A Patient-Centered Approach to Psychedelic-Assisted Therapy - Dr. Manish Agrawal, Co-Founder and CEO of Sunstone Therapies

Shiv Gaglani: Hi, I'm Shiv Gaglani. Interest in the use of psychedelics to treat mental health problems continues to increase as word spreads about promising clinical trials, and media outlets shine a light on the issue. Regular listeners to Raise the Line will recall a fascinating conversation we had with Dr. Jim Fadiman, one of the pioneers in psychedelic research, as well as other guests who have weighed in on the question. 

Today, we're delighted to add another voice to this discussion, Dr. Manish Agarwal, who has extensive background and experiences that span medicine, engineering, philosophy, ethics, and research. He's the co-founder and CEO for Sunstone Therapies, a company focused on the delivery of psychedelic-assisted therapy and defining the standards for optimal patient delivery through clinical trials. Previously, he was the co-director of clinical research at Maryland Oncology Hematology, where he cared for cancer patients for fifteen years. 

I'm really looking forward to exploring his interest in whole-person healing and the potential of psychedelic therapies among related topics and before we get started, I'd like to thank our mutual friend and former Osmosis advisor and investor Zeshan Muhammedi for introducing me to Manish. So, Manish thanks for taking the time to be with us today.

Dr. Manish Agarwal: Absolutely, looking forward to it, Shiv.

Shiv Gaglani: So, we always like to ask our guests to describe in their own words some professional highlights, and in your case, what got you interested in medicine and then winding up specializing in oncology?

Dr. Manish Agarwal: It's an interesting story. I had Indian parents, and when I was an undergrad I wanted to study philosophy, so my father said, you know, I didn't come to this country for you to be a philosopher. So I went into engineering, and then when I was a fourth year, I felt like I liked engineering – I was getting good grades – but I didn’t love it and I wanted to do something more with people. So I was going to do biomedical engineering, and then just go to med school, and you can do what you want from there. I went to medicine and then, after medicine, I did my residency at Georgetown, and they had a four-year program in medicine and philosophy and so I was able to get my Master's in philosophy. During that time, I realized how much I was interested in these questions around meaning and death, and why are we here, and oncology is a natural place where these issues come up all the time. So, it was a specialty that was sort of the laboratory where philosophical questions were obvious for me.

Shiv Gaglani: Yeah, absolutely and doing end-of-life care for sure. One book that we recommend highly to our readers is Atul Gawande's Being Mortal, which talks a lot about this and has introduced many students like me and others to the concepts of palliative medicine, which is a good transition, I think, to how you maybe you got interested in psychedelic therapy. Can you give us a bit of that backstory, and then what led to the founding of Sunstone Therapies?

Dr. Manish Agarwal: Sure. So just carrying on with that story, then I did my fellowship at the NIH and at the NCI and was on faculty in oncology there. I then went into practice and after eighteen years of seeing cancer patients pretty much every day and dealing with their families, you realize that you're really able to treat the cancer very well, but in terms of a patient's experience, their emotional health is a big determinant and we really didn't have very good tools for that. I think over time, being an oncologist really started to wear me down. I had feelings of burnout and even depression from seeing innocent people suffer and not having good tools and really not being able to impact them. It started to really get to me. 

Then at the same time, I started reading the research that was happening around psychedelic therapy in patients with cancer. I couldn't believe that there was actually an intervention that was directed towards this hardest of things that any human can go through. If you're told you have a cancer diagnosis, and you might die, it raises all these questions around meaning -- why am I here, what matters, what relationships really matter to me, was it all worth it? And so to go from not having tools, and then having something that was promising is what sort of led me down that path. Then I've visited people that have been doing research in this and said "Wow, whether it works or not, it's worth looking into because at least it takes this aspect seriously."

Shiv Gaglani: Yeah, for sure. So, tell us a bit about maybe those original kind of visits. Was it Roland Griffiths you first met with at Johns Hopkins?

Dr. Manish Agarwal: Yeah, it was. Initially, it was Mary Cosimano at Hopkins. She's a therapist there, and then I went up and visited Mary and Roland. Then Mary Cosimano told me about Bill Richards, and so I met Bill Richards and he said, "You should think about doing this fellowship in psychedelic research at CIS" and so while I was in practice, I took a year to do that and to really learn about psychedelic therapy and research in that setting. Then Paul Thambi, one of my clinical partners, and I wrote a study using psilocybin for cancer patients and submitted to the FDA and the IRB and I can tell you lots of stories, but it was a long journey to get there.

Shiv Gaglani:  I'm sure. I may have mentioned that our former board member, Mitch Rothschild -- who was instrumental in Osmosis's story - his wife, Dr. Rachel Yehuda runs the MAPS trials for MDMA-assisted therapy for PTSD at the VA and we're going to have her collaborator, Rick Doblin, who I think you know well, as well on the podcast.

So, definitely, I've heard a bit about the bureaucratic hoops and all the stigma around psychedelics that happens, but the reason we even have you on, and there's so much interest in the space, is there seems to be this renaissance that's happened over the past five or ten years and a resurgence of interest in psychedelics, largely driven by these validated studies, as well as that we just can't train enough mental health professionals. Plus, COVID obviously exacerbated mental health crises, etc. So, can you tell us a bit about what's the state of the art right now for psychedelic therapy? Specifically, what is Sunstone working on and why is it so unique in this space?

Dr. Manish Agarwal: Psychedelic therapy was being researched in the 1950s and 1960s and there was really promising early work being done. This guy Eric Kast was doing some work with cancer patients at the University of Chicago, where he was actually first testing it to see if it helped with pain. He was just giving people psychedelics and some of their pains were improving, but then he said that he notices they're starting to feel better about dying or having less death anxiety. Then that was carried on with Stan Grof and Bill Richards at the Maryland Psychiatric Institute and they actually introduced this concept of the setting and of how you give it. So, instead of just giving somebody a psychedelic, you should prepare them for it and do it in a safe place. That research was promising and then it went into hibernation because of the Controlled Substances Act. The drugs fell into popular culture, were abused, and so everything got shut down. 

Then, in the late 1990s and early 2000s, I think psychiatrists and mental health professionals were starting to realize that maybe they're starting to run against the limits of what they could do with antidepressants in how to treat diseases like treatment-resistant depression, complex PTSD and they said, "Well, these drugs looked promising, let's take them back off the shelf." And so, research slowly began at that time.

In the last five years, there's just a huge torrent of studies going on. MAPS has just completed their second Phase 3 study. They, COMPASS Pathways and Usona all have breakthrough designation at the FDA for PTSD. MAPS is for PTSD, Usona is for MDD, major depression, and then COMPASS Pathways was for treatment-resistant depression. I think the field has gone from like, “Wow, these drugs are bad,” to maybe they have clinical utility to real research being done. I think the next two, three years are really going to determine where they come in to use and whether the FDA approves them.

Sunstone Therapies is really founded on the belief that the delivery is more important than the drug. Lots of people take psychedelics, and they may or not benefit, right? If MDMA cured PTSD, then nobody that went to a rave would have PTSD anymore. So, the belief is that the right context with the right amount of support, and understanding could help people resolve these difficult emotions and so rather than focus on the drug, per se, we're focused on the delivery. We spent a lot of time creating a space -- physical and cultural - that people can feel safe in, and then we do a lot of work around therapy and what makes it most effective, and so Sunstone was born out of that.

Shiv Gaglani: That makes a lot of sense. So, can you talk to us a bit about what is the patient experience like at Sunstone? I know these are trials you're running, but fast forward five or ten years, hopefully, the trials are successful, and this becomes mainstream therapy in some way. What does it look like? Because I mean, you're talking about the wraparound experience. So there's the period before taking the psychedelic, there's the during, and then there's the integration afterward. Talk to us a bit about how you guys have designed that and what a good patient experience should look like?

Dr. Manish Agarwal: We’ve spent a lot of time on our love and rigor. So, when people come through Sunstone, we want them to feel loved and held -- because they're dealing with very difficult issues -- but also the rigor and the discipline of a very thorough process that is very safe. We're always balancing those two and, you know, if you've had an interaction with medicine, it tends to be very strict and sometimes you don't feel the care, and then sometimes people do alternative medicine and there's a lot of care, but sometimes it's not clear what you're doing, so we're trying to always combine that.  

Every aspect we think about is how can people feel cared for because in order for people to have the best and deepest psychedelic experience, they have to trust the experience, they have to trust their therapists, trust themselves, and that begins the moment they call you or enter your website. How we receive them, where they don't feel like they're a number; that we actually hear them, screen them, make sure that the safety is there; then we spend time preparing them, understanding whether it's a good fit; and then so many details, from the way the bed is made the lighting, the therapist that works with them. Then afterwards, not just to have an extreme psychedelic experience and you go home, but actually, how do you make sense of that? How do you integrate into your life? How do you then connect back into the existing mental health community? How does it become an ongoing way of growth?  

We spend so much time and effort on this. Whether it's the tool that you first learn about Sunstone through, when you come in through the center, the way it is built, -- you know, it's on the medical campus, but doesn't feel like a medical space -- it has soft lighting. It's very well thought about. It's not just sort of thrown together. Then we spend a lot of time on the culture. So for example, psychedelic therapies can be very intense. In fact, we were just treating somebody last week with MDMA for PTSD and it was pretty severe. I mean, the person was suicidal, then after these two sessions, they're really not suicidal anymore. But the impact on the therapist was very intense. To be able to hear that amount of information and process it is hard for the therapist, and so we have a built-in place where the therapist after the session processes what happened for them with our senior therapists who is Bill Richards, and then they spend time later on thinking about what questions came up for them. So, part of good patient experiences is a good therapist and good employee experience. That's just one example of a facet that leads to an important patient experience, because the therapist has to be fully present and equipped to be able to do that.

Shiv Gaglani: That's fascinating. There's research that came out of Hopkins a decade ago sharing whether what clinicians do in their daily life -- like if they are smoking or if they're obese -- influences patients. So it's almost like clinicians have to take care of themselves first – like putting on their own oxygen mask in the airplane analogy -- before they can take care of patients. That’s pretty salient now, especially with the burnout crisis we're seeing and the fact that we don't even have enough healthcare professionals to begin with, let alone ways to keep them in the profession for long especially with all the stressors they have these days. 

So, maybe talk to us a bit about that. What does it take to train a generation of psychedelic therapists? Who are the people you're looking for? How do you hire them? I liked the fact that you've mentioned that you care a lot about them and the employee experience because you want to be able to retain them. What are some thoughts you may have on burnout? Like, is this something that maybe ten years from now you think the average clinician could be taking psychedelic therapies to combat symptoms of burnout or trauma that happens from caring for patients?

Dr. Manish Agarwal: Yeah, for sure, that's something we've been thinking about. We've even talked to the hospital about how COVID was really hard on a lot of hospital staff, especially ICU, and so what kind of support could we provide for them using psychedelics that might at least alleviate some of that trauma and burnout? I think one of the first things is what you're doing and we're talking about is, medicine tends not to talk about feelings and emotions, because they're sort of soft. We talk about sodium and potassium levels and EKG changes but this is a very real part of medicine and so to reduce some of the stigma -- that it's okay to feel tired or burned out and or exhausted or depressed -- that I think that's the first part. The second is that you can really get help around it, whether it's therapy or maybe psychedelics, but really building in some of those programs and taking some of the stigma are a big piece of it. 

In terms of psychedelic therapists, right now that's being led by FDA. Generally on the trials, the lead has to be an MD or Ph.D. Then the second therapist can be a bachelor's to master’s level, but some mental health experience. Being a good therapist is really important. I actually call it therapy assisted by psychedelics, and so somebody that doesn't understand the therapeutic process won't be a great psychedelic therapist. It's really about the relationship, that the more the patient can trust the therapist, the deeper they can let go and have a deeper experience. So, it takes a therapist that understands experience, that has some formal training and is really open to a new way of providing therapy. In the session, and even afterward, it's not as directive of like, “You are under the psychedelic and now you should think about your mother or this aspect of your history.” It's letting the patient guide you and what's coming up for them, what their psyche is bringing to the surface of what they need to deal with.  

It's a different model in medicine, rather than the doctor being the expert, saying, "This is what you should do, or what you should think about." It’s actually providing support and letting the patient direct, but then helping them during difficult circumstances. It's a subtle craft and we spend a lot of time thinking about that and training is something that we do spend a good bit of time and effort on. Bill Richards is our chief therapist who's, you know, trained hundreds of thousands of people and sat with a lot of people, so he mentors our therapists and talks to them. It's one thing to read a slide about trust or to hear a podcast about trust, but when you see Bill talk about trust, he embodies it and so you can borrow some of his trust. So sometimes if you're doubtful of the medicine, or what it can do, he's seen enough that you can actually feel his trust, and that's contagious.

Shiv Gaglani: That's awesome. I love that and certainly the conversation we've had before about training and scale -- how do you scale that out -- is something we're deeply interested in at Osmosis and something we should continue the conversation around. 

What are the current focus areas for Sunstone in terms of what studies are you most excited about? And then also, apart from the rigor that you mentioned, what are some of the patient anecdotes that stand out the most in your career using therapy assisted psychedelic research?

Dr. Manish Agarwal: We have three studies open right now and we'll be opening up two more. The one that I'm super excited about is we have a study where a cancer patient and a family member both take MDMA at the same time with two therapists and so they talk about how the cancer has affected their relationship, because we believe that it affects not just the person, but the context, and so I'm excited. There's not been a study done like that with cancer patients and a family member because the caregiver is really important, and to highlight that as part of our work. One study with major depression using psilocybin and the other one I'm excited about is MDMA for PTSD. We've treated some people and, you know, one of my therapists who's been a therapist for eighteen years said she's never seen such complex PTSD and to see that relief is really, really heartening. 

We're opening up another group study. We're very interested in the approach around group therapy and psychedelics and so we did the first group approach to psychedelic therapy. We treated four people at a time where they came together in a room and talked about the cancer diagnosis, and why they're doing the study. Then the next day, all four of them took psilocybin at the same time, went to four adjacent rooms -- right next to each other where they could hear each other but had separate experiences -- and then the next day, they came back and talked about their experience as a group.  I'm still blown away by the connection between the people in the group.  At the end of the eight weeks, this guy who's pretty quiet said, "I just went to war with these people. I can't stop meeting." It's two years later, and they're still meeting because they made us continue the group even though the study is over. So, we're going to be opening up another group study and I think that this combination of a shared experience and talking about it with people that understand is a very powerful aspect of healing.

Shiv Gaglani: That's really exciting super novel types of studies you're leading at Sunstone and I'm excited to see the results. And as we've talked about, when I'm back at Hopkins for med school, I would love to even intern or do an elective or something with you guys because this is fascinating to me.

Dr. Manish Agarwal: For sure. Part of our training is that we have a video room where people can actually observe some of the sessions and so depending on where you are, we try to pair up some of our experienced therapists with people that are newer in order to get some of that mentoring. 

Regarding anecdotes, there are so many, but I think one of the ones that are very touching for me has been one of the most difficult aspects: when you have a younger cancer patient and they have younger kids. Maybe the patient is in their forties and their kids are younger. It's so difficult. Most of their sadness is that their kids will grew up without them and it's hard to console that and to make sense of it, even as a physician, and to see how they deal with it in the psychedelic has been really powerful. There's a young guy with three young children and that's what he was thinking a lot about, and it was a very grueling session for him. But in it, you know, he talked about seeing this tree, and that he was this tree, and even though the tree might die, the branches were still there and the kids could play off them. That the roots would still continue to nurse the children even when he wasn't there. So, he had the sense that even when he's gone, he's going to be able to provide for his children. 

And how did that translate? He told me a few days or weeks after the session that something had happened to make him bleed -- not cancer-related -- and his seven-year-old was like "Dad, are you dying?" And he's said "No, no. This is what happened." That moment allowed him to have a conversation with his son about cancer and about death. It's something that he would have never done before that, but he was able to talk to him about these difficult things while he was alive with his son, which is a way to teach his son in a way that he wouldn't have been able to before. His mother was also having a hard time because her son has a cancer that's potentially fatal, and after that diagnosis, the relationship changed. After that, he went back to his mom, and he said, "Mom, I want to have our old relationship back. I don't know how much time we have. But let's talk about things. Let's be together." So, this person that was in the middle of the cancer diagnosis was able to change both generations and that's the impact even when he's gone, the roots continue to nourish the other trees coming up.

Shiv Gaglani: That's beautiful. That's really the type of perspective shift that psychedelics can bring, just like having a new friend or reading a book. Those are perspective shifting, but this is obviously more visceral, as we've heard from guests like Jim Fadiman. 

We also had Scott Carney on the podcast. He wrote the book The Wedge where he talks about him and his wife doing psychedelic-assisted therapy for couples. I don't know if there are any FDA studies for that kind of stuff yet, but I think yours maybe the first I've heard of where it involves the caregiver and the patient. That's very interesting. 

Dr. Manish Agarwal: That's a good thing you picked up on, because, well, what are psychedelics doing? And I think it is this visceral felt experience. A lot of things that you hear about are concepts in your mind. You could tell someone, “You'll still have an impact when you're gone,” but for them to feel it in their body and in their soul level, that's what's transformative. I think so many of us have busy lives and live in our heads, and to actually have an embodied experience, that's what's transformative. That's a good pickup.

Shiv Gaglani: Likewise. Thanks for articulating that in a way that I think will resonate with our audience. What are some of the concerns around psychedelic therapy? You know, the medical community still stigmatizes this, but it seems like things are turning around with all these FDA-approved studies, and companies like yours and COMPASS.

Dr. Manish Agarwal: I think it's still early days. I don't know that we fully know how to best use them and how they should fit into current standards of care that we have around mental health and other diseases. We need to do rigorous studies to see how to optimize our treatment. Do people need one or two treatments? How many integration sessions? There's so much still more to learn.

I think one cautionary tale I have is that I do think we fluctuate between really being scared of them and having hype. I don't think they're a magic bullet. I think they are a very powerful tool that can change someone's perspective and with the proper support and guidance and context, they can lead to a real transformation. But it's not that you take a pill and everything is fine and your problems go away. So, sometimes I worry about the hype, that this is somehow a magic bullet that's going to cure all of people's ills. Then there's what you mentioned, the other thing of ‘oh, these are bad, woo-woo drugs that we should not look at.’ I think that they're a very powerful tool and probably will change the way we think about mental health, but we really need to look at them with rigor of how to best incorporate them.

Shiv Gaglani: Yeah, I agree. There's always a hype cycle when it comes to these kinds of innovations. There's no silver bullet, it seems, but certainly, this is something that shows a lot of promise. So, as you look toward the future, you have some very exciting studies, some great results already. Where do you see Sunstone Therapies in the next five years?

Dr. Manish Agarwal: I think we'll have centers throughout the country, and we want to be a trusted place. If you needed neurosurgery, you're going to go to somebody that knows how to do that, and so if you're doing deep psychological or soul work, you want to go to a place that's been down this path and knows how to do it. So, we want to build centers of excellence that really know how to take care of people and hold them in a way that is effective and transformative.

Shiv Gaglani: Yeah, that's very, very exciting. It'd be good to see how that expands, especially with certain cities and states being very open-minded around psychedelic-assisted therapy. Oregon, Colorado and California being three of the main ones. We are a teaching company, as you know, and we like to fill in knowledge gaps so I'm wondering, if you could snap your fingers and teach any community, any group of people -- whether it's med students, or patients or the general public -- about any topic, what it would be and why?

Dr. Manish Agarwal: I think mental health to med students and the medical community, too. All through med school and residency, I don't feel like I got great education around that. It's sort of stigmatized and taught in what I found to be quite a boxy way. The education needs to be more real about how much of an impact it has as you as a person, as a med student and as a clinician and to raise awareness around that and understand the subtleties of what it is and not sort of stigmatize it or put it away. I didn't appreciate the full impact of it until much later in life.

Shiv Gaglani: Yes, I agree. I think a lot of med students -- especially this was true for me a decade ago when I first started med school -- they just haven't lived life enough. Many of them do come in with significant things, they've gone through -- family issues and whatnot -- but who you are in your thirties is very different than who you are in your twenties, generally and so that lived experience breeds an interest in things like this, and philosophy. Ultimately, it's all abstract until you actually live it or treat patients like you've done for decades now. I just had two last questions. The first is, you're a clinician and you're an entrepreneur as well. What advice would you give to our audience about meeting the challenges of their career moving forward?

Dr. Manish Agarwal: Keep pursuing your interests because they may not make sense until much later. If I was an engineer, and then philosophy and medicine and oncology. Now, I finally feel like I'm actually doing what I was meant to do. It's taken a long time to get here, but I would say that now I'm using all of those tools every day -- the engineering, philosophy, the oncology. In the moment, sometimes it feels like you're meandering or are you really doing your thing. Life is long. Keep going, because sometimes it comes together later. So be curious. Direct is always not the best path.

Shiv Gaglani: That's great advice and reminds me of a quote Steve Jobs once said, which is "You can only connect the dots looking backwards, not forwards." So, taking those disparate interests and just following those makes a lot of sense. Is there anything else you want to get across our audience about you, about Sunstone, about this space in general?

Dr. Manish Agarwal: In terms of the space, I would again just emphasize that with psychedelics right now there's a lot of hype around the compound, which is somewhat important, but I think the delivery is really important. And so as you think about psychedelics and learn about them if you're curious, the context and setting and the way you approach it and how you receive it is really going to determine the safety and efficacy. I worry because as the hype grows, people just want to get psychedelics and take them and then bad outcomes can occur. So, do the work to understand the right context of where they should be used.

Shiv Gaglani: Yeah, perfect. That's a great point and I know Zeshan speaks very highly of you and Sunstone because you've designed it with, as you said, the therapy is first and the psychedelics are just a tool that makes therapy more effective, not the other way around.

Dr. Manish Agarwal: Yes. At Sunstone we're obsessed with patient experience and how to really create a safe and effective place, and so every detail is focused around that.

Shiv Gaglani: Awesome. Well, I'm super thrilled about the work that you're doing and very excited to meet up in person when I'm back in med school back in Baltimore. Manish, thanks for taking the time to be with us today.

Dr. Manish Agarwal: Thanks for asking me. I'll see you in February.

Shiv Gaglani: Awesome, with that, I'm Shiv Gaglani. Thank you to our audience for checking out today's show and remember to do your part to raise the line and strengthen our healthcare system. We're all in this together. Take care.