Making Sense with Sam Harris - #337 — The Future of Psychedelic Medicine

Episode Date: October 4, 2023

Sam Harris speaks with Jeannie Fontana and Robin Carhart-Harris about the TREAT Initiative in California and the growing promise of psychedelics for mental health care. If the Making Sense podcast logo in your player is BLACK, you can SUBSCRIBE to gain access to all full-length episodes at samharris.org/subscribe. Learning how to train your mind is the single greatest investment you can make in life. That’s why Sam Harris created the Waking Up app. From rational mindfulness practice to lessons on some of life’s most important topics, join Sam as he demystifies the practice of meditation and explores the theory behind it.

Welcome to the Making Sense Podcast. This is Sam Harris. Today I'm speaking with Jeanne Fontana and Robin Carhart-Harris. Jeanne is a MD-PhD and a leader in the healthcare space. She's been instrumental in increasing federal funding for ALS research and is a founding trustee of the California Institute of Regenerative Medicine, where she played a pivotal role in creating the world's largest stem cell granting agency with an $8.5 billion budget. Under her influence, the agency achieved FDA approvals, fast-track designations, and launched groundbreaking clinical trials.

Additionally, it helped create over 55,000 jobs in California, 50 new companies, and $10 billion in added state revenue. And now Jeanne is focused on a new initiative, which we'll be talking about. It is called Treat California, T-R-E-A-T, and this is a citizen-led ballot initiative that will provide $5 billion in funding for research and affordable access to mental health treatments using psychedelic medicines. You can get more information at the website treatcalifornia.org, but the immediate need now is that they have to collect 1 million signatures from registered California voters. So if you are a registered voter in California, you can go to treatcalifornia.org

and download a petition, print it out, and sign it. And whether you're a registered California voter or not, you can collect signatures from California residents. And there's more information on the Treat website about how to do that. And wherever you live on earth, you can donate to Treat, because gathering one million signatures is actually a very expensive thing to do. It usually costs many millions of dollars, because it all has to be done physically. You can't just sign the petition on the website. You'll hear much more about the initiative from Jeannie in a few moments, but I just wanted to give you the call to action up front.

Once again, that website is TREAT, T-R-E-A-T, california.org. Jeanne and I are also joined today by Robin Carhart-Harris, who founded the Center for Psychedelic Research at Imperial College London, the first center of its kind, in 2019. Then in 2021, Robin became the inaugural Ralph Metzner Distinguished Professor of Neurology and Psychiatry at the University of California, San Francisco. He's also been listed by Time Magazine as among the 100 next. This is a group of emerging leaders from around the world who are shaping the future. He holds a PhD in psychopharmacology from the University of Bristol, and he's led neuroimaging studies with LSD, psilocybin, MDMA, and DMT,

as well as several clinical trials, psilocybin, MDMA, and DMT, as well as several clinical trials for psilocybin therapy. And the topic of discussion today is the TREAT initiative in California and the growing promise of psychedelics for mental health care. We cover some of the recent research and just generally explore how we seem to be at the tipping point here after all the time that was lost when these compounds were criminalized. It seems that the commitment to be at the tipping point here. After all the time that was lost when these compounds were criminalized, it seems that the commitment to research at this point feels rather unstoppable. And it is certainly no exaggeration to say that what happens in California could well determine what happens in the United States as a whole. And now I bring you Jeanne Fontana and Robin Carhart-Harris.

I am here with Jeanne Fontana and Robin Carhart-Harris. Jeanne, Robin, thanks for joining me on the podcast. Thank you, Sam. Thank you, Sam. So we're going to talk about psychedelics and their therapeutic potential and the current state of the scientific research, but also we're going to talk about this very ambitious initiative that Jeannie, you are launching in California. Before we start, perhaps each of you can summarize your professional background and tell me how you came to focus on this particular issue. So, let's start with you, Jeannie. Thanks. Robin and I are pointing fingers at each other. You first.

Well, I'm trained as a MD, PhD, trained as an internist, and then I have a PhD in biochemistry and molecular biophysics. I started as a young woman thinking that I was going to develop some therapeutic that would help treat millions of people. So I've always kind of had this drive in me since I was young. As I finished all my training, which was long and extensive, my mother was diagnosed with ALS. And at the time, I remembered it was one of those horrible diseases that I read in my textbook, but I really did, there was not much known about this. This was back in the late 1990s. And so I thought with all my education and my privilege in life, that I had an opportunity to dive into drug discovery to help find a therapy, of course, starting off trying to find one for

my mother, but then also getting involved with the ALS community and realizing that, you know, there's such a desperate need here for research and patient care. So I dove all in. And I don't know how long, which time you want me to spend on this, but this experience brought me to participating in changing federal legislation for ALS, and that was really empowering for me to know how to work within the system to change laws that impact the lives of tens of thousands of ALS patients in perpetuity until the law was changed. And also going back to the Department of Defense and increasing funding for ALS and understanding and learning quickly how to work within the system to increase funding, because

at the time there was next to zero funding from the National Institutes of Health, which is where most of the funding comes from for basic research. So that was interesting. And then at the same time, human embryonic stem cells were just discovered in the late 1990s. And I happened to be working with a very wonderful medical research institute in San Diego where the top scientists there, and one was a leading stem cell scientist, and brought this to my attention is not to replace neurons in a dish, but to create a disease in a dish because we can't study human brain tissue easily. So that was very exciting to think about having the capability of a large scale pharmaceutical companies where we could identify molecules, a disease of modifying

molecules. At the same time, George Bush put a moratorium on the funding of embryonic stem cells for political reasons. And so it was one of those aha moments where you say, wait, there's some real therapeutic benefits from this research and not having any funding and watching all research stopping, in essence, just screeching halt, and reacting to that. Unfortunately, there was a force of nature here in California from Silicon Valley whose son had juvenile diabetes, and he was always looking for a therapeutic cure and had been speaking with the scientists at Stanford, and they were talking about the promise of stem cells and recognizing that the federal government was limiting the amount of funding on it. So there's a pathway in California where the citizens can demand that the California government actually provide services that they want. In this case, we launched a citizen-driven ballot initiative to create the first-of-its-kind funding agency for embryonic stem cells. And I was on that campaign and educating the public about it and educating doctors and

patients and participated in editorials and things like that. And I honestly did not think the bill would pass. We were in a bleeding economy at the time. And when I was lobbying at the Sacramento with some of the politicians there, they said, wow, this is, yes, it seems to be promising. And the time it really was in its basic research level. But we can't pay our teachers and our police department and our firemen. And why should we spend this kind of money on basic research? And I didn't have an answer. I agreed with them. I said, you know, we have to pay our teachers.

But what I learned is that in 2004, it was the citizens of California that approved this citizen-driven ballot initiative and created the first of its kind and the largest in the world, a $3 billion funding agency focused on stem cell research. So I was honored by being a board member creating this new institute, and we were charged with expediting bench-to-bedside research, which normally takes about 15 years to go from the lab to a therapy at the bedside. And on average in the 2000 dollars was about 1.5 billion dollars. So we wanted to set up a granting agency that was improved upon the NIH's system and we had people from all over the country and the world actually reviewing the different granting

agencies and we set up something that I think by all accounts ended up being pretty successful. season, we set up something that I think, by all accounts, ended up being pretty successful. So by the end of the 15 years when the money ran up, we had two FDA-approved therapeutics and about nine breakthrough and fast-track therapeutics. And importantly, we had 60 compounds, what we say in the pipeline, that were deserving of further funding. So the same force of nature went back to the voters of California during the height of the pandemic and qualified for the ballot. And the voters of California approved an additional $5.5 billion. So, you know, in addition to bringing therapies to the patients, CIRM is also credited with bringing about 55,000 jobs, additional jobs to California, and 50 companies born out of this, and additional about $10 billion in revenue to the state.

So I recognize now that we created and built what is now the regenerative medicine infrastructure. And it took me a while to really appreciate how amazing that was. And I'm so proud of participating in something where we actually, you know, delivered on our promise, which was, you know, expediting bench-to-bedside research and bringing therapies to patients and creating a whole new industry of which now we'll combine it with gene editing and other future breakthroughs that we have in medicine that we combined and we will actually cure some incurable diseases now. Nice. So this is a long introduction. I've stopped here because I could keep on going. Yeah, well, no, we'll pick up the trail there talking about that initiative pathway. But let's bring in Robin.

Robin, how did you come to study the brain and the nervous system? And what have you focused on? And how did you come to focus on psychedelics? Yeah. So I was a curious teenager. You could say I had some experiences. And I felt a gravitational pull to psychology. I did a degree in psychology in my hometown of Bournemouth on the south coast of England.

And then towards the end of that, I enrolled to do a master's in psychoanalysis. So I was especially drawn to depth psychology. psychoanalysis. I was especially drawn to depth psychology. But that said, I was also drawn to rigorous scientific approaches to the mind. Perhaps psychoanalysis can be a little weaker in that sense. A few parts of it have not aged especially well. But maybe some of them have, maybe some, sometimes a little bit underappreciated. But yeah, I was drawn to neuroscience and I ended up getting lucky with an opportunity at the University of Bristol to do a PhD in psychopharmacology, focusing on the serotonin system, doing some polysomnography, so sleep recordings

of MDMA users and matched controls who had their serotonin system stressed with something called tryptophan depletion, a dietary manipulation. But anyway, this was kind of my way in. And I did come to that unit. It was David Nutt's unit, Professor David Nutt, former so-called drug czar in the UK, the chief scientific advisor to the UK government on drug policy. And I came knocking on his door asking to do psychedelic research. And he opened it saying, well, you can do some serotonin research and we'll see how things go.

But I was especially interested in psychedelics. I'd learned of their history being used as tools to assist psychotherapy. And actually, often that was a kind of depth psychotherapy and a similar, in a sense, quite similar to psychoanalysis, albeit an accelerated version. And that was kind of my way in. So on completing my PhD, then I had, again, a good opportunity, some good fortune through a visionary philanthropist, Amanda Fielding of the Beckley Foundation, to do some brain imaging work. That's really what I wanted to do. I came to David initially wanting to do an LSD fMRI study. I had this hypothesis that the psychedelic state was like a waking dream state, a hybrid, you know, dream sleep waking state. And I thought through, you know, the lens of fMRI, functional brain imaging, I could,

in a sense, prove that hypothesis. That was my naivety at the time. But that was the initial thread that drew me in. And since then, I've done a series of brain imaging studies with a range of different psychedelic drugs, psilocybin, LSD, MDMA, DMT. And off the back of that, off the back of some of the insights that we were getting from the brain imaging, I set up first a clinical trial with psilocybin therapy in treatment-resistant depression. And then since then,

that kind of got a ball rolling at a certain time. And I guess we're going to go there. But yes, a lot of momentum now in psychedelic medicine. Yeah. Well, I want to talk about the state of the research and how you differentiate the promise of the various compounds you mentioned and perhaps others. But before we go there, let's talk about the TREAT initiative, because I want people to know about it up front here. My wife, Annika, is the one who told me about it, and she's been involved with Eugenie helping it along. And she, in preparation for this conversation, she has let me know that she thinks it's difficult to communicate the full vision of this initiative.

And so I'm wondering, Jeannie, can you explain what you're hoping to accomplish and perhaps anticipate any common misunderstandings of what you're attempting to do? and misunderstandings of what you're attempting to do. I laugh because it's an enormous project with many layers. So it is a challenge to try to sum it up in a few words. But I've been practicing this quite a bit because I think what we have here is an opportunity to transform the way we deliver mental health care to start in California. These medicines are showing great promise through clinical trials performed from our top academic institutions that are nothing short of jaw-dropping to me. And as a scientist who looks at data,

it's rare that one comes across such promising preliminary data with the outcomes of patients who otherwise aren't treatable. So the goal of the TREAT Institute is to bring these medicines to the public in a responsible, safe, and ethical manner. the high perspective and talk about how we have to show these medicines to be safe and efficacious running large-scale clinical trials and tracking safety data, tracking outcome data, not just during the clinical trial period, but over lengths of time. And if for your listeners that are aware of medical studies, something like the Framingham study, where we tracked through generation, a lifetime actually, the outcomes of the patients. I think it's important to look at the different indications

that these medicines can help with. Right now, we know that it requires a therapist in the room, that seems to be the combination of therapy, talk therapy with these medicines. And that resonates with me as an athlete who was taught how to play a sport. When you're taught how to do something, you can do it better. And I think in our society, we're not taught how to manage our emotions in a healthy way. So I think the patients need to be prepared and educated with how to experience these medicines and what to importantly do with the insights and not just those that through their insurance policies they're able to take and others are not. We're well aware that the hardest hit communities in any society are the underserved communities and mental health while affecting every citizen of America right now, either personally with their family members or certainly with their friends,

is being touched by this. So the tools, though, that are provided to the underserved communities are particularly sparse. So the main impetus of the TREAT initiative is to make sure that these medicines and treatments are available to all. So I think I'll stop there because I can take up all your time here telling you about it. So I'll remind people at the end of our conversation, but I want to get up front the specific call to action, if there is any, for California residents now? And what is the actual initiative?

We are running a campaign, and it's called the TREAT California Campaign. And TREAT stands for Treatments, Research, Education, Access, and Therapies for Mental Health Using Psychedelic Assisted Therapies. In order to qualify for the ballot, which we're going to begin to do in two weeks, we need a million signatures to sign the petition saying they're interested in this to get on the ballot. The signatures need to come from registered voters. So we appreciate people going to our website and signing up so that when we get our green light to start collecting signatures, we'll be able to reach you and have you sign this petition. If we don't get the million signatures to qualify for the ballot, then this dream

dies. So we are prepared to do what it takes to make sure we qualify for the ballot. Once we've qualified for the ballot, which we intend to do by the year end, we spend all of 2024 educating the public on mental health, on psychedelic assisted therapies. And then as we get closer to the vote, and we know that there will be a lot of mayhem because it's a big presidential election, but we have to remind people to vote yes on our proposition on November 5th of 2024. And I'll have a link to the website in the show notes, but what is the website? It's treatcalifornia.org. And is there, you need to get signatures, but is there some component of fundraising here? I mean, is there something you need money for to

get those signatures? Thank you very much. Yes, I do. Running a campaign like this is enormously expensive. In California, it is on average $30 million. So we need donations. We have a 10-10-10 campaign. We're asking people to donate at least $10. think, you know, two Starbucks coffees from the people to help us pay for the tools that are required to make us be successful with this campaign. And obviously you don't have to be in California to donate to the campaign. No, thank you for that. In fact, one of our biggest donors thus far is a conservative Republican from Florida. The ideas are that once we run the trials here in California with the FDA, we get FDA approval, these medicines will be available to everybody in the country. So yes, everybody in the country can donate. Yeah, I'm glad you mentioned that you had a conservative Republican, at least one, backing, because I want to talk about the coalition you're building in support of this. It is surprising, and it does suggest that there's

a path here toward bypassing some of the obvious mistakes we made in the 60s around trying to study these compounds and their promise, and then also trying to enfranchise everyone in the society to take them. And that translation from the lab to the streets was less principled and governable than seemed wise in retrospect. Timothy Leary standing at the front of it. I guess my next question here is, there are some dichotomies that seem in opposition to one another, but they really might not be. I mean, people in the psychedelic space seem to think that there's this either-or decision between focusing on decriminalization versus research and field research versus lab research. You can have a medical model by which you frame this or a spiritual model.

How do you think about those dichotomies, Jeannie? Is this a hallucination we're having about hallucinogens? Thank you. And I've actually spent a lot of time thinking about this. I was born in the 60s and raised in the 60s and 70s and witnessed the counterculture revolution and the hippie generation. I also was subject to the Dare to Say No campaign by the Reagans.

They did a really good job scaring me to death. You know, this is your brain on drugs, that frying pan and the fear. And then also feeling the societal unrest around the Vietnam War and this cultural revolution that was happening, and the drugs were very front and center. So I was in it. I didn't participate myself in taking them, but I lived in it. I lived through it so I could feel the societal push and pull from all parties. And then not really appreciating what it meant when these medicines were locked up, basically. And then what I've learned subsequently is that they were sort of driven underground. And there's a couple of paths that I want to share here. One is the reason why I'm sitting here is because of the great work that was done out of our academic institutions, at Johns Hopkins and Yale and NYU, and now Robbins works in front of me,

recognizing that these studies were funded by philanthropists, and philanthropists whose lives have been changed by their use of psychedelics early on. and I think most famously is Steve Jobs, who attributes his LSD use to helping build the iPhone. So I also have great respect for these medicines as a clinician. So when you're a clinician, you have to think about all types of patients that come to you, and you have to think about best practices for all your patients. And while I appreciate and respect the psychedelic community's experience with the medicines, I hesitate when I think about these medicines being available to the general public without any safety guardrails, any guidance, any supervision.

And I am concerned about negative consequences and then having these negative consequences blown up so that the research can't proceed because of political actions again. And in fact, there's this wonderful group of mothers who I recently befriended that their children, college-age kids, were using psychedelics and for different reasons ended up dying. They were not supervised and they thought they could fly and jumped off a bridge, which I always thought was a sort of a folklore story from the government to try to scare us all. But indeed, that can happen.

And while I appreciate that these mothers are pushing for safe supervision of these medicines, that they're not protesting that these medicines should never be brought to the public. In fact, quite the contrary. They say that it should never be brought to the public. In fact, quite the contrary. They say that it needs to be brought to the public in a safe, responsible, and ethical way. So allow me a little more time to share with you the vision that I have for what the Treat Institute will do. So we are not directly a decrim or legalization effort.

While I don't believe people should be thrown in jail for the use of psychedelics or cannabis for that matter, we are not focused on decrim. Legalization is something I don't support at this period of time because when you're bringing it out to the general public, you have to think about all people who are having access to these medicines. And I believe these medicines need to be treated with respect. The persons need to be prepared and educated and supervised and allow the information revealed in these medicines to be shown how to incorporate them into their own lives so they can take power and control and agency over their emotional well-being. So what we plan to do at the TREAT Institute, which is this $5 billion funding agency,

where we'll have monies allocated towards running large-scale clinical trials with the known medicines with known indications like anxiety, depression, and PTSD, as well as others, is that it's important to look at the way these medicines have been administered. We know for thousands of years it's been ceremonially. We also know they've been used in religious settings. We know that sometimes it's used in group settings. And there are benefits for patients under each condition. group settings. And there are benefits for patients under each condition. So I can foresee a situation where we look at, once we show these medicines are safe, effective with the model that's mandated by the FDA right now, which is our two therapists in the room at all times,

that we can look at how does a patient respond to being in a group setting? Likewise, how would they respond to being in a ceremonial setting and even a religious setting? And can we show that it is safe and effective for those people? And if so, can we scale it to maintain safety? So I sort of look at it like going to a restaurant. And as we defined more the criteria of what works for the one patient, we're leaving this model of one pill per person for a symptom, which sort of masks symptoms. We say, what will benefit that person more as the individual, a more of an integrative approach? So I may prefer to be in a more clinical setting with a one-on-one therapist. And as I work through some of my issues, I may benefit from being amongst a group setting because

there's some healing to be gained by these group settings where there's safe containers and people can reflect for you the emotions that you're working through. And there's something very beautiful in those group settings. Likewise, the wisdom keepers and the way these medicines have been delivered to man for, I mean, you could maybe even argue tens of thousands of years, 70,000 years, have been through these ceremonies. And I think there's some truism to it, and I think we need to look at it. We need to study it, and how do we safely bring this model to the citizens first of

California and then the rest of the country. And lastly, we have to honor the spirituality of this. Religious leaders, it's been really one of the more surprising things for me to start exploring religion, and I don't mean the organized religion, but the spirituality behind religion. And there's really not that much of a difference when you're in one's altered state of consciousness and the common descriptions people have of feeling at one or with this love. And if you happen to be religious, you can relate to it as being God, or you can feel Jesus's love, or whatever religion it is that you subscribe to can strengthen that emotion. So I think the Treat Institute offers an opportunity to really address the real healing potential of these different therapeutic modalities. Always keeping in mind, though, is how we can scale it and scale it safely. Well, on the point of scale, where does the federal government come in and how would Treat influence federal policy if it passed in California?

Well, we're planning on passing. And what we're going to set out doing is to test the safety and efficacy of these medicines. While we all believe these medicines to be safe. There's really no well-run study that looks at safety. And I think it would be irresponsible for us to, if some untoward side effect is revealed when you start looking at thousands of patients, tens of thousands of patients, that something comes up that is deemed too difficult to get around. We're going to stop funding. We're not intended to fund just because we've been approved for $5 billion. So I'm going to assume that this is safe and that it actually works. And we're working with the FDA and the DEA for approval. And when we get that approval, it becomes available to

the country. We will continue to run trials with different medicines and different indications, collecting data all along the way. I talk about our three trifecta of our goals, which is to improve patient outcomes, to show that it's cost-effective, and that we make it accessible to all. So copying the model that we did with the stem cell agency, we actually helped the federal government come up with their own guidelines and regulations around stem cells and how they should be administered to the rest of the country. So I view us as working with the existing system, bringing evidence and data to support the decisions that we make. You know, I'm not naive about this,

but I believe that, you know, we should make decisions based upon evidence and data as best we can. So before we get into the state of the research, I just want to see if I can get more information from you on the coalition you have built in support of TREAT. And perhaps there are people who support you who aren't ready to go public yet, so feel free to edit your response. But I just know that there's a fairly bewildering diversity of people and groups that actually support you, bewildering diversity of people and groups that actually support you. And you seem to have quite a talent for bringing together collaborators and supporters who wouldn't normally find themselves on the same team. Can you say more about that? Well, first of all, I'm just honored. I'm so honored to work with the people on my team. And I think we are all aligned. And what I

love about this project, there's so many things I love about this project, is that we're showing up as very competent, credible, experienced human beings who are aligned to help and serve others. And so in this case, I can touch every person because there's not one person, I'm going to repeat this, in our country that is not personally touched by mental health issues, depression, anxiety, addiction. Their family members are, addiction, their family members are, and certainly their friends. So that when we're discussing bringing a new tool, we're bringing a new tool to the healthcare provider to help people that aren't otherwise helped. And we're doing it with rigorous research, oversight, and not just the black and whites of evidence as we're bringing heart to this. We want to bring compassion to how we're treating people.

with competency, and importantly, with compassion, I'm able to pull in other like-minded, extraordinary human beings, and I'm so lucky. So to that end, you know, I have to brag about my campaign manager. This is a man who was the senior advisor, essentially the right hand of Rich Trumka, who was the president of the AFL-CIO unions. And if you're not aware about unions, which I was not before this, there are about a handful of incredibly powerful unions that represent the workers. And the AFL-CIO union represents about 60 different unions, each representing the workers, the backbones of America. They make our country run. These are the people who take care of our children, of our, in the hospitals, in our home, the nursing homes, the plumbers, the people who create the roads, the postal workers, the fire departments, the nurses, the teachers. Because of Ramon, has been in this business for 30 years, has run hundreds of campaigns, including supporting presidential campaigns. His wealth of experience is bar none. And because he's such an honorable person,

the doors are open for us. So he puts me in front of the leaders of some of the major unions in our state and in our country and allows me to share the vision of the Treat California Act. And every single meeting we've had, they are supporting us. And they are in the process of working through the procedures that they do to endorse us. And I'm proud to share with you that we got the endorsement from the Long Beach Firefighter Union before we even submitted our legislation, which was the first in union history. We also got the support of the American postal workers for the Los Angeles area and San Diego areas. This ground-level support from the people, these are everyday workers who are

suffering themselves, their family members are, and they're also taking care of people who are suffering. So when we show up and we say, you know, this is not a cure-all, I do not think psychedelic-assisted therapy is going to cure every person, but I say if we can address 10% of the population that's suffering from depression, anxiety, addiction, just 10%, they're otherwise not treated by. We're saving, we don't even talk about money, but we're saving people's lives. And those workers who, you know, have to miss days of work either because they're suffering from something or they're family members and they have to take a day off to go help with a family member who needs help, and the people that they're also taking care of.

We're in the state of a mental health care crisis, so that when I'm in front of these union leaders and I'm talking to them about their members, they feel this. This is not just another political campaign. This is not just a way to go waste some more money of the government. This is actually a real solution. And so they line up. And so then in addition to that, we've got the veteran community, because this is where it all began for me with the great work that MAPS did, the nonprofit MAPS and the clinical trials that they were looking at the veteran community. And of course, the veteran community is near and dear to me. But we're talking about our vets right now, 40 suicides or self-harm a day in our veteran community, in large part by PTSD.

And I have met many of them. And in fact, we have six former Navy SEALs on our team. We have two generals on our team. I have a three-star general, the former commanding officer of the U.S. Marines on our team. And he has been educating the federal government and the VA about the importance of funding this research for our vets who right now are failing therapies and they have to leave the country to undergo psychedelic-assisted therapies. And they come back, many of them, not all, many of them come back, changed human beings. And in fact, I like to go off on this little tangent here for you because it's so important. Rick Perry, a self-professed knuckle-dragging Republican

from Texas, had an aide on his team who was a former vet who was struggling with PTSD. And on average, these people, you know, it's decades of struggling, barely making it to work and all that kind of thing. And he left the country and underwent psychedelic assisted therapy and came back and Rick Perry noticed. And he said, what's going on? What's the difference? And the guy shared it with him. And he said, oh my God, I have to do something. So he went to his legislation and in 2020 passed a bill that afforded $100 million in Texas to study psychedelic assisted therapy for the veterans. So the veteran community is one that is so desperately in need, like so many Americans are. But the veterans are something that the political right can relate to.

So we pick this community to help bridge the divide that is tearing our country apart right now and say this is not a Republican issue or a Democratic issue. This is a human issue, and that we have to take care of our veterans as well as our first responders. I've gotten to know the firefighters. I've learned, shockingly, that suicide is the second leading cause of death amongst our firefighters

now. I met with the head of the California Firefighters Union, and I'm working with Dr. Sarah Abadie, who is another remarkable human being. And she left her practice at UCLA as an ER physician because she was so tired with patients repeatedly coming into the ER and not being able to treat them at all. And because she's this caring, compassionate person that she is, she's met a few of them that actually left patients, that left the country, that underwent psychedelic-assisted therapy and came back and visited with her. And she just couldn't believe the change. And she herself was traumatized being in the ER during COVID. And they call it this wounded healer, this moral deterioration of not being able to really to help people and not having any support about all the trauma, the emotional trauma

of which, you know, these are our first responders taking care of us and they are having problems. And so she left and became trained as a psychedelic assisted therapist and participated in clinical trials. And they're launching a trial at the VA again to help address this unmet need within the VA. So we've got the veteran community supporting us. We've got the union people supporting us. And now we've got the LGBTQ community where there are about 3 million voters that identify as LGBTQ. voters that identify as LGBTQ. And this community is being particularly hard hit in today's political environment. And they are rallying behind us to help. They're very politically active as well. And then lastly, we're reaching the university students. We believe that the future is in the youth. And they don't have the hangover, what I call the hangover from the Dare to Say No campaigns. They're much more open-minded. They're much more interested in problem-solving. And I ache for the world that this generation is inheriting from us, but I also have great hope because it's a great generation. So we've got the kids, too, that are supporting this. And they're showing up.

to hear from you about what it's like on the front lines there. You've named some of the clinical applications here, addiction, depression, PTSD. We can also add end-of-life anxiety. Probably we can extend the list beyond that, but then there's also just the betterment of well people, which I know Roland Griffiths, who I've spoken with on the podcast before, has been focusing on. Robin, take any piece of this that you want, but I think we should discuss what compounds we're talking about and how do you think we should prioritize or how are you prioritizing the study of them and what seems most promising? What do you think we're going to see at the bedside first? I mean, just what's happening here on the research front? Well, clearly a lot. It's having such an impact now.

I mean, even as we speak, another big paper has landed in nature medicine. It was the second of two phase three trials that MAPS sponsored, Rick Doblier, the Multidisciplinary Association of Psychedelic Studies and MDMA therapy for post-traumatic stress disorder. And the results of this trial are as positive as the previous phase three trial. And so, you know, the FDA asked for two positive phase three trials. They've got them now. So, you know, the FDA asked for two positive phase three trials. They've got them now. Those results are in the public domain.

So MDMA therapy is the furthest along in terms of being federally approved as a prescribable medicine. And we know, you know, how it has to be delivered as a combination treatment. It's not just the drug. That's a really important principle of psychedelic therapy. It's not just the drug. That's a really important principle of psychedelic therapy, the clues in the name. It's not just psychedelics we're talking about, it's this combination with the way the drugs are given. And so MDMA is front of the queue, and the forecasts are for next year in terms of approval. We'll see. are for next year in terms of approval. We'll see. And would the approval be for narrowly for PTSD or is it for these other conditions as well, like depression or end-of-life anxiety? It's for PTSD. Those were the specific trials. That was the specific indication. So that's on

the label. That's the first indication on the label. But clinicians can prescribe off label and they do. So it's possible that they could be providing that intervention for other indications. But it's sort of baby steps once it's through the gate and it will be PTSD. And it'll be a slow process of collecting safety data before large numbers of people are being treated with MDMA therapy. But it's the big milestone is getting the first psychedelic therapy through FDA approval. So these state-level initiatives are another thing,

but that's the sort of classic traditional formal medical model with the FDA that MDMA therapy is on the cusp of getting that approval. And next in the queue is psilocybin therapy. So there's a phase three trial currently underway, sponsored by Compass Pathways. And there the indication is treatment-resistant depression, somewhat building on the work that we did at Imperial College London doing the first psilocybin therapy for depression trial there, and that was in treatment-resistant depression published in 2016. So yeah, that's going to be the first phase three trial of psilocybin therapy for treatment-resistant depression. And I think forecast something in the domain of

26, 2026 for having that work done and that going to the FDA. So that's kind of where we are right now. Then there's a bunch of other compounds, of course. Ketamine already is used as a medicine and ketamine therapies is happening right now at some scale, treating depression and so on, rapid acting antidepressant. Somewhat a different model and also a different compound. I'm not sure I would lump it in with psychedelics personally. I think sometimes that term is a little too fuzzily defined or there's a lack of a crisp definition really, but that's there. And then there are other compounds, other classic psychedelics such as LSD. Trials are being done and published on LSD therapy for depression, also alcohol dependence, Michael Bogan shoots. And there's DMT, that's a rapid acting classic psychedelic.

It's given intravenously in some of the work that's being done at the moment. Some of the studies we've done at Imperial with brain imaging has given that drug intravenously. It's the main psychedelic component of ayahuasca, the Amazonian brew. And then there's mescaline, Journey Collab are looking at that with an interest in addiction. So there's quite a lot. How about Ibogaine? There's quite a lot. How about Ibogaine? Yeah, Ibogaine as well. There's some very, very interesting naturalistic work having been done with Ibogaine in veterans with different aspects of mental illness, addictions, PTSD, likely some brain injury issues as well.

And so some very promising data coming out of that from Nolan Williams at Stanford doing sort of observational work and also some brain imaging in people going off to Mexico to have these treatments. Very exciting, interesting compound, exciting findings. So that's another one too. Yeah, there's a lot going on. Well, notwithstanding what Jeannie said about the need to do a lot more research to assess the safety of these drugs, what do we know about the physiological toxicity or safety of the various compounds? I mean, because my understanding is with something like psilocybin or LSD, there really is no indication that it's physically toxic apart from the possibility of having a bad psychological outcome and, you know, in the worst case, obviously hurting yourself or killing yourself the way Jeannie described, you know, taking these medications out in the wild.

Jeannie described in taking these medications out in the wild. But with a drug like MDMA or ketamine, you're talking about something where there really is an LD50, a lethal dose that could be easily specified. And perhaps there's some physiological toxicity that we know about in those drugs, even at safe doses, many times repeated. So what can you say to safety? In reality, there are a lot of people listening to this who are, you know, they might be very supportive of everything we're talking about here and building a well-governed therapeutic model for helping people with the most relevant compounds. But in reality, there are also millions of people who have taken these, quote, recreationally. You happen to be talking to one of them right now. And in making decisions about what to take, there are differences here. And obviously, we should add the caveat that not everyone should take these compounds,

certainly not in a situation where they haven't seen to all of the necessities of set and setting. And I've talked about that at great length on other podcasts with people like Roland Griffiths and James Fadiman and others. But there are just differences here. And we should also stipulate that in many cases, unless you're in the presence of something like psilocybin mushrooms, you're taking something that unless you've had it studied in a lab, you can't be sure you're taking the compound you think you're taking. So all of those caveats aside, in the presence of the actual compounds, can you differentiate any safety concerns at the physiological level? Yes, absolutely. I mean, the compounds are often

too easily lumped together as, you know, say psychedelics, but they're really quite distinct and the toxicity profiles are quite distinct. I mean, the dose makes the poison. So even those compounds with the better therapeutic indices, meaning that a therapeutic dose to a dangerous or lethal dose could be massive. And in the case of, say, psilocybin, it is a very large therapeutic index. So that's very positive. So that's very positive, you know. But tighter with LSD, actually, you know, LSD is very potent. So it is not so hard to overdose on LSD. And then it's not just a psychological risk, but there's also some physiological risk as well. MDMA carries some toxicity in high doses. That's some evidence of neurotoxicity.

But in therapeutic doses, it seems unlikely. Then you have other organs where MDMA can be toxic to those as well. The liver, ketamine has high toxicity, some appreciable toxicity for the bladder and a metabolite of that. So that can be a problem. There've been cases of people having their bladders removed from excessive use of ketamine. Ketamine is also addictive, right? It is. Another part of the risk profile, elevated risk profile, I'd say with ketamine. I see ketamine, you know, ketamine therapy is a kind of placeholder for interventions like psilocybin therapy coming down the line. A number of different angles in which psilocybin therapy I think is superior to ketamine. The toxicity, it's got the rapid action, but it's also got a more enduring action. In my mind, it's a deeper quality of action as well. A lot of effect on psychological insight, emotional release that perhaps you don't get so easily with ketamine. That's probably part of the reason why it has a longer tail in terms of a therapeutic response, psilocybin versus ketamine.

So a lot of differences. And we talked about ibogaine a little bit there. There's some cardiotoxicity questions. And actually, that's really hampered some of the clinical research with that compound. There hasn't been much in terms of control studies with ibogaine because of question marks over how safe it is in terms of, you know, cardio risk. Most people don't differentiate ketamine, which is an analgesic, and MDMA, which is a type of amphetamine, don't really fall into the class of a true hallucinogen, which are mainly tryptamine derivatives. And so I also want to point out that both ketamine and MDMA are addictive

and have different physiological properties. I'm not so sure on MDMA. Yeah. Okay, to be explored, because amphetamines in general. Amphetamines, yes, but MDMA is quite different to other amphetamines in terms of amphetamines as a class have that very strong dopamine release, but serotonin release is 10 times that of dopamine. So it's quite distinct, I would say, from most other amphetamines. And also there isn't clear evidence that people take MDMA in a sort of Moorish way, you know, crave it. So what I'm hoping, of course, is that we can actually really study this and track data and

track and determine if it is indeed addictive or not. But until we have the funding to do this, these are all open-ended questions. And I just also wanted to highlight, I think for ketamine, I think one of the best applications will be for acute suicidality. Some of the studies are showing for people that are showing up acutely suicidal in the ER. Oftentimes, you sedate the person, you admit the person, you put them on a hold, and you wait until the SSRIs kind of kick in. It's just a standard of care. But ketamine, the fast-acting effect, appears to allow the patient to feel not depressed for a moment and in that feeling they can hold on to that thread actually of hope of not always feeling

so depressed which is what leads people to be suicidal so but when we're talking about what Mm-hmm. at all the qualities of these medicines and the impacts on the individuals. And I also want to highlight that what we hope to do is we're going to create what will be the largest bioinformatics data bank in the world focused on mental health. And of course, we'll make it cyber secure and anonymous and patients will opt in. But we plan on doing complete genomic sequencing, genetic sequencing, including all the omics, the panomics, the proteomics, the epigenetic changes, and then also including the information coming from all the scanning devices, the fMRIs, the wearable devices, and then overlay that with what we call the phenotypic expression. So a patient presents with anxiety, depression, PTSD, and oftentimes complex stuff and or addiction, as well as all the other mental health issues, what we can call.

And that by understanding perhaps the biology of, say, Robin sitting across the table from me has a different makeup of his serotonin receptors and his dopamine receptors that may be more amenable to a particular type of psychedelic versus another type. And so it's truly becoming more patient-specific, what is best for him, what will improve his probability of healing from these medicines or gaining insights that empower him to incorporate new habits in his life. And likewise, he may be more open to being in a group therapy to start or not. Maybe he wants to be in a one-on-one to get more comfortable with the medicines and then be in a group therapy. So we don't see it as such a prescriptive therapeutic approach where each person gets this amount for this amount of time

under these settings. I think it's important to talk about the variety by which we can learn to heal and make that available. So I'd add that. On this issue of further research, study by study, can you give me a sense of what a well-run study costs at the moment? Sure. Well, gosh, a well-run study, how do you define that? I mean, I know there's a wide range and Jeannie just floated the idea that we would be tracking thousands of people ideally in studies. But the sorts of studies that are being run now, let's say the MAPS study that's in, you know, stage three clinical trials. What do those studies cost? Hundreds of millions.

Yeah, I mean, I think it's fair to say, I mean, it took MAPS 37 years, I believe, from its beginning to finish two phase three trials to the tune of about $150 million. So it took, you know, 37 years. trial infrastructure here in our state with incredible academic institutions as well as contract research organizations will determine which ones can be most efficient and most cost effective. We can run trials with thousands of patients in a short period of time because we want to try to find a therapy that actually is safe and efficacious and then determine under what parameters should those patients receive this medicine. and then determine under what parameters should those patients receive this medicine. Yeah. You know, those phase three trials, the total sample, what's it going to be? In the ballpark of 300 people or something. You know, 300 people, it's a very difficult number to quantify because I've run another startup company and depending upon who you get and how you get and how many people you have to have in it. But, you know, it's on the order of, I mean, I think the smallest you can do

is almost a million, you know, maybe, really realistically with people that you know. But on average, I think it'd be fair to say that it's at least 100 million. Yeah, yeah. But, you know, of course, there's so many different types of studies and trials. And the first investigator-led trials, like the treatment-resistant depression trial we did at Imperial, we got some UK Medical Research Council money to make that possible. And that was, let's see, the first amount amount was I think it was even half a million so that ended up being a 20 patient trial open label because of some philanthropy that came in

but for a long time you know we were we were very much working on fumes we had volunteer staff you know working on the trials and we were just doing it kind of out of passion as much as anything. Things have changed a huge amount since then. What do you think is happening in the brain at this point, Robin, when we take one of the classic serotonergic psychedelics, so LSD, psilocybin. I'd be interested to know what you think is happening with MDMA as well. I think you said you did an fMRI study on DMT too. Give me the mapping that we are reasonably confident in at this point. Yeah, I think it's fair to say we're reasonably confident now because we've had,

I think it's fair to say we're reasonably confident now because we've had, personally, I've done three studies with three classics. DMT was the most recent. And so there are some principles that are emerging. One of them is that if we look at brain networks, which is more the way that we think of human brain function and making mappings to high-level cognition and conscious states. We're much more thinking about brain networks now, their dynamics. And there we see that across the board with psilocybin, LSD, DMT, you see a breakdown in the integrity of brain networks. And this is actually quite true across a repertoire of major brain networks, but especially so in high-level brain networks,

networks that we describe as transmodal, meaning they don't just do one thing, but they do a few things. They're involved in a lot, including the highest level aspects of human cognition or consciousness. So we see the integrity of those networks, the different nodes, the different parts that make them up, that breaks down. And at the same time, those networks open up their communication profile. So rather than being very segregated from each other, very insular, they start to communicate more with each other. And we can describe that a few different ways. We could call it desegregation, network desegregation.

So you have within network disintegration, and you have between network desegregation where at the global level, as in the whole of the brain, you could describe a global increase in functional integrity. more there's always more of course and you know i haven't even gone into the pharmacology that with the classic psychedelics one of the ways that we could define them i don't think we can we should only define them this way because it glosses over the phenomenology which i actually think is is key for a definition of these drugs but we do know with a high degree of confidence really mostly from the human research, and I think that is pivotal here, actually. We know that stimulating directly a certain serotonin receptor is key to their action. And we know that because there's a very tight positive correlation between the affinity

or stickiness or binding potential of a given psychedelic for that receptor specifically and its potency. Are these still the 2A receptors? Yeah, the serotonin 2A receptors. So higher affinity, more potent. LSD, very high affinity, very potent compound. And then we also know that if you pre-treat with a serotonin 2A receptor blocker, we call those antagonists, then the psychedelic can't hit its target because it's blocked and you don't trip. You don't have a psychedelic

experience. And then we also have more recent evidence that you can abort a trip by giving the blocker after giving the psychedelic. So, you know, these are just a few examples of really converging evidence on the 2A receptor as being the key initiation site to where it all begins, in a sense, with the action of at least the classic psychedelics. Is MDMA also active through the 2A receptors? Not directly, but really the key sort of signature pharmacological action of MDMA is its serotonin release. Yeah, it's really pretty unique in that sense. There aren't many compounds that release serotonin as potently. Yeah, I mean, we have the selective serotonin reuptake inhibitor,

antidepressants, Prozac-like drugs, but they're just blocking the reuptake. MDMA actually stimulates the release of serotonin. So I sometimes playfully call it a turbo SSRI. It's sort of spitting out serotonin into the synapse, that gap where all the key chemical information transfer happens between neurons. Well, in some possible dystopian future, it will be sold under that name in a drugstore near you to teenagers. What do you make of the fact that DMT is actually an endogenous neurotransmitter? Do we know what it might be doing at this point on its own at its ambient level? We don't, but it's one of the great mysteries.

And, you know, Rick Strassman has classically speculated on that in The Spirit Molecule. It is there. You can find it in the body and you can find it in the brain and there's also some rodent evidence now that it's released or at least its concentration spikes up in a dying brain and the problem there is a specificity question because a lot a lot spikes up in a dying brain because cells are dying and spilling their content in a sense. So serotonin itself spikes up massively. So there's just a little bit of a question mark on there. Some people have also questioned whether there's enough of DMT endogenously to really have an appreciable

sort of functional effect. But then people say, well, you know, during these extreme states, as was shown in that rodent work, maybe it spikes up and then maybe then well, you know, during these extreme states, as was shown in that rodent work, maybe it spikes up. And then maybe then, you know, that could explain things like the near-death experience because you enter a psychedelic-like state through the action of this endogenous psychedelic. It's a very fun hypothesis, but that's kind of what it is still right now, a hypothesis. There are overlaps in the phenomenology. It's just whether or not we can commit to DMT specifically, you know, responsible, being responsible for that phenomenology. Or, for example, you know, it could be established endogenous neurotransmitters like serotonin, you know, and that's spiking up and hitting its 2A targets and so on.

Is there any prospect, do you think, in the near term of us developing and discovering new compounds that we just haven't named here? we just haven't named here. I mean, we're talking about, we can almost count on one hand the number of compounds we're excited to study. But I remember meeting the rogue chemist, Sasha Shulgin. I don't know if either of you ever knew him, but to hear him talk about it, it sounded like if you just walked into his house, he could produce hundreds of different compounds that he had privately experimented with and cataloged. He wrote some very interesting books on that topic. And so there's this kind of this thicket of adjacent compounds that are sitting there to be explored, I think some of which were described by him as, don't go there again. But what do you think about the prospect that we are at the very beginning of exploring in a much wider search space? even sort of, you know, libraries of billions of potential molecules by doing, you know,

in silico modeling, computer modeling, and looking at how these possible chemicals dock at, say, the serotonin 2A receptor. So, you know, there could be almost endless possibilities there in terms of new drugs. Yeah, so, and we could play with the pharmacology and try and find, you know, drugs with where we could reduce some of the off target effects. Say, for example, serotonin 2B receptor stimulation is a problem. If you have drugs that do that, it can sort of fatten up the heart valves and cause this valvopathy. So maybe, and you have compounds like psilocybin, which is metabolized into psilocin, actually hitting the 2B receptor. So that's been a question mark for things like microdosing or regular use of low doses of psilocybin.

So, you know, we could improve on the drugs. There is another, in a sense, that's a given and to the point that we don't know what we don't know. And, you know, science is always iterative and it will go on forever, improving, advancing how we understand things. But there is another thing to say, which is we could be very drug-centric here. And if fundamentally with psychedelic therapy, we have a combination treatment, then maybe, you know, there's a lot to be learned about the other side of this, the other side of this bio-psycho-cial intervention that isn't just giving the drug. And so we can make advancements there too. Sam, I'd like to share a fun folklore story, if you don't mind,

about the Shoguns, because somebody on my team spent quite a bit of time with them. He was fresh out of college at Princeton way back when and got his PhD in philosophy and taught at Yale. And then... Oh, yeah. I forgot. I met him. Yeah. What's his name again?

David Blinder. Yeah. And it's just a wonderful story, but he befriended the shoguns and participated regularly. Sasha would create these compounds and pass them out to everybody and ask them what the side effects were, and then he would meticulously write them down. So upon his death and his wife's deaths recently, there is the Shogun Library, and there are about 200 compounds

that there are efforts to help and preserve them and to bring them to the world of research. And one effort which I hope we will be able to do is, if there are some of them that are deserving of studying, that we can look at it. Because I also want to point out in addition to, and I want to go into what Robin just left off about the spiritual part of this too, because I think it's really important and would like to bring that up. But there are other treatment paradigms that this is really seemingly promising for, and traumatic brain injury is one, and the neurodegenerative diseases, you know, because of the neuroplasticities, whether there's growth factors in there that seem

to perhaps be a disease-modifying compound for Alzheimer's. I know there's one study that was using psilocybin, I believe, for the treatment of new-onset depression that's oftentimes associated with neurodegenerative disease. In this particular case, it was Parkinson's disease. And they noticed that the motor symptoms were improving. So not only did their depression symptoms improve, but they noticed that the motor symptoms improved. So I think that there is room for these medicines to be studied for different applications. I'm also aware of a scientist who's using this to study inflammatory diseases, in particular asthma. And I think, wow, you know, when I was in medical school or even practicing medicine, when you hear about a cure-all, right, you think of the snake oil salesperson peddling the goods that this is going to help everything, but these are actually well-run studies. And so it just begs the question that I think that there are many applications that are possibilities and that we need to look at them.

And then I want to leave that and go back to where Robin left off, because I had a couple questions for you, Robin, and I was so curious about this study, and you mentioned about desiloing or desegregating, you said, certain areas of the brain. And I wonder if you would just elaborate on that a little bit more, because it's something that I have personally felt in my own brain. And I want to share that by way of saying, if I've studied as a biochemist and I want to share that by way of saying if you know I've studied as a biochemist and I have that area of my brain is well developed in math and then I'm also you know an athlete there's a different part of my brain that works and I like music and that's a different part of my brain that

works and then the ability to think abstractly is a different part of my brain and I just personally have noticed that since using these medicines therapeutically that I feel like I have access to these otherwise siloed parts of my brain are now seemingly available to me at the same time. And I was wondering if you could speak to that in some of the fMRI studies that you, I thought you participated in them or you're certainly aware of them. Oh, yeah. Yeah. Did you run that trial, Robin? Probably. Yeah. that you participated in them or you're certainly aware of them. Oh, yeah. Yeah. Did you run that trial, Robin? Probably.

Yeah. Well, yeah. Of course, we have to be a bit careful what we feel in our brain. But, yeah, I mean, yeah, there's a few different principles. As I said, you have, in a sense, organization and structure that's recognized in the brain, like say a brain network, that you can then see decrease in its organization under drugs. So that's, you know, example of that disintegration or a loss of structure or a loss of regularity, a dysregulating action. So that's stuff breaking down, you know. I call that, there's a hypothesis I introduced about 10 years ago called the entropic brain hypothesis, which is somewhat related here. You can think of entropy in a thermodynamic sense of it takes us back to the definition of these compounds, at least, you know, true classic psychedelics, psyche as mind or more accurately soul. And then the other

term means to make manifest or visible. So, you know, while we have aspects of brain function, dysregulating or breaking down? What of, you know, the hidden order amidst the disorder or the cosmos in the chaos, as Carl Jung would say? You know, what accounts for that? What accounts for the insight? What accounts for the apparent, you know, seeing of things, of content. Say on DMT, classic aspect of the phenomenology there

is that people report these apparent encounters with other sentient beings. What's doing that? I know that really throws people. When they have the experience, they're left bamboozled thinking that it must be something beyond the brain. Of course, I think that's a false inference.

Well, that brings us back to your naive thesis that you mentioned that we're in the presence of other autonomous beings, right? And everyone's had that experience. You're talking to somebody who you really think is there, and then you wake up and you realize it wasn't what you thought it was. So does that offer some phenomenological clue to what might be happening during the DMT flash? Yeah, I think it was. So does that offer some phenomenological clue to what might be happening during the DMT flash? Yeah, I think it does. Yeah, I think it's a useful analogy. The dream is entirely compelling. There's no doubt that you're experiencing that in the moment, and yet you're not, you know? I guess the one thing that fans of some metaphysical claim here would want to say at this point is that that doesn't explain the apparent convergence phenomenologically in the reports that people give of the kinds of entities they

encounter while on DMT. I don't know. I remember Rick Strassman's book on this topic, but I haven't followed whatever research has been done of late. I can imagine it'd be somewhat hard to find a volunteer for a DMT study who had never heard Terence McKenna or anyone else rave about the phenomenology. How impressive is that convergence of report on what the landscape looks like during the experience? Well, there's some convergence, but of course, I say of course, there's this thing called the collective unconscious and archetypes and, you know, certain human themes that get, in a sense, imprinted because we experience them a lot, themes that get in a sense imprinted because we experience them a lot you know like the hero's journey it's classic it's arguably you know universal and and somewhat culturally independent

at the most basic level at the most foundational level so it would be surprising if it was any other way that we wouldn't have archetypal-like experiences, you know, under these compounds, experience, you know, tricksters that can then morph into a, you know, maternal archetype, a mother archetype, and then switch back again. So that's the human, you know, that's human nature, the human psyche. So I don't think there's anything that should draw us into beyond the brain kind of speculations based on any kind of convergence. It just speaks to, in my mind, the collective unconscious. Yeah, I could go on.

But, you know, I mean, a dominant model in cognitive neuroscience now is one that a friend and a colleague of mine shamil chandaria spoke about recently on your podcast the hierarchical predictive processing model very compelling model of how the brain works in a sense that's increasingly influential including in psychiatry and there you know the model says that we experience the world through these generative models this kind of coarse graining of what's what but the key principle is that there's a dominant directionality to the information flow that that in a sense you could describe as top down and that's what's carrying the prediction, carrying the inference, is that we're experiencing the world through our internal models.

That's what's dominating, you know, the handshake, if you want, is that top-down model, model-first kind of flow. Into that mix, I dropped psychedelics, in a sense, and proposed that what psychedelics do is they impact the what's called in technical terms the precision waiting but in more sort of accessible terms we could just call the waiting the waiting or the influence of the predictive models and psychedelics dial it down so that our internal models are less convincing and stuff can come up because of that. Yeah. Yeah. I mean, it's just in a very basic psychological sense, when you look at why people suffer, and this is, you know, leaving aside even extreme clinical cases,

just the ordinary routine suffering of ordinary people who may not have any diagnosis to speak of. So much of the character of our suffering is this imprisonment in certain patterns of thinking and reacting to just ordinary experience. I mean, we're ruminating all day long. We're having a very unprofitable conversation with ourselves that, in my view, also impressively resembles what it's like to be asleep and dreaming. I mean, there's something about identification with thought that is just as spurious in the end as being asleep and dreaming and not knowing that you're dreaming. And it's pretty easy to see that certain ways of disrupting that would offer a kind of, you know, disrupting and resetting would offer a kind of opportunity for relief. Quite. Yeah, I mean, it's true of psychopathology, I think, mental illness, so much of it, depression, anorexia, you know, these habits of thinking, getting fixated on certain ideas in a sense, you know, that we're worthless or that we're too big.

But also it's the case, you know, in domains that we wouldn't ordinarily think of as psychopathological or of mental illness, you know, even politics or religion, we can, I borrow a term from evolutionary science, which is canalization. It means the entrenchment of traits so that they become stamped in and resistant to change, resilient to change. It's the opposite, actually of of the most basic definition of plasticity which is the ability to be to change to be shaped or molded um so canalization is the inverse of that you know but but even our very sense of self or identity or ego is a product

of the same canalization or identifying with thoughts. Yeah, yeah. On that point, how much of it is a story still of the default mode network being down-regulated during the psychedelic experience? Is that still part of the signature of what's happening? Yeah, I'd say we've moved on a little bit. That was a finding of ours in the first fMRI study that we did. In fact, the first fMRI study of psilocybin, 2012, we found that the

default mode network was especially implicated. Its integrity broke down, as I was describing, this disintegration effect. And other changes also kind of pointed at this default mode network, this dominant network in the brain that is kind of capital city in the brain. It's a hub of connectivity, of high metabolism, tonically active in the background, hence default mode. Yeah, so we saw that that dysregulated and in a sense disintegrate under the psilocybin. And we also saw that effect correlate in different analyses over time with ratings of ego dissolution. So we made a kind of one-to-one mapping there that

maybe it's related to that experience of ego dissolution. That had a big impact as an idea, and it sort of became, in a sense, this canalized story in itself. I'd say we've moved on a little bit because I think it was a little too centered on one particular network. There are other neighboring networks, also high level,

that break down under psychedelics and are also implicated or, you know, that breakdown correlates with ratings of ego dissolution as well. So I just think it was too focused on one particular network. I don't think it's wrong as an idea. There's just more to it as there always is, of course. How about the critical window period that Goal is introducing? Well, that's a nice one too. Yeah. So, you know, we have these periods early in life when we're

hyperplastic. You know, just think of kids and how they can pick up languages so easily in the early years. And then that window of plasticity or sort of spongibility that you take on so much closes and we become less plastic and less able to learn. So yeah, that critical period plasticity has been especially well articulated by Gould-Dolan and it very much fits the model, you know, that psychedelics reopen these critical periods of plasticity or just generally open windows of plasticity. Has that been tested with respect to learning of anything, languages or otherwise?

Not very well in humans in terms of learning paradigms and accelerating learning. We did do one study with LSD where we had a certain cognitive flexibility paradigm where we were able to look at a learning rate, how quickly you could learn, in this case, a rule. And just like the way symbols relate to each other is quite sort of low-level psychological paradigm. But we did see that there was an acceleration in learning rate there. But there should be more work in that kind of space than there has been.

Yeah, let's see. You mentioned microdosing and passing at some point. Where does the research stand there? I remember a study that came out not long ago suggesting that it really was some version of the placebo effect. Yeah, that's another one of ours. Yeah, so that was Balash-Sageti. And there we did an interesting design,

a self-blinded citizen science study. So we sort of advertised to people, really Balash led this, and he advertised to people intending to microdose that, oh, why don't you get some capsules and close some empty capsules and do your own blinding paradigm as if you're running a double-blind randomized

control trial. It was very clever. Yeah, we got a couple of hundred people to do it. So the biggest sample, I think, to date on microdosing, it was LSD and mushrooms. You could do either. And there we found that most of the positive effects that people were reporting could be explained by thinking you were getting a microdose. So if you got placebo and thought it was a microdose, you did as well as if you actually got the microdose. So the evidence is a bit mixed. And I think the rationale is good and the theory is good that low doses of psychedelics could, in a sense, lubricate the mind, lubricate the brain, open a bit of plasticity without necessarily having a big trip. And maybe you could do something with that window of opportunity, that window of plasticity.

Problem is, there hasn't been good enough research done yet. It's hard to do microdosing studies because, you know, by definition, it's a dosing regimen. So you're going to be doing a lot of dosing. And are the ethics boards, the IRBs going to allow you to give participants psychedelics to take home to do this? Probably not. So then you have to do it in a lab. And the typical protocol with microdosing is a few weeks of sort of one day on, one day off or some variation on that. So that's a lot of visits and that's going to be, you know, horribly expensive. And it's these kind of practical challenges that have meant that we haven't done very

good microdosing studies. And when the control studies have been done, they haven't really come through with compelling evidence. So I would just say, watch this space on microdosing as an idea. It's quite interesting, if not even compelling, but the evidence isn't there yet. Well, another reason to fund some research. Well, another reason to fund some research. to seemingly tap into what we experience in the psychedelic space of this boundary between the spiritual slash metaphysical and the biological, you know, the chemistry, the biochemistry, the physics that's happening in our brains. And I'm guessing you've considered this quite a bit, and I just wondered if you would share. Yeah, well, I talk about it a lot, especially over at Waking Up, our meditation app. I mean,

it's a very big question. I think there's a few high-level things I would demarcate. I mean, one is I think, you know, I have been for many years now a fairly vociferous critic of organized religion, not because I don't think the core experiences that lie at the founding of all or most of our religions are valid and interesting and worth having and exploring and understanding, but because I think they are so important and interesting and we obviously need a 21st century, truly non-denominational, non-sectarian, non-divisive, not irrational framing of those experiences. So the reason why I want to get out of the religion business is because I think these mutually incompatible claims of our various Iron Age and

medieval religions just are blocking a more sophisticated and useful and not divisive conversation that's possible. So insofar as I can help inspire that conversation, I've been trying to do that. And in various moments, my criticism of organized religion has been fairly denigrating, but I'm also realistic that I don't think I'm going to live to see a day where there are no longer Christians, Muslims, Jews, Buddhists, Hindus, all vying for recognition of the unique veracity of each of their faiths. And I also, I just think we're in very different lanes here. I think I would just do nothing but celebrate the fact that you could reach out to a fundamentalist Christian and convince them that they want to support the Treat Initiative very much within the context of their Christianity,

right? Like, this is, you know, I don't think you should be in the business of pointing out what is wrong with Christianity. That's my job. But, um... Can I share with you, can I share with you real quick? Yeah, go for it. The first, I had submitted the legislation, I think it was July 17th, and putting in long hours. And at the end of the night, there was a voice memo.

And I debated whether I wanted to listen to it or not, because if it was something that might upset me, it might upset my sleep. But for some reason, I decided to listen to it. And I wanted to share this with you because I think it's just jaw-dropping, remarkable to me. It was from a very conservative Christian white man who said, I read your legislation, and I think it's the most impactful and important legislation I've ever read. And he said, and I'm a conservative white Christian, and we get a bad rap these days. But I want you to know we're not all bad, and I support you 100%. So of course, I called him later and asked him if he could post it on our website. So I didn't mean to interrupt, but it was just

further affirmation that this goes beyond politics and religion and that there's so much suffering out there that people are starving for a new solution. Yeah. What it promises to me is something like a 21st century version of a new Mysteries of Eleusis. century version of a new mysteries of Eleusis, right? This is the secretive right that was at the foundation of a fair amount of Greek philosophy. But by its very nature, it was organized, it was orderly, it was not a matter of handing out these compounds to everyone to use recreationally. I mean, I'm very supportive of decriminalization, but I'm also very supportive of circumspection and how we move into this space. And I mean, I say that, you know, it's a fair amount of apparent hypocrisy to untangle here

because, you know, my own personal and illegal use of these compounds was absolutely indispensable back in the day. It really got me started in thinking about all these things. And I really don't think I would have become interested in the nature of the mind and the contemplative life. I just think I was a hard enough case when I was an 18-year-old undergraduate in college that if you had taught me to meditate at that point, contemplative life. I just think I was a hard enough case when I was an 18-year-old undergraduate in college that if you had taught me to meditate at that point, I think I just would have bounced off the whole project. So I just think we, as a culture, as much as I want to get out of the religion business and get past all of the political liabilities of that as I see them and the unscientific bias that I think is built into it, I think secular culture is really starving for a fully wise language by which to organize our lives. And so we have to make the best uses of all of the human conversations that have preceded this moment.

So I think we should grab everything that's useful in religion and philosophy and literature and art and every other corner of discourse. personally and collectively is consciousness and its contents and our only dimly emerging understanding of how anything that seems to be happening is happening in the first place. And science remains the leading edge of that understanding. And what we need is a really rich first-person side of that inquiry. And the introduction of psychedelics into the conversation puts the furthest reaches of human well-being and insight into reach for normal people. I mean, normally you would have to be the kind of person

who would be willing to spend a year on silent retreat to begin to touch what someone can touch in four hours under proper guidance given a compound like MDMA or psilocybin. And so it's not to say that there aren't differences between meditation and psychedelics. I've talked about those in other contexts, but there's a fair amount of overlap there as well. And so I just think it's fantastic what you guys are doing, and I really appreciate you both coming on the podcast to talk about it. Well, thank you. And just a quick shout out to Brian for his book, The Immortality Key, where it's just a brilliant recounting of that time. And again, I want to highlight that it was the women priestess

that were there to serve these medicines. And that's what we intend to do in today's age, to bring these medicines thoughtfully to the public in a safe way, but introducing a new model, way, but introducing a new model, a completely new model, where we do embrace the human being human again, and being able to talk about that, and being able to connect with one another with compassion and understanding, appreciation for we are more than just a collection of neurons in our brain. We are part of a collective group, a superorganism, if you will, of this, you know, Homo sapiens, and that it's time for us to focus our efforts on helping others and also taking agency over one's own sense of self. And I believe, you know, there's oftentimes I've been involved with some

really interesting research projects and oftentimes ahead of the curve. And so timing in life is so crucial too. And I hope that what I'm feeling is this groundswell, this need, this readiness of society, actually, to be open to a new approach to dealing with pain and suffering. And I say, welcome to Treat California. Nice. Give me that website again. Treatcalifornia.org. Excellent. Well, I look forward to supporting you and I hope our listeners will as well. Jeanne, Robin, thank you for your time. Thank you.