The Tim Ferriss Show Transcripts: 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 (#605)

Please enjoy this special episode of The Tim Ferriss Show, in which Dr. Mark Plotkin takes over as host for an episode of the Plants of the Gods podcast with guest Hamilton Morris.

Who is Mark? Mark (@DocMarkPlotkin) is an ethnobotanist who serves as president of the Amazon Conservation Team, 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, 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. 

Hamilton Morris (@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, in which he explores the chemistry and traditions surrounding psychoactive drugs. You can find my most recent interview with him at tim.blog/hamilton.  

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. 

Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!

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Mark Plotkin: 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.

Hamilton 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 Rettig, 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 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 the milking of 2,000 toads from one man. And you add to that his partner, Gerry Sandoval or his former partner, makes that 4,000 toads. And then everybody else 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 this, if it continues to gain popularity at the current rate, it’s going to become a problem very quickly.

Mark 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 O’odham 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.

Hamilton Morris: Yeah, 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 I began to produce it fully synthetically would be totally impossible for a normal person to do on a multi-gram scale to supply a clinic for something like that. But if it were 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. This is one of the advantages is that it could be produced industrially for a pharmaceutical company. There are 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 in a region where they 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 really 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. 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.

Mark 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.

Hamilton 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 in part of a religion called Bwiti. 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. But so this idea that ibogaine or iboga could serve as a treatment for substance abuse 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. 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 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 third to a quarter of people that undergo this therapy are able to stop using heroin or other opioids.

Mark 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 floor. 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 variety of purposes.

Hamilton Morris: Well, yes, microdosing is difficult to talk about because it doesn’t really have a precise definition. So what I might call 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. For some people they define microdose is 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 the therapeutic endpoints aren’t well defined in a lot of these microdosing. What is it exactly that people are looking for? Enhanced creativity, enhanced focus, enhanced energy, mood lift. People seem to be pursuing microdosing for an almost unlimited number of different applications. And so maybe it works for one thing for one person, maybe somebody suffering from chronic inflammation with a certain psychedelic could have some benefit and maybe for someone else there would be no benefit at all. 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?

Mark 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 floor, 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.

Hamilton 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 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 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 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 Nelson, 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 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. 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. And at the beginning it was obscure. There were psychedelic cognoscenti 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-MeO-DMT 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 Bufo alvarius venom. It just was never talked about as much. And there’s something I suppose, something cool about the idea of smoking toad venom. 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 Octavio Rettig and Gerry Sandoval started going on a crusade as toad venom evangelists, that this really became the phenomenon that we’re currently talking about.

Mark Plotkin: Well, that’s a new phrase for me, toad venom evangelists. I’m going to have to be lifting that one. So why are people calling this the God molecule versus just plain old DMT?

Hamilton 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, very, very closely related to DMT, but psilocin, the active metabolite psilocybin and a component of psilocybin-containing mushrooms is closer to DMT than 5-MeO-DMT is structurally. You could call psilocin, 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-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 N,N,O-Trimethyl-Serotonin, 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 often see you’re in environment in a different way. 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. 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.

Mark 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 of the gods and fungi of the gods and frogs of the gods may have a downside.

Hamilton 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. And with 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.

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 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 this is the tendency as 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.

Mark 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.

Hamilton Morris: Oh, certainly. Yeah. 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 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 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. 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 this, during the pandemic, I had a friend who this happened to cause 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 taking showers five times a day? Why is he always so wet? And he then told me, “I don’t know what’s going on. I’ve just been vomiting all the time and a hot shower is really the only thing that helps.” And I thought, wow, all right, I know what you have. So that’s… 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.

Mark Plotkin: Well my mentor Richard Schultes would often describe mind-altering plants as scalpels in the hand of a shame and 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 approached with reverence and carefully. And that’s why I often tell people you shouldn’t be experimenting on your own with very powerful substances. I’m 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 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?

Hamilton Morris: Mm, I love frogs and they are amazing chemists. 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 as a norbornene ring, which is just bizarre. 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.

Mark Plotkin: Well, I have read recent reports of two venomous frogs found in Eastern Brazil, Genus Corythomantis 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 is to find, utilize, and protect these creatures at the same time that we seem to be destroying them faster than ever. There’s about a thousand species of frogs are known in the Amazon and we’re finding more all the time.

But I wanted to turn to one of your idols or mentors or heroes, I don’t know how you’d best describe him, 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.

Hamilton Morris: Oh yeah, yeah, of course. 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 going to be, it’s a painful procedure. He drank it and the morphine had this miraculous analgesic effect. And he thought that was great. “That was exactly what I needed.” And later he asked the nurse how much morphine was that in the juice? And she said, “Oh no, that was sugar. Those were sugar crystals.”

So he came to realize that his own mind was capable of producing these sorts of experiences. 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. 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, this could be some kind of cardiac talks and 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.

Mark 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?

Hamilton 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 act of substance. Well, the whole issue with placebo is that you can’t tell. That’s the whole purpose of this effect. 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.

Mark 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 masculine and masculine?

Hamilton Morris: I love that question because 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 Nauclea latifolia. 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. 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 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 one group is saying, “This is being biosynthesis 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? 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 masculine and masculine biosynthesis by a plant? Hypothetically, the biosynthesis masculine would be slightly more radioactive, but this is not something that would have any health consequence. We’re talking about amounts of radio activity that are barely detectable with the most sensitive known analytical instruments, but effectively the short answer is nothing.

There’s 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 drive masculine 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. 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 psycho-pharmacology of these effectively identical substances.

Mark 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?

Hamilton Morris: 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 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 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. It could be sweet foods, it could be a specific comfortable bed. And you feel that if you don’t have that thing 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.

Mark 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 María Sabina did, but the local people considered her every bit as powerful. And at one point she told me, she said, “Before the Gringo started showing up here, before people like Wasson showed up here, we used the Niños Santos, the little sainted ones, the mushrooms, to heal and to search for lost objects.”

Hamilton Morris: Yes.

Mark Plotkin: 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 traditions and these new uses?

Hamilton 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, “I just did a combo ceremony with Phyllomedusa bicolor,” and I’ll say, “Oh, where was it?” And they say, “Oh it was in Brooklyn.” And I’ll say, “Okay, what was it like?” And they say, “They gave me five burns and then as soon as I’d recovered from the vomiting, they gave me Bufo alvarius venom.” And 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 Bufo alvarius venom, they gave me Sananga eye drops.” And I’m thinking, wow, all right, they’re just really giving you the Whitman’s Sampler.

Mark Plotkin: Quite a buffet.

Hamilton Morris: And that is not uncommon. I actually, when I talk to people that are not a part of an indigenous group, but they’ve created a sort of, it sounds mean but, 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 that I would be very cautious about. And I think is a cause for concern because they’ll do these multi-day multi-substance retreats where day one, you do ayahuasca, day two, you do psilocybin-containing mushrooms, then you do ibogaine. Then you end the whole thing with Bufo alvarius 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 Huautla in the early 2000s?

Mark Plotkin: Mm-hmm.

Hamilton Morris: I’m curious, and María Sabina was dead by then, and I’m curious what it was like then?

Mark 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 Hofmann book going like, “I think I’ll try that one,” sort of like a Chinese menu. So it was changing at the time.

Hamilton Morris: Tourists were doing this.

Mark Plotkin: Tourists.

Hamilton Morris: Yeah.

Mark Plotkin: Gringos.

Hamilton Morris: Yeah.

Mark Plotkin: But I was working with a Mexican physician who had lived with the Huichols 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 wanted to ask you about because you talked about good intentions.

And Michael Pollan in his book talks about the fact that a lot of people who are seeking out the 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 we see.

Hamilton Morris: Yeah, and this is one of the fundamental changes that occurs in a medical model. If you talk to somebody like William Leonard Pickard, 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 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. That’s not how the FDA works, for better or worse. 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. And if somebody says, “Hey, ibogaine 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 ibogaine thinking that this is going to cure all of their problems. 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, let’s say a toad venom retreat, then what? Is there a follow up? No. Then they’re on their own. 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.

Mark 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 ayahuasqueros in the Northwest Amazon that Shultes 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’ll 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 this 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 trouble. And I think, again, this is one of the reasons why their medicine is effective in some cases when ours is not.

Hamilton Morris: Yeah.

Mark Plotkin: But I’m just wondering if you think that fungi is as promising as frogs in terms of new substances, new mind-altering substances, new stuff from microdosing, what’s your perspective?

Hamilton 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 genre 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. 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 Huautla 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 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, by necessity, they had to make this voyage. And instead, it had a effect 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. It’s 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.

Mark Plotkin: Excellent point. We send ethnobotany to the jungle, searching for magic frogs, and it turns out here they are in Arizona. Richard Schultes left Massachusetts to the wild to Oaxaca in 1936 in search of magic mushrooms. But according to Giuliana Furci, who was on Tim Ferriss’ show recently, there’s probably 12 or 15 magic mushroom species growing in Massachusetts. 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? It is the coral reef. Is it the boreal forest? You’re the natural product chemist, what do you think?

Hamilton Morris: Well, 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-Bromo-DMT, 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. Thankfully people don’t really like 5-Bromo-DMT that much because, and also, thankfully, it’s easy enough to synthesize that nobody has considered attempting to poach the sponge source, [inaudible 00:44:52].

But what if that were not the case? 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 or some shaman or zealot would say, “Well, 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.”

Mark Plotkin: I think it’s going to present a more challenging case for these neoshaman to claim that it was always used as hallucinogenic by the indigenous people 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?

Hamilton Morris: I think one answer seems to be that people have not looked as hard. People are finding new species of psilocybin-containing mushrooms. There was a species found in Congo not so long ago that just, it seems very possible to me that nobody had looked until somewhat recently. There was 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. 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.

Mark 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 La Barre, who was on Schulte’s early expeditions to Oklahoman’s 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 a hundred thousand years ago.

Hamilton 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. They’ve even done experiments with a treatment for hair loss called Finasteride. And they gave one group of people information where they said, “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. And the people had 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.

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

Hamilton Morris: Have you ever tried it?

Mark Plotkin: I have not tried it.

Hamilton Morris: Yes. But yeah, 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.

Almost everything that we call a poison, under some circumstances — at least conceivably — could have a therapeutic effect, including radiation. So, yeah. So in terms of strychnine use, I’ve always been curious about it because one thing that I’ve learned over the years is almost anytime somebody classifies the 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.

Mark Plotkin: Agreed. We’re not advocating for the use of poisons to see what the therapeutic dosage is. I mentioned 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, to the ethnobotanical world. And I wonder what you think that tells us about what’s still out there waiting to be discovered?

Hamilton Morris: Yeah. I love the story of salvia because it was studied by no shortage of brilliant researchers. This was Albert Hofmann, who had little trouble isolating and then synthesizing psilocin and psilocybin. He obviously synthesized LSD. He did very complicated work with ergolines. 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 José Luis Díaz who did that work. And it was clear that it was having a effect on animals. Humans tried it. It was also seemed clear, it was having an effect, but the effect was somewhat subtle. And part of this had to do with the way that it was administered usually as an aqueous infusion. So 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 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 Bryan Roth actually started working with another citizen scientist named Daniel Siebert 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. So that is quite a curve ball coming from a plant that there was some ambiguity, whether it was active at all.

Mark 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 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.

Hamilton Morris: Did you chew the leaves or use a aqueous infusion?

Mark Plotkin: No, it was the leaves. Yeah, 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 these shamans often give you medicines when you’re not sick, what we’d probably call adaptogens or immuno stimulants, 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.

Hamilton Morris: And what was it that you didn’t like?

Mark Plotkin: I felt that I was underwater in the dark for nine hours. I didn’t feel sort of healing therapeutic effect. It just was almost like a punishment. But shamans will tell you if you want a light show, go to Disneyland. If you take ayahuasca and you don’t see anything, it doesn’t mean it’s not working. That the [inaudible 00:54:18] 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’m not a person who is seeking thrills this way. It’s just that many times we’ve all had experiences with these substances where we felt better for it or felt relief or stressed or whatever.

And sometimes you don’t and sometimes maybe you feel a little worse off kind of how I felt. So anyway, I want to wind up here, but since you brought up our friend, Dennis McKenna. Dennis McKenna is organizing a conference, which we’ll discuss among other things, the drunken, the stone aped 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 subs may have 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 there 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. 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.

Hamilton Morris: Well, evolutionarily, I think the evidence for that is pretty slim to nonexistent. And I think that Terence McKenna sometimes taken too literally. 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 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 these distractions? 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 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 or purposeless and have no historical value or 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.

Mark 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, Nicolas Langlitz and the primatology of primatologists.

Hamilton Morris: Yes. Yeah, Nicolas Langlitz is a really brilliant medical doctor who then became an anthropologist and he wrote a book called Neuropsychedelia, 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 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 Neuropsychedelia, this was somewhat of a fringe issue.

He was spending time with the dozen or so researchers that were doing this work like Franz Vollenweider, but now it’s hard for somebody to keep track of it, even if it’s their full-time job. 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. This is really expanding at a pace that has never before been seen. 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.

Mark Plotkin: Last question. Timothy Leary’s legacy and from your perspective.

Hamilton Morris: Well, 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. 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 create a counterculture that would de-legitimize psychedelics. And I think that’s a really uncharitable interpretation of what was going on. 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.” Is that the most responsible thing to have done? Probably not. But I think that, 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, whether or not that was a good or bad idea. And if it hadn’t been him, it would’ve 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. I remember somebody criticizing me and saying, “Well, don’t you realize 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?

Mark Plotkin: Agreed, thank you very much. This is great.

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