Rethinking Research: Novel Approaches to Studying LSD Microdosing

Podcast Highlights

• Dr. Muthukumaraswamy shares his academic and professional background, and what led him to studying psychedelics.
• Dr. Muthukumaraswamy explains the origin story and unique design of his LSD microdosing study.
• How study volunteers generally respond to microdosing in a lab vs. in their normal daily environments.
• Design elements Dr. Muthukumaraswamy plans to implement in future LSD microdose studies.
• Considering how Dr. Muthukumaraswamy’s take-home LSD microdose study might impact research and policy in other countries.
• The legal landscape of psychedelics relevant to New Zealand’s indigenous Māori community.

Show Links

1. Protocol for Dr. Muthukumaraswamy’s LSD microdose study
2. Suresh’s lab, Auckland Neuro- Psycho- Pharmacology Research Group on Facebook
3. Scopolamine, “Devil’s Breath”
4. Ep. 172: Paul Stamets & Pamela Kryskow, M.D. - The Future of Microdosing: Legislation, Research, & Science
5. Ep. 107: Mendel Kaelen - Music and Psychedelic Medicine: Healing Through Sound

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Podcast Transcript

0:00:00.6 Paul Austin: Hey, listeners. Today's episode is with Dr. Suresh Muthukumaraswamy who is a researcher in New Zealand.

0:00:09.8 Suresh Muthukumaraswamy: So I think the set and setting, I think it applies to microdosing as well. And there's a clear difference in our data between a dose taken in a laboratory and a dose taken out in the wild as people do daily activities. And I think that's why those other studies haven't replicated what the community is reporting because they're doing it in a boring laboratory.
[music]

0:00:31.9 PA: Welcome to the Psychedelic Podcast by Third Wave, audio mycelium, connecting you to the luminaries and thought leaders of the psychedelic renaissance. We bring you illuminating conversations with scientists, therapists, entrepreneurs, coaches, doctors, and shamanic practitioners, exploring how we can best use psychedelic medicine to accelerate personal healing, peak performance and collective transformation.
[music]

0:01:08.9 PA: Hey, listeners. I am so excited to have Suresh Muthukumaraswamy on the podcast today. Suresh has been researching LSD microdosing in New Zealand in a very novel way. Most of the clinical microdosing trials thus far have been done in a lab setting. And what Suresh did in New Zealand is he did clinical research but in a naturalistic setting, and that's because he got approval from the New Zealand government to allow the patients in the study to take the LSD home with them, which is fascinating. And so I interviewed Suresh at the Wonderland conference in Miami in early November 2022. We went deep into this LSD microdosing clinical trial, how it is set up what they ended up finding as part of the results and it really was a reaffirming conversation 'cause a lot of the early research that's come out on microdosing has not necessarily found statistically significant results. And so we've heard a lot around oh, it's a placebo, and all of us who have properly done and calibrated microdosing, no, this is not placebo.

0:02:13.6 PA: So it was really amazing to go deeper into the science and research with Suresh. Before we dive in today's episode, a word from our sponsors. Hey, listeners.
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0:05:24.0 PA: All right. That's it for now. Let's go ahead and dive in to this episode with Dr. Suresh Muthukumaraswamy. I hope you enjoy our conversation. Hey, everyone. Welcome to a special edition of the psychedelic podcast. Today We are at the Wonderland conference brought to everyone by Microdose. We're here in Miami, Florida and today we have the honor of speaking with Suresh. Suresh, you're going to have to help me out with your with your last name. It is...

0:05:51.2 SM: Muthukumaraswamy.

0:05:54.5 PA: Suresh.

0:05:55.3 SM: Paul. [chuckle]

0:05:56.5 PA: Great to meet you. Thank you for joining us. Suresh is from New Zealand and the reason we brought him in today is to talk a little bit about the LSD microdosing trial that he is currently or has already, we'll get into it, carried out in New Zealand. And before we get into that, Suresh, just would love to hear a little bit about what brought you to the conference today.

0:06:18.3 SM: To bring the conference today was to present the LSD microdosing results to the conference. Actually, this will be the first time we've presented the results to the public. So this is... Yeah, it's kind of finally after three years, the results are going to see the light of day. So it'll be here and then the results are also in submission to an academic journal as well.

0:06:38.8 PA: Have you presented them yet at the conference?

0:06:42.1 SM: No, we'll be presenting them tomorrow.

0:06:45.2 PA: Okay. And and for those results, what are you most excited about in terms of communicating it to the public?

0:06:50.2 SM: You know, I think the results on microdosing so far in the scientific literature have largely been no results. That people haven't found very much. And that sits in quite contrast to what people in the community are saying and people like yourself are saying. And actually, I would say that our results are much more consistent with what the community is saying about what microdosing does relative to the existing trial literature. And it really does fit, with, yeah, the community reports. So that's interesting and we can get into the details about why we think that's happened and what that disparity is.

0:07:35.4 PA: And I would love to do that and we can even maybe review what is some of the clinical research that's happened so far. For example, at the University of Chicago with Harriet De Wit. There's been some that's come out of Imperial College as well with psilocybin. And so I think...

0:07:46.8 SM: We can totally go into the weeds of that.

0:07:48.7 PA: Yeah. I'll be really curious to hear sort of how your research defers, what you did differently, the dose levels, all that. And so what we love to do for the listeners is just provide a little bit of context about your background, your origin story, what we do in some of our retreats. As we say, you have seven minutes to tell your life story. What would you tell and how does that lead to you doing of all things LSD microdosing in in New Zealand?

0:08:13.3 SM: Oh, I think my seven minute story could probably done in two. It's a pretty boring middle class upbringing. I come from a long line of medical doctors. I studied science instead of medicine, but didn't stray too far from the family line. And, I was interested in pharmacology as a university student. I even wrote a second year pharmacology essay about LSD and then late '90s, a long time ago, but there was no option to study that and research that kind of stuff at that time. This was right in the... In the '90s there was nothing like that happening. So I just took a standard academic track, PhD, etcetera, through neuroscience. And then in the 2010s, that's when I started doing psychedelic research.

0:09:04.4 SM: I was already doing neuropharmacology researching at GABA drugs and stuff. And then I was working with David Nutt and Robin Carhart-Harris, collaborating with them on some of the early psilocybin studies. And I was already working with David on other GABAergic drugs and then got into it from there really. So, kind of just stumbled my way in. But I guess my background isn't in psychedelics. My background is in general neuropharmacology and neuroimaging and neuroscience. And now part of my research is doing psychedelic drugs. But I guess that gives me a more traditional academic background than maybe other researchers do. And I never came into research thinking I really want to study psychedelics. I was like, I just want to study the brain and see what makes things tick up up there. And that's why I'm doing what I'm doing. And psychedelics is interesting because in pharmacology, most of the drugs we study just make people sleepy, to be honest. [chuckle] Or they stimulate them, but psychedelics make people think unusual thoughts, creative thoughts, etcetera, etcetera. But that has a neuropharmacological basis. So that's interesting, trying to unpick what that basis is in terms of, as a reductionist, admittedly scientist.

0:10:21.8 PA: Would you consider yourself a reductionist?

0:10:24.6 SM: I consider myself an open-minded reductionist. Yeah. Yeah.

0:10:29.9 PA: And that'll be helpful as well for flushing out microdosing LSD, the clinical trials. I know some of the work that you've done has also been on ketamine. So I'd love... In terms of that path for you, started in 2011?

0:10:42.5 SM: Yeah, so we did an EMG study of psilocybin on healthy volunteers, trying to work out how psilocybin would change brain function, following up from Robin's fMRI study of psilocybin. And then we did an fMRI and EMG study of LSD macro doses. And that was challenging. And then I was studying ketamine 'cause I was interested in how ketamine works and its relationship to psilocybin and LSD. This was back in 2014, so before the psychedelic bubble had started growing. And then I moved to New Zealand and it was very difficult to just go straight into doing psychedelics research in New Zealand. So I kept doing ketamine because it was an approved drug, we could do it. And I spent a few years just bearing my way into ketamine and scopolamine as well. And then most recently switched to going back to doing LSD, and we're also doing some other bits and pieces as well.

0:11:48.2 PA: What's scopolamine?

0:11:50.4 SM: Scopolamine is an anticholinergic drug that at very high doses, causes sort of deliria. The doses we were looking at were as far as antidepressant, well, it's purported antidepressant effects that we did not find.

0:12:07.7 PA: Is that similar to Datura then? There's overlap?

0:12:12.5 SM: Yeah, it's found in Datura.

0:12:14.0 PA: Gotcha.

0:12:16.1 SM: Yeah. The Devil's Breath, I think they call it. But we didn't dose that high. It's an interesting one that we didn't see those kind of effects that people report at the dose...

0:12:25.2 PA: I've never heard of a clinical trial with scopolamine before.

0:12:28.1 SM: Yeah. There's a handful of them out there. We were giving it intravenously, through an infusion pump. And so it's a very controlled setting with anesthetists. Anesthetists use scopolamine in surgery for its anticholinergic properties.

0:12:44.2 PA: Well, let's get into the microdosing LSD. 'Cause I think that's sort of the star of the show. It'd be great to hear. Let's first provide some context about what clinical research had been done leading up to your choice to do this microdosing LSD trial. Why did you choose to do a microdosing LSD trial and how did you structure the experiment for the research, when you were going into it?

0:13:05.9 SM: Yeah, it took a long time to get this trial off the ground because of how we decided to run it. This is back in that time before the pandemic. [chuckle] It seems so long ago now. But we wanted to start doing psychedelics research. And at the time people were talking a lot about microdosing, but there was very little research had been done on it. I think maybe there was a trial or something, so no one really knew what the hell was going on. There's been more trials since then. But one of the things that, and one of the reasons it took so long to do, or at least to set up, was that the trials that had been conducted at the time had only been done in a laboratory. So they were like, okay, let's give someone a very low dose of psilocybin or LSD in a laboratory, record some stuff like we do, get into some tests, and then send 'em on their way. And to me that didn't seem to have much ecological validity. Because the people that were being described in Fadiman's book and subsequent literature and stuff that... It's been described Third Wave, for example. That's a very different scenario. People are taking LSD microdoses at home. And I think that that's a very different scenario because many of the listeners, maybe yourself may not have been into a clinical research laboratory before, but then these are boring places.

0:14:38.7 PA: And that environment matters even at lower doses, the context, the set and settings, things...

0:14:42.7 SM: Yeah. Well, so that's part of maybe what could be important. I think people are doing or intuitively know this, but as scientists that's something we think, well, we have to test that. So these previous studies had only been stuck in the lab. We wanted to do it out in the wild basically and give people the microdoses to take home. But obviously with drug laws, that creates some challenges. Because now you're taking a Schedule I substance and you are essentially giving it for people to take home. And it took a long time to navigate through the complexities of how you deal with that legally and from a regulatory perspective. But we got there. And we now have the agreements and the understandings in place with our regulators in New Zealand that we can now essentially prescribe people LSD or psilocybin.

0:15:38.1 SM: If we were to do a psilocybin microdosing trial, we can now prescribe it for people to take home. So we don't have to do it in some... And we could do that. New Zealand has a highly regulated regulatory system, so we don't have to go to Jamaica or something to do this. We can do it in a well-regulated medical system. And we have full clinical trial facilities, but we can still do these studies where we prescribe people their LSD to take home and then we can... And that was the basis of our experiment. So it took a while to undertake that. And then just as we were starting the experiment, the pandemic started. [laughter] But we managed to collect the data through the pandemic. Yeah, so the trial itself was 80 healthy volunteers, which is quite a lot.

0:16:33.7 SM: Half of them took a placebo, half of them took the LSD microdoses, and it was a six week microdosing course. Pretty similar to maybe what you do, you get clients to do. They take a dose every third day for six weeks. They come in for a screening session. So we make sure that that... For this trial, where the other trials on clinical populations are going to come up, we'll talk about that later. But what they did was they do a screening session, come in, we do a whole bunch of baseline brain recordings, all that kind of stuff, and they come in for their first dose, their first dose we give in the lab and we record.

0:17:10.2 PA: Was that part of the agreement then between you and the regulators in terms of...

0:17:13.2 SM: Yeah, it was part of that, but also we wanted to do that because we wanted to take their blood and do all the crazy testing that we do and also just check that people were okay. Because one of the things was that we didn't want to... And this will be where we took our other literature, we didn't want to get a population of people that had already microdosed. None of our participants had ever microdosed before. And indeed 30% of our participants had never even taken a psychedelic before. The median psychedelic use of our population was two. So some had basically taken a couple of LSD trips like 20 years ago, and none of them were... The age range was 25 up, so there were no undergraduates, which is unusual for a university study. So it was a very different population, very naive population that we studied, that we brought in. And so that was why we wanted to do that first dose check in the lab so we could check safety, get a whole bunch of more data, and then they start their six week course for 13 doses. Every night, they fill out on their mobile phone a questionnaire about how they're feeling, and the adverse events, etcetera. And then after six weeks, we bring them back in and repeat all the invasive measurements again.

0:18:34.7 PA: Before and after sort of as bookends for the entire experience.

0:18:38.6 SM: Yeah, bookends and then yeah, six weeks of constant feedback. And then we also do this long qualitative interview at the end as well.

0:18:45.7 PA: And how much LSD were they taking? And how do you source the LSD? What's that process?

0:18:47.9 SM: The LSD was pharmaceutical grade and produced to good manufacturing practice. So it was...

0:18:55.5 PA: Good stuff. Yeah.

0:19:00.3 SM: Yeah. I was trying to find the right words, but yeah, it was pharmaceutically pure and we knew exactly how much we were giving. So it was interesting. We started with 10 micrograms. It was 10 micrograms free base in single use oral syringes. So it was already measured out in dose units for the participants. And interestingly, what we found, and it was unexpected to us, was that actually... We were running our participants in waves. And what we actually found was in that first wave, we had people who it was just too much. There was just... 10 micrograms was... They were having... They lost daily functioning.

0:19:41.2 PA: Really?

0:19:41.4 SM: It was just too strong.

0:19:42.5 PA: At 10 micrograms?

0:19:43.7 SM: 10 micrograms. It was too strong.

0:19:45.8 PA: Interesting.

0:19:47.3 SM: Because these were naive participants, right?

0:19:47.4 PA: Right. And it's also pharmaceutical grade. So a lot of times what we think might be 15 micrograms in the black market could actually be... We don't know oftentimes, right?

0:19:57.1 SM: You don't know, but at least in New Zealand, we're talking about this follow-up project we're going to do on this, actually trying to get people's samples. But we'll do another... But yeah, so we know exactly what we're giving. And 10 micrograms was too strong. This is only for about like 10-20% of the participants. It was too much. And so what we actually ended up... We amended our protocol halfway after observing this and said, "Okay, if a person has this overstimulating experience... " Because we don't want to disrupt people's daily function.

0:20:27.4 PA: Sure. It's the point of a microdose.

0:20:27.4 SM: Yeah, yeah. So then what we did was we implemented a titration procedure where if it's too high, we drop them down to 5, and then we build them back up again. And we still had to withdraw four participants out of 40 from the trial because they developed this anxiety about taking it. So that was interesting that...

0:20:48.2 PA: Like it just brought up a lot of...

0:20:49.9 SM: Yeah, and what we discovered was that if they... It was in the pandemic. So people were stressed out as fuck. It's not my language, but it wasn't a good time to be doing this. So people had extra life stress. And then you put the microdoses on top of that and that seemed to cause some kind of interaction between their ongoing life stress. And these are healthy volunteers. And then we decided in some of these cases, just pull them from the trial and go, "You know what, you're a healthy volunteer. There's no benefit to you in doing this. Let's just pull you." And the anxiety resolved after a couple of... Yeah, with some light supportive care. That was enough. So that's on that side. And then on the flip side, though, is when we looked at the data, we actually see for the... When we compare it to the placebo group, we actually found that when we look at those daily questionnaires they're completing on the days that they dose, there's very significant effects on their ratings of how well they're feeling, how happy they feel, how connected they feel, creative they feel, was one other thing that came off, slips my mind, and how much energy they feel, which is exactly what you might expect to see. So we see that clearly over the placebo. So that was the big finding that we found that we've analyzed so far. So we see all those things that people are reporting, we see those in our data.

0:22:19.1 PA: And so just to land at... So you gave them 10 micrograms, some titrated down to 5 and started to work their way back up?

0:22:27.0 SM: Yeah.

0:22:27.0 PA: Were there any participants where 10 micrograms didn't do anything at all, or they decided to go to 15 or 20?

0:22:35.2 PA: We didn't have the option of going up because of...

0:22:37.0 PA: You did not have the option of going up?

0:22:39.0 SM: Yeah, because we didn't actually have the dose units to do that, the way we'd prepare the doses. And that's something we would love to do in the future because there was some... So it's really remarkable, even though our population is still relatively homogeneous, somewhere between five and... I think 10 was probably for most participants probably okay, but somewhere between 5 and 10. I reckon there's a set of pop that could have gone probably up higher. And in our subsequent trials, we're going to be doing this. We're going to range it now from 5-15. But I think there's a significant individual variability across people and we have no idea what causes it. We're trying to investigate that at the moment, why some people's sweet spot might be 6 and some might be 13, which is almost double the dose. But it's like they're all essentially healthy people with the same bodies, but they might have twice the sensitivity.

0:23:32.8 PA: And they were all men?

0:23:33.2 SM: Yeah, they were all men. Yeah.

0:23:34.5 PA: And were any of them on SSRIs or any pharmaceutical medications?

0:23:39.3 SM: None of them had any psychiatric history. None were on central nervous system acting medications. Some might have had some things peripheral, things that there would be no interactions for. But there's no pharmacological interactions why that would be the case. Just some endogenous difference in sensitivity. But it's interesting because what we've discovered validates a lot of what the community is saying is start low, go slow. It seems to be the way to do it. [laughter]

0:24:11.3 PA: You can always take more, you can't necessarily take less, right?

0:24:13.1 SM: Yeah, yeah. And once you take more, if you've taken too much, then you've got to unwind the process. So what we're going to do in our follow up trials now is do that and actually start lower, probably at 8 and build up. And then if 8 is too much, we drop down and we actually titrate much like people do. Now, as pharmacologists and scientists, we're like, "Oh, we don't want to do that 'cause it makes our data more complicated." We like to give people the same dose, then everyone's the same and it makes it really easy to analyze. But it's not the way this works.

0:24:46.6 PA: Psychedelics are different in that way. It is a breaking of that more traditional model.

0:24:52.4 SM: Yeah, there are other drugs we... And there are other drugs... This is done in the literature and in general pharmacology is kind of a titration thing. So we're not way beyond the thing, beyond the thing. But it does make things more complicated when we... So we're now setting up to run trials in depressed patients and we'll be doing this titration procedure where we start them at 8 and hopefully build them up to find that right dose for them, and obviously we have it precisely measured. So I think our literature is probably much more convergent with the way you've been doing things and what the community is reporting compared to other literature.

0:25:34.0 PA: And there's been... Paul Stamets has published some research that's been done through Quantified Citizen, an app, more observational rather than experimental. A lot of the experimental research that's been published has shown more or less like, "Hey, not much is going on here." There is some dose response, like with the University of Chicago, 6 versus 13 versus 20. The Beckley Foundation has found similar things. But there's a lot of Twitter conversation and general conversation around microdosing placebo, not a placebo. I think part of this has to do with the definition of microdosing, right?

0:26:10.3 SM: Yeah.

0:26:10.4 PA: So when Jim Fadiman initially talked about it was, hey, this is sub perceptible...

0:26:14.2 SM: Sub hallucinogenic.

0:26:16.7 PA: Well, and I think this is sort of the context is just sub hallucinogenic or is it sub perceptible? Because if we can perceive that we're feeling it, then that could be potentially perceived as being a mini dose or a moderate dose. So what did people report when they were going through this experience? Did people feel it? Was there a noticing?

0:26:38.7 SM: Yeah, it was definitely a noticing, but it's kind of subtle. And I think the ideal scenario is where it is that subtle, around the edges of perception where could be... I think that's where we're trying... Because once you start going too high, then you start to disrupt daily functioning. And that's not what we're trying to do. So, yeah. And I think one of the things we were able to demonstrate in the data, though, is that... So those papers from Harriet De Wit's group or the the group at Maastricht is that we were able to compare the first dose in the lab compared to the other doses. And we don't see any effects on that first dose when it happens in the lab. So when they take it... So they do the dose in the lab and then they report how creative they felt that night, how much energy. Nothing.

0:27:31.7 PA: Really?

0:27:32.6 SM: And then the next dose, where they take it at home, boom, it bounces up. So it's an effect...

0:27:38.8 PA: That's interesting.

0:27:39.0 SM: It's an effect of being...

0:27:39.1 PA: Why is that?

0:27:40.4 SM: It's because they're out doing their life. So it's the same dose. But if they take it in the lab and they're sitting around for six hours doing nothing, 'cause our labs are boring. They sit there for six hours going, "You got half an hour until your next assessment." [chuckle] You can't... "I'll just sit on my phone for half an hour." Whereas when they're out in the wild, they take a dose and they go do something and they start to feel it. So it's about the sitting and the context of what... So I think the set and setting, I think it applies to microdosing as well there. And there's a clear difference in our data between a dose taken in a laboratory and a dose taken out in the wild as people do daily activities. And I think that's why those other studies haven't replicated what the community is reporting because they're doing it in a boring laboratory.

0:28:30.8 PA: And that's the set and setting. That's the environment. It's very sterilized. It's very linear. It's very uninspiring and boring.

0:28:37.1 SM: Yeah, yeah. People need to be doing what they need to be doing.

0:28:39.8 PA: Out in life, moving, hiking.

0:28:42.8 SM: Yeah, yeah. And we have a lot of interviews of the participants reporting doing all that kind of stuff. How some of them are on placebo is all right. And there's definitely placebo responses.

0:28:53.4 PA: For sure.

0:28:54.4 SM: Absolutely, right?

0:28:55.0 PA: For sure.

0:28:55.1 SM: But we are able to start to demarcate those that were placebo responses and those that were things. So it certainly doesn't seem to all be placebo response at all. So our data are not telling us that at all. There's definitely placebo responses to some things, but not to all of it by any stretch. And we're using that now as our guide for what we do when we... Now we want to do depressed patients.

0:29:18.4 PA: That's what I was going to ask you next. Now that you have this sort of baseline, healthy 40 and 40, what comes after this trial? How would you change it? How would you shift it?

0:29:27.3 SM: Yeah. So we're going to start running... Our first depression trial will be just an open label trial to try to get it right. But there's a few... We've learnt things and we're also borrowing from the community and the ideas from the community is firstly, dose titration is really important. We've got to be careful about going too high too quickly. So dose titration we'll definitely be doing, flexibility about those things that every third day thing sounds nice in theory but actually, for most people, it doesn't work. They're working or whatever. They've got a 5:00 to 2:00 type job, then we need to provide them more flexibility than that. Because when we say every third day, we mean every day like a metronome.

0:30:15.5 PA: Yeah, to keep the variables consistent.

0:30:16.9 SM: Yeah, yeah.

0:30:17.3 PA: Minimize that as much as possible.

0:30:19.3 SM: We mean like every third day tick tock, tick tock and there's no variation allowed. But we need to allow that variation so that people can fit it in with their lives. So we're building in that flexibility. And then we're also now thinking about well, things like intention.

0:30:34.4 PA: A tincture?

0:30:38.1 SM: Intention.

0:30:38.6 PA: Oh, intention, yeah, yeah. Yeah.

0:30:38.7 SM: The intention people have when they microdose. And so we're actually writing an app that will go along with the microdosing that will basically... So it won't just be people LSD microdosing, and we're running that as our trial, it'll be intention setting and journaling and all sorts of stuff that goes along. So it's a kind of therapeutic package, much like what is done on the community. So we'll be testing that therapeutic package versus active placebo eventually.

0:31:08.0 PA: And one thing that I often talk about publicly as it relates to microdosing is so much of the clinical trials with psychedelic assisted psychotherapy. So whether it's MDMA or psilocybin, the high doses, they come with Prep, they come with therapy between, they come with integration. They've even shown in research that some of the efficacy is because of the quality of the care and the talk therapy. It's not all the psychedelic.

0:31:32.8 SM: Yeah, yeah.

0:31:32.9 PA: And so one thing I've often communicated is like microdosing by yourself, it's a great first step. But like anything, having a therapist, having a coach, having someone who is actually there to help you cultivate that intention, to help you navigate some of the uncertainty, to help you dial in that dose level. I think that's something that is... It's really missing from some of the clinical research. And in conversations that we've had with various different parties, we've really asked how... Even with Third Wave, we're training a lot of coaches now. How could we support for free with... You're setting up a clinical trial. They just get connected or paired with a coach. They can help them set their intention or could help them integrate after. 'Cause I think then we'll see even another boost in efficacy, even beyond just an app that you journal in necessarily, right?

0:32:18.8 SM: Yeah. I mean, they'll have a few more features in there.

0:32:20.9 PA: Yeah, yeah, yeah.

0:32:23.1 SM: But it's also part of a... We work with pharmaceutical companies. So it's also part of product development for them as well.

0:32:30.4 PA: So talk a little bit about that, the pharmaceutical company, the reason for... Is it a for-profit? Is it a non-profit? What's the deal there in terms of...

0:32:39.1 SM: We're working with a company called MindBio Therapeutics that we have a licensing agreement in place with them. So we're heading down a commercial development route for it in terms of... So they're interested and we're interested as well, because one of the things, we're interested... So there's also a pharmaceutical manufacturing point of view. So you want to have good, really controlled dosing where the stuff that you're poor, that people out of the community have the sourcing issues and purity and all that stuff. So that will be resolved from the pharmaceutical product and then a standardized app that people can use.

0:33:17.7 SM: And that's essentially like a product that could go to a regulator, that kind of app and thing. Sort of cuts out the person, but we actually have another study where we're actually doing... We have psychotherapists. So we have one study that's going to be app-based and we have actually an end-of-life microdosing study that's going to kick off next year. And then that is something called meaning-centered psychotherapy, which is used and has been well validated in end-of-life care as a way to relieve existential distress. And so what we're going to do is a trial of meaning-centered therapy with and without LSD microdosing, with the idea that the LSD microdose might boost that ability, that therapeutic relationship between the person. So we've got one which is more app-based and one which is more therapist-based. So that'll be interesting to dig in there.

0:34:14.0 PA: When you say meaning-centered, like existential sort of like...

0:34:17.4 SM: Yeah, existential questions with someone as they... This isn't my area, but we have psychologists that are working on this.

0:34:23.9 PA: You're just a researcher.

0:34:24.0 SM: Yeah, yeah. Well, I'm this sort of scientist, but we have psychologists that are working and have all that training to deliver that meaning-centered therapy. So it's interesting. So we're taking both angles from it. So one is the more human-centered approach and one is a more app-based approach. In terms of deployability, there's an advantage to an app and a medicine, really cheap. If you want to be able to hit a large population for very low cost in terms of health care provision, that has advantages but then also maybe human element is important.

0:35:00.4 PA: The polarity that I often set up with that is a shaman versus a playlist.

0:35:03.9 SM: Yeah. Yeah.

0:35:04.0 PA: So a shaman is not scalable necessarily, but there's going to be more personalization, potentially higher quality, potentially greater efficacy. Whereas a playlist, it's pretty... It's X, Y and Z. There are some interesting companies like Wavepaths, Mendel was at Imperial as well. It's trying to personalize that. But I think that is somewhat what are the trade-offs of an app versus person-centered care? When is each appropriate? Because it's not either or.

0:35:29.8 SM: Yeah, yeah. No.

0:35:30.0 PA: We could do both, right?

0:35:32.1 SM: Yeah. Yeah. As a scientist, I feel I have to test both. And we have to get data on both, and that's what we did. So we're in an interesting position because we have... We're a university, we work with MindBio Therapeutics from a funding and commercialization point of view. And we also get funding from the government for our trials as well.

0:35:52.6 PA: Oh, wow. Okay.

0:35:53.8 SM: So we received quite a lot of money from funding the trials from the New Zealand government, from our health research council. So we're a triumvirate relationship. But our ambition... Well, we're testing to see if these interventions can work from a formalized regulatory point of view. And we'll see what comes in the next few years. I just follow the data. So it's kind of interesting.

0:36:23.7 PA: So the follow up question that I would have to that is New Zealand, about 5 million people live there. We were just joking that there's probably 10 sheep.

0:36:32.2 SM: 10 for every person.

0:36:32.6 PA: For every person.

0:36:32.8 SM: I think it's more like five, but whatever.

0:36:35.3 PA: Yeah, it's like four to five. But there's not a ton of people that live in New Zealand necessarily. And yet there's 350 million people that live in the United States. There's 500 million people that live in Western Europe. Let's say you bring this through the various trials that you need to bring it through in New Zealand, can that then be regulated and sold in the United States and in Europe and in some other markets? Or is only that data usable for New Zealand?

0:37:06.1 SM: That's a question for MindBio Therapeutics to cross when they get there about when they start opening up their FDA filings for this product. What we can certainly do with the studies in New Zealand, at some point, they'll have... When they want to cross markets, they'll have to open up the separate filing submissions. But for now, just getting the data and working out how to do it, 'cause we are now getting increasingly confident that we know how to run these trials. So that when they do, if they're successful and then they do decide to go down those routes, that there's going to be a high probability of success. New Zealand has a relatively small... We are a small country, but we're relatively flexible and we can work relatively quickly without this giant regulatory system interface. So just being able to work quickly and flexibly will have advantages. And there's no reason why it won't work. If we can make it work in New Zealand and it does work, then it should work anywhere else, and they just have to go through those processes.

0:38:13.3 PA: Which just might take...

0:38:14.3 SM: Longer.

0:38:15.4 PA: $100 million and all the FDA approval. And hopefully that happens at a point then where MDMA is already rescheduled, where they're considering psilocybin. There's a lot that we're moving through particularly in the United States, around rescheduling, descheduling, making this cheaper to do. But I also imagine that the FDA might have different regulatory structures than New Zealand. Would it be possible in the United States to set up an experiment where people can take home acid with them?

0:38:42.3 SM: Probably not. Not at this point.

0:38:42.9 PA: Probably not.

0:38:43.8 SM: Not at this point.

0:38:44.9 PA: Not at this point.

0:38:44.9 SM: Not at this point. That's why it's good to do these experiments in New Zealand.

0:38:49.9 PA: Because you can show it's safe. You can show nothing bad is going to happen. You can show there's still so much stigma, too with LSD, particularly in the States, that doesn't help.

0:38:58.6 SM: It's very strange. And I don't really understand it as a scientific person. I don't understand why psilocybin, everyone's like, "Psilocybin, that's okay." But acid is still frowned upon. I don't understand. I think it's probably that the interface with natural health products is probably where it's coming from. But the pharmacology in terms of what it does to receptors, it doesn't make any sense that one is still held with much more stigma. 'Cause you have all these things like in Colorado, these decriminalization things, but they only apply to psilocybin. It's like, well, why doesn't it apply to other synthetic 2A drugs? I don't know. [chuckle]

0:39:42.4 PA: One, that could be because LSD is so much more potent. And I think there's a trauma from the '60s around people doing thumbprints...

0:39:49.6 SM: A cultural trauma.

0:39:49.8 PA: There's a cultural trauma.

0:39:53.2 SM: A cultural trauma.

0:39:53.3 PA: For sure.

0:39:53.4 SM: Yeah. That's probably true.

0:39:54.9 PA: Logically, rationally, I agree all of these medicines should be decriminalized. There should be no war on drugs. They should be accessible and available.

0:40:02.6 SM: Yeah, for me, actually, I really like LSD because actually, as a scientist, one of the things I like about it is because there is that Western cultural baggage, but actually there's no indigenous use of LSD. So we're not appropriating anything. We don't have to worry about that. We're not trying to appropriate DMT from some other culture and then having to deal with all that.

0:40:28.1 PA: The considerations of that.

0:40:29.0 SM: The considerations of that.

0:40:30.4 PA: What that entails.

0:40:31.1 SM: Yeah. And I think that's really important to have to deal with. But with LSD, that doesn't exist. We're not appropriating the drug from any indigenous cultures. It's fair game for us to just use within an appropriate context. But we don't have to worry about that. Whereas with DMT and psilocybin, you have to start thinking about that.

0:40:52.3 PA: Cultural reciprocity.

0:40:52.3 SM: Exactly.

0:40:54.1 PA: What is ethical with this?

0:40:55.4 SM: And for DMT in particular, that's... So, yeah. So for me, that creates quite a degree of simplicity, an ethical simplicity for me that I quite like. And it's quite liberating to some extent.

0:41:09.1 PA: LSD is very... It's a crystal. It's beautiful. It's loving. One cool thread here, which I'll weave back into one of our final questions, is LSD is made from ergot. Ergot was also part of this Kykeon that the ancient Greeks drank. So there is this also cool lineage from what was the first psychedelic that really Western civ, Western culture utilized? Well, probably Kykeon, this thing that came from ergot. What is the psychedelic that has brought us back into relationship with these plant medicines from a Western purview? Well, LSD. So there's also that cool tie together. And so the only reciprocity is maybe to our ancestors of Western philosophy, of Western civ, of those who were thousands and thousands of years ago. But it's not anyone living today.

0:42:02.7 SM: Yeah. It's interesting. The psychedelic renaissance has been built off psilocybin. The only reason psilocybin was chosen was because if Hopkins or London had just tried to study LSD, they would have been just tiffed away by the regulators. Because no one knew what the fuck psilocybin... Can I swear? Sure. No one knew what the hell psilocybin was. So they're like, "Sure, you can do this." It wasn't that easy, but relatively speaking. So it's nothing to do with scientific merit or anything. It's just that was expedient.

0:42:34.2 PA: Expedient. And also less expensive.

0:42:39.4 SM: Yeah, less expensive.

0:42:39.5 PA: Psilocybin is six hours. LSD is 12 hours.

0:42:40.5 SM: Yeah, absolutely. Sure, yeah.

0:42:41.3 PA: To hold space for a therapist for 12 hours instead of six.

0:42:43.9 SM: It's a long time. I know. It's a long time when you have 12-hour sessions. It's a staff, it's a human resources management issue to deal with.

0:42:55.7 PA: Long periods.

0:42:55.8 SM: Long day, yeah.

0:42:57.6 PA: Sure. All right. One of the final questions before we wrap is talking about lineage, talking about ancestry in New Zealand, the Māori are the indigenous people who are from New Zealand. And we talked briefly about this before we went on air and you were like, "I'll save it for when we go into the podcast." Do the Māori have any sort of practice with plant medicines, with psychoactives? Is there any sort of research or ethnobotany or archaeology that has discovered that? What's going on there historically?

0:43:30.1 SM: Yeah, so it's interesting because actually, I think Māori are the only indigenous population where we are not aware of any indigenous use of any psychotropic substance.

0:43:42.1 PA: Wow.

0:43:43.2 SM: Which is very unusual. Now, what's even stranger, though, is that New Zealand actually has indigenous mushroom species, indigenous psilocybin mushroom species. So we have some that are endemic that are not found anywhere else and some that are around. But it's interesting that Māori don't even have word for these different mushrooms. And now this is insane. Because they knew their land and they knew all the species on their whenua, on their land, had words for everything. But what? There's these species that exist and they didn't know that they would trip off these things? Doesn't make sense. Because what happened during colonization was in 1906, there was something called the Tohunga Suppression Act. Tohunga were the indigenous healers. And so one theory is that maybe Māori just didn't know about it, but maybe it was actually just completely suppressed out by the Pākehā colonizers when they came out and actually just completely killed that element of knowledge.

0:44:47.6 SM: And we've been asking around and some of my colleagues have been asking around trying to find that knowledge, but we haven't found anyone who knows it or is willing to share it. 'Cause it's how that kind of knowledge around plant medicine is held really tightly by those.

0:45:04.5 PA: It's like magic, basically in some ways.

0:45:06.1 SM: Yeah. It's spiritually really sensitive.

0:45:08.6 PA: Talk to me. Yeah, very sensitive.

0:45:09.4 SM: But also because they are an indigenous species of New Zealand, the psilocybin mushroom, Māori have indigenous rights to that under our Treaty of Waitangi. The Crown has granted anything that is indigenous to New Zealand, Māori have rights to that because it's in law. Because we have a treaty that was signed. And so even though they might not have used it in the past, they still have prospective rights over that. So they have the right to...

0:45:42.3 PA: Potentially work with mushrooms...

0:45:43.4 SM: To work with these mushrooms, and the Crown shouldn't be able to stop them from doing it because it's their Tohunga, their treasure, because it's growing on their land. And so there will be legal disputes to be had in the future about the status of these mushrooms because they are owned essentially by Māori population because it's their land and we're just guests on it.

0:46:08.0 PA: So as a final question for that, what is the environment around psychedelics, around psychoactive substances in New Zealand? For example, in the Netherlands, it's legal. You can go into any store and buy truffles, but only maybe four to five percent of people actually use it. Is there a lot of stigma still around these things? Is there more education and understanding how to...

0:46:30.0 SM: It's similar to most European countries or America. You gave us the drug war. We're eternally grateful for it. [chuckle] So we've suffered under it for as much. So we still have that stigma, but it's slowly, I would say, disappearing. But we had a referendum on cannabis a couple of years ago and it didn't get passed.

0:46:54.9 PA: Wow.

0:46:55.3 SM: So we do have a lot of work to do in terms of education. But one of the things is, across the political spectrum and across the entire country, we know that we have mental health problems and whatever solutions are needed. There will probably be hopefully some consensus in the future. So if psychedelics were to play a role in that, I think that would be seen as being... There would be probably agreement on that if the evidence was there. So, yeah. But there's still going to be a long path for us. So I think we're good for running trials. But in terms of deploy...

0:47:36.4 PA: Wider cultural acceptance.

0:47:37.1 SM: Wider cultural acceptance, that will take more time.

0:47:39.0 PA: Gotcha.

0:47:41.4 SM: So, yeah.

0:47:41.8 PA: Well, time will tell.

0:47:43.6 SM: Interesting. It'll be an interesting couple of decades.

0:47:45.6 PA: Absolutely. So I'm really grateful that you joined us. We got a really strong overview of the clinical trials, the research on LSD microdosing. We talked a little bit about New Zealand, the Māori. We'll link to all of these in the show notes. So people want to read the paper, we'll provide a link. I'd love to read the paper as well. I'll have to come to your talk tomorrow to...

0:48:06.7 SM: Yeah. The paper is in submission at the moment.

0:48:07.8 PA: It is.

0:48:08.0 SM: It'll probably be a couple of months till it emerges into the scientific literature.

0:48:13.1 PA: Okay. We'll then include that. If people want to support your research, if people want to support the work that you're doing, if people just want to learn more, any websites or resources to point them to?

0:48:25.6 SM: Oh, God. I don't even think about that. I don't really do social media. [chuckle] We have a Facebook group, I think. And there's the company as well, MindBio Therapeutics, investors can go into there to help us out through the company. And then I guess they can get in touch through our Facebook, Auckland Neuropsychopharmacology Group. We post updates about what we're doing on there. I don't do it. My postdocs do. I'm a hermit. [chuckle]

0:48:54.9 PA: I love it. Well, thank you for joining us.

0:48:56.7 SM: Thanks, Paul. It was a really fun conversation.
[music]

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