Please enjoy this transcript of my interview with Dr. Suresh Muthukumaraswamy.
Dr. Muthukumaraswamy completed his PhD in Psychology at the University of Auckland in 2005, after which he joined the newly established Cardiff University Brain Research Imaging Centre as a postdoctoral fellow. While at Cardiff, he started research work with psychedelics in 2011 in collaboration with Professor David Nutt and Dr. Robin Carhart-Harris, investigating the neuroimaging correlates of the psychedelic drugs psilocybin and LSD. In 2014, Suresh received a prestigious Rutherford Discovery Fellowship and returned to the University of Auckland where he works in the School of Pharmacy at the Faculty of Medical and Health Sciences and leads the Auckland Neuropsychopharmacology Research Group.
This special episode of the podcast is a live recording from an event hosted by the Edmund Hillary Fellowship (EHF). EHF began in 2016 as a pilot immigration program and has matured into a fellowship of more than 500 technologists, creatives, investors, entrepreneurs, educators, and systems designers, committed to New Zealand as a base camp for global impact. From more than 50 different nationalities, including New Zealand, fellows span a range of high-value sectors: media, education, cleantech, venture capital, and mental health initiatives/research just to name a few. EHF and its fellows aim to make a meaningful impact in New Zealand/Aotearoa with projects that often have global applications.
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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Tim Ferriss: Hello, boys and girls, ladies and germs. This is Tim Ferriss. Welcome to another episode of The Tim Ferriss Show. This episode is a special episode. It is a live recording from an event hosted by the Edmund Hillary Fellowship. The Edmund Hillary Fellowship, otherwise known as EHF, began in 2016 as a pilot immigration program, and has matured into a fellowship of more than 500 technologists, creatives, investors, entrepreneurs, educators, and systems designers, among many other things, committed to New Zealand as a base camp for global impact. From more than 50 different nationalities, including New Zealand, fellows span a range of high-value sectors, such as media education, cleantech, venture capital, and mental health initiatives and research, as we will hear in just a few moments. And that’s just to name a few.
EHF and its fellows aim to make a meaningful impact in New Zealand/Aotearoa with projects that often have global applications. We talk a bit about that and certainly explore a lot more with today’s guest. You can learn more about EHF at ehf.org.
Michelle: Greetings to you all and welcome to today’s EHF live session. The Edmund Hillary Fellowship is a collective of entrepreneurs, scientists, storytellers, creatives, and investor changemakers who want to make an impact globally from Aotearoa, New Zealand. In this session today, you’re going to hear from Tim Ferriss, he’s an EHF fellow who’s an early stage technology investor and advisor, and Tim will be interviewing Dr. Suresh, an associate professor at Auckland University.
The topic today is on mental health and breakthrough therapeutics. There’ll be plenty of time for Q&A with Tim and Suresh during the 90-minute session, but nearer the end. Over to you, Tim.
Tim Ferriss: Thank you very much, Michelle. It’s a pleasure to be here and it’s a pleasure to be doing a live session. I have been looking forward to this for some time. And without further ado, let me introduce the main attraction, and the guest of the hour. And that is Dr. Suresh Muthukumaraswamy. I will here forward refer to him as Suresh.
Suresh is an associate professor of psychopharmacology at the University of Auckland. And he completed his PhD in psychology at the University of Auckland in 2005, after which he joined the newly established Cardiff University Brain Research Imaging Center as a post-doctoral fellow. While at Cardiff, he started research work with the psychedelics and psychedelic compounds in 2011 in collaboration with two very well known names, professor David Nutt and Dr. Robin Carhart-Harris investigating the neuroimaging correlates of the psychedelic drug psilocybin and LSD.
In 2014, Suresh received a prestigious Rutherford Discovery Fellowship and returned to the University of Auckland where he works in the School of Pharmacy at the Faculty of Medical and Health Sciences, and leads the Auckland Neuropsychopharmacology Research Group. Suresh’s main research interests are in understanding how therapies alter brain function and behavior. And in testing methodologies to measure these changes in both healthy individuals and patient groups, particularly in depressed patients. And, of course, this session will have a focus on mental health. So we will delve into that. At the University of Auckland, he has conducted clinical trials in depressed patients involving ketamines, scopolamine, and transcranial magnetic stimulation, TMS.
He has received several Health Research Council of New Zealand research grants to support this work, including a grant to investigate the effects of micro doses of LSD on brain and cognitive function. Suresh has published 117 papers. And his work has received more than 8,000 citations.
Suresh, welcome to the session. Thanks for being here and taking the time.
Dr. Suresh Muthukumaraswamy: My pleasure, Tim. Nice to see you.
Tim Ferriss: Hopefully, I didn’t butcher the name too badly. And I will start with trend lines and perhaps just an overview of where we sit currently, and perhaps you could just take some time to describe mental health and/or addiction statistics, trend lines in New Zealand. That may be a meaningful place to start and serve as a canvas upon which we can discuss other things.
Dr. Suresh Muthukumaraswamy: Yeah, so New Zealand has pretty good data on this because every year the Ministry of Health runs a survey called the New Zealand Health Survey. And they’ve asked for a long time about psychological distress, and the amount of psychological distress that the adult population is experiencing. So in terms of trend lines, so this is conducted every year. So in 2000, I think ’11/12 when the survey was conducted, 4.6 percent of adults experienced psychological distress in the last month. And we’ve seen that slowly creeping up to the last data point from 2021/2020, where it was now at 9.6 percent.
So we’ve seen a doubling over the last 10 years in the amount of adults experiencing psychological distress, which is anxiety, depression, or sort of psychological fatigue. So it’s more than doubled. And COVID is definitely going to impact on that. We see a little bump on the last one from the first sort of impact to the first wave of COVID, and those lockdowns. And I expect that’s going to only get worse when the next year’s data point comes out because in New Zealand, you might not be aware, but in New Zealand the second lockdown was quite hard that just finished at the end of 2021. So that will definitely have impacted on people’s mental well-being. So we’ll expect that to go up so it’s not, it’s not a good place we’re in. So it’s not just COVID, it’s been trending up for a long time, and it’s not getting any better.
Tim Ferriss: And I would imagine, although I don’t want to assume, that the costs, and there are many different types of costs, but the healthcare costs of these upward trend lines with mental health issues, let’s just call them depression, chronic anxiety, treatment resistant depression are, if anything like the United States, quite high in New Zealand as well. Not to mention the personal costs. Let’s talk about just a few compounds first. And actually, as way of background, could you mention just a few other classes of compounds that you’ve also done research with because I think it’s important to note that you have done more than study what we would consider to be psychedelics. So perhaps you could just give a bit of context there.
Dr. Suresh Muthukumaraswamy: Yeah, so my background is in general psychopharmacology. So before studying psychedelics and, concurrently, just studying psychedelics, I’ve spent a lot of time studying anesthetics and GABAergic drugs. So GABAergic drugs tend to be kind of sedative. So alcohol is a GABAergic drug, benzodiazepines, so a lot of the anesthetics like propofol. So I’ve studied all those drugs at various times, various anti-epileptic drugs. So that kind of class of drugs.
And then, also, we recently did a study of scopolamine, which is a muscarinic drug and remifentanil we’ve looked at in the past. I’ve done a lot of psychopharmacology studies that have nothing to do with psychedelics. Although, the psychedelic studies are the ones that probably are most well known for in the public discourse, because they attract some interest, I suppose.
Tim Ferriss: They catch the attention. So we’re going to talk about the contrast between, say, ketamine and traditional or classical psychedelics.
But before we get there, because I am personally very curious, why did you decide to study scopolamine? And what did you find in terms of its effects on conditions, whether depression or otherwise? Because scopolamine, for those who don’t know, is also naturally occurring in many plants that are considered psychoactive, or a hallucinogenic. Some of which are considered quite risky. But how did you determine this as a subject of interest for research?
Dr. Suresh Muthukumaraswamy: Yeah, so we had been doing studies on the antidepressant effects of ketamine. And we’ll talk about this later, but you see this wrapped antidepressant effect. And so what we were interested in was are there other compounds out there that might show similar rapid antidepressant effects? And there was a series of studies that came out of the NIH Intramural Program. There was two or three intravenous scopolamine studies that appeared to show a similar sort of pattern of antidepressant effects. And scopolamine works very differently to ketamine, or other antidepressants being a muscarinic antagonist. So I thought, “Well, that’s really interesting. If that works, then we can study that. And even though it’s got a completely different kind of receptor binding mechanism that we could investigate that.” In our study, we looked at depression. And then, if we could then identify neurobiological markers that would go along with that, then we would sort of have a converging theory of maybe what causes rapid antidepressant responses.
The downside, of course, is that we found no antidepressant response in that study. But that’s the data. We did a really carefully controlled study. Unlike the previous research that used a inactive placebo, and we’ll get back into this, we used a active placebo, a compound called glycopyrronium, that’s used a lot in surgery that doesn’t cross the blood-brain barrier, but still as antimuscarinic. And it creates a slightly drowsy feeling, and dry mouth, and a lot of the kind of side effects that you might get. And so we were able to show that participants could no longer distinguish which of the drugs that they had. And, actually, we are ascribing most of the antidepressant response that we see to a placebo response. So lesson learned.
Tim Ferriss: Yeah, that’s fascinating. Scopolamine, I don’t want to take us too off track, but has some very interesting effects on memory, or at least it’s thought to have some very interesting effects on producing amnesia.
Dr. Suresh Muthukumaraswamy: Yes it does, yeah absolutely.
Tim Ferriss: While still having agency on some level. It’s a fascinating compound.
So let’s jump to ketamine. Most people or, say, many people have perhaps heard of ketamine. Very commonly used. And please correct me if I get any this terminology incorrect, but anesthetic, dissociative anesthetic, does not suppress respiration, at least at the doses that I’m familiar with. It is very widely used in medicine. I believe it’s one of the World Health Organization’s top 100 most essential medicines.
Could you discuss ketamine and classical psychedelics, and how they differ? And just from an anecdotal perspective, although there’s a lot of really good research, which of course you’ve been a part of, looking at the antidepressant effects ketamine, I know multiple people now who would credit their lives being saved to ketamine. And part of what makes it so fascinating to me is not that it’s a silver bullet that works for all people, but it’s the rapid onset of some of the effects in certain subjects compared to, say, traditional or conventional SSRIs, which in some folks it can take six to eigh weeks say to exert those types of effects. If the people respond at all. So could you just perhaps give us a primer on ketamine, and classical psychedelics and how they differ because both can be described as having psychedelic effects.
Dr. Suresh Muthukumaraswamy: So maybe the easiest thing to start is with this classical psychedelics because it’s relatively simple compared to ketamine. So LSD and psilocybin, DMT, they all seem to work through a common receptacle, the serotonin 2A receptor. And we think that most of their effect — there’s probably some other receptors that are involved in parts of the response. But, overwhelmingly, we think that most of that sort of psychedelic experience is generated from this serotonin 2A receptor and binding there.
So, conversely, ketamine, even though it has these kind of dissociative or psychedelic effects, it’s receptor binding. So it’s many and complicated. So principally binds to an antagonist receptacle called the NMDA receptor and that’s a glutamate receptor. So glutamate is the most common neurotransmitter in the brain. We don’t hear about it a lot. And the NMDA receptor’s kind of interesting because it’s actually the receptor that’s really heavily involved in neuroplasticity. And it’s something called long-term potentiation. So that’s essentially how brain cells — it’s the receptor involved in how brain cells learn to communicate and strengthen synapses. So that receptor is really important there.
But then, it also has a host of other effects. So it binds to GABA receptors. Those are kind of the ones involved in inhibition and sedation. It also binds to opiate receptors. And everyone familiar with opiates. And then, there’s other monoamine sites that it interacts with. Serotonin, dopamine, norepinephrine, HCN channels, sodium channels. The list goes on and on as you go up through the concentration. So it’s an extremely complicated pharmacology. And it goes even worse because actually ketamine metabolizes into norhydroxyketamine, which has neuroactive sites as well. And most compounds exist in the left and right state they’re called racemic. So there’s a left and a right state. And so there we have S-ketamine and R-ketamine. And normal ketamine is both of those, but actually the R and S ketamines probably have different receptor binding profiles in addition to all of that. So what we’re left with is there’s a stew. You could either call it a very rich drug, or you could call it a dirty drug, depending on your perspective.
Tim Ferriss: It’s very promiscuous in terms of its receptor affinity.
Could you explain for a second two things? So the first is why scientists would wade into this soup of variables, clinically from the perspective of mental health, what makes it interesting? And then second, what an antagonist does just for people who may not have that vocabulary?
Dr. Suresh Muthukumaraswamy: Sorry. Yeah, so when drugs are in the brain, it’s more complicated, but broadly speaking, an antagonist is something that blocks the activity of something that is going on. So an NMDA antagonist blocks the NMDA receptor so it stops glutamate working there. For ketamine, there’s both a clinical and a scientific interest there, and they’re both really interesting to study, which is why I’ve been studying ketamine for nine or 10 years now.
The clinical significance is what you mentioned before. You can take patients into the lab. And patients that have had treatment-resistant depression, unremitting for years and years and years. And you can give them a ketamine infusion and they’ll get this really rapid remission in symptoms. And that would manifest itself in hours. Now, people will know ketamine is a street drug. And they will say, “Oh, well, maybe that’s just because the person’s high that they’re experiencing this intoxication.”
So my response to that would be, well, actually if you then measure the person’s depression symptoms at 24 hours after the ketamine infusion, you’ll see that they’re still not depressed. Now, what we know about the pharmacokinetics is how long ketamine lasts in the body, the half life’s about four hours for ketamine. So, at the 24-hour time point, there’s really no ketamine left in the body at all. So the ketamine’s gone, they haven’t been high for 20, 22 hours. So they’re not high anymore. The ketamine’s entirely left the body, but they’re still not depressed.
And then what that shows is that the ketamine has changed something in their brain. So there’s caused some kind of functional change in the brain. And to move them from a depressed to a non-depressed state. So that’s really interesting that there’s kind of like a switch in there that actually can be clicked. And ketamine’s, obviously, working on some kind of target that can flip that switch. And understanding what that is scientifically is really interesting.
And while other things can flick that switch, they do it much slower. Like SSRIs, they switch it in maybe four to six weeks. Or TMS, transcranial magnetic stimulation, that might take a month to work as well. But here we can switch it in a day. For a scientist, that’s really interesting because you can run really good experiments because you no longer have to wait six weeks and all these extraneous variables that get in the way of your interpretations. You can just go depressed, non-depressed within a day. And that leads to really tight experimental design.
Tim Ferriss: So I want to preface what I’m about to say with the statement, which is I know that the plural of anecdote does not equal data. Nonetheless, I do think case studies are interesting. And I can speak to one very acute example. A friend of mine in law enforcement who was suicidal, he had acute suicidal ideation. And many people in law enforcement, or in the military, pilots would be another category, are very hesitant to admit to any type of mental challenges, or to seek treatment because it can result in leaves of absence, and basically penalties, professionally speaking. And ketamine did exert those rapid effects. And, again, not to say that this should be the expectation for every patient, but there are people who I know who go in acutely suicidal, and have come out literally saying, “I don’t know what I was so upset about. I don’t know how I was so concerned about X, Y, or Z.”
And what I’d love to ask you next, just again to contrast the say classical psychedelics, and you mentioned a number of them, which are in the say tryptamine class, and we probably won’t get into the phenethylamines and mescaline, and MDA and so on, which can be very different in some of their subjective effects. But if we’re looking at, say, LSD, psilocybin, and then ketamine, if you look at the durability of some of the effects, say, for anti-depression, what is your personal perspective on how they might differ in why they have durable effects?
And I raise this because I was recently in a conversation with Roland Griffiths from Johns Hopkins Medicine, who’s done a lot of work with psilocybin, and also John Krystal at Yale, who’s done a lot of work with ketamine. And Roland’s perspective was that he thinks a lot of the durability of anti-depression effects, six months, 12 months that follow up, let’s just say, have a lot to do with a change in content. Meaning that people are actually able not just to suppress the symptoms of depression, but to address some of the kind of root narratives that are leading to depression. And he was less sure about ketamine. And maybe there’s sort of more of a mechanistic explanation like neurogenesis, or increasing dendrite growth where it’s sort of fixing the machinery, so to speak, on some level. What are your perspectives?
Dr. Suresh Muthukumaraswamy: Yeah, I mean, it’s a good question. I guess the background to this for people is that the antidepressant response that we see to a ketamine infusion that will last, in our experiences, anywhere from a day or two to couple of weeks to a month. Whereas, the data for like psilocybin that seems to indicate like months, half a year, year-long antidepressant responses. But I think that this kind of falls into the, we don’t know pile from a data perspective because the models that have been used to — the experiments have been done between ketamine versus the classical psychedelics have been really different in terms of the therapeutic approaches tried. So when people have been doing these psilocybin-assisted therapies, they’ve been wrapping around an intense amount of psychotherapy. And I think it’s really important for people to understand when they think about because you just read these headlines, “Psilocybin improved depression.”
Well actually it’s not just psilocybin. It’s the fact that the person’s gone into the psychotherapy regimen with a therapist and they’ve done hours of preparation for the experience. The therapist has sat through them through the experience. And then, they’ve spent hours and days on integration afterwards. So it’s probably about 40 hours of psychotherapy for one psilocybin course. So it’s not just the drug alone. It’s psychedelic-assisted psychotherapy.
Now, whereas the model for ketamine that’s mostly being used is basically anyway, seems to be used in [inaudible 00:20:34] is that people just go into a ketamine clinic, and they smash in an infusion for an hour, and they go away. And there hasn’t really been much studies where people have actually done ketamine-assisted psychotherapy and tried, “Well, what would happen if we wrap that similar level of psychotherapeutic support around ketamine, would that make that ketamine response now stretch out beyond two weeks to maybe a similar kind of time course?” And because the people in the psilocybin world have come from that kind of more traditional psychedelic-assisted therapy world. And the people that have been studying ketamine have come from more of a kind of traditional psychiatry world. And I’m not aware of any data that really has kind of tried to find the man in the middle, or strip back psilocybin to just psilocybin, which I think people would ethically struggle with trying to do that kind of experiment.
Tim Ferriss: And do you say that just because of the difficulties that can come up in navigating that experience?
Dr. Suresh Muthukumaraswamy: Yeah, because 3something like psilocybin is very powerful in terms of psilocybin, and DMT, LSD these have very powerful psychological effects, and they can be destabilizing for people. So people need to be well-prepared that they’re going to experience very unusual, profound, potentially disturbing things. And to not provide that preparation might not be ethical to strip it back to nothing like is done for ketamine.
Tim Ferriss: Right. But then, there’s probably a middle point where it could be stripped down to sort of the minimal viable support on the front side, and then still provide the support on the post-session side. And this also highlights for me, I don’t know, that we are really in a very fertile nascent period of psychedelic research. And even though studies were conducted much earlier, say in the ’60s, they don’t really meet our standards for study design that we would have today. And, certainly, with the imaging techniques that you have, fMRI and others that are now at hand, you can simply, you can examine these tools with a set of lenses that you couldn’t before. And it’s really been astonishing to me to see how far very little money can go in this space compared to perhaps other areas like oncology or cardiology. For instance, could you speak to how you pick your studies? For instance, the LSD microdosing study? Why did you choose to pursue that study?
Dr. Suresh Muthukumaraswamy: So I had returned to New Zealand in 2015 and having previously done classical psychedelic. So I went and I started my research group here. I thought, “Well, we’ll start with ketamine,” because you know, it’s approved. It’ll be reasonably, be easy to get approval for. And no one’s going to blink too many eyelids about a new guy coming into town, wanting to study ketamine.
New guy, coming to town, wanting to do LSD is probably going to fluffle a few more feathers around the faculty, I would have thought back in those days. But having sort of built a bit of a reputation and I decided it was time to get back into doing some classical psychedelic research. Now the microdosing specifically was, well, no one had really looked at microdosing in a RCT at that point. And —
Tim Ferriss: That’s a randomized control trial.
Dr. Suresh Muthukumaraswamy: Randomized control trial. And I guess, should we explain what microdosing is maybe, first?
Tim Ferriss: Why don’t you explain what that is? And it also might segue into one of the design challenges, meaning placebo control, in psychedelics overall. So yes, please define microdosing.
Dr. Suresh Muthukumaraswamy: So microdosing is when people take very low doses of psychedelics, about the 10th the dose of a big dose of a, when people are going to be tripping. So people might trip on a hundred, 150 micrograms of LSD, but for microdose, they might take 10 micrograms, say. So about a 10th. And it causes — well, we don’t really know exactly what it causes yet, because we haven’t studied it properly, but users report that they have improved mental well-being, concentration increases. And so what they do is that they take these microdoses, maybe every third day is the most common schedule. This was popularized by James Fadiman, who wrote a book in 2011.
And it’s really taken off since then. Before 2011, not many people were doing it. And there was really not much consciousness about it, but now we’re seeing hundreds of thousands probably of people around the world now microdosing. You look at the size of the Reddit forum subscriptions, just going up and up and up. So there’s a huge amount of people out there microdosing these classical psychedelics, every third day. Many are giving up their antidepressant medications to do this, but there’s really no clinical trial evidence about it. And not even in mental health patients, just not anything. Now the reason that is is because if you were to run a proper RCT, a proper randomized controlled trial of microdosing a psychedelic, then you have to prescribe a class A substance, a schedule one substance, for people to take home and most legal systems won’t allow you to do that. I don’t think you could do that in the United States. I don’t think the DEA is going to be very happy about —
Tim Ferriss: I think they might be a little grumpy about that.
Dr. Suresh Muthukumaraswamy: Yeah. And so there’s not many jurisdictions where that could be done. So however, there is one jurisdiction where it can be done legally and that’s little old New Zealand. So as I was, as you do every now and then, reading the Misuse of Drugs Regulations from 1977 and the Misuse of Drugs Act that goes along with it, we kind of discovered this loophole. I don’t know if you call it a loophole, where actually we are allowed to prescribe class A substances.
It’s not ever really been done, but it’s just sitting in the legislation saying that this is allowed to be done. So we engaged in a long process with the Ministry of Health, and provided a legal reasoning for why this could be done. And so we did it and applied to them. Then we got the appropriate approvals from the Ministry, various parts of the Ministry to do it. And that allowed us to run the study that we’ve just finished collecting data for, which was to give 80 healthy volunteers a six-week LSD microdosing course, where they would take the first one in the laboratory. And there are other 13 doses that were taken out in the wild as it were much like people do in real life.
Tim Ferriss: Let’s dig into that a little bit. So were they given the other 13 doses to take home all at once, or did they come back to get one at a time?
Dr. Suresh Muthukumaraswamy: Yeah, they were —
Tim Ferriss: Or two at a time?
Dr. Suresh Muthukumaraswamy: Yeah, they were given packs of four, four and five. So we never gave them like a hundred and forty micrograms to take home so that they couldn’t just stack them all up. But actually, there’s a lot of theoretical concern about this, but actually to get into one of our trials, participants have to do multiple screening sessions. They spend hours getting scanned and having all sorts of probes attached to their body to record all their physiology, getting pricked with needles and blood taken and all sorts of stuff. Hours and hours. There are a lot more efficient ways to get doses of LSD.
Tim Ferriss: Oh, for sure. Yeah, absolutely.
Dr. Suresh Muthukumaraswamy: We track — every single dose was administered and video recorded by the participants and sent to us. So we knew there was a hundred percent adherence to protocol.
Tim Ferriss: And a part of the reason that I’ve been engaging with science in New Zealand is precisely for this reason. I mean, you have, on some levels, a very agile ecosystem compared to the United States. And you have legislation that would allow you to even consider designing a study like this. Could you speak to how New Zealand can, or does foster scientific and research innovation? You could speak to certainly what you’ve already mentioned, any regulatory differences, but what else makes New Zealand unique? What else could make New Zealand unique?
And we can go from there. I would love to hear what else is happening in New Zealand that you find interesting from a scientific standpoint in this domain, but let’s begin with, how does, or how can New Zealand foster scientific and research innovation?
Dr. Suresh Muthukumaraswamy: Yeah, that’s a good question. I think we do have — we have a strong regulatory environment, but it’s — so I’m not saying our regulatory environment is weak. It’s strong, but it’s capable of being agile. And it’s small. We’re a small country. So it’s possible to just ring the person up who’s involved in this, that, or the next thing. Whereas in another place you might be trapped behind five layers of bureaucracy to these hidden figures that, making these decisions. In a country of five million, there’s only so many people who know, are involved in these kind of decisions. So if you are sensible and polite and inappropriate, you can ask questions and get things to move. So, we do have that. So with small size, I think does come agility.
I know that there are certainly pharmaceutical companies that are investing into New Zealand psychedelics industry, and our general medical — into clinical trials here. We’re an attractive place to run clinical trials. Because also we’re relatively cheap in terms of the what you can get on a per dollar basis compared to what you might get in Europe or the United States. So that’s attractive. So we do have a good regulatory environment in terms of how we can promote more innovation. I think at the moment the government does take reasonably hands-off approach, particularly in this area, it’s taken a completely hands-off approach. By comparison, and where we risk falling behind, by comparison Australia, they created a 15 million fund specifically for these sort of breakthrough mental health therapeutics to kind of prime the pump. Because you do need a certain amount of capacity.
You need a certain amount of infrastructure. You need people. So they’ve set that up as a pump-priming exercise, really to provide all the capability they need. So we haven’t seen any signs of that yet from government, that they’d actually be sort of a more dedicated funding pathway. Now we are able to get funding, but we have to go into the general pot of funding. So we have to compete with all the cancer researchers and the heart researchers, which does mean that when we do stuff and get funds, that our work is of very high, has to be of very high quality. Because we are competing with our peers that are producing, doing very high quality stuff. So we know when we get funded that what we’re doing is rigorous.
Tim Ferriss: Yeah. So good news is, there are regulatory frameworks and federal funding for this type of work. Bad news, you don’t have something like the NIMH. I think it’s the National Institute on Mental Health in the United States, which might give grants specifically to this type of work. You have to compete against every researcher in any given medical field who is seeking funding.
Dr. Suresh Muthukumaraswamy: Yeah, that’s right. I guess. But yeah. There’s actually some data on that and actually what we’ve seen, and not just psychedelics, just mental health in general has been underfunded in New Zealand for a very — mental health research, let alone treatment services. Mental health research has been underfunded in New Zealand relative to the burden of disease that we see in the country. So there are some parts, things like neurology has been relatively speaking overfunded, and we’ve spent a huge amount of research dollars on things like neurology and cancer and heart.
They’ve actually, relative to the burden of disease, they’ve done very well, but actually mental health, relative to the burden of disease we’re seeing in the population, this can be quantified using disability-adjusted life years. And you can look at research income relative to disability-adjusted life years, and mental health is not being given the funding it needs. So there’s an argument that New Zealand does need to carve out specific, not psychedelics, but mental health research, so that to make sure that we’re getting that research done to serve the disability that we’re seeing in the population and the health needs.
Tim Ferriss: Do you have something equivalent in New Zealand to breakthrough therapy designation? And I ask because the FDA here in the US has granted both psilocybin and MDMA-assisted psychotherapy, breakthrough therapy designation for depression, different types of depression and PTSD, posttraumatic stress disorder, respectively. Do you see ways that the New Zealand government could foster innovation and more experimentation with some type of designation like that?
Or for instance, I’m sitting here in the state of Texas in the United States, which for those who don’t know is generally thought to be a very conservative place. But nonetheless there was legislation recently passed both by the Republican — so let’s just call it conservative and liberal parties, to get state funding set aside for psychedelic research related to veterans, for instance. That was bipartisan. And that will be coming online soon. Do you see any particular tools or approaches that New Zealand might use to further foster, what is, I think what already is pretty vibrant ecosystem, but it could certainly do quite a bit more. What are your thoughts?
Dr. Suresh Muthukumaraswamy: Yeah, I think for — I think the latter would be the way to go. So I think in terms of things like breakthrough designation, we don’t have, we in New Zealand sit at the end of the pipeline for when treatments come. Because the way our treatments come is, an international pharmaceutical company will apply for registration here and they’ll use all the data, basically they’ve submitted to the FDA. So once they’ve got FDA or EMA approval, then they might come here for approval after a few years, and they bother to put the marketing application together. So we are kind of at the back end of that process here. And that’s why we have in New Zealand, sadly, a relatively weak pharmacopeia, where a lot of drugs that are available in the US or Europe aren’t available here because they’re just not marketed, because we’re a small market.
So I don’t see that first approach, but the second approach could certainly work, where the government sets aside — probably won’t be through legislation. Would direct one of its funding bodies to say — and it does this for other areas of research. It says, “Okay, let’s fund this.” Let’s fund, this — things like growing up in New Zealand. So New Zealand has a really good history of funding longitudinal research. So there’s the Dunedin Study and the Christchurch Study.
And now growing up in New Zealand, we’ve got really strong longitudinal studies that have been going on for like 40, 50 years that have been centrally funded. So that would be a mechanism that could certainly work.
Tim Ferriss: I’m very excited about New Zealand as the tip of the spear for studies along the lines of what you have done, you and your team have done with the LSD microdosing study, where you have the ability to pilot and innovate in a way that is simply not possible in some larger places like the United States. I mean on some level similar to the way that large global brands, in some cases, even though you might be last in line or at the back of the line for certain types of say global drugs that are available elsewhere, you also have companies like, I want to say Adidas and Nike and so on, who will actually do pilot studies and launches in New Zealand because you have sort of all of the ingredients for English speaking first world country with incredible research faculties.
And I mean, in this particular application, they’re looking at commercial interest, but you can pilot and run experiments on a small or longitudinal basis that you can then apply elsewhere, which I think is incredible. So it’s a huge gift that New Zealand also has to offer the world, in a sense. Who are other scientific inspirations inside of New Zealand? Are there other scientists who you think are doing particularly interesting work? Could be limited to psychedelics or adjacent compounds, or could be applied really anywhere else?
Dr. Suresh Muthukumaraswamy: New Zealand has a rich biomedical tradition. I work in a general medical faculty, so the people sitting next to me are doing cancer research or — so we have really amazing people doing work in place in New Auckland called the Liggins Institute, where they’re doing work on preterm babies and they do really amazing interventional work there. There’s also really strong stroke research happening in New Zealand, looking at how stroke recovery research is doing really well in New Zealand. And down in Otago, I really like the group down there that are doing, in the more psychedelic space, they’re doing — Paul Glue’s been doing a huge amount of work with ketamine and then various ketamine analogs. And different ketamine formulations that they’ve been working at. There’s quite a rich group of research happening down at Otago as well. So I guess it’s mostly centered around where the two medical schools are located in New Zealand, is where things are happening in the biomedical realm.
Tim Ferriss: What do you find interesting with the — are there any particular ketamine analogs that you find interesting? And maybe you could just define what that means for a minute. And I also want to just to refer to something you mentioned earlier. You were talking about the metabolites of ketamine being bioactive or psychoactive themselves, just for those who have a general interest in psychedelics. This is true for a lot of compounds. I mean, it’s true for ibogaine and noribogaine and so on, which certainly makes them more interesting to study. But what is a ketamine analog and are there any analogs or approaches to analogs that you find particularly interesting?
Dr. Suresh Muthukumaraswamy: Yeah, so maybe it’s not an analog. One of the things they’ve been studying, looking at slow release formulations as one way to go. And this comes back to that thorny issue about, with ketamine, how important is actually having the psychedelic experience? But maybe if you could slow down the metabolism of ketamine, then you could potentially — if you could slow down the absorption of ketamine, so it’s not such a hit, but came in slower. So there’s really interesting work happening with slow release formulations. There’s a New Zealand company who have been looking at that. Douglas Pharmaceuticals, who have been looking at this kind of slow release ketamine. That’s quite interesting. And then there’s different companies overseas as well, looking at — and I described that left and right formation. They’ve been stripping ketamine into its R and S formulation. Now, Janssen, as you’ll be aware, they took the S-ketamine, the S part of ketamine and put that in a nasal spray. And so that they could —
Tim Ferriss: Spravato.
Dr. Suresh Muthukumaraswamy: Yes. Spravato. And this is essentially a marketing exercise, right? It doesn’t seem that — it doesn’t has any more efficacy than normal ketamine, but it allowed them to achieve a patent on it. And in New Zealand, that’s quite —
Tim Ferriss: What is the price differential? I think it’s something like one to $5, generic. Several hundred dollars, Spravato, USD, something like that?
Dr. Suresh Muthukumaraswamy: I mean, in New Zealand, it’s, there’s even bigger differential. Because in New Zealand, ketamine is pharma subsidized. So we can get a vial of ketamine for like $20 or something. Of course the Spravato is like five or $6,000. So yeah, so it’s just — the differences are insane. But you know, for a clinician who may not be comfortable with prescribing ketamine off label. Because ketamine is not indicated for depression, it’s an off-label treatment. And because it’s a controlled substance, people — there are clinicians that get antsy about that, and fair enough.
But that ketamine, as ketamine, is allowed to be prescribed on label, that may make things easier. The problem with ketamine, the only reason ketamine is — not probably, is. Because it’s a generic compound. I guess this is a sort of background in how medicines get approved. Is, you need a company to sponsor the research. In New Zealand, to go to MedSafe and say, “Look, here are all our data. Ketamine should be indicated for depression.”
But no company is going to do that for ketamine because it’s just too expensive and basically any generic competitor can just come in, make more ketamine, and sell it instead. So there’s no return on investment to be had there.
Tim Ferriss: With intellectual property.
Dr. Suresh Muthukumaraswamy: Yeah.
Tim Ferriss: Let’s talk for a second, if you wouldn’t mind expanding on Paul Glue and his work a bit. Because I think some of it may give indications for other approaches that can be taken by researchers to do this type of work. Would you mind just elaborating a bit on what type of work he’s doing?
Dr. Suresh Muthukumaraswamy: Yeah. So he’s been looking at that. He’s been doing slow release work. The other thing he’s been looking at is other internalizing disorders. So he’s done a lot of work looking at ketamine and anxiety disorder. And he’s starting to build up quite a good evidence base that ketamine isn’t — just might not just have efficacy in depression, but in a range of internalizing disorders. So I think he’s done anxiety and social anxiety. And so ketamine is, seems to have therapeutic effects beyond just the category of depression. These are all kind of, there’s less data on these at the moment.
You would be even more reluctant to prescribe a label for those things where there’s a smaller evidence base, but there is an emerging evidence base that other things — and Paul’s definitely been contributing to that.
Tim Ferriss: I wanted to, also for people who may not have familiarity with the odd medley of indications that psychedelics can be used for. First of all, I would recommend to those who haven’t read it, How to Change Your Mind by Michael Pollan gives a pretty good overview. Some of it would be contested, like the importance of the default mode network in the down regulation of such — in some of these experiences. But it would appear, and certainly the, I think a lot of data would support this, but the case studies themselves also would, that the — let’s just say, DSM described, in our parlance over here, at least. I’m not sure if you guys have an equivalent of a DSM. But for —
Dr. Suresh Muthukumaraswamy: We use the DSM, yeah —
Tim Ferriss: — yeah, for insurance reimbursement purposes, you need an indication and a code, right? So you could have anorexia nervosa, you could have obsessive compulsive disorder, whatever the latest rephrase of that is, alcohol use disorder, otherwise known as alcoholism, et cetera, et cetera. What is plausibly the case is that these conditions actually share a lot of common DNA, so to speak, because there are certainly studies being run right now, and this is not to say that psychedelics are a panacea at all. That’s not the point I’m making. But that from opiate use disorder to anorexia nervosa to OCD to chronic anxiety, there may be shared characteristics such as a rigidity in thought looping or patterning that are interrupted by these tools, which then provide a window of plasticity within which you can do very, very interesting things, which then begs the question that we were discussing a little earlier, of how much the therapeutic wrapper impacts the clinical outcomes.
So if you’re heating up the clay, so to speak, and adding some moisture by using these compounds, who is actually molding? Is it the patient? Is it the therapist? Is it the combination of the two? Is it the experience itself that’s just bathing your neurons and various chemicals that produce dendrite growth? Part of why this whole field is so exciting to me is because there’s still so many open questions, the answers to which have just supremely potentially important ramifications. Are there any particular studies that you would like to do or see done in the near future, in the next few years?
Dr. Suresh Muthukumaraswamy: There’s endless possibilities. We’re only at the really beginning of what we’re doing. We’ve only been doing this stuff for a couple of years, and essentially all the stuff, everything that’s been done so far is essentially just elaborate pilot studies. We’re just beginning to learn, and that’s come from 50 years of prohibition where we haven’t been able to do this work. Things were looking, and people might know this history, that in the 1960s, when this research started slowing down, in the early 1960s, there was promising signals, but everything just stopped for almost 50 years. We are only just a couple of years into learning how to do these kind of studies again. That means that we’ve got a lot to learn, and it’s going to take a while before we figure this stuff out because studies take a long time to do.
The other thing is these are really complicated interventions. When you put them into a clinical trial, and you try to work out what the hell is going on because you alluded to the first problem we have is diagnosis. Unlike for mental health, the really thing to be aware of is unlike cardiology or cancer, we can’t just stick someone, get an echocardiogram done, and realize they’ve got some kind of thing going wrong with their heart or some regurgitation or valve thing or whatever it is, or we can’t measure a tumor size and go, “Oh, yeah, this is it.” So the physician is based entirely basically, putting aside some organic issues, the diagnosis is basically just subjective reports of symptoms and the diagnostic categories are completely wooly. We don’t understand the biology of what’s going on in terms of the diagnosis.
Then we have the problem that we give this intervention that we have only a partial knowledge of what it’s actually doing in the body. Then how we actually measure the clinical response is also kind of wooly because we have to use these kind of subjective scales. Like, how are you feeling? I’m feeling better. Okay. You’re feeling better. Yeah, which if you’re measuring tumor size in a petri dish, or tumor growth, that’s — so we have a long way to go to harden up the science.
But to answer your question more specifically, the interventions themselves are really complicated. We have this strong drug intervention with these therapeutic wraparounds, and we have to start to systematically deconstruct what’s going on there and start to manipulate some of those factors as variables. So how much wraparound therapy do you need? The question that’s never really been asked is, well, what type of therapy do you provide or is all therapy the same? Or is it just, heck, actually talking to somebody? What is the actual requirements there to get? Because you will have no shortage of case reports, like you said, of people that just took psilocybin by themselves and said, “Oh yeah, I started feeling better,” with no thing — I’m not saying anyone should do that, by the way. But just people will report that, of course, at the same time, people report taking psilocybin and having a terrible experience with terrible psychological shock involved afterwards.
So we do have to start to deconstruct what’s actually going on in the intervention. But these are long, complicated experiments that require a lot of people, a lot of manpower, and each intervention is really complicated. So each data point is like gold dust to collect.
Tim Ferriss: Yeah, absolutely. I want to add just a little bit of commentary for people who don’t have the history. You mentioned the prohibition, meaning the banning of common use of these substances for 50 plus years. I would say, at least when we look at the case in the United States, that it was mostly, if not entirely, for political reasons as opposed to scientific reasons. One can really learn quite a lot about the history, including Nixon and other colorful characters, like Leary and so on and so forth. But the punishment didn’t really fit the crime in the sense. And that’s my perspective, that if you look at the, say, LD 50, so the dose at which 50 percent of a given subset of the population would be expected to die of overdose for these compounds, you have incredibly high, if not unknown, ceilings for a lot of them. They’re physiologically very innocuous compared to even something like acetaminophen, for instance, where at least in the US, I don’t know about New Zealand, the rate of ER admission emergency room admissions for acetaminophen is through the roof. It’s got to be top 10.
That is not to say that there are not significant psychological implications, particularly for those who are generally going to be excluded by study criteria, like those with family history of schizophrenia. We’re going to jump into Q&A in about five minutes. But what I would just make note of really quickly is that I feel the LSD microdosing study that you just finished gathering data for is a really important, first of its kind, and please poke holes in this if I’m getting any of it wrong, for a number of different reasons. But I’d to highlight one of them.
One of them is placebo control in psychedelic studies or studies involving psychedelics, where it’s incredibly difficult to have placebo controls at larger doses with something like psilocybin or LSD because it is tremendously obvious to anyone who has taken it that they’ve taken it, and if they haven’t taken, it’s very clear that they have not taken it, and there’s going to be expectancy effects. Generally, people are going to come in knowing on some level what psychedelics are or believing that they do, and having done some reading and so on. So you have placebo effects. We won’t even get into nocebo effects, which people should read up on because that’s also something worth looking at. But in the case of microdosing, it seems like you really can begin to apply placebo controls. Just for people listening, could you describe how you thought about that and whether you decided on a passive or active placebo?
Dr. Suresh Muthukumaraswamy: Yeah. For this study, we went with an inactive placebo just because no one had ever done an LSD microdosing before. For in the community, we wanted a inactive control so that when we looked at safety and physiological measures of safety, we had a really — we’ve not actually done anything to these people. We haven’t given them any drug. This is just pure — so we had a very pure safety group to look at. In terms of LS — whether people are able to detect the effects, some are, some aren’t. So we were around the threshold.
Tim Ferriss: This was at around 10 micrograms?
Dr. Suresh Muthukumaraswamy: Yes .About 10 micrograms in male volunteers. There’s quite a variability though, actually. We saw that some participants were particularly sensitive to it and we had to reduce doses for some participants. And some hardly noticed. So there’s quite a variability in people’s response. That’s interesting in and of itself.
It suggests to me that we’re probably, when we move on to the next phase and actually want to look at a clinical population and run, for example, a depression trial, that we may need to start looking at lightly active placebos because we are now interested in the clinical outcome, not just sort of can you do it? What do you people experience? If we are wanting to kind of try to fool people a bit better, then probably some kind of light placebo and with a little bit of, I wouldn’t say deception, but just ambiguity in the information that we provide to participants might be enough to get us over the top in terms of blinding the study successfully, unlike psychedelic studies, which aren’t blinded at all, and this is a real problem, a methodological problem that the field has to try to conquer in some way. And we’re working on it.
Tim Ferriss: Yeah. I Just want to jump in for a second. I would say also that the fact that placebo controls are so difficult is it’s, I don’t want to say a feature and not a bug, because it does present, just from the standpoint of rigor and publication, a whole lot of challenges. But the fact that this effectively entire class of drugs has so much trouble with placebo controls is very interesting in and of itself.
Dr. Suresh Muthukumaraswamy: Yeah. I’ve written a whole massive paper on this topic, so. Yeah.
Tim Ferriss: Yeah. It is fascinating that it’s so hard. Do you have any, and you don’t have to give away your secrets, but anything on the short list for potential active placebos you would use in such a case? Niacin? Something else?
Dr. Suresh Muthukumaraswamy: Niacin’s not a great option. That’s a vitamin. Actually, niacin was used in the 1960s, and it’s been determined even in 1960 that niacin is a poor control for psilocybin. But people still use it for some reason. And I’m not sure why.
Tim Ferriss: Yeah. Skin flushing.
Dr. Suresh Muthukumaraswamy: Skin flushing.
Tim Ferriss: I mean, maybe a subtype of subjective experience so that people think it’s doing something.
Dr. Suresh Muthukumaraswamy: Yeah. So we can —
Tim Ferriss: That’s why it’s added to a lot of dietary supplements as well —
Dr. Suresh Muthukumaraswamy: We’re getting into the weeds here. But what I would say is actually what the compound is, isn’t as important is what the participant thinks it’s going — it’s their belief about what they’re receiving that’s the important thing because blinding or not being — so blinding, I guess we should step back and to say, look, blinding in clinical trials is really important to prevent expectancy instances. Because if a person goes into a clinical trial thinking they’re going to get psilocybin and they do get psilocybin, and they think it might make them better, they work out that they’ve had it and they go, “Ah,” and maybe that over accentuates their clinical response, which we would call a confound.
Now, that’s potentially a problem. But what’s important is it’s not the compound itself. It’s what the participant believes that they’ve had. It’s not as much potentially around what the actual active placebo is, but what you tell the participant about the active placebo and the information that you provide them because you’re not trying to manipulate your physiology, you’re trying to manipulate their beliefs about what they’re having. So I think these are subtle things that we need to really think about in our experimental science. This is why I really enjoy doing research in this area because these are fascinating problems. It’s a really fascinating area to try and work out these scientific problems that’s — I reckon we can do it. Give me another 10 or 15 years and I might give up, but right now I think we can totally crack it if we put our brains to it as a scientific discipline.
Tim Ferriss: It’s a really exciting time to be, for me certainly observing, watching, and to the extent that I can supporting the ecosystem, and a really exciting time for people you to be doing the research. It’s really kind of a blue sky opportunity. The payoffs, as I think we established very early on in the conversation, are potentially huge. If we look at the trend lines of various diagnoses and illnesses and the costs, both on a personal level, familial level, and societal level. So let’s jump to Q&A at this point. If that makes sense. And I’ll hop over to Michelle to see if you have any questions for us. I think we have quite a number.
Michelle: We do, actually. Yeah, we’ve got heaps of questions here. What I’m going to do though, Suresh, is I want to start it off. The first question is going to be an ask. So you can put your ask out there to the audience because someone has said is, how can we speed this up? What can be done to make the benefits of this coming forward a lot quicker?
Dr. Suresh Muthukumaraswamy: Oh, that’s a great question. I think we’ve got plenty of awareness around mental health, generally, in New Zealand. We haven’t seen government or any signals from funders about — I think that’s where we haven’t really seen any kind of movement. That’s where pressure can potentially be applied. There’s not much in the way of foundational advocacy for this kind of stuff in New Zealand, or there’s not a huge amount of push to make government do anything about it. So I think it’s probably where things can be accelerated is by trying to get government to start paying attention and for them to take the attitude that in New Zealand, we can be at the forefront of this. And we already are. We’re way betting above our, in terms of us being this tiny little country at the back end of the world, we are betting way above our weight. We could get onto the front of these things being introduced if they are appropriate to be introduced, but a bit more push from government would potentially accelerate that and really establish us as leaders in the field.
Tim Ferriss: Suresh, just to piggyback on that, for those in the audience who might want to support, as in a philanthropic capacity, certainly I’ve been interested in this space for a long time. It’s deeply affected my life and the lives of many I know, and the science is important at the end of the day, to push the ball forward. So whether with you at University of Auckland or at University of Otago, there are some interesting things happening in New Zealand. Are there any recommendations you might have for people who would like to consider supporting philanthropically?
Dr. Suresh Muthukumaraswamy: Yeah. In terms of philanthropics, the best thing is to get in touch with either myself or Paul. We’re not top secret — there’s plenty of mechanisms. But what I would say is that suddenly philanthropic money is really important. The funding that you provided us was essentially seed money that we could use to then get the feasibility you need to then get a government grant to do the research —
Tim Ferriss: Yep. Definitely.
Dr. Suresh Muthukumaraswamy: — to establish that we can run this trial. We can do it. Because when you have nothing, you just can’t get started and you apply for grant and then the grant people say, “Well, you can’t do this. You can’t do that. You haven’t shown us that you can do this, that, and the next thing,” and then they turn your grant away. So philanthropic money can also be seen as a seed, not just as you’re funding the whole thing, but as a seed for future investment. So —
Tim Ferriss: Definitely, yeah. That is so important. I just want to say it again, that not only do you sort of punch above your weight class in the research that I’ve seen so far, but the amount of money that you commit from a philanthropic standpoint can also have much more impact and amplifying effect as a signal because then it allows researchers to fundraise that much more easily from other sources. So the money’s important, of course, but the signal is also really important.
Dr. Suresh Muthukumaraswamy: Absolutely.
Tim Ferriss: Yeah. Michelle, do you have more? I’m sure you do.
Michelle: I do, yeah. So this one, what are the risks of microdosing? So if it’s patients that are diagnosed with bipolar or schizophrenia, so they’re not looking for a medical advice, but just any general commentary about how safe is it, and is it dangerous?Dr. Suresh Muthukumaraswamy: We don’t have a lot. We have a dataset that we have collected, and it’s really the first dataset that’s been collected. So far we haven’t seen any negative safety things, but it’s a very small dataset in a very healthy population. I think potentially there are indications such as schizophrenia or bipolar where it’s possibly not a good idea. We know that high doses of psychedelic can trigger psychosis occasionally and cause psychological distress. So I think doing this kind of on your own, particularly if you’re trying to treat a severe mental health disorder, could be you’re heading into the unknown, I guess, is that kind of thing. But yeah. Potentially the biggest risks probably apply actually in the application area of mental health and with particular comorbid disorders. So I think it’s important to tread lightly, carefully.
Tim Ferriss: I’ll add something to that really quickly, which is there are also questions of provenance and legitimacy. So there are some synthetic, well, I mean a lot of synthetic, thousands of synthetic psychedelic compounds that are sometimes confused with or sold as LSD, that can launch you into some very at best uncomfortable and at worst, very dangerous circumstances where you could be in an experience for 24, 48 hours. On top of that, it’s critical, I would say, to consider legal ramifications. There are legal risks if you’re dealing with schedule I compounds. Secondly, just because I’ve seen this quite a few times, we’re dealing with, in the case of LSD for instance, micrograms. To explain what that means, Suresh, please correct me if I’m getting this wrong. But you’ve got, let’s just say, milligrams, which are a thousandth of a gram. Am I right so far?
Dr. Suresh Muthukumaraswamy: Yep. Milligrams is thousandths.
Tim Ferriss: And microgram is a millionth of a gram, if I’m getting that right.
Dr. Suresh Muthukumaraswamy: Yep.
Tim Ferriss: Or is that a —
Dr. Suresh Muthukumaraswamy: Yep. That’s right.
Tim Ferriss: Yep. All right. If you’re dealing with millionths of a gram, even the Albert Hofmann is the father of LSD, went on his first famous, huge trip while bicycle riding because he got it on his fingers. You’re dealing with such incredibly small quantities that the ability to misdose or to absorb it through the skin can lead to something that is most certainly not a —
Dr. Suresh Muthukumaraswamy: Microdose.
Tim Ferriss: — microdosing experience. If you’re doing it without supervision and you happen to get in a car, expecting it to be a microdose, for instance, that could be very, very tragic indeed. Not to be the stern dad about it all, but felt the need to say that.
Dr. Suresh Muthukumaraswamy: No. These are absolutely true, that the non-physiological risks are probably far greater than the physiological risks. In New Zealand, even though the law enforcement deals with things like schedule C class like cannabis relatively lightly these days, actually, they’re not so forgiving with schedule I substances. So that is important to bear in mind. I forget often, you’re absolutely right again, about the purity of supply and dosing. I forget this because we have, I like to say the best LSD in town in my lab, but joking aside, illicitly obtained LSD or psilocybin could be cut with other things. It’s very hard to know.
Tim Ferriss: Yeah. Absolutely.
Dr. Suresh Muthukumaraswamy: But we do have drug tracking services in New Zealand that can provide that kind of information though.
Tim Ferriss: I’ll just actually, that’s a really good point to just add one thing to, which is in the US, there are services like DanceSafe and others that will provide drug testing kits, which is not to say I recommend illicit use of drugs, but the reality is that people are going to use what they believe certain compounds to be, and there are tools also for testing so that you try to mitigate some of the risk.
Michelle: There’s a few people in the audience, Suresh, that are doing studies themselves in Toronto and the US. And one of them is about — the question is about open science. So what are your thoughts about open science replication crises? And will you be sharing your data or will you be keeping it private?
Dr. Suresh Muthukumaraswamy: Well, it depends on — yeah. It depends on the study and it depends what you’re trying to do. Open science is admirable and it’s good, but it’s not always possible, depending on who’s —
Tim Ferriss: Suresh, could you define that just for people listening who are not familiar?
Dr. Suresh Muthukumaraswamy: Yeah. So open science is essentially releasing your data to the world when you have it. And it goes with another thing which is called pre-registration, which is basically publishing your clinical trial protocols before you actually do the study. So my lab group has definitely started publishing clinical trial protocols before we do it, and we’ve done open science things. So I’m in favor of it where you can do it, but there will be times where, for example, you’re doing industry funded work where that’s not possible because that’s intellectual property of said company. So I’m generally in favor of it, but also we do end up, with the open science, of having a lot of data in the world, but no interpretive framework. So we can all do thousands of experiments and release terabytes and petabytes of data into the world of potentially bad data which hasn’t been collected well, and just adds confusing signals to the noise. So I don’t know that it’s a panacea for actually a deep, theorical understanding of what’s going on.
Michelle: Thank you. Now we’re going to shift to a training question. So anticipating legislation change and increasing access to psychedelic assisted psychotherapy, how do we prepare the workforce to be able to provide this? So what training pathways exist already for psychologists, clinical social workers to up upscale and become involved?
Dr. Suresh Muthukumaraswamy: This is a big controversy. Tim, do you want —
Tim Ferriss: I can take a stab. I can take a stab. There are a number of concurrent experiments being run. So in the United States, a lot of eyes are on Oregon. And within the state of Oregon, there will be a lot of action in the next six to 12 months looking at developing effectively a parallel structure for registering and supervising administration of psilocybin for psilocybin-assisted therapies. So that is a very live question for the state of Oregon. So I’d encourage people to watch that very closely on a political medical level. Also, my foundation, so the Saisei Foundation, S-A-I-S-E-I foundation.org for people who are interested, has also participated in funding a joint program, which is focused on psychiatry. And this is at Hopkins, NYU, Yale, and possibly a few other institutions, I apologize I’m forgetting where, and I’m going to get some of the details wrong here.
But in effect, a certification program is being created that can be applied into this funnel, which already exists, and that is the psychiatry MD training. And people can elect to then add this type of training and qualification to their preexisting track, if that makes sense, which is not to say that this should be limited to being administered by MDs or MD PhDs. I don’t think that will come close to addressing the demand and need, more importantly the need.
Forgetting about healthy normals, which is a whole separate conversation, let’s just talk about people with actual clinical diagnoses. So I do expect that there will be similar experimentation with nursing schools. I hope there will be also experimentation within accredited social work programs for allowing social workers. But the fact of the matter I think is that this is one of the most challenging issues that will be faced in the next five years, next five to 10 years, because not only is it necessary to develop a pipeline for training, but the training is extremely controversial because there are people who feel like the sacred is being secularized. And therefore, if there aren’t enough legally trained, let’s just say therapists or facilitators to administer these drugs, that there will be a lot of gray market and black market charlatans who are going to pop up to provide services to those in need, which will cause its own large host of problems. So it’s going to be a challenging road ahead, but there are experiments being done and people can see some of them at the foundation website.
Michelle: And now is there a way, this is for New Zealanders, is there a way we can access psychedelic therapy, microdosing now, or how far off is this?
Dr. Suresh Muthukumaraswamy: Certainly not now. Ketamine is potentially available through — there are a couple of clinics around the country offering ketamine services for those with depression, but psychedelics and microdosing are still in the future. The microdosing particularly has got a long way to go. That’s going to be two to five years, probably it’s on a three to five year track to progress that depending on how the results look. But I think the first thing that’s going to come down the pipeline, if anything, will be the MDMA-assisted therapy, because that’s the most advanced psychotherapy for PTSD. So that’s the most advanced that’s in phase three clinical trials in the US. We have a group of MAPS-trained therapists actually in New Zealand that could actually deliver that therapy if the data was seen to be okay and our regulator were to approve it, which would’ve invariably happened after FDA, if that were to be approved there. So we have that, and that might be only a couple of years away and that would be the first kind of cab off the rank, I think.
Tim Ferriss: Yeah. And I’ll just add that if I could make an unrealistic request of these psychedelic communities, per se, although with the amount of infighting that goes on it’s sometimes hard to view it that way, that it’s really important to focus on ketamine and MDMA and getting those two right. And I think it’s very risky. It’s fraught with incredible risk to try to boil the ocean at once with adding in MDMT, 5-MeO-DMT, ayahuasca and every other compound you can imagine to try to get them all dealt with in a responsible way simultaneously. Now I don’t think anyone’s actually going to follow that advice, but I have a pretty broad spectrum of interaction with these things and I would just say, not as an expert by any stretch but just someone looking at the risk benefit profiles of these things, I think a focus on ketamine and MDMA-assisted psychotherapy would go very, very long way.
And psilocybin certainly is in the works, and I think it has tremendous potential for a number of different conditions, whether that be major depressive disorder, treatment resistant depression, alcohol use disorder, and I think many others, I mean, those are the three that are furthest along. But each of these compounds has its own complexities and difficulties, and I think slow is smooth and smooth is fast with this stuff. We’ve just come through half a century of prohibition. We don’t need to figure it all out in the next six months.
Dr. Suresh Muthukumaraswamy: Yeah. I totally agree with that. And you know why, because there’s this massive unmet need to get things out to address these things. And it’s a heartbreaking and pressing problem, but at the same time, you have to think, well, if these things really are effective the last thing you want to do is rush it and get it wrong, and then to be safety issues that come up or badly regulated things and then all these horror stories start emerging into the popular consciousness, and then we put ourselves 50 years back in the hole again. So I think that’s what we really need to avoid with this. So treading really carefully, but hopefully that won’t happen, because we do have a stronger regulatory environment than there was in the 1960s. So hopefully we can avoid that kind of issue. But I think it requires us to work diligently, honestly, and carefully.
Tim Ferriss: Yeah. And then, I mean, not to paint a bleak picture, but I think we really want to mitigate the risk of catastrophe that then becomes a political soap box. And then, before you know, you have an executive order that sends us back to where we were, which is not an impossibility. People might laugh about that because they feel like this isn’t the ’60s, and the generational differences no longer exist, and there’s bipartisan support, et cetera. But politicians have certain sets of incentives, and I would really say that it is a non-zero percent chance that things get sent back to prohibition if, say, one senator’s child dies of cavalier administration of 5-MeO-DMT in fill-in-the-blank location, right? And not to throw 5-MeO-DMT under the bus, I think it’s very interesting, but high percentage of thrashing within the subset of people who use it.
So bad things can happen and bad things will happen, also, and I think the people involved, which is why the Saisei Foundation’s also involved with the Harvard POPLAR Project, which is a law and policy project focused on psychedelics, because there are going to be suicides that are attributed to psychedelics. There are going to be deaths attributed to psychedelics via accidents of various types, and this would be true with any drug used at scale. It’s not specific to psychedelics. This is certainly true for SSRIs. It’s true for just about every drug you can imagine, sleep medications — so it’s just the law of big numbers in a sense, and I do think the community needs to be prepared for that eventuality and how to deal with it because it’s going to take the culture quite a bit to metabolize that. And I do think we’re going to see a, not backlash, but sort of a pendulum swing into negative coverage because the positive coverage has just lasted too long. And I think if we want to be strategic about it, we accept and expect that on some level, because inevitable with anything that is purported to have this much promise, and certainly anything that has this much coverage. Michelle, what else do we have?
Michelle: Is your research expanding a little bit further and going into addiction, which is more dangerous and obviously deadlier than depression and anxiety? Are you doing any research in that area?
Dr. Suresh Muthukumaraswamy: We are starting to talk about it. We’re starting to talk about a project that will be more Maori-based intervention that we run by Maori researchers, and we’re just in the very beginning stages of starting to sketch some ideas together about how that might be done for that population in methamphetamine use or alcohol use. But it’s very early stages for us, but definitely that’s something we are not leading, that we are just providing support for in terms of intellectual support and learning how to navigate the regulatory system on this stuff. So that could be really interesting. And there are elements of, for example, spirituality that have some synergy with Maori culture that would be interesting for those researchers to explore.
Michelle: So just on that a little bit then, have you included women in studies or has it been mostly males?
Dr. Suresh Muthukumaraswamy: We had this one LSD microdosing study where it was males only, because, I won’t say it was pitched warfare trying to get this trial approved, but it was, and so we just had to take risk down as much as we could in certain places. So the problem of potential pregnancy was something that, for this stage, we just wanted to avoid that as an issue. And there was also menstrual cycle compounds in that we wanted to avoid for the first trial. We think we’ve now got the steps that we need to expand in the future trials, and I’ve taken a lot of flack for this. And, well, my response is, well, you try and get this study approved, because I spent years aging trying to get this thing approved. So we did the best that we can while we could, and we always hope to do better. But certainly all our other studies have included females, and the next studies will now that we’ve got over that first hurdle.
Tim Ferriss: And I will also say that there are studies that have very mixed gender ratios. If you look at some of the end-of-life depression, end-of-life anxiety studies, say, involving psilocybin, you see a much more heterogeneous group. So yeah, definitely easier to do when you have a little bit of escape velocity after the first one or two pilots.
Dr. Suresh Muthukumaraswamy: Yeah. There’s actually some interesting anecdotal reports in terms of microdosing for premenstrual dysphoric disorder, people have been using for that and that it might affect actual menstrual cycles and menstrual cycle timing. So there’s potentially interesting separate studies to be done there that we have considered and will consider in the future.
Michelle: So if someone’s wanting to sort of get into this type of research, what education do you recommend for anyone wanting to help assist?
Dr. Suresh Muthukumaraswamy: Oh, so I get this all the time. Undergraduate student size. I’d say the best option is just go be a medical doctor, because then you can you learn a university degree. Maybe I’m just promoting the University of Auckland, because it’s my employer who pays the bills. But for young people getting a science degree or a health sciences degree, medicine, psychology, I think that’s where the forefront of things will be. In New Zealand, it’s going to be basically psychiatrists and psychologists that are going to run this. I suspect that will be where things fall. So if you want to get into being able to prescribe or be involved in this kind of therapy, I think psychology and psychiatry and general medicine are the places to study or the things to do. And then there’s also scientific degrees you can do like medical sciences. Strong background in mathematics is always good.
Michelle: I’m just going to go into one about corporate. Have you looked into the clinical trials of the larger public companies? So there’s MindMed, Compass, Atai, and numerous — and do you feel there are any red flags in how these current corporations are going about improving their respective drugs? So that’s like LSD, MDMA.
Dr. Suresh Muthukumaraswamy: Yes. And I should say as a disclosure that I have consulted for some of these companies and yeah. So as a disclosure. And actually collaborating with one of them. So my observation is that the people that these companies are employing seem to be really experienced pharmaceutical people with a lot of industry experience in pharmaceuticals, and they seem to do quite a rigorous job. There’s obviously going to be tensions there for those companies in terms of wanting to get things through reasonably speedily, because they’ve only got so much capital, and the pathways long and expensive, and the intellectual property that they need to gain because these are generic medicines is going to be an issue. But red flags, there’s red flags in every area. So what I would say is, well, there’s red flags in every area of pharmaceutical development. Are there any more red flags in this area than there are in other parts of the pharmaceutical industry? Probably no more, no less. So yeah. I’m comfortable with the gray.
Tim Ferriss: Yeah. I’ll hop in with just a few things. So I would say on the clinical actual the study side, I think pre-registration is very important, but as you mentioned, Suresh, that doesn’t apply uniquely here, but it does apply here. So pre-registration, publishing your protocol ahead of time so that you can’t torture the data or move the goal posts and declare victory when in fact was not a victory, I think is incredibly important. And then I recommend people take a look at, there’s a journalist named Shayla Love, who’s done a fair amount of writing about the intellectual property battles that are ongoing in the space. And there certainly are, I believe, non-obvious innovations that should be granted patents, because that is how one in a market-based economy raises funds and builds companies and justifies the R and D expense.
There are also obvious, relatively unhelpful, non-improvements that people sometimes get patents for, which are obstructionist in nature that actually gum up the works and cause problems in the ecosystem overall, especially if they use said patents to try to lock up manufacturing processes to dominate a given molecule that has existed for decades, if not millennia in some cases. So I do think the IP side of things is very important to keep an eye on and an organization that might be worth checking out is Freedom to Operate, which was created by Carrie Turnbull, and that is an area that will be increasingly active. Mason Marks and I. Glenn Cohen, I. Glenn Cohen, C-O-H-E-N, co-authored a paper on intellectual property and patents, for those who are interested, that’s out of Harvard Law School.
Michelle: It’s enough time for our questions today, Tim.
Tim Ferriss: All right.
Michelle: Goes fast.
Tim Ferriss: Well, fantastic. Thank you so much everybody, and thank you so much, Suresh, for making the time. I’m very excited to see what you do next.
Dr. Suresh Muthukumaraswamy: Cool. Thank you.
Michelle: Great. Thanks, Tim. I’ll just close this off with a karakia. It’s been a great session today. Then, hopefully, this will set you on the rest of your way.
[foreign language 00:00:27]. Thank you. [foreign language 00:00:45]. Enjoy the rest of your evening or day.
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