#619: Dr. Suresh Muthukumaraswamy — LSD Microdosing, Classical Psychedelics vs. Ketamine, Science and Speed in New Zealand, Placebo Options, and The Infinite Possibilities of Studying Mind-Altering Compounds

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Hello boys and girls, ladies and germs, this is Tim Ferris. Welcome to another episode of The Tim Ferris 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 five hundred 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 fifty 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. 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 change makers who want to make an impact globally from LTR, New Zealand. In the session today, you're gonna hear from Tim Furis.

He's an EHF fellow who's an early stage technology investor and advisor. And Tim will be interviewing Dr Sharesh, an associate professor at Auckland University. And the topic today is on mental health and breakthrough therapeutics. There'll be plenty of time for Q<unk>A with Tom and Sharish during the 90 minute session, but nearer the end. Over to you, Tom.

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 Mutu Kumara Swami. I will hear Forward referred 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 postdoctoral fellow. While at Cardiff, he started research work with the psychedelics. And psychedelic compounds in twenty eleven in collaboration with two very well known names, Professor David Nutt and Dr. Robin Carhart Harris, investigating the neuroimaging correlates of the psychedelic drugs psilocybin and LSD. In twenty fourteen, 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 ketamine, 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 microdoses of LSD on brain and cognitive function. Suresh has published one hundred and seventeen papers and his work has received more than eight thousand citations. Suresh Welcome to the session. Thanks for being here and taking the time. My pleasure, Tim. Nice to see you. 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 a meaningful place to start and serve as a canvas upon which we can discuss other things. 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 um psychological distress and the amount of psychological distress that

The adult population. is experiencing so so in terms of trend lines, so this is conducted every year. So in two thousand and I think eleven, twelve when the survey was conducted, four point six percent of adults experienced psychological distress in the last month. And we've seen that slowly creeping up. So the last data point from twenty twenty one, twenty twenty, where it was now at nine point six percent. So we've seen a doubling over the last ten years in the adults experiencing psychological distress, which is anxiety, depression, or um sort of psychological fatigue. So it's more than doubled and actually the last and Covet is definitely going to impact on that. We see a little bump on the last one from

the first sort of impact of the first wave of covet and those lockdowns, then I expect that that's gonna only get worse when the next year's data point comes up because in New Zealand, um you might not be aware but in New Zealand the second lockdown was quite hard. that just finished at the end of twenty twenty one, 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 to run, but so it's not just Covid, it's been trending up for a long time and it's not getting any better. And I would imagine Although I I don't want to assume that the costs right 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. Uh. If anything like the United States quite high. in in New Zealand as well, not to mention the the personal costs.

Let's talk about a f 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. Yeah, so my background is in general psychopharmacology, so before studying psychedelics and and currently just studying psychedelics, I've spent a lot of time studying anesthetics and gaboergic drugs. So gabaritic drugs tend to be kind of sedative, so alcohol is a gabargic drug. Benzodiazepines, 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 Remy Fintonel 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 I'm most well known for in the public discourse.'Cause they attract some interest, I suppose. They catch the attention. So we're gonna 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 its effects on conditions, whether depression or otherwise, because Scopalamine, for those who don't know is also naturally occurring in many plants that are considered psychoactive.

or a hallucinogenic, some of which uh are considered quite risky. But how did you determine This as a as a subject of interest for For research. We had been doing studies on the antidepressant effects of ketamine and w we'll talk about this later, but y you see this rapid antidepressant effect and so what we were interested in was are there other compounds out there that might show a similar rapid antidepressant effects? And There was a series of studies that came out of the NIH intramural program

It was Two or three intravenous scopolamine studies that appeared to show a similar sort of pattern of antidepressant effects, so And Scopolamine is works very differently to ketamine or other antidepressants being a muscarinic antagonist. So we 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 and then potentially look at in our study we looked at anti 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 it rapid antidepressant. Responses? The downside, of course, is that we found no antidepressant response in the in the study. But you know, th that's the data, right? We uh we did a really carefully controlled study.

We unlike the previous research that used a inactive placebo and we'll get back into this. We used an active placebo. A compound called glycoporonium that's used a lot in s uh surgery that Doesn't cross the blood brain barrier, but still is anti muscarinic and it creates a slightly drowsy feeling and dry mouth and a lot of the kind of side effects that you might get. we were able to show that distants could no longer distinguish which of the drugs they that they had. And actually

We are ascribing most of the antidepressant response that we see to a placebo response. So less and learned. Yeah, that's fascinating. Yeah, Scopalamine, w I don't wanna take us too off track, but has some very interesting effects on memory, or it's at least is thought to have some very interesting effects on producing amnesia. Yes, it does. While while still having yeah 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 of the terminology.

Increment, but And aesthetic. 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 the World Health Organization's top one hundred 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 of 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

The rapid onset. of some of the effects subjects compared to, say, traditional Or conventional SSRIs, which in some folks it can take. six to eight 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 and how they differ? Because both can be described as having psychedelic effects.

Maybe the easiest thing to start with is with this skuscarpsychedelics because it's remo relatively simple compared to kid I mean. So L S D and SIRTACE and DMT they all seem to work through a common receptor called the serotonin two A receptor. And we think that most of their effect you know, there's probably some other receptors involved in parts of the response, but overwhelmingly we think that most of that sort of psychedelic experience is generated from this serotonin two A receptor And binding gear. So Conversely, ketamine has a very different

Even though it has these kind of this dissociative or psychedelic effects, it's Receptor binding sites are mini and complicated. So principally Antagonizes a receptor called the N MDA receptor, and that's a glutamate receptor. So glutamate is the most common neurotransmitter in the brain.

And we don't hear about it a lot. And the NMDA receptor is kind of interesting because it's actually the receptor that's really heavily involved in neuroplasticity and something called long term potentiation. So that's essentially how brain cells it's a receptor involved in how Brain cells learn to communicate and strengthen synapses. So that 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 It binds to opiate receptors. And if everyone were familiar with opiates.

And then these other Monoamine sites like that it interacts with serotonin, dopamine, noropinephrine, H C N channels, sodium channels. It just the list goes on and on as you go up through the concentrations. 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 it also most compounds Exist in a left and right state. They're called Recemic, so there's a left and a right.

State? And so there we have is ketamine and aramine. and normal ketamine is both of those, but actually the R and S ketamine's probably have different receptor binding profiles in addition to all of that. So what we're left with is this a stew. You could either call it a very rich drug or you could call it a dirty drug, depending on your perspective. It's very promiscuous in terms of its receptor affinity. Could you explain for a second

Two things. why scientists would wade into this Soup of variables. 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. When drugs are in the brain, you know, broadly speaking it's more complicated, but broadly speaking an antagonist to something that blocks the activity of something that So an N MDA antagonist blocks the N MDA receptor, so it stops glutinate working there. In terms of

For kidding in terms of is There's both a clinical and a scientific interest here that's And they're both really interesting to study, which is why I've been studying ketamine for nine on ten years now. The Clinical significance is what you mentioned before. It's you ha you can take patients into the lab

Patients that have had treatment resistant depression, unremitting for years and years and years and you can give them a ketamine infusion and they will get this really rapid remission in symptoms and that will manifest itself in hours now. People will know ketamine is a street drug, right? And they'll say, Oh, well, maybe that's just because the person's high, you know, that they're and experiencing this intoxication. So

My response to that would be Well actually, you know, if you then measure the person's depression symptoms at twenty four hours after the ketamine infusion, You'll see that they're still not depressed. No. What we know about pharmacokinics that's how long ketamine lasts in the body.

The half life's about four hours for ketamine, so at the twenty four hour time point, there's really no ketamine left in the body at all. So the kinamine's gone, they haven't been high. Four. You know, twenty, twenty, twenty two hours. So they're not high anymore, the kidney's entirely off the body, but they're still not depressed.

And then what that shows is that The ketamine has changed something in their brain. So that's caused some kind of functional change in the brain. And that suggests and that 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 this Obviously working on some kind of target.

that can flick that switch and that understanding what that is scientifically Is it Really interesting. And And while other things can flip that switch. They do it much slower, like S R I switch it in maybe four to six weeks or

Transcranial mag TMS, transcranial magnetic stimulation that might take. a month to work as well. But here we can switch in a day for a scientist it's really um interesting'cause you can run it 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. So I wanna 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 uh I I can speak to one very cute example, friend of mine in law enforcement who was suicidal. He had a cute suicidal ideation.

And many people in law enforcement or the military, pilots would be another category, are very hesitant to 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 Cetamine.

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 XY or Z. And What I'd love to ask you next Just again to

contrast the say classical psychedelics. And uh you mentioned a number of them, which are in the say triptamine class. We probably won't get into the phenethyl amines and mescaline and MDA and so on, which which can be very different in some of their subjective effects. But if we just if we're if we're looking at, say, LSD Silocybin. And then ketamine. If you look at the durability of some of the effects.

Save 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 Crystal at Yale, who's done a lot of work with ketamine. And you know, Roland's perspective was that he he thinks a lot of the durability of antidepressant effects Six months, twelve months of follow up, let's just say.

have a a lot to do with a change in content. meaning that people are actually able Not just to Suppress the symptoms of the Depression.

but to address some of the kind of root narratives that are leading to depression. 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?

The background to this for people is that The antidepressant response that we see to a kidamine infusion, you know, that will last any you know, now experiences anywhere from a Day or two to couple of weeks. A month? Whereas the data for like sort of cyber that seems to indicate yeah, like months, half a year, year long interpressant responses.

But I think it This kinda falls into the we don't know. File. from a data perspective. Because the models that have been used the experiments that we've 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 side to cyber assisted therapies, they've been wrapping around an intense amount of psychotherapy, right? So It's and and I think it's really important for people to understand when they Think about'cause that you know, you just read these headlines are you know, psychocybin improved depression. Well actually it's not just psychocybin and it's the fact that the person's gone into the psychotherapy regimen you know, 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 forty hours of psychotherapy.

The one one side of Saddam course. So it's not just the drug alone, it's psyched assisted psychotherapy. Now whereas the model for ketamine that's mostly been used is basically Anyway, it's seems to be using your flavor was that people just go into a kidamine clinic and they smash in an infusion for an hour and they go away. And there hasn't really been much

Studies with People have s actually done ketamine assisted psychotherapy and tried to Well what if we do Wrap that similar lip. What would happen if we wrapped that similar level of psychotheraputic support?

Around ketamine. Would that make That ketamine response. Now stretch out beyond two weeks to maybe a similar kind of time for us. Because the the people in the s sort of cyber world have come from that kind of more traditional s psychedelic assisted therapy world.

And the people that have been studying ketamine have come from more of a kind of Traditional psychiatry world. And so we haven't We don't really I'm not aware of any data that really has kind of Try to

Find the the man in the middle or or strip back side aside then to just soda sideman, which I think people would ethically struggle with trying to do that kind of experiment. Do you say that just because of the difficulties that can come up in navigating that experience? Yeah, because you know, these uh um So something like psilocybin. is very powerful in terms of

So Cybernot D and T, L T these very powerful psychological fix 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 be not be ethical. To strip it back to nothing, like it's done for ketamine.

Right. Then there's probably a middle point where it could be uh 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

You know the I don't know. that we are really in a in a very fertile nascent period of psychedelic research. And even though studies were conducted much earlier, say in the sixties, 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 and others that are now at hand.

You can examine these these tools. With a set of lenses that you couldn't before. And it 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

Two Pursue that study. So I had returned to New Zealand in twenty fifteen and Having previously done classical side, so I went my and I started my research group here, I thought well this we'll start with ketamine because It's approved. It'll be eas reasonably easy to get approval for.

And no one's gonna blink too many eyelids about A new guy coming into town wanted to study You know me? New guy coming to town wanting to do LSD, it's probably going to Flopple 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, I decided it was time to Get back into

doing some classical psychedelic research. Now the microdosing specifically Well yeah. No one had really looked at microdosing in a R C T at that point and Randomized control trial and I guess does uh should we explain what microdosing is maybe Yes.

Why don't you explain what that is and it also might segue into One of the design challenges, meaning Placebo control. Uh psychedelics overall. So yes, please uh define micro dosing. Yeah, so microdosing is When people take very low doses of psychedelics, about the tenth the dose of a

Big dose of uh when people are gonna tripping, so You know, people might trip on like, you know, a hundred or hundred fifty micrograms of L S D, but for a microdose they might take ten micrograms, say. So about a tenth. 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 So what they do is that they take these microdoses maybe every third day is the most common schedule that's called

This was popularized by James Faderman, who wrote a book in two thousand and eleven. And it's really taken off since then. You know, like before twenty eleven 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 the size of the read up 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 wanted to run a proper R C T

Proper randomized control trial of Microdosing? Exactly. Then you have to prescribe a class A substance uh 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 Think it'd be I think they they might be a little grumpy about that. Yeah, yeah. And uh 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 uh Little Old New Zealand. So As I Was As you do, every now and then read the uh reading the Misuse of Drugs Regulations from nineteen seventy seven. And the misuse of drugs act that goes along with it.

We're kind of discovered this blue hole. I don't know if you call Lupo we're Actually uh We are allowed to prescribe class A substances. It's not ever really done 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 Uh Could be done. And so we

Did it and we applied. Two Then got the appropriate approvals from ministry, various parts of the ministry to do it. And That allowing us to Run the study that with

Just finished collecting data for, which was to give eighty healthy volunteers. six week L S D microdosing course to Where they would take the first one in the laboratory and there were other thirteen doses that were taken out in the wild, as it were. Much like people do. In real life.

So let's let's dig into that a little bit. So were they given the other thirteen doses to take home all at once, or did they come back to get one at a time? Or two at a time. They were given packs of four, four, and five. So we never gave them like a hundred and thirty Hundred and forty fifty micrograms to take home so that they couldn't just stack'em all up. But actually, you know There's a lot of like

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 Cricked with needles and blood taken and all sorts of stuff, right, can Hours and hours. There are a lot more efficient ways to get doses of L S D Oh, for sure. For sure. Yeah, absolutely. And we track 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. Protocol. And uh 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? We have a strong regulatory environment.

So I'm not saying our environment is weak. It's strong, but it's It's capable of being agile and it's small. When 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 you know making these decisions. In a country of five million is only so many people who know are involved in

These kind of decisions. So if you sensible and polite and appropriate. You can ask questions and and get things to move. So with s small size I think does come agility and And I know that

You're a Certainly pharmaceutical companies that are investing into New Zealand's psychedelics industry and and our general medical Into clinical trials, yeah, we're an attractive place to run clinical trials'cause also we're relatively cheap in terms of what you can get on a per dollar basis compared to what you might get in Europe or the United States. So So that's intra attractive.

We do have a good register environment in terms of How we can promote more sort of innovation. I think At the moment the government does take a reasonably hands off approach, particularly in this area, it's taken a completely hands off approach. And is so by comparison And where we risk falling behind by comparison, Australia, they created a fifteen million dollar fund specifically for these sort of breakthrough mental health therapeutics.

To kinda 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 sort of provide all the capability that they need. So we haven't seen any signs of that yet from government that that there would actually be sort of a more dedicated funding pathway. Now we are able to get funding, but we have to go into the general pop

The 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're competing with our peers that you know, doing very high quality stuff. So we know when we get funded that What we're doing is

Rigorous. 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 are seeking funding. Yeah, that's right. And it yeah. And there's actually some there's actually some data on that. And actually what we've seen, and not just psyched outs, just mental health in general has been underfunded in New Zealand for very mental health research. Alone 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 over funded and we've spent a huge amount of research dollars on things like neurological And cancer and heart they've actually relative to the burden of disease That done very well. But actually meant to health. Relative to the burden of disease we're seeing in the population, this can be quantified using an Disability adjusted life years.

And you can look at research income relative to To discipline adjusted life is, and mental health has not been 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. 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.

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 M DMA assisted psychotherapy. Breakthrough therapy designation for Depression, different types of depression and

PTSD. post traumatic 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 uh liberal parties. to get state funding set aside for psychedelic research related to veterans, for instance. And that 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? I think the lesser 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 as, you know, an international pharmaceutical company We'll apply for registration here. And they'll use all the data basically they've submitted to the F D A. So, you know, 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're kinda at the back end of that kind of process here, and that's why we have in New Zealand sadly a relatively weak pharmacopia where a lot of drugs that are available in

The US or Europe aren't available here. Because they're just not market here'cause we're a small market. So I don't see that the that first approach work, but the second approach could certainly work where You know, the government s sets aside legisl probably won't be through legislation. We'd direct one of its funding. Bodies. To sort of you know.

To say and it does just spa the read. Okay, let's Let's fund this. Let's fund this uh things like growing up in New Zealand. So New Zealand has a really good uh 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 forty, fifty years that have been essentially funded. That would be a mechanism that could certainly work. Yeah, I'm I'm very excited about New Zealand as the

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 and 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 uh 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, we're the they're looking at commercial interest, but you 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. Really any anywhere else. Yeah. Uh well, you know, there's a New Zealand has a rich

Biomedical I work in a general medical faculty, so the people sitting next to me are doing, you know, cancer research or you know, so we have a really amazing um People doing work in place in Auckland called the Liggins Institute, where they're doing work on preturned 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 do is doing really well in New Zealand. And down 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 h a huge amount of work with ketamine and in various ketamine analogs that he in Different ketamine formulations that they've been working at and so there's a lot of there's quite a rich

Group of research having down at a target as well. So I guess it's Mostly centered around where the two medical schools are located in New Zealand is where they're kind of where things are happening in the biomedical realm. What do you find interesting with 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 ibegaine and noribegaine and so on, which certainly makes them more interesting to study. But what is academy analog and are there any analogs or approaches to analogs that you find Particularly interesting. Maybe it's not an analogue. One of the things is they've been they've been looking at like slow release formulations as as one way to go. And this comes back to that thorny issue about

With kidney, like how important is actually having the psychedelic experience, but if maybe if you could slow down the absorption of ketamine. So it's not such a Yes. um but came in slower. So there's really interesting work happening with slow release formulations. It's a New Zealand company.

Who have been looking at That is Douglas pharmaceuticals 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 Uh, I described that left and right formation. That means stripping ketamine to its R and S formulation. Now Janssen, as you'll be aware, they Took the is part of ketamine and put that in a nasal spray.

And so that they can bravado. Yes, bravado. And this is essentially a marketing exercise, right? Like there's no it it doesn't seem that it does any has any more efficacy than normal kidney, but it allowed them to Achieve a patent on it. What is the price differential? I think it's something like One to five dollars generic, like several hundred dollars. So we can get a vial of ketamine for like Yeah. But the Spravado is like five or six thousand dollars. 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 it's an off label treatment and because it's a controlled substance, people you know, there are clinicians that get, you know, antsy about that and and fair enough. But that ketamine is 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 there's'cause it's a generic compound. I guess this is uh sort of background on how

medicines get approved is you need a company to sponsor the research to go to in New Zealand to go to MidSate 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 and make more ketamine and and sell it instead. So there's no return on investment to be had there. With intellectual property.

Let's talk for a second, if you wouldn't mind expanding on uh Paul Glue and his work a bit. 'Cause 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?

Yeah, so he's been looking at He's been doing a slow release, but 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. So and he's starting to put up quite a good evidence based that ketamine might not just have efficacy in depression, but in a range of sort of ruminant internalizing disorders. So I think he's done anxiety and social anxiety.

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. So there's You would be even more reluctant to prescribe off label for those things where there's a smaller evidence base, but there is a an emerging evidence base that other things in pool's definitely been contributing to that.

And I 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 I would recommend to those who haven't read it, How to Change Your Mind by Michael Pollan gives a pretty good overview. You know, some of it would be contested, like the importance of the default mode network and the downregulation of such in some of these experiences, but

It would appear. And certainly that 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 the DSM. Yeah, for insurance reimbursement purposes, you need a

An indication and a code, right? So you could have anorexia, nervosa, you could have obsessive compulsive disorder, or whatever the latest rephrase of that is, alcohol use disorder, right, otherwise known as alcoholism, et cetera, et cetera. And 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 O C D

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 political outcomes. So if you're heating up. the clay, so to speak, and adding some moisture by using these compounds. Like

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 in 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 the near future, in the next few years. Oh there's so there's endless possibilities. You know, like

Yay. We're only at the really beginning of what we're doing, right? We've only been doing this stuff for like a couple of years. And essentially all the stuff everything that's been done so far is essentially just elaborate pilot studies, right? We just

Beginning to learn And you know, that's come from fifty years of prohibition where We haven't been able to do this work, so you know, things were looking And people will notice this. might might know this history that in the nineteen sixties when this research started slowing down, early nineteen sixties, you know, there was promising signals, but everything just stopped for like almost fifty years. And So we're only just

You know A couple of years into like learning how to do these kind of studies again. So That means that We've got a lot to learn and it's gonna take a a while before we figure this stuff out because studies take a long time to do.

And the other thing is these are really complicated interventions, you know, when you put them into a clinical trial when you try to work out what the hell is going on. You know, because you alluded to the first problem we we have is diagnosis, right? We Unlike for mental health, the really thing to be aware of is unlike

Cardiology or cancer, right? We can't just like stick someone Get an ecocardiogram done and realise I've got some kind of thing going wrong with their heart, some regurgitation or valve or whatever it is, or we can't measure a tumor size and oh yeah, this is it. So the 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 woolly and we don't understand the bul biology of w what's going on in terms of the diagnosis. And then we have the problem that we give this intervention that we have a Only a partial knowledge of what it's actually doing in the body. And then actually out. how we actually measure the clinical response is also kind of woolly because We have to use these kind of subjective scales, you know, like

How are you feeling? I'm feeling better. Okay. You're feeling better. So and we don't Yeah, which you know which if you're measuring like, you know, tumor size in a chitry dish, you know, that's uh or tumour growth. So we have a long way to go bef to harden up the science, but To answer your question more specifically, the interventions themselves are really complicated where you 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 like 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 like 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 cyber cyber by themselves and said, Oh yeah, I started feeling better and with no like thing. Not I'm not saying you should do anyone should do that, by the way. But I just uh people report that. Of course at the same time people report taking Saraside and having a terrible experience and

With terrible psychological shock involved afterwards. So We do have to start to deconstruct what's actually going on in the intervention. So 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 to collect. Yeah, absolutely. So I wanna add just a little bit of commentary for people who don't have the history. So you mentioned the prohibition, meaning the banning of common use of these substances for fifty plus years. And 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. And one can really including Nixon and other colorful characters like uh like Leary and so on and so forth, but the Punishment didn't really fit the crime in the in the sense, and that's my perspective that If you look at the

Say L D fifty, so the dose at which fifty 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. Right. I mean the they're physiologically. very innocuous compared to even something like

acetamine, for instance, where at least in the US, I don't know about New Zealand, but the rate of ER admission, emergency room admissions for acetominophon is is through the roof. It's gotta be top ten. 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 of schizophrenia. And we're going to jump into into Q and A in about five minutes, but What I would like to just make note of really quickly is that

I feel the L S D microdosing study that you just Mm. 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 like to highlight one of them. And uh 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 It is tremendously obvious to anyone who has taken it that they've taken it. And if they haven't taken it, it's very clear that they have not taken it. And there's gonna be expectancy effects and generally people are gonna come in knowing

on some level what psychedelics are or believing that they do and having done some reading and so on. Right. We won't even get into no SIBO 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.

Pasebook. Controls. And uh just for people listening, could you describe how you thought about that and whether you decided on passive or active placebo? For this study we went with an inactive placebo just because Because no one ever done L S D microding before. We wanted a rant for

in the community, we wanted a inactive control so that When we look at safety. And like 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. And

In terms of analyst With the people are you know. Able to detect the effects. Summer. Summer. So we are around the threshold. This was at around uh ten micrograms? Yeah, it's about ten micrograms in male volunteers, so There was quite a heterogeneity though, actually. We we saw that some participants were particularly sensitive to it and we had to reduce doses for some participants.

And some hardly notice. So there's quite a variability in people's response. And 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 like a for example a depression trial. We may need to start looking at lightly active placebos. 'Cause we're now interested in the clinical outcome, not just sort of like can you do it?

What do people experience if we're wanting to kind of try to fool people a bit better? In Probably some kind of light placebo. The little bit of I wouldn't say deception, but just ambiguity. in 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 methodological problem that the field has to try to conquer in some way. And we're working on it. I just wanna jump in for a second. So I would say also that the the fact that placebo controls are so difficult Is

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 right in and of itself. I've written a whole mess of paper on stomach, so I mean it's fascinating that it's so hard. Do you have any you don't have to give away your secrets, but anything on the short list for potential active placebos that would you you would use in such a case? Niacin? Niacin's niacin's not a great option. That's um yeah a vitamin. So actually niacin was used in the nineteen sixties and it's been determined Even in nineteen sixty the niacin is a poor control for size. I'm people you still use it for some reason. And I'm not sure why. Skin flushing. I mean maybe subtype of sub subjective experience so that people think it's doing something. Yeah, it's added to a lot of dietary supplements as well. 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 in clinical trials is really important to prevent expectancy. Because if a person goes into a clinical trial thinking they're gonna get side and they do get sidecybin and if they think it might make them better, they work out that they've had it and they go ah And maybe they're over insulate. over accentuates the clinical response, which we would call a confound. So that's potentially a problem. So but what's important is it's not the compound itself. It's what the participant believes that they've had.

And so 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 in the 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 designs. You know, this is why I really enjoyed doing research in this here, because these are fascinating problems and it's a really like

fascinating area to try and work out these scientific problems. I reckon we can do it. I'm I'm not you know Give me another ten or fifteen years and I might give up. But right now I think, you know, we can totally crack it if we put our brains to it as a scientific discipline. It's a really exciting time to be

For me, certainly observing, watching to the extent that I can supporting the ecosystem and a really exciting time for people like you to be doing the research. It's really Kind of a blue sky opportunity and 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 cost first. on a personal level, familial level, and societal level. So let's jump to Q and A. At this point.

if that makes sense. And I'll hop over to Michelle to see if you have any any questions for us. I think we have quite a number. Yeah, we've got heaps of questions here. What I'm going to do though, Sharice, is I want to start it off. First question is going to be um 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? I think You know, we've got plenty of awareness around mental health generally in New Zealand. I think

We haven't seen government. Or any signals from funders. And 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 like foundational advocacy for this kind of stuff in New Zealand. Or there's not a huge amount of push to like Make government. do anything about it. So I think it's probably where things can be accelerated is by trying to get government to s start paying attention. And For them to take the attitude that we can be at the forefront in New Zealand, we can be at the forefront of this, and we already are, like we're way betting above our

In terms of like Us being tiny little countries back into the world. We are betting way above our weight, and we could get onto the front of These things being introduced if they are appropriate to be introduced. But a few bit more push from government would potentially accelerate that and you know

And really Establish us as leaders in the field. Stress, just to piggyback on that, for those in the audience who might want to support 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 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 uh any recommendations you might have for people who supporting philanthropically. Uh yeah, in terms of philanthropic sport, the best thing is to get in touch with either myself or Paul. Uh you know, we don't we're not top secret uh things and you know, just there's plenty of mechanisms, you know, but what I would say is that certainly philanthropic money is Really important.

And you know, the funding that you provided us was like essentially seed money that we could use to Then get The feasibility you need to then get a government grant to do the research. You know, to establish that, you know, we can run this trial, we can do it. Because when you have nothing, you just can't get started and then you apply for a grant and this 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 way, right? So

Philanthropic money. Can also be seen as a C, not just as you're funding the whole thing, but as a seed for future investment. So Definitely. Yeah, that's so important. I just wanna 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 uh sort of amplifying effect as a signal. Right, because then it allows researchers to fundraise that much more easily from other sources. So the the money's important, of course, but the signal is also Really important.

Yeah, Michelle, do you have more? I'm sure you do. I do, yeah. So this one, um, what are the risks of micro dosing? 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 it is it and is it dangerous. We have a data set.

That we've collected and w it's really the first data set that's been collected. And so far we haven't seen any negative safety things, but it's a very small data set and a very healthy population. So 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 severe mental health disorder, could be You know? Uh you're hitting into the unknown, I guess. That kind of thing. So

Potentially the biggest risk probably apply. Actually in the application area of mental health and particularly with Particular comorbid disorders, so I think it's important to treat lightly. Carefully.

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

twenty four, forty eight hours. And on top of that, it's critical, I would say, to consider legal ramifications. There are legal risks if you're dealing with schedule one compounds. And secondly, just because I've seen this quite a few times. We're dealing with in the case of LSD, for instance, micrograms. Okay, so to explain what that means, Suresh, please correct me if I'm getting this wrong. You've got

Let's just say milligrams, which are a thousandth of a gram, am I right so far? Yep. Milligrams is thousands, yeah. And microgram is a millionth. Of a gram?

If I'm getting that right, or is that a yep. So if you're dealing with millionths of a gram. Even the Albert Hoffman, who's the father of LSD, I mean went on his first famous huge trip while bicycle riding because he got it on his fingers. And so 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

micro dosing experience. And 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 So I just Not to be the stern dad about it off, but felt the need to say. No these are absolutely true that the non physiological risks are probably far greater than the physiological risks. Even though Law enforcement.

Deals with things like Schedule C crafts was like cannabis relatively lightly these days. Actually, they're not so forgiving with Schedule One substances, so that is important. Uh never mind. And I forget often, yeah, that you're right here, that's the purity of supply and dosing. I mean I forget this because we have I like to say the best L S D in town in my lab. But uh joking aside, yeah, like Illicitly in pain D or set aside and could

be cut with other things. It's very hard to know. But we do have drug tracking services in New Zealand that can Provide that kind of information though. And 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 Dance Safe.

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. There's a few people in the audience, Shar that are doing studies themselves. And say Toronto and and the US. And one of them's about the questions about open science. So what are your thoughts about open science replication crisis and will you be sharing your data?

Or you'd be keeping it private. So it depends on the study and it depends on what you try and do. So open science is is admirable and it's good, but it's not always possible, depending on, you know, who's Suresh, could you define that just for people listening who are not familiar? So open science is um essentially

Sort of 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 doing Publishing clinical trial protocols before we do it. So 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 you, for example, you're doing industry funded work where that's not possible because that's intellectual property of

Of Sid Company. So you know. I'm generally in favourite, but I think We do end up with the open science of having A lot of data in the world But no interpretive framework.

We can all do thousands of experiments in r in release. And Peter bytes of data into the world with potentially bad data. Which you know hasn't been collected well, or and just adds confusing signals to the noise. So I don't know that it's a panacea for actually a a deep theorical understanding of what's going on. Now we're going to shift to a training question. So anticipating legislation and increasing access to psychedelic assisted psychotherapy, how do we prepare the workforce?

And to be able to provide this. So what training pathways exist already for psychologists, clinical, social workers to upskill and become involved? This is a big controversy. I can take a stab. There are number of Concurrent experiments being run. So uh in the United States A lot of eyes are on Oregon.

And within the state of Oregon, uh there will be a lot of action in the next six to twelve 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 uh Political, medical.

level. Also in my foundation, so the Sise 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 a few other institutions. I apologize that I'm forgetting where And I'm 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 sort of psychiatry MD training. And people can elect

To then add this type of training and and qualification. to their pre existing track, if that makes sense. Which is not to say that this should be limited to being administered by M Ds or M D PhDs. I don't think that will come close to addressing

the demand and need. More importantly, than need. forgetting about healthy normals, which is a whole separate conversation. Let's just talk about people with actual Sort of clinical diagnoses. 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 ten 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 were gonna 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. Now is there a way this is for New Zealanders, is there a way that we can access psychedelic therapy microdosing now or how far certainly not now. You know you

Kidamine is potentially available through um there are a couple of clinics around the country offering ketamine services for those with depression. But psychedelics and um microdosing are still Microsoft in particular has got a long way to go. There's gonna be two to five years, probably. It's on a three to five year track to To progress that. Depending on how the results look. But I think the first thing that's gonna come down the pipeline, if anything, will be the MDMA assisted therapy, because that's the most advanced psychotherapy for PTSD sets, the most advanced sets 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 a regulator were to improve it, which would invariably happen after Fifty eight, if that were to be approved. Yeah. Um so we have that. And that might be only a couple of years away. That would be the first kind of cab off the rank, I think.

Yeah. And I and I'll just add to that 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 N N DMT, five 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 gonna follow that advice, but you know, I have a a pretty broad spectrum of interaction with these things and I would just say uh 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 a very, very long way. And uh Silocybin 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 kind of 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. Yeah, I I totally agree with that. And you know why,'cause there's this massive unmet need, right, to get things out to address these things. And it's 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 like rush it. and get it wrong and then to be safety issues that come up or like badly re regulated things and you s then all these horror stories start emerging into The popular consciousness and then we put ourselves fifty years back in the hold again. So I think that's what we really need to avoid with this. So treating really carefully, but hopefully that won't happen'cause we do have a stronger regulatory environment than there was in the nineteen sixties. So hopefully we can avoid that kinda issue, but I think it requires us to work

Diligently, honestly, and carefully. I mean, not to paint a bleak picture, but it's just like he we I think we really want to mitigate The risk. Of catastrophe that then becomes a political soapbox.

And then before you know it, 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 sixties and the generational differences no longer exist and there's bipartisan support, et cetera. But politicians are 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. Size of the Yeah.

Cavalier administration of five MEO DMT or in fill in the blank location, right? Not to throw five MAO DMT under the bus. I think it's very interesting, but high degree of thrashing, high percentage of thrashing within the subset of people who use it. So You know, bad things can happen and bad things will happen also. And I think the the the people involved, which is why the Decise Foundation is also involved with the Harvard poplar. Project.

Which is a law of 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 accident of various types. And this is 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 with anything that It's purported to have this much promise and certainly anything that has this much coverage. Michelle, what else do we have? Is your research expanding a little bit further and going into addiction?

Which is more dangerous and obviously deadly than depression and anxiety. Are you doing any research in that area? We're starting to talk about it. We're starting to talk about A project.

There will be a more Maori based intervention that will be run by Maori researchers and we're just in the very beginning stages of starting to sketch some ideas together. Well How that might be done. for that population and with amphetamine use or alcohol use. But it's very early stages for us, but

Definitely. There's something we're not leading that we're just providing support for in terms of intellectual support and learning how navigate the regulatory system on this stuff, so that could be really interesting and There are elements of For example, spirituality that had some synergy with Mary culture that

Um would be interesting for those researchers to explore. So just on that little bit then, what about have you included women in the studies or has it been mostly males? We had this one s L E C microdacing study where it was w where it was males only because we um I won't say it was ditched warfare trying to get this Trial approved.

But it was? So and so we just had to like take risk down as much as we could in certain places. So the idea of the problem of potential pregnancy was something that we just for this stage we just wanted to avoid that as an issue. And there was also menstrual psycho confounds in that that we wanted to avoid for Your first trial. We think we've now got the steps that we need to expand in the future trials, but And I've taken a lot of flack for this and and I say, Well my response is well you try and like get this study approved over mine,'cause I spent years

aging trying to get this thing approved. Um so Yeah, we did the best that we can while we could and we always hope to do better. But certainly, um Or other studies of him. Good females in the next day as well. Um now that we've got over that fifth turtle.

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

sort of heterogeneous group. So Definitely Easier to do when you have a little bit of escape velocity after the first one or two pilots. Yeah. There's actually some interesting Anecdotal reports of

In terms of microdosing for um People have been using it for that and that it might affect actual menstrual cycles and menstrual cycle timing. So that's actually quite an interesting there's potentially interesting separate studies to be done there that we have considered And We'll consider in the future.

So if um someone's wanting to sort of get into this type of research, what education do you recommend for anyone wanting to help assist? Oh, so I get this all the time Undergraduate student side. Well I'd say, you know, the best option is just go be a medical doctor'cause then you can uh You don't but uh A university degree? I'm just promoting the university working'cause it's my employer who pays the bills. But uh you know, for young people getting a s a science degree or a health sciences degree Um medicine, psychologies, those are

I think That's where the forefront of things will We'll be and will be in either mid In New Zealand, it's gonna be basically psychiatrists and psychologists that are gonna run this. I

Suspect that that will be where Things. Full. So if you want to to Get into being able to So

Describe what be involved in this kind of therapy, I think psychology and psychiatry and general medicine are the places to study. So things to do. And then there's also scientific Degrees you can do like medical sciences.

Strong background in mathematics is always good. And just gonna go into one about um corporate. So Have you looked into the clinical trials of the larger public companies? So this MindMeb Compass, AT AI, and numerous. And do you feel there are any red flags and how these are current corporations are going about.

pro improving their respective drugs. So that's like L S D M D M A. Yes, and I I should say as a disclosure that I uh consult for some These companies? As a disclosure. So and actually collaborating with one of them. So my observations is that The people that these companies are employing are really ex seem to be really experienced, um pharmaceutical people with a lot of industry experience in pharmaceuticals and they seem to do quite a rigorous job.

You know, there's obviously gonna be tensions there for those companies in terms of wanting to get things through reasonably speedily. Because they've only got so much. Capital. You know, the pathway's long and expensive and the intellectual property that they need to

Game because of You know, these generic medicines is is going to be an issue, but There's red flags with 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, you know. Not uncomfortable with the grey.

I'll hop in with just a few things. So I would say on the 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 uh pre registration Publishing your protocol ahead of time so that you can't sort of torture the the the data or or move the goalposts and you know declare victory when in fact it was not a victory, I think is is incredibly important. And then you know 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. sort of raises funds and builds companies the R and D expense. There are also Obvious

Relatively unhelpful non improvements. that people sometimes get patents for which are obstructionist in nature. and 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 process. to dominate a given molecule that has existed for

Decades, if not. you know, millennia in some cases. So I do think the IP side of things is very important to to keep an eye on. And an organization that might be worth checking out is Freedom to operate, which was created by Carry Turnbull. And that is an area that will be increasively Active. Mason Marks and I Glenn Cohen, I period, Glen Cohen, C O E H E N co authored a paper.

on intellectual property and patents. For those who are interested, that's out of Harvard Law School. It's enough time for our questions, actually, Tank. Guys five. Alright. Well

Well, fantastic. Thank you so much, everybody, and thank you, uh so much, Suresh, for for making the time. I'm very excited to see what you do next. Cool, thank you. Good, thanks Tim. I'll just close us off with a cut here. It's been a great session today and then hopefully this will set you on the rest of your way. Kito.

Ranging the yeah. Uti rang in no e ta e home. Or Papanuku e Tako na. O Tate Ona Ahime. Kurunga e Tato Tato.

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