 Kia ora kato, nā mai, hari mai. We will open this session today with a kata kia. A kata kia is a blessing and is a practice of the indigenous peoples of Aotearoa and the Māori people. We'll be utilising a kata kia today to clear the space and set good intentions for the day to come. This one is my favourite. It reminds me of one of the two places I grew up, Taupo Nui Aotea, and recently, over Easter Break, when I visited Taupo, I was cycling around the lake and there was a plaque with this kata kia on it. And the pathways are etched with the parts of the verse. Aruhu atu, aruh mai. So settling in. Kia hōrā te marina, kia whakapapa pana mō te moana. He arihi ma tātu e te rangenei. Aruhu atu, aruh mai, tātu e e tātō katoa. Greetings to you all and welcome to today's EHF Live session. The Evan 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 is an early stage technology investor and adviser. And Tim will be interviewing Dr Shuresh, 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&A with Tim and Shuresh during the 90 minute session, but there are the end. Some housekeeping first. We're currently live streaming to our Facebook page. The link is on the chat if you want to share it. The recording of the session will be on the EHF website and YouTube channels afterwards. Please use the Q&A box at the bottom of the Zoom window for questions at the time during the session, and then I'll harvest them out of it. If you're on Facebook, post the comment section and we will add it to our Q&A box and Zoom. Over to you, Tim. 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 Shuresh Mutu Kumaraswami. I will here forward refer to him as Shuresh. Shuresh 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 Centre as a postdoctoral 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 drugs psilocybin and LSD in 2014. Shuresh 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. Shuresh'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 and depressed patients involving ketamine, capolamine 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. Shuresh has published 117 papers and his work has received more than 8000 citations. Shuresh, welcome to the session. Thanks for being my time. All right, 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. Yeah, so New Zealand has pretty good data on this because every year the Minister 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, this is conducted every year. So in 2000 and I think 1112 when the survey was conducted, 4.6% of adults experienced psychological distress in the last month. And we've seen that slowly creeping up to the last data point from 2020, 21, 2020, where it was now at 9.6%. 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 actually the last 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 that's going to only get worse when the next year's data point comes up 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 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. Now, I would imagine, although I don't want to assume that the the costs and there are many different types of costs, but the health care costs of these upward trend lines with mental health issues. Let's just call them depression, chronic anxiety, treatment resistant depression. Or 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 just a few compounds first and actually is way of background. Could you mention just a few other classes of compounds that you've 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, yeah. So my background is in general psychopharmacology. So before studying psychedelics and concurrently to 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, a lot of the anesthetics like propofol. So I've studied all those drugs at various times, various antiepileptic 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 Fintanil. We've looked at in the past. So I've yeah, I've had a done a lot of psychopharmacology studies that have nothing to do with psych 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 they catch the attention. So we're going to 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 hallucinogenic, some of which are considered quite risky. But how did you determine this as a as a subjective interest for for research? Yeah, so we had been doing studies on the antidepressant effects of ketamine and we'll talk about this later. But you see this rapid antidepressant effect. And so what we were interested in was are the 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 programme. There 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 we can investigate that and then potentially look at in our study, we looked at antidepressant. 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, you know, that it's the data, right? We we did a really carefully controlled study. We, unlike the previous research that used an inactive placebo, and we'll get back into this, we use an active placebo that a compound called glycopyrinium that's used a lot in surgery that doesn't cross the blood-brain barrier, but still was 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. And so we were able, we were able to show that participants could no longer distinguish which of the drugs that they had. And actually, we are describing most of the antidepressant response that we see to a placebo response. So listen learned. Yeah, that's fascinating. Yes, Kapalamin, I don't want to take us too off track, but has some very interesting effects on memory in or at least it's thought to have some very interesting effects on producing amnesia while still having agency on some level. It's it's a fascinating compound. So let's 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 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. Believe it's one of the the World Health Organization's top 100 most essential medicines. Could you discuss ketamine and classical psychedelics and how they differ in 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 in certain 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 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. So maybe the easiest thing to start was with the classical psychedelics because it's relatively simple compared to ketamine. So LSD and Sata Saibhan, DMT, they all seem to work through a common receptor called the serotonin 2A receptor. And we think that most of their effect, you know, 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 has a very different, even though it has these kind of this dissociatable psychedelic effects, it's receptor binding. So it's a mini and complicated. So principally, it binds to antagonises a receptor 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 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, so 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 the ones involved in inhibition and sedation. It also binds to opiate receptors and everyone will be 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 metabolises into nohydroxyketamine, which has neuroactive sites as well. And it also, 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 is ketamine and are ketamine. And normal ketamine is both of those. But actually the aren't is ketamines probably have different receptor binding profiles in addition to all of that. So what we're left with this is 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? So the first is why scientists would wade into this super 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. Yes, sorry. So when drugs are in the brain, broadly speaking, 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. In terms of for ketamine, in terms of there's both a clinical and a scientific interest there that's and they're both really interesting 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 you patients that have had treatment resistant oppression unremitting for years and years and years and you can give them a ketamine infusion and they'll get this really rapid remission and symptoms and that will manifest itself in the next 10 or 11 hours. Now, people will know ketamine is a street drug, right? And they would say, 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 that's how long ketamine lasts in the body, the half-life is about four hours for ketamine. 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, you know, 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, right? 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 ketamine's obviously working on some kind of target that can flick that switch. And that, you know, 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 transcranial mag, 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 it really good experiments because you no longer have to wait six weeks in 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 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, a 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 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 a repatient, 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 fenethylamines 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 raised this because I was recently in a conversation with Roland Griffiths from Hopkins, 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 Roland's perspective was that he thinks a lot of the durability of anti-depression, anti-depression affects six months, 12 months of follow-up. Let's just say have a lot to do with a change in content. So 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 true 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? Yeah, I mean, it's a good question. I guess the background to this for people is that the anti-depressant response that we see to a ketamine infusion that will last in our experiences is a scenario from a day or two to a couple of weeks to a month, whereas the data for psilocybin, that seems to indicate months, half a year, year-long anti-depressant responses. But I think 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 that 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, right? So, and I think it's really important for people to understand when they think about it because you just read these headlines, are 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 psyched-assisted psychotherapy. Now, whereas the model for ketamine that's mostly been used is basically, in a way it seems to be used in your label is that people just go into a ketamine clinic and they smash it in the fusion for an hour and they go away. You know, so like, and there hasn't really been much studies where people have actually done ketamine-assisted psychotherapy and tried to, well, what if we do, you know, wrap that similar lip? 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 force? We've kind of, 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 so we haven't, we don't really, 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. So... And do you say that just because of the difficulties that can come up in navigating that experience? Yes, yeah, yeah, absolutely, yeah, because, you know, these are, you know, very powerful. So something like psilocybin is very powerful in terms of psilocybin and DMT, LST. These are very powerful psychological, have very powerful psychological effects and they can be destabilising 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, 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, you know, the 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 micro dosing study, why did you choose to pursue that study? Yes, so, yes, so I had returned to New Zealand in 2015 and having previously done classical side killers, 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 easily 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. A 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 built a bit of a reputation, I decided it was time to get back into doing some classical psychedelic research. Now, the micro dosing specifically was, well, no one had really looked at micro dosing in an RCT at that point. And it's a randomized control trial, randomized control trial. And I guess, should we explain what micro dosing is? Maybe why don't you explain what that is? And it all it also might segue into the one of the design challenges, meaning placebo control looks overall. So, yes, please define micro dosing. Yeah, so micro dosing is when people take very low doses of psychedelics about the tenth the dose of a big dose of a when people are going to tripping. So, you know, people might trip on like, you know, 150 micrograms LSD, but for micro dosing might take 10 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 wellbeing, concentration increases. And so what they do is that they take these micro doses maybe every third day is the most common schedule that's called this was popularized by James Faderman who wrote a book in 2011. And it's really taken off since then, you know, like before 2011, not many people were doing it and there was really not much consciousness about it. But now we're seeing, you know, hundreds of thousands or hopefully of people around the world now micro dosing. 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 micro dosing, 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 RCT, a proper randomized control trial of micro dosing, 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, 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. I think they might be a little grumpy about that. Yeah, 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 a little old New Zealand. So as I was, as you do every now and then, reading the misuse of drugs regulations from 1977 and misuse of drugs act that goes along with it, we kind of discovered this loophole, I don't know if you call it loophole, where actually we're allowed to prescribe class A substances. It's not even 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 and got the appropriate approvals from ministry, various parts of 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 to 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. So 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? Yeah, two at a time. Yeah, they were given packs of four, four and five. So we never gave them like 130, 140 micrograms to take home so that they couldn't just stack them all up. But actually, you know, there's a lot of theoretical concern about this, but actually to get into one of our trials, you know, 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 like this, hours and hours. There are a lot more efficient ways to get doses of LSD. Oh, for sure, for sure. Yeah, absolutely. And we track every single dose was administered and video recorded by the participants and sent to us. So we knew there was 100% adherence to the protocol. And 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 and 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? Yeah, it's a good question. I think in terms of... I think we do have a... 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 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 are making these decisions. And a country of five million is only so many people who know or are involved in these kinds of decisions. So if you're a sensible and polite and appropriate, you can ask questions and get things to move. So we do have that. So with small size, I think, does come agility. And I know that there are certainly pharmaceutical companies that are investing into New Zealand's psychedelics industry and our general medical... Into clinical trials here, we're in an attractive place to run clinical trials because 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 that's attractive. So we do have a good regulatory environment in terms of how we can promote more sort of 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. So by comparison... And where we risk falling behind by a comparison in Australia, they created a $15 million fund specifically for these sort of breakthrough mental health therapeutics where 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 sort of provide all the capability that they need. So we haven't seen any signs of that yet from government 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 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 workers have to be of very high quality because we're competing with our peers that are 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 is seeking funding. Yeah, that's right. And there's actually some data on that. And actually what we've seen and not just psychedocs, just mental health in general has been underfunded in New Zealand for 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 it's being 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 has not been given the funding 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. 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, 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 liberal parties, to get state funding set aside for psychedelic research related to veterans, for instance. And 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? Yeah, I think the last one would be the way to go. So, I think in terms of things like breakthrough designation, we don't have... We in New Zealand set at the end of the pipeline for when treatments come, because the way our treatments come is an international farmer, a suitable company will apply for a registration here and they'll use all the data basically they've submitted to the FDA. So, once they've got FDA or EMA approvals, then they might come here for approval after a few years and they bother to put the marketing application together. So, we're at the back end of that 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, because we're a small market. So, I don't see that first approach work, but the second approach could certainly work where the government sits aside and just... Probably wouldn't be through legislation. We'd 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 need in study in Christchurch. So, that would be a mechanism that could certainly work. 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. 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, global drugs that are available elsewhere, you also have companies like, I want to say, Adidas and Nike 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, really any... Yeah, well, you know, New Zealand has a rich, biomedical conditions. So, I work in, you know, I don't work in a... 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 people doing work in a place in Auckland called the Liggins Institute, where they're doing work on preterm babies and there's also how stroke recovery research is doing really well and so on. And down in Otago, I really like the group down there that are doing in a more psychedelic space. They're doing... Paul Glu'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. And so, there's a lot of... 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 the kind of... where things are happening in the biomedical realm. 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 wanted 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? Yeah, so maybe it's not an analog. One of the things is they've been looking at like slow release formulations as one way to go to see if they... And this comes back to that thorny issue about with ketamine like how important is actually having the psychedelic experience. But if maybe if you could slow down the metabolism of ketamine or 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. It's a museum company who have been looking at that is Douglas Pharmaceuticals. They've been looking at this kind of slow release ketamine that's quite interesting. And then there's different companies overseas as well looking at... I described that left and right formation. They've been stripping ketamine into its R&S formulation. Now, Janssen, as you'll be aware, they took the S ketamine, the S part of ketamine and put that in nasal spray. Spravata. This is a... Yes, spravata. And this is essentially a marketing exercise, right? Like there's no... It doesn't seem that it has any more efficacy than normal ketamine, but it allowed them to achieve a patent on it. And then in New Zealand that's quite... What is the price differential? I think it's something like one to five dollars generic, like several hundred dollars spravata USD. In New Zealand, there's be even bigger the differential because in New Zealand we can get a bottle of ketamine for like $20 or something. But of course the spravata was like five or $6,000. So it's just... The differences are insane. For a condition who may not be comfortable with prescribing ketamine off-label because ketamine is not indicated for depression. It's 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, S 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 sort of background in how medicines get approved is you need a company to sponsor the research. To go to 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 computer can just come and make more ketamine and sell it instead. So there's no return on investment to be added. With actual property. 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? Yeah, so he's been looking at he's been doing a slow release work. The other thing he's been looking at is other internalising disorders. So he's done a lot of work looking at ketamine and anxiety disorder. So, and it's time to put up quite a good evidence space that ketamine isn't just might not just have efficacy in depression but in a range of sort of rumen internalising disorders. So I think he's done anxiety and social anxiety. And so ketamine seems to have therapeutic effects beyond just the category of depression. And these are all kind of there's less data on these at the moment. So there's, you know, you would be even more reluctant to prescribe our flavour for those things where there's a small evidence space, but there is an emerging evidence space that other things and pools definitely been contributing to that. And 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 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 insurance reimbursement purposes, you need an indication and a code, 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. 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 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, right? 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 fuel 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? There's endless possibilities. You know, like, 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, like, and essentially all the stuff, everything that's been done so far is essentially just elaborate pilot studies, right? We're just beginning to learn. And, you know, that's come from 50 years of prohibition where we haven't been able to do this work. So, you know, things were looking and people might know this history that in the 1960s, when this research started slowing down in the 1960s, you know, there was promising signals, but everything just stopped for like almost 50 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, you know, 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. But the things that we... 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 the first... You alluded the first problem that we have is diagnosis, right? Like, we... Unlike for mental health, you know, the really thing to be aware of is unlike cardiology or cancer, right? We can't just like stick someone, get an echocardiogram done and realise they've got some kind of thing going wrong with their heart for some regurgitation or valve, you know, whatever it is, or we can't measure a tumour size and know, yeah, this is it. So the physician is based entirely basically, you know, 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 biology of what's going on in terms of the diagnosis. And 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 and then actually 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. OK, you're feeling better. So, yeah, which, you know, which if you're measuring, like, you know, tumour size in a petri dish, you know, that's what tumour growth, that's, you know, so we have a long way to go to harden up the science but to answer your question more specifically, the things that we really need to, 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, 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 actually, like, talking to somebody, you know, like, you know, what is the actual requirements there to get? Because you will have no shortage of, like, case reports, like you've said, of people that, you know, just took a side of side and by themselves and said, ah, yeah, I started feeling better with no, like, thing. I'm not saying you should do, anyone should do that, by the way, but just people report that. Of course, at the same time, people report taking side of side and having a terrible experience and, you know, and with terrible psychological shock involved afterwards. So, we do have to start to deconstruct what's actually going on in the intervention. So, 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. Yeah, absolutely. So, I want to 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 for these substances for 50-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 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, LD50s, so the dose at which 50% 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, 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, but there are, I mean, 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 gonna be excluded by study criteria like those with family history of schizophrenia. And we're gonna jump into Q&A in about five minutes, but what I would like to 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 like to highlight one of them. And 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, 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? So you have placebo effects, we won't even get into no-cebo effects 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 and just for people listening, could you describe how you thought about that and whether you decided on a passive or active placebo? So for this study, we went with an inactive placebo just because no-one had ever done LSD microdosing before. We wanted to rent for, in the community, we wanted an 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 or as a safety group to look at. And in terms of whether people are, you know, able to detect the effects, summer, summer, so we were around about 10 micrograms. I suspect, yes, about 10 micrograms in male volunteers, so there might be, there's quite a heterogeneity 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 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, that we may need to start looking at lightly active placebos that, because we're now interested in the clinical outcome, not just sort of like, can you do it? What are people experiencing? If we're 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 give 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 it some way. And we're working on that. So, I just want to jump in for a second. So, I would say also that 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 in and of itself. I've written a whole massive paper on this topic. Yeah, I mean, it is 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 placebo that you would use in such a case, Niacin, something else? Niacin's not a great option. That's a vitamin. So 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 used to use it for some reason and I'm not sure why. Yeah, skin flushing, I mean, maybe some type of subjective experience so that people think it's doing something to add it to a lot of dietary supplements as well, just like they are. We're getting into the weeds here, but what I would say is actually what the compound is, isn't as important as 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 at Vargas, we should step back and to say, blinding in clinical trials is really important to prevent expectancy because if a person goes into a clinical trial thinking they're going to get psilocybin, they do get psilocybin and if they think it might make them better, they work out that they've had it and they go, and maybe they over accentuate the clinical response, which we would call a compound. Now, 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 act of placebo was, but what you tell the participant about the act of 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 and it's a really fascinating area to try and work out these scientific problems that, you know, I reckon we can do it. I'm not, you know, give me another 10 or 15 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, you know, certainly observing, watching and 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 just, 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 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. We do, actually. Yeah, we've got heaps of questions here. What I'm going to do, those addresses, I want to start it off, 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? That's a great question. I think, you know, we've got plenty of a we are in a mental health generally in New Zealand. I think we haven't and we haven't seen government or any signals from funders about. And I think that's where we haven't really seen any kind of movement. So if any of you have like that's where pressure can potentially be applied, right? And there's not much is 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 start paying attention and and taking for them to take the attitude that we can be at the forefront and 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 as tiny countries that back into the world. We are betting way above our way and we could, you know, 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. 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 the space for a long time. It's 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 some interesting things happening in New Zealand. Are there any recommendations you might have for people who would like to consider supporting philanthropically? Yeah, in terms of philanthropics, what the best thing is to get in touch with either myself or Paul. We don't we're not top secret things that, you know, this 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, you know, the feasibility you need to then get a government grant to do the research to establish, you know, to establish that, you know, we can run this trial, we can do it because starting when you have nothing, you you just can't get started and you apply for 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 the next thing and then they can grant way. Right. So philanthropic money can also be seen as a seed, not just as you're funding a whole thing, but as a seed for future. Definitely. Yeah, that's 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 sort of amplifying effect as a signal right because then it allows researchers to fundraise that much more easily from other sources. So the money is important, of course, but the signal is also really important. Michelle, do you have more? I'm sure you do. I do. Yeah. So this one, 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 and is it dangerous? You know, we don't have a lot. We we have a data set and that we have collected and it's really the first data set that's been collected. And so far, we haven't seen any negative safety swings, 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 probably 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, this sort of could be, you know, you're heading into the unknown, I guess, is that kind of thing. So but yeah, so there are potentially the biggest risks probably apply actually in the application area of mental health in particular 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 there are some synthetic. Well, a lot of synthetic. Thousands of synthetic psychedelic compounds that are sometimes confused or sold, confused with or sold as LSD that that can launch you into some very at best uncomfortable and at worst very dangerous circumstances where you could you could be in an experience for 24 or 48 hours. And on top of that, it's it's critical, I would say to consider legal ramifications. There are legal risks if you're dealing with these kinds of 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. OK, so to explain what that means, Sir Ash, please get me to correct me if I'm getting this wrong. What you've got, you've got, let's just say milligrams, which are a thousandth of a gram. My right so far. Yeah, and microgram is a millionth of a gram. If I'm getting that right, or is that it? Yep, that's right. Yep, so so all right. So if you're dealing with millions of a gram, even the Albert Hoffman is the father of LSD. I mean, went on his first famous huge triple bicycle riding because he got it in his fingers. And so you're dealing with such incredibly small quantities that the the ability to misdose or to absorb it through the skin can lead to something that is most certainly not a microdosing 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 be very, very tragic indeed. So I just not to be the stern dad about it all, but felt the need to say that. No, these are absolutely true that the non-physiological risks are probably far greater than the physiological risks. And we in New Zealand, yeah, even though the law enforcement deals with things like schedule C class is like cannabis relatively lightly these days, actually, they're not so forgiving with schedule one substances. So that is important to bear in mind. And I forget often, you're absolutely right again, and that's the purity of supply and dosing. I mean, I forget this because we have, I like to say, the best Dali Steen town in my lab. But joking aside, illicitly in pain, Dali Steen or psilocybin could be cut with other things. And it's very hard to know. Yeah, absolutely. But we do have drug trick and services in the zone that can provide that kind of information. 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 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. Yes. There's a few people in the audience that are doing studies themselves and say 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 crisis and will you be sharing your data or will you be keeping it private? Well, it depends on, you know, yeah, so it depends on the study and it depends what you're trying to 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 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 we're and we've done open science things. So I'm in favour 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 seed company. So, you know, so I'm generally in favour of it, but I think, you know, but also we do end up with open science, you know, of having a lot of data in the world, but no interpretive framework. So you can you can 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, you know, I don't know that it's a panacea for actually a deep theoretical understanding of what's going on. Thank you. Now we'll shift to a training question. So anticipating legislation change 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 this is a big controversy. I can I can take a stab. I can take a stab. The 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 political, medical level. Also, you know, my my foundation, so the Saisei Foundation, S-A-I-S-E-I Foundation dot 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 and I'm forgetting where and I'm going to get some of the details wrong here. But in effect, a certification programs being created that can be applied into this funnel, which already exists. And that is the sort of psychiatry and training and people can elect to then add this type of training and qualification to their preexisting track, if that makes sense, which does 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 there 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 grey market as sort of 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 can see some of them at the foundation. Someone can put that URL up. That'll be great for the audience. Now, is there a way this has been New Zealanders? Is there a way that we can access psychedelic therapy micro dosing now? No, no. You know, ketamine is potentially available through there are a couple of clinics around the country offering ketamine services for those with depression, but psychedelics and micro dosing are still in the future. You know, we're looking at, you know, micro dosing particularly has got a long way to go. Five problem 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 sets, most advanced sets in phase three, conical trials in the US. We have a group of maps trained therapists to actually know that could actually deliver that therapy if the data was seen to be OK and a regulator were to improve it, which would invariably happen after FDA if that were to be approved there. 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'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, you know, NNDMT, 5MEO, DMT, Iowatka 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, you know, I have a pretty broad spectrum of 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 a 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 mean those are the three that are kind of the best for this to long. But each of these compounds has its own complexities and difficulties. And you know, I think slow is smooth and smooth is fast with this stuff. We just come through half a century of prohibition. We don't need to figure it all out in the next six months. Yeah, I totally agree with that because, you know, like there's a design, you know, and you know why? Because there's this massive need to get things out to address these things, but and and and it's heartbreaking and pressing problem. But at the same time, you have to think, well, if these things really are effective, you know what the last thing you want to do is like rush it and and get it wrong and then to be safety issues that come up or like, you know, badly, badly regulated things and you then all these horror stories start emerging into the popular consciousness. And then we put ourselves 50 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 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. Yeah, I mean, all all it I mean, not to paint a bleak picture, but it's just like we I think we really want to mitigate the risk of catastrophe that then becomes a political soap box. 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 60s and the generational differences no longer exist and there's bipartisan support, et cetera, but politicians have certain sets of incentives, have certain sets of incentives. And I would really say that it is it is it is a non-zero percent chance that things can send back to prohibition if, say, one senator's child dies of cavalier administration of five MEO DMT in fill in the blank location, right? And not to not to throw five MEO DMT under the bus. I think it's very interesting. But you know, 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 people involved, which is why the Accessive Foundation is 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 is this is this would be true with any any drug used at scale, right? Like it's it's 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, vaccines. Yeah, yeah, right. Vaccines, so it's it's 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 we accept and expect that on some level because it's inevitable with with anything that is purported to have this much promise and certainly anything that has as much coverage. Michelle, what else do we have? Yeah, 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 that will be more Maori based intervention that we run by Maori intervention, 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 and methamphetamine use alcohol use, but it's very early stages for us, but definitely that's something we're not leading that we're just providing support for in terms of intellectual support and learning how to navigate the regulatory system on the stuff. So that could be really interesting. And there are elements of, for example, spiritual reality that have some synergy with Maori culture that would be interesting for those researchers to explore. Yeah, I agree. So just on that a little bit then, what about any included woman in studies or has it been mostly males? We had this one LSE microeasing study where it was males only because we we I won't say it was pitched warfare trying to get this trial approved, but it was. And so we just had to take risks 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 a menstrual life cycle confounds in that that we wanted to avoid for their first trial. We think we've now got the steps that we need to expand in the future trials. But and and I've taken a lot of flack for this. And and I say, well, my response is, well, you try and get this study approved. Because I spent years ageing trying to get this thing approved. So, you know, we did the best that we can while we could. And we always hope to be better and but certainly while other states have been equipped with females in the next stage. Well, now that we've got over that first hurdle, 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 you see how 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 premenstrual dysfobaric disorder. People have been using it for that and that it might affect actual menstrual cycles and menstrual cycle timing. So that's actually quite interesting. There's potentially interesting separate studies to be done there that we have considered and will consider in the future. 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? Oh, so I get this all the time. Undergraduate students, I'd say, you know, the best option is just go be a medical doctor because then you can you learn, but, you know, a university degree, maybe I'm just promoting the university because it's my employer who pays the bills, but, you know, for young people, getting a science degree or a health sciences degree, medicine, psychology, those are, you know, I think that's where the forefront of things will will be and will be in either in New Zealand, it's going to be basically psychologists and psychologists that are going to run this. It would I suspect that that will be where things fall. So if you wanted to, you know, 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. So all the things to do. And then there's also scientific degrees you can do like medical sciences. Strong background in mathematics is always good. True, and just going to go into one about corporates. So have you looked into the clinical trials of the larger public company? So there's MindMed, someone to shift to my stuff, Compass, ATAI and Numerous. And do you feel there any red flags and how these are current corporations are going about improving their respective drugs? So that's like LSD in DMA. And yes, and I should say as a disclosure that I consult for some these companies and have, yeah, so as a disclosure. So and actually collaborating with one of them. So my observations is that they tend they are people that are really the people that these companies are employing are really seem to be really experienced. Pharmaceutical people with a lot of industry experience in pharmaceuticals and they seem to do quite a rigorous job. You know, 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, you know, the pathway is long and expensive and the intellectual property that they need to gain because of these generic medicines is going to be an issue. But red flags, you know, there's red flags in every area of, you know, so you have to what I would say is, well, you know, there's red flags in every areas 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. So, yeah, I'm comfortable with the grey. I'll happen 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 sort of torture the data or move the goalposts and declare victory when, in fact, it was not a victory, I think, 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 and justifies the R&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 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 Kerry Turnbull. And that is that is an area that will be increasingly active. Mason Marks and Glenn, I, Glenn Cohen, I period, Glenn Cohen, Co-N-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. It's enough time for our questions actually, Ting. All right. 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. Oh, thank you. Good. Thanks, Ting. I'll just close as I've got to cut it here. It's been a great session today. And then hopefully this will set you on the rest of your way. Kietau tia rangamaria o tia ranginue e ta e hō nei, o papanukiu e tako nei, o ta te o na ahi nei, kōrunga e ta to o ta to, tii hei mori ora. Kia ora, Ting. Thank you. Ka kite. Enjoy the rest of your evening or day.