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

00:00:00.000 Welcome to the Making Sense Podcast, this is Sam Harris.

00:00:25.200 Today I'm speaking with Jeannie Fontana and Robin Carhart-Harris.

00:00:30.840 Jeannie is a MD-PhD and a leader in the healthcare space.

00:00:35.880 She's been instrumental in increasing federal funding for ALS research

00:00:39.420 and is a founding trustee of the California Institute of Regenerative Medicine,

00:00:44.760 where she played a pivotal role in creating the world's largest stem cell granting agency

00:00:49.340 with an $8.5 billion budget.

00:00:51.900 Under her influence, the agency achieved FDA approvals, fast-track designations,

00:00:57.720 and launched groundbreaking clinical trials.

00:01:00.200 Additionally, it helped create over 55,000 jobs in California,

00:01:04.360 50 new companies, and $10 billion in added state revenue.

00:01:08.920 And now Jeannie is focused on a new initiative, which we'll be talking about.

00:01:13.480 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

00:01:23.600 for research and affordable access to mental health treatments using psychedelic medicines.

00:01:29.220 You can get more information at the website, treatcalifornia.org.

00:01:34.700 But the immediate need now is that they have to collect 1 million signatures from registered California voters.

00:01:40.960 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.

00:01:50.340 And whether you're a registered California voter or not, you can collect signatures from California residents.

00:01:56.400 And there's more information on the Treat website about how to do that.

00:01:58.980 And wherever you live on Earth, you can donate to Treat.

00:02:04.060 Because gathering 1 million signatures is actually a very expensive thing to do.

00:02:08.320 It usually costs many millions of dollars.

00:02:11.000 Because it all has to be done physically.

00:02:12.820 You can't just sign the petition on the website.

00:02:15.480 You'll hear much more about the initiative from Jeannie in a few moments.

00:02:18.520 But I just wanted to give you the call to action up front.

00:02:20.640 But once again, that website is treatcalifornia.org.

00:02:27.580 Jeannie 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.

00:02:38.260 Then in 2021, Robin became the inaugural Ralph Metzner Distinguished Professor of Neurology and Psychiatry at the University of California, San Francisco.

00:02:46.860 He's also been listed by Time Magazine as among the 100 next.

00:02:51.460 This is a group of emerging leaders from around the world who are shaping the future.

00:02:55.380 He holds a PhD in psychopharmacology from the University of Bristol.

00:02:59.280 And he's led neuroimaging studies with LSD, psilocybin, MDMA, and DMT.

00:03:05.080 As well as several clinical trials for psilocybin therapy.

00:03:08.800 And the topic of discussion today is the TREAT initiative in California.

00:03:13.440 And the growing promise of psychedelics for mental health care.

00:03:15.840 We cover some of the recent research and just generally explore how we seem to be at the tipping point here.

00:03:23.200 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.

00:03:32.620 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.

00:03:40.380 And now I bring you Jeannie Fontana and Robin Carhart-Harris.

00:03:50.160 I am here with Jeannie Fontana and Robin Carhart-Harris.

00:03:53.940 Jeannie, Robin, thanks for joining me on the podcast.

00:03:56.420 Thank you, Sam.

00:03:57.160 Thank you, Sam.

00:03:58.020 So we're going to talk about psychedelics and their therapeutic potential and the current state of the scientific research.

00:04:07.580 But also we're going to talk about this very ambitious initiative that, Jeannie, you are launching in California.

00:04:14.660 Before we start, perhaps each of you can summarize your professional background and tell me how you came to focus on this particular issue.

00:04:23.400 So let's start with you, Jeannie.

00:04:26.720 Thanks.

00:04:27.700 Robin and I are pointing fingers at each other.

00:04:29.800 You first.

00:04:32.040 Well, I'm trained as an MD, PhD.

00:04:35.940 I'm trained as an internist and then I have a PhD in biochemistry and molecular biophysics.

00:04:42.140 I started as a young woman thinking that I was going to develop some therapeutic that would help treat millions of people.

00:04:49.480 So I've always kind of had this drive in me since I was young.

00:04:54.220 As I finished all my training, which was long and extensive, my mother was diagnosed with ALS.

00:05:01.660 And at the time, I remembered it was one of those horrible diseases that I read in my textbook, but I really did.

00:05:08.380 There was not much known about this.

00:05:09.620 This was back in the late 1990s.

00:05:12.060 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.

00:05:25.160 Of course, starting off trying to find one for my mother, but then also getting involved with the ALS community and realizing that there's such a desperate need here for research and patient care.

00:05:37.260 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.

00:05:54.500 And that was really empowering for me to know how to work within the system, to change laws that impacted the lives of tens of thousands of ALS patients in perpetuity until the law was changed.

00:06:06.720 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.

00:06:16.500 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.

00:06:25.040 So that was interesting.

00:06:27.140 And then at the same time, human embryonic stem cells were just discovered in the late 1990s.

00:06:32.820 And I happened to be working with a very wonderful medical research institute in San Diego, where they're top scientists there.

00:06:40.960 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.

00:06:53.380 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.

00:07:03.120 At the same time, George Bush put a moratorium on the funding of embryonic stem cells for political reasons.

00:07:10.000 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.

00:07:27.520 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.

00:07:46.260 So there's a pathway in California where the citizens can demand that the California government actually provide services that they want.

00:07:56.260 In this case, we launched a citizen-driven ballot initiative to create the first-of-its-kind funding agency for embryonic stem cells.

00:08:05.580 And I was on that campaign and educating the public about it and educating doctors and patients and participated in, you know, editorials and things like that.

00:08:18.380 And I honestly did not think the bill would pass.

00:08:21.220 We were in a bleeding economy at the time.

00:08:25.020 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.

00:08:31.240 And at the time, it really was in its basic research level.

00:08:34.620 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?

00:08:43.420 And I didn't have an answer.

00:08:45.120 I agreed with them.

00:08:46.380 I said, you know, we have to pay our teachers.

00:08:48.000 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.

00:09:06.400 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.

00:09:23.680 And on average, in the $2,000 was about $1.5 billion.

00:09:27.800 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.

00:09:40.460 And we set up something that I think, by all accounts, ended up being pretty successful.

00:09:45.300 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.

00:09:53.800 And importantly, we had 60 compounds, what we say, in the pipeline that were deserving of further funding.

00:10:00.060 So the same force of nature went back to the voters of California during the height of the pandemic and qualified for the ballot.

00:10:07.300 And the voters of California approved an additional $5.5 billion.

00:10:12.020 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.

00:10:32.820 So I recognize now that we created and built what is now the regenerative medicine infrastructure.

00:10:42.080 And it took me a while to really appreciate how amazing that was.

00:10:46.160 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 will be combined.

00:11:09.780 And we will actually cure some incurable diseases now.

00:11:14.400 Nice.

00:11:14.880 So this is a long introduction.

00:11:16.840 I'll stop here because I could keep on going.

00:11:19.240 Yeah, well, no, we'll pick up the trail there talking about that initiative pathway.

00:11:24.620 But let's bring in Robin.

00:11:25.940 Robin, how did you come to study the brain and the nervous system?

00:11:31.060 And what have you focused on?

00:11:32.320 And how did you come to focus on psychedelics?

00:11:35.240 Yeah.

00:11:35.860 So I was a curious teenager.

00:11:39.500 You could say I had some experiences and I felt a gravitational pull to psychology.

00:11:47.460 I did a degree in psychology in my hometown of Bournemouth on the south coast of England.

00:11:54.280 And then towards the end of that, I enrolled to do a master's in psychoanalysis.

00:12:00.680 So I was especially drawn to depth psychology.

00:12:05.100 But that said, I was also drawn to, you know, rigorous scientific approaches to the mind.

00:12:12.800 I think to have psychoanalysis, you know, can be a little weak in that sense.

00:12:18.520 But a few parts of it have not aged especially well.

00:12:21.940 But maybe some of them have.

00:12:23.580 Maybe some are sometimes a little bit underappreciated.

00:12:26.680 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.

00:12:45.200 So sleep recordings of MDMA users and matched controls who had their serotonin systems stressed with something called tryptophan depletion, a dietary manipulation.

00:13:00.040 But anyway, this was kind of my way in.

00:13:02.640 And I did come to that unit.

00:13:04.840 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.

00:13:15.820 And I came knocking on his door asking to do psychedelic research.

00:13:19.220 And he opened it saying, well, you can do some serotonin research and we'll see how things go.

00:13:25.280 But I was especially interested in psychedelics.

00:13:28.340 I'd learned of their history being used as tools to assist psychotherapy.

00:13:35.600 And actually, often that was a kind of depth psychotherapy and a similar in a sense, quite similar to psychoanalysis, albeit an accelerated version.

00:13:46.260 And that was kind of my way in.

00:13:49.280 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.

00:14:03.120 That's really what I wanted to do.

00:14:04.600 I came to David initially wanting to do an LSD fMRI study.

00:14:08.980 I had this hypothesis that the psychedelic state was like a waking dream state, a hybrid, you know, dream sleep waking state.

00:14:20.420 And I thought through, you know, the lens of fMRI, functional brain imaging, I could, in a sense, prove that hypothesis.

00:14:28.680 That was my naivety at the time.

00:14:30.600 But that was the initial thread that drew me in.

00:14:33.520 And since then, I've done a series of brain imaging studies with a range of different psychedelic drugs, psilocybin, LSD, MDMA, DMT.

00:14:43.640 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.

00:14:57.340 And then, since then, that kind of got a ball rolling at a certain time, and I guess we're going to go there.

00:15:06.980 But yes, a lot of momentum now in psychedelic medicine.

00:15:12.140 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.

00:15:22.360 But before we go there, let's talk about the TREAT initiative, because I want people to know about it up front here.

00:15:31.600 My wife, Annika, is the one who told me about it, and she's been involved with Eugenie, helping it along.

00:15:40.460 And she, you know, in preparation for this conversation, she has let me know that she thinks it's difficult to communicate the full vision of this initiative.

00:15:50.780 And so I'm wondering, Eugenie, can you explain what you're hoping to accomplish and perhaps anticipate any common misunderstandings of what you're attempting to do?

00:16:04.740 I laugh because it's an enormous project with many layers.

00:16:11.680 So it is a challenge to try to sum it up in a few words.

00:16:17.580 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.

00:16:31.800 These medicines are showing great promise through clinical trials performed from our top academic institutions that are nothing short of jaw-dropping to me.

00:16:46.240 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.

00:16:59.640 So the goal of the Treat Institute is to bring these medicines to the public in a responsible, safe, and ethical manner.

00:17:11.520 Now, in order to do that, there's a lot of details that need to be addressed.

00:17:18.860 But I think we can take the high perspective and talk about how we have to show these medicines to be safe and efficacious,

00:17:25.760 running large-scale clinical trials, and tracking safety data, tracking outcome data,

00:17:32.320 not just during the clinical trial period, but over lengths of time.

00:17:35.900 And for your listeners that are aware of medical studies, something like the Framingham study,

00:17:41.860 where you tracked through a lifetime, actually, the outcomes of the patients.

00:17:49.060 I think it's important to look at the different indications that these medicines can help with.

00:17:55.480 Right now, we know that it requires a therapist in the room,

00:17:59.260 that it seems to be the combination of therapy, talk therapy, with these medicines.

00:18:05.800 And that resonates with me as an athlete who was taught how to play a sport.

00:18:11.220 When you're taught how to do something, you can do it better.

00:18:14.540 And I think in our society, we're not taught how to manage our emotions in a healthy way.

00:18:20.100 So I think the patients need to be prepared and educated with how to experience these medicines

00:18:27.540 and what to importantly do with the insights and emotions elicited through the medicine.

00:18:34.840 So integration is a huge component of this.

00:18:37.920 And then importantly is access.

00:18:40.280 I believe strongly that these medicines need to be available to all,

00:18:45.020 not just the rich right now and not just those that,

00:18:49.660 through their insurance policies, they're able to take it and others are not.

00:18:53.840 We're well aware that the hardest-hit communities in any society are the underserved communities

00:19:00.240 and mental health, while affecting every citizen of America right now,

00:19:06.760 either personally, with their family members, or certainly with their friends,

00:19:11.260 is being touched by this.

00:19:12.540 So the tools, though, that are provided to the underserved communities are particularly sparse.

00:19:19.400 So the main impetus of the TREAT initiative is to make sure that these medicines and treatments

00:19:24.840 are available to all.

00:19:26.640 So I think I'll stop there because I can take up all your time here telling you about it.

00:19:30.980 Yeah, well, so I want to, I'll remind people at the end of our conversation,

00:19:34.760 but I want to get up front the specific call to action, if there is any, for California residents now.

00:19:43.620 And what is the actual initiative?

00:19:46.420 We are running a campaign, and it's called the TREAT California Campaign.

00:19:51.540 And TREAT stands for Treatments, Research, Education, Access, and Therapies

00:19:55.600 for Mental Health Using Psychedelic Assisted Therapies.

00:19:58.740 In order to qualify for the ballot, which we're going to begin to do in two weeks,

00:20:04.300 we need a million signatures to sign the petition saying they're interested in this to get on the ballot.

00:20:10.740 The signatures need to come from registered voters.

00:20:13.800 So we appreciate people going to our website and signing up

00:20:17.760 so that when we get our green light to start collecting signatures,

00:20:21.900 we'll be able to reach you and have you sign this petition.

00:20:25.400 If we don't get the million signatures to qualify for the ballot, then this dream dies.

00:20:32.800 So we are prepared to do what it takes to make sure we qualify for the ballot.

00:20:37.620 Once we've qualified for the ballot, which we intend to do by the year end,

00:20:41.540 we spend all of 2024 educating the public on mental health,

00:20:46.600 on psychedelic-assisted therapies.

00:20:49.320 And then as we get closer to the vote,

00:20:51.820 and we know that there will be a lot of mayhem because it's a big presidential election.

00:20:57.040 But we have to remind people to vote yes on our proposition on November 5th of 2024.

00:21:03.580 And I'll have a link to the website in the show notes, but what is the website?

00:21:07.680 It's treatcalifornia.org.

00:21:10.240 And is there, you need to get signatures,

00:21:14.100 but is there some component of fundraising here?

00:21:17.060 I mean, is there something you need money for to get those signatures?

00:21:19.620 Thank you very much. Yes, I do.

00:21:21.820 Running a campaign like this is enormously expensive.

00:21:24.580 In California, it is on average $30 million.

00:21:28.380 And so we need donations.

00:21:32.900 We have a 10-10-10 campaign.

00:21:34.780 We're asking people to donate at least $10.

00:21:37.580 And of course, it would be nice to have more.

00:21:39.200 But we think, you know, two Starbucks coffees from the people

00:21:43.020 to help us pay for the tools that are required to make us be successful with this campaign.

00:21:52.460 And obviously, you don't have to be in California to donate to the campaign.

00:21:56.980 No. Thank you for that.

00:21:57.960 In fact, one of our biggest donors thus far is a conservative Republican from Florida.

00:22:02.760 The ideas are that once we run the trials here in California with the FDA,

00:22:09.260 we get FDA approval, these medicines will be available to everybody in the country.

00:22:14.120 So yes, everybody in the country can donate.

00:22:17.180 Yeah.

00:22:17.300 I'm glad you mentioned that you had a conservative Republican, at least one,

00:22:22.400 backing you because I want to talk about the coalition you're building in support of this.

00:22:27.200 It is surprising.

00:22:29.160 And it does suggest that there's a path here toward bypassing some of the obvious mistakes

00:22:36.580 we made in the 60s around trying to study these compounds and their promise,

00:22:42.400 and then also trying to enfranchise everyone in the society to take them.

00:22:49.020 And that translation from the lab to the streets was less principled and governable

00:22:57.400 and seemed wise in retrospect.

00:23:00.520 Timothy Leary standing at the front of it.

00:23:02.180 I guess my next question here is there are some dichotomies that seem in opposition to one

00:23:11.980 another, but they really might not be.

00:23:14.740 I mean, people in the psychedelic space seem to think that there's this either-or decision

00:23:21.040 between focusing on decriminalization versus research and field research versus lab research.

00:23:29.260 You can have a medical model by which you frame this or a spiritual model.

00:23:35.900 How do you think about those dichotomies, Jeannie?

00:23:40.200 Or is this a hallucination we're having about hallucinogens?

00:23:44.400 Thank you.

00:23:45.400 And I've actually spent a lot of time thinking about this.

00:23:49.380 I was born in the 60s and raised in the 60s and 70s and witnessed the counterculture revolution

00:23:55.940 and the hippie generation.

00:23:57.160 I also was subject to the Dare to Say No campaign by the Reagans. 0.94

00:24:05.080 They did a really good job scaring me to death.

00:24:07.500 You know, this is your brain on drugs, that frying pan and the fear.

00:24:11.720 And then also feeling the societal unrest around the Vietnam War and this cultural revolution

00:24:20.260 that was happening.

00:24:20.960 And the drugs were very front and center.

00:24:26.140 So I was in it.

00:24:28.420 I didn't participate myself in taking them, but I lived in it.

00:24:32.420 I lived through it so I could feel the societal push and pull from all parties.

00:24:38.600 And then not really appreciating what it meant when these medicines were locked up, basically.

00:24:46.860 And then what I've learned subsequently is that they were sort of driven underground.

00:24:52.360 And there's a couple of paths that I want to share here.

00:24:54.920 One is the reason why I'm sitting here is because of the great work that was done out of our academic institutions.

00:25:01.800 Johns Hopkins and Yale and NYU.

00:25:05.480 And now Robin's work sitting in front of me and recognizing that these studies were funded by philanthropists

00:25:15.560 and philanthropists whose lives have been changed by their use of psychedelics early on.

00:25:21.720 And I think most famously is Steve Jobs who attributes his LSD use to helping build the iPhone.

00:25:29.780 So I also have great respect for these medicines as a clinician.

00:25:38.040 So when you're a clinician, you have to think about all types of patients that come to you.

00:25:43.860 And you have to think about best practices for all your patients.

00:25:48.640 And while I appreciate and respect the psychedelic community's experience with the medicines,

00:25:56.900 I hesitate when I think about these medicines being available to the general public

00:26:01.780 without any safety guardrails, any guidance, any supervision.

00:26:07.580 And I am concerned about negative consequences and then having these negative consequences blown up

00:26:15.120 so that the research can't proceed because of political actions again.

00:26:21.900 And in fact, there's this wonderful group of mothers who I recently befriended

00:26:26.760 that their children, college age kids, were using psychedelics

00:26:33.360 and for different reasons ended up dying.

00:26:38.680 They were not supervised and they thought they could fly and jumped off a bridge,

00:26:42.620 which I always thought was a sort of a folklore story from the government to try to scare us all.

00:26:49.340 But indeed, that can happen.

00:26:52.740 And while I appreciate that these mothers are pushing for safe supervision of these medicines,

00:26:59.380 that they're not protesting and that these medicines should never be brought to the public.

00:27:05.700 In fact, quite the contrary.

00:27:07.020 They say that it needs to be brought to the public in a safe, responsible, and ethical way.

00:27:12.380 So allow me a little more time to share with you the vision that I have

00:27:15.960 for what the Treat Institute will do.

00:27:18.300 So we are not directly a decrim or legalization effort.

00:27:23.020 While I don't believe people should be thrown in jail

00:27:25.720 for the use of psychedelics or cannabis for that matter,

00:27:28.880 we are not focused on decrim.

00:27:33.440 Legalization is something I don't support at this period of time

00:27:36.780 because when you're bringing it out to the general public,

00:27:39.340 you have to think about all people who are having access to these medicines.

00:27:43.400 And I believe these medicines need to be treated with respect.

00:27:46.880 The persons need to be prepared and educated and supervised

00:27:51.300 and allow the information revealed in these medicines

00:27:57.580 to be shown how to incorporate them into their own lives

00:28:01.360 so they can take power and control and agency over their emotional well-being.

00:28:07.020 So what we attempt to, what we plan to do at the Treat Institute,

00:28:11.760 which is this $5 billion funding agency,

00:28:14.680 where we'll have monies allocated towards running large-scale clinical trials

00:28:18.420 with the known medicines, with known indications like anxiety, depression, and PTSD,

00:28:23.460 as well as others, is that it's important to look at the way these medicines have been administered.

00:28:30.220 We know for thousands of years it's been ceremonially.

00:28:33.980 We also know they've been used in religious settings.

00:28:37.620 We know that sometimes it's used in group settings.

00:28:40.620 And there are benefits for patients under each condition.

00:28:45.220 So I can foresee a situation where we look at,

00:28:49.280 once we show these medicines are safe, effective,

00:28:51.300 with the model that's mandated by the FDA right now,

00:28:54.660 which is our two therapists in the room at all times,

00:28:58.060 that we can look at how does a patient respond to being in a group setting.

00:29:03.560 Likewise, how would they respond to being in a ceremonial setting

00:29:07.040 and even a religious setting.

00:29:09.280 And can we show that it is safe and effective for those people?

00:29:14.780 And if so, can we scale it to maintain safety?

00:29:19.460 So I sort of look at it like going to a restaurant.

00:29:22.080 And as we defined more the criteria of what works for the one patient,

00:29:27.160 we're leaving this model of one pill per person for a symptom,

00:29:32.600 which sort of masks symptoms.

00:29:34.720 We say, what will benefit that person more as the individual?

00:29:38.780 A more of an integrative approach.

00:29:41.600 So I may prefer to be in a more clinical setting with a one-on-one therapist.

00:29:48.680 And as I work through some of my issues,

00:29:50.960 I may benefit from being amongst a group setting

00:29:53.800 because there's some healing to be gained by these group settings

00:29:58.940 where there's safe containers and people can reflect for you

00:30:02.480 the emotions that you're working through.

00:30:05.060 And there's something very beautiful in those group settings.

00:30:08.940 Likewise, the wisdom keepers and the way these medicines have been delivered to man for,

00:30:14.820 I mean, you could maybe even argue tens of thousands of years, 70,000 years,

00:30:19.940 have been through these ceremonies.

00:30:23.500 And I think there's some truism to it.

00:30:28.240 And I think we need to look at it.

00:30:29.560 We need to study it.

00:30:30.420 And how do we safely bring this model to the citizens first of California

00:30:35.600 and then the rest of the country?

00:30:37.780 And lastly, we have to honor the spirituality of this.

00:30:42.080 Religious leaders, it's been really one of the more surprising things for me 1.00

00:30:46.060 to start exploring religion and not, and I don't mean the organized religion,

00:30:51.160 but the spirituality behind religion.

00:30:53.840 And there's really not that much of a difference when you're in one's altered state of consciousness

00:30:58.780 and the common descriptions people have of feeling at one or with this love.

00:31:06.300 And if you happen to be religious, you can relate to it as being God

00:31:11.360 or you can feel Jesus' love or whatever religion it is that you subscribe to

00:31:17.640 can strengthen that emotion.

00:31:20.800 So I think the Treat Institute offers an opportunity to really address

00:31:26.140 the real healing potential of these different therapeutic modalities.

00:31:31.140 Always keeping in mind, though, is how we can scale it and scale it safely.

00:31:36.300 Well, on the point of scale, where does the federal government come in

00:31:41.300 and how would Treat influence federal policy if it passed in California?

00:31:48.700 Well, we're planning on passing.

00:31:51.640 And what we're going to set out doing is to test the safety and efficacy of these medicines.

00:31:59.360 While we all believe these medicines to be safe,

00:32:01.800 there's really no well-run study that looks at safety.

00:32:07.880 And I think it would be irresponsible for us to,

00:32:13.240 if some untoward side effect is revealed when you start looking at thousands of patients,

00:32:19.840 tens of thousands of patients,

00:32:21.860 that something comes up that is deemed too difficult to get around.

00:32:26.620 We're going to stop funding.

00:32:29.240 We're not intended to fund just because we've been approved for $5 billion.

00:32:35.280 So I'm going to assume that this is safe and that it actually works.

00:32:39.260 And we're working with the FDA and the DEA for approval.

00:32:44.920 And when we get that approval, it becomes available to the country.

00:32:49.060 We will continue to run trials with different medicines and different indications,

00:32:54.540 collecting data all along the way.

00:32:57.200 I talk about our three trifecta of our goals,

00:33:00.660 which is to improve patient outcomes,

00:33:02.960 to show that it's cost-effective,

00:33:05.120 and that we make it accessible to all.

00:33:06.740 So copying the model that we did with the Stem Cell Agency,

00:33:11.540 we actually helped the federal government

00:33:14.100 come up with their own guidelines and regulations around stem cells

00:33:17.820 and how they should be administered to the rest of the country.

00:33:21.660 So I view us as working with the existing system,

00:33:26.340 bringing evidence and data to support the decisions that we make.

00:33:31.020 You know, I'm not naive about this,

00:33:32.940 but I believe that, you know, we should make decisions based upon

00:33:36.080 evidence and data as best we can.

00:33:40.000 So before we get into the state of the research,

00:33:42.960 I just want to see if I can get more information from you

00:33:45.640 on the coalition you have built in support of TREAT.

00:33:49.700 And, you know, perhaps there are people who support you

00:33:52.300 who aren't ready to go public yet,

00:33:54.200 so, you know, feel free to edit your response.

00:33:57.300 But I just know that there's a fairly bewildering diversity of people and groups

00:34:02.760 that actually support you.

00:34:04.820 And you seem to have quite a talent for bringing together collaborators

00:34:09.140 and supporters who wouldn't normally find themselves on the same team.

00:34:14.500 Can you say more about that?

00:34:15.880 Well, first of all, I'm just honored.

00:34:18.600 I'm so honored to work with the people on my team.

00:34:23.980 And I think we are all aligned.

00:34:27.440 And what I love about this project,

00:34:29.460 there's so many things I love about this project,

00:34:31.760 is that we're showing up as very competent, credible, experienced human beings

00:34:38.660 who are aligned to help and serve others.

00:34:44.400 And so in this case, I can touch every person

00:34:48.320 because there's not one person, again, I'll repeat this,

00:34:52.100 in our country that is not personally touched by mental health issues,

00:34:57.680 depression, anxiety, addiction, their family members are,

00:35:04.580 and certainly their friends.

00:35:06.660 So that when we're discussing bringing a new tool,

00:35:12.120 we're bringing a new tool to the healthcare provider

00:35:16.340 to help people that aren't otherwise helped.

00:35:19.920 And we're doing it with rigorous research, oversight,

00:35:26.260 and not just the black and whites of evidence,

00:35:30.380 as we're bringing heart to this.

00:35:32.660 We want to bring compassion to how we're treating people.

00:35:37.140 And by leading with competency and, importantly, with compassion,

00:35:44.040 I'm able to pull in other like-minded, extraordinary human beings,

00:35:49.300 and I'm so lucky.

00:35:51.500 So to that end, you know, I have to brag about my campaign manager.

00:35:55.240 This is a man who was the senior advisor,

00:36:01.640 essentially the right hand of Rich Trumka,

00:36:05.560 who was the president of the AFL-CIO unions.

00:36:09.560 And if you're not aware about unions, which I was not before this,

00:36:13.340 there are about a handful of incredibly powerful unions

00:36:16.880 that represent the workers.

00:36:19.320 And the AFL-CIO union represents about 60 different unions,

00:36:23.540 each representing the workers, the backbones of America.

00:36:30.660 They make our country run.

00:36:34.520 These are the people who take care of our children,

00:36:40.380 of our, in the hospitals, in our home, the nursing homes,

00:36:46.980 the plumbers, the people who create the roads,

00:36:50.600 the postal workers, the fire departments, the nurses, the teachers.

00:36:57.160 But because of Ramon, he's been in this business for 30 years,

00:37:01.980 has run hundreds of campaigns,

00:37:05.460 including supporting presidential campaigns.

00:37:08.640 His wealth of experience is bar none.

00:37:12.480 And because he's such an honorable person,

00:37:15.480 the doors are open for us.

00:37:18.840 So he puts me in front of the leaders of some of the major unions in our state

00:37:26.280 and in our country,

00:37:27.540 and allows me to share the vision of the TREAT California Act.

00:37:33.020 And every single meeting we've had,

00:37:37.620 they are supporting us.

00:37:39.120 And they are in the process of working through the procedures that they do to endorse us.

00:37:45.220 And I'm proud to share with you

00:37:47.820 that we got the endorsement from the Long Beach Firefighter Union

00:37:52.000 before we even submitted our legislation,

00:37:55.600 which was the first in union history.

00:37:59.160 We also got the support of the American postal workers

00:38:02.760 for the Los Angeles area and San Diego areas.

00:38:06.080 This ground-level support from the people,

00:38:11.900 these are everyday workers who are suffering themselves,

00:38:16.780 their family members are,

00:38:18.460 and they're also taking care of people who are suffering.

00:38:23.340 So when we show up and we say,

00:38:25.940 you know, this is not a cure-all,

00:38:27.700 I do not think psychedelic-assisted therapy is going to cure every person,

00:38:31.560 but I say if we can address 10% of the population that's suffering from

00:38:37.560 depression, anxiety, addiction,

00:38:41.260 just 10% they're otherwise not treated by.

00:38:44.180 We're saving, we don't even talk about money,

00:38:47.220 but we're saving people's lives.

00:38:49.880 And those workers who, you know,

00:38:53.160 have to miss days of work either because they're suffering from something

00:38:56.340 or they're family members and they have to take a day off to go help

00:39:00.660 with a family member who needs help

00:39:03.480 or, and the people that they're also taking care of.

00:39:06.400 It's just, we're in this state of a mental health care crisis

00:39:09.400 so that when I'm in front of these union leaders

00:39:13.500 and I'm talking to them about their members,

00:39:17.160 they feel this.

00:39:19.080 This is not just another political campaign.

00:39:21.520 This is not just a way to go waste some more,

00:39:23.640 you know, money of the government.

00:39:24.980 This is actually a real solution.

00:39:28.360 And, and so they line up.

00:39:29.860 And so then in addition to that,

00:39:31.900 we've got the veteran community

00:39:34.020 because this is where it all began for me

00:39:35.980 with the great work that MAPS did,

00:39:38.460 you know, the nonprofit MAPS

00:39:39.900 and the clinical trials that they were looking at

00:39:41.960 the veteran community.

00:39:43.000 And of course the veteran community is near and dear to me,

00:39:45.680 but we're talking about our vets right now,

00:39:49.180 40 suicides or self-harm a day

00:39:53.080 and our veteran community in large part by PTSD.

00:39:59.120 And I have met many of them.

00:40:01.820 And in fact, we have six former Navy SEALs on our team.

00:40:06.920 We have two generals on our team.

00:40:10.460 I have a three-star general,

00:40:12.660 the former commanding officer of the U.S. Marines

00:40:17.080 on our team.

00:40:19.300 And he has been educating the federal government

00:40:22.760 and the VA about the importance of funding this research

00:40:25.880 for our vets who right now are failing therapies

00:40:30.120 and they have to leave the country

00:40:32.340 to undergo psychedelic-assisted therapies.

00:40:34.680 And they come back, many of them, not all.

00:40:39.580 Many of them come back, changed human beings.

00:40:42.940 And in fact, I like to go off on this little tangent here for you

00:40:46.460 because it's so important.

00:40:48.640 Rick Perry, a self-professed knuckle-dragging Republican from Texas,

00:40:54.180 had an aide on his team who was a former vet

00:41:00.500 who was struggling with PTSD.

00:41:03.340 And on average, these people, you know, it's decades,

00:41:05.680 was struggling, barely making it to work

00:41:07.520 and all that kind of thing.

00:41:08.440 And he left the country

00:41:09.920 and underwent psychedelic-assisted therapy

00:41:12.020 and came back and Rick Perry noticed.

00:41:13.920 And he said, what's going on?

00:41:16.180 What's the difference?

00:41:17.680 And the guy shared it with him.

00:41:19.300 And he said, oh my God, I have to do something.

00:41:23.600 So he went to his legislation

00:41:25.320 and in 2020 passed a bill that afforded $100 million in Texas

00:41:32.520 to study psychedelic-assisted therapy for the veterans.

00:41:36.680 So the veteran community is one that is so desperately in need,

00:41:43.220 like so many Americans are.

00:41:47.540 But the veterans are something that the political right

00:41:52.020 can relate to.

00:41:54.300 So we picked this community to help bridge the divide

00:41:59.580 that is tearing our country apart right now

00:42:02.700 and say this is not a Republican issue or a Democratic issue.

00:42:07.820 This is a human issue.

00:42:10.620 And that we have to take care of our veterans

00:42:14.740 as well as our first responders.

00:42:16.520 I've gotten to know the firefighters.

00:42:19.200 I've learned, shockingly,

00:42:22.040 that suicide is the second leading cause of death

00:42:26.900 amongst our firefighters now.

00:42:30.300 I met with the head of the California Firefighters Union

00:42:34.660 and I'm working with Dr. Sarah Abadie,

00:42:37.980 who is another remarkable human being.

00:42:40.440 And she left her practice at UCLA as an ER physician

00:42:45.780 because she was so tired

00:42:47.280 with patients repeatedly coming into the ER

00:42:51.240 and not being able to treat them at all.

00:42:54.280 And because she's this caring,

00:42:55.840 compassionate person that she is,

00:42:57.440 she's met a few of them that actually left patients,

00:43:01.680 that left the country,

00:43:02.900 that underwent psychedelic-assisted therapy

00:43:04.660 and came back and visited with her.

00:43:06.160 And she just couldn't believe the change.

00:43:09.600 And she herself was traumatized

00:43:11.440 being in the ER during COVID

00:43:13.160 and they call it this wounded healers,

00:43:16.380 this moral deterioration

00:43:19.280 of not being able to really to help people

00:43:21.240 and not having any support about all the trauma,

00:43:24.520 the emotional trauma of which,

00:43:26.480 you know, these are our first responders

00:43:28.960 taking care of us

00:43:30.600 and they are having problems.

00:43:32.840 And so she left and became trained

00:43:36.040 as a psychedelic-assisted therapist

00:43:37.800 and participated in clinical trials.

00:43:41.200 And they're launching a trial at the VA again

00:43:44.320 to help address this unmet need within the VA.

00:43:47.660 So we've got the veteran community supporting us,

00:43:50.500 we've got the union people supporting us,

00:43:53.000 and now we have,

00:43:54.360 we've got the LGBTQ community

00:43:57.100 where there are about 3 million voters

00:44:00.680 that identify as LGBTQ.

00:44:04.440 And this community is being particularly hard hit

00:44:07.340 in today's political environment.

00:44:10.540 And they are rallying behind us to help.

00:44:13.220 They're very politically active as well.

00:44:15.660 And then lastly,

00:44:16.440 we're reaching the university students.

00:44:19.460 We believe that the future is in the youth

00:44:23.000 and they don't have the hangover,

00:44:25.940 what I call the hangover

00:44:26.840 from the Dare to Say No campaigns.

00:44:29.480 They're much more open-minded.

00:44:30.740 They're much more interested in problem solving.

00:44:33.640 And I ache for the world

00:44:36.240 that this generation is inheriting from us,

00:44:39.140 but I also have great hope

00:44:41.960 because it's a great generation.

00:44:43.900 So we've got the kids too

00:44:46.500 that are supporting this.

00:44:48.000 So, and they're showing up.

00:44:49.260 Well, it does sound like we have reached

00:44:52.100 a tipping point here culturally

00:44:53.860 and politically

00:44:55.500 and hopefully scientifically.

00:44:58.380 And it's just very exciting

00:45:00.100 to hear from you

00:45:01.780 about what it's like on the front lines there.

00:45:04.180 You've named some of the clinical applications here,

00:45:06.200 addiction, depression, PTSD.

00:45:08.660 We can also add end-of-life anxiety.

00:45:11.180 Yeah, yeah.

00:45:11.960 Probably we can extend the list beyond that.

00:45:13.980 But then there's also just the betterment

00:45:16.180 of well people,

00:45:17.240 which I know Roland Griffiths,

00:45:19.120 who I've spoken with on the podcast before,

00:45:21.260 has been focusing on.

00:45:22.820 Robin, what, you know,

00:45:24.160 take any piece of this that you want,

00:45:26.580 but I think we should discuss

00:45:28.780 what compounds we're talking about

00:45:31.900 and how do you think we should prioritize

00:45:34.700 or how are you prioritizing the study of them

00:45:38.600 and what seems most promising?

00:45:40.900 What do you think we're going to see,

00:45:43.080 you know, at the bedside first?

00:45:45.240 I mean, just what's happening here

00:45:46.920 on the research front?

00:45:47.720 Well, clearly a lot.

00:45:49.580 It's having such an impact now.

00:45:53.540 I mean, even as we speak,

00:45:56.220 another big paper has landed in Nature Medicine.

00:45:59.580 It was the second of two phase three trials

00:46:03.380 that MAPS sponsored Rick Dobler,

00:46:07.140 the Multidisciplinary Association of Psychedelic Studies

00:46:09.980 and MDMA therapy for post-traumatic stress disorder.

00:46:13.640 And the results of this trial are as positive

00:46:16.580 as the previous phase three trial.

00:46:19.580 And so, you know,

00:46:20.580 the FDA asked for two positive phase three trials.

00:46:23.580 They've got them now.

00:46:25.260 Those results are in the public domain.

00:46:27.760 So MDMA therapy is the furthest along

00:46:30.580 in terms of being federally approved

00:46:33.460 as a prescribable medicine.

00:46:36.940 And we know, you know,

00:46:39.200 how it has to be delivered

00:46:40.540 as a combination treatment.

00:46:42.760 It's not just the drug.

00:46:44.320 That's a really important principle

00:46:46.100 of psychedelic therapy.

00:46:47.480 The clue's in the name.

00:46:48.900 It's not just psychedelics we're talking about.

00:46:51.060 It's this combination

00:46:52.000 with the way the drugs are given.

00:46:54.060 And so MDMA is front of the queue

00:46:57.680 and the forecasts are for next year

00:47:02.140 in terms of approval.

00:47:04.080 We'll see.

00:47:05.500 And would the approval be for narrowly for PTSD

00:47:09.200 or is it for these other conditions as well

00:47:12.180 like depression or end-of-life anxiety or...

00:47:15.520 It's for PTSD.

00:47:16.860 Those were the specific trials.

00:47:18.360 That was the specific indication.

00:47:19.900 So that's on the label.

00:47:21.100 That's the first indication on the label.

00:47:23.960 But, you know,

00:47:24.980 clinicians can prescribe off-label

00:47:26.840 and they do.

00:47:28.260 So it's possible that they could be

00:47:31.700 providing that intervention

00:47:33.740 for other indications.

00:47:35.360 But, you know,

00:47:36.180 it's sort of baby steps

00:47:37.460 once it's through the gate

00:47:39.920 and it will be PTSD.

00:47:42.140 And it'll be a slow process

00:47:43.420 of collecting safety data

00:47:45.160 before, you know,

00:47:47.100 large numbers of people

00:47:48.160 are being treated with MDMA therapy.

00:47:50.860 But it's the big milestone

00:47:53.220 is getting the first psychedelic therapy

00:47:56.180 through FDA approval.

00:47:58.780 So these, you know,

00:47:59.480 state-level initiatives

00:48:00.420 are another thing,

00:48:02.080 but that's the sort of, you know,

00:48:03.980 classic, traditional,

00:48:06.140 formal medical model

00:48:07.540 with the FDA

00:48:08.360 that MDMA therapy

00:48:10.160 is on the cusp

00:48:11.060 of getting that approval.

00:48:14.120 And next in the queue

00:48:15.900 is psilocybin therapy.

00:48:18.280 So there's a phase three trial

00:48:20.680 currently underway

00:48:21.740 sponsored by Compass Pathways.

00:48:24.620 And there the indication

00:48:26.100 is treatment-resistant depression,

00:48:28.280 somewhat building on

00:48:29.340 the work that we did

00:48:31.000 at Imperial College London

00:48:33.140 doing the first

00:48:34.020 psilocybin therapy

00:48:35.520 for depression trial there.

00:48:37.160 And that was in

00:48:37.880 treatment-resistant depression

00:48:39.180 published in 2016.

00:48:40.900 So, yeah,

00:48:42.540 that's going to be

00:48:43.760 the first phase three trial

00:48:46.720 of psilocybin therapy

00:48:48.220 for treatment-resistant depression.

00:48:50.580 And I think forecast there

00:48:52.500 something in the domain

00:48:54.700 of 26,

00:48:56.540 2026

00:48:57.620 for having that work done

00:48:59.880 and that going to the FDA.

00:49:01.460 So that's kind of

00:49:03.340 where we are right now.

00:49:04.820 Then there's a bunch

00:49:05.440 of other compounds,

00:49:06.820 of course.

00:49:07.280 you know,

00:49:08.280 ketamine already

00:49:09.340 is used as a medicine

00:49:11.060 and ketamine therapies

00:49:12.560 is happening right now

00:49:14.180 at some scale,

00:49:15.560 treating depression

00:49:16.600 and so on,

00:49:17.260 rapid acting antidepressant.

00:49:19.260 Somewhat a different model

00:49:20.860 and also a different compound.

00:49:23.040 I'm not sure

00:49:23.760 I would lump it in

00:49:24.800 with psychedelics personally.

00:49:26.120 I think sometimes

00:49:27.500 that term

00:49:28.660 is a little too

00:49:30.140 fuzzily defined

00:49:31.720 or there's a lack

00:49:32.960 of a crisp definition really.

00:49:36.040 But that's there.

00:49:36.760 And then there are

00:49:37.720 other compounds,

00:49:38.620 other classic psychedelics

00:49:39.780 such as LSD.

00:49:41.340 Trials are being done

00:49:42.360 and published

00:49:43.000 on LSD therapy

00:49:44.380 for depression

00:49:46.240 and also alcohol dependence.

00:49:49.240 Michael Bogan shoots.

00:49:51.720 And there's DMT.

00:49:53.120 That's a rapid acting

00:49:54.500 classic psychedelic.

00:49:56.880 It's given intravenously

00:49:58.720 in some of the work

00:50:01.420 that's being done

00:50:02.000 at the moment.

00:50:02.640 Some of the studies

00:50:03.280 we've done at Imperial

00:50:04.920 with brain imaging

00:50:05.820 is given that drug

00:50:07.620 intravenously.

00:50:08.840 It's the main

00:50:10.160 psychedelic component

00:50:11.140 of ayahuasca,

00:50:12.100 the Amazonian brew.

00:50:13.740 And then there's

00:50:14.240 mescaline,

00:50:15.100 Journey Collab

00:50:15.920 are looking at that

00:50:17.060 with an interest

00:50:17.800 in addiction.

00:50:19.380 So there's quite a lot.

00:50:20.800 How about ibogaine?

00:50:22.400 Yeah, ibogaine as well.

00:50:24.280 There's some very,

00:50:25.540 very interesting

00:50:26.100 naturalistic work

00:50:27.440 having been done

00:50:28.780 with ibogaine

00:50:30.140 in veterans

00:50:31.760 with different aspects

00:50:34.480 of mental illness,

00:50:36.220 addictions,

00:50:37.100 PTSD,

00:50:38.560 likely some brain injury

00:50:40.200 issues as well.

00:50:42.300 And so some very promising data

00:50:44.680 coming out of that

00:50:46.020 from Nolan Williams

00:50:48.020 at Stanford

00:50:48.720 doing sort of observational work

00:50:52.340 and also some brain imaging

00:50:53.500 in people going off to Mexico

00:50:55.240 to have these treatments.

00:50:56.360 very exciting,

00:50:58.340 interesting compound,

00:51:00.880 exciting findings.

00:51:02.740 So that's another one too.

00:51:05.460 Yeah, there's a lot going on.

00:51:07.160 Well, notwithstanding

00:51:08.380 what Jeannie said

00:51:09.240 about the need

00:51:10.240 to do a lot more research

00:51:12.100 to assess

00:51:12.760 the safety

00:51:13.640 of these drugs,

00:51:15.200 what do we know

00:51:15.960 about the physiological

00:51:17.440 toxicity or safety

00:51:19.640 of the various compounds?

00:51:21.460 I mean,

00:51:21.600 because my understanding

00:51:22.580 is with something

00:51:24.060 like psilocybin or LSD,

00:51:26.440 there really is no indication

00:51:28.020 that it's physically toxic

00:51:30.180 apart from the possibility

00:51:33.240 of having a bad

00:51:34.240 psychological outcome

00:51:35.740 and, you know,

00:51:37.320 in the worst case,

00:51:38.000 obviously hurting yourself 1.00

00:51:38.920 or killing yourself 0.96

00:51:39.700 the way Jeannie described 0.98

00:51:41.240 in a, you know,

00:51:42.460 taking these medications

00:51:44.040 out in the wild.

00:51:45.440 But with a drug

00:51:47.300 like MDMA

00:51:48.300 or ketamine,

00:51:49.860 you're talking about something

00:51:50.660 where there really is

00:51:52.220 an LD50,

00:51:53.980 you know,

00:51:54.200 a lethal dose

00:51:55.780 that could be easily specified.

00:51:59.680 And perhaps

00:52:00.920 there's some

00:52:01.860 physiological toxicity

00:52:03.160 that we know about

00:52:04.500 in those drugs,

00:52:05.840 even at safe doses,

00:52:07.720 many times repeated.

00:52:09.040 So what can you say

00:52:09.980 to safety?

00:52:11.440 I mean,

00:52:11.740 in reality,

00:52:13.100 there are a lot of people

00:52:13.980 listening to this

00:52:14.820 who are,

00:52:15.660 you know,

00:52:15.820 they might be very supportive

00:52:17.440 of everything

00:52:18.940 we're talking about here

00:52:20.500 and building a well-governed

00:52:23.020 therapeutic model

00:52:24.280 for helping people

00:52:26.040 with the most relevant compounds.

00:52:27.960 But in reality,

00:52:29.100 there are also millions

00:52:29.900 of people

00:52:30.240 who have taken these,

00:52:32.340 quote,

00:52:32.700 recreationally.

00:52:34.000 You happen to be talking

00:52:34.920 to one of them right now.

00:52:36.660 And in making decisions

00:52:38.540 about what to take,

00:52:40.240 there are differences here.

00:52:41.280 And obviously,

00:52:42.100 we should add the caveat

00:52:43.420 that not everyone

00:52:45.680 should take these compounds,

00:52:47.500 certainly not in a situation

00:52:49.100 where they haven't seen

00:52:51.100 to all of the necessities

00:52:53.060 of set and setting.

00:52:55.380 And I've talked about that

00:52:57.120 at great length

00:52:58.260 on other podcasts

00:52:58.940 with people like

00:52:59.760 Roland Griffiths

00:53:00.760 and James Fadiman

00:53:01.700 and others.

00:53:02.720 But there are just

00:53:04.660 differences here.

00:53:05.500 And we should also stipulate

00:53:07.240 that in many cases,

00:53:08.520 unless you're in the presence

00:53:09.760 of something like psilocybin mushrooms,

00:53:12.460 you're taking something

00:53:13.340 that unless you've had it

00:53:14.320 studied in a lab,

00:53:15.200 you can't be sure

00:53:16.140 you're taking the compound

00:53:17.860 you think you're taking.

00:53:18.700 So all of those caveats aside,

00:53:20.900 in the presence

00:53:21.440 of the actual compounds,

00:53:23.460 can you differentiate

00:53:24.300 any safety concerns

00:53:26.740 at the physiological level?

00:53:29.640 Yes, absolutely.

00:53:30.560 I mean, the compounds

00:53:31.300 are often too easily

00:53:32.620 lumped together

00:53:33.320 as, you know,

00:53:34.020 say psychedelics,

00:53:35.060 but they're really

00:53:36.180 quite distinct.

00:53:37.240 And the toxicity profiles

00:53:38.720 are quite distinct.

00:53:40.420 I mean, the dose

00:53:41.560 makes the poison.

00:53:42.520 So even those compounds

00:53:44.380 with the better

00:53:46.040 therapeutic indices,

00:53:48.560 meaning that

00:53:49.240 a therapeutic dose

00:53:51.420 to a dangerous

00:53:53.220 or lethal dose

00:53:54.340 could be massive.

00:53:55.760 And in the case

00:53:56.540 of, say, psilocybin,

00:53:57.680 it is a very large

00:53:58.940 therapeutic index.

00:54:00.060 So that's very positive,

00:54:01.840 you know.

00:54:02.660 But tighter,

00:54:04.300 tighter with LSD,

00:54:05.400 actually, you know,

00:54:06.020 LSD is very potent.

00:54:07.240 So it is not so hard

00:54:09.440 to overdose on LSD.

00:54:11.120 And then it's not just

00:54:12.520 a psychological risk,

00:54:13.840 but there's also

00:54:14.360 some physiological risk

00:54:15.660 as well.

00:54:16.660 MDMA carries some toxicity

00:54:18.320 in high doses.

00:54:20.340 There's some evidence

00:54:20.980 of neurotoxicity.

00:54:22.700 But in therapeutic doses,

00:54:24.240 it seems unlikely.

00:54:26.160 Then you have other organs

00:54:28.120 where MDMA can be toxic

00:54:30.460 to those as well.

00:54:31.820 The liver, ketamine,

00:54:33.360 it has high toxicity,

00:54:36.520 some appreciable toxicity

00:54:38.020 for the bladder

00:54:40.520 and a metabolite of that.

00:54:42.920 So that can be a problem

00:54:44.000 that being cases

00:54:44.820 of people having

00:54:45.520 their bladders removed

00:54:46.600 from excessive use

00:54:48.280 of ketamine.

00:54:49.640 Ketamine is also

00:54:50.760 addictive, right?

00:54:52.340 It is.

00:54:52.840 Another part of the risk profile,

00:54:55.180 elevated risk profile,

00:54:56.300 I'd say,

00:54:57.000 with ketamine.

00:54:58.400 I see ketamine,

00:55:00.020 you know,

00:55:00.360 ketamine therapy

00:55:01.080 is a kind of placeholder

00:55:02.240 for interventions

00:55:04.100 like psilocybin therapy

00:55:05.500 coming down the line.

00:55:07.000 A number of different angles

00:55:09.120 in which psilocybin therapy,

00:55:10.920 I think,

00:55:11.300 is superior to ketamine.

00:55:12.820 The toxicity,

00:55:14.000 it's got the rapid action,

00:55:15.980 but it's also got

00:55:16.720 a more enduring action.

00:55:18.600 In my mind,

00:55:19.220 it's a deeper quality

00:55:20.540 of action as well.

00:55:23.320 A lot of effect

00:55:25.040 on psychological insight,

00:55:28.300 emotional release

00:55:29.540 that perhaps you don't get

00:55:31.020 so easily with ketamine.

00:55:33.700 That's probably,

00:55:34.800 you know,

00:55:35.260 part of the reason

00:55:36.180 why it has a longer tail

00:55:37.800 in terms of a therapeutic response,

00:55:40.380 psilocybin versus ketamine.

00:55:42.240 So a lot of differences.

00:55:43.540 And, you know,

00:55:44.000 we talked about ibogaine

00:55:45.200 a little bit there.

00:55:46.160 There's some

00:55:46.620 cardio toxicity questions.

00:55:50.620 And actually,

00:55:51.400 that's really hampered

00:55:52.380 some of the clinical research

00:55:53.960 with that compound.

00:55:55.680 There hasn't been much

00:55:57.060 in terms of control studies

00:55:58.420 with ibogaine

00:55:59.120 because of question marks

00:56:00.800 over how safe it is

00:56:02.460 in terms of,

00:56:03.380 you know,

00:56:03.980 cardio risk.

00:56:06.940 Most people don't

00:56:08.180 differentiate ketamine,

00:56:10.400 which is an analgesic,

00:56:12.680 and MDMA,

00:56:13.960 which is a type of amphetamine,

00:56:16.020 don't really fall

00:56:17.180 into the class

00:56:17.860 of a true hallucinogen,

00:56:19.900 which are mainly

00:56:20.480 tryptamine derivatives.

00:56:21.880 And so I also want

00:56:23.020 to point out

00:56:23.560 that both ketamine

00:56:24.300 and MDMA are addictive

00:56:26.020 and have different

00:56:28.080 physiological properties.

00:56:29.400 I'm not so sure

00:56:30.060 on MDMA.

00:56:31.060 Yeah.

00:56:31.580 Okay.

00:56:32.000 It's to be explored

00:56:34.580 because amphetamines

00:56:35.520 in general.

00:56:36.560 Amphetamines,

00:56:37.040 yes,

00:56:37.260 but MDMA,

00:56:38.380 MDMA is quite different

00:56:39.560 to other amphetamines

00:56:41.120 in terms of,

00:56:42.140 I mean,

00:56:42.340 amphetamines as a class

00:56:43.880 have that's very strong

00:56:44.900 dopamine release,

00:56:46.420 but serotonin release

00:56:47.600 is 10 times

00:56:48.560 that of dopamine.

00:56:49.420 So it's quite distinct,

00:56:52.180 I would say,

00:56:53.160 from most other amphetamines.

00:56:55.040 And also there isn't

00:56:56.440 clear evidence

00:56:57.580 that people take MDMA

00:56:59.160 in a sort of

00:57:01.100 Moore-ish way,

00:57:02.340 you know,

00:57:02.720 crave it.

00:57:03.940 So what I'm hoping,

00:57:05.020 of course,

00:57:05.360 is that we can actually

00:57:06.460 really study this

00:57:07.760 and track data

00:57:08.860 and determine

00:57:10.240 if it is indeed

00:57:11.180 addictive or not.

00:57:12.480 But until we have

00:57:13.400 the funding to do this,

00:57:14.660 these are all

00:57:15.480 open-ended questions.

00:57:17.300 And I just also

00:57:17.840 wanted to highlight,

00:57:18.640 I think for ketamine,

00:57:20.120 I think one of the

00:57:21.080 best applications

00:57:21.820 will be for

00:57:22.740 acute suicidality.

00:57:24.800 Some of the studies

00:57:25.660 are showing for people

00:57:26.460 that are showing up

00:57:27.440 acutely suicidal

00:57:28.620 in the ER.

00:57:29.360 Oftentimes you sedate

00:57:30.440 the person,

00:57:31.240 you admit the person,

00:57:32.360 you put them on a hold,

00:57:33.920 and you wait

00:57:35.420 until the SSRIs 0.72

00:57:37.360 kind of kick in.

00:57:38.740 It's just a sort

00:57:39.260 of standard of care.

00:57:40.900 But ketamine,

00:57:42.020 the fast-acting effect,

00:57:43.640 appears to allow

00:57:44.960 the patient

00:57:45.540 to feel

00:57:46.580 not depressed

00:57:48.100 for a moment.

00:57:49.380 And in that feeling,

00:57:51.100 they can hold on

00:57:52.240 to that thread,

00:57:53.440 actually,

00:57:54.120 of hope,

00:57:54.920 of not always

00:57:55.600 feeling so depressed,

00:57:57.660 which is what leads

00:57:58.580 people to be suicidal.

00:58:00.940 So,

00:58:02.160 but when we're talking

00:58:03.020 about what we're

00:58:04.360 going to be studying

00:58:05.020 in the Treat Institute,

00:58:07.000 it's mostly

00:58:07.680 the true

00:58:09.420 hallucinogens

00:58:10.400 that don't have

00:58:11.420 patents on them,

00:58:12.300 too,

00:58:12.540 because they don't

00:58:13.200 get funding.

00:58:15.420 Pharmaceutical companies

00:58:16.400 don't get involved

00:58:17.040 in them.

00:58:17.480 And so,

00:58:18.300 I think it's really

00:58:18.920 important to look

00:58:20.020 at all the qualities

00:58:20.820 of these medicines

00:58:21.720 and the impacts

00:58:22.520 on the individuals.

00:58:24.260 And I also want

00:58:24.920 to highlight

00:58:25.300 that what we hope

00:58:26.120 to do is

00:58:26.860 we're going to

00:58:27.800 create what will

00:58:29.080 be the largest

00:58:29.700 bioinformatics

00:58:30.600 data bank

00:58:31.480 in the world

00:58:32.460 focused on

00:58:33.400 mental health.

00:58:34.320 And,

00:58:34.980 of course,

00:58:35.200 we'll make it

00:58:35.640 cyber secure

00:58:36.420 and anonymous,

00:58:38.560 and patients

00:58:39.340 will opt in.

00:58:40.320 But we plan

00:58:40.920 on doing

00:58:42.060 complete

00:58:42.460 genomic sequencing,

00:58:44.260 genetic sequencing,

00:58:45.040 including all

00:58:45.980 the omics,

00:58:46.800 the panomics,

00:58:47.620 the proteomics,

00:58:48.600 the epigenetic

00:58:50.020 changes,

00:58:50.900 and then also

00:58:51.860 including the

00:58:52.760 information coming

00:58:53.540 from all the

00:58:54.220 scanning devices,

00:58:55.260 the fMRIs, 0.54

00:58:56.600 the wearable

00:58:57.100 devices,

00:58:58.260 and then overlay

00:58:59.040 that with what we

00:58:59.820 call the

00:59:00.160 phenotypic expression.

00:59:01.480 So,

00:59:01.660 a patient presents

00:59:02.540 with anxiety,

00:59:04.680 depression,

00:59:05.740 PTSD,

00:59:06.660 and oftentimes

00:59:07.060 complex stuff

00:59:08.500 and or addiction,

00:59:10.420 as well as all

00:59:11.420 the other

00:59:12.160 mental health

00:59:13.440 issues we can

00:59:14.480 call.

00:59:15.320 And that

00:59:15.660 by understanding

00:59:16.900 perhaps the

00:59:17.880 biology of,

00:59:19.300 say,

00:59:19.400 Robin sitting

00:59:19.980 across the

00:59:20.540 table from me

00:59:21.140 has a different

00:59:21.740 makeup of his

00:59:22.620 serotonin receptors

00:59:23.580 and his dopamine

00:59:24.480 receptors that may

00:59:25.480 be more

00:59:26.340 amenable to

00:59:27.280 a particular

00:59:28.260 type of

00:59:29.440 psychedelic

00:59:30.120 versus

00:59:30.540 another type.

00:59:32.260 And so it's

00:59:32.880 truly becoming

00:59:33.760 more patient-specific

00:59:35.500 what is best

00:59:36.520 for him,

00:59:37.840 what will

00:59:38.400 improve his

00:59:39.280 probability of

00:59:40.520 healing from

00:59:41.460 these medicines

00:59:42.160 or gaining

00:59:43.140 insights that

00:59:43.960 empower him

00:59:44.880 to incorporate

00:59:45.800 new habits

00:59:47.660 in his life.

00:59:49.280 And likewise,

00:59:50.560 he may be

00:59:51.480 more open

00:59:53.080 to being in

00:59:53.700 a group

00:59:54.000 therapy to

00:59:54.640 start or

00:59:56.020 not.

00:59:56.820 Maybe he

00:59:57.220 wants to be

00:59:58.540 in a one-on-one

00:59:59.760 to get more

01:00:00.320 comfortable with

01:00:01.080 the medicines

01:00:01.600 and then be

01:00:02.780 in a group

01:00:03.180 therapy.

01:00:03.980 So we don't

01:00:04.920 see it as

01:00:05.600 such a

01:00:06.560 prescriptive

01:00:07.600 therapeutic

01:00:08.440 approach where

01:00:09.240 each person

01:00:09.960 gets this

01:00:11.080 amount for

01:00:11.680 this amount

01:00:12.080 of time

01:00:12.480 under these

01:00:13.480 settings.

01:00:14.820 I think

01:00:15.180 it's important

01:00:15.780 to talk

01:00:16.420 about the

01:00:17.660 variety by

01:00:19.100 which we

01:00:19.600 can learn

01:00:20.000 to heal

01:00:20.540 and make

01:00:21.700 that available.

01:00:23.060 So I'd

01:00:24.160 add that.

01:00:24.680 On this

01:00:25.380 issue of

01:00:26.300 further

01:00:26.920 research,

01:00:27.660 study by

01:00:28.240 study,

01:00:28.780 can you

01:00:29.620 give me a

01:00:29.880 sense of

01:00:30.300 what a

01:00:31.660 well-run

01:00:32.280 study costs

01:00:33.680 at the

01:00:34.440 moment?

01:00:35.280 Sure.

01:00:36.520 Well,

01:00:37.060 gosh,

01:00:37.820 a well-run

01:00:38.920 study,

01:00:39.400 how do you

01:00:39.680 define that?

01:00:40.340 I know

01:00:42.500 there's a

01:00:42.920 wide range

01:00:43.480 and Jeannie 0.59

01:00:44.160 just floated

01:00:44.980 the idea

01:00:45.420 that we

01:00:45.700 would be

01:00:45.980 tracking

01:00:46.340 thousands of

01:00:47.620 people ideally

01:00:48.540 in studies,

01:00:49.220 but the

01:00:49.900 sorts of

01:00:50.300 studies that

01:00:50.720 are being

01:00:50.980 run now,

01:00:51.780 let's say

01:00:52.260 the MAPS

01:00:53.440 study that's

01:00:54.260 in stage

01:00:55.660 three clinical

01:00:56.300 trials,

01:00:57.300 what do

01:00:57.600 those studies

01:00:57.960 cost?

01:00:59.080 Hundreds of

01:00:59.600 millions.

01:01:00.300 Yeah,

01:01:00.600 I mean,

01:01:00.820 I think it's

01:01:01.120 fair to say,

01:01:01.760 it took

01:01:02.200 MAPS 37

01:01:03.060 years,

01:01:03.800 I believe,

01:01:04.240 from its

01:01:04.600 beginning to

01:01:05.340 finish two

01:01:06.820 phase three

01:01:07.540 trials to

01:01:08.440 the tune

01:01:08.800 of about

01:01:09.280 $150

01:01:10.380 million.

01:01:11.820 So it

01:01:12.580 took,

01:01:13.060 you know,

01:01:14.020 37 years.

01:01:15.460 So what we

01:01:16.320 hope to do

01:01:17.060 is,

01:01:18.220 because we

01:01:18.800 have this

01:01:19.200 great clinical

01:01:19.900 trial infrastructure

01:01:20.720 here in our

01:01:21.760 state with

01:01:22.380 incredible academic

01:01:23.460 institutions as

01:01:24.420 well as contract

01:01:25.140 research organizations,

01:01:26.220 we'll determine

01:01:26.980 which ones can

01:01:28.040 be most

01:01:29.020 efficient and

01:01:29.520 most cost

01:01:30.020 effective.

01:01:30.760 We can run

01:01:31.380 trials with

01:01:32.060 thousands of

01:01:32.660 patients in a

01:01:33.280 short period of

01:01:33.900 time because

01:01:35.340 we want to

01:01:36.120 try to find a

01:01:36.940 therapy that

01:01:37.540 actually is

01:01:39.260 safe and

01:01:39.680 efficacious and

01:01:40.500 then determine

01:01:41.080 under what

01:01:42.080 parameters should

01:01:42.900 those patients

01:01:43.460 receive this

01:01:44.160 medicine.

01:01:45.520 Yeah.

01:01:46.440 You know,

01:01:46.980 those phase

01:01:47.540 three trials,

01:01:49.340 a total sample,

01:01:50.560 what's it going

01:01:51.080 to be,

01:01:51.520 in the ballpark

01:01:52.460 of 300 people

01:01:53.420 or something?

01:01:54.100 You know,

01:01:54.300 300 people,

01:01:55.140 it's a very

01:01:56.840 difficult number

01:01:57.580 to quantify because

01:01:58.480 I've run another

01:01:59.220 startup company and

01:02:00.380 depending upon who

01:02:01.500 you get and how

01:02:02.340 you get and how

01:02:02.920 many people you

01:02:03.480 have to have in

01:02:04.100 it,

01:02:04.280 but it's on the

01:02:05.940 order of,

01:02:07.160 I mean,

01:02:07.400 I think the

01:02:07.780 smallest you

01:02:08.320 can do is

01:02:08.960 almost a

01:02:11.260 million,

01:02:12.020 you know,

01:02:12.880 maybe,

01:02:14.040 really realistically

01:02:15.220 with people that

01:02:16.660 you know,

01:02:17.080 but on average I

01:02:18.280 think it'd be fair

01:02:19.080 to say that it's

01:02:19.700 at least a

01:02:20.540 hundred million.

01:02:22.160 Yeah,

01:02:22.600 yeah,

01:02:23.180 but you know,

01:02:23.960 of course there's

01:02:25.060 so many different

01:02:25.700 types of studies

01:02:27.340 and trials and

01:02:28.240 the first

01:02:29.280 investigator-led

01:02:30.360 trials like the

01:02:31.760 treatment-resistant

01:02:32.960 depression trial we

01:02:33.760 did at

01:02:34.220 Imperial,

01:02:35.180 we got some

01:02:36.400 UK Medical

01:02:37.040 Research Council

01:02:37.880 money to make

01:02:39.700 that possible and

01:02:40.880 that was,

01:02:41.640 let's see,

01:02:42.220 the first amount

01:02:44.240 was,

01:02:45.200 I think it was

01:02:45.820 even half a

01:02:46.440 million,

01:02:47.400 so that ended

01:02:48.980 up being a

01:02:49.460 20-patient trial

01:02:51.620 open label

01:02:52.380 because of some

01:02:53.280 philanthropy that

01:02:54.100 came in,

01:02:55.280 but for a long

01:02:56.340 time,

01:02:56.900 you know,

01:02:57.160 we were very

01:02:58.440 much working

01:02:59.280 on fumes,

01:03:01.320 we had volunteer

01:03:02.240 staff,

01:03:03.520 you know,

01:03:03.820 working on the

01:03:04.480 trials and

01:03:05.240 we were just

01:03:06.220 doing it kind

01:03:07.020 of out of

01:03:07.560 passion as much

01:03:08.420 as anything.

01:03:09.680 Things have

01:03:10.220 changed a huge

01:03:11.000 amount since

01:03:11.600 then.

01:03:12.540 What do you

01:03:12.780 think is

01:03:13.080 happening in

01:03:14.380 the brain at

01:03:15.200 this point,

01:03:16.160 Robin,

01:03:16.540 when we take

01:03:18.000 one of the

01:03:19.120 classic serotonergic

01:03:20.780 psychedelics,

01:03:21.740 so LSD,

01:03:22.480 psilocybin,

01:03:23.640 I mean,

01:03:23.920 I'd be interested

01:03:24.580 to know what you

01:03:25.160 think is happening

01:03:25.760 with MDMA as

01:03:26.520 well,

01:03:26.740 but I think

01:03:28.880 you said you

01:03:29.280 did an

01:03:30.100 fMRI study

01:03:30.820 on DMT

01:03:31.620 too,

01:03:32.700 give me the

01:03:34.220 mapping that

01:03:35.540 we are

01:03:37.220 reasonably

01:03:37.540 confident in

01:03:38.180 at this

01:03:38.460 point.

01:03:39.540 Yeah,

01:03:39.940 I think it's

01:03:41.100 fair to say

01:03:41.560 we're reasonably

01:03:42.140 confident now

01:03:42.920 because we've

01:03:43.680 had,

01:03:44.660 personally,

01:03:45.780 I've done

01:03:46.240 three studies

01:03:47.040 with three

01:03:47.460 classics,

01:03:48.620 DMT was the

01:03:49.320 most recent,

01:03:50.880 and so there

01:03:52.020 are some

01:03:52.780 principles that

01:03:53.940 are emerging

01:03:55.280 one of

01:03:57.320 them is

01:03:58.160 that if

01:03:59.380 we look

01:03:59.940 at brain

01:04:00.660 networks,

01:04:01.540 which is

01:04:01.920 more the

01:04:02.320 way that

01:04:02.880 we think

01:04:03.440 of human

01:04:04.520 brain function

01:04:05.300 and making

01:04:05.840 mappings

01:04:06.360 to high

01:04:07.900 level

01:04:08.140 cognition

01:04:08.760 and conscious

01:04:10.620 states,

01:04:11.780 we're much

01:04:12.740 more thinking

01:04:13.260 about brain

01:04:14.260 networks now,

01:04:15.960 their dynamics,

01:04:17.860 and there

01:04:18.900 we see that

01:04:19.840 across the

01:04:20.520 board with

01:04:21.260 psilocybin,

01:04:22.240 LSD,

01:04:22.780 DMT,

01:04:23.340 you see a

01:04:24.300 breakdown

01:04:24.760 in the

01:04:25.860 integrity

01:04:26.580 of brain

01:04:27.860 networks,

01:04:28.640 and this

01:04:29.120 is actually

01:04:29.400 quite true

01:04:29.920 across a

01:04:31.440 repertoire of

01:04:32.340 major brain

01:04:32.980 networks,

01:04:33.840 but especially

01:04:34.400 so in

01:04:34.940 high level

01:04:35.500 brain

01:04:36.400 networks,

01:04:37.420 networks that

01:04:39.280 we describe

01:04:40.000 as transmodal,

01:04:41.240 meaning they

01:04:41.780 don't just

01:04:42.500 do one

01:04:43.220 thing,

01:04:43.760 but they

01:04:44.020 do a few

01:04:44.500 things,

01:04:44.860 they're involved

01:04:45.340 in a lot,

01:04:46.480 including the

01:04:47.500 highest level

01:04:48.100 aspects of

01:04:48.980 human

01:04:49.880 cognition

01:04:50.380 or consciousness.

01:04:51.800 So we see

01:04:52.360 the integrity

01:04:53.200 of those

01:04:53.980 networks,

01:04:54.400 the different

01:04:54.920 nodes,

01:04:55.500 the different

01:04:55.820 parts that

01:04:56.420 make them

01:04:56.840 up,

01:04:57.720 that breaks

01:04:58.500 down.

01:04:59.560 And at the

01:05:00.000 same time,

01:05:01.600 those networks

01:05:02.900 open up

01:05:03.920 their communication

01:05:05.020 profiles,

01:05:05.840 so rather than

01:05:06.840 being very

01:05:07.960 segregated from

01:05:09.120 each other,

01:05:10.060 very insular,

01:05:11.340 they start to

01:05:12.160 communicate more

01:05:13.380 with each other,

01:05:14.900 and we can

01:05:15.560 describe that a

01:05:16.400 few different

01:05:16.900 ways.

01:05:17.660 We could call

01:05:18.120 it desegregation,

01:05:19.460 network

01:05:19.760 desegregation,

01:05:20.860 so you have

01:05:21.240 within-network

01:05:22.740 disintegration,

01:05:24.840 and you have

01:05:25.800 between-network

01:05:26.820 desegregation,

01:05:28.600 where at the

01:05:29.960 global level,

01:05:31.620 as in the

01:05:32.500 whole of the

01:05:32.880 brain,

01:05:33.520 you could

01:05:34.240 describe a

01:05:35.180 global increase

01:05:36.860 in functional

01:05:38.160 integrity.

01:05:39.440 There's more,

01:05:40.440 there's always

01:05:40.940 more, of course,

01:05:41.860 and I haven't

01:05:42.760 even gone into

01:05:43.360 the pharmacology,

01:05:44.400 that with the

01:05:45.640 classic psychedelics,

01:05:46.820 one of the ways

01:05:47.480 that we could

01:05:48.140 define them,

01:05:48.800 I don't think

01:05:49.300 we should only

01:05:50.960 define them

01:05:51.620 this way,

01:05:52.200 because it

01:05:52.840 glosses over

01:05:53.640 the phenomenology,

01:05:54.700 which I actually

01:05:55.280 think is key

01:05:56.460 for a definition

01:05:57.580 of these drugs,

01:05:59.920 but we do know

01:06:00.680 with a high

01:06:01.160 degree of

01:06:01.580 confidence,

01:06:02.420 really mostly

01:06:04.060 from the human

01:06:04.860 research,

01:06:05.840 and I think

01:06:06.600 that is pivotal

01:06:07.460 here, actually.

01:06:09.000 We know that

01:06:09.580 stimulating directly

01:06:10.960 a certain

01:06:11.780 serotonin receptor

01:06:13.020 is key to

01:06:14.380 their action,

01:06:15.040 and we know

01:06:15.440 that because

01:06:15.920 there's a very

01:06:16.420 tight positive

01:06:17.800 correlation between

01:06:18.780 the affinity

01:06:19.440 or stickiness

01:06:20.260 or binding

01:06:21.400 potential of

01:06:23.040 a given

01:06:23.640 psychedelic for

01:06:24.640 that receptor

01:06:25.380 specifically and

01:06:26.520 its potency.

01:06:27.700 Are these still

01:06:28.380 the 2A receptors?

01:06:29.860 Yeah, the

01:06:30.320 serotonin 2A

01:06:31.040 receptors, yeah.

01:06:31.860 So higher

01:06:32.600 affinity, more

01:06:33.400 potent.

01:06:34.440 LSD, very

01:06:35.440 high affinity,

01:06:36.260 very potent

01:06:37.040 compound.

01:06:38.500 And then we

01:06:38.800 also know that

01:06:39.460 if you pre-treat

01:06:40.960 with a serotonin

01:06:42.320 2A receptor

01:06:43.000 blocker, we

01:06:44.040 call those

01:06:44.440 antagonists,

01:06:45.880 then the

01:06:46.900 psychedelic can't 0.99

01:06:47.720 hit its target

01:06:48.460 because it's

01:06:48.940 blocked and

01:06:49.660 you don't

01:06:50.140 trip, you

01:06:51.100 don't have a

01:06:51.540 psychedelic

01:06:51.960 experience.

01:06:52.860 And then we

01:06:53.720 also have

01:06:54.580 more recent

01:06:55.820 evidence that

01:06:56.400 you can abort

01:06:57.240 a trip by

01:06:58.300 giving the

01:06:58.780 blocker after

01:07:00.040 giving the

01:07:00.640 psychedelic.

01:07:01.520 So these are

01:07:03.260 just a few

01:07:04.080 examples of

01:07:05.200 really converging

01:07:06.460 evidence on

01:07:07.640 the 2A

01:07:08.280 receptor as

01:07:09.020 being the

01:07:09.880 key initiation

01:07:11.080 site.

01:07:11.900 It's where it

01:07:12.560 all begins in

01:07:13.440 a sense with

01:07:14.160 the action of

01:07:15.600 at least the

01:07:16.100 classic psychedelics.

01:07:17.180 Is MDMA

01:07:19.340 also active

01:07:20.340 through the

01:07:21.040 2A receptors?

01:07:22.500 Not directly,

01:07:23.440 but really the

01:07:25.000 key sort of

01:07:26.580 signature

01:07:27.140 pharmacological

01:07:28.260 action of

01:07:29.300 MDMA is its

01:07:30.920 serotonin

01:07:31.500 release.

01:07:32.780 Yeah, it's

01:07:33.640 really pretty

01:07:34.740 unique in that

01:07:35.660 sense.

01:07:36.000 There aren't

01:07:36.260 many compounds

01:07:37.160 that release

01:07:38.700 serotonin as

01:07:40.380 potently.

01:07:40.980 Yeah, I

01:07:42.560 mean, we

01:07:42.820 have the

01:07:43.160 selective

01:07:43.440 serotonin

01:07:44.020 reuptake

01:07:44.560 inhibits

01:07:45.120 antidepressants,

01:07:46.940 Prozac-like

01:07:48.360 drugs, but

01:07:49.740 they're just

01:07:51.020 blocking the

01:07:52.100 reuptake.

01:07:52.940 MDMA actually

01:07:53.640 stimulates the

01:07:54.500 release of

01:07:55.180 serotonin, so

01:07:56.120 I sometimes

01:07:57.180 playfully call

01:07:58.060 it a turbo

01:07:59.580 SSRI.

01:08:01.300 It's sort of

01:08:01.760 spitting out

01:08:02.560 serotonin into

01:08:03.600 the synapse,

01:08:05.100 that gap where

01:08:05.900 all the key

01:08:06.700 chemical information

01:08:09.260 transfer happens

01:08:10.240 between neurons.

01:08:11.580 Well, in some

01:08:12.760 possible dystopian

01:08:13.960 future, it will

01:08:14.660 be sold under

01:08:15.300 that name in a

01:08:16.240 drugstore near

01:08:17.060 you to

01:08:18.460 teenagers.

01:08:19.660 What do you

01:08:20.440 make of the

01:08:20.760 fact that DMT

01:08:21.920 is actually an

01:08:23.480 endogenous

01:08:24.140 neurotransmitter?

01:08:25.640 I mean, do we

01:08:25.940 know what it

01:08:26.840 might be doing at

01:08:27.760 this point on

01:08:28.380 its own at its

01:08:29.260 ambient level?

01:08:31.140 We don't, but

01:08:31.760 it's one of the

01:08:32.280 great mysteries,

01:08:33.700 and, you know,

01:08:34.480 Rick Strassman has

01:08:35.600 classically speculated

01:08:37.100 on that in the

01:08:38.900 spirit molecule.

01:08:40.380 It is there.

01:08:42.100 You can find it in

01:08:43.200 the body, and you

01:08:43.900 can find it in the

01:08:44.700 brain, and there's

01:08:45.360 also some rodent

01:08:47.180 evidence now that

01:08:48.080 it's released, or

01:08:49.640 at least its

01:08:50.060 concentration spikes

01:08:51.360 up in a dying

01:08:52.960 brain. 0.79

01:08:54.220 And the problem

01:08:55.480 there is a

01:08:56.420 specificity question

01:08:57.540 because a lot

01:08:58.340 spikes up in a

01:08:59.800 dying brain because

01:09:00.580 cells are dying and

01:09:02.280 spilling their

01:09:02.840 content in a sense.

01:09:04.160 So serotonin

01:09:05.020 itself spikes up

01:09:06.300 massively.

01:09:06.720 So there's just a

01:09:08.300 little bit of a

01:09:08.900 question mark on

01:09:09.720 there.

01:09:10.380 Some people have

01:09:11.060 also questioned

01:09:11.720 whether there's

01:09:12.600 enough of DMT

01:09:14.840 endogenously to

01:09:16.760 really have an

01:09:17.640 appreciable sort of

01:09:19.120 functional effect,

01:09:20.080 but then people say,

01:09:20.880 well, you know,

01:09:21.580 during these extreme

01:09:22.600 states, as was

01:09:23.760 shown in that

01:09:24.340 rodent work, maybe

01:09:25.720 it spikes up, and

01:09:27.220 then maybe then

01:09:28.340 it, you know, that

01:09:29.540 could explain things

01:09:30.460 like the near-death

01:09:31.340 experience because you

01:09:32.640 enter a psychedelic-like

01:09:34.700 state through the

01:09:35.800 action of this

01:09:36.620 endogenous

01:09:37.120 psychedelic.

01:09:38.260 It's a very fun

01:09:40.480 hypothesis, but

01:09:42.400 that's kind of what

01:09:43.520 it is still right

01:09:44.640 now, a hypothesis.

01:09:47.720 There are overlaps in

01:09:49.240 the phenomenology.

01:09:50.220 It's just whether or

01:09:51.540 not we can commit to

01:09:52.920 DMT, specifically,

01:09:55.460 you know,

01:09:55.900 responsible, being

01:09:57.060 responsible for that

01:09:58.080 phenomenology, or

01:09:59.120 for example, you

01:10:00.400 know, it could be

01:10:01.220 established endogenous

01:10:02.800 neurotransmitters like 1.00

01:10:03.960 serotonin, you know,

01:10:05.320 and that's spiking up

01:10:06.420 and hitting its 2A

01:10:07.940 targets and so on.

01:10:10.400 Is there any

01:10:11.220 prospect, do you

01:10:13.240 think, in the near

01:10:14.280 term of us

01:10:15.460 developing and

01:10:17.300 discovering new

01:10:18.960 compounds that we

01:10:20.260 just haven't named

01:10:21.760 here?

01:10:22.120 I mean, we're

01:10:22.880 talking about, we

01:10:24.100 can almost count on

01:10:24.820 one hand the number

01:10:25.980 of compounds we're

01:10:26.920 excited to study, but

01:10:28.340 I remember meeting

01:10:29.320 the rogue chemist,

01:10:31.300 Sasha Shulgin.

01:10:32.260 I don't know if

01:10:32.880 either of you ever

01:10:33.720 knew him, but, you

01:10:35.020 know, to hear him

01:10:36.980 talk about it, it

01:10:37.860 sounded like if you

01:10:38.660 just, you know,

01:10:39.780 walked into his

01:10:40.400 house, he could

01:10:41.700 produce, you know,

01:10:43.140 hundreds of

01:10:43.920 different compounds

01:10:44.720 that he had

01:10:45.980 privately

01:10:46.520 experimented with

01:10:47.480 and cataloged.

01:10:49.140 He wrote some

01:10:50.080 very interesting

01:10:50.840 books on that

01:10:51.440 topic.

01:10:52.480 And so there's

01:10:53.600 just kind of this

01:10:54.140 thicket of adjacent

01:10:56.260 compounds that are

01:10:58.120 sitting there to be

01:10:59.180 explored, I think

01:11:00.820 some of which were

01:11:01.560 described by him as

01:11:02.560 a, you know, don't

01:11:03.200 go there again, but

01:11:04.580 what do you think

01:11:06.040 about the prospect

01:11:06.940 that we are at the

01:11:08.800 very beginning of

01:11:10.040 exploring in a much

01:11:11.660 wider search space?

01:11:14.300 Well, we are.

01:11:15.360 I mean, we don't

01:11:16.420 know what we don't

01:11:17.280 know, but people are

01:11:18.400 searching vast

01:11:19.300 libraries, even sort

01:11:20.640 of, you know,

01:11:21.820 libraries of billions

01:11:23.280 of potential molecules

01:11:25.560 by doing, you know,

01:11:28.040 in silico modeling,

01:11:29.180 computer modeling, and

01:11:30.320 looking at how these

01:11:31.280 possible chemicals

01:11:33.600 dock at, say, the

01:11:34.800 serotonin-2A

01:11:35.620 receptor.

01:11:36.800 So, you know, there

01:11:38.040 could be almost

01:11:39.120 endless possibilities

01:11:40.340 there in terms of

01:11:41.380 new drugs.

01:11:42.840 Yeah, so, and we

01:11:44.960 could play with the

01:11:45.780 pharmacology and try

01:11:47.400 and find, you know,

01:11:49.420 drugs with where we

01:11:51.040 could reduce some of

01:11:52.280 the off-target effects.

01:11:54.060 Say, for example,

01:11:55.160 serotonin-2B receptor

01:11:58.180 stimulation is a

01:11:59.340 problem.

01:12:00.380 If you have drugs

01:12:01.380 that do that, it

01:12:02.560 can sort of fatten

01:12:04.100 up the heart valves

01:12:05.860 and cause this

01:12:07.400 valvopathy.

01:12:09.760 So, you know,

01:12:10.940 maybe, and you have

01:12:12.680 compounds like, you

01:12:13.500 know, psilocybin,

01:12:14.480 which is metabolized

01:12:15.420 into psilocin,

01:12:17.040 actually hitting the

01:12:18.180 2B receptor.

01:12:19.500 So, you know, that's

01:12:20.640 been a question mark

01:12:21.620 for things like

01:12:22.240 microdosing or regular

01:12:24.180 use of low doses

01:12:25.600 of psilocybin.

01:12:27.320 So, you know, we

01:12:28.480 could improve on the

01:12:29.480 drugs.

01:12:29.940 There is another, in a

01:12:32.280 sense, that's a given

01:12:33.180 and to the point that

01:12:34.740 we don't know what we

01:12:35.600 don't know and, you

01:12:36.960 know, science is always

01:12:37.940 iterative and it will

01:12:39.780 go on forever,

01:12:40.920 improving, advancing

01:12:42.140 how we understand

01:12:43.080 things.

01:12:44.020 But there is another

01:12:44.880 thing to say, which is

01:12:46.540 we could be very

01:12:47.280 drug-centric here.

01:12:48.860 And if fundamentally

01:12:50.380 with psychedelic

01:12:51.500 therapy we have a

01:12:52.420 combination treatment,

01:12:53.600 then maybe, you know,

01:12:54.800 there's a lot to be

01:12:56.240 learned about the

01:12:58.220 other side of this,

01:12:59.260 the other side of

01:13:00.520 this biopsychosocial

01:13:02.880 intervention that isn't

01:13:04.840 just giving the drug.

01:13:06.600 And so we can make

01:13:07.700 advancements there too.

01:13:10.100 Sam, I'd like to share

01:13:10.880 a fun folklore story,

01:13:12.660 if you don't mind,

01:13:13.360 about the shoguns

01:13:14.560 because somebody on my

01:13:15.460 team spent quite a bit

01:13:17.920 of time with them.

01:13:18.680 He was fresh out of

01:13:20.000 college at Princeton

01:13:20.900 way back when and got

01:13:22.020 his PhD in philosophy

01:13:23.980 and taught at Yale.

01:13:25.820 And then...

01:13:26.460 Oh, yeah.

01:13:27.080 I forgot.

01:13:27.740 I met him.

01:13:28.480 Yeah.

01:13:28.660 What's his name again?

01:13:29.580 David Blinder.

01:13:30.480 Yeah.

01:13:31.000 And it's just a

01:13:31.820 wonderful story, but

01:13:32.860 he befriended the

01:13:34.000 shoguns and 1.00

01:13:34.800 participated regularly.

01:13:37.840 Sasha would create 1.00

01:13:38.820 these compounds and

01:13:40.660 pass them out to

01:13:41.680 everybody and ask

01:13:42.980 them what the

01:13:44.800 side effects were and

01:13:45.660 then he would

01:13:46.100 meticulously write

01:13:47.400 them down.

01:13:48.720 So upon his death

01:13:50.000 and his wife's

01:13:50.660 deaths recently,

01:13:51.340 there is the

01:13:52.340 Shogun Library

01:13:53.280 and there are

01:13:53.900 about 200 compounds

01:13:55.420 that there are

01:13:56.520 efforts to help

01:13:58.180 and preserve them

01:13:59.280 and to bring them

01:14:00.960 to the world

01:14:03.060 of research.

01:14:04.040 And one effort

01:14:05.160 which I hope we

01:14:06.020 will be able to do

01:14:07.000 is if there are

01:14:07.700 some of them that

01:14:08.520 are deserving of

01:14:09.560 studying that we

01:14:10.860 can look at it.

01:14:11.960 Because I also want

01:14:12.620 to point out in

01:14:13.260 addition to,

01:14:14.020 and I want to go

01:14:14.560 into what's where

01:14:15.920 Robin just left off

01:14:17.020 about the spiritual

01:14:17.760 part of this too

01:14:18.640 because I think it's

01:14:19.300 really important and

01:14:20.060 would like to bring

01:14:20.640 that up.

01:14:21.340 But there are

01:14:21.940 other treatment

01:14:23.080 paradigms that this

01:14:23.980 is really seemingly

01:14:25.020 promising for and

01:14:26.220 a traumatic brain

01:14:27.100 injury is one and

01:14:28.180 the neurodegenerative

01:14:29.480 diseases, you know,

01:14:30.620 because of the

01:14:31.240 neuroplasticities,

01:14:32.160 whether there's

01:14:32.620 growth factors in

01:14:33.480 there that seem to

01:14:34.520 perhaps be a

01:14:35.820 disease-modifying

01:14:36.620 compound for

01:14:37.400 Alzheimer's.

01:14:39.080 I know there's one

01:14:40.000 study that was

01:14:40.760 using psilocybin, I

01:14:42.460 believe, for the

01:14:43.520 treatment of new-onset

01:14:44.480 depression that's

01:14:45.200 oftentimes associated

01:14:46.380 with neurodegenerative

01:14:47.580 disease.

01:14:47.980 In this particular case,

01:14:48.960 it was Parkinson's

01:14:49.840 disease, and they

01:14:52.020 noticed that the

01:14:53.200 motor symptoms were

01:14:54.400 improving.

01:14:54.920 So not only did

01:14:55.560 their depression

01:14:56.120 symptoms improve, but

01:14:57.440 they noticed that the

01:14:58.640 motor symptoms

01:14:59.860 improved.

01:15:00.400 So I think that there

01:15:01.260 is room for these

01:15:03.540 medicines to be

01:15:05.300 studied for different

01:15:07.220 applications.

01:15:08.380 I'm also aware of a

01:15:09.580 scientist who's using

01:15:10.620 this to study

01:15:11.500 inflammatory diseases,

01:15:13.360 and particularly

01:15:13.940 asthma.

01:15:14.900 And I think, wow,

01:15:16.420 you know, when I was

01:15:17.380 in medical school or

01:15:18.280 even practicing

01:15:18.900 medicine, when you

01:15:19.620 hear about a cure-all,

01:15:21.980 right, you think of

01:15:22.800 this snake oil sales

01:15:24.240 person peddling the

01:15:25.800 goods that this is

01:15:26.640 going to help

01:15:27.420 everything, but these

01:15:28.040 are actually well-run

01:15:29.900 studies.

01:15:31.000 And so it just begs

01:15:32.880 the question that I

01:15:33.840 think that there are

01:15:34.660 many applications that

01:15:36.000 are possibilities and

01:15:38.120 that we need to look

01:15:39.160 at them.

01:15:39.960 And then I want to

01:15:40.480 leave that and go

01:15:41.160 back to where Robin

01:15:42.620 left off, because I

01:15:43.520 had a couple questions

01:15:44.120 for you, Robin, and I

01:15:45.100 was so curious about

01:15:46.440 this study, and you

01:15:48.380 mentioned about

01:15:49.240 desiloing or

01:15:50.860 desegregating, you

01:15:52.000 said, certain areas

01:15:52.780 of the brain.

01:15:54.100 And I wonder if you

01:15:54.760 would just elaborate

01:15:55.380 on that a little bit

01:15:56.200 more, because it's

01:15:56.880 something that I have

01:15:57.580 personally felt in my

01:15:59.280 own brain.

01:16:00.520 And I want to share

01:16:01.160 that by way of saying

01:16:02.100 if, you know, I've

01:16:02.840 studied as a

01:16:04.380 biochemist, and I have

01:16:05.580 that area of my brain

01:16:06.440 as well-developed in

01:16:07.460 math, and I'm also,

01:16:09.380 you know, an athlete,

01:16:10.380 there's a different part

01:16:10.980 of my brain that works,

01:16:12.100 and I like music, and

01:16:13.280 that's a different part

01:16:13.940 of my brain that works,

01:16:14.920 and then the ability

01:16:15.620 to think abstractly is

01:16:17.240 a different part of my

01:16:17.960 brain.

01:16:18.880 And I just personally

01:16:19.880 have noticed that

01:16:21.520 since using these

01:16:23.000 medicines therapeutically,

01:16:24.660 that I feel like I

01:16:26.020 have access to these

01:16:28.340 otherwise siloed parts

01:16:30.400 of my brain are now

01:16:32.380 seemingly available to

01:16:34.440 me at the same time.

01:16:36.240 And I was wondering if

01:16:37.900 you could speak to that

01:16:38.720 in some of the fMRI

01:16:39.640 studies that you, I

01:16:41.240 thought you participated

01:16:42.060 in them, or you're

01:16:44.000 certainly aware of them.

01:16:44.920 Oh, yeah.

01:16:45.340 Yeah.

01:16:45.800 Did you run that trial,

01:16:47.220 Robin?

01:16:48.040 Probably.

01:16:48.700 Yeah.

01:16:49.900 Well, yeah.

01:16:51.140 Of course, we have to be

01:16:52.840 a bit careful what we

01:16:53.720 feel in our brain.

01:16:55.580 Um, but, uh, yeah, I

01:16:59.080 mean, yeah, there's a few

01:17:02.600 different principles as I,

01:17:04.440 as I said, you have, in a

01:17:08.660 sense, organization and

01:17:11.260 structure that's recognized

01:17:13.600 in the brain, like, say, a

01:17:15.080 brain network, that you can

01:17:17.500 then see decrease in its

01:17:20.460 organization under drugs.

01:17:23.380 So that's, that's, you

01:17:25.340 know, example of that

01:17:26.220 disintegration or, or a

01:17:27.940 loss of structure or a

01:17:29.960 loss of regular, you

01:17:31.340 know, regularity, a

01:17:33.100 dysregulating action.

01:17:34.920 So that's stuff breaking

01:17:36.020 down, you know?

01:17:37.900 I call that, there's a

01:17:39.700 hypothesis I introduced

01:17:40.960 about 10 years ago called

01:17:42.180 the entropic brain

01:17:43.000 hypothesis, which is

01:17:45.220 somewhat related here.

01:17:47.520 You can think of entropy

01:17:48.600 in a thermodynamic sense of

01:17:50.380 degradation, things, things

01:17:52.720 breaking down the arrow of

01:17:54.480 time.

01:17:55.280 But there's also this

01:17:56.280 intriguing possibility that

01:17:58.420 we have less of a good

01:18:00.060 handle on, which is, you

01:18:02.980 know, it takes us back to

01:18:03.880 the definition of these

01:18:05.020 compounds, at least, you

01:18:06.260 know, true classic

01:18:07.300 psychedelics, psyche as a

01:18:10.360 mind or more, more

01:18:11.700 accurately, soul.

01:18:12.960 And then the other term

01:18:14.360 means to make manifest or

01:18:16.140 visible.

01:18:17.000 So, you know, while we have

01:18:19.420 aspects of, of brain

01:18:21.600 function, dysregulating

01:18:23.200 or breaking down, what

01:18:25.740 of, you know, the, the

01:18:28.820 hidden order amidst the

01:18:30.860 disorder or the cosmos in

01:18:32.840 the chaos, as Carl Jung

01:18:34.040 would say, you know, what

01:18:35.500 accounts for that?

01:18:36.740 What accounts for the

01:18:37.500 insight?

01:18:38.320 What accounts for the, the

01:18:40.060 apparent, you know, seeing

01:18:43.580 of, of things, of content,

01:18:45.620 say on DMT, you know,

01:18:47.640 classic aspect of the

01:18:48.800 phenomenology there is that

01:18:50.260 people report these

01:18:51.940 apparent sort of encounters

01:18:54.360 with other sentient

01:18:55.440 beings.

01:18:56.580 What's doing that?

01:18:57.880 You know, I know that

01:18:58.780 really throws people when

01:19:00.160 they have the experience,

01:19:01.960 they're left bamboozled

01:19:03.080 thinking that they, it

01:19:04.820 must be something beyond

01:19:05.920 the brain.

01:19:07.080 Of course, I think that's a

01:19:08.280 false inference.

01:19:10.160 Well, that brings us, that

01:19:11.500 brings us back to your

01:19:12.800 naive thesis that you

01:19:14.740 mentioned a while ago,

01:19:16.140 which is the, the, by

01:19:18.060 analogy to dreams, right?

01:19:19.780 I mean, the dreams are an

01:19:21.900 experience where we

01:19:23.040 routinely seem to feel an

01:19:26.520 experience that we're in

01:19:27.600 the presence of, of other

01:19:29.420 autonomous beings, right?

01:19:31.640 And, you know, that's, you

01:19:33.440 know, everyone's had that

01:19:34.580 experience.

01:19:35.480 You know, you're talking to

01:19:36.320 somebody who you really

01:19:37.100 think is there and then you

01:19:38.100 wake up and you realize it

01:19:39.160 wasn't what you thought it

01:19:40.120 was.

01:19:40.440 So does that offer some,

01:19:42.680 some phenomenological clue to

01:19:44.720 what might be happening

01:19:45.680 during the DMT flash?

01:19:48.400 Yeah, I think it does.

01:19:49.300 Yeah.

01:19:49.540 I think it's a useful, useful

01:19:51.920 analogy.

01:19:53.780 The, you know, the dream is

01:19:56.440 entirely compelling.

01:19:57.940 There's no doubt that you're

01:19:59.560 experiencing that in the

01:20:00.960 moment and yet you're not,

01:20:03.180 you know?

01:20:03.860 I guess the one, the one

01:20:04.860 thing that fans of some

01:20:07.220 metaphysical claim here would

01:20:09.660 want to say at this point is

01:20:11.100 that that doesn't explain the

01:20:13.300 apparent convergence

01:20:14.860 phenomenologically in the

01:20:17.540 reports that people give of

01:20:19.180 the kinds of entities they

01:20:21.620 encounter while on DMT.

01:20:23.580 I don't know.

01:20:24.000 I remember Rick Strassman's

01:20:25.520 book on this topic, but I

01:20:28.020 haven't followed whatever

01:20:29.300 research has been done of

01:20:30.740 late.

01:20:31.480 I can imagine it'd be

01:20:33.200 somewhat hard to find a

01:20:35.200 volunteer for a DMT study who

01:20:37.180 had never heard Terrence

01:20:38.760 McKenna or anyone else rave

01:20:40.260 about the phenomenology.

01:20:41.900 How impressive is that

01:20:44.460 convergence of report on

01:20:46.960 what the landscape looks like

01:20:49.340 during the experience?

01:20:50.460 Well, there's some

01:20:51.360 convergence, but of course

01:20:52.600 there's, I say of course,

01:20:54.320 there's this thing called the

01:20:55.380 collective unconscious and

01:20:56.760 archetypes and, you know,

01:20:58.920 certain human themes that get

01:21:01.240 in a sense imprinted because

01:21:03.220 we experience them a lot, you

01:21:04.740 know, like the hero's journey.

01:21:06.400 It's classic.

01:21:07.200 It's arguably, you know,

01:21:08.620 universal and somewhat

01:21:10.460 culturally independent at the

01:21:12.880 most basic level, at the most

01:21:14.520 foundational level.

01:21:16.260 So it would be surprising if it

01:21:19.180 was any other way that we

01:21:21.460 wouldn't have archetypal-like

01:21:23.580 experiences, you know, under

01:21:26.460 these compounds, experience, you

01:21:29.060 know, tricksters that can, and

01:21:31.080 then morph into a, you know,

01:21:32.900 maternal archetype, a mother

01:21:34.760 archetype, and then switch back

01:21:37.540 again.

01:21:38.160 So that's the human, you know,

01:21:40.180 that's human nature, the human

01:21:41.500 psyche.

01:21:42.540 So I don't think there's

01:21:43.540 anything that should draw us

01:21:45.680 into beyond the brain kind of

01:21:48.640 speculations there based on any

01:21:51.300 kind of convergence.

01:21:52.240 It just speaks to, in my mind,

01:21:54.040 the collective unconscious.

01:21:55.500 Yeah.

01:21:56.820 I could go on, but, you know, I

01:21:58.880 mean, a dominant model in

01:22:00.500 cognitive neuroscience now is

01:22:02.280 is one that a friend and

01:22:04.940 colleague of mine, Shamil

01:22:06.540 Chandaria, spoke about recently

01:22:08.140 on your podcast, the

01:22:10.060 hierarchical predictive

01:22:11.240 processing model.

01:22:13.860 Very compelling model of how the

01:22:15.900 brain works, in a sense, that's

01:22:17.900 increasingly influential,

01:22:19.760 including in psychiatry.

01:22:21.860 And there, you know, the model

01:22:23.320 says that we experience the world

01:22:24.900 through these generative models,

01:22:27.240 this kind of coarse graining of

01:22:28.960 what's what.

01:22:29.660 But the key principle is that

01:22:31.840 there's a dominant

01:22:32.900 directionality to the

01:22:35.020 information flow that that in a

01:22:36.940 sense you could describe as

01:22:38.040 top down.

01:22:39.320 And that's what's carrying the

01:22:40.960 prediction, carrying the

01:22:42.080 inference is that we're

01:22:43.300 experiencing the world through

01:22:45.280 our internal models.

01:22:48.220 That's what's dominating, you

01:22:50.620 know, the handshake, if you want,

01:22:52.280 is that top down model, model

01:22:54.520 first kind of flow.

01:22:56.360 Into that mix, I dropped

01:22:58.480 psychedelics in a sense, and

01:23:01.140 proposed that what psychedelics

01:23:03.800 do is they impact the, what's

01:23:06.960 called in technical terms, the

01:23:09.300 precision weighting, but in more

01:23:10.960 sort of accessible terms, we could

01:23:13.240 just call the weighting, the

01:23:15.000 weighting or the influence of the

01:23:18.140 predictive models.

01:23:19.880 And psychedelics dial it down so

01:23:22.080 that our internal models are less

01:23:25.000 convincing, and stuff can come up

01:23:28.600 because of that.

01:23:30.480 Yeah.

01:23:31.040 Yeah.

01:23:31.580 I mean, it's just in a very basic

01:23:33.920 psychological sense, when you look

01:23:35.800 at why people suffer, and this is,

01:23:38.600 you know, leaving aside even extreme

01:23:41.960 clinical cases, just the ordinary

01:23:43.720 routine suffering of ordinary people

01:23:45.860 who may not have any diagnosis to

01:23:48.300 speak of, so much of the character of

01:23:51.180 our suffering is this

01:23:53.460 imprisonment in certain patterns of

01:23:56.920 thinking and reacting to just ordinary

01:23:59.720 experience.

01:24:00.440 I mean, we're ruminating all day long.

01:24:02.660 We're having a very unprofitable

01:24:05.080 conversation with ourselves that, in my

01:24:08.180 view, also impressively resembles what

01:24:11.480 it's like to be asleep and dreaming.

01:24:13.260 I mean, there's something about

01:24:14.840 identification with thought that is

01:24:16.780 just as spurious, in the end, as being

01:24:20.960 asleep and dreaming and not knowing

01:24:22.480 that you're dreaming.

01:24:23.500 And it's pretty easy to see that certain

01:24:26.520 ways of disrupting that would offer a

01:24:29.160 kind of, you know, disrupting and

01:24:31.100 resetting would offer a kind of

01:24:32.760 opportunity for relief.

01:24:35.500 Quite.

01:24:36.420 Yeah.

01:24:37.040 I mean, it's true of psychopathology, I

01:24:40.140 think, mental illness, so much of it, 0.75

01:24:41.880 depression, anorexia, you know, these

01:24:44.640 habits of thinking, getting fixated on

01:24:48.440 certain ideas, in a sense, you know,

01:24:51.580 that we're worthless or that we're too

01:24:54.020 big.

01:24:54.880 But also, it's the case, you know, in

01:24:58.040 domains that we wouldn't ordinarily think

01:25:00.080 of as psychopathological or of mental

01:25:03.700 illness, you know, even politics or

01:25:05.440 religion, we can, I borrow a term from

01:25:08.420 evolutionary science, which is

01:25:10.320 which is canalization, it means the

01:25:13.500 entrenchment of traits so that they

01:25:17.200 become stamped in and resistant to

01:25:19.920 change, resilient to change.

01:25:22.300 It's the opposite, actually, of the most

01:25:24.720 basic definition of plasticity, which is

01:25:27.760 the ability to be, to change, to be

01:25:30.360 shaped or molded.

01:25:32.100 So canalization is the inverse of that.

01:25:33.960 You know, but even our very sense of

01:25:36.040 self or identity or ego is a product of

01:25:40.760 the same canalization or identifying with

01:25:44.280 thoughts.

01:25:45.920 Yeah.

01:25:46.620 Yeah.

01:25:47.120 On that point, how much of it is a story

01:25:49.960 still of the default mode network being

01:25:53.780 downregulated during the psychedelic

01:25:56.600 experience?

01:25:57.180 Is that still part of the signature of

01:25:59.400 what's happening?

01:26:00.320 Yeah, I'd say we've moved on a little

01:26:02.500 bit.

01:26:02.700 That was a finding of ours in the first

01:26:06.200 fMRI study that we did.

01:26:08.400 In fact, the first fMRI study of

01:26:10.920 psilocybin, 2012, we found that the

01:26:14.720 default mode network was especially

01:26:16.520 implicated.

01:26:18.100 Its integrity broke down, as I was

01:26:20.720 describing this disintegration effect.

01:26:22.800 And other changes also kind of pointed

01:26:26.220 at this default mode network, this

01:26:28.780 dominant network in the brain that is,

01:26:33.140 you know, kind of capital city in the

01:26:35.280 brain.

01:26:35.960 It's a hub of connectivity, of high

01:26:38.960 metabolism, tonically active in the

01:26:41.960 background, hence default mode.

01:26:44.460 Yeah.

01:26:44.720 So we saw that dysregulated and in a

01:26:47.880 sense disintegrate under the psilocybin.

01:26:50.600 And we also saw that effect correlate

01:26:52.400 in different analyses over time with

01:26:55.220 ratings of ego dissolution.

01:26:56.940 So we made a kind of one-to-one mapping

01:26:59.420 there that maybe it's related to that

01:27:01.660 experience of ego dissolution.

01:27:04.040 That had a big impact as an idea and it

01:27:06.380 sort of became, in a sense, this

01:27:08.320 canalized story in itself.

01:27:11.160 I'd say we've moved on a little bit

01:27:12.820 because I think it was a little too

01:27:16.120 centered on one particular network.

01:27:18.440 There are other neighboring networks

01:27:20.120 also high level that break down under

01:27:23.680 psychedelics and are also implicated or,

01:27:26.860 you know, that breakdown correlates with

01:27:28.880 ratings of ego dissolution as well.

01:27:31.240 So I just think it was too focused on one

01:27:33.800 particular network.

01:27:34.840 I don't think it's wrong as an idea.

01:27:37.140 There's just more to it as there always

01:27:40.280 is, of course.

01:27:42.060 How about the critical window period that

01:27:44.260 Goal is introducing?

01:27:45.160 Well, that's a nice one too.

01:27:46.860 Yeah.

01:27:47.360 So, you know, we have these periods early

01:27:50.320 in life when we're hyperplastic, you

01:27:53.280 know, just think of kids and how they can

01:27:56.260 pick up languages so easily in the early

01:27:59.540 years.

01:28:00.000 And then that window of plasticity or sort

01:28:03.260 of spongibility that you take on so much

01:28:06.940 closes and we've become less plastic and

01:28:10.060 less able to learn.

01:28:11.060 So, yeah, that critical period plasticity has

01:28:15.760 been especially well articulated by

01:28:18.680 Gould Dolan and it very much fits the

01:28:21.860 model, you know, that psychedelics reopen

01:28:24.000 these critical periods of plasticity or

01:28:28.740 just generally open windows of plasticity.

01:28:32.060 Has that been tested with respect to

01:28:36.220 learning of anything, languages or

01:28:38.380 otherwise?

01:28:39.220 Not very well in humans in terms of

01:28:44.640 learning paradigms and accelerating

01:28:46.980 learning.

01:28:47.900 We did do one study with LSD where we had a

01:28:53.520 certain cognitive flexibility paradigm where

01:28:56.920 we were able to look at learning rate, you

01:28:59.760 know, how quickly you could learn in this

01:29:02.040 case a rule and just like the way symbols

01:29:05.800 relate to each other is quite a sort of

01:29:07.460 low-level psychological paradigm.

01:29:09.520 But we did see that there was an

01:29:10.740 acceleration in learning rate there.

01:29:12.660 But there should be more work in that

01:29:15.680 kind of space than there has been.

01:29:18.140 Yeah, let's see.

01:29:20.140 Where, you mentioned microdosing and

01:29:22.240 passing at some point, where does the

01:29:24.420 research stand there?

01:29:26.860 I remember a study that came out not long

01:29:29.220 ago suggesting that it really was a, some

01:29:32.760 version of the placebo effect.

01:29:34.480 Yeah, yeah, that's another one of ours.

01:29:38.160 Yeah, so that was Balash Segeti and there we

01:29:42.420 did an interesting design, a self-blinded

01:29:46.380 citizen science study.

01:29:47.920 So we sort of advertised to people, really

01:29:50.460 Balash led this and he advertised to people 1.00

01:29:53.360 intending to microdose that, oh, why don't

01:29:56.360 you, you know, get some capsules and close some

01:29:59.720 empty capsules and do your own, you know,

01:30:02.480 blinding paradigm as if you're running a

01:30:04.500 double-blind randomized control trial.

01:30:06.980 It was very clever.

01:30:07.920 Yeah, that's clever, yeah.

01:30:09.220 Yeah, we got a couple of hundred people to

01:30:11.380 do it.

01:30:11.880 So the biggest sample, I think, to date on

01:30:14.880 microdosing, it was LSD and mushrooms.

01:30:18.200 You could do either.

01:30:19.540 And there we found that most of the positive

01:30:22.660 effects that people were reporting could be

01:30:26.740 explained by thinking you were getting a

01:30:29.240 microdose.

01:30:30.660 So if you got placebo and thought it was a

01:30:32.200 microdose, you did as well as if you actually

01:30:34.460 got the microdose.

01:30:36.020 So the evidence is a bit mixed and I think

01:30:38.680 the rationale is good and the theory is good

01:30:41.340 that low doses of psychedelics could, in a

01:30:44.440 sense, lubricate the mind, lubricate the

01:30:47.600 brain, open a bit of plasticity without

01:30:50.440 necessarily having a big trip and maybe you

01:30:52.800 could do something with that window of

01:30:54.880 opportunity, that window of plasticity.

01:30:57.140 Problem is there hasn't been good enough

01:30:58.720 research done yet.

01:31:00.480 It's hard to do microdosing studies because,

01:31:03.800 you know, by definition it's a dosing

01:31:06.960 regimen.

01:31:07.840 So you're going to be doing a lot of dosing

01:31:09.780 and are the ethics boards, the IRBs, going

01:31:13.920 to allow you to give participants psychedelics

01:31:17.380 to take home to do this?

01:31:19.040 Probably not.

01:31:20.080 So then you have to do it in a lab and the

01:31:22.540 typical protocol with microdosing is a few

01:31:25.000 weeks of sort of one day on, one day off or

01:31:28.620 some variation on that.

01:31:30.640 So that's a lot of visits and that's going

01:31:33.700 to be, you know, horribly expensive and it's

01:31:37.300 these kind of practical challenges that have

01:31:40.040 meant that we haven't done very good

01:31:42.420 microdosing studies.

01:31:43.600 And when the control studies have been done,

01:31:46.720 they haven't really come through with

01:31:48.840 compelling evidence.

01:31:49.700 So I would just say, watch this space on

01:31:52.460 microdosing as an idea.

01:31:54.320 It's quite, quite interesting, if not even

01:31:57.100 compelling, but the evidence isn't there yet.

01:32:01.020 Well, another reason to fund some research.

01:32:04.400 Do you know, Sam, I would like to ask you,

01:32:07.160 your understanding of religion and religion

01:32:14.220 before it was even organized religion,

01:32:17.280 the ability of these religious leaders to

01:32:21.600 seemingly tap into what we experience in the

01:32:28.540 psychedelic space of this feeling of unity with

01:32:35.680 everybody and everything in the universe, as if it's

01:32:38.920 some form of, some religions would call it God,

01:32:43.200 and that boundary between the spiritual slash

01:32:46.620 metaphysical and the biological, you know, the

01:32:50.400 chemistry, the biochemistry, the physics that's

01:32:52.820 happening in our brains.

01:32:54.000 And I'm guessing you've considered this quite a bit,

01:32:58.440 and I just wondered if you would share.

01:33:00.620 Yeah, well, I talk about it a lot, especially over at

01:33:04.620 Waking Up, our meditation app.

01:33:08.560 I mean, it's a very big question.

01:33:10.340 I think there's a few high-level things I would

01:33:13.720 demarcate.

01:33:14.940 I mean, one is I think, you know, I have been for

01:33:17.800 many years now a fairly vociferous critic of

01:33:21.460 organized religion, not because I don't think the

01:33:24.920 core experiences that lie at the founding of all or

01:33:29.420 most of our religions are valid and interesting and

01:33:32.260 worth having and exploring and understanding, but

01:33:35.620 because I think they are so important and interesting, and

01:33:40.020 we obviously need a 21st century, truly non-denominational,

01:33:44.920 non-sectarian, non-divisive, not irrational framing of

01:33:49.380 those experiences.

01:33:50.260 So the reason why I want to get out of the religion 0.99

01:33:52.180 business is because I think these mutually incompatible

01:33:56.060 claims of our various Iron Age and medieval religions

01:34:01.360 just are blocking a more sophisticated and useful and

01:34:06.100 not divisive conversation that's possible.

01:34:09.420 So, you know, insofar as I can help inspire that

01:34:12.680 conversation, I've been trying to do that.

01:34:15.020 And in various moments, my criticism of organized religion

01:34:18.660 has been fairly denigrating, but I'm also realistic that,

01:34:22.800 you know, I don't think I'm going to live to see a day

01:34:24.640 where there are no longer Christians, Muslims, Jews, Buddhists,

01:34:27.580 Hindus, all vying for recognition of the unique veracity of 1.00

01:34:31.520 each of their faiths.

01:34:33.320 And I also, I just think we're in very different lanes here.

01:34:37.120 I mean, I think I would, you know, just do nothing but celebrate

01:34:39.780 the fact that you could reach out to a fundamentalist Christian

01:34:43.140 and convince them that they want to support the TREAT initiative

01:34:48.100 very much within the context of their Christianity, right?

01:34:52.000 Like this is, you know, I don't think you should be in the business

01:34:54.000 of pointing out what is wrong with Christianity.

01:34:56.720 No.

01:34:57.240 That's my job.

01:34:59.640 But, um...

01:35:01.340 Can I share with you, can I share with you just real quick?

01:35:03.620 Yeah, go first.

01:35:04.060 The first, I'd submitted the legislation, I think it was July 17th,

01:35:09.160 and putting in long hours, and at the end of the night,

01:35:12.460 there was a voice memo, and I debated whether I wanted to listen to it or not,

01:35:17.980 because if it was something that might upset me, it might upset my sleep.

01:35:21.940 But for some reason, I decided to listen to it,

01:35:24.660 and I wanted to share this with you, because I think it's just jaw-dropping,

01:35:27.960 remarkable to me.

01:35:29.520 It was from a very conservative Christian white man who said,

01:35:34.520 I read your legislation, and I think it's the most impactful

01:35:38.840 and important legislation I've ever read.

01:35:42.080 And he said, and I'm a conservative white Christian,

01:35:45.860 and we get a bad rap these days,

01:35:49.380 but I want you to know we're not all bad,

01:35:52.160 and I support you 100%.

01:35:54.340 So, of course, I called him later and asked him

01:35:56.320 if he could post it on our website.

01:35:58.740 So I didn't mean to interrupt, but it just...

01:36:00.520 It was just further affirmation that this goes beyond politics and religion,

01:36:06.980 and that there's so much suffering out there

01:36:08.900 that people are starving for a new solution.

01:36:13.820 Yeah.

01:36:14.440 Yeah, well, I mean, what it promises to me is

01:36:17.100 something like a 21st century version of a new Mysteries of Eleusis, right?

01:36:25.140 This is the secretive rite that was at the foundation

01:36:30.040 of a fair amount of Greek philosophy.

01:36:33.740 But by its very nature, it was organized, it was orderly,

01:36:39.140 it was not a matter of handing out these compounds

01:36:42.780 to everyone to use recreationally.

01:36:45.980 I mean, I'm very supportive of decriminalization,

01:36:49.140 but I'm also very supportive of circumspection

01:36:53.520 and how we move into this space.

01:36:56.440 And I mean, I say that, you know,

01:36:58.140 it's a fair amount of apparent hypocrisy to untangle here

01:37:02.260 because, you know, my own personal and illegal use of these compounds

01:37:06.400 was absolutely indispensable back in the day.

01:37:09.920 I mean, it really got me started in thinking about all these things,

01:37:14.100 and I really don't think I would have become interested

01:37:17.020 in the nature of the mind and the contemplative life.

01:37:20.980 I mean, I just think I was a hard enough case

01:37:22.760 when I was an 18-year-old undergraduate in college

01:37:26.020 that I just, if you had taught me to meditate at that point,

01:37:29.800 I think I just would have bounced off the whole project.

01:37:32.920 So it's, you know, I just think we, as a culture,

01:37:38.120 you know, as much as I want to get out of the religion business

01:37:40.280 and get past all of the political liabilities of that,

01:37:44.820 as I see them, and the unscientific bias

01:37:47.600 that I think is built into it.

01:37:49.380 I think secular culture is really starving

01:37:53.120 for a fully wise language by which to, you know, organize our lives.

01:37:59.960 And so we have to make the best uses of all of the human conversations

01:38:04.340 that have preceded this moment.

01:38:06.400 So I mean, I think we should grab everything that's useful

01:38:09.640 in religion and philosophy and literature and art

01:38:12.300 and every other corner of discourse.

01:38:15.180 But I just think we have to recognize that, you know,

01:38:18.380 what we have in each moment going forward personally and collectively

01:38:21.800 is consciousness and its contents

01:38:24.880 and our only dimly emerging understanding

01:38:28.500 of how anything that seems to be happening is happening in the first place.

01:38:33.360 And science remains the leading edge of that understanding.

01:38:38.240 And what we need is a really rich first-person side of that inquiry.

01:38:45.920 And the introduction of psychedelics into the conversation

01:38:48.200 puts the furthest reaches of human well-being

01:38:51.960 and insight into reach for normal people.

01:38:56.360 I mean, this is, you know, normally you would have to be the kind of person

01:38:59.480 who would be willing to spend a year on silent retreat, you know,

01:39:03.600 to begin to touch what someone can touch in four hours under proper guidance

01:39:10.220 given a compound like MDMA or psilocybin.

01:39:14.420 And so it's not to say that there aren't differences

01:39:17.200 between meditation and psychedelics.

01:39:19.480 I've talked about those in other contexts,

01:39:21.640 but there's a fair amount of overlap there as well.

01:39:24.400 And so I just think it's fantastic what you guys are doing.

01:39:28.220 And I really appreciate you both coming on the podcast to talk about it.

01:39:32.360 Well, thank you.

01:39:33.660 And just a quick shout-out to Brian for his book, The Immortality Key.

01:39:37.820 Yeah.

01:39:38.300 Where it's just a brilliant recounting of that time.

01:39:42.660 And again, I want to highlight that it was the women priestess

01:39:46.480 that were there to serve these medicines.

01:39:49.500 And that's what we intend to do in today's age,

01:39:54.580 to bring these medicines thoughtfully to the public in a safe way,

01:40:00.340 but introducing a new model, a completely new model,

01:40:04.200 where we do embrace the human being human again

01:40:09.400 and being able to talk about that

01:40:11.640 and being able to connect with one another

01:40:13.680 with compassion and understanding,

01:40:16.580 an appreciation for we are more than just a collection of neurons in our brain.

01:40:22.680 We are part of a collective group,

01:40:25.540 a superorganism, if you will, of this, you know, homo sapiens.

01:40:29.740 And that it's time for us to focus our efforts on helping others

01:40:37.400 and also taking agency over one's own sense of self.

01:40:41.780 And I believe, you know, there's oftentimes I've been involved

01:40:45.460 with some really interesting research projects

01:40:47.500 and oftentimes ahead of the curve.

01:40:52.560 And so timing in life is so crucial, too.

01:40:56.560 And I hope that what I'm feeling is this groundswell,

01:41:01.740 this need, this readiness of society, actually,

01:41:06.140 to be open to a new approach to dealing with pain and suffering.

01:41:15.220 And I say, welcome to Treat California.

01:41:18.760 Nice. Give me that website again.

01:41:21.840 TreatCalifornia.org.

01:41:23.800 Excellent. Well, I look forward to supporting you,

01:41:26.100 and I hope our listeners will as well.

01:41:29.120 Jeannie, Robin, thank you for your time.

01:41:31.260 Thank you.

01:41:31.700 Thank you.

01:41:31.780 Thank you.

01:41:31.820 Thank you.

Making Sense - Sam Harris - October 04, 2023

#337 — The Future of Psychedelic Medicine

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