Science Vs - Ayahuasca: WTF is up with DMT?

Episode Date: December 14, 2023

DMT might be the weirdest drug in the already weird world of psychedelics. It’s the active ingredient in ayahuasca, but on its own, DMT can give you what’s nicknamed “the businessman’s trip” — a psychedelic journey that can be done and dusted inside 15 minutes. So what is this drug doing to our brains? And could it help people with depression? We catch up with Dr Chris Timmermann, Dr Graham Campbell, Michelle Baker Jones and Dr David Olson to find out. Find our transcript here: https://bit.ly/ScienceVsDMT  Listeners, we need you! Tell us: What should we versus in 2024? Also, we’re looking for your questions on topics including sex, diet and menopause! In the U.S., leave us a voicemail at 774-481-1238 or send an email or voice memo to [e-mail]. Find us on Social Media! Instagram: @science_vs / TikTok: @wendyzukerman / Twitter: @sciencevs In this episode, we cover: (00:00) WE WANT TO HEAR FROM YOU! (00:59) Celebs love ayahuasca (04:58) DMT (08:06) The ‘Rick and Morty’ Trip (13:30) Is DMT a portal? (15:42) DMT in our brains (21:53) DMT for depression? (29:33) Plastic psychedelics (36:10) Risks of DMT and ayahuasca (39:09) Where do we land on DMT? This episode was produced by Joel Werner, with help from Wendy Zukerman, Michelle Dang, Rose Rimler, and Nick DelRose. We’re edited by Blythe Terrell. Fact checking by Diane Kelly. Mix and sound design by Bumi Hidaka. Music written by Bumi Hidaka, Peter Leonard, and Bobby Lord. Thanks to all the researchers we spoke to including Dr Rick Strassman, Dr David Erritzoe, Dr Jimo Borjigin, Dr. Steven Barker, Dr Brandon Weiss, Dr Pascal Michael, Dr Michael Gatch, Professor Jerome Sarris, Professor Deepak Dsouza, Sean Chiddy, and David Nickles. Special thanks to Jack Weinstein and Hunter, Katie Vines, Finn and Jules, Christian Darío Vásquez, Valentina Powers, Zac Schmidt, the Zukerman Family and Joseph Lavelle Wilson.  Science Vs is a Spotify Studios Original. Listen for free on Spotify or wherever you get your podcasts. Follow us and tap the bell for episode notifications.  Learn more about your ad choices. Visit podcastchoices.com/adchoices

Hi, I'm Wendy Zuckerman and you're listening to Science Versus. Today is the last episode for a little bit, just for a little bit. We're going to be back in the new year. We need a little break to work on some new episodes. And while we're finding out what our new episodes are going to be, we'd love your help. We want to know what you want us to versus. What have you been curious about? We want to hear it.

So let us know all the ways to contact us. There's a phone number, there's an email, there's social media. It's all in the show notes. Now, on top of just suggesting to us any idea that you have, we would also love to get voicemails of you guys on a couple of topics. So we want to know if you have questions in particular about sex, diet, any questions on that, and also menopause. If you've experienced it, menopause, perimenopause, I want to know all about your symptoms and any questions that you have. To get in touch, it's all in the show notes. All right, now let's let the show begin. Today, we are diving into the science of what is perhaps the weirdest and most mysterious

psychedelic drug, ayahuasca. If you're into late night talk shows, you'll know that this drug is the talk of Hollywood. You drank ayahuasca tea. It's like you can't swing a dead cat without some celebrity telling you a story about this adventure they went on where they took ayahuasca and things got wild. There's Miley Cyrus.

I had a very great ayahuasca experience. Prince Harry, Megan Fox. Do you guys know what ayahuasca is? Ooh, yes. Y'all know ayahuasca. Musicians, sports stars, comedians, podcasters all seem to be giving it a go. And all of these stories start basically the same way. You head into the jungles of South or Central America.

You really are in the middle of the jungle. Tens of millions of frogs and insects. F***ing howler monkeys, the most useless animal in the world. They scream at the top of their lungs. And while you're deep in the jungle, you sit in a circle with a bunch of people that you've never met. Someone is brewing this tea. You know, there's a guy, a shaman, looks like a shaman. And he's old and he's got a face like the map of the world.

And he calls you forward and you kneel before him. And I remember watching everybody go up and take theirs. They had one cup, one cup, one cup. Oh, man. Awful taste and stuff. As soon as this goes down, I'm gone. You might stop spewing. A ton.

Purge. They call it purging. Vomit everything out of your body. So you have a puke bucket too, but some people get the shits. I got the. But what's happening on the outside is nothing compared to what's going on inside your head. It was incredibly intense. I went to hell for eternity.

This was like somebody unzipped the universe. And I saw like gray, like it looked like sand coming from my body. What was that? Was that me? And she reached down my throat and pulled out every dead animal I had ever eaten and made me throw it up. And is that good? Well, apparently, it is good. Because all that hectic stuff, the vomiting, the pooing, the mind-bending hallucinations,

people say that it works miracles. It was one of the most important things that happened to me in my life. The plant was a medicine. Just felt wonderful about myself, about decisions I was making, about the direction I was headed in my life. So today on the show, we are entering the world of ayahuasca. Because while these ayahuasca ceremonies have been going on for ages, scientists have actually bottled the active ingredient in this brew.

It's DMT. That's the chemical that makes you trip balls. And amazingly, when you smoke it or inject it, you don't vom or yourself, which makes this drug way more tantalising as a medicine. A medicine that some say might cure depression where no other drugs have helped. So we are going to find out,

what on earth is this drug doing to our brains? Can we channel its powers to help us feel wonderful about ourselves? And with all these hectic stories, what are the risks here? When it comes to ayahuasca, there's a lot of... And she reached down my throat and pulled out every dead animal I'd ever eaten. But then there's science. Science vs. Ayahuasca is coming up just after the break. So Science Vest's ayahuasca is coming up just after the break. It's season three of The Joy of Why, and I still have a lot of questions.

Like, what is this thing we call time? Why does altruism exist? And where is Jan 11? I'm here, astrophysicist and co-host, ready for anything. That's right. I'm bringing in the A-team. So brace yourselves. Get ready to learn.

I'm Jana Levin. I'm Steve Strogatz. And this is... Quantum Magazine's podcast, The Joy of Why. New episodes drop every other Thursday, starting February 1st. What does the AI revolution mean? For jobs. For getting things done. Who are the AI revolution mean for jobs, for getting things done?

Who are the people creating this technology and what do they think? I'm Rana El-Khelyoubi, an AI scientist, entrepreneur, investor, and now host of the new podcast, Pioneers of AI. Think of it as your guide for all things AI, with the most human issues at the center. Join me every Wednesday for Pioneers of AI. And don't forget to subscribe wherever you tune in. Welcome back. Today on the show, we are guzzling down the science on ayahuasca and the chemical inside it to DMT that makes you trip balls.

And we're going to find out what is up with this drug, what's it doing in our brain, and can we use it for medicine? To tell us all about it is Joel Werner, supervising producer of Science Versus. Hey, Joel. Hey, Wendy. Do you know it's so hot and dry in Melbourne right now that my snot is drying in my nose? Is that better or worse than in winter where it just like

runs out of your nose constantly? I don't know. It's true. It's convenient. It's more convenient in a little hard package. So Joel, so you were supposed to do a completely different episode and then you started reading about DMT and couldn't stop. Why were you so intrigued? Yeah, look, I think, you know, I studied brain science at uni and I've always been fascinated with the way that this bit of mushy grey stuff in between our ears just creates this entire sense of the world that we have.

And when stuff gets in there and really messes with that, like, I want to know more. And I think DMT is a drug that messes with our grey stuff in a way that, like, not many other drugs do. Okay. So where do we begin? So yeah, for centuries, people in South and Central America have been drinking this ayahuasca brew and have been using it for healing ceremonies, for spiritual ceremonies. But like way more recently in the 1930s, scientists actually isolated the DMT molecule in a lab. But one super interesting thing about DMT is that it's not just found in the plants

that they use to make the ayahuasca brew, right? Like DMT is found in thousands of plant species. Oh, wow. And it's not just found in brew, right? Like DMT is found in thousands of plant species. And it's not just found in plants, right? DMT is like found in mammals. So we looked in the lung of a rabbit, for example, and we found DMT there. And we've also found DMT occurring in humans, like naturally occurring in humans. Like we produce DMT inside our bodies. It's in our brains. It's in our placentas. Really? But it's a big mystery, right? Like we don't really know what it's doing there. Wow. So there's been some speculation that DMT might play a role when we're dreaming, for example, or that like when people have near-death experiences that maybe DMT is wrapped up in that.

But we don't know. We don't know. It's so weird. So what do we know about DMT? So yeah, what we do know, we do know that if you give the body a big dose of it all at once, well, then that's when s*** really kicks off. Right, yes.

That is when you unzip the universe or whatever. Unzip the universe, you throw it off and it crumples in a pile in the corner. Poor universe. Okay, so let's dive into the brain of someone on this weird molecule DMT and see what happens as their universe unzips. I want you to meet Anya. Anya is a psychedelic researcher based in London. She's originally from Russia. And she's been a volunteer in a few DMT experiments being run out of Imperial College London. So she's sitting in the lab there when the team injects DMT straight into her arm. You feel the liquid going inside. So it's kind of

this cold flush going inside. And then you start feeling DMT effects which is tingling or a rush going through the body and this feeling of acceleration of going somewhere and then very very fast after that come very very strong visual hallucinations of like geometric patterns of something that's moving. I started to have the sensation that I'm being observed or probed or scanned somehow by some entities that I could see those tendrils coming inside me and like checking through every cell of my body. And at the time I was completely out of it

and it just felt absolutely real, like as real as when we are speaking right now. And in my head, I thought, I'm not sure I'm okay with them checking out every single cell of my body. So after the aliens examine every cell in Anya's body, they take her to what she describes as some sort of intergalactic hub. And I was going through different parts of this space hub, observing all the aliens that are there and it really felt like I'm in the episode of Rick and Morty on one of those planets. Then I wandered off to the slightly dodgy part of that space hub. And then I realized like, oh, this must be space pirates.

And that broke the illusion of how real it was. And I started to laugh. And then I thought, well, only my brain can come up with space pirates here. And with that, I realized like, oh, I'm not that representative of ours who was sent to this space hub.

I'm actually taking part in a GMT experiment and my brain just came up with space pirates. And so is that when you started to come out of the trip then? And that's when I started to come out of the trip. Saved by the space pirates. Exactly, exactly. Wow, that is a drug that makes you trip balls. I was wondering if the Rick and Morty fan base in her trip is just as toxic as it is in real life. I don't think we have a way of testing that.

What's really wild about Anya's experience? There's two things. There's two things that make these DMT trips like kind of bizarre, even in the bizarre world of psychedelics. The first one is just how quickly they happen, right? So like Anya's experience, like how long do you reckon that trip would have taken? I guess it felt like she would have been under for maybe half a day or something. Exactly right. Like ayahuasca ceremonies go on for like four to six hours depending on the

strength of the dose. In this particular study that Anya was part of, they were experimenting with longer than usual DMT trips. And so she was probably under for about 30 to 45 minutes here. But typically, if you smoke or inject DMT, the peak would have happened about two or three minutes into the trip. Two or three minutes. Yeah. And the whole thing is done and dusted inside 15 minutes on a DMT trip, right? So it's this super intense but also super short-acting psychedelic drug. Wow, wow. super intense but also super short-acting psychedelic drug. Wow.

Wow, wow, wow. And that's why it's sometimes been given this nickname of the businessman's trip. So, like, the idea is you could have this psychedelic experience in your lunch break and then still be back for the meeting with Harold from HR at 2 p.m. Joel, our workday sisters are about to get so much more fun look don't tell Harold from HR he's a bit of a stickler for no psychedelics in the lunch break but no no that's right okay so can I ask um okay so super short trips that is one of the things that makes DMT unique the the other thing so

the fact that she felt like it was really real, like what's going on there? Because I feel like with most sort of psychedelics, they're sort of imprinted on the world. Like you kind of know that you're tripping, but she didn't? A hundred percent. One hundred percent. So like the DMT experience is like fully immersive. And people also report that you don't necessarily feel high, that it still feels like you in your like sober brain. And you're just like, she felt like she was in that intergalactic spaceport. And that was just her life. And that

was what she was doing until the space pirates saved her from the trip. Like at the point of most intense experience, it felt absolutely real. Like absolutely real. When you talk to people who have done DMT and done other psychedelic drugs, they really talk about like how immersively real the DMT trip experience is and that nothing really compares to how much you feel like you're there in the intergalactic space hub or whatever and it feels just like your real life. It's so weird. And this has led a lot of people to think that these dimensions that they're visiting or these aliens or other entities that they're

encountering aren't just like your brain on an intense psychedelic drug, but are actually real dimensions and real aliens. So for example, here's what Joe Rogan said about this. I think it's some sort of a chemical gateway. That's what I think. I think there's a gateway in your mind that can lead to some other dimension that's probably there all the time. Wait. Oh, right. So he thinks the drug is literally a portal into another alien world that exists.

It's opening this gateway. Number one podcast on Spotify. Do you know, like, one way in which I can tell whether I'm going to be friends with someone or not is whether they understand that drugs are chemicals that do shit to your brain and people who think drugs are portals into alien worlds. It's a very good yardstick, Wendy. I think I have a similar kind of tolerance. Well, I do.

But I do want to know why DMT does feel so immersive and realistic because that is super interesting. Yeah, so like on this show, we don't jump straight to portals opening to alien dimensions. We talk about like the impact that molecules have on our physiology, right? That's why we're the number 25 podcast on Spotify. Proudly, proudly 25th. Yes, 25th in the US, in the US.

Okay, so to find out like what DMT is doing to our brains, I caught up with one of DMT science's top nerds. I'm the head of the DMT research group. You sure did. Who's the king? Dr. Chris Timmerman is the king. He's the guy running a lot of these DMT experiments at Imperial College London, including the one we just heard about from Anya. He also ran a study where he got 20 volunteers to slip on an EEG cap and then slide into the cramped, noisy tube of an fMRI machine where he'd inject them with DMT and watch what happened to their brains.

Cool. So what did he see? So when Chris started analyzing the brain data, it's pretty apparent that like DMT just gets inside your brain and messes everything up. Like it's knocking over the furniture in there, right? And he could see that. I mean, it's cool that he could just like see it in his data. Yeah.

So he compares like the brain activity without DMT and then watches what happens when the DMT gets in there. And what he saw was that there are a couple of brain networks in particular that are really massively affected by this dose of DMT. Now, what a brain network is, is like, as we grow up, as our brains develop, different parts of the brain become interconnected with each other in a really structured way. And like those interconnections become really set in stone. And so what Chris was seeing was that DMT completely scrambles a couple of these networks. So instead of being highly organized, they just became completely fluid, right? They were able to connect with parts of the brain they don't usually connect to.

Oh, so it's like those stairs in Harry Potter. Our brain, not on DMT, is like very fixed stairs. And then you take DMT and it's like everything's like moving around and parts of your brain are chatting to each other that weren't before. Totally. And what's really interesting is that the two brain networks that are most affected by DMT are those that work to produce our sense of reality,

like our place in the world. Here's Chris. So whenever we are thinking about the past, projecting ourselves in the future, thinking about our relationships, abstract thought, our ability to imagine, to conjure up things that are not present in the here and now, for example. So all of this stuff, like our ability to imagine things, to project ourselves into a scene in the future, like what's future Wendy going to do?

Like all of the brain networks that allow us to do this, when DMT gets introduced, they get completely scrambled and jumbled up. So then why does whatever we see look so real? So one thing I think people don't think about a lot, because it probably creates like massive existential crises, right, is that like our idea of the external world is mediated by our perception, right? So our brain is actually constructing our idea of reality. And so what happens when DMT gets in there is that it completely scrambles everything. All these networks that are usually like set in stone become like really loose and fluid but because our brains

are used to trying to make sense of stuff they do that and they construct these alternate realities like the intergalactic spaceport that feel quite real but it's just our sensible brain trying to make sense of noise and chaos yes yes this is. This is like when you might see something down a dark street and you're like, oh my God, I just thought I saw a person. But really, it was just the shadows doing something and your brain was like, ah, seems like a person to me. So I'll make you see a person. It's just that on steroids. That's DMT. 100. There is this noisy stream of information and we're just trying to put it together because our minds are meaning-making systems.

So they're immediately trying to make figures out of the noise. So yeah, that's why it feels so real when you're on one of these DMT trips because the parts of your brain that are responsible for creating your perception of the world have just gone bonkers. And in creating that world of your trip, remember when I said the brain networks get fluid and they're able to start talking to bits of the brain that they don't usually talk to? Yes, yes, yes, yes. Well, they start drawing in memories that you might have or your pop culture

knowledge. So it's using things that it's dragging from other parts of your brain to construct this new trip reality. And there's even this idea that Chris told me that because people will go online and, you know, write up their trip story for other people to read, that maybe when someone's about to go on a DMT trip, they might go and do some research and read other people's trip stories and information from other people's trip stories might get woven into their own DMT experience.

It becomes this like self-fulfilling prophecy. If you expect to be on DMT and be taken through an alien portal, then that's what is going to happen because that's been in your head. Oh, that's so funny. And then some people might think, I saw the portal too. Exactly. But really, it's the chemicals, bro. 100%.

100%. Now, you know, like whatever you think is causing the alien encounters and the otherworldly dimensions, people are having genuinely life-changing experiences on this drug. So much so that it's got a bunch of people wondering whether DMT could be the latest psychedelic to have therapeutic potential. And that's a trip we're going to go on after the break. Could this be a portal to your mental health?

Welcome back today on the show, DMT. It's a psychedelic 2.0, 3.0. I don't know. It's a wild one. And now we're going to talk about whether it could be used to maybe help our mental health. Joel, what's the thinking? Okay, so to get into this, I caught up with a couple of people

who are working on one of the most recent clinical trials into DMT. And we caught up for a chat early one London morning. I'm hoping that these microphones are not so good that they pick up my stomach rumbling. I think it's all right. We'll get you to breakfast soon, Graham. I promise, I promise. That is an absolute lie.

I know how long your interview is going for, Joel. Look, it was probably more like high tea by the time we got back to Graham and Michelle. So I'm Graham Campbell. I'm a psychiatrist. I'm Michelle Baker-Jones. I'm a therapist. Graham and Michelle are running the therapy side of this clinical trial. So they're offering support to the patients like before and after they have DMT. But because this drug produces like such bizarre psychedelic experiences, neither of them were very optimistic when they first started on the trial.

Well, I mean, to be fair, I suppose Graham and I were skeptical as to whether DMT would show promise. I remember thinking that DMT is just going to be too strange. Too strange, too intense, too quick. You know, you hear this kind of classic narrative about, you know, hyperspace and alien entities.

And I remember thinking, is this going to make sense to anybody? Is this going to actually provide experiences which are therapeutic and healing? So yeah, Graham and Michelle were kind of skeptical about whether this would work. But hey, it's a job and in this economy. I think this is your best joke all season.

I don't know if that's a compliment. Okay. Okay. So trial. Trial. Yes. Tell me about the trial. So this trial had 34 people in it.

They were all dealing with like moderate to severe depression. Everyone in the trial had to wean themselves off their antidepressants if they were on them before the trial started. So it was kind of a big deal for people to actually participate. Oh, yeah. And Graham has this really vivid memory of the first person that they gave DMT to as part of the trial. She was somebody who'd had four and a half

years of depression, pretty much continuously since the birth of her daughter. And she'd never had any drug experiences before, but she was incredibly tearful and distressed. It was very, very clear that her mood was incredibly low. And, you know, that led her to sort of feel a bit disconnected from her role as a mother. So when she had the DMT experience, for her, it was incredibly intense. And it felt very visceral. And as it was intensifying, you know, over the first 10-15 minutes, she got to a point where she felt that she was reduced to something very, very small, just a sort of fragment of herself was remaining,

and that she was going to disappear into some kind of void. And she suddenly realized that she liked herself and that she didn't want to disappear. And that was very, very profound for her to actually come to that realization. And her depression, you know, she was free of depression for the rest of the trial and all the follow-ups. Yeah, wow. Yeah, but not everyone had this kind of shimmeringly beautiful experience.

Right, right. So one guy, he was like a super high achiever, went to a top university, had this really stressful, high-powered job. He was dealing with a lot of depression and anxiety. And when he had the DMT, he had this trip experience where this kind of weird entity devoured him. But in a very indifferent way. And I think the thing that was so difficult for him was the indifference, you know, the casual indifference of this entity. And he did experience anxiety in the immediate aftermath of the psychedelic experience.

Being devoured indifferently. Oh, man. Yeah. Okay, yeah, that doesn't sound like traditional medicine. It makes my skin crawl a little bit just trying to, like, imagine that experience. Oh, absolutely. So, okay, so zooming out, there were some, what did you say,

34 people in the trial all had depression. How many ended up getting better? Yeah, so at the six-month follow-up after getting the DMT, 10 people, including the mum that we heard from, were no longer depressed. They were in remission. Wow. But what's a bit disappointing is that nine people didn't turn up

for the six-month follow-up, so we just don't know what happened to them. Okay. But still, 10 got better. I mean, I guess some of them might have gotten better anyway, but still, it's not bad, right? Yeah. And we do have some other data, right? So there was this other study out of Yale. It was very small. So seven people with treatment-resistant depression got DMT. And the next day, on average, their depression scores dropped as well. Okay, so we're getting like sprinklings of data here. That's DMT. Do we have anything on ayahuasca? Like what happens when you take the whole brew?

Yeah, so there's a bunch of studies where people have filled out surveys about their ayahuasca experience. And these surveys suggest that ayahuasca could be useful in treating depression and anxiety, but also substance abuse problems. And sometimes people report dealing with really intense trauma with an ayahuasca ceremony. But these are all people who have chosen to go

on these ayahuasca retreats, right? So there's probably a bit of a selection bias happening. Right. And then speaking of selection bias, what about our old friend, the placebo? I mean, people are choosing to go to the jungle, choosing to vomit everywhere. You know, there's got to be a whole lot of expectation that this is going to help them. How do we know that's not what's going on here? Yeah. So I found one randomized placebo-controlled trial of ayahuasca, and this was in treatment-resistant depression,

so people who had been trying a lot to help with their depression and hadn't found anything that worked. Okay. They had 29 patients who got a single dose of either ayahuasca or a placebo. I love this so much. They brewed an ayahuasca placebo that looked and tasted like this brew. Like right down to the... Thank you, scientists!

Right down to the bitter, sour taste and the brownish color. They even added in some zinc sulfate to produce, quote, low to modest gastrointestinal distress. Yes, yes, yes. Okay, okay. So how did it go? So they followed up one week after receiving the dose and they found there was a very strong placebo effect. So tick to the scientists, the little placebo brew they made did the job.

But the people who got the real stuff, the people who got the ayahuasca did better. So about two-thirds of those who got ayahuasca felt the severity of their depression dropped by 50% or more. Two-thirds, that's not bad. It's pretty good because in the placebo group, there's only a quarter could say the same thing. Great. That is promising. Yeah, yeah, totally. It's quite promising. But what none of these trials get at is how it's having this effect. And I wanted to know what was going on in the brain. Of course you did.

Your brain did. Giving these trials the results. I want to know too, because it doesn't make sense. You see some aliens, even you see yourself get smaller and your depression's healed. Totally. And to figure that out, I caught up with this guy. My name's David Olson. I'm the director of the Institute for Psychedelics and Neurotherapeutics

at the University of California, Davis. So David's trying to figure out how our brain cells might be changing when they get exposed to DMT and how this might be helping people with depression. But to do this work, you can't do it in people. You've got to give the DMT to rats. Okay. Okay. So what is a rodent tripping balls on DMT look like? Oh, snap. Because like, that's exactly the question I had for David. Like, what does a rat tripping on DMT look like? Well, for rats, when you give them high doses, they tend to flatten their bodies and stare. Have you ever encountered an alien rat, though?

They must be having some weird trips. Like if the DMT trips that humans have are weird, like rat DMT trips must be out of this world. Yeah, it's unclear what those are like. You know how Anya was imagining the tendrils of aliens looking through every cell in her body? In this case, it's David. David's the alien of that poor rat on DMT. It's not a hallucination, totally.

It's not. So the rats, the rats, like, get the DMT. They have their little ratty trip. They live their life for 24 hours and then they sacrifice their lives for science. Well, we chop up their brains to see what's going on in them. Right. So David's taking slices of these rat brains.

And for the neuro nerds out there, the areas of the brain he's working in are the prefrontal cortex and the hippocampus. And he's trying to figure out what's happening to the brain cells after they interact with DMT. Okay, so analogy time. Brain cells look like trees. Yes. Stick with me. No, they do.

They actually do. The axon is like the trunk. Yes. And then the branches, the bits that communicate with the other brain cells, those branches are called the dendrites. It turns out that neurons look so much like trees that we actually use the term arbor to describe their dendritic branches. It's very poetic. Yeah, like sometimes science is super complicated

and sometimes it's just saying what you see in front of you. Yeah, yeah. So like when some people have, say, depression, their canopies, instead of being densely filled with lots of branches, like bushy, bushy trees, they look kind of barren. So if you prune back those branches and you lose all the leaves, so it looks like wintertime and the arborist has come by. That's what a lot of brain disorders look like. And what David and his team are doing is giving rats either DMT or placebo and then counting the leaves on those branches. We had to do some very painstaking experiments where we were under the microscope for, I don't know how many, hundreds of hours,

tracing, manually tracing these dendrites and counting these dendritic spines. And you're just doing this thousands and thousands of times over. And, you know, one of my graduate students basically locked himself in a dark closet for weeks at a time so that he could trace all of these neurons manually. And what David and his team found is that like after they'd been exposed to DMT, the brain cells were healthier. Like there were more leaves on the branches of their trees. What DMT seems to do is to act like Miracle-Gro in a lot of ways. It promotes the growth of the branches and the leaves start sprouting again so that the canopy can be a lot fuller than it was.

That's really cool. That's really cool. And so if this plays out in people, like people with depression, is the idea that if they have this like bare canopy with now more leaves in it, they themselves will be healthier. Totally, totally. Bushier trees, healthier brain is the idea, which is really interesting because for ages, scientists have been trying to figure out whether like the subjective experience of going on one of these psychedelic trips, like all of the weird stuff that you see, whether that was what was really doing the heavy lifting in terms of these drugs being therapeutic or if something else was going on. But then when we saw that there was

physical changes in the structure of the brain, we thought that there might be this alternative explanation. And so even though David's study was being done in rats, he's pretty confident that like what he's seeing in these rodents is happening in humans as well. Because like this mechanism of growing leaves, it doesn't just happen with DMT. It happens with other psychedelics as well. And it even happens with antidepressants like SSRIs because they have this effect. So they cause the leaves, new leaves to grow on the branches of the brain cells. But as anyone who's taken antidepressants would know, they're no businessman's trip, right? Like they take weeks

or even months to kick in. But a psychedelic, you can take a single dose and see large changes in growth within 24 hours. And then that effect can be sustained for several weeks. And that is really the difference between psychedelics and more traditional antidepressants. That's great. That's exciting. So a super interesting part of David's research is that he also found that DMT could promote what's called neuroplasticity, so this growth of new branches, at a dose of DMT that was sub-hallucinogenic. And so this kind of suggests that maybe you don't need the whole psychedelic experience to get the benefit from psychedelics, which is like exciting from a research point of view but also like totally no fun at all, right?

Right. Yeah, I guess so. I guess it depends how fun it is to be probed by aliens. Yeah. So speaking of no fun at all, I think my last question is like can DMT or ayahuasca, I don't know, like all this brain plasticity shaking up the snow globe between my ears. Can that cause harm? Can you shake it up in a way that is bad? Can you end up worse

after you take these trips? Look, for such a hectic drug, a bunch of the scientists I spoke to told me that it's actually pretty safe. So one review paper looked at some people in Brazil who'd been using ayahuasca in their religious ceremonies over a long time. And that review didn't find any evidence that it was harmful to those people. There are a few things to watch out for. So with DMT, the big risk is your heart health. So that initial rush of the drug, it really increases your heart rate. And in studies of DMT and ayahuasca, there's the odd case where people get hypertension.

But for Chris, his biggest concern was to do with people's minds. The main risks are psychological. So people can have extreme anxiety and fear responses. When you go in the higher doses of DMT, people can have very, very extreme experiences that can be extremely confronting for some individuals. Some people do need to go to therapy to deal with the visions that they saw when they were on their trip. So one survey of 10,000 ayahuasca users

found that 12% got professional help after going on one of these retreats. There are even stories of people experiencing psychosis after taking ayahuasca, which can be pretty full on. Yeah. Right? But it's also quite rare. So of the estimated hundreds of thousands of users of ayahuasca, I could only find some case reports of this. Has anyone ever died from of ayahuasca. I could only find some case reports of this. Has anyone ever died from taking ayahuasca? Because, like, every now and then you do read these stories

of people going to these retreats and not coming back. It is rare for this kind of thing to happen. Like, one report looks through more than 20 years of media articles from around the world and found 58 deaths that had been attributed to ayahuasca during that time. 58 deaths over 20 years. But in a lot of cases, it's not clear if ayahuasca or DMT is to blame because like during an ayahuasca ceremony, there's other stuff that's mixed into the brew. It's not just the drug. Right. And then sometimes people mix ayahuasca with completely different drugs. So there's one

case study of a guy from Australia who used ayahuasca and died with a, quote, perforated esophagus from vomiting. Oh, gosh. Yeah, it's really full on. But that same night, he'd also ingested the poison from an Amazonian tree frog. So it can be hard in cases like this to determine what the exact cause of death was. Okay. So Joel, it's time to wrap up this DMT adventure we've been on. Let's wrap it. It's funny. I came into this episode, I don't want to say skeptical, would you believe, about ayahuasca. You? Skeptical? In this economy? Yeah. I mean, the fact that it has this very long tradition makes it very interesting. But

then this celebrity retreat vibe around it is just, it's hard not to roll your eyes. But the science is, it is really intriguing. Where are you at with DMT? Yeah, I mean, influences are going to influence, right? But I'm super pumped by the science. The idea that psychedelic drugs are helping these little leaves on the branches of our brain trees grow after just 24 hours, that's super exciting.

But then, you know, I think about DMT as a therapy and it's like, our societies tend to be so uptight about drugs generally like if you think about the path that weed has taken and like weed's such a like a smaller deal than DMT it just makes me wonder like if and when this idea of having a kind of businessman's lunch where you deal with some sh** in this really short-acting psychedelic experience. Like, when will we as a people be ready? So I'm kind of like, I'm struggling to see how these therapies break through into the mainstream. Yeah.

You know, I am really curious if I would ever take this, if I would start to believe that this was an alien portal. Oh, totally. I've been thinking about, like, what my brain would choose to turn into this super immersive trip. And, you know, like, I'd probably want some, like, mystical sci-fi experience, but I'd probably end up getting, like,

like a Google Doc with one of our scripts coming to life or something. Yeah, exactly. I reckon you'd get all of the citations that you've ever put in a Science Versus episode. Just devouring me indifferently. Thanks, Joel. Thanks, Wendy. Who's this? Your worst nightmare.

I have one more question, it turns out. How many citations are in this week's episode? We had 79 citations this week. 79. And if people want to see them in all of their glory, where should they go? Well, each week we put a link to the full transcript of the episode in the show notes.

And so if you follow that link, you can read along while you listen and you can deep dive into all the extra information that we put there for you. Yes. And while you're looking at the show notes, you're also going to see ways to get in touch with us while we're on a break. So if you have an episode that you think we should do,

what should we versus, please tell us. And also, we really want to hear your thoughts on, remember, those three topics, sex, diet, any questions you have about diet, how much protein should you be eating every day? I don't know. Whatever you're thinking, we want to know. And also your questions about menopause. You can email us,

send us a voice message to scienceversus at gimletmedia.com. And there's a phone number in the show notes too. And then finally, Joel, there was one fact in this episode that you were like, we cannot put an ayahuasca episode down the feed without this. And Blythe and I were like, we cannot put an ayahuasca episode down the feed without this. And Blythe and I were like, nah, I don't know. Tell us now. Tell us now what is this fact? So when you make the ayahuasca brew, like the way that the brew is brewed is super cool, right? Because you get the DMT by crushing up the leaves of this particular plant.

But if you just ingest the leaves, like so if you eat them or if you drink them in this brew by themselves, then the DMT gets broken down super quickly by an enzyme and not enough of it gets absorbed to give you this psychedelic experience. So what you have to add into the brew is a vine, right? And so you put the leaves in, you put the vine in, and there's a secret ingredient in the vine that inhibits the action of that enzyme which allows you to absorb all the DMT and gets you high on ayahuasca. And I just think that's such a super cool idea that, like,

it's not just getting the DMT out of the leaves, that you need to, like, have this, like, interactive relationship between the leaves and the vine to make the ayahuasca brew super potent. Yes. But if you get it from the scientists, inject it straight in you, you can bypass that whole system. Yeah, choose your own adventure on that one.

All right. Thanks so much, Joel, and we will see all of you guys in the new year. Thanks so much for listening to us. Thanks, Joel. Thanks, Wendy. Bye. Bye. This episode was produced by Joel Werner with help from me,

Wendy Zuckerman, Michelle Dang, Rose Rimler, and Nick Delrose. We're edited by Blythe Terrell. Fact-checking by Diane Kelly. Mix and sound design by Bumi Hidaka. Music written by Bumi Hidaka, Peter Leonard and Bobby Lord. Thanks to all of the researchers that we spoke to for this episode,

including Dr. Rick Straussman, Dr. David Eritzo, Dr. Jimo Borijin, Dr. Stephen Barker, Dr. Brandon Weiss, Dr. Pascal Michael, Dr. Michael Gatch, Professor Jerome Saras, Professor Deepak D'Souza, A special thanks to I'm Wendy Zuckerman, and we will fact you in a couple of months.

I'll see you then. Bye.