Dr David Erritzoe

[Music] Hello and welcome to the midpoint. We've got something a little bit different today. I've been fascinated by the increase in the noise around the use of psychedelics for mental health issues for a while now, while not knowing anything about it. It really is outside of my comfort zone. But late last year I was made aware of Dr David Arutso and the work he's doing in this space. He's a clinical reader in psychopharmacology and psychiatry at Imperial College London and the CNWL Mental Health NHS Foundation Trust. And since David arrived at Imperial in 2009, he's conducted and overseeing clinical and neuro-imaging trials into the treatment of disorders and addictions using psychedelics and has authored 145 peer reviewed scientific papers and five book chapters. So I feel we have the right person here to tell us all we need to know about this growing area of medicine. So let's go meet David. Dr David Arutso, welcome to the midpoint. Thank you so much. You've just revealed as you walked in that you've come fresh from Davos, which I think actually tells us and I said in the introduction the increasing noise around psychedelics. I think that tells us everything we need to know about the direction of travel of psychedelics in the mainstream. If you're if you're invited to talk at Davos then at least just in a psych programme but still quite a lot of yeah for airtime down there for what we're doing. Because the money men must see there's an opportunity here right? Yeah thanks so. So also in your introduction say I know nothing about psychedelics. I've never done them but I also am probably one of those people that needs a few myths busting about them. So I hear the noise and I hear the good work that potentially is being done in terms of mental health issues and addictions but don't understand how they work. So we've got a lot to get into. Yeah that's good. Tell us how you started in this area and what drew you in. So I came from medicine and neuroscience and during my PhD 20 years ago I came in a bit of a boring nerdy way because the the place I was trained they were very good at methods to understand the brain serotonin system in particular and I got interested in the biology behind addiction because it's there's a lot you can actually understand from the brain about addiction then the methods we had available were actually on the side of that and therefore when it came to drugs to understand impacts on the brain in that system the drugs that are very active there and working that system are psychedelics and MDME and therefore I ended up pursuing trying to understand the effects of those drugs. In the beginning it was about the impacts of you know recreational use of the drugs and then when I moved after my PhD here to London to Imperial College the colleagues there were planning work to try to understand the drug when we gave the drugs that I've just tried to understand the impacts of people using them then tried to see what they do to the brain and looking back in history and the knowledge already existing a lot of wisdom there around these compounds how they can be beneficial so then it sort of took that direction not just us also Johns Hopkins and a few other places were pursuing that so it was an early opening of this new era of interest in psychedelics. When you mention the recreational use we think back to kind of the 1970s in particular late 60s 70s and the association with the hippie movement and people going on trips that could last days you know that we usually using mushrooms or kind of things like that so is that what you're talking about when you say recreational use? Yeah I mean apart from one myth we can shoot down that mushroom experience last maybe four or five hours not days right. It is deep bit long up still not days unless you keep on taking it and if you do it they actually don't work you very quickly get tolerant so it doesn't really work if you take them days in a row so it's not days that people were tripping on these drugs but yeah there was a big sort of counter-culture in the Western world using these drugs and having great communities and experiences and and use them for some of the things that are actually therapeutically relevant also for the development we're in now and there were also in that era in the 50s and 60s 40,000 people patients are so being treated by clinicians with these treatments and then worn drugs late 60s around 1970s new new and conventions nixon worn drug counter-culture also impacting into perception around Vietnam war so there are a lot of reasons why they were pretty demonized and a lot of myths were also in the interest of some people to create and and therefore got pretty bad names and and which also in a way informed somewhat why we focused on the mushroom compound called psilocybin instead of elistice because everybody knows and let's say 20 years ago super stigmatized elistice where psilocybin nobody could spell up her nouns so there was a psilocybin psilocybin okay and that's the mushroom compound yeah so are the psychedelics that you're dealing with and the research you are looking into and have done and all the papers just dealing pretty much with mushrooms is that what you're focused on? the most of what we have been doing in our team is on psilocybin absolutely so it's not actually necessarily coming from the mushrooms yeah you can synthesize it some of the new trials we're doing it actually has been extracted and purified so it actually comes from mushroom but we're not giving the mushrooms it's difficult in drug development because of all the other things in the mushrooms it needs to be quite pure for us to be sure that we know what we're testing exactly and get it through these processes and approval processes to so we work with a pure compounds but we also do work with a DMT which is another classic psychedelic related to psilocybin that's the one that people have might have heard about or maybe not heard about that name but it's the psychedelic active compound in the amazonian brew called ayahuasca that has thousands of years of cultural, ceremonial, shamanistic use so the psychedelic from there is that also comes from nature like psilocybin as DMT and then a third one five amoeo DMT comes from the toxin in a toad and that one we have also done a bit of work with but for the sort of clinical studies and people suffering mental health conditions most of what we have been doing is with psilocybin we have also done work with a list DMT may and kids men but mainly psilocybin so in terms of the mental health issues that you're looking at and addictions what are you what are you coming to the kind of conclusion of in all the work that you've done in terms of how effective they can be and is there a specific area of mental health where you're getting better results than others so you know bringing this field back us and others not not that many actually 20 years ago you know you we we needed to make some decisions of what compound to focus also how to give it to to be given intravenously or through the mouth with psilocybin or should a BLSD and and what indication once we had done the initial work got it familiar with the experience that people are having and and the effects and the safety and the dosing and also some the imaging work that we did in people without any mental health indication to understand the drugs and how they work and what is the brain signature of these experiences that had never been on before because in the first era we didn't have the scanners when say we so you would look first of all at somebody who had a healthy brain and a good mental health I heard it actually endeavours the colleagues said near normal which might be a nice okay near normal near normal brain yeah so you would be able to see the effects of the drugs on the brain literally through through scanning yeah exactly and some of what we saw there added to the list of good reasons to consider taking it in the direction of depression and so that is what we decided to do so we did the first study in modern time with any psychedelic for a group of people with depression and and so really good results that was not a perfectly designed trial there was a proof of concept you can make trials more complex and sophisticated and this one was an early proof of concept to see if we could do this safely and what came out of it and also with brain imaging again and we did that and in a way then that was taken forward by others and there were new companies forming in the space and they have then accelerated that development take that further and don the next lines of next line of trials and now it's in the late to the final phase of testing in patients so that means the psilocybin is the most advanced one for mental health in the case and that is for depression treatment resistant depression meaning nothing else has worked yeah I mean not nothing else but they have tried a couple of conventional approved treatment and sufficient dose and duration and so on and if they still suffer with the depression which we already know that there's quite a large group doing then they can enter that trial and that trial is is completing and in follow up and that's not us doing it but that came from the early work the early work So when you say completing, so I know it takes a long time, doesn't it, to get a medicine on the shelves and for a doctor to be able to prescribe it? How far away is that trial from that stage? I think already in a year it might be filed around that time to the FDA. The focus always typically is on America due to the market and then other markets and regulatory bodies to send in the data for considering approval will happen. In the UK and Europe after that. So already and then they take a while to consider the data and so on. So it could happen during 27 with Silocybin. MDMA which is not a classic psychedelic, some more a typical psychedelic but very, very fascinating, interesting compound. We have not done that much with it but just to put that in there. The trials were completed, it was filed and now it has been rejected initially and more work needs to be done with MDMA. So that several of them might end up coming quite close to each other and that's for PTSD with MDMA. Right. So can you explain how it's actually working and in terms of how it's rewiring neural pathways, is it changing the structure of the brain forever or is this something that something is going to be on for the rest of their life? Yeah. So I think an important detail for people who are not that familiar with these drugs. The model that the paradigm is really different from giving a person a tablet, let's conventional antidepressant medication, SSRIs that is used for a lot of indications. People take them daily for a long time. Silocybin and the other classic psychedelics, they are framed and packaged into therapeutic context. And given very, very few times. So it's a single standing session or a few where you are under the influence of this drug after having been psychologically prepared by the team and then supported, guided, supported through it and then some psychological integration work. So what's happening in that period of time then when you've taken the drug? In the session where you actually take the drug, then you feel the experience of the drug and it's not very easy to predict what comes up because they are sort of access into your deep psyche in a way that's also what the word psychedelic mean, mind, soul revealing or manifesting. So things come up, deep psychological materials can be interrelational, it can be trauma, it can be beauty, it can also be more spiritual bliss type, renovations, reframing, often as profound. But really has been a theme when we do interviews and get people's stories, people's narratives for what happened and what was helpful for them. A theme is that people often out of these sessions change from a degree of avoidance, which is a big thing in any mental health condition, which also speaks to why they might work across. Things are so difficult that you can't really approach and work with it and face it and some of that often on a psychedelic afterwards goes in the direction of some degree acceptance and coming to terms and its settles and also. And that's a permanent stake then. In these trials, let's not make them absolutely too amazing and magic bullets. That's what I mean, is it something that you've still got to that person has then still got to have therapy to work through that? That's the way we use them, that's the way the paradigm has been and also back in the days used when it was used thoughtfully, safely. But it doesn't mean that people who have a psychedelic experience can't really get a lot out of it without any psychological packet. They often can, but then the risk is also that it can be overwhelming, challenging, psychologically and difficult and maybe end up being disturbing for the person. So therefore that whole embedding in thoughtful therapeutic processes and efforts and support we believe is the right way of using these drugs in a responsible way. And that's why we do it like that. And also if you have all these insights and opportunities for some positive meaningful change, whether it's lifestyle, psychological reframing, so deep psychological processes that come in order to really get max out of them and use them fruitfully and also work safely, thoughtfully with person, people, therapists to spot you. Then that work after integrating it and finding out how to integrate it into your life to move in a better direction, to break habits. And that's where addictions can play as well. Absolutely. And because a lot of mental health, whether it is depression, anxiety, also PTSD, even eating disorder, OCD, and those are all and then addictions, all conditions that we are investigating with these compounds. And there are some shed features in these were things psychedelics are incredibly interesting and powerful. So this feeling of being trapped, this feeling of being stuck is very classic, no matter who you speak to, who really suffer from a mental health condition, no matter which one of them in different ways. And also very sort of negative bias, then a bit inverted into your own life and lack the connection to others and what happens around you and being part of something bigger, a bit like 12 step kind of thinking, some higher power or being more connected. And psychedelics, one of the absolutely key features that people very often express very clearly is the profound sense of being connected, can be to others, can be to your own more emotional life. The difficulties and the beauties, but also even nature, even the universe and that we are, and also this transcendence that we are part of something that goes forth and back through time and space and that sounds very spiritual, but that is really very classic with these. And as you point out, that's kind of the thinking of the 12 steps isn't it in terms of being part of something greater than yourself. Yeah, which an interestingly sorry, Wilson, one of the founders of of AA program the 12 step, he recovered himself after having tried a thing a number of times, then he had an altered state of experience with a compound, not any of these ones, but and and that really really helped him and that made him recover and maintain abstence. And there were discussions between him and others early on about integrating psychedelics into the children program because it actually fits really well, but that that was not that will receive those. See much more difficult to grow 12 steps as they did, wouldn't it, if it was at the time, if they'd had to. In a very stigma type. Yeah, yeah, and so immediately my kind of thought is, well, if you've got somebody who has got some addictions, why would they not become addicted to the feeling they're getting when they take the compound? Yeah, that's a meaningful and also very logical question. I mean, it's because they are not euphoric, pleasant, easy experiences. And also due to some of the pharmacology, these drugs work very specifically in the serotonin system of the brain. The drugs that people get addicted to typically work in the dopamine system, opiod system of the brain, all the others you can think of that, that you know that people can get in trouble with. Yeah, these drugs are very, very different and they do not form addiction. They do not push people out addiction. And you may tiny bit more, but it's also a little bit different pharmacology. And then you have ketamine that's also related compound, but have more likelihood different pharmacology with some downstream effects on the brain that are overlapping with the classic psychedelics. But that also has more risk of people becoming addicted. Still a very interesting, also therapeutically very interesting compound. But the classic psychedelics do not really, they don't get people dependent. It's not that you seek a rush after. It's not that it hijacks your brain's reward circuits like some of the others do. Often actually people say that they don't need an experience, except that was tested early on. That was for smoking cessation by our colleagues at Johns Hopkins. And they offered, I think, people a third experience with psilocybin and most people said they didn't really want that it's challenging. It's an effort. It's a lot of work. It's a lot of things that are brought to surface that you need to deal with and work with. And again, why we want to embed them in therapy. So from what you said there and before, then the people who are most likely to get a successful outcome will be very invested in there. This is not something that necessarily just going to be dished out by a GP at the first meeting of somebody having depression. No, not at all. And actually they're not likely to come. They're not going to come as first line treatment. Like very few things like in sort of it will be. But you know when you hear people kind of very glibly saying, well, they should be on antidepressants. They need to be on antidepressants. And apparently, you know, from people that I spoke to, they're not that hard to come by antidepressants. No. Increasing number of people in the world in the Western world on antidepressants. But this is not that. No, it's not going to rip. It's it's it's okay. It's it's as a sort of parallel thing about cognitive behavior. therapy. It's a relatively regimented, maybe 10, 12 sessions, kind of very manualized with some homework. And so if we compare normal, anti-depressant, like SSRISES to the, then the psychedex are more like deep analysis work. And if you look at who's getting what kind of talking therapy, most people are getting some CBT once in a while. So this is deeper, more complex, more invested work, and it will be done by people who are trained in it, and not prescribed to use at home. And that's the model. Of course, it's in the interest financially, and due to regulatory constraints as well for some of the companies, developing these new treatments to get rid of the talking therapy. And that's a big issue, because that is not the optimal and best way and also most effectful way and most safe way of using them without if you take all the psychology of the therapy away. But that's where the model, this paradigm struggled to fit perfectly into the existing structures, for how to get a new treatment, a new drug to market. This is a mix of talking therapy and pharmacology, and that is confusing for the system. It's not really the system's fault. They just regulated and consider drugs and not talking therapy. And this is a mixed model. Is it possible to describe what the brain looks like when somebody's having a psychedelic experience? Yeah. So not only from through development, from childhood and to adulthood, your brain through experience becomes more and more efficient, more and more connected, different parts of the brain need to be efficiently connected and work together in order to efficiently and quickly with minimal effort, solve tasks and understand and process inputs and so on. And if that is done in a sort of unfortunate way, maladaptive way through life experiences and you end up suffering with a mental health indication conditions, then some of these pathways are maybe not optimal. What happens in the psychedelic state acutely is that all that is shaking a little bit like a snow globe. If you imagine one of those because it's a closed system, it's not that anything adds to the brain, it's still the brain, but if you shake that and the snow falls, it might be that the little snowman or the Santa Claus in the snow dome has a path through the snow in a specific direction to get from A to B, from his little house over to the workshop making the Christmas present or whatever. And once it's really being shaken in the experience and then the snow gets up and falls down and then he can in a way take many different parts. So it allows for a bit of a reshape, remolding the brain becomes very flexible and moldable. And in a scan you can see, we can see the brain meshes of these phenomena. We can even see to continue with snow and now our brain into the mountains. So yeah, so if we instead of being in the snow that we are on in a big area with mountains, then there might be a path to ski down that you have used many time for and that's easiest to use, but after with the shake of the mountain you can go different directions, but to make it even more fascinating and this is maybe take the analogy far, but it's something we have brain data on that let's say you want to go from this area of this mountain chain to another one to another place. If the mountains are very tall and the valley is very deep, then you will have to take the easiest route and that will be the same route every time. And you're a bit constrained in how you can move across. It's complicated to get from A to B, but with this psychedelics also after the experience we can see that in a way the landscape is flattened. There's change to the hierarchy and there's a flattening to the landscape of the brain activity and that means that there's an opportunity to consider different paths. And all that comes on a foundation of brain plasticity. So a window or opportunity for the brain to reshape and reform and even sprout will some new synapses, some new connections. Most of that we know from animal work with psychedelics. We are heavily investigating as well as we can with the methods we have available in humans at the moment, but they are very powerful in inducing a very plastic biological plastic brain. And if you then have these profound experiences in such a plastic state and an ability to reshape a bit and take new paths, that is in a way how the site works. Hearing you describe that and that great analogy, I'm thinking about people who might have Alzheimer's earlier on set of dementia, those those kinds of mental illnesses and diseases. Would there be any impact at all that psychedelics might have on those kinds of brains? Yeah, it's a very different question. Your area of expertise, but it's hurt any work. Yeah, it is something that people are starting looking into. It's more in the sort of neurology side of things. The issue is that these experiences that can be very profound, very deep and also a little bit unbelievable at what comes up psychologically, your perceptions or visuals, all that is changing during these experiences. Giving that to a person who struggled to provide and send it, it's a bit of a possibly brutal thing to a person who is quite unwell with dementia, but very early stage, could you. Or those who are genetically predisposed that we now know, obviously, have a genetic link, would there be potential? Possibly. And could also be that you could do some maybe some tasking to in order to sort of train the brain and you might do that on some low doses of psychedelics to have that plasticity, the opportunity for the brain to improve, could potentially be improved by psychedelics, but there's not much yet in that direction. It's so far has mainly been in the mental health side that we have investigated, the field has been moving also because there's a yeah, also there, same file sound, but there is a lot coming file sound, it's been a lot of resource put in mental health, absolutely, under-pro-autized for many, many, many decades, completely out of portion to other fields of medicine, and there's a massive, underserved group of the population of patients with a lot of diseases, not even having any medication, that's also why we're for instance launching new trials and gambling disorder with psychedelics and also opioid use disorder, because of all the incredible horrible mortality, mortality and for government it has to also be an incentive to save money, doesn't it? So can you see a world in which the NHS is actually prescribing psychedelics and it's obviously saving money down the track because that's what you know, drug yeast ultimately comes down to, isn't it? It's a financial consideration for the government. Absolutely, in a way fair enough when you have ex-amount of money and you need to prioritise it, you need to do the health economics, but the suffering and the, I mean the mental health in case depression, the most prominent one in terms of burden of disease and also how much cost society, there's really a lot to gain, so I would put it the other way around, can we afford not to help people if we have something new and you paradigm that actually does look really, really promising, you also asked earlier that I didn't really address how they were, how efficient are they compared to what we have and it looks like a bit more efficient in terms of the health data for the different indications or typically more efficient than what we have right now, that's how it looks and that's why it's very exciting at the same time being a complicated new paradigm, but if you think about what you get, so if you just see the hard measures of let's say depression, that's one thing, think about all the addition, think we've already talked about, increased related connection to nature, increased connectedness in general, pro-social traits being pushed and enhanced, agreeableness, trait going up, openness, flexible psychological thinking, creativity and so on, there are so many things that the psychedelics also typically in our studies and other people's studies bring with them, that is kind of a bonus in a world that is going down in climate problems, having people more connected to nature, there's a lot of extra things that we do not regulate, us do not look at when they just need to look at the hard measures and do the health economics, but I would say we need to be able to fund such treatment paradigms to be implemented into healthcare including NHS and we are piloting stuff into NHS at the moment. Who's doing it best globally then? You're from Denmark originally, you study here, yeah, or you've done a majority of your study here and your papers, is there any other countries who are really leading the way in terms of integrating psychedelics? Yeah, there are, I would say the UK strong in the science development and the understanding of these drugs and early trials in the beginning, in period, but also now other great colleagues at other institutions in the UK. America always in there. But what has happened is that some countries have in a way stepped forward clinically by allowing early access, compassionate use clinically. And that those countries are Switzerland early on 2014 and then Australia, Canada, there are places where there's sort of gaps and gray zones where people can can use and provide these drugs. So I think to make a Costa Rica, there are a lot of people there offering. There's a gap in the law in Holland allowing psychedelic troubles to be used. But the healthcare wise, it's Canada, Australia and Switzerland. And now also check with public in Germany more recently that are changing and several states in the US. So it's more and more happening. We're learning a lot from those countries as well. I mean, in a way, we could. Yeah, we can. If data is collected, if they have good employees, then that'll be news national registries collecting data from real world use clinical use that then that is really important. That's something called phase four. So after the one, two, three clinical phases of testing on new compound, then it's out in reality. That in real world, that's actually what they kind of are doing before the phase three trials have been in a way. Yeah, even completed. And that I think is meaningful. I think it's okay. As long as you do it in a thoughtful way. And you monitor it and you used it understanding from what is to somebody's listening to this now and they're feeling quite desperate for themselves or somebody they love and they think this could be the way that they could help them all themselves. Is it possible in this country to go and save these psychedelics? Yeah, it is. But because humans have used these drugs and I'm not going to say just because we sit and do that people because they grow out in nature, you know, the sort of things that I mean, but doing it in a, you know, meaningful setup with clinicians and therapy that you can't do in the UK because they don't have that not decided to do what some of the other countries do with early access programs, compassion, just clinically, however, and this is actually my main thing and that is what we're piloting at the moment. There is a bit of a forgotten. Perfect solution to bridge the gap to serve the demand. Of patients asking for these treatments because they have read about them and heard about them and that's ketamine ketamine is already a medicine that has started as a medicine. It just used in physical health in intensive care for other indication also sedative and high doses if you use it in a lower dose. Is that in the present and actually also trials that show work for other indications such as alcohol use disorder that is worked on in the UK by exit to see the market stories though about ketamine in the news. Yeah, about ketamine addiction and ketamine being something that's being used as a recreational drug. So yeah, it's a complex door to. Yeah, yeah, it's a complex door, but that one does not rule out the other. If we were to for the first time introduce some kind of opiate to me, that's still incredibly useful if you're broke in your leg and your hospital doesn't mean that that's a really great idea to use a wildly every weekend. And you'll be dependent and is it the same company so somebody this weekend who is using ketamine in a recreational manner. Is that the same thing that you're talking about using is it the same compound? Yeah, it is. So a company did something to the compound chemically and then did all the trials put billions into it and developed it and had it approved also in the UK as a nasal spray formulation. That one, it has a license, it's expensive, not endorsed by nice guidelines for to work to use in the NHS really. So therefore it's not really available, but it has a license. It can be used, but the old version of it, which is kind of the same as people are taking the streets and the same as my clinical physical health colleagues use in all hospitals all over. And also if you drive out a doctor out to a traffic accident, ketamine is used there. But in the lower dose, same drug cost nothing. That should be and that is what we're piloting in a talking therapy model into NHS. That my big encourage is to put pressure on to do more of that because it will take a while before the others are there. What it will also not only will it give access for a very related model of treatment that is fully evidence based. There's tons of evidence for that. That catamine a series of of dosing sessions work and that it can be safely and meaningfully embedded in therapy similar to what we do with the cyber and MDMA. It would also serve an incredibly important purpose in addition to give access for patients and that is to prepare the system to find out how do we smartly without inventing and putting really clunky expensive, complete new treatment services into the NHS. How can we navigate what's already there, what training experience, what staffing, what care paths are there and that's what we are trying to do. What I'm struggling to understand there is how it has become such a apparently an insidious drug for young people hearing stories of blood or failure and people becoming seriously addicted to the same compound. Is it just dosage? It is. So if you use these drugs to help. Why are those kids using it, not having the psychedelic experience that you're talking about? Yeah, I understand that it is confusing. When the drugs are used, they're very, very context dependent on that one thing. If the model, the clinical model you're setting up has X number of treatments, like five sessions, that's what we are currently piloting. Every week embedded in 10 sessions of therapy and it's joined, joined between the talking therapy services and the NHS and us on the psychiatry side. We work together, joints of revision and so on. We're all co-thinking about and with this patient that we are trying to help. We implement behavioral activation, we're goal setting and so on into the model. It's a very contained supported model and people that are being offered the treatment like that in a clinical setting. They are motivated, they are working, taking agency and involved in their own recovery in such a model. They don't go out and do it completely out of context. They don't go out in recreation, they dose the drugs to have a fun time. It's a completely different user of the drug and people do not seem to seek it. I can't rule out that if you treat one million that won't be a few who will end up buying it in the street and be heavily dependent. That might be the case but we already know from the data. You wouldn't treat cataman addict with cataman. We could. Potentially, I don't think it has been done but possibly yeah, I know it's confusing. I would say that also you can say if you are 17 year old and you eat mushrooms with your friends and you run down the mall and have a funny giggly time. Is that therapeutic? Not probably not that much. They are very, very contested. When people say, "If you close your eyes and go inwards and use it in a setting, in a surrounding with the music, the blindfold, the therapeutic support, the preparations are going to. " Then you are using that drug in a very, very different way from if you go to a rave and take it. There is nothing wrong. You can say that's a political policy legal thing. Whether you think that's wrong and that's drug policy and you can discuss that. But it's not obviously the core of my expertise and field of work. But yeah, these drugs, if they are used out of hand, out of context and are too high doses, too frequently. People can be dependent outside of clinical care with the same compound. Again, a bit. Think about the opioids. If you have broken a leg or you have undergo surgery, it's not that everybody then run out and become addicted to her and after having been given when they need it in a specific way. This is even framed more safely because it's saved in a therapeutic frame. Right. We've got to think of it in that way. In a medicalized way. Almost catalyzed psychotherapy. More than a medical, yeah, it's medical. But it's way beyond just the biological agent to the brain. We use it for psychological work to catalyze that work. That I think is the best use of these compounds. They might, some of them come out in a very biological mold. The natal spray, very biological. But if you really want to use all the beauty of what these drugs can do to your mind, with your mind, for yourself, for reframing, they are best used together with talking to me. In terms of a near normal brain, we called it earlier on. What would the benefits, if any, would you ever come to a state where you'd say, "You know, you hear this, but everybody can benefit from therapy." Even an unphabetic person could benefit from that. Would everybody benefit from psychedelics? That I would categorize in no. Not everybody would, because there's no such thing. That's, I think, magical thinking that anywhere. But overall, we already know from studies in health, these many centers have done it. We have done it. That people overall benefit. There might be a couple who struggle. It might open up something that requires some psychological work after. Definitely. But overall, when we look at the data, we also have population data where we do surveys onto real world, without any clinical input, where we don't even meet the people, or sometimes we do trials where we give near normal psychedics. And do people, when we measure measures of psychological well-being, and defend. other interesting features in a near normal person, we do see improvements overall. So if they ask some people where it's tricky, then they sort of drown in the data because most people really benefit. And then the million dollar question is, is that something we should also then develop the drugs for? Right. Yeah. But is that not, I mean, you hear about microdosing and people doing their own kind of, you know, and you're smiling away there. What a draw. I've just been in demos, doing that. There's a lot of microdosing going on there. No, but there's a prominent, wonderful colleagues working also in marketers and whether it's pulse damage from North America. And we, you know, we have different views on the dates and the evidence for microdosing. So yes, a lot of people are microdosing. And there's a big industry around it as well. It's purely for recreational use or does it have any impact on their day-to-day cognitive function? What might take on it right now is that if you do a study really testing microdosing, you will get amazing improvements in all studies. However, when you bother to randomize people, meaning you allocate them to either the microdosing or to an inactive placebo condition, you test them and you make sure people don't know what they got. Then the data coming from the, the arm of the study that had the placebo typically suffocates the effect seen in the other arm. And that is what you need to do scientifically to understand whether it's a real effect or whether it could be driven by expectancy and placebo effects. And for microdosing specifically, which is not the same as what we just talked about with full doses, with an altered state of consciousness in a safe setting, the microdosing is a regular use, so sometimes a week for a longer period of tiny doses of the same drugs. They might give a little bit of plasticity and they could maybe be tested together with other inputs, could be mediation, talking therapy, lifestyle changes and so on. Those studies need to be done on its own. Does it work if you ignore the placebo arm and that regulators don't, medics don't, investors don't. So that means if you are individual and it helps you, even if it was all placebo, who cares? But it does for drug development and to get them into medicine. So I would, and it has been tested for a few mental health indications. There's an ADSD study with it is demigodosing, great improvement, but exactly the same in the placebo group, right? So microdosing is maybe not the hottest topic for psychedelics in terms of drug development and investments, but it's a big market outside of medicine. That's what makes acting as confusing because it exists. I'm going to ask you about the downside and the contraindicators that you've experienced, don't you've seen experienced? What would they be? So so far we have cautiously, when we try to take, understand, the people going into the trials, we take mental health and physical history, family history and so on. So people who have experienced psychosis, we have not included in the trial for caution. There are some data from the 5060s that could be very problematic to do. If part of what you are struggling with involves some degree of fragmentation to your sense of self, to your ego understanding and boundaries around the ego, then it might be destabilizing to in a way make that more fragmented in the state of a psychedelic, at least theoretically and with some data supported from the 5060s. Therefore, we have had that caution. That might not be the same with MDMA for instance, or for that matter, maybe ketamine, but we so there's these caution in autism, interesting, but that could possibly also at least theoretically maybe be a bit destabilizing. I'm sure it would be brilliant and helpful for some, but if you go for some indications, another example could be emotional unstable personality, where again, the bit the same thing with the sense of self, if you fragment that on top, it might be destabilizing. But I still think, and we have some data to support it from surveys, where we have follow people out in the real world, that it might still be helpful overall as a group, but they likely would have been being really tricky and challenging seems higher. It looks higher. Therefore, if you were to do such proper trials, at least do it with the experts who are really good at providing the right to poor and care for that specific group of patients in order to do such trials safely, and really monitor them as they are reacting, making worse for some people. So I think there are some caution in some directions, but the field will keep on moving and expanding, and hopefully we will be colleagues who are really cautious about, I'm sure it will be. Do you feel the myths have been busted, or do people still have quite negative preconceptions when you tell them what you're studying? You know what I think that acts as a science is helpful for moving this forward, also way outside of science, that as we understand more about how they work in the brain, when we see the trials that the safety data are convincing and the effects and the help that people feel and the improvements, that data that is being published, there's been covered by media including right now here, by you, that makes people shift a bit and that does break the stigma down, that as so many other things, although the ketamine story is really complex story to tell, it's not that black and white, and when people get better understanding of the nuances and the pros and cons and where it might be beneficial, where caution is really important, then these stigma is being reduced, and that's always healthy to put more nuance on to the story, and that will also mean that people will be re-creasing and we are seeing that more psychedelics. And just finally, if somebody has a severe addiction, and this is the way that they are led to hopefully cure or treat that addiction, because addicts tend to say their addicts for their rest of their lives don't know in terms of how they deal with it. How quickly do you see people turning their lives around? What's the kind of addiction? Specifically, we are doing these new trials, we're the gambling disorder, gambling disorder and opus use disorder at Imperial with therapy. So we haven't actually ourselves done a full addiction study, but the colleagues who have what you see in those trials is with like Samus and all other psychedelic studies, you have that profound experience. We can even see that measures of how profound that experience was and how rich and maybe spiritual mystical, it is the better clinical outcomes across a lot of these trials, which is fascinating and really speaking to a very different paradigm to what we are used to. But the effects come, they are immediate, they are immediate effects. Like ketamine also has been a revolution in depression treatment because you have the antitipresent effect immediately, whereas with SSRIs, typically a lack time of weeks. So these are very immediate effects. It's more about trying to prolong the effects by integrating and implementing and find out how this opportunity for change and that flexibility, how that can be used far after the experience on the drug. So the effects are. So I'm getting from you, it's not a magic bullet, but it does take work still. Like a lot of therapy takes work and it does take work for individual who is going through it. It's just a bit like it's interventional. Like physiotherapy. It's something it's an intense period and there's a lot of work to be done by the individual agency on the individual and work after, but you can get better. You can get better. It's an effort, but it's an intense period. It's not that you're parked on a drug. Not that I speak down, it's a Zoriza, other mental health psychiatrists. We do prescribe them absolutely. But there's something appealing and beautiful about coming with more nagging intervention and see if you can make things much better for people without needing to be on a medication forever. I think that's where we're moving. Also with neuro stimulation, completely different field, we're working together and doing trials that incorporate both. And that's bit-same thinking. It's interventional rather than just being on a maintenance treatment forever that sometimes doesn't even really help you that much to be a bit critical to what. So some of what we are doing day-to-day in psychiatrists. Yeah. Dr. David Aurets, so thank you so much. That was absolutely fascinating. Thanks so much for having me. Pleasure. Well, I hope you found that as interesting as I did. I know there's a lot to take in there, but if you're like me, it was an area that I think I really needed educating on. So hopefully you've taken something away from David's incredible knowledge. Do join us next time on the midpoint.