and now for something completely different but highly relevant. Um So this this has come about as Chester said, I'm I'm pretty passionate about this. This is something that I really started thinking about about five years ago in terms of developing a program at ST john's and P. And I. And um we we've finally done it. And so this is really about a four year progress progress report and I'm going to try and give you some background and some information as to why I think this is so important. I really think this is if not the most um potentially impactful development in medicine, certainly in the Neurosciences and behavioral health. I think it's the most impactful thing going on right now with the most potential. There's my disclosures. But so we developed this program called Trip Treatment and Research and psychedelics. And and it's the mission is really about developing safe and effective and FDA approved psychedelic assisted therapies for a variety of conditions um including anxiety, depression, addiction and PTSD and other related conditions. And we really want to try to help advance psychedelic science and our understanding of the neurobiological mechanisms underlying um the benefits and the potential risk of psychedelics. And then we want to expand um psychedelic and consciousness medicine um in a manner that ensures that treatments are accessible to those in need and and our focus is really gonna be on psilocybin, LSD M. D. M. A ecstasy and ketamine. And remember that ketamine is currently the only approved um psychedelic and it's it's sort of a non classical psychedelic And I have to give a lot of credit to Dr. Keith Hinds Sterling, who who we recruited a few years ago in 2019 who's an addiction medicine specialist and Keith runs the trip program for us and he's just done an amazing job as you'll see. So if we think about the magnitude of behavioral health disorders and some of the things that we treat commonly at P. And I, and because of this conference, I put in my head in a cancer, it's a lot of patients with brain tumors, stroke Alzheimer's five million patients. But if we look at some of these other factors or conditions ptsd depression, anxiety, and addiction, they really dwarf these other conditions. And we know that a lot of these are interrelated and we know that for many patients, our current therapies really have limited success and poor sustainability and significant side effects well. So the story around psychedelics is an old one. Um shamanic cultures have been using psychedelics um for many, many years um for probably over 5000 years, they are also referred to as n theologians, accessing the Divine within and many of these substances have been used such as Ayahuasca, peyote san Pedro cactus and psilocybin um dating back for for centuries, probably the modern era of psychedelic research really began with Arthur Hefter, who was a german pharmacologist and a chemist and he identified mescal in as the active alkaloid and peyote back um In 1897 and he self tested. He figured out what these common compounds were by, by self testing. Albert Hoffman similarly, who was the discoverer of LSD inadvertently dosed himself in the lab while he was lurking, looking, working with ergot alkaloids um for him, a static agents for for the Sandoz company in Basel Switzerland. And on April 16, 1943, as he was working in the lab, he recounts later in his book, I laid down and sank into a not unpleasant, intoxicated like condition characterized by an extremely stimulated imagination in a dreamlike state with eyes closed. I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense kaleidoscopic play of colors and then being the intrepid scientist three days later, because he wasn't sure what had happened, he dosed himself with LSD 25 again and that is now a official holiday in Switzerland called bicycle day and its celebrated around the world for bicycle knots. And Albert Hoffman went on to be a big advocate for psychedelics. Uh and he lived to be 102 years old um and wrote an amazing book called LSD My Problem Child, which really highlights some of the amazing benefits to society and some of the dangers as as things went off the rails As all allude to. But because of that discovery, Sandoz began production of LSD in 1947 and later they were provided psilocybin. He also was the one who um found the active component in psilocybin mushrooms. And so Uh psychedelic use in the psychiatric community community really took off across Europe and the United States and from the 1950s to the 70s, they were intensely investigated for their therapeutic potential for things like addiction and depression And cancer-related distress. There was over 1000 peer reviewed studies and and over 40,000 research subjects. So it's really almost mainstream psychiatry Back in the 60s and the 70s. But as we know, things later deteriorated. But another big influence influencer in the in the psychedelic Um interest was Aldous Huxley and he wrote this book called the doors of perception, which was published in 1954. And he had his first Mexican journey in 1953 and he described his experience and looked back at the way the brain normally works, which he referred to as the result reducing valve of the brain and nervous system and that really has some significance as to the mechanistic effects of how these classic psychedelics work. Well, Timothy Leary, got very interested in this as a young Harvard professor and he started something called the Harvard Psilocybin project in 1960. They went on to do some groundbreaking work there and developed the concept of set and setting, which is essentially the mindset of the patient, You know, what are the patients intentions and the setting in which the journey occurs and of course the drug itself and the dowsing and this still is really um one of the fundamental concept of psychedelic assisted therapies and how it's so different from traditional uh pharmacological treatment of of some of these these conditions. And so these three Timothy Leary, Ralph Metzner and Richard Alpert really sort of paved the way. But they got they got more and more interested in the potential for societal change um with psychedelics and really thought this should be something that should be given out to the society at large and things essentially went off the rails, timothy leary and Richard Alpert eventually got fired from their Harvard professorships. Um Richard Albert went on to become Ram does um timothy leary became called the Most Dangerous man in the world by Richard Nixon. And because timothy leary was promoting this concept of turn on tune in and drop out and and on the west coast you had um ken Casey who was also similarly advocating societal change. He's the one who wrote one flew over the cuckoo's nest and that was related to some of the psychedelic experiences that he had. And while he was working for a C. I. A sponsored psychedelic trial um in in California psychedelic bands, the original psychedelic band, the Grateful Dead. Many of you are familiar with all this. So, bye! By the early 1970s, about 31% of the armed forces were using psychedelics. Um and many were taking cocaine and other substances and this led to the controlled Substances Act in 1970. And all psychedelic Research basically ground to a halt at that point, it all went into the into the deep freeze. But as we know, psychedelics are back Um in 2018, Michael Pollan published his book called How to Change Your Mind. Which is a really wonderful read. If you've read anything by Michael pollen, there's been innumerable articles. Um And our own Ira Byock who is part of the providence system, he directs the um he directs a program looking at palliative care and that sort of thing at in providence. There's been lots of articles in the new york Times, the L. A. Times um iris paper taking psychedelics seriously back in 2018. And the Journal of palliative Care Was the 3rd most read article that year. So a lot of interest, it's been on 60 minutes. So if you if you haven't been hearing anything about it, you're you're probably not paying attention. It's good you're listening in on this talk. So if we look um since the night since 1990, the number of psychedelic publications publications on psychedelics has really dramatically increased. And the very first clinical trials at academic institutions in the US. Recommenced in the early 19 nineties with D. M. T. In 1990. M. D. M. A. In 1992 and psilocybin in 1999. And this was in part led by some groups um called maps most importantly, which is directing the M. D. M. A. Studies maps is the multidisciplinary Association for Psychedelic Studies. It's run by a guy named Rick Doblin who was way ahead of his time and been working on this since the mid eighties. But you can see that the number of publications is going up, the level of academic interest is really going up high And then psychedelic sinners are showing up around the world. The very first one that was really named is at Imperial College London. This was an article in April 2019. The Johns Hopkins Group has been involved in this since around the year 1999. Um This is Roland Griffiths and Matthew johnson, the two leaders of this program. They have published many landmark studies in this area, as has the group in Imperial College of London and they're getting a lot of philanthropy on the West coast. Berkeley UCSF and UC SD all have psychedelic directed programs now. So this is becoming more and more mainstream neuroscience and changing behavioral health care. So what's what's all the interest, why is there so much attention to this now? Well um we just heard a great great discussion about hearing and we know that we have as humans, we have a limited perspective on the universe, both visually um from from auditory stimuli and the way our brains work um stan graph who's a psychologist from Austria. I wrote that it does not seem to be an exaggeration to say that psychedelics used responsibly and with proper caution would be for psychiatry. What the microscope is for biology and medicine or the telescope is for astronomy. So it really gives us a new way to look at ourselves. Look at our situation, look at look at the cosmos. So how does it work? So the classic psychedelics include psilocybin, psilocybin and LSD. They're very similar, their serotonin serotonin agonists. The real difference between suicide and and LSD there are some qualitative differences but is the duration. So it's psilocybin journey lasts about 5 to 6 hours and LSD journey lasts usually around 10 hours much longer but both of them lead to introspection and new insights, altered perspective. Reframing of experience and relationships. Whereas M. D. M. A, which is a synthetic compound is an amphetamine also is referred to as an M pathogen because it promotes these emotional effects of interpersonal warmth, empathy and openness and M. D. M. A. Does a lot more. It's a lot more messy drug. It triggers released not only of serotonin but also dopamine and or adrenaline but also acts on the hypothalamic pituitary axis and causes release of oxytocin and cortisol and oxytocin as you know is important in bonding with mothers and I think that is really one of the keys of why why MDMA is such an empathic experience for individuals. So there's a lot of theory as to how these these compounds work and this is just showing some of the key structures for psilocybin and LSD. The prefrontal cortex is a big area involved with all of these. The thalamus is the claustrophobia. Um And this this area the prefrontal cortex, the prick Yunus, the post your singular area also referred to their part of what's called the default mode network which is an important concept. Um and then I'll get to in a minute. M. D. M. A. Similarly with the prefrontal cortex also much more involved in the insula and the amygdala which are related to emotion and fear. Um And again the hypothalamic pituitary axis as it relates to cortisol and oxytocin. And so we're starting to get through functional MRI studies pet studies a better idea of how these work but it's still very theoretical and it's similar to even anesthetics. We don't even know how an aesthetics really work that well but we're learning and um so these are not only one of the things that's most interesting about this is you can look at psychedelics, not only is therapeutic molecules but as investigative molecules um as ways to probe and understand how the brain actually works. So your brain on psilocybin. So the oral effects began in about 30 minutes. It peaks within an hour persists over another couple hours. And generally you come down over about six hours at the end of six hours significant alterations in mood, emotion, cognition, consciousness and perception, both visually and auditory and at the higher dose is very significant increase introspection de realization what are called dream like your mystical states, frank hallucinations, synesthesia which I'll get into. And significant alterations in time and space. And this concept of mystical or spiritual experience is very important and it's really thought to occur by altering or dampening down what's referred to as the default mode network, which is really kind of where you reside in terms of your ego and your fears about the future. Your regrets about the past. One of the, one of the interesting things that psychedelics does is it causes these these visual and auditory mixing things. Um and this is thought to occur from um a loosening of what's referred to as thalamic gating the thalamus is this relay center that takes in a lot of sensory information and psilocybin and LSD changed that so that you're getting a lot of different signals going to different areas and you're you're seeing your, you can hear colors and music will have a colorful component to it. And this is called synesthesia. It's one of the one of the hallmarks of of the experience. This is a really nice study that that a fairly simple diagram in a way which gives you a sense of how our neural networks work under the condition of placebo in a functional MRI or under psilocybin. And this is just in 15 patients, healthy volunteers and these these different colors indicate neural networks. And you can see that most of the crosstalk is within network. But under the influence of psilocybin, there's a tremendous amount of crosstalk that occurs and this is really what what is believed to be part of the the fundamental re wiring and re awakening of your brain and working through these new strategies. And so this would be sort of the ego dominated uh psyching versus ego disillusion where you sort of lose yourself and uh reach this potential therapeutic space. This would be what um Aldous Huxley referred to as the reducing valve of the brain. This is where we normally are. This is where hopefully all of us are right now in this room. Um we're in this state. Okay. Um but under the influence of psilocybin or LSD, you will have this amplified state of consciousness or a mystical experience. And these effects are thought to help explain increases in imagination, novel thinking and creativity experienced during the psychedelic space. The importance of the mystical experience. And it has been defined and it's it's something that we measure in the clinical trials that we do. So there's a sense of unity, a sense of transcendence of time and space. There's a no epic quality to it and intuitive knowledge. It's individuals see the experience is sacred and awesome. There's a positive mood. Um and yet it's very hard to describe. It's ineffable and often paradoxical when these are most of these components are hit. It leads to feelings of openness, empathy, love and new meaning and new, new perspective about about one's life and interestingly the strength of the mystical experience, at least for psilocybin and LSD trials is the best predictor of the therapeutic healing process and even when challenging. So this idea of a bad trip. This is the importance of having guides and having someone with you so that even when you hit these challenging periods which most people will and most of their journeys in the end it will be it will be worth it. So this is really, wow, it keeps really off the off the slide. Sorry about that. What it says that there is a fundamentally different approach to mental health care. And if we think about traditional therapy, the daily pharma copia to daily medication, ongoing psychotherapy or not, it's more of a suppressive approach managing it superficially adjust mood. It's a relatively slow process and side effects are common. And here's just a list of the typical antidepressants, tricyclics, srs you're familiar with these um lots of people that you may know or treat are on these Psychedelic assisted therapy. It's one or 3 journeys 123 um over the course of several weeks intensive prep and integration. It's a more expansive psycho spiritual approach Where one delves deeply into fundamental issues and ruminative processes. Um and it really promotes neural plasticity. Um cognitive and emotional flexibility and it's so this is why it is so fundamentally different and music is foundational to the process. Um In the journey um Playlists are provided, there's many um psychedelic playlists out there now on Spotify, but this is really an important part and as to why music is so foundational to the to the process. Um That's a that's a good question and something that's being looked at and it's relatively rapid, you know, keith and I in looking at this, we like to think of it as similar to a surgical procedure um to the work that we do in the operating room. Um It it involves the same the same issues um for having a safe and a good outcome. So you've got to have very careful patient selection and screening um Pre treatment preparation, gotta have experienced clinicians. Those are the guides of the facilitators. Got to have the appropriate setting the monitoring and safety measures. And you've got to have careful follow up or what's referred to as integration and the mantra that is given to the patient before they go on their journey is trust, let go and be open. Trust the process. Let go and be open. If you think you're gonna die, you're not going to die if you see a dark well. And this is very true. People people have ego death in the in the in the middle of their journey and they think they're going to die or they they see a very dark stairwell that they go to the dark door at the bottom and the the encouragement is go there, go experience it, you're not going to die, you're here with this but go on this this internal journey. So that's that's really an important part of it. And one of the essential things is having really experienced and seasoned guides. And this is this woman, Janice Phelps wrote this paper on guidelines and this is the California Institute for Integral Studies has probably the biggest program in in psychedelic assisted therapies and research keith has taken this course I've taken it, it's an excellent course um and they teach these essential competencies, competencies of the therapists of you know empathy, trust knowledge of self awareness and obviously ethical integrity. The important thing to understand and there's been some of this in the news lately that you know like any um psychology or psychiatric setting. The patients are very vulnerable and this is a very vulnerable setting for the for the patients. And so all the clinical trials now utilize two facilitators and we're very fortunate to have Karina Sir Guy and Michael linton who are two main um psychedelic guides. But keith also does it. I have done a couple shanti going Jonathan is doing some of this and we have one other individual and and a and a couple others that have come from the C. I. S. Program. So the guides are really essential to making sure that the patients are comfortable and that they are properly prepared. Um you know a lot of people have worried given what happened in the 60s and 70s that this is going to go off the rails again and so you know safety guidelines for doing research are are critical. Um the drugs are very safe physiologically. You cannot overdose from psilocybin, it's not going to kill you, you could walk off the top of a building or run out into traffic but you're not gonna have a physiologic death due to an overdose of LSD or psilocybin. M. D. M. A can raise your blood pressure some but again fairly state physiologically. But you want to be looking for these sorts of things. The bad trip prolonged psychosis is extremely rare. Almost never occurs. But again, avoidance is with all of these factors here of of prep and um having a season team. And this is just a this was from a study that came out of the UK on the um what's called the harm scale, harm to users which is in blue or harm to others. Based on a large survey of UK experts and you can see that psilocybin mushrooms, LSD and ecstasy which is India are all down here at the very very bottom of this scale. So perceived as very very safe drugs. Yeah they're all scheduled one um at the moment. So this is the set and setting model that is being used essentially in all clinical trials right now which includes the screening of all these issues, psychiatric status, prior treatment, substance abuse etcetera preparation. The journey itself where we ask the patient to trust, let go and be open, hopefully at least with psilocybin and LSD, they achieve a mystical experience. Um and then uh the the process of integration um interpreting the the events and processing hopefully leading to improved mood and behavior. So, you know, the preparation generally takes a few weeks. The journey itself is a few hours. And then there's this long term follow up. One of the interesting things now is looking at psychedelics more as neuro plastic surgeons. And so when you think about this, the underpinnings of the neural behavioral things going on, we're really trying to address behavioral rigidity um that's what this is all about and by creating structural plasticity and ultimately that will lead to behavioral plasticity. And there's very good evidence that psychedelics are you're a plastic surgeons in the terms of in terms of creating synaptic genesis and neurogenesis, elevating production of BDNF and M Tour. And so there's there's some very good data on that in animal models. And now coming in some some human models as well. So in terms of studies, how am I doing on time, I'm okay, okay, good. Okay, just let me know um we can bring you back down to Earth if you want. Okay, So I'm gonna just run through a few kind of landmark studies that were done um that have been done. So this is a cancer study done by the Johns Hopkins Group, published in 2016. So this has been out for a while. It's not one cancer, it's actually 51 cancer patients, 37% have depression, 31 anxiety, about a third had mixed. Um And over half had tried um various medications. So a single um Dose of psilocybin in these individuals at six months, depression and anxiety reduced in 78 and 83% of patients respectively. Pretty durable effects, no serious adverse events. And what's really interesting in these studies is they asked them, you know, where would this rank in the most meaningful experience that you've ever had in your lifetime or the most spiritually significant lifetime experience. And you can see at the high dose group, they did it, they had a high dose and low dose group. Um you know, 60-70% said this was in the top five most meaningful lifetime experience of my life and similar numbers for most spiritually significant. And this is something that is repeated over and over in these in these studies. So that's that's a pretty pretty impressive number. Um This was a study that um came out in the new England Journal of Medicine last year about a year ago looking at psilocybin versus Lexapro and the and again that the numbers overall were somewhat similar, but the way they powered the study um they didn't see as as much significance in in relief of depression. But when they looked at all the secondary measures they were all in favor of sillah Simon over Lexapro and you can see that there and all those measures so and again no no serious adverse events. Um There's a number of studies going on with addiction. Both for psilocybin but well with psilocybin but for smoking And alcohol. And these were two very small studies wanted wanted Hopkins where they only did 15 patients they're going to do. They're doing a larger study now in that But 80% of these individuals had biologically verified abstinence. So that's way over what you would normally get for se chan tricks or other methods. Um And then um the N. Y. U. Group Did a small study in alcoholism one or 2 doses and again abstinent significantly increased afterwards. So very promising. But but small numbers PTSD they're way ahead the maps. People this is Rick Doblin who started maps in um 1986. They are in their second phase three trial. Now the first phase three trial is published here in Nature medicine about a year ago And really impressive results. You can see down here. I don't know if you can see but but basically at 18 weeks PTSD had completely was in complete remission or loss of diagnosis in 67 2 3rd of the patients versus one third of those that that had placebo with with the M. D. M. A. It's a little bit different. They do three, they do three sessions experimental sessions. So they do and they have integration in between each one of those. So it's it's a little bit more prolonged. Um and and this this hopefully their their second Phase three study will will be equally as positive and if so it will be FDA approved. It will be the first one. But so just to look at this a little bit more. Um One of the points in the paper is that is you know how does it work again? And they say M. D. M. A. May catalyze therapeutic processing by allowing patients to stay emotionally engaged while revisiting traumatic experiences without becoming overwhelmed and and that's really the key to it again. It works on the amygdala. Um probably the insula as well and here's just a few quotes that I think are really informative from individual patients. One thing the M. D. M. A. Facilitates is thinking about traumatic experiences in the neutral safe manner. I could objectively think about them and talk about them. Then it seems those memories are put back in their place in the brain in a different configuration a configuration that does not cause as many problems such as bad dreams, intrusive thoughts all the time are having horrible insomnia. This has continued to this day a year and a half after the last M. D. M. A. Session pretty impressive. It gives you euphoria, euphoria and love. You can go into the darkness and not be afraid. He said, referring to addressing the trauma of war. It allows me to see my trauma without fear hesitation and finally processing things and move forward. And the important thing about this study is that it's all types of PTSD, it could be um, people, you know, military who were traumatized in, in the war to be firemen or policemen. It can be rape victims. Um, you know, sexual assault victims and it seems to be equally effective. So very impressive and stay tuned on on that. And then, you know, what about just, you know, helping, um, what people like to refer to as the betterment of the well or the worried. Well, there's another study from the Hopkins group where they combined psilocybin with meditation or spiritual practice. And you can see that at six months it led to these durable changes in interpersonal closeness, gratitude, life meaning forgiveness, Death transcendence, their daily spiritual ritual and coping. So it raises the question, you know, should it be in the water? Maybe? No, but it does raise the question that it can certainly help people a lot of normal people who get stuck in things and are having challenges on the, on a day to day basis. So if you look at standard therapy across these, these entities of depression, anxiety, smoking cessation, for example, in PTSD, you can see standard of therapy and you can see the psychedelic therapy at least in these Phase two trials is usually is on average about double. Um in terms of efficacy obviously doesn't work for everyone and there are people who um it's not appropriate for and so these are promising early results. Um but but clinical trials um the phase three trials need to keep going. So in terms of where we are on the road to FDA approval, you know ketamine as I mentioned is being used. We used it in the in the clinic now keith and Karina do it frequently for patients with depression and some with addiction with good results in a psychedelic assisted therapy model um maps is way ahead on for M. D. M. A. And phase three trials. And psilocybin um is in the midst of a bunch of phase two trials around literally around the country mostly in europe and the U. S. Which were involved in. There's not very much NIH funding for this now but hopefully it's going to change. There are other avenues to non criminal use. Um And for example, Denver legalized or decriminalized psilocybin a year or so ago and Oregon legalized it for um for therapeutic treatment beginning next january and there is a push in California as well to decriminalize it but we'll see that that has a ways to go. Our program. Um We were very fortunate in 2019. We got a $700,000 gift from the Annenberg foundation that allowed us to recruit keith. Um We do ketamine assisted therapy. Um keith was able to get the D. A. License for Schedule one drugs. We've completed two clinical trials already with psilocybin. Um We've completed our visual healing trial which I mentioned very briefly, 20 patients, 40 journeys I think, 39 journeys in that group. And we were we participated in a multi center phase two trial with you sona for major depression. And I don't we don't have any results for either of those trials because the data is being analyzed upcoming trials um were going to do a pilot trial and brain tumor patients with anxiety, depression. They've been excluded from all clinical trials to date because they're worried that they that psilocybin might lower the seizure threshold when in fact there's probably evidence that actually it there is no evidence that it does that and we think it will be safe. We're gonna hopefully be in a LSD trial for generalized anxiety disorder and covid related grief we're looking at. And some other things, potentially a migraine trial as well. This is where the clinic is. It's at 13:01 on the third on the on the fifth floor we have to to journey rooms, one with a large screen monitor here. One that that has this with blackout shades but looks out toward the toward the West. Um We've developed a really fun collaboration with Louie Schwartzberg who was the director and producer of fantastic fungi. Um And we are first clinical trial was an alcohol use disorder which we started back in March of last year and we just completed enrollment. It's called pilot trial of visual healing. And the premise is that alcoholics may require a higher dose of psilocybin or LSD to achieve a mystical experience. And we know that nature connectedness um can help reach that state of mystical experiences, something that Albert Hoffman pushed a lot for. And so the hypothesis is that if the individual were to watch a beautiful nature film as they're going off into their journey with that prime the tank, so to speak to help them achieve a mystical experience. And basically using some of Louie Schwartzberg, you know, cinematic nature mastery. We put together this trial Of 20 patients where it was an open label trial. Each subject got two different doses of 25 mg of psilocybin. And they would they were randomized to watch the video or not at the beginning on their first journey and then they could watch it on the second journey or not and data analysis underway. But so it went, it seemed to go very well. The one patient that I was with, it was a pretty remarkable experience. She actually didn't watch the video. But the her psilocybin journey was was remarkable in her, you know alcohol intake was significantly decreased. So this is a little snippet of mm hmm of what they see. Um It was a very large flat panel monitor and I won't play the whole thing but it goes on for about 40 minutes at the beginning and then they go put on eye shades and music. So um if you're interested in learning more there's a lot of great books out there that I have listed here. Um Some that are including Michael Pollan's book Sacred Knowledge by by Bill Richards is really excellent. Excellent if you want to get a really interesting history. Um Acid dreams is is excellent. But anyway there's lots published on this and if you prefer podcasts or websites the tim Ferriss show or Sam Harris. And there's a there's a website called Psychedelic alpha or psilocybin alpha which is really an amazing clearinghouse of what's going on in the psychedelic space now That's a good one. So you know in summary the psychedelic renaissance is in full swing. Um and rightly so as we have massive mental health issues that pervade our our society and the current treatments are not working all that well. And so psychedelic assisted therapy with its shamanistic roots really does offer a paradigm shift with an expansive psycho spiritual approach that seems to promote brain plasticity and connectivity. And what's really interesting is that these substances seem to be trans diagnostic. They work across many different types of disorders um including ptsd grief and probably things such as O. C. D. And anorexia which I didn't get into and very important to consider for end of life issues and helping people uh come to grips with their their mortality. So we think FDA approval for MDM a will probably occur sometime in 2023. Um psilocybin for depression maybe by 2025 2026. We'll see. Um this is a ripe area for the Neurosciences um for clinical and basic research um as as the neuro plastic effects not only in behavioral health but also in things like stroke and TBI. I didn't get into that pain. There's a lot of interest in these areas and the concept of the betterment of humanity or the betterment of the wealth through psychedelics remains an intriguing question. Both um with macro and micro dosing I didn't get into micro dosing. And there is a corporate um free for all right now it's really the Wild west. There's over two or 300 new companies in the psychedelic space. And so investors Beware because a lot of them are going to fail and um it's very way too early to know and I'll end there. Thank you. Mm hmm. Any questions for dr kelly. Mhm. I'm waiting. Hello? Hey um dr kelly a couple of things. One there's always been a concern about brain damage and things of overuse and and of these type of products um potentially um And to um it's just would you say there's some kind of mechanism akin to like electric shock therapy with that hyper excitability of the brain and all across languages and all that. I've never read anything that there's any any similarities whatsoever to electroshock therapy to E C. T. No. No. And I and I think I would stress again most of these, you know, um, psilocybin and LSD or serotonin agonist and um are are somewhat gentle on the brain and gentle physiologically. Um, there's there's very little data that um like I said, you can't overdose on psilocybin or LSD. There was a tremendous amount of disinformation that went out um when things went off the rails, you know about chromosome damage and frying your brain. I mean, certainly, you know, there's these are in a different class compared to things like, you know, cocaine and amphetamines. And it's just a completely different, fundamentally different kettle of fish. Not that they don't have risks. So, um, you know, the safety issues are really paramount to that. These clinical trials are being done, you know, properly and safely with all the important safeguards. So, right, memory scans before and after these. Mm hmm. Yeah. That's what the the Imperial College of London Imperial College London is doing a lot of that. They've been sort of the leaders on that. Um, but a number of groups are doing that. And looking at changes in and looking at neural networks and it's a lot of good stuff to come I think. Thank you. Thank you very much, dr kelly. Um, that was awesome.