Making Sense - Sam Harris - #377 — The Future of Psychedelic Medicine 2

00:00:00.000 welcome to the making sense podcast this is sam harris today i'm speaking with doctors

00:00:27.680 jennifer mitchell and sarah betty jennifer mitchell is a professor in the ucsf department of neurology

00:00:34.720 and associate chief of staff for research and development at the san francisco va her research

00:00:40.800 is focused on identifying and developing novel therapeutics for drug and alcohol abuse ptsd

00:00:46.800 stress anxiety and depression and on understanding the neural mechanisms responsible for these

00:00:52.880 disorders dr mitchell has extensive and diverse experience with human and animal pharmacology

00:00:58.960 hypothesis driven neuroscience human proof of concept studies and clinical trials for the past

00:01:05.280 few years her work has centered around the development of psychedelic medicines for a

00:01:08.480 broad range of mental health conditions including ptsd which we will discuss dr sarah betty is a

00:01:15.520 board-certified emergency medicine physician and psychedelic facilitator for clinical trials she

00:01:21.280 has worked as a psychedelic facilitator at pacific neuroscience institute and is set to join the

00:01:26.400 psilocybin and mindfulness study at the usc center for mindfulness science which i think my friend jonas

00:01:32.000 kaplan is also associated with she works on policy change to expand funding for mental health research

00:01:39.680 she has served as chief medical officer and deputy campaign manager for the treat california initiative

00:01:45.440 which i discussed on a previous podcast this was a citizen-driven initiative aimed at establishing a

00:01:51.680 five billion dollar funding agency to explore novel therapeutics including psychedelics and that will

00:01:57.680 be coming back around i trust currently sarah is the chief medical officer at treat humanity an

00:02:03.920 organization dedicated to advancing the research of medical health therapeutics including psychedelics and

00:02:09.760 we've posted the relevant links for jenny and sarah in the show notes as well as one that gives more

00:02:15.520 information about the upcoming decision that the fda is making with respect to mdma assisted psychotherapy

00:02:21.680 for ptsd which is pretty much the focus of today's discussion we talk about recent developments in

00:02:28.080 research on psychedelics and related compounds mdma especially we discuss the history of this research and

00:02:34.800 the war on drugs a recent setback in the fda approval process mdma is a promising treatment for ptsd the

00:02:43.120 challenges of conducting this research allegations of therapist misconduct new therapeutic models for

00:02:49.840 mental health treatment psychoneuroimmunology the so-called non-psychedelic psychedelics good and bad

00:02:57.120 trips the fda's coming decision on mdma assisted therapy right to try policies for pharmaceuticals

00:03:04.800 the role of psychedelic therapists the problem of having this work being done underground

00:03:10.320 and other topics and now i bring you dr jennifer mitchell and dr sarah betty

00:03:21.760 i am here with dr jennifer mitchell and dr sarah betty jenny sarah thanks for joining me thank you

00:03:28.000 absolutely thanks for having us so um we're going to talk about the state of

00:03:32.960 research into psychedelics this is a topic i've covered a few times on the podcast i have an

00:03:39.600 interest in this that i have not made a secret but it's you know what we we seem to be approaching

00:03:45.040 a kind of critical moment here in the progress in this research so um i want to cover that and

00:03:51.440 perhaps we can just start with um each of you briefly describing your backgrounds in science and

00:03:58.720 medicine and how you came to take an interest in this topic jenny let's start with you sure so i am

00:04:05.280 a neuroscientist by training i'm a professor at ucsf in the departments of neurology and psychiatry

00:04:11.760 and behavioral science at ucsf and i'm also the associate chief of staff for research at the san

00:04:18.160 francisco va medical center and i've been studying psychedelics in clinical populations for the past

00:04:25.280 approximately seven years now primarily work with psilocybin and mdma for ptsd and uh in terms of

00:04:33.440 how i i came about it i'm a native san franciscan i got to see a thing or two as a kid i went to a

00:04:39.440 college that uh was uh very proactive when it came to psychedelic use and got to see a thing or two there

00:04:47.200 as well and thought that these could potentially be intriguing compounds to study and develop as

00:04:53.360 therapeutics and so that's me nice yes so so i'm an emergency medicine doctor and what actually really

00:05:01.760 led me down this path was probably what i saw and more in the emergency room and so you know before i

00:05:07.840 actually started even in the field of er i really thought most of what i would be seeing would be acute

00:05:13.600 emergencies and that was actually could not be farther from reality and so a lot of what i would

00:05:19.440 actually see were chronic medical problems with really an emphasis i would say on untreated mental

00:05:24.880 health issues and it felt like this revolving door in my er and i can't tell you how much as a

00:05:30.800 clinician it was difficult day in day out to see patients coming in asking for treatment and help and

00:05:37.680 there was really nothing i could offer them and so that's when i really got curious you know is there

00:05:42.720 something else that we're missing and so that's what really began my exploration and i actually

00:05:47.920 started doing research in the field so i've worked as a facilitator a psychedelic facilitator

00:05:52.800 at pacific neuroscience institute studying various effects of psilocybin and lsd on mental

00:05:58.960 health issues as well as i will be joining the team at usc center of mindfulness science

00:06:04.640 looking at psilocybin's effects on mindfulness and separate even anecdotally as i was understanding

00:06:11.600 more about these compounds i found countless people whose lives in their words were saved by

00:06:18.080 psychedelics and they ranged from everyone moms first responders students navy seals and you know

00:06:26.000 they would report that they had tried every conventional medical treatment available and it

00:06:30.960 didn't work and so usually they saw psychedelics as this last-ditch effort this hail mary and so many

00:06:37.520 would report having been on countless pharmaceuticals and they felt like it would numb or blunt their

00:06:43.120 symptoms and then they emphasized how important it was to do it therapeutically and so what i was

00:06:48.800 curious about is what what is the hurdle what are we what's that roadblock that is not allowing us to

00:06:55.680 explore this as a treatment or understand it further and so what it always came down to me was funding

00:07:02.000 there's an issue with funding here and so for many reasons including the war on drugs the

00:07:06.880 stigmatization of these medicines it's been really hard to get government funding to fund this work

00:07:12.080 and so for the past few decades philanthropists have really had to foot that bill and so that's actually

00:07:17.680 where i got involved more in the policy space with psychedelics and so i was involved with the treat

00:07:23.040 california ballot initiative and i'm not sure if your listeners remember um the prior podcast you had

00:07:28.640 interviewed jeannie fontana where she was dr jeannie fontana where she was discussing this project

00:07:33.680 and so just as a reminder it was a citizen-driven ballot initiative in california that would have

00:07:38.480 created a five billion dollar funding agency to research and support this field of psychedelic medicine

00:07:45.200 as many i think who understand the complexity of this field recognize that this is a completely

00:07:50.480 new paradigm and it doesn't really fit in the structures and frameworks that we currently have

00:07:56.720 and so that initiative would have allowed us to do research and to understand the risks it would have

00:08:03.280 helped us provide education and access and so you know maybe a little bit of an explanation of what

00:08:09.040 happened um we had built a very powerful coalition and there was this incredible movement and when we

00:08:14.720 pulled on the language that we actually had received from the attorney general this would be actually the

00:08:18.880 language you'd see on the ballot we found that while californians really believed in psychedelic medicine and

00:08:24.640 researching it and understanding it they actually did not have confidence that a government agency could

00:08:29.920 uphold its promise and there's this growing distrust in the government to get anything done

00:08:36.000 and so educating the public on why the treat initiative stands apart it was difficult so we didn't

00:08:43.760 yeah we had to unfortunately stop and we've shifted now to treat humanity so that's what i'm doing

00:08:48.880 um now is i'm the chief medical officer at treat humanity where we're looking at the same issue how

00:08:54.880 to unlock the necessary capital to fund this research and build the infrastructure which i actually would

00:09:00.720 argue would help address a lot of the issues that we're seeing come up with the fda committee

00:09:05.600 and mdma and so you know some of the things we're looking at is possibly a campaign in 26 in california

00:09:12.080 federal options global options and it's a joint effort so we need the best and brightest on this

00:09:18.560 so that's a little bit of what i'm doing right now nice uh yeah maybe i should just take a moment to

00:09:24.720 review some of the history here because it will remind people of why the involvement of government

00:09:30.400 and the attitude of government is is so complicating and um why we're at some risk of of losing

00:09:38.480 the hard-won progress that um many people had begun to take for granted in recent years so i mean just

00:09:44.560 to quickly run through this i mean many of the compounds we would talk about i think we're going

00:09:48.880 to focus on mdma because of the the recent study and and fda advisory ruling and mdma is not technically

00:09:56.880 a psychedelic we might add a footnote there later but most of these drugs mdma lsd psilocybin have been

00:10:04.080 around for quite some time you discovered in the in the 20s 30s 40s i mean psilocybin goes obviously way

00:10:12.560 back in native medicine in in the form of mushrooms but the interest of western science is for the most

00:10:21.120 part in an early and mid 20th century project and much of this was bearing fruit in in scientific

00:10:29.200 research and and seeming to hold great promise and then uh the 60s came around and timothy leary who

00:10:35.840 was one of the phds at harvard who was doing this research also became a great uh proselytizer of the

00:10:43.680 countercultural potential of these drugs you know lsd in particular and he in uh i think it was about

00:10:51.200 1966 or thereabouts he told uh a generation to turn on tune in and drop out and we had a great

00:10:59.920 counter reaction to this countercultural moment which culminated in the war on drugs in 1971 uh when

00:11:08.480 more or less you know all of the most promising compounds were officially ruled schedule one and

00:11:14.240 therefore declared dangerous and and worthless and so a full generation of of research on psychedelics

00:11:20.720 and and other therapeutics just went into eclipse actually mdma is a bit of a once again an outlier

00:11:27.360 here and that people really didn't rediscover it and begin taking it until the the 80s and um so it

00:11:35.680 wasn't covered by that initial schedule in in 1971 but then it was quickly ruled to be you know

00:11:42.240 at the moment it became popular it was ruled to be schedule one and therefore forbidden and illegal and

00:11:48.720 then if memory serves i think in more or less in response to that i mean the many people in the

00:11:55.360 therapeutic community recognized at the time that mdma held immense promise for healing of various kinds

00:12:04.320 and when it was ruled illegal uh rick doblin formed maps the multidisciplinary association for

00:12:10.400 psychedelic studies and began working to change our drug laws and to restart research and he was working

00:12:17.680 you know by definition on the fringes of society for quite some time and then there was this quiet

00:12:23.840 resurgence in research i think uh roland griffiths started in johns hopkins at 19 in 1999 and his he

00:12:34.000 published a paper on psilocybin that got a lot of attention in 2006 and then the floodgates really

00:12:40.800 opened when michael pollan the journalist published his new yorker piece in 2015 and his book how to

00:12:47.040 change your mind in 2018 and then this is you know it's in these last six to ten years that we have been

00:12:54.320 talking more or less as though it were a fait accompli that the psychedelics were coming back and that we

00:13:00.800 were simply going to not make the mistakes that had been made in the 60s uh you know so floridly by

00:13:08.160 timothy leary in particular is so as to create a counter-reaction from the government and and in

00:13:15.840 some understandable paranoia that that you know handy in these powerful compounds to everyone in sight

00:13:21.760 could create a lot of unintended harm which i think we we would agree is is quite possible so here we are

00:13:29.120 you know more or less in the present re maps uh and this you know the spinoff uh pharmaceutical

00:13:35.840 company lycos has brought research through uh now i'm coming to you jenny through stage three clinical

00:13:45.040 trials and this is where jenny you to my understanding join the story explicitly tell me about your

00:13:51.440 involvement with maps and lycos and the study you have done and where we are and what and because

00:13:59.040 there was recently a fair amount of press attention about the fda's advisory panel reaction to the study

00:14:07.280 that you ran for lycos and so so talk us through that and sure you know complete my sentence for me

00:14:13.520 sure i think my original interaction with what was then maps pbc was was accidental i was accidentally

00:14:21.440 invited to their phase three planning meeting i didn't know it was a phase three planning meeting

00:14:25.440 i myself had never done what we call phase three so phase three is like the last step in the fda

00:14:30.800 clinical development pipeline it's a multi-site study typically it involves a high number of subjects

00:14:36.800 you're sort of already past your dose finding stage and your safety stage and uh so i went to this phase

00:14:43.600 three meeting and i i met some of the people that were maps pbc at the time and and accidentally

00:14:49.760 participated in this day with them and then by the end of the day it was very clear that there was great

00:14:53.680 opportunity to work together and so at that point i agreed to join their phase three program

00:14:59.520 and investigate the efficacy and safety of mdma for ptsd and so we started with a study that

00:15:05.360 involved participants that had severe ptsd and then the replication phase involved a slightly broader

00:15:12.480 study population that had either moderate or severe ptsd but remarkably the outcomes of of both studies

00:15:19.280 were very similar and i didn't know this at the time myself having been sort of new to phase three

00:15:24.000 studies but that's i guess kind of unheard of for the results to be so similar especially as you

00:15:30.240 brought in your study population a bit but in short approximately what 70 percent of the participants

00:15:36.160 over the course of the two studies lost their diagnosis of ptsd and that is a remarkable outcome

00:15:44.480 when compared to our current gold standard treatments for ptsd and i think that's why it raised so much

00:15:51.360 interest and and garnered so much hope for actually jenny i i assume everyone believes they understand

00:15:58.480 what ptsd is but you might take a moment to just talk about how we think about it and why it has been

00:16:06.000 so difficult to find therapy for and i mean just how much suffering is is under that acronym right okay

00:16:13.840 so that's a very good point i think that so post traumatic stress disorder is ptsd and we have a book

00:16:20.240 called the dsm that tells us sort of how to define ptsd and that book says that ptsd has to occur in

00:16:26.000 response to experiencing or witnessing a traumatic event and that traumatic event must often involve

00:16:31.120 death or serious injury so you can imagine first of all that there are a lot of people that say i have

00:16:34.640 ptsd we throw the term around kind of colloquially at this point but a lot of the time we don't have

00:16:39.280 people that meet that diagnostic criteria when they do unfortunately ptsd is is particularly hard to

00:16:45.360 treat it also often occurs it's not like a standalone diagnosis which would be really

00:16:50.560 convenient it often occurs with other comorbid diagnoses such as depression anxiety tbis drug

00:16:58.960 and alcohol use disorder and unfortunately those comorbidities make it much more treatment intractable

00:17:04.560 much more difficult to treat ptsd and so one of the issues that we've had of course then is that we

00:17:09.520 we don't have any great we don't have any great pharmacological therapeutics for ptsd we have

00:17:14.960 two fda approved ssri so the selective serotonin reuptake inhibitors that were developed for

00:17:20.640 depression sertraline and paroxetine those two ssris are often prescribed for people that are suffering

00:17:27.520 from ptsd they don't work for a majority of the subjects that have ptsd but i think that the hope has

00:17:33.840 always long been that because depression and ptsd are so often comorbid that perhaps you're tamping

00:17:40.160 down the depression and that helps the ptsd more generally in a subset of subjects i don't i don't

00:17:45.920 know so that's one problem is that we don't have good pharmacological agents for it we have these

00:17:51.280 two talk therapies right cognitive behavior therapy prolonged exposure therapy and the problem with

00:17:57.760 those and those are typically considered gold standard therapies for treatment of ptsd especially in

00:18:01.680 veterans but the problem there is that you're asked to live and relive and re-relive your trauma

00:18:07.680 until you sort of it doesn't have the same impact that it had originally is the idea but you can

00:18:12.720 imagine that that process is extremely painful most people don't complete a full course of treatment

00:18:17.680 because it actually sort of stirs the pot and generates even more symptoms as you're reliving

00:18:23.040 that trauma so that's why we really needed a new therapeutic for ptsd it's a it's a huge there's

00:18:28.400 a huge unmet need ptsd often especially in our veteran population triggers suicidality and so you

00:18:34.960 know we lose almost a veteran an hour to suicide and my personal belief is that better therapeutics could

00:18:40.880 improve those numbers yeah yeah so in that context hearing rumors of a a 70 response rate that's fairly

00:18:51.440 thrilling data right people seemed thrilled i mean i i was i myself was genuinely surprised at the

00:19:01.760 remarkable efficacy that the compound demonstrated i mean i did think that there'd be a signal there i

00:19:06.640 didn't think it would be that robust i didn't think it would be that durable but it it has shown to be

00:19:12.000 so i think that that's all great news and i think that it originally generated a lot of enthusiasm and

00:19:17.600 then more recently there's been this pushback right the pendulum's been swinging can you say something

00:19:22.400 about the pushback sure i mean i think as many people know there was an advisory committee meeting

00:19:28.240 that was held by the fda recently and that advisory committee believes that there isn't enough evidence

00:19:34.400 of efficacy and safety to move forward on approval of mdma for ptsd as advisory committee is not the fda

00:19:41.280 itself right so i think it's important to remember it's not that the fda ruled that mdma was not

00:19:46.880 approvable as a a therapy for in conjunction with therapy for ptsd it was the advisory committee but

00:19:53.200 still that that seemed like a a setback and suggested that there's some confusion in the

00:19:58.240 field exactly about how mdma assisted therapy works and about how safe and efficacious it actually is

00:20:06.240 well what were the actual and sarah feel free to chime in here at any point but just sticking with you

00:20:13.040 jenny what what were the actual criticisms i mean there were criticisms about um unblinding with

00:20:21.040 respect to you know what what was the active agent and what was the control i mean this is kind of a

00:20:26.560 comical problem that one runs into and this goes all the way back to the original research in the in

00:20:33.760 the 50s and 60s and the problem is these in most medical research when you want to do a double blind

00:20:39.840 control study you can effectively do that because it remains a mystery to the participants who's taken

00:20:45.600 the active compound and and who hasn't but when you're giving people drugs like mdma or psilocybin

00:20:50.960 or lsd the effects of these drugs are so powerful and so unignorable that in its most comical variant

00:20:59.360 there was the um the study i think it was run by leary and albert back in the early 60s usually described as

00:21:06.800 the good friday experiments where they gave a bunch of seminarians you know they gave half placebos and

00:21:12.000 half i think it was synthetic psilocybin might have been lsd and you know half of the room was

00:21:18.880 within the hour was having the beatific vision and the other half was you know looking over their

00:21:23.520 shoulders wondering why they weren't uh weren't seeing god and it was just absolutely clear to

00:21:29.920 everyone although i think i think one of the controls also had a mystical experience if i'm not

00:21:34.480 mistaken uh but in any case it's very hard to keep these blind experiments blind was that the

00:21:40.560 problem that you had with the study i myself didn't think it was a problem with the study it

00:21:46.240 was definitely something that the adcom brought up as a problem for them so i think there you've

00:21:51.280 raised a couple of interesting points i mean the first one is that it's very hard to blind psychedelics

00:21:55.760 trials most people know that they've taken the active drug some people don't so we had people in

00:22:01.040 phase three that guessed wrong in both directions which i still find kind of fascinating there were

00:22:04.880 people that received md may and they were like nope i got the placebo and there were people but

00:22:09.120 still got better mind you and then there were people that received the placebo and and thought that

00:22:15.600 they'd received md may and i think i attribute that mostly to the fact that you know it's a eight

00:22:20.640 hour talk therapy session and you're typically wrapped in a nice warm blanket and you're reclined and

00:22:27.040 you've got headphones on and you've got eye shades on and you've got two therapists at your elbow and

00:22:32.320 so you know not so surprising that some people felt that they still had a remarkable therapeutic and

00:22:38.080 transcendental experience so there's that yes it's hard to blind these trials but also it's hard to

00:22:44.000 blind mental health treatment trials in general because what you want is for your drug to work and if

00:22:50.480 your drug does people typically know it right in other words if you're giving a drug for depression

00:22:55.600 and people come in and say my depression's gone typically they also know that they're on the

00:22:59.520 active drug because their depression's gone so in general when you're asking if you're looking at

00:23:04.480 like what rheumatoid arthritis and you're looking at inflammatory markers or swelling or whatever

00:23:09.360 you're not asking someone how they feel as much in a mental health trial you're typically asking them

00:23:13.360 if they feel better and if if that's the the end point then it's often going to be tainted by the

00:23:19.680 efficacy of the drug so this wasn't a surprise i think to anyone as the fda and at that time maps pbc

00:23:28.560 sat down and discussed the study design and what they decided was that this would be you know

00:23:35.680 relatively impossible to to blind completely and it took them many years of as i understand it this is

00:23:42.800 before i was involved but as i understand it it took like 13 years to decide on the study design and the

00:23:47.120 study design ultimately involved telemedicine and so i guess you know it was sort of fortuitous that

00:23:52.880 it happened when it did 13 years prior we didn't have the telemedicine platforms that we have today

00:23:58.000 so we have zoom now and that means that instead of determining at the study site if someone looks like

00:24:05.680 they're doing better you instead have them call in to a completely anonymous person that they haven't

00:24:12.560 ever interacted with before far away via telemedicine and that person assesses these outcome measures

00:24:19.360 with them and that way this this assessor doesn't know where this person's calling from if they thought

00:24:26.240 they received placebo or active drug if you know they're at the beginning of the trial or the middle

00:24:31.920 or the end or in follow-up and that was the the study design that the fda and the sponsor agreed on

00:24:38.640 together to ensure that this lack of blinding was minimized as much as possible when it came

00:24:43.680 to assessing and evaluating the drug efficacy so there's that and i think that was oddly lost in

00:24:50.080 the adcom and i didn't hear the fda say very much about it at the time even though again they had

00:24:56.560 agreed to this study methodology years before with what is now lycos therapeutics so that was kind of

00:25:03.760 that was a surprise to me yeah that people had so much issue with the blinding i also thought

00:25:07.760 it was kind of a surprise because i mean if we were talking about a cancer drug those studies don't

00:25:13.040 typically have a comparator arm anymore and so you don't need the comparator arm to receive fd approval

00:25:18.560 for a novel therapeutic and what about allegations of therapist misconduct yeah right so i think that's

00:25:25.840 one of the things that most plagues maps pbc and lycos therapeutics are these claims this one in

00:25:32.800 particular from a phase two study that happened many years ago in which a a therapist inappropriately

00:25:39.520 began a relationship with somebody that had been involved in one of the trials and obviously that's

00:25:45.040 that's horrific it's it's inappropriate it's malpractice that was not somebody that was involved

00:25:51.120 with phase three that was not a therapist that was allowed to continue after these allegations came to

00:25:57.600 light and also perhaps most importantly the therapy component of the treatment is not under the purview

00:26:07.120 of the fda like the fda doesn't talk about the therapy in general because they have no control no say

00:26:13.760 over therapy right we have state boards and licensing boards and accreditation boards that keep track of

00:26:20.640 therapists and their practices and that's what would happen if mdma assisted therapy were to be fda

00:26:26.240 approved so it was odd to hear the adcom sort of go down that rabbit hole and talk so much about

00:26:31.040 therapy and previous behavior of therapists and how the therapy would be monitored when none of that

00:26:37.200 really was supposed to as i understand it be part of the adcom meeting it's definitely not part of what

00:26:43.360 the fda will evaluate during the approval process sarah do you want to jump in here on any side of this

00:26:50.400 sure yeah i actually think there are a few things that are important to touch on one being that psychedelics

00:26:57.120 really offer a completely new therapeutic model and i think it's important to talk about how different that

00:27:03.120 is from our current existing model and i really do think it's important that we talk about what can go wrong

00:27:09.360 so that we can prevent create structures to prevent it from happening as best as we can and lastly i think it's

00:27:16.400 important to look at how we may need to evolve our current institutions to meet the demands of the

00:27:22.560 people and so what i mean by that is you know we would not be here having this conversation if our

00:27:28.320 current medicines worked for everyone there's i believe nearly a billion according to world health

00:27:33.200 organization of people suffering from some sort of mental health condition one billion and if we look

00:27:39.360 at americans in particular one in five right are living with some sort of mental health illness so that's

00:27:44.800 about 50 million people in the united states so if we hone in on ptsd in particular i believe it's

00:27:50.640 somewhere around 13 million and mdma would be one of the first to offer a new treatment i think in around

00:27:55.840 25 years and so i think it's just important to note that there there is this desire to find something else

00:28:03.680 because the current conventional medicines work well for some really well and for others they're failing them

00:28:08.960 and so i think there's a lot to touch on here you know one of the um some of the critics of the vote

00:28:15.120 for the committee actually had mentioned that there was just one member of the fda advisory committee that

00:28:20.960 had had expertise in psychedelics saying that the committee may not as jenny was talking about have a

00:28:26.800 full understanding of all aspects of the treatment and he actually did vote in favor of the treatment's

00:28:32.640 efficacy and as jenny was touching on this the fda does you know regulates medications but they

00:28:38.480 never regulate psychotherapy or a medication whose effects are really closely tied to therapy

00:28:44.720 and so this really raises the question about you know is there a belief that they need to

00:28:49.280 standardize and create protocols for some sort of therapeutic aspect of psychedelic treatment

00:28:54.800 and i think that really gives us an opportunity to see where there's room for growing in our current

00:28:59.680 medical model and so a lot of researchers i think believe that because of as you were mentioning sam

00:29:05.920 the really complex history of these classes of medicines we're seeing the data face significant

00:29:12.080 scrutiny probably more so it's actually definitely more so than any other drug class any new drug

00:29:17.760 discovery and so i think it's important to note that some of some people see these medicines as a

00:29:23.520 movement right and not a scientific endeavor and so scientists want to be careful to say you know if

00:29:29.520 there's a preconceived notion within an organization that these medicines are effective and all we need to do

00:29:35.120 is substantiate that belief then where is the confirmation bias here and and how is it going

00:29:40.880 to have us maybe overlook some blind spots and you know as jenny was saying you know researchers in the

00:29:46.720 field might actually see this as some sort of period of recalibration so maybe we're moving initially past that

00:29:52.800 hype and really thoughtfully considering any potential risk and i think they're emphasizing that we want to

00:29:59.200 know when they can go wrong before we bring them to the market and so i feel as we embrace all the

00:30:04.480 aspects of this field it really shows the maturity of it and you know i think it's really important to

00:30:10.720 discuss that you know you know as we're talking about this challenge of double blinding right so

00:30:15.280 in evidence-based medicine you have these placebo controlled double blind clinical trials they're gold

00:30:19.760 standard patient doesn't know experimenter doesn't know we're talking about how that's really difficult

00:30:25.120 when someone is taking a psychedelic they usually know so i think for me what has been really helpful

00:30:30.480 to break this down is to really reflect on the type of research model we're using and understanding how

00:30:37.760 this new paradigm maybe it does not fit really well with this research model and what are the limitations

00:30:43.520 of our current method so that we can develop and evolve to other methods that would actually capture this work

00:30:50.080 and so i may actually touch a little bit if it's okay sam about what i feel like is the groundwork

00:30:56.000 for modern biomedical science sure and i really feel like it's actually predicated on mechanistic

00:31:02.160 reductionism so this concept you know was born in the scientific revolution around the 17th century

00:31:08.400 thinkers like newton and descartes would apply really mechanistic and reductionistic approaches to

00:31:14.640 understand the natural world so i think descartes especially really saw the body as a machine

00:31:20.000 he thought that all physiological processes could be really explained in terms of a mechanical

00:31:25.680 principle and they wanted to to try to explain really complex biological systems in terms of their

00:31:32.800 simplest components so in this model you're looking at linear cause and effect relationship you're

00:31:38.720 going to simplify the system to isolate the variable and that approach helps us understand specific

00:31:45.360 mechanisms of action of a drug at a molecular level which i think is really important

00:31:50.320 and it's been highly successful in treating a lot of things in human biology with targeted

00:31:55.600 interventions you know pathogen recognition genetic mutations but on the other hand i think what we are

00:32:04.160 feeling right now with psychedelics is that it takes a bit more of a systems thinking approach

00:32:09.040 so it's actually viewing the entire system it's emphasizing the interactions and interconnectedness of its parts

00:32:16.960 so this model actually really operates on the premise that the human ecosystem is more dynamic

00:32:22.800 dynamic it's more non-linear it embraces that there's a lot of complexity here and i think a lot

00:32:28.960 of people will argue that this approach is actually much better suited for chronic diseases and mental health

00:32:34.400 issues and just to point out that that's actually what we're seeing an exponential rise of in this

00:32:40.240 country and around the world is chronic diseases and mental health issues so you know when we're taking

00:32:45.280 that reductionistic approach you know it's targeting specific components or drugs that target a molecular

00:32:50.960 pathway whereas complex than systems thinking is looking at multi-faceted strategies right we're looking

00:32:56.960 at the social implications environmental behavioral and so while i think that mechanistic reductionism can

00:33:02.960 really provide powerful tools to understand these systems and i think we can absolutely use them to

00:33:08.560 understand the pathways in psychedelics there's something about complex systems thinking that offers

00:33:14.080 more comprehensive framework to understand the interconnectedness of human health and ecosystem

00:33:20.240 and you know as i'm speaking i want to share an example because this can sometimes be a little bit

00:33:24.640 elusive so you know an example of systems thinking in my eyes is this this field and it's fairly new

00:33:31.520 of psychoneuroimmunology so you know this is a prime example of systems thinking in medicine

00:33:37.200 as it's looking at the effects of psychology on the nervous system and the immune system and so if we're

00:33:42.720 using this field to understand for example trauma's effects on the body we actually see that trauma can

00:33:48.560 lead to a dysregulation of the hypothalamic pituitary adrenal axis that will spike up your

00:33:54.560 cortisol your stress hormones it will increase inflammation in the body that chronic inflammation

00:33:59.920 we're actually seeing is linked to a lot of different diseases and so we see this actually

00:34:05.040 with people with ptsd they have higher rates of cardiovascular disease diabetes autoimmune conditions

00:34:10.960 and we actually think that's probably from a dysregulation of their immune system

00:34:15.120 and to tie this in further there's another study in this field and it's um around the childhood

00:34:22.080 adverse childhood experiences so this study actually looked at individuals with a really high number

00:34:27.920 of adverse childhood experiences and they actually found that numerous health problems were associated

00:34:34.560 in adulthood so children that had higher numbers of trauma linked to physical disease as an adult so

00:34:41.760 heart disease diabetes really illustrating this long-term impact of trauma on health you can you know

00:34:48.560 find this questionnaire on the cdc website so why i bring this up is that you know this is where i feel

00:34:53.920 that the fda can continue to evolve right we i believe think we need to take a little bit more

00:34:59.280 of a systems-based approach and so when i think about that therapy component of psychedelic medicine which

00:35:05.200 is really tied in right now to the medicine so you know the medicine and the therapy that is it's almost

00:35:10.720 really you know we don't think we can do one without the other in this trial right so it's really

00:35:15.200 emphasizing this this integrative approach that i don't know aligns really well with traditional

00:35:21.920 rigid protocols of clinical trials right to that that are designed for conventional pharmaceuticals

00:35:27.680 and anyone that's been to therapy can really attest you know to that non-linear framework yeah and

00:35:34.080 and and i think another thing i actually want to touch on that i always think is so fascinating is

00:35:38.880 is is this exploration of you know when we when we see this complexity here and we want to move

00:35:45.440 to maybe finding something that fits better in our model and that actually think is the exploration of

00:35:50.800 quote-unquote these non-psychedelic psychedelic compounds you know we it's the term is psychoplastigen right

00:35:57.360 so you know many participants feel that that non-ordinary state is at the cornerstone of this healing but scientists

00:36:03.840 want to see is that true and so they want to understand you know is that psychedelic experience

00:36:09.360 itself essential or is there some sort of underlying neuromodulation that's responsible for this shift

00:36:15.840 and there's a lot of contention in the field about this and i think proponents of the psychedelic experience

00:36:22.640 report that they feel you know some of the most meaningful experiences of their life right so they've gained

00:36:28.160 this insight that they felt would be otherwise inaccessible shifts their perspective on how

00:36:33.920 they see the world and it actually reminds me of what an astronaut would feel right when they go to

00:36:38.640 earth they call this the overview effect this state of incredible awe and overwhelming emotion

00:36:44.320 and this connectedness to other people and so when people have these experiences they feel that this

00:36:50.480 hasn't just helped them with their objective depression ptsd they feel that another layer has been

00:36:57.520 added on so they're now learning reported by them that they are living with purpose a more meaningful

00:37:04.080 life they feel like they're part of something part of a community really part of earth which i actually

00:37:09.600 think some would argue is is a central tenet to being a human being that need to to belong and so again

00:37:16.240 this is where i think we can evolve our research methods right to encapsulate the entirety of this

00:37:21.600 and not just an objective decrease on a measurement scale so for some people it might not be enough to

00:37:27.600 live ptsd free or depression free that's great but surviving you know maybe the goal should be more

00:37:34.720 a deep sense of thriving and optimal success so that makes me have to reflect on what are the scales that

00:37:40.880 we use to capture success you know in our current model do these system you know assessment scales fail to

00:37:47.600 address some of the more complex whole person dynamics and does this suggest that we may need

00:37:53.520 more validated scales to capture this and the last thing i'll touch on is i think this is why it's so

00:37:59.280 complicated is that we also need to talk about the cost benefit analysis that insurance companies will

00:38:05.200 will complete so an insurance company will probably prioritize a treatment actually definitely will

00:38:10.720 that addresses medically recognized conditions right with a measurable outcome that are clear

00:38:16.640 quantifiable and align with most importantly traditional medical criteria so an insurance company

00:38:24.000 you know when they assess whether the benefits of a treatment justify its cost you know if a treatment

00:38:29.040 significantly improves overall well-being but it's expensive or lacks robust evidence of cost

00:38:34.880 effectiveness insurers actually may be hesitant to cover it so that's why i think it's important to

00:38:40.560 really look at our current model and see you know what parts are are begging for some evolution

00:38:46.640 yeah all of that's very interesting i i think it's made to i guess make contact with a few of the

00:38:52.480 points you made there i mean one reason why the therapy seems like it needs to be an integral part of

00:39:00.240 this and why it's why it's unsurprising that it would be is that what you know here when you're talking

00:39:06.640 about a few treatments with mdma or psilocybin being efficacious you're not talking about taking

00:39:14.640 a drug for the rest of your life and therefore you're not talking about the the ongoing you know

00:39:19.840 pharmacological consequences of being on this drug and and that's simply having some neurophysiological

00:39:27.120 effect that improves your condition just of necessity you're talking about a very punctate experience in your

00:39:35.120 life and from the first person side of this or for one who has had these experiences it seems quite

00:39:41.440 obvious that it's a matter of in the end thinking and feeling differently about yourself and your place

00:39:49.680 in the world and your and your past experiences i mean it's a very i mean this is why i would be willing

00:39:53.840 to bet that the phenomenological component of the psychedelic experience rather than merely the

00:39:59.200 the the pharmacological one is going to prove necessary right so i am i'll be fascinated to

00:40:05.600 see where that research goes with the so-called non-psychedelic psychedelics but right the idea that

00:40:10.880 you could unconsciously uh have all of the benefits you know that that will be surprising because you know

00:40:17.680 from the first person side it really does seem to be that it's a matter of using these compounds to get

00:40:24.320 tremendous leverage over one's mind based on the power of ideas and insights and changes in in perception

00:40:34.640 and feeling that if they're not actually truly durable i mean they you know they because they're not

00:40:40.400 every experience comes and eventually goes but what you have at a minimum is the new reference point that

00:40:48.640 that such an experience is possible right like that you can you you know what it was like to have felt

00:40:54.720 that way yesterday and it is so it's by definition opened a door in the architecture of your mind which

00:41:04.880 you again even as even as a mere memory it reframes your sense of what is possible for you as just as a person

00:41:13.520 you know living a life of painful ups and downs perhaps still it just it it potentially changes

00:41:19.440 everything even if the if the ongoing character of your experience hasn't changed all that much and

00:41:25.280 and and that's even that's probably the least uh successful case we're talking about so you know

00:41:31.680 leaving aside the the real downsides and dangers which you know we should probably address because

00:41:36.960 obviously there are some people who shouldn't take these compounds and right as there are you know

00:41:41.440 for every great experience one can have on on many of these drugs there are equally awful and

00:41:47.280 harrowing experiences one can have uh i i hesitate to say that in the context of talking about mdma

00:41:53.200 because i'm i'm not aware of the liability for bad trips being quite as obvious as with lsd or psilocybin

00:42:00.320 but still nonetheless i'm sure there are people who take the drug and and have a bad time jenny do

00:42:05.920 would you like to jump in here sure i think you're absolutely right i think it's rare but that there

00:42:10.560 are people that take mdma and they feel that it opens a door to bad and dark things that they don't

00:42:17.360 have an opportunity to address and that leaves them feeling worse instead of better i think that in

00:42:23.360 general we probably all agree psychedelics don't work well for everyone maybe shouldn't be given to

00:42:29.440 everyone there may be a number of comorbidities that uh should you know limit one's access to a

00:42:37.120 psychedelic at least at these early stages of development of some of the some of the drugs so

00:42:43.280 i agree with all of that yeah and i actually think that's probably why you know that's the argument of

00:42:48.640 of exploring these non-psychedelic psychedelics so these psychoplastogens and and sam as you were

00:42:54.080 talking about it i i felt like it's important to also note that let's say you know we are actually

00:43:01.120 opening a window of neuroplasticity we should probably also consider what new tools we'd want

00:43:07.360 to add during that time so not not keeping it as the strict pharmacological intervention that

00:43:13.360 it possibly could be where it's it's similar to taking an antidepressant every day or for a period of

00:43:18.400 time and so you know without maybe integration you know this class of medicine might really miss a

00:43:24.480 crucial opportunity for an added benefit and as you were touching on you know how we can speak a little

00:43:30.560 bit about you know some more of the controversy that is has been coming up around this study i think

00:43:36.400 one important one to touch on is that you know this new paradigm this framework is using a system

00:43:43.440 to understand the system of a more of an intrinsic healing capacity that i think is really important

00:43:50.320 to touch on because i i feel like that's the one of the cornerstones of this work so if you're if

00:43:55.280 you're okay with that let's i'd like to discuss that that how this concept compares actually to our

00:44:01.280 current conventional model of medicine you know where it can aid and actually where there could be

00:44:06.640 harm in this model and i think it's really interesting to note that you know there's this this um

00:44:12.160 discussion that psychedelics can have this intrinsically regenerative action and researchers

00:44:18.160 want to explore that and they want to see you know that we have seen a lot of people report that and they have had a lot of

00:44:23.280 a lot of success but but can it also elicit something false you know like a false insight

00:44:28.480 you know belief and how do we support a participant through that process so again to me when i see

00:44:34.640 when something might be going wrong like i want to know so that we can start building those structures and

00:44:40.800 frameworks to really understand it and so similar to you know like thinking about how psychedelics could have

00:44:47.360 this ability to have this intrinsically regenerative action on the mind and brain you know there's a

00:44:52.800 similar thought of the intrinsic healing mechanism of let's say the physical body so after an injury or

00:44:58.320 sickness so i think it's important to to break down this concept you know is it myth-making is it centered

00:45:04.240 on this role of priming and expectation after being shaped in therapy or is there really some sort of

00:45:11.200 legitimate mechanism that exists in a self-regulating living system um it's interesting that there's some

00:45:18.000 scientists that are actually studying this and um there was something that was released a few months ago

00:45:22.640 looking at this where you know patients had received a placebo over psilocybin and they both had psychological

00:45:28.480 support and they were both given a scale to assess this concept of this intrinsically regenerative action

00:45:35.520 and they found that the scores on that assessment were actually significantly higher for those that

00:45:40.560 received psilocybin than placebo and i think to me it's this really warrants let's investigate this

00:45:46.000 more let's understand this new paradigm that we're bringing forth and so i think another part of it that

00:45:52.640 feels really central and different than what our current conventional model offers is that it's somewhat

00:45:58.400 more involving the individual to have agency in their own mental health so i think this approach

00:46:05.040 you know is enabling participants to examine those core beliefs themselves to be able to go in look at

00:46:11.760 them see how it governs their lives identify which ones could be maladaptive and no longer serves them

00:46:18.880 and so you know it's important to recognize i think you know these maladaptive mechanisms they were once

00:46:24.400 evolutionary responses they helped us survive at a particular point in life but now we have the ability i think

00:46:30.960 with these medicines to become consciously aware of them to become aware of maybe the long-term

00:46:36.320 imprint that these survival mechanisms have had and maybe see how we can transition from a state of

00:46:43.120 mere survival to one that's more thriving and so i think this is about teaching people to have more

00:46:49.280 adaptive coping skills and you know how they can actually be more aligned with who they are and so you

00:46:56.160 know when i look at this paradigm of psychedelics like we've actually seen as you had mentioned in

00:47:00.560 the beginning of this podcast that this is a cornerstone of health for many cultures we've seen

00:47:05.120 it in a lot of indigenous communities around the world and it really differs from our current pathology

00:47:11.440 based medical system so you know this biomedical model and i think it's important to touch on because

00:47:17.680 you know when i think of the pathology based system it's really focused on diagnosing it's focused on

00:47:23.040 treating disease isolating symptoms and really treating specific conditions as i was discussing

00:47:28.320 before but this model is different right so it's it's really emphasizing the interconnectedness of it

00:47:34.960 all the physical the emotional the mental and that it's really the whole person and not just the disease

00:47:41.280 and so you know what i oh sorry go ahead no i was going to say you're raising some really great

00:47:46.720 points and implications i think for clinical use of these compounds because let's say that they are

00:47:51.280 neuroplastic right yeah and let's say that they open up a window of opportunity that lasts longer

00:47:57.680 than an eight-hour treatment session right which is basically what you're suggesting here i believe

00:48:02.160 and that you're sending a participant home at the end of that eight hours and you're hoping for the

00:48:07.840 best and perhaps that window is open for another 14 days i think it raises a bunch of issues around

00:48:14.640 clinical care and around disparities in access to drug treatment because if you've got somebody that

00:48:21.040 has ptsd and they're from a marginalized place and they don't have a lot of money and they don't have

00:48:26.720 a really healthy community to go back into and you've put them back in that community after that

00:48:32.400 eight-hour treatment session i wonder what happens over the next 13 and a half days and whether or not

00:48:38.240 that negates some of the effects the efficacy of the drug in treating whatever you were trying to

00:48:42.880 treat right and so what you're talking about too is how we'd sort of bolster that with a lot of

00:48:47.920 integration work and a lot of care and a lot of attention and it's unfortunate but as you've

00:48:53.520 already said our current manner of clinical practice doesn't typically allow for that

00:48:58.320 or have ways to easily enable it and so i think that's something that we also have to talk about

00:49:03.440 as as a group and i think it's something that managed care and insurance providers and everybody

00:49:07.200 else are particularly worried about is this is a potentially great therapeutic or series of

00:49:12.800 therapeutics for somebody that has means to engage in a lot of integration work perhaps for for days

00:49:20.880 months you know years into the future but if somebody doesn't have access to those additional

00:49:26.720 resources are we potentially opening them up to fail or to get worse in some way i think that's

00:49:33.200 just something that we really have to address before these therapeutics move much farther forward

00:49:37.680 you nailed it jenny i think that's such an important part that you know we need to be able to hold it

00:49:45.200 all right and and that that's why i think the systems thinking actually helps understand this more

00:49:50.160 because it's not just a biological mechanism that's causing this ptsd there's a lot of other interconnected

00:49:58.080 issues at play you know what is going on societally what is going on in the family dynamics what is going on

00:50:03.760 etc etc so looking at that entire picture is crucial and i think that's actually a big reason why i really

00:50:10.720 was a proponent of the treat initiative is because we were looking at that that you cannot you know

00:50:16.720 have someone take a psychedelic medicine and then put them back into what some might call a toxic

00:50:22.880 environment after they've had these profound insights you know people they need child care they

00:50:27.920 need time to actually process and integrate they need time off of work they need a very

00:50:33.120 comprehensive space to be able to do this work up front to actually be able to see the benefits i

00:50:39.360 really appreciate that you touched on that yeah that's fascinating in listening to what you both

00:50:46.400 just said i guess i'm beginning to worry that the perfect can become the enemy of the good here where

00:50:53.920 we acknowledge that these the experiences that many people have perhaps even most people have on

00:51:00.480 these compounds tend to be so powerful and so reshaping of a person's sense of you know what

00:51:09.920 what life is good for in the end that it sounds like we could be in danger of deciding well it's just too

00:51:18.080 potent right it's just you're pulling it the threads of a person's life but here you've got some kind

00:51:23.600 of central thread that can unravel everything you know we've we've given someone an experience for

00:51:30.160 five hours in the case of mdma or 12 hours in the case of lsd after which they may decide they're in

00:51:37.520 the wrong job they may decide they're married to the wrong person they may decide that they really

00:51:42.880 that everything needs to change in their lives and there's going to be a vast difference in people's

00:51:50.560 ability to respond to that 20 megaton upheaval in their lives and again we're stipulating that in

00:51:58.240 many cases these upheavals are very very good but i mean again it can take the form of you know now

00:52:04.160 they're all of a sudden they believe in god when they didn't or or they no longer believe in the

00:52:09.440 religion of their parents or they a sea change in who they are and how they want to live is possible in

00:52:16.560 a way that it's not when you are approving a um you know how to uh repair an acl tear in a person's

00:52:25.040 knee so it's but you know admitting all of that and admitting that there is a there are very wide

00:52:31.440 disparities in how lucky people are right so there are people who will come you know there are two

00:52:37.120 people with ptsd coming in for for the now approved mdma treatment for it but one will be returning to a

00:52:46.000 a life of affluence and a happy marriage and healthy kids and one will be returning to a life

00:52:52.000 of chaos right and exactly we can't fix all those problems but the question is can we put enough in

00:52:58.480 place so that it will be unambiguously good most of the time for the person to have had this intrusion

00:53:06.560 into their lives for 12 hours or 24 hours or 36 hours or whatever the protocol is that has to at some

00:53:13.600 point be bounded by the sheer limitation of of what any clinical practice can deliver to any

00:53:20.480 person right i really think we can i think we just have to be particularly thoughtful about the guard

00:53:25.520 rails that we put in place and how we do them and i think sort of that's what came up during the

00:53:30.640 adcom fda meeting but it's just not the purview of the fda to come up with those right it's who you

00:53:36.240 know as sarah probably would suggest it's it may be the purview of the states that states need to come up

00:53:41.120 with a system for psychedelic facilitation and oversight of the facilitators and sort of determine

00:53:47.120 how much of that facilitation is a standard of care so that you don't sort of high five somebody at the

00:53:52.960 end of a six or an eight hour session and tuck them back in their car and wave goodbye but that

00:53:57.200 you know that if they need that integration work and if they need a safe environment that you've got

00:54:01.840 one available for them so that they can make the most of their therapy yeah and i think just to touch on

00:54:06.240 what you were saying sam you know a big part of this again to me is just what a new paradigm this

00:54:12.240 is right so you know as we were touching on looking at this pathology based model that we are very

00:54:17.600 familiar with the fda has been it's a huge part of something that fda is very comfortable with but you

00:54:24.320 know the the participant is very passive right as they receive this care there's that heavy reliance on

00:54:30.320 pharmaceuticals medical interventions when necessary standardized protocols so one size fits all

00:54:36.640 and right now we are trying to move and evolve and offer this new paradigm that is completely different

00:54:43.840 right so the patient is really active in that process you know there is a deep connection between

00:54:49.680 the mind and body we feel like the mental and emotional state can significantly impact physical health

00:54:55.520 and you know there's really personalized care for each person so i think even one one thing to touch

00:55:01.280 on is you know one of the criticisms was that there was not adequate possible reporting of some adverse

00:55:06.320 events including you know increased suicidality so irrespective of of it not being okay to have you know

00:55:12.560 inadequately documented that i think the more we explore what is that telling us this is how we can learn

00:55:19.520 as you were saying to create the frameworks and the safeguards so you know if i hear that increased

00:55:24.800 suicidality kind of as jenny was mentioning what's going on is this a biological issue of mdma is it

00:55:30.800 the non-linear nature of healing you know when some individuals will initially experience you know

00:55:36.320 exacerbated symptoms before improvement is this a very emotionally taxing process you know of any type

00:55:42.480 of new therapy where you're recalling these distressing events and the last part is you know

00:55:47.840 do we need for some people maybe a smaller portion more comprehensive support and what does that look

00:55:53.600 like what you know would that be something as jenny was saying you know as the states or other places

00:55:58.160 think about that that therapy component do some people just need more integration and so i think the

00:56:05.200 last thing i want to touch on in in this part is you know some people would may have reported that you

00:56:10.800 know they're feeling better right or sorry no they're not feeling better but the actual measurements that

00:56:16.800 we're using show that they're getting better and i think this is again another um moment to to examine

00:56:23.680 the current you know scales and methods that we're using to see if quote unquote someone is getting

00:56:28.480 better and really noting that this is a completely non-linear process so for example you know the one

00:56:34.880 of the primary instruments that was used in this map study which is you know the gold standard is the

00:56:39.200 caps 5 right so it's the clinician administered ptsd scale it's given by a clinician and a patient is

00:56:45.520 there to identify trauma or traumas that they feel like are at the source of their symptoms and so

00:56:51.120 you know in psychedelic therapy we often see that there can be previously unconscious memories that that

00:56:57.920 can can arise and that newfound awareness might have a patient initially seem to be approving on the cap

00:57:05.040 scale um in relation to that known trauma but they're simultaneously experiencing new distress from this

00:57:11.920 so i think it's really important to look again at how non-linear and dynamic this work is and create

00:57:18.960 systems that actually really can understand that okay so let's talk about the moment we're in

00:57:26.800 with respect to the fda's deliberations and and what if anything is at stake here and what what would be

00:57:36.240 useful for for anyone who's in a position to to make policy on this topic to hear at this moment i mean so

00:57:44.320 if you could imagine that the people in charge were listening to this conversation or people poised to

00:57:52.320 influence the people in charge were listening what what would be useful for them to hear and think about that

00:57:59.120 that we haven't touched on already i mean from my perspective i think part of it is that

00:58:05.120 there's this plan called a risk evaluation and mitigation strategy that the fda can ask lycos the sponsor to provide

00:58:14.400 to show that they've established these guardrails around some of the concerns that the adcom brought up

00:58:20.560 and that would be a way to enable regulatory approval of mdma assisted therapy and ensure that data were

00:58:28.000 still being collected to look at adverse events side effects etc in what we'd call phase four testing so

00:58:34.720 post-approval testing of the compound and i think this would be particularly useful for mdma assisted

00:58:39.840 therapy in part because once it's out of phase three testing as sarah sort of suggested there's is

00:58:46.640 probably going to be a lot more you know variability in terms of how it's administered into who and so

00:58:52.240 we'd want to know if it really does need to follow this sort of strict methodology that's been enacted

00:58:58.320 for phase three or whether it's actually much more effective in a different uh under a different set of

00:59:04.240 circumstances different set of procedures and i think that it would be useful for people to know what

00:59:09.920 a what a rems plan is and that it could be enacted here and it could allow for this therapeutic but

00:59:16.320 also psychedelics in general to move forward with additional oversight post-approval yeah i agree very

00:59:22.800 much jenny i feel like it's also important you know we've spoken a lot about you know the details of

00:59:28.160 this and i think it's it's important to look at it from a patient perspective you know and and part of

00:59:34.720 the the committee when there were um actual just a public criticism there were a lot of veterans that

00:59:40.640 actually spoke about looking at the risk reward of potentially saving millions of lives you know when

00:59:46.640 you know you had alluded to jenny there are nearly 20 veteran suicides a day the current treatments

00:59:51.040 aren't working there are countless veterans that are saying that they're healing with this after having

00:59:56.320 given up hope and they feel this frustration with these continued obstacles and roadblocks and

01:00:02.000 this anger and that we're not actually even caring about what about the over medicalization of the

01:00:07.520 veterans you know what what are the limitations of the current treatments and really feeling

01:00:12.160 frustrated that you know they've served in this country they've suffered subsequent mental ailments

01:00:17.280 from this but they have to seek these therapies elsewhere and so as jenny was saying you know this

01:00:22.000 really begs the question how can we address maybe some of the pitfalls in this research while still

01:00:26.960 making it available to people who arguably maybe could be on the brink of of death and i i see an

01:00:34.080 importance in really including subject matter experts on the review committee that can really

01:00:38.400 understand this completely new paradigm you know encouraging a collaborative and interdisciplinary

01:00:44.320 research model right where you know psychiatry psychology neuroscience pharmacology all of them

01:00:50.000 are there and there's a discussion with academia industry and government that can really facilitate a

01:00:56.640 different way to look at this and we can consider you know the expanded access programs and and

01:01:02.720 making them more accessible allowing patients that really have these conditions that they've exhausted

01:01:08.720 all other treatments access these investigational drugs out of clinical trials but we're still

01:01:14.640 collecting additional safety and efficacy data i think that's totally right i don't think we talk

01:01:19.360 enough about right to try especially with respect to our veteran population right we talk a lot about

01:01:24.480 that for other end-of-life conditions right if you've got cancer and you don't have a lot of time left

01:01:29.840 there are a lot of therapeutics that are available to you that have a you know a very complicated risk

01:01:35.280 benefit profile but you're still allowed once you've been you know administered the education around that

01:01:40.560 compound to try it if you feel like that compound is something that you want to try and we don't treat

01:01:45.840 ptsd in my opinion as dire and life-threatening a condition as we do typically cancer and so there are a lot

01:01:52.560 of veterans that as per sarah's comments would say look i've tried everything else i've put a gun in my mouth

01:01:57.840 i've done all these other things and i'm going to kill myself if somebody doesn't give me the the

01:02:02.960 another idea another opportunity to try something different and for them i think that they definitely

01:02:08.240 deserve right to try and that there must be a way if we're all clever and we put our heads together to

01:02:13.360 figure out how to allow veteran access to these populations to these substances and maybe even that

01:02:20.320 could be a way to allow for fda approval of mdma assisted therapy as an example like within the

01:02:28.160 veteran within the va system that might be a way to start the ball rolling and acquire data in a

01:02:34.720 population that really i think in my particular opinion needs access to the drug the most yeah i must say

01:02:42.000 the fact that we're focused in the research on veterans gives me some hope that we're not going

01:02:50.160 to see a just a simple reboot of the war the war on drugs and the same kind of political consequences

01:02:56.800 that we experienced post 60s because i mean obviously the concern about veterans and and all that we uh

01:03:05.680 do and don't do for them and you know are in many cases scandalous failure to take care of them

01:03:12.320 that concern cuts against the grain politically that you know we frame the war on drugs as we came to

01:03:19.440 know it right i mean this is you know if you're going to generalize uh as you move right of center

01:03:24.560 politically you get greater and greater squeamishness and concern around the certainly the the off-label and

01:03:31.200 extracurricular use of drugs but you get more and more concern about our nation's veterans and so i

01:03:37.280 just think is it for just purely pragmatic political reasons starting here makes a lot of sense to say

01:03:44.880 nothing of the fact that so much of the need is here as well therapeutically jenny you also mentioned

01:03:50.240 end-of-life care and the right to try compounds i think end-of-life care is also one of these areas

01:03:56.960 where it's just so obvious ethically speaking that the censorious logic of the war on drugs just is

01:04:04.880 not making contact with the reality of human suffering and is compounding it pointlessly uh and so you know

01:04:12.960 getting people who are terminally ill the right to to take you know any compound they they want in the

01:04:19.600 end it's just so easily defended okay so the the fda has to make some kind of ruling in is it the middle

01:04:28.960 of august correct i mean and i guess there's some fear that they may just decide to close the door to

01:04:35.520 this research and not give approval why might they do that and what what are the um we've flagged some of

01:04:43.520 the the issues here but can one of you tell me more about what really could actually present a real

01:04:51.360 impediment to this research moving forward yeah something that was touched upon in the committee

01:04:56.400 meeting was some of this the boundary violations and sexual abuse that had come up and so you know

01:05:02.000 i think when any sexual abuse arises you know whether it's in the underground whether it's above ground

01:05:06.880 psychedelic community whether it's in any other field we really need to talk about it we we don't want

01:05:11.920 to sweep it under the rug a therapist having sex with patient is unethical full stop so let's bring

01:05:19.120 that common sense into the room the more we understand i think the dynamics at play the more

01:05:24.000 i think we can educate and prevent while continuing to create mechanisms of safety for the field and i

01:05:30.080 just want to point that we've seen similar issues in other fields and it doesn't stop their progress i

01:05:35.280 think instead you know a mature response would be to put significant effort to prevent such harms

01:05:41.280 get curious about what's going on is there increased suggestibility is there increased vulnerability you

01:05:47.040 know we see that increased vulnerability in normal talk therapy right when patients are sharing very

01:05:52.480 deeply personal and sensitive information it's placing a lot of trust in the therapist and so this

01:05:58.000 vulnerable psychological state you know can make them more susceptible to manipulation and you know

01:06:04.480 we can take this further that you know this dissolution of personal boundaries with psychedelics

01:06:09.280 in these non-ordinary states can be exploited by untrained or unethical practitioners you know and

01:06:15.680 this deep connection that's fostered by psychedelics can exacerbate so you know the way i look at it is this

01:06:22.400 vulnerability that's created in any therapy space is essential for for i think the healing work and the

01:06:29.360 space allows for deeply held emotions and thoughts and i see this in normal talk therapy as well that will

01:06:35.840 allow for an exploration of defense mechanisms so how have they been there to protect us you know you're

01:06:41.520 being seen and heard in these therapy sessions and so i think because of the power of that human

01:06:47.120 connection there's a closeness that develops and that can become confused right with romantic or sexual

01:06:53.280 intimacy so i think it's just really important to note that these emotions come up and the lines can get

01:06:59.280 blurred and you can set a boundary and you don't act on them and so you know it's just important to note

01:07:05.840 that sexual abuse power dynamics they're inherently and unfortunately seen in human nature we see them

01:07:12.720 in all fields in all walks of life and we really need to hold that these abuses can happen in this

01:07:18.320 context and so what could we do to prevent it so you know the reason why i think this work is so

01:07:23.840 important to come above ground is this is what will allow us to establish very clear ethical guidelines

01:07:30.400 and protocols that we can continue iterating on so you know there will be very clear comprehensive ethical

01:07:36.720 guidelines in my eyes that will address boundaries consent appropriate behavior it will make sure that

01:07:43.280 the participant really understands this and what the safeguards are and that consent is ongoing and that you're

01:07:49.520 aware that an emotion like this can come up and you don't act on it and furthermore this is again the

01:07:56.400 need for having more rigorous training that includes therapists understanding their own boundaries educating

01:08:03.360 on sexual abuse and trauma-informed care and ethical conduct and the most important part of you know this

01:08:09.760 coming above ground is the accountability and reporting mechanisms which i think are essential

01:08:14.240 exactly because you know when we don't have them what i worry about is you know the underground

01:08:20.320 psychedelic community is flourishing because people are desperate for treatment and so it will become

01:08:25.840 very difficult for a sexually abused patient to come forward not only do they have shame around this but

01:08:31.360 they feel that they might even get in trouble for having taken an illicit substance so can they even report

01:08:36.720 this so it just feels even more essential to bring this above ground and start creating those those

01:08:42.640 structures and frameworks now i completely agree with sarah i think one of the best things that could

01:08:47.200 happen with with approval of these substances is bringing it all into the light and allowing for

01:08:52.880 additional accountability there's so much responsibility involved in being a therapist and any therapeutic

01:09:00.720 alliance can be abused and so there needs to be additional oversight for psychedelic therapy

01:09:05.760 and approval i i firmly believe is one way forward to enabling that yeah i mean the fact that the

01:09:13.440 current therapeutic work that is happening all over the place is by definition illegal and could land

01:09:20.560 its practitioners in prison makes any reporting of anything incredibly fraught you know whether it's

01:09:28.640 just the pressure applied to somebody to you know not report the bad experience they had with a therapist

01:09:34.480 could be coming from the place of listen not only do you not want this person to go to prison for

01:09:39.440 the thing you didn't like that they did but you you stand a chance of setting back this whole area because

01:09:47.040 you know you're going to reboot the war on drugs for everybody and i'm not saying that's an ethical

01:09:52.240 pressure to be brought to bear on somebody who had a bad experience with a therapist but

01:09:55.760 you can see the the social dynamics of it happening because this whole thing is underground and

01:10:01.920 by definition unregulated exactly that's as sarah knows that's what wakes me up at night is the

01:10:08.880 inbox full of people that did something in the underground that destabilized them and then they

01:10:15.040 got ghosted by their therapy team and now they're looking for help and they don't even know where to go

01:10:21.040 okay well well it should be obvious uh if it were not obvious already that therapists facilitators

01:10:28.160 caregivers should have some something like a hippocratic oath that they follow right and

01:10:34.880 there should be guidelines and there needs to be training there needs to be a selection process and

01:10:39.760 there needs to be training to uh put people in these roles who are qualified to serve in them

01:10:46.080 um i don't know if there are any other possible pitfalls and and downsides we want to talk about

01:10:50.880 i mean perhaps there's something we can say about what this training could look like and the

01:10:55.600 opportunity it actually offers for a um i mean it's it it's hard to imagine a career that could be

01:11:05.760 more fulfilling than this when you think about what it looks like when it actually works right

01:11:11.520 i mean it's just this is the very picture of compassion i mean it's just the role of a psychedelic

01:11:18.080 therapist again is happening underground in a way that is far from ideal but if you could imagine the

01:11:24.320 true professionalization of this and you know all the appropriate guard rails and the academic study

01:11:32.560 that would facilitate you know a selection process and a and the generation of expertise you know

01:11:38.400 relevant to deliver this care it would just be an amazing thing for people to be able to do and you

01:11:45.280 know along with you know plumbers massage therapists and nurses it will probably be one of the last things

01:11:51.440 that ai will capture uh there will be no radiologists but there will be psychedelic therapists if we play

01:11:57.440 our cards right what if anything can we say about the training of these therapists well i can say that

01:12:03.600 one of the nice things about the the phase three clinical trials was that it was an opportunity for

01:12:09.440 what is now lycos therapeutics to stand up their own training program and to sort of cherry pick

01:12:14.560 providers that already had a background in in ptsd and in trauma treatment and then administer these

01:12:19.600 additional trainings to them to get them up to speed with a psychedelic facilitation and so that could

01:12:24.960 be added into their rems plan as an example so that they had oversight over the first generation of

01:12:30.640 therapists that would deliver this cutting-edge care and that would also give all of our states a chance to

01:12:36.240 enact their own training and credentialing programs oversight maybe even insurance for psychedelic providers so

01:12:44.400 that they were all very well trained and and monitored and that there was a system of recourse for

01:12:50.720 reporting or addressing misconduct yeah and to further touch on that i think that's why it's essential to

01:12:57.280 have really comprehensive training programs because as we were touching on it you know when it goes right

01:13:03.280 it's beautiful but what i'm really interested in is when the psychedelic or the paradigm of psychedelics can

01:13:09.440 can show some challenge and so you know one of the things that i think could be addressed well in

01:13:15.120 psychedelic programs is you know people can have false insights in psychedelics right and so having

01:13:21.200 a comprehensive training program that includes a lot of this information includes the potential of false

01:13:26.640 insights and really how to incorporate that knowledge you know using case studies role play where you can

01:13:33.920 simulate these scenarios and understand how you know when they're coming up how to hold it in a non-directed

01:13:41.120 way instead of actually maybe adding more fuel to the fire and i just think it's just important you know

01:13:46.960 there's going to be a lot of critical thinking um necessary you know you're not going to be dismissing

01:13:52.400 some of these beliefs outright but how can you foster you know an environment of open inquiry and i think the

01:13:59.040 most important part for me is supervision right and continued education just like you know when i

01:14:04.880 finished medical school you know and i was um training to become an er doc like residency to me

01:14:11.120 was where i learned everything and so i thought i knew how to interact with patients and there's a lot

01:14:16.720 that i learned on myself but to reflect that back to someone that has you know understood this space and

01:14:22.400 can help me glean some insight i think that is very important so i think some of those would be high on

01:14:28.880 my list and why i'm really looking forward to having this come above ground so we can really start

01:14:34.640 iterating and improving upon these models well jenny sarah has been uh an education and fascinating

01:14:43.520 is there anything anything that either of you want to say in closing that um might be relevant for

01:14:49.120 someone to hear in the um again you know now now i'm focused on the decision that the fda has to

01:14:56.160 make next month i mean i personally truly believe there's still a path forward and i hope the fda follows

01:15:02.240 the data and and feels likewise yeah i agree and and i think one step further is you know as we're continuing

01:15:09.200 to explore how to really elevate and understand this field again to me it still comes back to funding and

01:15:15.600 so you know what we're trying to do with treat humanity is is to access more capital to be able

01:15:22.080 to answer these questions and so i would really encourage anyone in your audience sam because

01:15:27.280 this some of the most intelligent people in the world that listen join us on that mission to explore

01:15:33.920 the different ways that that we can bring these things i don't think we have to move slowly i think we

01:15:38.800 can actually with the proper funding move quite efficiently and get the help needed to people

01:15:44.640 that desperately need it well there'll be links to whatever websites you guys want me to link to

01:15:50.240 in the show notes and um again jenny sarah thank you so much for your time absolutely thank you for

01:15:56.880 for doing this thank you sam thanks jenny thanks sarah

01:16:11.520 you

Making Sense - Sam Harris - July 26, 2024

#377 — The Future of Psychedelic Medicine 2

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