The Possibilities of Mind-Altering Compounds | Dr. Suresh Muthukumaraswamy | The Tim Ferriss Show | Transcription

Transcription for the video titled "The Possibilities of Mind-Altering Compounds | Dr. Suresh Muthukumaraswamy | The Tim Ferriss Show".

1970-01-01T03:12:07.000Z

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Introduction

Start (00:00)

optimal minimal this altitude I can run flat out for a half mile before my hands start shaking can I also request you? now what a sit-and-aprope time what a fight to the island I'm a cybernetic organism living to show a metal empress going leave to ferris show Hello boys and girls ladies and germs this is Tim Ferriss welcome to another episode of the Tim Ferriss Show. this episode is a special episode it is a live recording from an event hosted by the Edmund Hillary Fellowship the Edmund Hillary Fellowship, otherwise known as EHF, began in 2016 as a pilot immigration program and has matured into a fellowship of more than 500 technologists, creatives, investors, entrepreneurs, educators, and systems designers, among many other things, committed to New Zealand as a base camp for global impact. From more than 50 different nationalities including New Zealand and fellow span range of high value sectors such as media, education, clean tech, 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 Aotearoa, New Zealand. In the session today you're going to hear from Tim Fureus, who is an EHF fellow who is an early stage technology investor and advisor 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 have been plenty of time for Q&A with Tim and Shuresh during the 90-minute session but near the end. 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. Suresh Mutu Kumaras Swami. I will hear from you. I will refer to him as Suresh. Suresh is an associate professor of psychopharmacology at the University of Auckland and he completed his PhD in psychology at the University of Auckland in 2005 after which he joined the newly established Cardiff University Brain Research Imaging Center as a 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 of the psychedelic drug psilocybin and LSD. In 2014 Suresh received a prestigious Rutherford Discovery Fellowship and returned to the University of Auckland where he worked 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, scapolamine and transcranial magnetic stimulation, TMS. He has received several health research council of New Zealand research grants to support this work including a grant to investigate the effects of micro doses of LSD on brain and cognitive function. Suresh has published 117 papers and his work has received more than 8,000 citations. Suresh, welcome to this session. Thanks for being here and taking the time.


Current And Future Psychedelic Research In New Zealand

Current mental health and addiction trend lines in New Zealand. (03:44)

My pleasure Tim Lassizi. 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. 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 have 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 2011-12 when the survey was conducted, 4.6% of adults experienced psychological distress. In the last month, we have seen that slowly creeping up to the last data point from 2021-2020 where it was now at 9.6%. So we have seen a doubling over the last 10 years and 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 can 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 out because in New Zealand you might not be aware but in New Zealand the second lockdown was quite hard that just finished at the end of 2021 so that will definitely have impacted on people's mental wellbeing. So we'll expect that to go up. So it's not a good place to run but 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 costs, right, 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 New Zealand as well, not to mention the personal costs, let's talk about just a few compounds first and actually is way of background.


Compounds Suresh has researched. (05:37)

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. Yes and 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 in various times, various anti-apoleptic drugs so that kind of class of drugs and then also we recently did a study of scapolamine which is a muscarinic drug and Remethanol we've looked at in the past. I've done a lot of psychopharmacology studies that have nothing to do with psychedelics although the psychedelic studies are the ones that probably are most well known for in the public discourse because they attract some interest I suppose. They catch the attention so we're going to talk about the contrast between say ketamine and traditional or classical psychedelics but before we get there because I am personally very curious why did you decide to study scapolamine and what did you find in terms of its effects on conditions whether depression or otherwise because scapolamine for those who don't know is also naturally occurring in many plants that are considered psychoactive or a hallucinogenic some of which are considered quite risky but how did you determine this as a subjective interest for research?


Does scopolamine have potential as an antidepressant? (07:13)

We had been doing studies on the anti-depressin effects of ketamine and we'll talk about this later but you see this rapid anti-depressin effect and so what we were interested in was are the other compounds out there that might show a similar rapid anti-depressin effects and there was a series of studies that came out of the NIH intramural program. There was two or three intravenous scapolamine studies that appeared to show a similar sort of pattern of anti-depressin effects so and scapolamine works very differently to ketamine or other anti-depressants being a muscarinic antagonist so I thought well that's really interesting if that works then we can study that and even though it's got a completely different kind of receptive 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 and rapid anti-depressant responses. The downside of course is that we found no anti-depressant response in that study but you know that that's the data right 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 a compound called glycopyronium that's used a lot 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 participants could not distinguish which of the drugs that they had and actually we are ascribing most of the anti-depressant response that we see to a placebo response so listen learned. Yeah that's fascinating yes capolamine I don't want to take us too off track but has some very interesting effects on memory or at least is thought to have some very interesting effects on producing amnesia. Yes it does yeah while still having agency on some level it's a fascinating compound so let's jump to ketamine most people or say many people have perhaps heard of ketamine very commonly used and please correct me if I get any other terminology incorrect but anesthetic dissociative anesthetic does not suppress respiration at least of the doses that I'm familiar with it is very widely used in medicine believe it's one of the world health organizations top 100 most essential medicines. Could you discuss ketamine and classical psychedelics and how they differ and just from an anecdotal perspective although there's a lot of really good research which of course you've been a part of looking at the anti-depressant 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 SSRI's which in some folks it can take six to eight weeks say to exert those types of effects if the people respond at all.


How ketamine differs from other psychedelics. (09:55)

So could you just perhaps give us a primer on ketamine and classical psychedelics and how they differ because both can be described as having psychedelic effects? Maybe the easiest thing to start was with the classical psychedelics because it's relatively simple compared to ketamine so LSD and cytosybine 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 in relevant 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 very different even though it has these kind of dissociative or psychedelic effects it's receptor binding so it's a mini and complicated so principally binds to antagonizes receptor called the NMDA 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 is the receptor involved in how brain cells learn to communicate and strengthen synapses so that receptor is really important there but then it also has a host of other effects so it binds to GABA receptors those are kind of the ones involved in inhibition and sedation it also binds to opiate receptors and it's normally familiar with opiates and then these other monoamin sites like that it interacts with serotonin dopamine norepinephrine hcN channels sodium channels it just the list goes on and on as you go up through the concentration so it's an extremely complicated pharmacology and it goes even worse because actually ketamine metabolizes into norehydroxyketamine 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 eschitamine and arachitamine and normal ketamine is both of those but actually the aren't eschitamines probably have different receptor binding profiles in addition to all of that so what we're left with is this astute 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 when drugs are in the brain you know broadly speaking it's more complicated but broadly speaking and 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 the clinical and assigned to the country said it's and they're both really interesting study which is why I've been studying ketamine for nine or ten years now the clinical significance is what you mentioned before it's you have 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'll get this really rapid remission and symptoms and that would manifest itself in hours now people will know ketamine as a street drug right and they would say oh well maybe that's just because the person's high you know that they're experiencing this intoxication so my response to that would be well actually you know 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's about four hours for ketamine so at the 24 hour time point there's really no ketamine left in the body at all so ketamine's gone they haven't been high for you know 20 2022 hours so they're not high anymore the ketamine's entirely left the body but they're still not depressed and then what that shows is that the ketamine has changed something in their brain so there's caused some kind of functional change in the brain and that suggests and to move them from a depressed to a non-depressed state so that's really interesting that there's kind of like a switch in there that actually can be clicked and this ketamine's obviously working on some kind of target that can flick that switch and that understanding what that is scientifically is really interesting and 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 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 very cute example friend of


The durability of antidepressant effects. (16:20)

mine in law enforcement who was suicidal he had acute suicidal ideation and many people in law enforcement or in the military pilots would be another category are very hesitant to admit to any type of mental challenges or to seek treatment because it can result in leaves of absence and basically penalties professionally speaking and ketamine did exert those rapid effects and again not to say that this should be the expectation for every patient but there are people who i know who go in acutely suicidal and have come out literally saying i don't know what i was so upset about i don't know how i was so concerned about x y 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 triptamine class and we probably won't get into the phenethylamines and mesculine and mda and so on which which can be very different in some of their subjective effects but if we just if we're looking at say l_s_d_ syllisibon 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 rolling griffiths from john's hopkins medicine who's done a lot of work with syllisibon and also john crystal at eel who's done a lot of work with ketamine and in a rolling perspective was that he thinks a lot of the durability of anti-depression effects six months 12 months to follow up let's just say have a lot to do with a change in content meaning that people are actually able not just to suppress the symptoms of depression but to address some of the kind of root narratives that are leading to depression 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 anti-depressant response that we see to a ketamine infusion you know that will last any you know in our experiences anywhere from a day or two to a couple of weeks two months whereas the data for like sort of siren that seems to indicate the like months half a year year long anti-depressant responses but i think it just kind of falls into the we don't know pile from a data perspective because the models that have been used the experiments have been done between ketamine versus the classical psychedelics have been really different in terms of the therapeutic approaches tried so when people have been doing these cytosybine 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 because that you know you just read these headlines are you know cytosybine improved depression well actually it's not just cytosybine it's the fact that the person's gone into the psychotherapy regimen you know with the 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 one cytosybine course so it's not just the drug alone it's psyched out assisted psychotherapy now whereas the model for ketamine that's mostly being used is basically and where it seems to be using your flavor was that people just go into a ketamine clinic and they smash in infusion for an hour and they go away and there hasn't really been much studies where people have actually done ketamine assisted psychotherapy and tried to what what if we do 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 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 them the man in the middle or or strip back side of sibin to just side of sibin 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 are um so something like psilocybin is very powerful in terms of psilocybin dnt i see these very powerful psychological effects and they can be destabilizing for people so people need to be well prepared that they're going to experience very unusual profound potentially disturbing things and to not provide that preparation might be not be ethical to strip it back to nothing what is done for ketamine right 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 in a very fertile nascent period of psychedelic research and even though studies were


How Suresh picks the focus of his research (example: LSD microdosing). (21:45)

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 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'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 so i had returned to New Zealand in 2015 and having previously done classical side calisto i went and i started my research group here i thought well this will start with ketamine because it's approved it'll be reasonably 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 the new guy coming to town wanting to do LSD is probably going to fluffle a few more feathers around the faculty i would have thought back in those days but having sort of built a bit of a reputation i decided it was time to get back into doing some classical psychedelic research now the micro dosing specifically was well yeah no one had really looked at micro dosing in a RCT at that point and it's a randomized control trial randomized control trial and i guess this should we explain what micro dosing is maybe first why don't you explain what that is and it also might segue into one of the design challenges meaning cebo control yeah psychedelics 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 be tripping so you know people might trip on like you know 150 micro grams LSD but from micro dosing might take 10 micrograms say so about a tenth and it causes well we don't really know exactly what it causes 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 micro doses maybe every third day is the most common schedule that's called this was popularized by James Fademan who wrote a book in 2011 and it's really taken off since then you know like


Why New Zealand is unique for fostering psychedelic innovation. (24:43)

before 2011 not many people were doing it and there was really not much consciousness about it but now we're seeing hundreds of thousands probably of people around the world now micro dosing you look at the size of the red up 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 would just run a proper RCT proper randomized control trial of micro dosing a psychedelic then you have to prescribe a class A substance a scheduling 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 could be 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 all New Zealand so as I was as you do every now and then read the reading the misuse of drugs regulations from 1977 and the misuse of drug tech that goes along with it we're kind of discovered this loophole I don't know if you call it a loophole where actually we are allowed to prescribe class A substances it's not you've already 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 this could be done and so we did it and we applied to them and got the appropriate approvals from ministry various parts of the ministry to do it and that allowed us to run the study that with just finished collecting data for which was to give 80 healthy volunteers the 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 do 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 130 140 30 micrograms to take home so that they couldn't just stack them well 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 pricked with needles and blood taken and all sorts of stuff right things hours and hours there are a lot more efficient ways to get those as well as taking oh for sure 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 to particle and a part of the reason that i've been engaging with science in New Zealand is precisely for this reason i mean you have on some levels a very agile ecosystem compared to the United States and you have legislation that would allow you to even consider designing a study like this could you speak to how New Zealand can or does foster scientific and research innovation you could speak to certainly what you've already mentioned any regulatory differences but what else makes New Zealand unique what else could make New Zealand unique and we can go from there i would love to hear what else is happening in New Zealand that you find interesting from a scientific standpoint in this domain but let's begin with how does or how can New Zealand foster scientific and research innovation we have a strong regulatory environment so i'm not saying our regulatory 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 are sensible and polite and appropriate you can ask questions and and get things to move so with small size i think does come agility and 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 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 so that's attractive 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 it is so by comparison and where we risk falling behind by a comparison Australia they created a 15 million dollar fund specifically for these sort of breakthrough mental health therapeutics to kind of prime the pump because you do need a certain amount of capacity you need a certain amount of infrastructure you need people so they've set that up as a pump priming exercise really to sort of provide all the capability and 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 are 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


How could New Zealand improve the impact of scientific research? (31:01)

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 a 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 yeah and there's actually some there's actually some data on that and actually what we've seen and not just psychobics just mental health in general has been underfunded and you zone for very mental health research or alone little-owned treatment services mental health research has been underfunded and you zone relative to the burden of disease that we see in the country so there are some parts things like neurology has been relatively speaking overfunded and we 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 the population this can be quantified using um disability adjusted life years and you can look at research income relative to disability 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 psychobics but mental health research to make sure that we're giving 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 break through therapy designation and I ask because the FDA here in the US has granted both psilocybin and MDMA assisted psychotherapy break through 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 I think the latter would be the way to go so I think in terms of things like breakthrough designation we don't have we in New Zealand sit at the end of the pipeline for when treatments come because the way our treatments come is you know an international pharmaceutical company will apply for registration here and they'll use all the data basically they've submitted to the FDA so you know once I'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 kind of at the back end of that kind of process here and that's why we have in New Zealand sadly a relatively weak pharmacopoeia where a lot of drugs that are available in the US or you're unavailable here because they're just not marketed because we're a small market so I don't see that the that first approach where but the second approach could certainly work where you know the government sets aside a little bit probably going through legislation with direct one of its funding bodies to sort of you know to say and it does this for other areas of research says okay let's let's fund this let's fund this things like growing up in New Zealand so New Zealand has a really good history of funding longitudinal research so there's the Dunedin study and the Christchurch study and now growing up in New Zealand we've got really strong longitudinal studies that have been going on for like 40-50 years that have been centrally funded that would be a mechanism that could certainly work yeah I'm very excited about New Zealand as the the tip of the spear


Inspiring research currently underway in New Zealand. (35:13)

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 levels similar to the way that large global brands in some cases even though you might be last in line or at the back of the line for certain types of say global drugs that are available elsewhere you also have companies like I want to say Adidas and Nike and so on who will actually do pilot studies and launches in New Zealand because you have sort of all of the ingredients for English speaking first world country with incredible research faculties and I mean in this particular application they're looking at commercial interest but you can pilot and run experiments on a small or longitudinal basis that you can then apply elsewhere which I think is incredible so it's a huge gift that New Zealand also has to offer the world in a sense who are other scientific inspirations inside of New Zealand are there other scientists who you think are doing particularly interesting work could be limited to psychedelics or adjacent compounds or could be applied really really anywhere else yeah well you know there's a museum has a rich biomedical tradition so yeah I work in a general medical faculty so the people sitting mixed in me are doing you know cancer research or you know so we have a really amazing people doing work in place in Auckland called the Liggins Institute where they're doing work on pre-term babies and they do really amazing interventional work there there's also really strong stroke research happening using looking at how stroke recovery research is doing really well in New Zealand and down in a tiger I really like the group down there that are doing in the more psychedelic space they're doing all glues been doing a huge amount of work with ketamine and in various ketamine analogs that 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 happening down there at a tiger 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 I began and nor I began and so on which certainly makes them more interesting to study but what is academy and analog and


Obstacles to getting ketamine labeled as an antidepressant. (37:40)

are there any analogs or approaches to analogs that you find particularly interesting maybe it's not an analog one of the things is they've been having nothing like slow release formulations as as one way to go right to see if they and this comes back to that cornea issue about with ketamine like how important is actually having this psychedelic experience but if maybe 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 as a New Zealand company who have been looking at that is Douglas pharmaceuticals who have been looking at this kind of slow release ketamine that's quite interesting and then there's different companies overseas as well looking at 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 part of ketamine and put that in nasal spray and so that they could this is just bravado yes bravado and this is essentially a marketing exercise right like there's no it doesn't seem that it doesn't have any more efficacy than normal ketamine 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 yeah well bravo USD something like I mean in New Zealand there's been even bigger the differential because in New Zealand receiving ketamine is far-macked subsidized so we can get a vial of ketamine for like twenty dollars or something but of course this bravado 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's off-labeled treatment and because it's a controlled substance people you know there are clinicians that get you know answer 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 no reason ketamine is not probably is because it's because it's a generic compound like guess this is a sort of background and how medicines get approved as you need a company to sponsor the research that go to in New Zealand to go to mid-safe and say look here 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 basic any generic computer can just come and make more ketamine and sell it instead so there's no return on investment to be had there with intellectual property yeah 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


Ketamine research by University of Otago’s Professor Paul Glue. (40:39)

at he's been going to slow release work the other thing he's been looking at is other internalizing disorders so he's done a lot of work looking at ketamine and anxiety disorder so and this starting to build up quite a bit evidence based that ketamine might not just have efficacy in depression but in a range of sort of rumin internalizing disorders so I think he's done anxiety and social anxiety so ketamine seems to have therapeutic effects beyond just the category of depression these are all kind of these list data on these at the moment so there's you would be even more reluctant to prescribe our flavor for those things where there's a small evidence base but there is an emerging even space that other things and Paul's 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 you know some of it would be contested like the importance of the default mode network and the down regulation of such in


Future studies Suresh would like to see (and their challenges). (41:48)

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 please the DSM for insurance 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 whatever the latest rephrase of that is alcohol use disorder right otherwise known as alcoholism etc etc 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's like delta or panacea at all that's not the point I'm making but that from opiate use disorder to anorexia nervosa to OCD to chronic anxiety there may be shared characteristics such as a rigidity in thought looping or patterning that are interrupted by these tools which then provide a window of plasticity within which you can do very very interesting things which then begs the question that we were discussing a little earlier of how much the therapeutic wrapper impacts the clinical outcomes so if you're heating up the clay so to speak and adding some moisture by using these compounds 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 and various chemicals that produce dendrite growth part of why this whole field is so exciting to me is because there's still so many open questions the answers to which have just supremely potentially important ramifications are there any particular studies that you would like to do or see done in the near future in the next few years this so you know this endless possibilities you know like we're any of 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 has 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 we're looking and people will know this might know this history that in the 1960s when this research started slowing down early 1960s you know there was promising signals but everything just stopped for like almost 50 years and so we were 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 going to take a while before you 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 the first problem we have this diagnosis right we unlike for mental health they're really thing to be aware I was unlike cardiology or cancer right we can't just like stick someone get an eco-cardiogram done and realize I've got some kind of thing going wrong with their heart some regurgitation or valving or whatever it is or we can't measure a tumor size and know how you this is it so the physician is based entirely basically putting aside some organic issues the diagnosis is basically just subjective reports of symptoms and the diagnostic categories are completely 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 a only a partial knowledge of what it's actually doing in the body and then actually out how we actually measure the clinical responses also kind of woolly because we have to use these kind of subjective scales you know like how are you feeling and 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 future dish you know that's uh or tumor growth so we have a long way to go to harden up the science but to answer your question was specifically the interventions and cells 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 what is the actual requirements there to get because you will have no shortage of case reports like you'd see the people that just took side-of-siding by themselves and said I yeah I started feeling better and would know like thing not I'm not saying you should do any what you do that by the way but just uh people report that of course at the same time people report taking side-of-siding 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 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 collect yeah absolutely so I want to add just a little bit of commentary for people you don't have the history so you mentioned the prohibition meaning the banning of common use of 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


Challenges And Concerns In Psychedelic Research

The difficulty of applying placebo controls to psychedelic research. (47:25)

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 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 LD50 so the dose at which 50 percent of a given subset of the population would be expected to die of overdose for these compounds you have incredibly high if not unknown ceilings for a lot of them 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 the rate of ER admission emergency room admissions for acetaminophen is through the roof it's got to be top 10 that is not to say that there are not significant psychological implications particularly for those who are generally going to be excluded by study criteria like those with family history of schizophrenia and we're going to jump into 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 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 going to be expectancy effects and generally people are going to come in knowing on some level what psychedelics are or believing that they do and having done some reading and so on right so you have placebo effects 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 placebo controls and 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 the LSD microdosing before we wanted to rent for in the community we wanted a inactive control so that when we looked 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 how is whether people are you know able to detect the effects summer summer so we are around the threshold this was at around 10 micrograms yes about 10 micrograms in male volunteers so 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 we may need to start looking at lightly active placebos because we're now interested in the clinical outcome not just sort of like can't do it what do people experience if we're wanting to kind of try to fool people a bit better then probably some kind of light placebo the little bit of I wouldn't say deception but just ambiguity and 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 it some way and we're working on it 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 right in and of itself I've written the whole mess of paper 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 shortlist for potential active placebo is it would you would use in such a case niacin nice and nice and nice and it's not a great option that's yeah a vitamin so actually niacin was used in the 1960s and has been determined even in 1960 that niacin is a poor control for the side of some but people you still use it for some reason and I'm not sure why skin flushing maybe subtype of subjective experience so that people think it's doing something yes so we added to a lot of dietary supplements as well just 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 clinical trials is really important to prevent expectancy since it's because if a person goes into a clinical trial thinking they're going to get side-aside and they do get side-aside and if they think it might make them better they work out that they've had it and they go and maybe they're over it's an insuite over accentuate cyclical response which we would call a compound 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 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 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 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 dissimilar it's a really exciting time to be for me certainly observing watching to the extent that I can supporting the ecosystem in 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 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 any questions for us I think we have quite a we do actually yeah we've got a heaps of questions here what I'm going to do those resources 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


Getting the public to benefit from this research in a timely manner. (54:49)

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 so 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 start paying attention and for them to take the attitude that we can be at the fourth in New Zealand we can be at the forefront of this and we already are like we're way batting above our in terms of like us being this tiny little country that's back into the world we are batting way above our way 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 the space for a long time it's deeply affected my life and the lives of many I know and the science is important at the end of the day to push the ball forward so whether with you at University of Auckland or at University of Otago there are some interesting things happening in New Zealand are there any recommendations you might have for people who would like to consider supporting philanthropically uh yes in terms of philanthropic sport the best thing is to get in touch with either myself or Paul we don't we're not top secret uh things and you know 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 to establish 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 you apply for a grant this and then the grant people so when 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 go to your grant later right so philanthropic money can also be seen as a seed not just as you're funding the whole thing but as a seed for future investment so definitely yeah that's 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. Yeah Michelle do you have more I'm sure you do.


Risks of microdosing and relying on unregulated supplies. (58:17)

I do yeah so this one what are the risks of micro dosing so if it's patients that have diagnosed with bipolar or schizophrenia so they're not looking for a medical advice but just any general commentary about how safe that is it and is it dangerous. We have a data set 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 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 good at it 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 potentially the biggest was 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 24 or 48 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 and 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 sir Ash please correct me if I'm getting this wrong but you've got let's just say milligrams which are a thousandth of a gram my right so far yeah milligrams of 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 millions of a gram even the Albert Hoffman is 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 miss dose 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 micro dose 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 know these are absolutely true that the non physiological risks are probably far greater than the physiological risks and even though law enforcement deals with things like casual sea class was like cannabis relatively lightly these days actually they're not so forgiving with scheduled one substances so that is important to bear in mind and I forget often you know that you're right so you're right again that's the purity of supply and dosing I mean I forget this because we have I like to say the best LSD in town in my lab but joking aside yeah like illicitly in pain dalisty or suicide and could be coupled other things it's very hard to know but we do have drug tricking services and you saw them 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


Open science replication crises. (01:02:21)

that are doing studies themselves and say to ron toman in 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 were you be sharing your data or you be keeping it private so it depends on the study and it depends what you try and do so open science is admirable and it's good but it's not always possible depending on you know who's syresh 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 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 ced company so you know i'm generally in favor but i think we do end up with open science of having a lot of data in the world but no interpretive framework we can all do thousands of experiments and release terabytes and petabytes 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 deep etheric or understanding of what's going on 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


Training clinical personnel in new science as it becomes available. (01:03:56)

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 step there are number of concurrent experiments being right so in the united states a lot of eyes are on organ and within the state of Oregon 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 cystic therapies so that is a very live question for the state of Oregon so i'd encourage people to watch that very closely on a political medical level also you know my foundation so the cySA foundation saisai sai foundation.org for people who are interested has also participated in funding a joint program which is focused on psychiatry and this is at Hopkins NYU Yale and possibly a few other institutions i apologize and i'm forgetting where and i'm going to get some of the details wrong here but in effect a certification program is being created that can be applied into this funnel which already exists and that is the sort of psychiatry and de-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 mds or mdphds 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 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 the 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 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 challenging road ahead but there are experiments being done and people can see some of them at the foundation website and now is there a way this has been museum does is there a way that we can access psychedelic therapy microdosing now or how far not certainly not now 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 microdosing are still the microdosing particularly has got a long way to go that's going to be two to five year probably it's on a three to five year


Where can New Zealanders access psychedelic therapy now? (01:07:20)

track to to progress that depending on how the results look but I think the first thing that's going to come down the pipeline if anything will be the MDMA assisted therapy because that's the most advanced psychotherapist PTSD sets 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 our regulator were to improve it which would invariably have an after if the a if that were to be approved there so we have that and that might be on your couple years away and 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 the 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 an NDMT five MEODMT, Iowaska and every other compound you can imagine


Research Directions And Inclusion In Psychedelic Studies

Avoiding another 50 years of psychedelic research darkness. (01:08:25)

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 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 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 it's slow as smooth and smooth as 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 totally agree with that and you know why because 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 regulated things and you thin all these horror stories start emerging into the popular consciousness and then we put ourselves 50 years back in the hole again so I think that's what we really need to avoid with this so treating really carefully but hopefully that won't happen because we do have a stronger regulatory environment and then it 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. I mean not to paint a bleak picture but it's just like hey 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 60s and the generational differences no longer exist and there's bipartisan support etc but politicians have certain sets of incentives and I would really say that 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 5m eo dm t in fill in the blank location right not to throw 5m eo dm t 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 people involved which is why the decisive foundations 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 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 is just last 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 is purported to have this much promise and certainly anything that has as 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


Is any of Suresh’s research focused on addiction recovery? (01:13:08)

to talk about a project that will be more mari based intervention that we run by mari researchers and we're just in the very beginning stages of staying 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 there's something we're not leaving that we're just providing support for in terms of intellectual support and learning how to navigate the regulatory system on this stuff so that could be really interesting and there are elements of for example spirituality that have some synergy with mari culture that would be interesting for those researchers to explore so just on that a little bit then what about any included woman in studies or something mostly males we had this one LSD micro-resing study where was males only because we I won't say it was pitched 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


Why women haven’t been as widely included in these studies as men. (01:14:08)

there was also an instal-cry cycle compounds 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 i've taken a lot of flak for this and and i see my response is where you try and like get this study approved of like because I spent years aging trying to get this thing approved um so you know we did the best that we can while we could and we always hope to do better but certainly um well other studies have included females and the next studies will um 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 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 being instrumental disfark disorder people have been using it for that and that it might affect actual menstrual cycles and neutral cycle timing so that's actually quite an interesting there's potentially interesting separate studies to be done there that we have considered and will 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 assess 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 know you learn but uh a university degree i'm just promoting the university walking


Where aspiring psychedelic researchers should focus their education. (01:15:56)

because it's my employer who pays the bills but uh you know the young people getting a science degree or health sciences degree um medicine and psychology those are 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 psychiatrists and psychologists that are going to run this i suspect that that will be where things fall so if you wanted to get into being able to prescribe or be involved in this kind of therapy i think psychology and psychiatry and general medicine are the places to study 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 and just going to go into one of our um corporates so have you looked into the clinical trials of the larger public companies so this mind me compass atai and numerous and do you feel there any red flags and how these are current corporations are going about proving their respective drugs so that's like alipathy in dma yes and i should say is a disclosure that i consult for some these companies as a disclosure so and actually collaborating


Red flags in the private sector. (01:17:02)

with one of them so my observations is that the people that these companies are employing are really seem to be really experienced farmers' suitable people have a lot of industry experience of 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 you know these are generic medicines is is going to be an issue but there's red flags within 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 but i'm comfortable 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 sresh 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 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 and justifies the rnd 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 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 kara turnball and that is an area that will be increasingly active mason marks and i glenn coen i period glenn coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen coen co author to 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 christians actually take your spot all right well well fantastic thank you so much everybody and thank you so much suresh for for making the time i'm very excited to see what you do next cool thank you good thanks team i'll just close us off for the karaokea it's been a great session today


Closing Remarks

Parting thoughts. (01:20:14)

and then hopefully this will sit you on the rest of your way kia tote rangamaria or te rangi nue eta ejome or papanuku eta korne or tate ona ahi nae korunga eta totato tate ota tihai mori ota kia ota tae thank you kiki te and enjoy the recidio eta ejend korte hey guys this is tim again just one more thing before you take off and that is five bullet friday would you enjoy getting a short email from me every friday that provides a little fun before the weekend between one and a half and two million people subscribe to my free newsletter my super short newsletter called five bullet friday easy to sign up easy to cancel it is basically a half page that i send out every friday to share the coolest things i've found or discovered or have started exploring over that week kind of like my diary of cool things it often includes articles i'm reading books i'm reading albums perhaps gadgets gizmos all sorts of tech tricks and so on they get sent to me by my friends including a lot of podcast guests and these strange esoteric things end up in my field and then i test them and then i share them with you so if that sounds fun again it's very short a little tiny bite of goodness before you head off for the weekend something to think about if you'd like to try it out just go to tim.blog/fryne type that into your browser tim.blog/fryne drop in your email and you'll get the very next one thanks for listening you you you


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