Episode Transcript
[00:00:00] Speaker A: Here's the first group study ever done using psychedelics for cancer patients. What I was seeing in that study compelled me to leave my cancer career and focus on psychedelic research.
[00:00:15] Speaker B: Well, Manish, hey, thank you so much for taking the time to have this conversation. I really appreciate it. I've been looking forward to this for quite some time for the audience. Manish is the co founder and CEO of Sunstone Therapies, a practice where he focuses and specializes in the research and delivery of psychedelic therapies. Manish, thank you so much for coming on the show.
[00:00:32] Speaker A: Thanks, Brendan. I'm looking forward to speaking with you. Yeah.
[00:00:34] Speaker B: So maybe just to get us started here, if you could give us a quick kind of overview of your career and how you ended up doing this work, we'd love to hear that.
[00:00:42] Speaker A: To make a short story long, I actually wanted to study philosophy in college. And my father said, I didn't come to this country for you to be a philosopher. And so I ended up becoming an engineer, got bored with that, ended up going into medicine and then in medicine went into oncology. But during my internal medicine fellowship, I did a fellowship in bioethics and got a master's in philosophy. A long winded way to say. When I got into oncology, you know, I did a fellowship at the nih, I was on faculty there and did clinical research, and then left that and joined a large private practice and ran the research department there. And over my, you know, 18 years of practice, increasingly as an oncologist, I saw that I was able to take care of patients in terms of treating the tumor, shrinking it. But then a large part of the quality of life was determined by emotional issues, psychosocial issues, I would say. And so the things above the iceberg are like chemotherapy, radiation, surgery, but underneath it are the things that really determine how people live. And so I felt an increasing gnawing feeling of like, wow, I'm not really able to meet the needs of my patients. And that got me into interest psychedelics, as there were studies that were done at NYU and Hopkins initially that showed some promise in cancer patients. And that led me to write an investigative initiated study using psilocybin for cancer patients. It was the first group study ever done using psychedelics for cancer patients. And so we purpose built the space out and started the study and published that study last year in JAMA oncology. But seeing what I was seeing in that study made me compelled me to leave my cancer career and focus on psychedelic research.
[00:02:15] Speaker B: And you've kind of just kind of dived right into that. So I was quite curious to hear about any like, specific challenges that you might have faced in kind of pivoting as an oncologist into this space.
[00:02:25] Speaker A: Well, I mean, I've done a lot of research and psychedelic assisted therapy is really novel and a new way to do research. You're combining a drug, psilocybin, mdma. There's various compounds obviously which alter a person's internal state in a profound and deep way. And they need psychological support. And so to build infrastructure and care around that is quite complicated. It's closer to oncology than it is to most mental health conditions. When you go to a psychiatrist, they do an hour of therapy or prescribe medications and you go home. In psychedelic assisted therapy, there's a preparation period, then there's a treatment with someone next to you, then there's follow up integration, and that's closer to oncology in terms of are you qualified, are you prepared? Chemo education, then you get chemo and there's follow up. So this multidisciplinary is complicated and this is all new. So the field is still learning how to do this. So I think that makes it challenging. And the other thing that's really challenging, that I don't think people always appreciate is, you know, in cancer and many other studies, we're studying something fairly objective. And so I can measure your tumor size and here I'm really a subjective experience and yet how you feel. And yet we're asked to measure that and to quantify that and to treat that in our current paradigm. And so that can be challenging.
[00:03:41] Speaker B: I can only imagine that after 18 years, in almost 18 years in oncology work, it must have been a little bit, I don't know, scary to kind of pivot and kind of like create a new platform in this space. How did you think about that?
[00:03:55] Speaker A: Yeah, so I mean, that's why I said a little bit about the college thing is when we conducted the study that I wrote and about, we treated, I don't know, 10 or 12 people. And I was somewhat skeptical, honestly about psychedelics and what they could do. But the profound shift I saw in a few patients made me realize, like, this is adult medicine and this is different than what we currently do and this needs to be studied. And so there came almost an existential moment of I've had a very established career, I'm a well known researcher, oncologist, you know, 10 years, I can sort of think about retirement and I'm going to leave and start something novel. But if I don't do this I'm always going to wonder, what if? And I have something to contribute here. So in many ways, my experiences in medicine, engineering and philosophy and oncology were preparing me for this, for this task that I'm doing now. And so I could have. I could not do it.
[00:04:51] Speaker B: I totally hear you. I think in many ways reminds me of Jeff Bezos regret minimization framework that I kind of hear from a lot of folks who go off to kind of start a new thing. I'd love to actually just start to dive into the patient experience here a little bit. Since starting Sunstone, I know that there's been almost this renaissance of research. How do you think about the landscape of research and options for patients today?
[00:05:15] Speaker A: You know, since I've been doing it, the landscape has been shifting and changing. I think there was a lot of hype initially and there was this promise, but the landscape is changing that it's maturing that these drugs are not magic bullets, they're not safe for everyone. How do you really treat someone that's going to be helpful, minimize harm is where we're really moving into, rather than sort of the hype and promise of them. We've done over 200 treatments in the last 12 to 18 months with various psychedelics. We use a lot of different agents, six or seven of them in all different indications. And so that experience is really allowing us to see that, wow, there's a lot more to learn here. And the field is just getting going on it.
[00:05:53] Speaker B: How do you think about selecting almost between, like, options? I know that you're doing a bunch of research across a couple different studies. Like, how do you. How do you think about the kind of various options that are on the table for an individual? I know that, you know, there's a few programs going for, like, treatment resistant depression, a few programs going for mdd. How do you. How do you think all that?
[00:06:12] Speaker A: Yeah, I mean, so when we tried. When we evaluate a person, you know, we try to talk to them about studies that we have, but also standard of care treatments. And the first thing we're really trying to assess is for safety. And you're right. I mean, I think that states it shares where things are right now in mental health in many ways. You know, just saw somebody today and the question is, does a person have complex PTSD or treatment resistance depression? And there can be a lot of overlap. You know, I had a patient walk in and said, I had a psychiatrist told me that I have trd and another one told me I have ptsd. Which one do I have. And he had early childhood experiences that were difficult. He has feelings of depression. And so we really try to spend a lot of time sifting through what the underlying condition is, what the symptoms are. And then right now, because everything that we do is clinical research, you know, see which study makes the most sense. Would they be eligible for and would they be safe for and trying to navigate, Is this the right time for that person? It's not that everyone should just go on psychedelics. It really has to be safe and an appropriate candidate for that.
[00:07:13] Speaker B: Tell me a little bit more about safety. Of course, patient safety is priority number one. So how do you, how do you make that assessment?
[00:07:21] Speaker A: Yeah, I mean, so there's the ones that people talk a lot about, there's medical safety. And so we look at things like blood pressure, CKGs, seizure disorders, there's psychiatric ones. Is there a personal history of psychosis, a family history of schizophrenia, brain mess? Those are the typical ones that we sort of look to to make sure they're eligible. But then, you know, another aspect that's not always talked about is it can be a very powerful experience and someone has to be prepared to have that type of experience and have enough support around them while they go through it. And so if you just give it and the person doesn't have those things in place or they're not prepared, it's not going to go well. In fact, if you'd ask me, well, what have you learned in some of the people that you've seen? Sometimes it's not the person that's depressed. They're already living with suicide or thinking about it and they actually do okay. Sometimes it's a person that just wants to take a drug and be fine, but not really deal with what might be underneath that's causing the depression. And sometimes things can surface that are difficult for patients. And if they're not wanting to deal with that, sort of a cat has come out of the bag and what do they do with that?
[00:08:25] Speaker B: That must be so hard to assess a priority. How does one even go about that?
[00:08:31] Speaker A: Yeah, so we do a fairly thorough clinical interview. We use scales and we sort of know how to look for some of those pieces. And then if it looks like they're eligible but there's some concerning, maybe there may be a concern, we proceed potentially. But then we talk to them about it. And then they have two or three preparation therapy sessions and see how they deal with that. Are they able to connect with a therapist? Are they able to go inside and then all the way up to dosing. And so if we feel like somebody's not making that progress, we'll say, look, this may not be safe for you, and we pull out. And so you're right, it's not just check the box and you enroll. And it's just a one time assessment. It really is a team of the physician, the therapist, the research coordinator that's sort of assessing and making real time decisions.
[00:09:13] Speaker B: And having seen research in a couple different settings across oncology and in this space, I'm curious to hear your take. What is uniquely difficult or different about doing research in this space versus the rest of the world of clinical research? Maybe.
[00:09:28] Speaker A: So I hinted at one of them. One is the nature of subjective experiences. And so, you know, in cancer we reported nausea, tumor size, blood work, blood pressure, things that are really easy to measure. But here we're asked to report on adverse events of special interest. So you could. One of them is like feeling grounded or feeling a sense of peace. So you have to like report that, you know, these subjective feelings that people have, somehow you have to quantify them and report them. And that's then something sort of purely objective. And then the other one, I think that's really important in this treatment, almost unlike any other, is the drug plus the therapy. The drug plus the experience is the treatment. You know, in oncology, of course it matters, but then you want the right drug, the right chemotherapy, the right dosage, you want the doctor to be kind and you want the nurse to be good. But the tumor is going to shrink or not shrink. In this case, the drug may or may not work as well depending on that other context. And that's much harder because again, it's a human experience. So that's different than most other things in medicine where it's like the drug is doing everything and there's not. That is other element.
[00:10:37] Speaker B: Yeah. You know, this reminds me of a conversation I had with Srini over at Italian.
I asked him what he would change if he could change anything. And he said it was, it would be the size of the placebo response or the kind of the nature of the placebo response. In this space, as a trialist, like on the ground working with patients, how do you think about that?
[00:10:54] Speaker A: Caring for someone is very powerful. And so I don't have an issue with the placebo response. I think that people coming in, they're feeling heard and seen, they do feel better. If that works without psychedelics, that's great.
So I don't have any issues as a researcher. To me, the placebo is More interesting in that it's not the sugar pill, it's that our minds are able to get better on their own with the right circumstances. So what is it about the mind that allows that? So the drug may facilitate it, but there's more going on. Why place placebos work are more interesting that they work tells you more about brain and mind than it does about placebo or psilocybin.
[00:11:29] Speaker B: You know, one of the things that I'd love to just spend a little bit of time on is stigma. Have you found this to be a challenge in working with patients in your practice?
[00:11:38] Speaker A: For sure, some. You know, it's a spectrum, so it's not one set of patients. Equally as challenging, I would say, is the hype. And so there's people that come in and they've read on the Internet or watch something on Netflix and they want you to give them a treatment and have the big experience. And they also being very profound and deep, but it's not what they imagined it to be. And so some of it is really preparing for what the psychedelic experience can be, the heterogeneity of it. And it could be helpful in many different ways. And so having realistic expectations on the other side, it's over feared many times. And people say, well, does it make you go crazy? Or there's all these druggies? And so that's something we talk through as well. It's almost like I want people to forget what they know about psychedelics, both good or bad, and just come in with an open mind, look at the data and study it for itself. And so I think there is stigma, but it's decreasing for sure. I mean, I have lots of people that are very interested in psychedelic instant therapy studies because their current treatments are not working. So even in the last five years, the stigma is increasing really quite steadily.
[00:12:48] Speaker B: One thing you said reminded me about the conversation we were just having before we started recording here, which was around showing the data and maybe this idea of agency amongst patients. How do you think about providing the data in a way that is accessible and appropriate for the individuals who are considering the research?
[00:13:05] Speaker A: Yes, we talk about the studies that have been done. We talk about there's a risk, you know, there's a physical risk of nausea, some of the symptoms they have. We talk about risk of psychoses, potentially dissociation or becoming unstable. Sometimes there's an increased risk of suicide. All these are relatively small, but we sort of talk about all of those pieces. It's just like in oncology or anything else, we talk about the Potential risk and the benefits of that.
[00:13:28] Speaker B: Maybe one of the things that I'm kind of curious about is priming, right? Like, some of the kind of early studies are so positive that, like, are you. Are you worried at all about, like, potentially priming or over priming the individuals?
[00:13:39] Speaker A: I guess in theory, yes, but the people that we see are really quite complicated. I mean, they've had depression or trauma for 18, 20 years. They've been on multiple medications, have tried lots of different therapies. And, you know, if it's as simple as, like, telling something's going to work and getting ready and it works like it just isn't. It's quite a. When it works, it's quite a deep, profound experience for people. It's not. I don't think you can prime your way there.
I mean, as a physician, I mean, I've been in practice for 20 years. I've used lots of interventions. There's something happening here. When it happens for somebody, it doesn't happen for everybody. It's not a magic bullet, but it's not as simply explained away as that.
[00:14:17] Speaker B: And I'd love to just continue polling on this thread. Then you must have seen so many profound patient experiences, lives changed, maybe kind of help us take a peek behind the curtain here.
What have some of those stories look like?
[00:14:29] Speaker A: I'll share.
Cancer patient. She had advanced cancer, was on psilocybin, had a very difficult experience. Like, it was challenging. She felt like she was facing her death, felt like she was going to die in the session. I mean, she knew she wasn't dying, but that's what it felt like. And so she got through it. And then she came back, you know, a week later, and she said, you know, I had this really profound experience two days later in the late fall, like November, this time of year, when she went and she was at the lake. And she said, you know, I had this sense of peace come over me. And I said, what happened? And she said, well, it was. The sun was setting and all these crickets were super loud. And then all of a sudden, I got the sense of peace. And what I realized was, come winter, all these crickets are going to die, and in the spring, there'll be a whole crop of new crickets. And in the same way I was born, there were all these humans that have died over my lifetime, and there'll be new ones as I go on. For her, it was this connection of, like, this is not personal to me. This is like the nature of life, and I'm just part of all of that. And so it's one thing to say it and to even intellectually get it, prefer to feel it in some, you know, deep cellular level where it's like, wow, this is something larger that's going on. Really helped her sort of bring. Get some acceptance around that, you know. Another person, he was on a study for trauma, and I had given him his drug. And then you come in later to give a booster. And when I came in, he said he did not want the booster. And I said, that's fine. Can I ask why? What's going on? He said, well, I'm in so much pain. I don't want to take a drug that's going to make it last longer. And I said, what do you mean? And he said, well, I realized my mother hated me and I don't want to take something that's going to make me feel that even more. And what we got to talk about was that he's been aware of this feeling his whole life. It's not something that's new, it's just. It's coming into his awareness. And this feeling that I'm bad and that's why she didn't love me is now something he's lived with that's affected all his relationships. And that's a core belief he had. And starting to work with that to say, wait a minute, I'm not necessarily bad. She may not have liked me. That doesn't make me bad. And that feeling of me being bad that's carried him throughout his life has affected him and that became. Start to shift that. So those are two stories. And other people have had the typical sort of mystical like experience where they feel this oneness, this unity and just this profound peace. And for them it's really powerful because they've felt depressed for so long, they've never felt that feeling as they can remember. And that itself, knowing that it's capable. And they felt that something they can go back to and has been helpful for them. So, you know, I say there's not a typical psychedelic experience. It's a heterogeneous experience. And it helps some people in different ways.
[00:17:15] Speaker B: One of the things you said earlier was that there's no silver bullet. It is such a heterogeneous experience. Have you noticed anything, any hypotheses as to when or for whom these experiences really make a difference?
[00:17:29] Speaker A: So when I say it's not a magic bullet, I don't think it's that for many people, you don't take one and it's done. But you begin to crack the, the ice. You start beginning to do work that gets access to these things which you need to change. So that person I told you about, you know, he learned this at a very, very young age. Like pre verbal almost. And so if you're a young age, you know, you might say like chair door and you say bad chair or bad. But you learn that you're learning language. And so as an adult, someone can tell you in therapy, you know, a chair, but you're not bad. And you can say that, but you do not feel that. But I think in that experience it allows you to start saying, huh. I tell these people like it's like Prince. You know how you said, I'm the artist formerly known as Prince, I'm the person formerly known as bad. The person formerly is bad to then I'm actually good. And that might take a year or two. But entering into that area where you can access that and maybe reshape that belief is what psychedelics open up. But the work isn't usually done at that moment. So I think people that want a one and done and want an instant fix, it doesn't work for as well. The ones that are willing to work at it and let it become another tool. Along with the journey's on. I've seen that to be the most profound help.
[00:18:47] Speaker B: A lot of the sponsors that are doing work in this space will assert that. Oh actually they're, they're trying to actually isolate the kind of drug effect from that, like the kind of ongoing relationship and the kind of therapist experience. But it sounds like to you like that's been impractical. Like, might I say, like, how do you, how do you think about that?
[00:19:03] Speaker A: Yeah, I mean, I think it's a limit that we have currently in medicine that's like we understand drug and we have boxes that fit into that. I give you this, this happens, you get better and this is more complicated. I do think that it doesn't have to be as complicated as people make it. I do think the ongoing therapy is important, but there are basic safety parameters that are needed for preparing somebody dosing and treatment and, and that's like a clinic. It's the practice of medicine. It's like, how do you, you know in cancer. We gave cisplatin based chemotherapy for testicular cancer and it was curative, but people were sick and they would throw up and then in the hospital for five days and now it's all outpatient because we learned how to give the right antiemetics, the fluids, the sequencing and that evolved from the practice of it doesn't make that go away. But it's not like it's, you know, all of it upfront. And so I don't think that all has to be get defined by the pharma companies. Ultimately it'll be the sites that are doing the practice that we will help establish the standards of care. And that will take time.
[00:20:02] Speaker B: I'd love to start talking a little bit more about the site experience and potentially even the foreshadowing to the potential provider experience. What are some of the unique challenges of running a site that's entirely focused on this space in terms of studies?
[00:20:16] Speaker A: One of the challenges, the studies are pretty restrictive and so there's lots of people that are not eligible and so there's a lot of interest in them. Having to disqualify people can be a challenge and so you have to screen a fair number to figure out who it makes sense for. It's challenge because this is novel therapy and treatment. So a lot of times the person undergoing the treatment doesn't understand the family member or even providing therapy, the providing network. And so there's a lot of education, a lot of effort that's needed and then just logistically in operation it's quite complicated. Like for one treatment there's like 20 appointments between the screening and the rater assessments and the blood work and the EKG and the therapy and the dosing. And so it's a coord between the whole team and that person, that schedule. That's one person for one study. But if you have 10 patients on five studies, that really gets to be an infrastructure and operational challenge. And that's a lot of times underappreciated.
[00:21:12] Speaker B: One of the things that seems to be a, let's call it a competitive frontier is the length of the experience, the kind of as a result of burden on the kind of care team. How are you starting to see things shake out as you think about, knock on wood, a few of these get approved. How are you thinking about the become delivery setting Evolving?
[00:21:32] Speaker A: Yeah, we think a lot about that. And so one of the things is that the therapy team that's providing that, you know, you can't do this treatment. A therapist can't treat someone every day for five days. It's way too draining, it's too much. And so we usually limit them to one, no more than two treatments a week, you know, usually about six treatments a month. And then they need a lot of support in terms of processing what happened, giving time to think about it. So we Provide supervision, we provide a lot of training. And so the care of the team is going to be really important in providing this care. It's not like sort of light treatment, it's intense. It's like surgery in your brain, except for surgery in your soul. And so. But it's intense and it can be profound. Which is different than sort of little trips and traps.
[00:22:16] Speaker B: It sounds like for the, for the therapists, you, you're kind of limiting the number of sessions that they also do in a week. That's exactly how did that practice come to be? I haven't heard much about that before.
[00:22:27] Speaker A: You know, to treat one person in one week you do two hours of preparation. The treatment is eight hours, the follow up is two hours. So that's in self 12 hours. And after that the person is exhausted, you know, they're not sort of ready to just pick right back up. And so we saw that. And then if it's not as intense of a treatment, they could maybe do another treatment, you know, sort of the back half of the week, but they would never do it back to back. And so just in practice seeing it and talking to a therapist and being in relation with them, we realize what they need for self care and how to provide that because if they are not in a good place, they're not going to provide really good care to the patient and the therapy won't work.
[00:23:04] Speaker B: How much more attractive does that make some of these DMT or 5 Meo DMT programs in your mind because they're shorter acting?
[00:23:12] Speaker A: Yeah, I think time will tell. I think at the end of the day if something works is what people are going to go after. And so some of the ones that we work with, dmt, we've worked with psilocybin and for someone that has been stuck for 5, 8, 10, 20 years, it's not that much time to really shift in a meaningful way. They've spent hours and hours in therapy or on medications for years with like minimal to incremental benefit. So at the end of the day, whether it's four hours or eight hours of treatment, it's really whether it works or not.
[00:23:47] Speaker B: I guess there's like a prevailing hypothesis that at least I can totally see it from a patient perspective the kind of difference being marginal, but from a provider perspective the difference being significant. Is that how you see it or I mean potentially.
[00:23:59] Speaker A: I mean I certainly think from a pharma or insurance or reimbursement perspective it would be better. The best scenario is you could use this and not need any therapy. At all. It makes it easier. Then less therapy and less drug and less time is even better. It's going to be more, it is more of a burden or a cost on a site if the treatment takes eight hours rather than four hours. But I. Yes, that's true. But I don't want to wish that into existence because that's what I wanted to happen because it's easier for me. At the end of the day, it has to work.
[00:24:31] Speaker B: Yeah. The pragmatic provider and you have heard is, hey, what matters is that it works.
[00:24:36] Speaker A: Yeah. And so I hear lots of these debates and sometimes I just think it's what you want. You know, you'd love for the to be short. You don't need anybody in the room.
Great, that works. And it's easy and it's delivered. Everybody understands that paradigm. But reality always wins.
[00:24:53] Speaker B: I'm curious, have you encountered yet individuals who have had a response to one but not another? And the reason I ask is because as we think about maybe the commercial feature of some of these options, I'm curious, do you see a world where people have to be trying a few of these to find the one that really works for them? Or am I not thinking about that?
[00:25:14] Speaker A: Right. No, I think that's right. I think that or it may be just be more personalized. You know, I think we're getting better and better about thinking about where the person is in their life story and what they might need. And so there are probably, there are some psychedelics that are being developed that are shorter acting and lighter and that may be sufficient for many people to get things moving and they may be ready for a deeper, bigger experience. They may not need that for someone else. They might need that to sort of, if they've been really stuck, to get that moving and then come back. And so I think we think a lot about, you know, for a person that comes in, what's the right thing they need before then? Is it more therapy? Is it learning mindfulness? What are the other aspects? And then where do psychedelics fit into that and which psychedelic? And then to me we're not there yet. But it would be to make a personalized tailor made approach for that person because each biography is somewhat different and we're still really learning that.
[00:26:09] Speaker B: Yeah, it's so interesting, this idea of like, I mean, right now we're in a phase where dose control is so important, but it sounds like from the healthcare provider's perspective it's actually kind of like a variable equation that you need to solve.
[00:26:23] Speaker A: Yeah, I mean Right now, it's one size fits all. It's like one dose, one drug for this thing, and you put everybody in it, and it's going to work in that percentage, but it's just not going to end up being like that in the long run.
[00:26:34] Speaker B: That'll be really interesting to watch as things progress. I'm curious, you see the whole world here. What are some of the exciting programs you're kind of particularly really interested in or particularly watching closely right now?
[00:26:44] Speaker A: So we do commercially sponsored studies, but we also do our own IITs. And I'm really interested in some of the things that we've been doing in terms of the group. One of our studies, we treat four people simultaneously. So they do a group preparation together, and then they come in at the same time, all take psilocybin at the same time in separate rooms. But then the next day they come back for integration. They talk about their experience together. And what's been really exciting for me is to see the connection that people form and how long that lasts. And so this study ends in eight weeks. The first study we did ended eight weeks, but that group is still meeting three years later, once a month. And so from that trial, so not everyone goes, but we have. And it was because they asked for it, you know, that the trial ended, and one of the participants said, I can't stop meeting. You guys have to, like, put something together. And so the trial ended, but we opened up a monthly group that one of our therapist leads. And if you've been on our study, you could go on it. And that's been going on for three years. And so I think there's something really powerful in the group approach done correctly. Another study that we're doing is with a cancer patient and a family member, both getting MDMA together to see how the cancer has affected their relationship. And again, that's very exciting to me to see changing the dynamics and the culture of a person, how much that affects it. And so those kind of things are really interesting to me. And then, you know, I would like to see more different dosages. And sometimes I think less is more. And so what is supposed to look like right now, we are in this phase of let's get these drugs over the line. This is the standard, and I totally agree with that. We do have to do that work. But really starting to look at what is happening, what is the role of therapy? How do you best design something for a person is what excites me.
[00:28:29] Speaker B: And maybe this is a good kind of dovetail into the Future here. How do you envision kind of the integration of some of these therapies into mainstream healthcare, mainstream psychiatric care over the next, let's call it five, 10 years?
[00:28:41] Speaker A: I think it has to be integrated into that. It can't be isolated on its own entity. So I see it as a continuum that people will come in, they'll be evaluated, they might need an ssri, they might need therapy. And then knowing this is another tool in the toolkit and after they've had this experience, they're able to continue on. And so I think designing a program and a path for a person that's individualized to them is, I think, where it's going. And so not everything has to be recreated. Some of those things work. We find a lot that after people have gone through psychedelic experience, things that didn't work as well before seem to be a lot more effective, like yoga or mindfulness or group therapy or just therapy in general. They just have unearthed so much material that now therapy is much more effective. And so that to me is very interesting is the intersection between what's already available and how that fits into to support this work and how this can support other ongoing tools.
[00:29:35] Speaker B: What do you think it would take for psychedelics to be kind of first line options instead of like SSRIs?
[00:29:41] Speaker A: Well, I don't know that they should be first line options for everyone. I think it really depends on the person again, and I think we need to understand better safety who it's not right for. I think we need to make sure that we have the systems in place to provide that support, not just sort of take a psychedelic and go home. And so those things would make me more comfortable with making it first line. But I think, you know, so if someone has been doing relatively well and they have a bout of depression, I don't think the first thing they should do is do a psychedelic.
[00:30:08] Speaker B: Sounds like you're triangulating in on, oh, this is actually best for more severe cases, more serious cases.
[00:30:15] Speaker A: I wouldn't even say this more severe. I think for some people that have had a serious event or they're depressed and they're going to. You want it to become chronic. And for those people it could be, but I think identifying that is really important. And so we are treating a lot more severe. But I don't know that the first time someone has experienced grief they should just go straight to a psychedelic. Maybe, but I would want them to, you know, if they've done no therapy and have done no not able to be with their inner Experience and on a psychedelic what you really notice is your inner experience. They're not going to get as much out of it. So you know, during a psychedelic experience you have eye shades and music on and it's a very internal experience. And the main thing you're doing is noticing what's going on inside. If you're not able to do that at all, not on a psychedelic and not curious about that, psychedelics probably won't be harmful, but it probably won't be as helpful as it could be if we don't do other things first.
[00:31:05] Speaker B: There's kind of a debate I think going around of whether it's the kind of experience, the neuroplasticity or both together that matter. Curious where you sit in this, like.
[00:31:17] Speaker A: In this debate, I guess I don't see the. I mean, so I think that in the psychedelic experience you're able to access parts of your mind that's the remarkable things about our brain, that they can be remade and that things that you held deeply as profound truths can be questioned about yourself and the world that shaped you. And so that's the neuroplasticity because you may have formed those at a very young age, but what allows that to happen is a safe environment. And that's the experience piece. And so I don't know that I see that as separate. What allows neuroplasticity is a safe, supportive environment that understands experience that you're having. I don't think you can have one without the other.
[00:31:58] Speaker B: Well, Manish, hey, I've so enjoyed this conversation. Maybe, maybe last kind of closing question for you here is if you could wave a magic wand and change anything about how psychedelic research is being done today, what would you change?
[00:32:09] Speaker A: You know, I think one of the hardest things been as a site is I don't always think the sponsors, the regulators or people out understand how hard it is for patients that are looking for this treatment. And the studies are well written and they can be really restrictive. And for many people they're coming and this is one of their last hopes and for them disqualified can be really difficult. And I would want us to really think about designing studies to both answer the scientific question, but also patient care in mind. And sometimes I think they're done in a vacuum or can be thought of, conceived of. This is what's the best design study. But these are actual human beings that are going through this and how does this impact them And I would like more consideration placed on that.
[00:32:51] Speaker B: Okay, so I got to ask the follow up question. Are there a Few offending criteria that you'd most like to see rethought.
[00:32:58] Speaker A: Yeah. So, I mean, one of the. One of the ones is like, come in for the study and you're screened to be eligible. And we do what's called a madras to assess your depression and then you begin therapy. And then the day before treatment, we do another assessment of the madras. And if your depression is improved, then they cancel and you can go on to your psilocybin. And that is really upsetting for a participant. And the rationale is, well, their depression is better, maybe they won't need it, but sometimes is that they're looking forward to their session next week and they've seen some progress and they're really hopeful and then they don't get their treatment and they're devastated and their depression again. So that's something that's really, I don't think, always well thought out.
And then I think sometimes on paper the diagnoses are black and white, but in real life, it's not like that. It's the border. They're really borderline. That's mental health. It's our mind. It's not, again, like a tumor is 3 centimeters. It's like you have depression and when it's treatment resistant, it has to be this number of treatments left to be felt for this long, you know, so if you were on it for five weeks and it failed, it doesn't count because you weren't on it for an adequate duration, but six weeks would have counted. Is that really a different person or not? And so I think it's not always based in real clinical world. And so those are sort of the things that. And that's hard for people because they don't understand why they aren't eligible. And so we feel that a lot at the site level.
[00:34:22] Speaker B: Have you seen any. Gosh, I know that was my last question, but I'm just too curious to keep going here. What have you seen that has been, I guess, effective or productive to kind of solve for these kinds of scenarios?
[00:34:33] Speaker A: You know, I know a lot of the people that are sponsoring the study, so we have good conversations with them and trying to have these types of. I think it's going to be slow. I think mental health is generally misunderstood. And so it's raising awareness. I think people advocating, patients advocating for themselves. I think us raising these issues is going to be part of the progress. And then, you know, a challenge is like, do you really need to have this criteria or is this just sort of a nice to have? But I think the work that you're doing, raising awareness, I think galvanizing people at the end of the day, I think the agency needs to go back to the patient and the patient groups and have their voice heard and their needs addressed. And I think that will change how some of this happens.
[00:35:13] Speaker B: Yeah, absolutely. Well, powerful stuff. Manish, again, thanks for taking the time to have this conversation. Yeah.
[00:35:20] Speaker A: It was great talking to you.
[00:35:21] Speaker B: Likewise. SA.
