#605: Hamilton Morris and Dr. Mark Plotkin — Exploring the History of Psychoactive Substances, Synthetic vs. Natural Options, Microdosing, 5-MeO-DMT, The “Drunken Monkey” Hypothesis, Timothy Leary’s Legacy, and More

Hamilton Morris and Dr. Mark Plotkin — Exploring the History of Psychoactive Substances, Synthetic vs. Natural Options, Microdosing, 5-MeO-DMT, The “Drunken Monkey” Hypothesis, Timothy Leary’s Legacy, and More | Brought to you by Athletic Greens http://athleticgreens.com/tim all-in-one nutritional supplement and 5-Bullet Friday https://go.tim.blog/5-bullet-friday-1/?utm_source=timblog&utm_medium=timblog&utm_campaign=podcast-sponsorship, my very own email newsletter. More on both below. Welcome to The Tim Ferriss Show http://tim.blog/podcast, where it is usually my job to deconstruct world-class performers, to tease out their routines, habits, et cetera that you can apply to your own life. This time around, we have a very special edition featuring two of your favorite guests: Dr. Mark Plotkin and Hamilton Morris. Mark takes over my duties as host and interviews Hamilton for an episode of the Plants of the Gods https://podcasts.apple.com/us/podcast/plants-gods-hallucinogens-healing-culture-conservation/id1549464922 podcast. You, my dear listeners, are hearing the audio before anyone else, so this is a Tim Ferriss Show exclusive. I’ve previously featured some of my favorite episodes from that show at tim.blog/plantsofthegods https://tim.blog/2021/04/08/plants-of-the-gods/. These episodes cover a lot of fascinating ground. Who is Mark? Mark (@DocMarkPlotkin https://twitter.com/DocMarkPlotkin) is an ethnobotanist who serves as president of the Amazon Conservation Team https://www.amazonteam.org/, which has partnered with ~80 tribes to map and improve management and protection of ~100 million acres of ancestral rainforests. He is best known to the general public as the author of the book Tales of a Shaman’s Apprentice https://www.amazon.com/Tales-Shamans-Apprentice-Ethnobotanist-Medicines/dp/014012991X/?tag=offsitoftimfe-20, one of the most popular books ever written about the rainforest. His most recent book is The Amazon: What Everyone Needs to Know https://www.amazon.com/Amazon-What-Everyone-Needs-Know%C2%AE/dp/0190668296?tag=offsitoftimfe-20. You can find my interview with Mark at tim.blog/markplotkin https://tim.blog/2020/09/30/mark-plotkin/. And the guest today is Hamilton Morris. Hamilton (@HamiltonMorris https://twitter.com/HamiltonMorris) is a chemist, filmmaker, and science journalist. A graduate of The New School, he conducts chemistry research at Saint Joseph’s University. Hamilton is the writer and director of the documentary series Hamilton’s Pharmacopeia https://www.amazon.com/Magic-Mushrooms-in-Mexico/dp/B01M7UV0KE/?tag=offsitoftimfe-20, in which he explores the chemistry and traditions surrounding psychoactive drugs. You can find my most recent interview with him at tim.blog/hamilton https://tim.blog/2021/04/27/hamilton-morris-2/. This is a tightly packed 60-minute interview. Mark and Hamilton cover the history of different psychoactive substances, Timothy Leary’s legacy, the “drunken monkey” hypothesis, conservation, microdosing, the differences between 5-MeO-DMT and DMT, a disease that afflicts people who smoke enormous quantities of cannabis, causing them to vomit continuously and only find relief from their nausea by taking a hot shower (yes, really), the impact of the placebo effect, a synthetic vs. a natural product, the role of ritual, and much, much more. Please enjoy! * This episode is brought to you by Athletic Greens https://www.athleticgreens.com/tim. I get asked all the time, “If you could use only one supplement, what would it be?” My answer is usually AG1 https://www.athleticgreens.com/tim by Athletic Greens https://www.athleticgreens.com/tim, my all-in-one nutritional insurance. I recommended it in The 4-Hour Body in 2010 and did not get paid to do so. I do my best with nutrient-dense meals, of course, but AG https://www.athleticgreens.com/tim further covers my bases with vitamins, minerals, and whole-food-sourced micronutrients that support gut health and the immune system. Right now, Athletic Greens https://www.athleticgreens.com/tim is offering you their Vitamin D Liquid Formula free with your first subscription purchase—a vital nutrient for a strong immune system and strong bones. Visit AthleticGreens.com/Tim https://www.athleticgreens.com/tim to claim this special offer today and receive the free Vitamin D Liquid Formula (and five free travel packs) with your first subscription purchase! That’s up to a one-year supply of Vitamin D as added value when you try their delicious and comprehensive all-in-one daily greens product. * This episode is also brought to you by 5-Bullet Friday https://go.tim.blog/5-bullet-friday-1/?utm_source=timblog&utm_medium=timblog&utm_campaign=podcast-sponsorship, my very own email newsletter that every Friday features five bullet points highlighting cool things I’ve found that week, including apps, books, documentaries, gadgets, albums, articles, TV shows, new hacks or tricks, and—of course—all sorts of weird stuff I’ve dug up from around the world. It’s free, it’s always going to be free, and you can subscribe now at tim.blog/friday https://go.tim.blog/5-bullet-friday-1/?utm_source=timblog&utm_medium=timblog&utm_campaign=podcast-sponsorship. * [06:22] The Sonoran desert toad's celebrity star is rising [08:18] The role of the chemist in preserving plants, animals, and fungi from which compounds are traditionally derived [11:18] Who is Howard Lotsof? [14:02] Microdosing [16:39] Ken Nelson and the celebrated Bufo Alvarius: The Psychedelic Toad of the Sonoran Desert pamphlet [20:11] God molecule vs. just plain old DMT [22:25] There are potential downsides to these compounds (even cannabis) [27:58] Undiscovered compounds [30:15] Lessons learned and questions pondered from Alexander Shulgin's thumb surgery [34:05] Synthetic vs. natural [37:21] The role of ritual [39:49] Combining traditions [42:27] Mark's account of Huautla in the early 2000s. [42:58] Downsides of psychedelic tourism [47:46] Effectiveness of fungi vs. frogs [49:52] Where do we go in search of new substances? [53:11] How far back do shamanic traditions go? [54:40] Poisons as medicines and vice versa [56:34] Salvia, and stoned vs. drunk apes [1:04:20] Nicolas Langlitz and the primatology of primatologists [1:06:03] Timothy Leary's legacy * For show notes and past guests on The Tim Ferriss Show http://tim.blog/podcast, please visit tim.blog/podcast https://tim.blog/podcast/?utm_source=podcast&utm_medium=podcast&utm_campaign=podcast-description. For deals from sponsors of The Tim Ferriss Show http://tim.blog/podcast, please visit tim.blog/podcast-sponsors http://tim.blog/podcast-sponsors Sign up for Tim’s email newsletter (5-Bullet Friday) at tim.blog/friday https://go.tim.blog/5-bullet-friday-1/. For transcripts of episodes, go to tim.blog/transcripts http://tim.blog/transcripts. Discover Tim’s books: tim.blog/books http://tim.blog/books. 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• 0:00Tim Ferriss?

  This episode is brought to you by Athletic Greens. I get asked all the time what I would take if I could only take one supplement. The answer is invariably Athletic Greens. I view it as all-in-one nutritional insurance. I recommended it, in fact, in The Four Hour Body. This is more than 10 years ago, and I did not get paid to do so. With approximately 75 vitamins, minerals, and whole-food sourced ingredients, you'd be very hard-pressed to find a more nutrient-dense and comprehensive formula on the market. It has multivitamins, multimineral, greens complex, probiotics and prebiotics for gut health, an immunity formula, digestive enzymes, adaptogens, and much more. I usually take it once or twice a day just to make sure I've covered my bases if I miss anything I'm not aware of.

• 0:44Tim Ferriss?

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• 1:30Tim Ferriss?

  and five free travel packs with your subscription. Again, that's athleticgreens.com/tim.

• 1:40Tim Ferriss?

  This episode is brought to you by Five Bullet Friday, my very own email newsletter. It's become one of the most popular email newsletters in the world with millions of subscribers, and it's super, super simple. It does not clog up your inbox. Every Friday, I send out five bullet points, super short, of the coolest things I've found that week, which sometimes includes apps, books, documentaries, supplements, gadgets, new self experiments, hacks, tricks, and all sorts of weird stuff that I dig up from around the world. You guys, podcast listeners, and Book readers have asked me for something short and action-packed for a very long time. Because after all, the podcasts, the books, they can be quite long. And that's why I created Five Bullet Friday. It's become one of my favorite things I do every week.

• 2:23Tim Ferriss?

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• 3:08Tim Ferriss?

  If you listen to this podcast, it's very likely that you'd dig it a lot. And you can, of course, easily subscribe anytime. So, easy peasy. Again, that's tim.blog/friday. And thanks for checking it out, if the spirit moves you.

• 3:24Speaker 01

  At this altitude, I can run flat out for a half mile before my hands start shaking. Can I ask you a personal question? No, it would seem inappropriate to me.

• 3:34Speaker 02

  I'm a cybernetic organism, living tissue over metal endoskeleton.

• 3:47Tim Ferriss?

  Well, hello, boys and girls, ladies and germs. This is Tim Ferriss. Welcome to the Tim Ferriss Show, where it is usually my job to deconstruct world-class performers, to tease out their routines, habits, et cetera, that you can apply to your own life. This time around, we have a very special edition of this podcast, featuring two of your favorite guests from the past, Dr. Mark Plotkin and Hamilton Morris. Mark takes over my duties as host and interviews Hamilton for an episode of the Plants of the Gods podcast. You, my dear listeners, are hearing this audio before anyone else, so it's A Tim Ferriss Show exclusive. I've previously featured some of my favorite episodes from the Plants of the Gods podcast here on this podcast, and you can find all of those at tim.blog/PlantsOfTheGods.

• 4:32Tim Ferriss?

  These episodes cover a lot of fascinating ground. So let's get to the bios. Who is Mark? If you don't know, Mark on Twitter @DocD. Mark Plotkin is an ethnobotanist who serves as president of the Amazon Conservation Team, which has partnered with roughly 80 tribes to map and improve management and protection of roughly 100 million acres of ancestral rainforests. He is best known to the general public as the author of the book Tales of a Shaman's Apprentice, one of the most popular books ever written about the rainforest. His most recent book is the Amazon What Everyone Needs to Know. You can find my interview with Mark at tim.blog/MarkPlotkin. That's M-A-R-K-P-L-O-T-K-I-N. And the guest, his guest today is Hamilton Morris. Love Hamilton.

• 5:17Tim Ferriss?

  Hamilton on Twitter @HamiltonMorris, M-O-R-R-I-S, is a chemist, filmmaker, and science journalist. Graduate of the New School, he conducts chemistry research at St. Joseph's University. Hamilton is the writer and director of the documentary series Hamilton's Pharmacopeia, pharmacopeia, depending on how you like to say it, in which he explores the chemistry and traditions surrounding psychoactive drugs, very often subjecting himself to personal intake. You can find my most recent interview with him at tim.blog/Hamilton. And what you're about to hear is a tightly-packed 60-minute interview. Mark and Hamilton cover the history of different psychoactive substances, Timothy Leary's legacy, the drunken monkey hypothesis, conservation, microdosing, the differences between 5-MEO,

• 6:00Tim Ferriss?

  DMT, that's five-methoxy-dimethyltryptamine, and DMT, a disease that afflicts people who smoke enormous quantities of cannabis, yes, really, the impact of the placebo effect, synthetic versus natural options in this psychoactive spectrum of things, the role of ritual, and much, much more. Please enjoy.

• 6:22Mark Plotkin?

  Well, Hamilton, I want to thank you for agreeing to do the interview. And I would like to start by talking about the Sonoran Desert toad, which, as you know, is an object of fascination, not only regionally, but certainly nationally and perhaps internationally. So perhaps you give us some thoughts on this recent fascination with this intriguing creature.

• 6:45Hamilton Morris?

  Yes, it really does seem to be gaining popularity. Every time I think that it's peaked, it gets more and more popular. And in the last month, there were two major articles that came out one day after another in The New York Times and The New Yorker. The New York Times one actually was largely focused on conservation issues. I thought that that was pretty responsible in its orientation. The New Yorker one was more a profile of Octavio Reddig, but I think that even though it wasn't focused on conservation, implicitly, a lot of those issues were evident, if only in terms of the magnitude of his work. How many people?

• 7:30Hamilton Morris?

  I think he claimed to have personally turned on 10,000 people. And so if you want to use a rough estimate that each mature Bufo alvarius toad, when milked, if all of the glands are milked, could produce enough venom to supply five people, that's, you know, the milking of 2,000 toads from one man. And you add to that his partner, Jerry Sandoval, or his former partner, makes that 4,000 toads. And then everybody else that was inspired by them, you can just easily knock that up to 10,000 toads. And I think it becomes clear that even if it wasn't a problem for a few people to do

• 8:13Hamilton Morris?

  this, if it continues to gain popularity at the current rate, it's going to become a problem very quickly.

• 8:18Mark Plotkin?

  There's an excellent ethnobotanist by the name of Gary Nabhan, very prolific, but his best book, my favorite, is called The Desert Smells Like Rain, came out about 40 years ago. And it talks about how the Ho'okum people have expanded agriculture in the desert. And this apparently has expanded the habitat for this toad. But I think as you're pointing out, that there'd be a lot more habitat needed to support this toad. And I know you've been one of the leaders in terms of natural product chemistry and recreating some of these chemicals in the lab. So I wonder if you could share with us your thoughts on the role of the chemist in terms of taking the heat, taking the pressure off natural populations of plants, animals, and fungi?

• 9:00Hamilton Morris?

  Yeah, I mean, it's an interesting time because a lot of these things can be synthesized somewhat trivially in an industrial lab with the appropriate resources. So something like Ibogaine, to produce it fully synthetically would be totally impossible for a normal person to do on a, you know, multi-gram scale to supply a clinic for something like that. But if it were, you know, a large industrial manufacturing operation, it would then be possible. And that was what Howard Lotsof was trying to do with Ibogaine. The same is not true of something like 5-MEO DMT. It's synthetically more approachable, which is really nice.

• 9:42Hamilton Morris?

  This is one of the advantages, is that it could be produced industrially for a pharmaceutical company. There's actually quite a few different pharmaceutical companies right now that are pursuing 5-MEO DMT as a therapeutic product. And all of them are using synthetic material, which I think is really a good thing, actually a necessary thing, because there's no way that the toads could supply a pharmaceutical demand. But what's nice about this is that there's a sort of intermediate that exists. It doesn't need to be pharmaceutical, and it doesn't need to be extracted from a toad. It's possible for somebody, if it is done legally, you know, in a region where they

• 10:25Hamilton Morris?

  won't potentially lose their freedom for doing this, it's possible to produce it synthetically in a one-step reaction, starting from 5-methoxytryptamine. And this is very approachable, somewhat safe chemistry. I don't want to say that it's completely safe, because it isn't, but I would say in the grand scheme of synthesis, this is certainly on the easier side of the balance. And That means that if somebody were operating a clinic in Mexico, they conceivably could hire a chemist to make enough to supply their clinic for years very easily at a low cost. And that was what I was trying to show people. Because this idea that, okay, chemistry, there's no way. That's not accessible to an average person.

• 11:09Hamilton Morris?

  Well, maybe not to everybody, but it is accessible to people with a little bit of training. And so people should be aware that that exists as a viable option.

• 11:17Mark Plotkin?

  Well, you mentioned Howard's name, and I heard you talk a bit about him in an interview you gave with our friend Tim Ferriss. And I'll link to that interview in the show notes. But I wonder if you could tell a little bit of background about Howard's story and how he discovered that this was, in some cases, an effective treatment for addiction.

• 11:34Hamilton Morris?

  Yeah, it's a fascinating story because if you look at the history of iboga and even the early pharmaceutical history of ibogaine, in Central West Africa, it's a religious sacrament and part of a religion called Bouiti. And it's used for medicinal purposes there, but it is not traditionally used as a treatment for addiction. There was not opioid addiction in Central West Africa until the 21st century. So at least on a large scale, I'm sure there were a couple people. So this idea that ibogaine or iboga could serve as a treatment for substance abuse

• 12:18Hamilton Morris?

  disorders was not something that was circulating at all. And there was a guy in New York named Howard Lotsof, who was friends with a chemist. And the chemist gave him ibogaine because it was a psychedelic that was available. I believe that he had either synthesized it or ordered it from a chemical supply catalog. And Howard Lotsof was dependent on heroin at that time. And he took the ibogaine not because he wanted to stop using heroin necessarily, he just wanted to use a psychedelic. And what he found in the wake of that experience was that he lost his craving for heroin.

• 13:00Hamilton Morris?

  And not only did he lose the craving for it, the very way that he conceptualized the heroin had changed. He didn't think of it as something that was desirable or good. He started to think of heroin as...

• 13:13Hamilton Morris?

  Essentially a symbol of death, something that was, not only did he not need it, he didn't want it either. And this was something that emerged accidentally. This was a serendipitous discovery. He wasn't looking for this, but he found it. And what he experienced was not unique. Other people tried ibogaine and iboga for the same purpose as a treatment for addiction. And it was found to be the case that actually quite a large number of people responded similarly. And this has even been demonstrated in animal models of addiction. So this is a demonstrated effect. It doesn't work for everyone all the time, but it seems that maybe a solid

• 13:54Hamilton Morris?

  third to a quarter of people that undergo this therapy are able to stop using heroin or other opioids.

• 14:02Mark Plotkin?

  Well, there's many fascinating nuggets of information tucked in that answer, but one that stands out to me is that this is a powerful and effective use for something that the indigenous peoples weren't using it for. And so what the point of this, and I think the relevance for this podcast, is that not only are these mind altering substances important and useful for things they've always been used for, but there's new things that come to the fore. I'm reminded of Charles Nichols at LSU, who's using tiny doses of hallucinogens to treat asthma. And they're not causing hallucinations. And I'm wondering if you think that this kind of explains this whole microdosing movement, that people aren't really sure how it works or what it's for, but people seem to like it and find it effective for a variety of purposes.

• 14:46Hamilton Morris?

  Well, yes, that's, microdosing is difficult to talk about because it doesn't really have a precise definition. So what I might call a microdose could be completely different, especially when you factor in the issue that psilocybin containing mushrooms and LSD are the two psychedelics that people typically have access to. And both of these are psychedelics where people do not know the precise dose of chemical they're consuming due to variation in mushrooms and due to uncertainty about the concentration on blotter. So you might say a microdose is half of one. Tab of a blotter, but you don't know how much LSD is on that tab. So it could be completely different. For some people, a microdose is a low dose of a psychedelic.

• 15:30Hamilton Morris?

  For some people, they define microdose as sub perceptual. And in the research that has been done thus far, it seems like it's a placebo effect. But that's not to say that low doses of psychedelics couldn't have some kind of therapeutic property under the appropriate circumstances. And like you said, the work of Chuck Nichols is great evidence of that. So maybe, the other thing is that, you know, the therapeutic endpoints aren't well defined in a lot of these microdosing. You know, what is it exactly that people are looking for? Enhanced creativity, enhanced focus, enhanced energy, mood lift? I mean, people seem to be pursuing microdosing for an almost unlimited number of different applications.

• 16:13Hamilton Morris?

  And so maybe it works for one thing, for one person, maybe somebody with, you know, suffering from chronic inflammation with a certain psychedelic could have some benefit. And maybe for someone else, there would be no benefit at all. So I think the real issue with talking about microdosing is a lack of precision in the definition of what a microdose is, what psychedelic is being used, and what the application of that microdose of a psychedelic would be.

• 16:38Mark Plotkin?

  Excellent. Thank you. Which ties back into something else you're alluding to. The famous pamphlet by Albert Most that you've helped bring back to the fore was actually written by Ken Nelson. And he's a fascinating figure in his own right. So I wonder if you could give us a little bit of detail and background on this incredible fellow.

• 16:57Hamilton Morris?

  Yeah, and it was nice to see his name in these articles. It's nice to really see him integrated into this history because I think what he did is so fascinating. And, you know, I think that because our culture has done such a terrible job dealing with psychedelics and psychoactive drugs in general, it's just about as bad as it could possibly be. Locking people in cages for using them is really, has not been an effective strategy. And for that reason, I think we tend to look to indigenous cultures for guidance because they've done a far better job at learning how to use these things constructively and medicinally. And so-

• 17:42Hamilton Morris?

  We're almost uncomfortable with our own contributions. I think there's a tendency to try to exclusively look. Some people go too far. And in the case of Bufo alvarius, I think that they have done that. They have essentially fabricated an indigenous history of use because if it's ancient, if it's traditional, if it's indigenous, that means that it's good. That means that it's okay. That justifies it. Well, all known evidence points to there not being a tradition of using Bufo alvarius. This is something that emerged in the United States with a white man in Texas named Ken

• 18:20Hamilton Morris?

  Nelson, who was, he was actually inspired by a misunderstanding by an anthropologist named Jeanette Runquist, who had hypothesized that there was ancient use of psychoactive toads. So he read about this in Omni Magazine and thought, well, that's cool. I'd like to, you know, I'd like to try that myself, not realizing that in his imitation of what he thought was an indigenous practice, he was actually inventing a new practice himself. A very interesting twist in all of this. And so he was, by all known accounts, the first person to find this toad, milk it, and smoke the venom.

• 19:05Hamilton Morris?

  And at the beginning, it was obscure. There were, you know, psychedelic cognizanty like Andrew Weil or Wade Davis, who pursued this and were very interested in it. But this was not a phenomenon. The celebrities weren't talking about toad venom in the 1980s. And if it was popular, it was probably equivalent in popularity to synthetic 5-MeodMT at that time, which had been available from chemical supply companies since at least the 1960s. So The synthetic 5-MEO DMT history actually predates the use of Buvalvarius Venom. It just was never talked about as much. And there's something, I suppose, something cool about the idea of smoking toad venom.

• 19:50Hamilton Morris?

  People like to talk about it. We're talking about it right now. There's something weird about it. It's a good story. And it wasn't until celebrities really started doing this in the 21st century and until Octavia Reddick and Jerry Sandoval started going on a crusade as toad venom evangelists that this really became the phenomenon that we're currently talking about.

• 20:11Mark Plotkin?

  Well, that's a new phrase for me, toad venom evangelist. I'm gonna have to be lifting that one. So why are people calling this the god molecule versus just plain old DMT?

• 20:20Hamilton Morris?

  Well, the experiences are very different. This is one of the unfortunate things about 5-MEO DMT is its name. People think that because the name contains DMT, that it is a form of DMT, or that it is, you know, very, very closely related to DMT. But psilocybin, you know, the active metabolite of psilocybin and a component of psilocybin-containing mushrooms is closer to DMT than 5-MEO DMT is structurally. You could call psilocybin 4-hydroxy DMT. So it's really the name, more than anything, that I think causes people to have this association. It was actually a big problem when I was planning a large-scale synthesis of 5-MEO

• 21:03Hamilton Morris?

  DMT in Mexico, because the lawyers looked at this and they said, "Well, this is DMT." And I said, "No, it's not. It's 5-MEO DMT. It's 5-methoxy DMT." And they said, "Well, it contains DMT in the name." And I'd say, "Okay, well, what if I call it NNO-trimethylserotonin? Then can I synthesize it?" And they thought that was okay. Of course, it's the same chemical. So, but the difference experientially between 5-MEO DMT and DMT is enormous. I would say that DMT is very much a prototypical, classical psychedelic. It's highly, highly visual. You have profound visual distortions. You- You often see your environment in a different way.

• 21:48Hamilton Morris?

  You think about yourself, your relationships. It's a personal experience. Whereas 5-MEO DMT is often non-visual. It's often sort of impersonal. I think it tends toward universal, where it's not about your life, but life in general. And it doesn't have a lot of the qualities that people think of when they talk about psychedelic drugs. I mean, for many people, myself included, the experience is losing consciousness entirely for a brief period, and then having something that could be termed a near-death experience. Physiologically speaking, it isn't, but experientially, it does feel that way.

• 22:26Mark Plotkin?

  Well, I want to make the point here that we're not doing commercials for any of these substances. And in all the episodes, I point out that these things can be lethal. And you've mentioned that on your show and in some of your writings and interviews. But even cannabis, which people sort of think of as this harmless thing that can't hurt anybody. And I was reading something of yours recently that talked about problematic relationships with cannabis. So I wonder if you could give an example of that, so that people understand that all of these plants are the gods, and fungi are the gods, and frogs are the gods, may have a downside.

• 22:57Hamilton Morris?

  Yeah, I think it's very important to have a balanced perspective on these things, because there's been something really polarizing about the way they've been publicly discussed from the very beginning. They're either a panacea that's going to cure all of society's ills. They're going to prevent us from being mean to each other. They're going to end all wars. Or they're poisonous agents that will destroy your mind and leave you intellectually crippled. And of course, the truth is somewhere in the middle, where for some people, under some circumstances, they can have a tremendous benefit, and they can be truly life-changing. And under other circumstances, they can have a damaging effect.

• 23:41Hamilton Morris?

  And cannabis, I think, is an interesting example, because it also includes the political dimensions of all this. Because the people that have been using these substances for decades have been persecuted.

• 23:56Hamilton Morris?

  And that creates a sort of insecurity complex. Understandably, justifiably, if the government says that this is dangerous and they're willing to lock you in a cage for it, if your employer can terminate your employment, if they find traces of this substance in your hair or your urine, which is an insane invasion of privacy that nobody should tolerate, then it makes sense that you'd want to really stand up for this stuff and say, hey, wait a second, it's never killed anybody, it's safer than alcohol, safer than tobacco, this stuff is innocuous, and in fact, you can smoke it every single day and you'll be totally fine. And in many instances, that might be true, but that doesn't necessarily mean that you should. And it doesn't mean that, I think

• 24:40Hamilton Morris?

  this is the tendency, is we go too far in one direction or another, and a lot of it has to do with this, yeah, this insecurity from people demonizing these substances for so long.

• 24:52Mark Plotkin?

  Agreed, but can you give perhaps an example of a problematic relationship with cannabis? Because your point is well taken, but that it's even cannabis can have a downside.

• 25:02Hamilton Morris?

  Oh, certainly, yeah. I mean, I think one of the most interesting examples is there's a disorder called cannabis hyperemesis disorder. Are you familiar with this? It wasn't described into, in the medical literature until somewhat recently. It's a very odd phenomenon where people who smoke enormous quantities of cannabis will start vomiting continuously. And the only thing that relieves their nausea is taking a hot shower. And people started showing up in emergency rooms when they ran out of hot water because they couldn't control their vomiting. And this seemed really bizarre, because, wait a second, people have been using cannabis for thousands of years. What are the chances that...

• 25:48Hamilton Morris?

  Now, all of a sudden, a new cannabis-related disorder would emerge. It couldn't be the cannabis itself. It must be a pesticide. It must be some contaminant in the cannabis. Otherwise, how could this possibly be explained? And the explanation is that, yes, it is the cannabis itself. This is a product of chronic hyperstimulation of CB1 receptors. And the reality is that people are smoking more cannabis now than any other time in human history. So, new use disorders are actually emerging. And although this is described as a somewhat obscure phenomenon, it's not as obscure as people think. I've known two people that had this disorder, both of whom didn't know they had it.

• 26:31Hamilton Morris?

  And it's especially insidious because cannabis has an antiemetic effect. So, you're nauseous. You think, "Oh, man, I'm so sick. I need to smoke some cannabis because I'm really nauseous." But the cannabis is actually making it worse. It's the source of the nausea. And during the pandemic, I had a friend who this happened to because he was just getting really, really stoned all the time. And I had noticed that he was constantly soaking wet. And I thought, like, why is this guy... Is he, like, taking showers five times a day? Why is he always so wet? And he then told me, you know, "I don't know what's going on. I've just been, you know, vomiting all the time, and a hot shower is really the only thing that helps."

• 27:15Hamilton Morris?

  And I thought, "Wow, all right. Yeah, I know what you have." So, that's, you know, I don't want to bring that up as an example of something that everyone should be really terrified of because this is something that only afflicts people who are extremely stoned all the time. But it's just an example of how this plant that's considered totally innocuous, under some circumstances, can have a negative effect. Also, I think there's something to be said for maybe just not being stoned all the time. And I say this as somebody that likes cannabis personally. I'm not trying to hate on cannabis. It's just there's, like I said, a tendency to go to these extremes of either cannabis is terrible or you should be stoned all the time because cannabis is a medicine.

• 27:58Mark Plotkin?

  Well, my mentor Richard Schultes would often describe mind-altering plants as scalpels in the hand of a shaman. It can heal, but it can also harm if it's not used correctly. And so, once again, all of these plants, all of these fungi, all of these substances, need to be used with caution and a prostrith reverence and carefully. And that's why I often tell people, you shouldn't be experimenting on your own with very powerful substances. I also wanted to ask you, Hamilton, about other frogs before we move into a few other topics. And that is, when I was working on a book called Medicine Quest about 30 years ago, I interviewed John Daly. And at that point, 30 years ago, Daly had isolated 40

• 28:40Mark Plotkin?

  novel chemicals just from frogs, from 50 different species. So I'm wondering, what's your perspective on frogs and other plants, animals, and fungi as to what's still out there?

• 28:50Hamilton Morris?

  I love frogs, and they are amazing chemists. I mean, I imagine you're familiar with epibatidine. It's such a beautiful molecule. And for a terrestrial species to even produce a chlorinated natural product like that is already sort of unusual. Then you have the seven-azonorbornane ring, which is just bizarre. I mean, the chemistry of it is really, really fascinating. And these frogs and toads are capable of biosynthetic feats that would be very difficult for human chemists. It's remarkable. And I don't doubt that there are amazing things left to be discovered.

• 29:32Mark Plotkin?

  Well, I have read recent reports of two venomous frogs found in eastern Brazil, genus Corithromantis and Aparasphenodon, where they have toxins more poisonous than the bushmaster. And these are recent finds. So the idea that we've kind of got everything from the natural world, or even just from the frogs, is obviously not the case. Of course, the flip side of that is with chytrid fungi and climate change, these animals, which are probably the most sensitive of any group. So the race is on us to find, utilize, and protect these creatures at the same time that we seem to be destroying them faster than ever. There's about 1,000 species of frogs that are known in the Amazon, and we're finding more all the time.

• 30:15Mark Plotkin?

  But I wanted to turn to one of your idols or mentors or heroes, I don't know how you'd best describe them, Alexander Shulgin, better known as Sasha. And since we're talking about mental states, I wonder if you'd share with us the story about Sasha and the surgery on his thumb.

• 30:31Hamilton Morris?

  Oh, yeah, yeah, of course. And this is a sort of foundational story in psychedelic history because Alexander Shulgin was in the Navy. And when he was in the Navy, he was injured. He injured his thumb. And he was having, I believe, a small surgical procedure, maybe it was just stitches on his thumb. And the nurse gave him a glass of orange juice that had crystals that he could see present in the juice. And he thought, okay, well, they're giving me morphine in my orange juice. Makes sense. This is gonna be, you know, it's a painful procedure. He drank it, and the morphine had this miraculous analgesic effect.

• 31:16Hamilton Morris?

  And he thought, that was great. That was exactly what I needed. And later, he asked the nurse, you know, how much morphine was that in the juice? And she said, oh, no, that was sugar. Those are sugar crystals. So he came to realize that his own mind was capable of producing these sorts of experiences. I mean, this is the placebo effect, and it's very, very powerful. And as somebody who spent his career evaluating completely unknown substances, substances that did not exist in the known universe until they were synthesized in his lab, and he would be the first human being to try those substances, you have to be ultra-aware of not just the placebo effect, but also the nocebo effect.

• 32:00Hamilton Morris?

  The belief that something that is pharmacologically inactive that you have consumed is a poison because it could go either way. You could take something and suddenly think, oh, no, what did I just do? Oh, no, this could be some kind of cardiac toxin. I could be, I could be dying. You can have a, both are totally possible, and both are Established phenomena in the medical literature. This is not some kind of speculative thing. This is why placebo-controlled trials are done because the placebo effect is a real effect. This is one of the complicated things about it.

• 32:32Mark Plotkin?

  Understood. But we've got two pieces of the puzzle that don't fit together well. Here you have a man who invented more wild mind-altering chemicals than anybody ever had or ever will, and is a big fan of the placebo effect. So what's the lesson we draw from his life and work in terms of the future and healing if we get this right?

• 32:49Hamilton Morris?

  Well, I think the first thing is to not always believe your own senses immediately, to scrutinize your own experiences, and to try your best to be skeptical and to conduct your work in an evidence-based manner. Because, yes, there is nobody who is not vulnerable to the placebo effect. You might think, "Oh, that's just for the people out there that don't really, they're not really knowledgeable like me." But someone like me, so knowledgeable, I could obviously tell the difference between a placebo and an active substance. Well, the whole issue with placebo is that you can't tell. That's the whole purpose of this effect.

• 33:31Hamilton Morris?

  And so I think this actually comes back to the conservation issue because people will say, "Well, of course toad venom is different than a synthetic material, and of course iboga total alkaloid extract is different from isolated ibogaine, and of course one variety of psilocybin-containing mushroom is going to be different than another." Well, not so fast. If you're going to make that claim, especially if that claim could have serious ecological consequences, you need to be sure that it's real.

• 34:05Mark Plotkin?

  Well, everybody in our field is repeatedly asked or told, "I would never take a synthetic. I will only take the natural product." So what's the difference between synthetic mescaline and mescaline?

• 34:17Hamilton Morris?

  I love that question because it's, you know, there's a really beautiful study that was done between two groups of researchers, one in France and the other in Germany. And it was a group of natural product chemists in France who were studying a traditional medicine in Cameroon called Naukliolatifolia. And they knew that this plant had been used to treat pain for generations. So they brought it to the lab, they extracted it, what's in this stuff? And they find that it contains tramadol, which is a completely synthetic pharmaceutical opioid that was thought to have been discovered in Germany in the 1960s. So wait a second, there's now two parallel histories of tramadol.

• 35:02Hamilton Morris?

  One that is pharmaceutical, starting in Germany, and the other that is a multi-generational traditional medicine history in Central West Africa. And this was kind of a remarkable claim. It was very exciting to me. But then, a group of chemists in Germany decided that they were going to try to replicate these findings. They went back to the same region, they started collecting samples, and they found that tramadol was actually distributed throughout the environment. And then the question emerged, okay, so there, one group is saying this is being biosynthesized by a plant. The other group is saying this is a product of anthropogenic contamination of the environment. And if you're comparing these two samples, what is the difference?

• 35:47Hamilton Morris?

  How would you ever know? And what it came down to was radiocarbon. Because if something is a natural product, it will contain traces of radiocarbon. If something is synthesized from petrochemicals, it will contain no radiocarbon. So in the strictest sense, if you were going to say, what is the difference between synthetic mescaline and mescaline biosynthesized by a plant? Hypothetically, the biosynthesized mescaline would be slightly more radioactive. But this is not something that would have any health consequence. We're talking about amounts of radioactivity that are barely detectable with the most sensitive known analytical instruments.

• 36:26Hamilton Morris?

  But effectively, the short answer is nothing. There is nothing different. But again, back to the placebo effect, just because there's nothing different about it, doesn't mean that you won't have a different experience. This is why it's so complicated, because this is dependent on your values. So if you're somebody that really likes plants and you have a sort of animist relationship with plants, where you see them as having a vital essence of one kind or another, and that is important to you, then you are going to probably have a better experience with plant-derived mescaline because of the associations and the psychological priming associated with that. If you also think that synthetic artificial substances are bad and dangerous and undesirable, you will be inclined to have a negative experience.

• 37:08Hamilton Morris?

  So it's, again, this is not to say that people don't have different experiences, but that the experience is psychologically mediated as opposed to being mediated by the psychopharmacology of these effectively identical substances.

• 37:21Mark Plotkin?

  Which links to another issue that I want to discuss, and that is that of ritual, and the role of ritual, and the importance of ritual. The best description I was able to find, it was, "Ritual is the performance of ceremonial acts prescribed by tradition or sacred decrees." So many of these traditional uses involve a lot of ritual. So what in your view is the importance of this ritual, in terms of the placebo effect, setting the stage, or convincing you of something that might not happen without it?

• 37:53Hamilton Morris?

  I mean, there's so many different purposes that a ritual can have, depending on the ritual and the plant, and what is being done and where it's being done in the culture. But I think that ritual can be very important for emphasizing and accentuating certain dimensions of an experience. So traditionally, iboga was not used to treat substance abuse disorders in Gabon, but in recent years, it is being used that way. And what really struck me was that even without the ceremony being explicitly oriented toward that purpose, I felt that something of that nature was being implicitly communicated, which was a sort of...

• 38:32Hamilton Morris?

  Endurance feat, where you dance and you fast and you give yourself entirely to this experience and because you abandon comfort, because you abandon all of your associations in everyday life, it causes you to rely on yourself in a different way. And I think that that could have a sort of anti-addictive effect because it's, you know, what we refer to as addiction in the substance abuse sense, I think is a ramification of a far more common human tendency, which is a sense of being dependent on anything. It could be your phone, it could be someone that you're in a romantic relationship with,

• 39:17Hamilton Morris?

  it could be sweet foods, it could be a specific comfortable bed, and you feel that if you don't have that thing, you're just, that's necessary for your life. You're not whole without it. You need it. You're dependent on this external force. And I think that that ritual emphasizes a certain core independence and a endurance and a feeling that you have so much within you that you can withstand the deprivation of sleep or water because the reserves exist inside you.

• 39:49Mark Plotkin?

  Well, again, to drill down a little deeper on this, when I was in Oaxaca 20 years ago, I had the honor and privilege of working with Doña Julieta, who certainly didn't get the press that Maria Sabina did, but the local peoples considered her, "Every bit is powerful." At one point, she told me, she said, "You know, before the gringos started showing up here, before people like Wasan showed up here, we used the nino santos, the little sainted ones, the mushrooms, to heal and to search for lost objects." That was the two purposes. Very different than what people are going there for now. And so when I hear about people starting to combine cannabis with ayahuasca and things like this and saying it's traditional, what are your thoughts on this sort of combination of these different

• 40:34Mark Plotkin?

  traditions and these new uses?

• 40:35Hamilton Morris?

  Oh yeah, it's really actually remarkable. I'm repeatedly surprised by how common that has become. And this is something that's actually not talked about. I'm glad you brought this up because I'll talk to people and they'll say, you know, I just did a combo ceremony with filum bedusa bicolar. And I'll say, where was it? And they'll say, oh, you know, it was in Brooklyn. And I'll say, okay, what was it like? And they say, you know, they gave me five burns. And then as soon as I had recovered from the vomiting, they gave me bufalvarius venom. I'll say, oh, huh. So they're throwing that in the mix as well. And they'll say, and then when I came down from the bufalvarius venom, they gave me sananga eyedrops. And they'll think, wow, all right, they're just really giving you the women's sampler. Quite a buffet.

• 41:21Hamilton Morris?

  And that is not uncommon. I actually, when I talk to people that are, you know, not a part of an indigenous group, but they've created a sort of, let's, it sounds mean, but you know, sort of pseudo-traditional, pseudo-indigenous practice where they use pieces of those ceremonies, but they're not actually from those groups themselves. And the way, I know that that sounds kind of unsavory, the way I just described it, but I think some of these people have good intentions and they're not necessarily harming anyone, but they do tend to mix and match these traditions in a way that is surprising to me. I don't even want to go so far as to say it's necessarily bad, but it's something

• 42:02Hamilton Morris?

  that I would be very cautious about and it is a, I think, cause for concern because they'll do these multi-day, multi-substance retreats where, you know, day one, you do ayahuasca, day two, you do psilocybin-containing mushrooms, then you do ibogaine, then you end the whole thing with bufalvarius venom. And I don't know, I think your guess is as good as mine when it comes to whether or not that's a constructive practice. I also wanted to ask you one thing really quickly. So you were in Wautla in the early 2000s?

• 42:34Hamilton Morris?

  I'm curious, and Maria Sabino was dead by then, and I'm curious what it was like then.

• 42:40Mark Plotkin?

  It was sort of just becoming discovered, and I remember being in the plaza and there would be people walking through the plaza with plants of the gods, the Schultes and the Hoffman book going like, "I think I'll try that one," sort of like a Chinese menu. So it was changing at the time.

• 42:55Hamilton Morris?

  Tourists were doing this.

• 42:56Mark Plotkin?

  Tourists.

• 42:56Hamilton Morris?

  Yeah.

• 42:56Mark Plotkin?

  Gringos.

• 42:57Hamilton Morris?

  Yeah.

• 42:58Mark Plotkin?

  But I was working with a Mexican physician who had lived with the Weechhols for eight years and was actually dating the daughter of the most powerful shaman. So I kind of sidled into a very traditional healing tradition, rather than being all these guys who showed up in the plaza looking for people saying, "Mushrooms, mushrooms, hongos, hongos." So it was just at that cusp where things were becoming more commercial and more open to the outside world. And as you know, this type of psychedelic tourism has positive and negative aspects. And that's one of the things I want to ask you about, because you talked about good intentions. And Michael Pollan, in his book, talks about the fact that a

• 43:41Mark Plotkin?

  lot of people who are seeking out this psychedelic healing tend to be people with emotional problems, who may not be all that together, and are the ones most likely to come apart if they're not under the care of really a skilled practitioner who's not in it for the money or just for the money. So I'd like to get your thoughts on this type of psychedelic tourism and the potential downsides, and the real downsides that, you know, we see.

• 44:08Hamilton Morris?

  Yeah, and this is one of the fundamental changes that occurs in a medical model. If you talk to somebody like William Leonard Picard, who is a very prominent LSD chemist and is considered to have been responsible for producing more LSD than any person in history, and his...

• 44:29Hamilton Morris?

  Philosophy when it came to the distribution of LSD was you give it to healthy people. This is not a substance that you give to somebody who just broke up with their boyfriend or girlfriend. This is not something you give to somebody who's mentally unstable. This is something that is used for the betterment of healthy people. And in a medical model, that is the complete opposite. And instead, these by necessity must be used for treatment of disease because this is the way our current medical system works. There is no provision for the use of medicines by healthy people. That's not how health insurance works. It's not how the FDA works, for better or worse.

• 45:11Hamilton Morris?

  And so in these trials and at these retreats, so this occurs on both the gray market, black market, and the medicalized market, there is a tendency for people who are pursuing these things for treatment of disease. And you run the full gamut of problems that can come with that. I think on one end, you have a lot of the sorts of things that happen in the realm of unregulated cancer treatments where you have desperate people because a lot of diseases will put somebody in a state of serious desperation. You have a terminal neurodegenerative disease, you want something that will halt that degeneration, and you'll try anything.

• 45:56Hamilton Morris?

  And if somebody says, hey, Ibegane is a treatment for Parkinson's disease, which is a claim that is made quite often, and the evidence for it is not very strong. I've actually talked about this in the past. And is it possible that it could treat Parkinson's? Yeah, I think it's possible, but there certainly isn't sufficient evidence that people who have Parkinson's disease should take Ibegane, thinking that this is going to cure all of their problems. I mean, it really has not been adequately studied. So you have that sort of thing happening. And then you have the problems with aftercare, with integration, where if somebody has some kind of trauma and they have this experience at, let's say, a Toad Venom Retreat, then what? Is there a follow-up?

• 46:41Hamilton Morris?

  No. Then they're on their own. And what, and we don't live in a society that has provisions for caring for people after an experience like that, which can be really disruptive to their functioning.

• 46:54Mark Plotkin?

  I think this integration issue is much overlooked in our field. My organization, the Amazon Conservation Team, does a lot of work with the original ayahuascheros in the Northwest Amazon that Chilis worked with in the 40s. And many times you'll finish a ceremony and three days later you're walking down the street and you'll get some realization or you have some weird sort of semi-vision. And you're able to go back to the shaman and say, "What does that mean?" And they'll be able to explain it to you, usually. But in our culture, where you go to the doctor and then you're done, what happens afterwards? It's your issue, your problem. And these powerful substances in our heads, our minds and our souls, if you don't have somebody there guiding you through the aftermath, I think you're kind of asking for, asking for trouble.

• 47:38Mark Plotkin?

  And I think, again, this is one of the reasons why their medicine is effective in some cases when ours is not.

• 47:44Hamilton Morris?

  Yeah.

• 47:46Mark Plotkin?

  But I'm just wondering if you think that fungi are as promising as frogs in terms of new substances, new mind-altering substances, new stuff for microdosing? What's your perspective?

• 47:58Hamilton Morris?

  Well, from a sustainability perspective, mushrooms are about as good as anything anyone could ask for. And a lot of that has to do with the natural abundance of proliferation of different species and different genera that produce psilocybin. And that is a product of people being obsessed with mushrooms and searching for them everywhere. Because this wasn't always the case. You know, there was a time when people thought this was exclusively something that was found in Oaxaca, and if you wanted to try psilocybin-containing mushrooms, you had to go to Wautla. And it wasn't until people started finding them in the United States, and more importantly, until Dennis McKenna adapted laboratory techniques for the cultivation of psilocybin-containing

• 48:41Hamilton Morris?

  mushrooms and published it in an underground, non-scientific guide intended for lay readers, that not only did people recognize that these things grew naturally in the United States, but that they could cultivate them themselves. And that really sparked a revolution that dramatically increased the availability of psilocybin-containing mushrooms. They went from something so obscure that essentially nobody could try them to the most common psychedelic. And that was exclusively a product of innovation, really scientific innovation and cultivation techniques. And I think that- That is why it's so important to think about these things. If people hadn't done that, it could have been very different. It could have been even more overcrowding in tourism to Mexico if people thought that

• 49:24Hamilton Morris?

  by necessity they had to make this voyage. And instead, it had a fact where people were empowered to pursue these things independently, which I think can be a very positive thing. And the issue is that we just haven't developed equivalent techniques for a lot of these other things. That was sort of what I was trying to do with 5-MeO DMT. It's a little more complicated. But if there were a way to empower people to use these things sustainably, then a lot of these problems would go away.

• 49:52Mark Plotkin?

  Excellent point. I mean, we send ethnobotanists to the jungle searching for magic frogs, and it turns out here they are in Arizona. Richard Schultes left Massachusetts to the wilds of Oaxaca in 1936 in search of magic mushrooms. But according to Juliana Ferchi, who was on Tim Ferriss's show recently, there's probably 12 or 15 magic mushroom species growing in Massachusetts.

• 50:13Hamilton Morris?

  Yeah.

• 50:14Mark Plotkin?

  So on one hand, it's a bit like the Wizard of Oz. There's no place like home. But I think that what it brings home is that all species everywhere are valuable and need to be investigated. So where do we look next for these new and wild substances? Is it the coral reef? Is it the boreal forest? You're the natural product chemist. What do you think?

• 50:34Hamilton Morris?

  Well, to be, I don't actually do all that much work with natural products. Almost everything that I do is synthesis of novel compounds, although I've done a little bit. I've synthesized 5-BromodMT, for example, which is the only psychedelic that has ever been isolated from a marine organism. And it's really the only known psychedelic from the ocean and only the ocean. I think it is possible that there will be other marine psychedelics discovered. But again, the same problems emerge. I mean, thankfully, people don't really like 5-BromodMT that much because, and also thankfully, it's easy enough to synthesize, that nobody has considered attempting to poach the sponge source, SmenoSpongia aurea. But what if that were not the case?

• 51:19Hamilton Morris?

  What if it were like 5-MeO DMT and it produced a really remarkable, life-changing type experience? And that would rapidly become a conservation issue and you'd probably run into the same phenomenon where some...

• 51:31Hamilton Morris?

  Shaman or zealot would say, "Well, you know, look, I found an ancient engraving of a sponge, and this shows that, in fact, people have been using sponges for thousands of years, and it is our ancestral responsibility to remove these sponges from the ocean and figure out a way to smoke their alkaloids."

• 51:48Mark Plotkin?

  I think it's going to present a more challenging case for these neo-shamans to claim that it was always used as a hallucinogenic by the indigenous peoples who lived on the coral reef, but time will tell. Now, I'm wondering if you have any thoughts to share on the preponderance of hallucinogenic substances in the New World, the New World Tropics versus the Old World. A lot of people have paid a lot of lip service to this, and I haven't heard a convincing case as to why we have so much from Central and South America and relatively so little from Africa or Asia.

• 52:18Hamilton Morris?

  I think one answer seems to be that people have not looked as hard. I mean, people are finding new species of psilocybin-containing mushrooms. There was a species found in Congo not so long ago that, you know, just it seems very possible to me that nobody had looked until somewhat recently. There's even evidence of traditional use of psilocybin-containing mushrooms in Uganda, which would be really interesting, because that would suggest that this is, that there was maybe a parallel evolution of psilocybin-containing mushroom traditions in both Africa and in Mexico.

• 53:02Hamilton Morris?

  The evidence for the use in Uganda is relatively slim, but there is one paper on it that suggests that this could be the case. Yeah.

• 53:10Mark Plotkin?

  Well, if you get me that reference, we'll put it in the show notes, because I'm sure that'll be of great interest to a lot of people. Now, Weston Labar, who was on Schulte's early expeditions to Oklahoma in search of peyote, wrote a classic paper on the shamanic origins of religion and medicine. And I'm wondering if you have a personal opinion or insight as to whether these disciplines were essentially the same, or how much overlap there was thousands, tens of thousands, or maybe 100,000 years ago.

• 53:41Hamilton Morris?

  Oh, well, certainly, traditionally, there would have been an enormous amount of overlap, depending on what culture you're talking about as well. And I think that this is one of the things about modern medicine that has been lost, is these sort of ceremonial or ritual or psychological dimensions to the administration of a medicine, which will necessarily change the outcome. I mean, they've even done experiments with a treatment for hair loss called Finasteride, and they gave one group of people information where they said, you know, this drug, it's going to cause sexual dysfunction, it's going to cause depression, it's going to have some negative side effects. And the other group, they didn't say any of this.

• 54:22Hamilton Morris?

  And the people who'd been told that there was risk of these adverse effects experienced them more prominently. So there's no question that the way a medicine is administered changes the outcome, and that's something that is not really integrated into our current medical practices.

• 54:39Mark Plotkin?

  You have talked about the importance of strychnine in medicine. In Sarnum, where I've done a lot of my work, they have long sold a male aphrodisiac tea made from a species of strychnine. Now, I don't know whether there's strychnine in it, and I'm not advocating the use of strychnine, but I wonder if you could elaborate on this use of poisons as medicines and vice versa?

• 55:01Hamilton Morris?

  Have you ever tried it?

• 55:03Mark Plotkin?

  I have not tried it.

• 55:05Hamilton Morris?

  Yes. I mean, but, yes, strychnine was used as a medicine. It was actually used as a performance-enhancing drug by athletes. Whether or not that is really effective for that purpose is unclear to me. Obviously, it's potentially very unsafe, but I think strychnine is a really good example of this foundational concept in toxicology, which is the dose makes the poison. There is nothing that is inherently therapeutic or inherently toxic. These are all a function of dose. So there is a dose of strychnine that is not dangerous to consume. It's a very low dose. The therapeutic index of strychnine is quite a bit lower than other substances, but that doesn't mean that it is intrinsically a poison.

• 55:47Hamilton Morris?

  Almost everything that we call a poison, under some circumstances, at least conceivably, could have a therapeutic effect, including radiation. So, yeah.

• 55:58Hamilton Morris?

  So in terms of strychnine use, you know, I've always been curious about it because one thing that I've learned over the years is almost any time somebody classifies a substance as really, really bad or extremely dangerous, it tends to be the case that it's at least partially misunderstood. And it wouldn't surprise me all that much if maybe a very, very low dose of strychnine did elicit some kind of desirable effect. But obviously, I am not suggesting anyone listening to this go out and try to evaluate that on their own.

• 56:29Mark Plotkin?

  Agreed. We're not advocating for the use of poisons to see what the therapeutic dosage. I'm interested in the case of salvia. You know, we talked about medicinal plants before we knew much about medicinal fungi. And then Wasson comes back from Oaxaca, the medicinal mint. This was stunning to the chemical world, the ethno-botanical world. And I wonder what you think that tells us about what's still out there waiting to be discovered.

• 56:55Hamilton Morris?

  Yeah, I love the story of salvia because it was studied by no shortage of brilliant researchers. I mean, this was Albert Hofmann, who had little trouble isolating and then synthesizing psilocybin. He obviously synthesized LSD. He did very complicated work with ergalines. And yet, when he was given a sample of salvia divinorum, he couldn't figure it out. And that was the case for many people for many years. They would make extracts of it. They would inject that extract into a cat. There's a Mexican psychiatrist named Jose Luis Diaz, who did that work. And it was clear that it was having an effect on animals. Humans tried it. It was also seemed clear it was having an effect, but the effect was somewhat

• 57:40Hamilton Morris?

  subtle. And part of this had to do with the way that it was administered, usually as an aqueous infusion. So, you know, Wasson tried it, Hofmann tried it. They said that there was some effect, that it was sort of mushroom-like, but they couldn't quite put their finger on it. And People were trying to figure out, what is this stuff? What does it do? If you extract it, inject it into a cat, it does something, it has a subtle effect in humans. What chemical is responsible for this? There's no nitrogenous alkaloid in it that's responsible. So what's going on here? And I was actually talking to Dennis McKenna on my podcast recently, and he told me a really funny anecdote, where he was working for Shaman Pharmaceuticals, and he was studying extracts of salvia and looking at their affinity for the kappa opioid receptor. And it was off the charts.

• 58:25Hamilton Morris?

  And he thought, okay, this doesn't make any sense. There's no way that this plant contains something this potent. I must have made a mistake. So he actually discovered this, but then discounted his own finding because it seemed too extraordinary to be real. And it wasn't until Brian Roth actually started working with another citizen scientist named Daniel Seibert, that they were able to definitively demonstrate that the active principle of salvia divinorum was salvinorin A, and that salvinorin A was an extraordinarily potent and selective agonist for the kappa opioid receptor, and that it was the most potent naturally occurring psychedelic.

• 59:06Hamilton Morris?

  So that is quite a curveball coming from a plant that there was some ambiguity whether it was active at all.

• 59:13Mark Plotkin?

  Well, when I was in Oaxaca and asked the shaman about it, she said, I'm not going to give it to you. It's too strong and you don't need it. And eventually she changed her mind, but it was really very unpleasant. And I didn't feel a healing result from it, but now that it's obtained such wide popularity, I have to say, I remain very surprised. But it clearly is not similar to many of the other mind-altering substances that I've had experiences with.

• 59:42Hamilton Morris?

  Did you chew the leaves or use aqueous infusion?

• 59:45Mark Plotkin?

  No, it was the leaves.

• 59:47Hamilton Morris?

  Yeah.

• 59:48Mark Plotkin?

  So that's how she administered. She said she didn't use it much because it was so powerful. And it was like sort of a last ditch or very serious cases. Whereas, as you point out, that the shamans often give you medicines when you're not sick. What we probably call adaptogens or immunostimulants, which 20 years ago weren't words that were in common parlance. But I was just struck by how different it was and how unpleasant it was, frankly.

• 1:00:13Hamilton Morris?

  And what was it that you didn't like?

• 1:00:16Mark Plotkin?

  I felt that I was underwater in the dark for nine hours. I didn't feel a sort of healing therapeutic effect. It just was almost like a punishment. Hmm. So, but I mean, you know, shamans will tell you, if you want a light show, go to Disneyland. Okay. If you take ayahuasca and you don't see anything, it doesn't mean it's not working, that the behuco, the remedio is giving you what you need. And sometimes you see the ninth dimension and sometimes you just fall asleep, but you're getting out of it what you need. The plant knows, that's what they say. So, again, I can't say that I was disappointed because I didn't see fireworks. I mean, I'm not a person who is seeking thrills this way.

• 1:00:59Mark Plotkin?

  It's just that, you know, many times we've all had experiences with these substances where we felt better for it, it felt relief, or stressed, or whatever, and, you know, sometimes you don't, and sometimes maybe you feel a little worse off, kind of how I felt. Yeah. So, anyway, I want to wind up here, but since you brought up our friend Dennis McKenna, Dennis McKenna is organizing a conference which will discuss, among other things, the drunken, the stoned ape theory, first promulgated by his late brother Terence. And at the same time, we have people who are putting forward the drunken monkey theory. And I wonder what you think of these ideas that these mind-altering substances may have

• 1:01:42Mark Plotkin?

  played a fundamental role in not only human culture, but human evolution. The stoned ape theory, which was put forward by Terence McKenna, is of course stating that once we discovered mushrooms, whatever mind-altering substances, it created consciousness. And we began to wonder, it wasn't just about what's to eat, or what plant do I use when I get sick. The drunken monkey theory is that our ancestors lived in the trees, and the ripest fruit would fall to the ground, which is the sweetest fruit, which in some cases is fermented fruit. So, they were catching a buzz from alcohol. And so, these are sort of presented as different cases, but they kind of point in the same direction.

• 1:02:24Mark Plotkin?

  And so, we can just talk about the stoned ape theory, as to whether mind-altering substances really played a fundamental role, or may have played a fundamental role, or may have played no role, in the evolution of consciousness, culture, history, and evolution.

• 1:02:41Hamilton Morris?

  Well, evolutionarily, I think the evidence for that is pretty slim to nonexistent. And I think that Terrence McKenna is sometimes taken too literally. You know, I think of him as a poet. I love everything that he says, and I think that a lot of the things that he said were intended to provoke people, to cause them to really think about these things and to value them. And I think that in that capacity, he was extraordinarily effective. But from an evolutionary biological perspective, that would not be my first explanation for how consciousness emerged in humans. That said, I think that if today, in our culture, with all of the distractions and all of the

• 1:03:20Hamilton Morris?

  things that exist, we can still look to this experience and see it as one of the most momentous and amazing in an entire life, you think, well, what would that have been like if you didn't have all of these distractions? If it's that, if it's this valuable to us now, what would it have been like in the past? And if it allows people to have religious epiphanies and even start religions now, then what would it have been like in the past? And I think that it's reasonable to assume that it might have been similar. That said, I think that people get into trouble when they, you know, try to explain everything with psychedelics, which is the extreme that people tend to go to. They either want to, again, back to these polarizing dichotomies, either psychedelics

• 1:04:04Hamilton Morris?

  are purposeless and have no historical value, or they're the origin of consciousness, religion, and everything else. And I don't doubt that they did play a role in some ancient religions, but the question is how significant that role was. And, yeah.

• 1:04:20Mark Plotkin?

  So, I want to thank you for your kindness and your insights. It's a pleasure to listen to somebody so well spoken. But I want to conclude by asking you about your mentor, Nicholas Lengletz, and the primatology of primatologists.

• 1:04:36Hamilton Morris?

  Yeah, I mean Nicolas Langlitz is a really brilliant medical doctor who then became an anthropologist and he wrote a book called Neuropsychopedia, which I really admire, which is an anthropological analysis of neuroscientific research on psychedelics. And he's really great at taking a different perspective on these issues and really asking questions about what are the motivations for these people, why are they doing it, what biases are integrated into the work they do. And I, he then switched to doing a sort of meta-primatology analysis where he'd look at the primatology of primatologists, which I thought was also really interesting. But I think he might get back into psychedelics right now because when he wrote Neuropsychopedia,

• 1:05:20Hamilton Morris?

  this was somewhat of a fringe issue. You know, he was spending time with the dozen or so researchers that were doing this work, like Franz Wolandweider. But now it's hard for somebody to keep track of it, even if it's their full-time job. I mean, by some estimates, there are hundreds of pharmaceutical startups that are pursuing these things therapeutically. I am repeatedly amazed by the proliferation of new scientific papers and patents coming out on psychedelics. I mean, this is really expanding at a pace that has never before been seen. I mean, only rivaled by the 1960s. And so it's good that there are people carefully monitoring what's happening because it's an important time in history.

• 1:06:02Mark Plotkin?

  Last question. Timothy Leary's legacy, from your perspective.

• 1:06:09Hamilton Morris?

  Well, I get, like McKenna, I think that Leary is somebody who's often misunderstood and possibly taken too literally. I see Leary as a comedian and a very good one at that. I mean, when I read his books, when I listen to him speak, I am repeatedly struck by how hilarious he is. And I think that he was blamed for a lot of the problems that emerged in relation to psychedelic drug use because people would say, okay, everything was going right, this is all going to be a medicine, and then Timothy Leary came along and this zealot wanted to go on some kind of ego crusade to...

• 1:06:52Hamilton Morris?

  Create a counterculture that would delegitimize psychedelics. And I think that's a really uncharitable interpretation of what was going on. I mean, I think that the history of psychedelics had been profoundly elitist. And Timothy Leary was somebody who wanted to break with that tradition of elitism. And he wanted to say, this experience was good for me, and I think it's going to be good for you as well. I have no reason to say that this isn't going to be good for you. So in fact, go for it. You know, is that the most responsible thing to have done? Probably not. But I think that there was something honest about it and something democratic about it and something that actually put faith in the intelligence of the broader community,

• 1:07:36Hamilton Morris?

  whether or not that was a good or bad idea. And if it hadn't been him, it would have been somebody else. I think that's the other thing to keep in mind with all of this. You can't... Hiding is a great short-term strategy, and it's a terrible long-term strategy. And if people think that these problems are going to be solved by hiding or being silent, it's just not the case. Maybe for one person, for one generation, you can hide. But if you want to see progress in the long run, you have to be open. You have to be honest. And ultimately, what Timothy Leary did in the long term is the right thing. Because he was honest about what he felt about these things. He thought they were amazing. He wasn't going to hide that and say, oh, no, this is only for medical use, because he didn't believe that. And I think that the same is true for these conservation issues.

• 1:08:21Hamilton Morris?

  I remember somebody criticizing me and saying, well, don't you realize that by even talking about toad conservation, you're simply informing more people about toads? So what you really should do is just not talk about it. And again, that might be true if I were the only person talking about it. But people are going to talk about it whether I like it or not. And so the question is, are you going to talk about it responsibly?

• 1:08:41Mark Plotkin?

  Agreed. Thank you very much. This is great.

• 1:08:45Tim Ferriss?

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• 1:09:30Tim Ferriss?

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