contributions to both psychedelics and also drugs in general.

1:01:10.4 Hamilton Morris: Thank you, I appreciate that. I enjoyed the conversation.

1:01:21.3 Paul F. Austin: Hey, listeners, Paul here. I hope you enjoyed this conversation with the brilliant Hamilton Morris. If you got something from this conversation, please consider sharing it with a friend who might also benefit from it. You can also follow the link in the description to go deeper into this episode with full show notes, transcript and any links that we mentioned today. And finally, we have a free private community at community.thethirdwave.co. Check it out, log in, join, introduce yourself. And we have a little area there, a space is what they call it, where you can dive in deeper on this episode if you want to get into some rich discussion around it. All right, that's it for now, until next time.