Dr David Erritzoe

0:04Hello 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.

0:30the CNWL Mental Health NHS Foundation Trust. And since David arrived at Imperial in 2009, he's conducted and overseen clinical and neuroimaging 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.

0:58Dr David Oritza, 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 invited to talk at Davos, then... At least just in a psych programme, but still quite a lot of airtime down there for what we're doing Because the money men must see there's an opportunity here, right? Yeah, I think so. So I also, in your introduction, say I know nothing about psychedelics.

1:34I'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, sounds 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 place I was trained, they were very good at methods to understand the brain serotonin system in particular.

2:15and I got interested in the biology behind addiction because 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 work in that system are psychedelics and MDMA and therefore I ended up pursuing, trying to understand the effects of those drugs. In the beginning, it was about the impacts of 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.

2:58When we gave the drug, instead of just trying to understand the impacts of people using them, then try 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 the early opening of this new era of interest in psychedelics. So 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 were usually using mushrooms or kind of things like that.

3:44So 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 lasts maybe four or five hours, not days. LSD a bit longer, still not days, unless you keep on taking it. And if you do, 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 counterculture in the Western world using these drugs and having great communities and experiences and use them for some of the things that are actually therapeutically relevant also for the development we're in now.

4:29And there were also in that era in the 50s and 60s, 40 ,000 people, patients or so being treated by clinicians with these treatments. And then war on drugs, late 60s, around 1970, new conventions, Nixon war on drug, counterculture 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 therefore got pretty bad names and which also in a way informed somewhat why we focused on the mushroom compound called psilocybin instead of LSD because everybody knows, let's say 20 years ago, super stigmatized LSD where psilocybin nobody could spell or pronounce.

5:19so that was 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 most of what we have been doing in our team is on psilocybin absolutely so it's not actually necessarily coming from the mushrooms right so it's synthetic yeah you can synthesize it some of the new trials we are 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 are testing exactly and get it through these processes and approval processes too so we work with the pure compounds.

6:11But we also do work with 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 that also comes from nature, like psilocybin as DMT. And then a third one, 5-A-MEO 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 in people suffering mental health conditions, most of what we have been doing is with psilocybin.

7:00We've also done work with LSD and MDMA and ketamine, but mainly psilocybin. So in terms of the mental health issues that you're looking at and addictions, 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 that many actually 20 years ago, So, you know, we needed to make some decisions on what compound to focus, also how to give it. Should we give it intravenously or through the mouth with psilocybin or should it be LSD?

7:43And what indication, once we had done the initial work, got it familiar with the experience that people are having and the effects and the safety and the dosing, and also some of 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 done before because in the first era, we didn't have the scanners. So you would look, first of all, at somebody who had a healthy brain and good mental health. I heard it actually in Davos. A colleague said near normal, which might be a nice term.

8:18Okay, a near normal brain. So you would be able to see the effects of the drugs on the brain literally 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 saw really good results. That was not a perfectly designed trial. It 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.

9:02And 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, taken that further and done the next line of trials. And now it's in the final phase of testing in patients. So that means the psilocybin is the most advanced one for mental health indicators. And that is for depression treatment, resistant depression, meaning people have... Nothing else has worked. Yeah. I mean, not nothing else, but they have tried a couple of conventional approved treatment, insufficient dose and duration and so on.

9:43And 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 completing and in follow-up. And that's not us doing it, but that came from the early work. So when you say completing, 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.

10:33So already, and then they take a while to, you know, consider the data and so on. So it could happen during 27 with psilocybin. MDMA, which is not a classic psychedelic, some more atypical psychedelic, but very, very fascinating, interesting compound. Now, we have not done that much work 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, several of them might end up coming quite close to each other, and that's for PTSD with MDMA. Right, okay. So, can you explain how it's actually working, and in terms of how it's, is it rewiring neural pathways?

11:16Is it changing the structure of the brain forever? Or is this something that's going to have 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, the paradigm is really different from giving a person a tablet. Conventional antidepressant medication, SSRIs, that is used for a lot of indications. People take them daily for a long time. Psilocybin and the other classic psychedelics, they are framed and packaged into a 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.

12:08So 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 or soul revealing or manifesting so things come up deep psychological material it can be interrelational it can be trauma it can be beauty it can also be more spiritual bliss type relevations reframing often as profound what 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 in any mental health condition, which also speaks to why they might work across, that things are so difficult that you can't really approach and work with it and face it.

13:16And some of that often on a psychedelic afterwards goes in the direction of some degree of acceptance and coming to terms and it settles. 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 is it something that you've still got to that person has then still got to have therapy to work through that 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 uh but it doesn't mean that people who have a psychedelic experience can't really get a lot out of it without any psychological package they often can but then the risk is also that it can be overwhelming, challenging psychologically and difficult and maybe end up be disturbing for the person.

14:11So 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 um 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 with person people a therapist to support you then that work after integrating it and finding out um yeah how to integrate it into your life to move in a in a better direction to break habits.

14:59And that's where addictions can come into play as well. Yeah, 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 shared features in these where I think 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.

15:44And also a very sort of negative bias and 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, higher power or being more connected. And psychedelics, one of the absolutely key features that people very often express very clearly is a profound sense of being connected. It can be to others, it can be to your own more emotional life, the difficulties and the beauties, but also even nature, even the universe, and also this transcendence that we are part of, something that goes forth and back through time and space.

16:26And that sounds very spiritual, but that is really very classic with these. And as you point out, that's kind of the thinking on the 12 steps, isn't it? In terms of being part of something greater than yourself. And interestingly, Wilson, one of the founders of AA program, the 12 Step, he recovered himself after having tried, I think, a number of times. Then he had an altered state of experience with a compound, not any of these ones, and that really, really helped him. And that made him recover and maintain abstinence. And there were discussions between him and others early on about integrating psychedelics into the Cholster program because it actually fits really well.

17:07But that was not that well received. It would be much more difficult to grow 12 steps as they did, wouldn't it, if they were at the time, if they'd had to. In a very stigmatized. 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.

17:46The drugs that people get addicted to typically work in the dopamine system, opiate system of the brain, all the others you can think of that you know that people can get in trouble with. Yeah. So these drugs are very, very different and they do not form addiction. They do not push people out to addiction. MDMA, tiny bit more, but it's also a little bit different, pharmacology. and then you have ketamine. That's also a 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.

18:26Still 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 extra. 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.

19:01It'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 is 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've spoken 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 okay let's as a sort of parallel if you think about cognitive behavioral therapy it's a relatively regimented maybe 10, 12 sessions, kind of very manualized with some homework.

20:09And so if we compare normal antidepressants like SSRIs to that, then the psychedelics are more like deep analysis work. And if you look at who's getting what kind of talking therapy, most people are getting some CPT 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 a bit of the talking therapy. And that's a big issue because that is not the optimal and best way and also most effective way and most safe way of using them.

20:57without if you take all the psychology, 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 regulate it 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 is having a psychedelic experience? Yeah. So normally through development, from childhood and to adulthood, your brain through experience becomes more and more efficient, more and more connected.

21:41Different 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.

22:27But if you shake that and the snow falls, it might be that the little snowman or 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, I don't know, the workshop making the Christmas present or whatever. And 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 paths. So it allows for a bit of a reshape, remoulding. The brain becomes very flexible and mouldable. And in a scan, you can see? Yeah, we can see the brain measures of these phenomena.

23:06we can even see to continue with snow and now bring it into the mountains so yeah so if we instead of being in the snow that we are on in a in a big area with mountains yeah then there might be a path to ski down that you have used many times 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 and this is maybe take the the analogy far but but it 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 and you're a bit constrained in how you can move across it's complicated to get from a to b but with the psychedelics also after the experience we can see that in a way the landscape is flattened um there's change to the hierarchy and the and there's a flattening to the landscape of the brain activity and and that means that there's an opportunity to consider different the different paths and all that comes on a foundation of brain plasticity so a window of opportunity for the brain to reshape and reform and even sprout with some new synapses, some new connections.

24:35Most 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 psychedelics... Just hearing you describe that and that great analogy, I'm thinking about people who might have Alzheimer's, earlier onset of dementia, those kinds of mental illnesses and diseases. Would there be any impact at all that psychedelics might have on those kinds of brains?

25:21Yeah, it's a very good question. I know it's not your area of expertise, but you've heard 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, what comes up psychologically, your perceptions, your visuals, all that is changing during these experiences. Giving that to a person who struggled to provide the consent, 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...

25:57Or those who are genetically predisposed that we now know obviously have a genetic link. Would there be potential? Possibly. And it could also be that you could do some maybe some tasking 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 um also because there's a yeah also there same for alzheimer but there is a lot coming for alzheimer it's a there's been a lot of resource put in mental health absolutely under prioritized for many many many decades completely out of proportion to other fields of medicine and there's a massive underserved group of of the population of patients with a lot of diseases not even having any medication that's also why we for instance are launching new trials and gambling disorder with psychedelics and also opioid use disorder because of all the incredible, horrible mortality.

27:09Mortality 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 drug use ultimately comes down to, isn't it? It's a financial consideration for the government. Absolutely. And in a way, fair enough, when you have X amount of money and you need to prioritize it, you need to do the health economics. But the suffering and the, I mean, the mental health and depression, the most prominent one in terms of burden of disease and also how much it costs society, there's really a lot to gain.

27:53So I would put it the other way around and say, can we afford not to help people if we have something new, a new paradigm that actually does look really, really promising? You also asked earlier that I didn't, really address how they work how efficient are they compared to what we have and that it looks like a bit more efficient in terms of the yeah 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.

28:34Think about all the addition things we have 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. And 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, regulators do not look at when they just need to look at the hard measures and do the health economics.

29:16But 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, or you've done the majority of your study here and your papers. Are there 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 in early trials, in the beginning, Imperial, but also now other great colleagues at other institutions in the UK.

30:00America 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 those countries are Switzerland early on, 2014, and then Australia, Canada. There are places where there are sort of gaps and gray zones where people can use and provide these drugs. So I think Jamaica, Costa Rica, there are a lot of people there offering. There's a gap in the law in Holland allowing psychedelic truffles to be used. But healthcare-wise, it's Canada, Australia and Switzerland and now also Czech Republic and Germany more recently that are changing and several states in the US.

30:44So it's more and more happening. So you're learning a lot from those countries as well? I mean, in a way, we can. If data is collected, if they have good employees that are being used, national registries, collecting data from real world use, clinical use, then that is really important. That's something called phase four. So after the one, two, three clinical phases of testing a new compound, then it's out in reality. In real world, that's actually what they kind of are doing before the phase three trials have been, in a way, Yeah, even completes it. 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 use the understanding from what is used.

31:28So if 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 or themselves, is it possible in this country to go and safely use 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 psilocybin, 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 induced clinically.

32:04However, 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. It has started as a medicine. It's just used in physical health, in intensive care, for other indications. Also a sedative in higher doses. if you use it in a lower dose, is antidepressant. And actually also trials that show it work for other indications such as alcohol use disorder that is worked on in the UK by Exeter, Celia Morgan.

32:44The current stories, though, about ketamine in the news are about ketamine addiction and ketamine being something that's being used as a recreational drug. Yeah, so it's a complex story to tell. It's a complex story, but that one does not rule out the other. If we were to, for the first time, introduce some kind of opiate treatment, that's still incredibly useful if you have broken your leg and you're in hospital. It doesn't mean that it's a absolutely great idea to use wildly every weekend. You'll be dependent. But 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?

33:21Is it the same compound? It is. So a company did something to the compound chemically, 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 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.

34:06But in the lower dose, same drug costs nothing. That should be and that is what we're piloting in a talking therapy model into NHS. that my big encouragement is to put pressure on to do more of that because it will take a while before the others are there. 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 ketamine, a series of dosing sessions work, and that it can be safely and meaningfully embedded in therapy similar to what we do with psilocybin 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.

35:09So what I'm struggling to understand there is how it has become such apparently an insidious drug for young people hearing stories of bladder failure and people becoming seriously addicted to the same compound. Is it just dosage? It is. So if you use these drugs to have... And why are those, sorry, but why are those kids who are 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. That's one thing. If the model, the clinical model you're setting up, has X number of treatments, let's say five sessions, that's what we are currently piloting, one every week, embedded in 10 sessions of therapy, and it's joined between the talking therapy services in the NHS and us on the psychiatry side.

36:05We work together, joint supervision and so on. we're all co-thinking about and with this patient that we are trying to help we implement behavioral activation with goal setting and so on into the model then it's a very contained supported model and people that give 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 and recreationally dose the drug to have a fun time. It's a completely different use of the drug and people do not seem to seek it outside of trials.

36:44I can't rule out that if you treat one million, there won't be a few who will end up buying it in the street and be heavily dependent. But that might be the case, but we already know from the data. You wouldn't treat a ketamine addict with ketamine? We could. You could? Potentially. I don't think it has been done. But possibly, yeah, and 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? Probably not that much. They are very, very contested. And when people say, but 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 preparation to go into it, then you are using that drug in a very, very different way from if you go to a rave and take it.

37:40There's nothing wrong. I mean, you can say that's a political policy, legal thing, whether you think that's wrong and that's drug policy, and we can discuss that, but that's not obviously the core of my expertise and field of work. But yeah, these drugs, if they're used out of hand, out of context, and 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 undergo surgery, it's not that everybody then run out and become addicted to heroin after having been given when they need it in a specific way.

38:16And this is even framed more safely because it's saved in a therapeutic frame. Right. Okay. So we've got to kind of think of it in that way, in a medicalized way. Yeah. Almost catalyzed psychotherapy. Right. Okay. More than a medical, yeah, it's medical, but it's way beyond just a 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 mode. 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 therapy.

38:58In terms of a neonormal brain, we called it earlier on, what would the benefits, if any, be? Would it ever come to a state where you'd say, because you hear the expression, everybody can benefit from therapy. Even a neonormal person could benefit from that. Would everybody benefit from psychedelics? That I would categorically say no. Not everybody would, because there is no such thing. That's, I think, magical thinking. But overall, we already know from studies in healthies. 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 um 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 normals like this and and do people when we measure measures of psychological well-being and different other interesting features in a near normal person, we do see improvements overall.

40:06So if there are 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, and you're smiling away there. I've just been in devours to having that. There's a lot of microdosing going on there? No, but there's some prominent, wonderful colleagues working also in microdosing. One of them is Paul Stamets from North America. And we, you know, we have different views on the data and the evidence for microdosing.

40:44So yes, a lot of people are microdosing. And there's a big industry around it as well. Is it purely for recreational use or does it have any impact on their day-to-day cognitive function? My 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 arm of the study that had the placebo typically suffocates the effects seen in the other arm.

41:24And that is what you need to do scientifically to actually 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 regular use several times 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. It could be meditation, talking therapy, lifestyle changes and so on. Those studies need to be done on its own.

42:03Does 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 an 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. And it has been tested for a few mental health indications. There's an ATSD study with LSD microdosing. Great improvements, 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 psychedelics confusing because it exists outside.

42:42I was going to ask you about the downside and the contraindicators that you've experienced or 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 health history, family history and so on. So people who have experienced psychosis, we have not included in the trial for caution. There's some data from the 50s, 60s that 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.

43:40and with some data to support it from the 56s. Therefore, we have had that caution. That might not be the same with MDMA, for instance, or for that matter, maybe ketamine. So there are these cautions 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 a 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 followed people out in the real world, that it might still be helpful overall as a group, but the likelihood of being really tricky and challenging seems higher.

44:34It looks higher. Therefore, if you were to do such work, proper trials, at least do it with the experts who are really good at providing the right support and care for that specific group of patients in order to do such trials safely and really monitor them and see are we actually making it worse for some people. So I think there are some cautions in some directions, but the field will keep on moving and expanding, and hopefully it will be colleagues who are really cautious about, I'm sure it will be. Those kind, yeah. Do you feel the myths have been busted, Or do people still have quite negative preconceptions when you tell them what you're studying?

45:10You know what? I think that access of 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 that's being 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 a 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 you know then these stigmas are being, you know, reduced.

46:03And that's always healthy to put more nuance onto the story. But that will also mean that people with recreation will be using it. We are seeing that more psychedelics. And just finally, if somebody has a severe addiction and this is the way that they, you know, are led to hopefully cure or treat that addiction because addicts tend to say they're addicts for the rest of their lives, don't they, in terms of how they deal with it. How quickly do you see people turning their lives around? What's the kind of time frame? For addiction specifically, we are doing these new trials with gambling use disorder, gambling disorder and opiate use disorder at Imperial World Therapy.

46:41So 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're used to. But the effects come, they are immediate effects. Like ketamine also has been a revolution in depression treatment because you have the antidepressant effect immediately.

47:21Whereas with SSRIs, typically a lap 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 from the start. 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 the individual who's going through it. A bit like physiotherapy. Yeah. It's a bit similar. You're a sport expert. Yeah, well, somebody can come and do physio on you, but you still have to do your own rehab and prehab afterwards.

48:07And what is beautiful about it, and I think that's, as I see, the shift in psychiatry, if we just now focus on the treatment for mental illness, that it's a bit like it's interventional, like physiotherapy. right it's something it's an intense period and there's a lot of work um to be done by the individual agency on the individual and work after but you are really you can get better you can get better it's an effort but and it's an intense period it's not that you're parked on a drug not that i speak down is a psoriasis or other mental health i'm a psychiatrist we we do prescribe them absolutely um but there's something appealing and beautiful about coming with more like an intervention and see if you can make things much better for people without needing to be on a medication forever.

48:55So more interventional psychiatry. I think that's where we are moving. Also with neurostimulation, completely different field. We are working together and doing trials that incorporate both. And that's a bit the 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 towards some of what we are doing day-to-day in psychiatry. Dr. David Aritzow, thank you so much. That was absolutely fascinating. Thanks so much for having me. Pleasure.

49:27Well, 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.

49:48You