Peter Hendricks, PhD. November 2023
November 22, 2023Information
Title: Psilocybin in the treatment of substance use disorders.
Description: This presentation will discuss the older and contemporary literature on psychedelics in the treatment of substance use disorders. Preliminary data of a pilot trial of psilocybin-assisted treatment (PAT) for cocaine use disorder will be presented, and a novel theory explaining the transdiagnostic nature of PAT—Self Entropic Broadening (SEB) theory—will be described in detail.
ID11010
To CiteDCA Citation Guide
- 00:00Welcome everyone. Thank you for joining.
- 00:05This is our November meeting of the
- 00:08Psychedelic Science Seminar series.
- 00:09Coming up in December will be
- 00:11the third Wednesday of December.
- 00:14We're going to have our own Janet,
- 00:16Jerry Santa Cora together with Ben
- 00:19Kalmandi presenting on the Usona,
- 00:22The Usona funded multi site study of
- 00:24psilocybin and depression both of
- 00:26them were we were a site on them,
- 00:28both of them were Co investigators on.
- 00:29So I'm looking forward to hearing some of
- 00:31their inside perspective on that study.
- 00:35But today we have a treat.
- 00:36We have Peter Hendricks,
- 00:38who's joining us virtually, obviously,
- 00:40from the University of Alabama,
- 00:42Peter's a clinical psychologist
- 00:44and the Heersink Endowed Chair
- 00:46of Psychiatry and at Alabama.
- 00:48And he describes himself as having
- 00:50happily stumbled on the field
- 00:51of psychedelics in 2006 and even
- 00:53happier to still be involved.
- 00:55He's doing work on psilocybin
- 00:57and cocaine disorder,
- 00:58as well as in smoking cessation,
- 01:00fibromyalgia and demoralization.
- 01:04So I think we're going to
- 01:05hear mostly about cocaine,
- 01:06but anything you want to share with us today,
- 01:08Peter, would be great.
- 01:08We're happy to have you here.
- 01:09Thank you.
- 01:10Thank you. So I think I need to be
- 01:12able to share my screen and this will
- 01:15probably be a few moments of trying
- 01:16to figure that out on my end. I think
- 01:19OK it should be enabled. OK
- 01:23you're let's see then So here's
- 01:25the PowerPoint let's see if
- 01:28this works. So let's start.
- 01:30There you go. Yep
- 01:33that worked. You we. OK.
- 01:36I'm trying to see what you except
- 01:38it's. We're not seeing the presentation.
- 01:40We're seeing the edit mode.
- 01:42Yeah. How do I get to
- 01:44it? Usually works best if you
- 01:46go into presentation 1st and
- 01:47then share your screen. All
- 01:49right, let me try that. Is
- 01:51anyone gonna be phone
- 01:52screening this afternoon?
- 01:55No, no phone screening this afternoon.
- 02:01All right, just a second. Now let's try.
- 02:13Does that work? Perfect. Yeah.
- 02:15OK, good. I figured it out more
- 02:19quickly than I typically do.
- 02:20All right, well, so I mean,
- 02:23this is a first for me.
- 02:25I think this is the first time I've
- 02:26talked to a group of people who are
- 02:28specifically interested in this topic.
- 02:30So I'm. I'm sure that I'll be covering a
- 02:33number of points that are known to you.
- 02:37But you might think of this in
- 02:38some ways as how I often pitch what
- 02:40I'm doing to people who are not
- 02:42familiar with this line of work.
- 02:44And I've been doing that for a while now.
- 02:46And of course doing that from the
- 02:49perspective of of realizing that it may be,
- 02:51especially in the state of Alabama,
- 02:52that many people think I've lost my mind.
- 02:57And I'm, I'm happy to say now
- 02:59that that has changed.
- 03:00And when I started this study,
- 03:03must have been late 2015,
- 03:06most of my colleagues would have
- 03:07reacted by saying that, well,
- 03:09why would you pursue a line of work
- 03:12that has no funding future at best?
- 03:15And others asked if I was second
- 03:17coming of Timothy Leary,
- 03:18neither of which are true.
- 03:20Now, fortunately,
- 03:21at least I'm not the second
- 03:23coming of Timothy Leary,
- 03:24but I'm very happy that
- 03:25things are where they are.
- 03:26But I did have this idea early on
- 03:28that this would be the first and last
- 03:30study of psilocybin I'd ever do.
- 03:32So I'm really happy that things
- 03:33are where they are.
- 03:36So let's see. I'll, I'll try to
- 03:38offer some interesting little bits
- 03:40of trivia too, about Alabama.
- 03:45I'm at the University of Alabama
- 03:47at Birmingham and the University
- 03:49of Alabama is in Tuscaloosa.
- 03:51They have the football team.
- 03:52We have the medical campus and the research.
- 03:55And Speaking of Leary,
- 03:58Timothy Leary graduated,
- 03:59in fact from the University of Alabama.
- 04:02Not many people know that
- 04:03he was at West Point.
- 04:04I think he was kicked out, nearly kicked
- 04:06out of the University of Alabama,
- 04:08but finished his degree by correspondence
- 04:11and then also a little known fact.
- 04:13Humphrey Osmond.
- 04:14I wish we were.
- 04:15I wish I could see a show of hands.
- 04:17But I'm sure most of you know
- 04:19who Humphrey Osmond is.
- 04:20He coined the term psychedelic.
- 04:23Humphrey Osmond's last academic home was
- 04:25at the University of Alabama at Birmingham.
- 04:27So back in 2015 or 14 or so,
- 04:30my first thought was to do an intervention
- 04:33in the criminal justice system and maybe
- 04:36in some ways replicate the findings
- 04:38of the Concorde Prison experiment.
- 04:40I've learned a lot about drug
- 04:41development in the meantime.
- 04:42Of course,
- 04:43you know,
- 04:43being in the criminal justice system is
- 04:45not an indication that you can target.
- 04:47But I was still hoping to do
- 04:49that study in that population.
- 04:50And the my colleague here at UAB
- 04:54who was directing the the Community
- 04:56Corrections Diversion program that I work in,
- 04:59he was very receptive to the idea
- 05:01because he had been friends with
- 05:03Humphrey Osmond in the late 90s.
- 05:05When Humphrey was here,
- 05:07we ended up not going in that direction.
- 05:09There were some cold feet,
- 05:10as you might imagine,
- 05:11at the last moment there were
- 05:13some concerns about, you know,
- 05:15political optics around doing a
- 05:17study with the psychedelic and
- 05:18the criminal justice population.
- 05:20But that's something that I
- 05:21think we will eventually do.
- 05:23But I was very pleased to know
- 05:24that Humphrey was here and there
- 05:26were people here who knew him
- 05:27and then even sort of tickled to
- 05:29know that Timothy Leary graduated
- 05:31from the University of Alabama.
- 05:32So,
- 05:32you know,
- 05:33in some ways people think that
- 05:34what we're doing makes no sense
- 05:36because we're in the state we're in.
- 05:37But we we have a long history here.
- 05:39Not only that,
- 05:40but it appears that the celosity
- 05:42mushrooms grow rather prolifically in
- 05:45the wild in this part of the world.
- 05:48And you know Birmingham,
- 05:49the city is a very blue dot and the Red Sea.
- 05:51But you know the Red Sea tends to
- 05:53be very libertarian in nature and
- 05:54many of the people I've met in
- 05:56those areas have shared stories
- 05:57of of sort of routing the the cow
- 06:02patties of of mushrooms and and
- 06:04looking up at the stars and having a
- 06:07positive experience in the in their
- 06:09youth and that the government has
- 06:10no business what telling us what
- 06:12we can put in our bodies anyway.
- 06:14So I haven't had much problem
- 06:15doing the work here.
- 06:16All right,
- 06:16let's dive into it.
- 06:21OK. So many of you know classic
- 06:24psychedelics seem to be almost
- 06:26everywhere in nature in some ways
- 06:28and from what we can tell had been
- 06:30used throughout recorded history
- 06:31by a number of different cultures,
- 06:33usually in highly ritualized
- 06:35contexts and they appear to have
- 06:37been used to promote healing,
- 06:38divine the future, enhanced learning,
- 06:40facilitate the dining process.
- 06:41But you know,
- 06:41I should point out there there are also
- 06:44documented cases of of psychedelics,
- 06:46in particular philosophy,
- 06:48mushrooms being used to facilitate
- 06:50child psych sacrifice and warfare.
- 06:53So they're not universally,
- 06:54or they have not been universally used in
- 06:57in the settings that we would think of as,
- 06:59you know, benevolent.
- 07:04The Western world,
- 07:04again many of us probably knew,
- 07:06forgot about Psilocybin,
- 07:08it appears, until our Gordon Wasson,
- 07:11that gentleman there on the right,
- 07:13made contact Maria Sabina here
- 07:17and was allowed to participate
- 07:20in a a mushroom ceremony.
- 07:23A little known fact is that our
- 07:26Gordon Wasson was asked by Maria
- 07:27not to reveal her name or location,
- 07:29and he apparently promised not to do so,
- 07:32but almost immediately revealed her
- 07:33name and location in Life magazine.
- 07:35And then in a book that he
- 07:37wrote with his wife,
- 07:38she really regretted having ever
- 07:40introduced him to the ceremony
- 07:42and allowing him to participate
- 07:44because there was sort of an influx
- 07:46of of hippies at the time that
- 07:49made life very difficult for her.
- 07:51Also a little known fact is that our
- 07:52Gordon Wasson may have been on the payroll.
- 07:54The CIA may not have known,
- 07:55but his activities may have been,
- 07:59may have been funded in part by the
- 08:01CIA that was very interested in
- 08:03discovering psychoactive medications
- 08:04that might be weaponized or they could
- 08:07enhance interrogation techniques.
- 08:08So there's there's a,
- 08:09there's a bit of a troubled history
- 08:11and I think sometimes the story
- 08:13that we hear in some circles that
- 08:15psychedelics have always been
- 08:16used for good and that that,
- 08:18you know,
- 08:19the stories around their discovery by
- 08:21Western medicine are generally happy tails.
- 08:24Unfortunately just not true.
- 08:26And I think like almost anything we
- 08:28might do or any any drug that exists,
- 08:31it could be beneficial or harmful.
- 08:33It really depends on the circumstances.
- 08:38A new slide I've added to my presentation,
- 08:40this is a slug eating a mushroom.
- 08:42So apparently slugs and snails
- 08:44have a preference for mushrooms.
- 08:46It's one of their favorite meals
- 08:48and one question is why do some
- 08:51mushrooms produce psilocybin?
- 08:53We don't really know,
- 08:54but it it seems that the the
- 08:55research would point to it being
- 08:57a a gastropod anti feedant,
- 08:58meaning it prevents slugs and
- 09:01snails from eating the mushroom.
- 09:03So so any slugger snail eating a psilosopy
- 09:05would get disoriented and wander away.
- 09:08It just so happens that it has the effects
- 09:10it has in the human nervous system,
- 09:12which are fascinating.
- 09:13But I I sometimes like to mention this just
- 09:17to in some ways de demystify the drug.
- 09:19I I mean,
- 09:20I think it is really interesting and special,
- 09:21but also it isn't in that it
- 09:23it serves as a pesticide,
- 09:24like many psychoactive substances
- 09:25we find in in nature.
- 09:29I do want to mention LSD.
- 09:31Many of you again know quite a bit about it.
- 09:33Albert Hoffman discovered LSD.
- 09:36Albert Hoffman also isolated and
- 09:38synthesized psilocybin from a
- 09:40batch of mushrooms that Maria
- 09:43Sabena provided and Al Hubbard,
- 09:47this gentleman dressed as a
- 09:49police officer in the middle,
- 09:51worked with Humphrey Osmond
- 09:53and really pioneered it.
- 09:54It would appear these early models
- 09:57of of treatment with with a
- 10:00psychedelic in particular LSD and I'm.
- 10:03I was really surprised to learn
- 10:05years ago that many of the treatment
- 10:08elements or components that are used
- 10:11today that started at Hopkins were
- 10:13originally pioneered by Al Hubbard,
- 10:15who was a Kentucky high school dropout,
- 10:19but nonetheless a very smart
- 10:21and entrepreneurial fellow.
- 10:23And I don't know that he was
- 10:24actually ever a police officer,
- 10:25but it sounds like he was a
- 10:27little bit of a huckster.
- 10:29And here he is again with Humphrey Osmond.
- 10:32Albert Hoffman's on the left.
- 10:33And as I mentioned,
- 10:34even with LSD,
- 10:35that the CIA was especially interested
- 10:38in what what promised LSD might hold is.
- 10:40A mind control drug is a drug that
- 10:42could produce the Manchurian Candidate,
- 10:44so to speak,
- 10:45and seems like they discovered
- 10:47better drugs along the way.
- 10:49But there's even more you might read,
- 10:52including a book called Poisoner
- 10:54in Chief about Sidney Gottlieb
- 10:57and a recent book called Chaos
- 10:59about Charlie Manson.
- 11:01And you know, it's speculative,
- 11:03but you know it.
- 11:04It appears that the number of people
- 11:07were working with psychedelics and and
- 11:09trying to determine what they might,
- 11:11what they might do with them and how
- 11:13they might manipulate people with them.
- 11:14And I think you know the the we'll
- 11:17we'll have to look at this further.
- 11:18But we do know that psychedelics do
- 11:20indeed make people more suggestible.
- 11:21And I think that's something that we
- 11:23we need to be on the lookout for,
- 11:24especially as as states legalize these
- 11:26compounds you know state by state.
- 11:28I think the possibility that that
- 11:30people might be especially vulnerable,
- 11:32especially outside of very carefully
- 11:33controlled medical settings,
- 11:34is high,
- 11:38but still one of my favorite pieces
- 11:40of one of my favorite documents from
- 11:43that first era of psychedelic research.
- 11:46And Al Hubbard, as I mentioned,
- 11:48was quite the character.
- 11:50Not only was he, you know,
- 11:52a high school dropout from Kentucky,
- 11:55he's also apparently a devout Catholic.
- 11:57And he had this idea that he might get
- 12:01support from Catholic leadership and
- 12:04and the there might be some support for
- 12:06this as a spiritual practice of sorts.
- 12:09And and this is something we
- 12:11hear today in some corners,
- 12:13that that psychedelics might find a
- 12:15place and organize religion and that
- 12:18religious professionals might even play
- 12:19a role in administering these compounds.
- 12:21Well, Al Hubbard was able to administer
- 12:24LSD to a Reverend Brown at the Cathedral
- 12:27of the Holy Rosary in Vancouver
- 12:30that that church is still there.
- 12:33And after his experience,
- 12:34this priest wrote to his congregation.
- 12:36And I think this is a good example
- 12:39here of of what what people thought
- 12:41of LSD in those early days.
- 12:43It wasn't a sensationalized drug at all.
- 12:45And here you have a representative
- 12:47from a long standing,
- 12:49rather orthodox institution
- 12:50raving about his experience.
- 12:52From my perspective,
- 12:53in case you can't read it,
- 12:55it says,
- 12:55friends,
- 12:56true scientific knowledge is
- 12:57the honorable objective of man's
- 12:59inquisitive intellectual faculties.
- 13:01The sciences have divided into
- 13:03myriad sections the vast,
- 13:04seemingly limitless data that is
- 13:06ours to learn.
- 13:07Over the centuries,
- 13:08man has gained collectively,
- 13:09drawing on his predecessors and sharing
- 13:11with his colleagues and successors.
- 13:13Each division of scientific knowledge
- 13:15has proved proof conclusive of
- 13:17the supreme Being responsible
- 13:18for the perfection of order,
- 13:20our scientific minds and cover.
- 13:21We are aware of man's pal ability and
- 13:23will be protected in our studies by
- 13:25that understanding and recognition
- 13:26of the first 'cause of all created
- 13:28things and the laws that govern them.
- 13:30So there's some set up here.
- 13:32He's taking some care to then
- 13:33say in this what 5th paragraph.
- 13:36We therefore approach the study
- 13:37of these psychedelics and their
- 13:39influence in the mind of man.
- 13:40Anxious to discover whatever
- 13:42attributes they possess,
- 13:43respectfully evaluating their
- 13:44proper place in the divine economy,
- 13:46we humbly ask our Heavenly Mother,
- 13:48the Virgin Mary,
- 13:49help of all who call upon her to aid
- 13:51us to know and understand the true
- 13:52qualities of these psychedelics,
- 13:54the full capacities of man's
- 13:55noblest faculties.
- 13:56And according to God's laws,
- 13:58you use them for the benefit of
- 13:59mankind here and in eternity.
- 14:05OK, that's not a question.
- 14:06I thought it was. Somebody might want
- 14:12to turn off their microphone.
- 14:14Can we mute, please?
- 14:18I'll just keep talking.
- 14:20I have the power. OK, good.
- 14:23There we go. I mean,
- 14:24this is interesting for me to see too,
- 14:25because some people are now aware of a
- 14:27book written by a man named Brian Moore,
- 14:29a rescue called the Immortality Key.
- 14:30And there's some argument here that
- 14:33early Christians were using psychedelics,
- 14:36that a a practice passed down by
- 14:39the Greeks or that had been a part
- 14:41of Greek tradition had had been
- 14:42incorporated into I guess the the,
- 14:45the, the Eucharist, you know,
- 14:47the the, the Christian tradition of
- 14:49of wine and bread during the Mass.
- 14:52I, as I understand it,
- 14:53most proper scholars reject the idea
- 14:55or scoff at it is rather ridiculous.
- 14:59But we still see today now,
- 15:00as we did in 1957,
- 15:02the date of this letter,
- 15:03this idea that there should be some
- 15:06embrace of psychedelics by religious
- 15:09institutions and religious professionals.
- 15:11I'm, I'm not opposed to that necessarily,
- 15:13but I think it's,
- 15:14it seems to be an intuitive
- 15:16conclusion that many people reach.
- 15:20So you know, the question is always
- 15:21what happened to psychedelics?
- 15:23And you know, I think a common
- 15:25explanation is, well, yeah,
- 15:27there there was a lot happening in
- 15:30the late 60s and they got caught up
- 15:32in the social and political tumult.
- 15:33And I I generally seem to
- 15:35think that that's the case,
- 15:36although I'm not a historian.
- 15:37What do I know?
- 15:38I can say that there was tremendous
- 15:39interest in the scientific community
- 15:41and it was really interesting for me
- 15:43to learn early on that there were
- 15:45over 1000 clinical studies that
- 15:47were conducted mostly with LSD where
- 15:49where around 40,000 people or so
- 15:51were administered as psychedelic,
- 15:53mostly LSD.
- 15:56And we saw a range of really
- 15:59interesting pieces of work.
- 16:00So I mean keep in mind of course
- 16:02the language was not especially
- 16:03sensitive at the time,
- 16:05but here was a study on LSD in the
- 16:07treatment of criminal psychopaths,
- 16:09you know,
- 16:10so there was interest in recidivism.
- 16:12There was a publication,
- 16:13a number of publications on LSD in
- 16:15the treatment of alcohol use disorder
- 16:17and it was really the most focused,
- 16:20it appears in alcohol use disorder
- 16:22and end of life distress.
- 16:24Now a very highly cited study given
- 16:26the fact that we're in the midst of
- 16:29an opioid crisis but publication
- 16:30and and the archives of general
- 16:33psychiatry which we now know is
- 16:35JAMA Psychiatry on the use of LSD
- 16:36for opiate use disorder and these
- 16:38findings look quite promising.
- 16:40In a fairly well conducted study
- 16:43there was also the interest in LSD
- 16:45and the treatment of end of life distress.
- 16:47This was a publication in in JAMA.
- 16:49I want to point out often to my
- 16:51colleagues that these these manuscripts
- 16:53were not published in fringe journals.
- 16:55These are to this day very
- 16:57highly respected journals.
- 16:58In the psychological Bulletin,
- 17:00which is sort of the the the
- 17:02leading journal of the American
- 17:04Psychological Association,
- 17:05we saw publications on the effects of LSD.
- 17:09Now a a very nice meta analysis
- 17:11conducted this was back in 2012
- 17:13by the Norwegian couple Krebs and
- 17:17Johansson gathered some of the
- 17:19more rigorous studies that were
- 17:20conducted at the time between 1966
- 17:22and 1970 on LSD and the treatment
- 17:24of alcohol use disorder and they
- 17:27reported an odds ratio here of
- 17:29almost two favoring the the LSD
- 17:31intervention over the control in in.
- 17:33In many ways when I saw this,
- 17:35at least quite surprising to me because
- 17:37prior to my exposure to this line of work,
- 17:40the assumption was that psychedelics
- 17:42are dangerous and addictive and that
- 17:44they have no medical application.
- 17:46That's what.
- 17:47That's what their placement and
- 17:48schedule one precisely would mean.
- 17:49But the the data would suggest otherwise.
- 17:52And what's really interesting,
- 17:52I don't know if you can see my cursor,
- 17:54but in some cases like this
- 17:55smart at all study,
- 17:57if I remember correctly there was
- 17:59almost no psychotherapy or preparation
- 18:01provided and participants were
- 18:03essentially strapped down to a Gurney,
- 18:06wheeled into a a a room
- 18:08by themselves and then
- 18:09given a pretty massive dose of LSDI
- 18:12think in this study was 800 micrograms,
- 18:15which I I I've wondered
- 18:16before what that must be like.
- 18:18I think someone once joked it.
- 18:19It must have been like when Frodo
- 18:21wears the Ring and Lord of the Rings.
- 18:23But even in this case,
- 18:24although we see a huge confidence interval,
- 18:26the the odds ratio still generally favored
- 18:29the the LSD condition over the control.
- 18:35So I, you know, I think there was some
- 18:38reason that scientists and clinicians
- 18:40at the time are really excited and
- 18:43it's interesting if you read some
- 18:44of the publications at the time,
- 18:46it's hard to know what to make of them.
- 18:47And sometimes they even read
- 18:49something like this. You know,
- 18:51John Smith was a difficult person and
- 18:53we gave him a series of LSD doses and
- 18:56at the end of his experience with us,
- 18:59he was much more agreeable
- 19:01and pleasant and balanced.
- 19:02And there's there's nothing
- 19:04really empirical there.
- 19:05But it was clear that even the
- 19:07clinicians are really excited.
- 19:09Cary Grant, the famous actor,
- 19:11had received LSD psychotherapy I believe
- 19:13from Sidney Cohen in LA and claimed
- 19:15that it made him a much better person.
- 19:17And Paul McCartney was out there saying,
- 19:19look,
- 19:19if if the world leaders used LSD just once,
- 19:22then we could achieve World
- 19:25Peace and eradicate famine.
- 19:27And I don't,
- 19:28I don't know that I'm ready to
- 19:29endorse those sort of ideas.
- 19:30But clearly people were really excited
- 19:33about the the promise of LSD that
- 19:35meanwhile there were sensationalized
- 19:37reports of recreational LSD use.
- 19:39And you know,
- 19:40I think we all know that though sometimes
- 19:43experiences with psychedelics can be
- 19:45profound and transcendent and beneficial,
- 19:47they can also be very, very unsettling.
- 19:49And people can have very bad
- 19:51experiences with psychedelics.
- 19:52And like anything we ever do,
- 19:53they carry risks,
- 19:55certainly risks outside of very
- 19:57carefully controlled settings.
- 19:59And we had this,
- 19:59you know,
- 20:00former Harvard professor Timothy
- 20:01Leary here on the left,
- 20:03who was extremely smart and charismatic,
- 20:07who is out there sort of doing what he could
- 20:10to attract as much attention to himself,
- 20:12I guess is possible and was labeled
- 20:14as the most dangerous man in the
- 20:16United States by Richard Nixon,
- 20:17which really seems pretty silly.
- 20:19But that still captures how at least some
- 20:21of the country felt about what whatever,
- 20:22what what was ever happening
- 20:25with psychedelics and.
- 20:26This is a picture on the right taken
- 20:28from my former neighborhood in San
- 20:30Francisco in the Haight Ashbury.
- 20:32I think there was the perception
- 20:33clearly that psychedelics were fueling
- 20:35this countercultural revolution.
- 20:36So almost every time I talk about this,
- 20:39I like to share this image.
- 20:40And I have.
- 20:41I've borrowed this from a
- 20:43Ted talk of John Height,
- 20:45who was a professor of mine in the mid 90s,
- 20:47when I was an undergraduate
- 20:49at the University of Virginia,
- 20:50one of my very favorite professors ever.
- 20:53And really influential in my
- 20:55pursuing an academic career.
- 20:57But here he uses this triptych
- 20:58by Hieronymus Bosch.
- 20:59It's called The Garden of Earthly
- 21:01Delights to describe the psychology
- 21:04of political orientation.
- 21:05You might wonder, where am I going with this?
- 21:06But on the far left,
- 21:07you see in the beginning things
- 21:09are ordered and as they should be.
- 21:10It's it's it's beautiful.
- 21:11It's it's calm.
- 21:12It's soothing.
- 21:13But the natural order begins to
- 21:15to be disturbed.
- 21:16And on the far right we see
- 21:19like a dystopian future.
- 21:21Like that's like like Gotham, Gotham City.
- 21:24You'd expect Batman to be
- 21:26there trying to solve crime.
- 21:27But this captures this idea that well,
- 21:29if we don't maintain order,
- 21:31that things could descend into
- 21:33complete chaos and darkness.
- 21:35And I think there was this
- 21:37perception in the 60s,
- 21:38certainly and late 60s and 70s that LSD,
- 21:41that psychedelics were fueling
- 21:42A countercultural revolution
- 21:43that could very could,
- 21:45could tear the very fabric
- 21:46of American Society.
- 21:47And I I think there's probably some,
- 21:50some validity to that argument.
- 21:52If an entire generation had
- 21:54said we're going to sign out of
- 21:56capitalism and move to communes.
- 21:57And if an entire generation had
- 22:00refused to go to Vietnam and burning
- 22:02their draft cards that that we could
- 22:04have seen quite a bit of chaos.
- 22:05And I could understand.
- 22:06I think I'm just trying to
- 22:07be empathic to Richard Nixon.
- 22:08I could see how how politicians
- 22:10at the time would say boy let's
- 22:12put a lid on this right away
- 22:13and let's let's pretend like
- 22:15psychedelics never even existed.
- 22:17And I think that's generally
- 22:18what we saw happen.
- 22:19And I I'm,
- 22:20I'm now fond of the the end
- 22:23of Raiders of the Lost Ark.
- 22:24If you've seen that movie,
- 22:25Indiana Jones,
- 22:26where they they take the ark and
- 22:28they put it in a box and they nail
- 22:30it shut and they put it away in a in
- 22:32a large warehouse somewhere and hope
- 22:33that the world will just forget all about it.
- 22:35And I think that's what some governmental
- 22:37officials thought might happen.
- 22:38But,
- 22:39you know,
- 22:40facts are stubborn things and we
- 22:42have a number of pioneering people
- 22:45to thank for our not forgetting
- 22:47about psychedelics entirely.
- 22:49I'll mention it here in a bit,
- 22:50but the question is were there
- 22:53were there scientific medical
- 22:55justifications for these legal changes?
- 22:57There are two studies published,
- 23:00one in 1993,
- 23:01one in 2004 that wanted to compare
- 23:04the dependence potential and
- 23:05toxicity of psychoactive substances.
- 23:08So on the horizontal axis you'll
- 23:10see those drugs with very high
- 23:12dependence potential would be on
- 23:13the far right and those with the
- 23:15severe risk of fatality would be at,
- 23:17at at the sort of top of the
- 23:19the vertical axis.
- 23:20Those at the bottom have a
- 23:22negligible risk of fatality.
- 23:23So the drugs you wouldn't want to use
- 23:25would be in the the top right quadrant.
- 23:27That's a bad place to be.
- 23:29And if you look there, you see,
- 23:30you know, one of the most dangerous
- 23:32drugs in these studies were heroin,
- 23:34IV, heroin, opium, morphine,
- 23:37alcohol, cocaine, amphetamine.
- 23:39The the drugs that you might think
- 23:42is as being a bit more safe would
- 23:44be in the bottom left quadrant.
- 23:46And you know, sure enough,
- 23:47that's where we see LSD and
- 23:49psilocybin taken by mouth.
- 23:50And you know, cannabis is there as well.
- 23:53Again,
- 23:53that's not to say they don't
- 23:54carry any risk at all.
- 23:55They certainly do.
- 23:56But if the question is were these
- 23:58legal changes justified and do
- 23:59these drugs belong in schedule
- 24:01one at least from these two studies?
- 24:03I think the answer is no.
- 24:04We've all seen this.
- 24:05I'm going to skip through this,
- 24:07but this was David Nutz study
- 24:10on on the harms posed by drugs
- 24:14of potential misuse through a
- 24:16sort of expert panel review.
- 24:17And we see that alcohol was
- 24:19ranked as the most harmful.
- 24:20I think this is in the UK
- 24:22specifically and and mushrooms,
- 24:24LSD, ecstasy, we're all near
- 24:25the very bottom of this list.
- 24:29So we're in the midst of a of a
- 24:31modest renaissance, I guess it's
- 24:33maybe more than a modest renaissance.
- 24:34It's a pretty robust renaissance now
- 24:36and we have in part Rick Strassman to
- 24:39thank for his work on DMT in the 90s.
- 24:42Here are some examples of that work.
- 24:44But in in my mind,
- 24:46it really all started here with
- 24:49Roland Griffith's 2006 study.
- 24:50And many of you probably know Roland
- 24:53recently passed away and this study was
- 24:56really influential in my own thinking.
- 24:58People always ask me the
- 24:59most commonly asked question,
- 25:00especially here is why am I
- 25:02interested in psychedelics?
- 25:02And I often disappoint people by saying
- 25:05it's not because I have any history
- 25:08of personal use and and you know it,
- 25:11my own introduction to the
- 25:13field is purely serendipitous.
- 25:14If you look at the top of this image,
- 25:17you'll see that this study by Roland
- 25:19was published in 2006 in issue 187,
- 25:21and that happens to be the same journal,
- 25:24same issue as my dissertation here,
- 25:28which if if you can get through the
- 25:29title without kind of snoozing off,
- 25:31I'm impressed.
- 25:32But I published this dissertation
- 25:35and I received a complimentary
- 25:37copy of this issue and I opened
- 25:39up the issue eager to see my name
- 25:41in print for the first time,
- 25:43and instead turned to Roland's article
- 25:45and was just fascinated at the time.
- 25:47And from that point forward,
- 25:48I was really interested in learning
- 25:50more and maybe doing some work in this
- 25:52area in large part because I know there
- 25:53are a number of of addiction scientists here.
- 25:56You know, our best interventions
- 25:58and certainly in my own,
- 25:59my kind of home field smoking cessation,
- 26:01even the very,
- 26:02very best interventions money can
- 26:04buy tend to perform really poorly.
- 26:06So I was really eager to find
- 26:07something that could really make a
- 26:09difference and I thought there might
- 26:10be potential there in psychedelics.
- 26:12And I I think so far things look good,
- 26:14but we'll have to see.
- 26:16So a little review before I
- 26:19talk about my trial.
- 26:21We've we've seen some of the findings here
- 26:25around psilocybin and demoralization.
- 26:27You know,
- 26:27there's a rather rapid and
- 26:29robust effect on demoralization.
- 26:32And this is the cancer work that
- 26:34that Roland and the team at
- 26:36NYU conducted back in 2016,
- 26:38very robust and rapid effects
- 26:41of these psilocybin experiences
- 26:44on depression and anxiety.
- 26:47Brian Anderson at UCSF conducted
- 26:49a great study of demoralization
- 26:51among gay identified men who were
- 26:54long term AIDS survivors.
- 26:56Of course this was open label,
- 26:57single arm, open label.
- 26:58So you know,
- 26:59take these findings with a grain of salt.
- 27:00But there seems to be a nice
- 27:02effect here that at least would
- 27:03suggest we we do more research.
- 27:07We've seen Michael Bogan shoots his
- 27:09work with alcohol dependence on this
- 27:11was his original proof of concept
- 27:13study and he recently published
- 27:14findings in in JAMA Psychiatry that
- 27:17would indeed suggest that psilocybin
- 27:19can reduce heavy alcohol use.
- 27:21And then Matt Johnson has done some
- 27:24great work with smoking cessation
- 27:26kind of breezing by so I can get to
- 27:28the the study that I'm doing now
- 27:30of course we've seen some of the
- 27:32work on on depression and I'm I'm
- 27:33gonna sort of move by that too.
- 27:37Here's the the compass findings.
- 27:40So why am I interested in cocaine dependence?
- 27:45There are a few reasons for that.
- 27:47One is there are no approved
- 27:49pharmacotherapies for cocaine use disorder.
- 27:54The second is if you look at dropout
- 27:57rates in in person psychosocial
- 27:59substance use disorder treatments.
- 28:01This is a meta analysis my postdoc Sarah
- 28:03Lappin and I conducted a little while back.
- 28:06You'll see that the rates of dropout,
- 28:08if you look closely are are especially
- 28:10high for major stimulant use.
- 28:12So the average rates of dropout for
- 28:15cocaine use disorder were 48 percent,
- 28:1748.7 For methamphetamine,
- 28:1953.5 for major stimulants,
- 28:22broadly speaking 46.8.
- 28:23And this is quite different than some of
- 28:26the other substances that were targeted.
- 28:29It's very difficult to work with people
- 28:33with major stimulant use disorder.
- 28:34Or put another way,
- 28:36you know people who have major stimulant
- 28:38use disorder have difficult lives
- 28:40and the the the chronic use of major
- 28:44stimulants has a way of disrupting
- 28:47cognitive behavioral control.
- 28:49And we we don't really have much of
- 28:51anything that works for this population.
- 28:53Contingency management may indeed
- 28:55be effective.
- 28:56But as many of you probably know,
- 28:58the problem there is once
- 28:59the contingency is removed,
- 29:00the drug use returns and there are
- 29:02you know political realities you
- 29:03have to deal with namely that like
- 29:05generally voters don't like the idea
- 29:07of paying people not to use drugs.
- 29:09So we we need something for major
- 29:12stimulant use disorder and I'll I'll
- 29:15add also and the Birmingham area and
- 29:17our very large sample of individuals
- 29:20in the criminal justice system,
- 29:21major stimulant use is frequently the
- 29:24single strongest predictor of recidivism.
- 29:27So there are implications I think
- 29:28for the criminal justice system.
- 29:29And you know, Alabama is a police state.
- 29:32I doubt Connecticut is to the
- 29:33degree that Alabama is.
- 29:35And we,
- 29:35we would like to see fewer people
- 29:36in the criminal justice system
- 29:37because once you're there,
- 29:39it's hard to get out and generally you
- 29:41can ruin your life if you're there.
- 29:42So we'd like to do something about that.
- 29:45So I'm just going to present some
- 29:47preliminary results and if you've
- 29:48seen me talk about this before,
- 29:49this might look very familiar to you.
- 29:50But we have dosed everyone in this trial.
- 29:53We have complete data on a 38
- 29:56out of 40 of the participants,
- 29:58but I'm only showing results from the 1st
- 30:0010 who have completed their participation.
- 30:02Those were 10 people who were
- 30:04unblinded per my Data Safety
- 30:06and Monitoring Board's request.
- 30:08We'll have all the data out
- 30:10I think this summer.
- 30:14So here's an overview of our protocol.
- 30:18So before we provide any treatment there's
- 30:20sort of a pre treatment screening period.
- 30:22We we will assess our participants
- 30:26for uncontrolled hypertension.
- 30:28We want to see they're just
- 30:29able to come to appointments.
- 30:31So they're they're two pre screen
- 30:32appointments as we call them and we just
- 30:34want our participants to show that they
- 30:36can they can come to appointments on
- 30:38time before we really begin the process.
- 30:40There's a medical exam and we we just
- 30:42required that our participants be
- 30:44generally healthy to have an an EKG
- 30:47and blood panel that our our physician
- 30:50collaborators felt deemed them healthy
- 30:53enough to receive psilocybin and then
- 30:56the psychotherapy began and and we had
- 30:58four so-called preparation sessions.
- 31:00The focus here was essentially
- 31:02establishing Rapport Alliance with
- 31:04our participants and we included at
- 31:06this time a a empirically supported
- 31:08manualized cognitive behavioral
- 31:10therapy for cocaine use disorder
- 31:13developed by Peter Monti and colleagues
- 31:15at Brown in the 90s.
- 31:16We tried not to do anything other
- 31:19than very standard rapport building
- 31:21reflective listening, expression,
- 31:23empathy along with the CBT.
- 31:26Now part of this did include a description
- 31:28of what the effects of psilocybin might be.
- 31:31We wanted people certainly to be
- 31:33prepared for the effects of the
- 31:35drug and to we try as best we could
- 31:37to mitigate the sometimes rather
- 31:39significant anxiety or panic that
- 31:42can accompany these experiences.
- 31:44We included MRI in the study if
- 31:45any of you are interested.
- 31:47We're we were taking a good look at
- 31:49resting state functional connectivity.
- 31:51I don't have those results present
- 31:52to you today,
- 31:53but we will in the summer and
- 31:55we're also looking at GLX via Mrs.
- 31:59After the MRI, we would administer the
- 32:01drug in a clinical research unit either
- 32:0425 milligrams per 70kg of psilocybin
- 32:07or 100 milligrams of diphenhydramine.
- 32:10I think a common question is, well,
- 32:13how were we able to maintain the blind?
- 32:15I think maybe now not much of A secret
- 32:18is it's really hard to maintain the
- 32:20blind and studies of psychedelics
- 32:22because the the effects are so
- 32:24transparent salient and profound.
- 32:26And maybe not all participants
- 32:29who received the placebo where
- 32:30where they had received a placebo.
- 32:32But I would gather that most of those
- 32:34who received the active drug thought
- 32:35they received an active drug and
- 32:37likely the the therapist involved in
- 32:39the study had a good idea as well.
- 32:41And that's that's something that
- 32:43we just have to consider when we
- 32:45interpret these results that as
- 32:46best in in this case we may have
- 32:49tried to maintain our objectivity.
- 32:51We are the investigators who
- 32:54who designed the study.
- 32:57We have hypothesis we have a bias and that
- 33:00bias likely had an impact on our findings,
- 33:03especially considering
- 33:04functional and blinding.
- 33:06And as much as we'd like to say
- 33:08that these are very objective,
- 33:09I think these are these are issues that we'll
- 33:11we'll have to contend with moving forward.
- 33:13I should I should mention also,
- 33:14because this was funded with a
- 33:16shoestring budget, not only was I,
- 33:18the PIII was also the the primary
- 33:20therapist for every participant.
- 33:21So consider how my own bias may
- 33:24have impacted these results.
- 33:26So one administration of psilocybin
- 33:29or diphenhydramine,
- 33:30we would usually the next day,
- 33:32sometimes two days after depending
- 33:34on participant availability,
- 33:35we would begin the so-called
- 33:37integration process.
- 33:38And I,
- 33:38you know,
- 33:39I think in retrospect I regret
- 33:41these these terms they sound
- 33:43again a little too magical.
- 33:45We would just begin discussing the
- 33:48experience and but we really don't
- 33:50know what in the world is happening in
- 33:52so-called psychedelic psychotherapy.
- 33:53My sense is that for the most
- 33:54part people have insights and
- 33:56I'll talk about this in a bit and
- 33:57much of our discussion might just
- 33:59focus on natural problem solving.
- 34:00So someone might say,
- 34:02I realize I need to spend more
- 34:03time with my children.
- 34:04OK What are some ways that that
- 34:06you can accomplish that goal.
- 34:08Otherwise we would continue with
- 34:10cognitive behavioral therapy.
- 34:11Over the course of the four sessions,
- 34:13I provided more rather than less
- 34:15treatment because I didn't want anyone
- 34:16to feel like after this experience we just,
- 34:18you know,
- 34:19cut cut them off and and sent
- 34:21them out without proper support.
- 34:23We then had assessments,
- 34:25assessment only at 90 and 180
- 34:28days after the end of treatment
- 34:29and I wasn't involved in that.
- 34:31I wouldn't even be in the building
- 34:32when when participants would
- 34:33come for these assessments.
- 34:34And they would,
- 34:35it would,
- 34:36it would conduct these assessments
- 34:38with members of my staff who were not
- 34:40involved in the treatment in any way
- 34:44and feel free to cut me off.
- 34:45Any questions you can.
- 34:46I guess since we're not here in person,
- 34:48I actually wouldn't
- 34:49know if anybody has one.
- 34:49But you can speak up if you'd like.
- 34:51May I ask a question?
- 34:53Yes. Hi. Can you
- 34:54exclude for use of other drugs?
- 34:58Oh, good question. Yeah. So.
- 34:59So we use DSM 4 criteria,
- 35:02I should say that.
- 35:03So we would have excluded for
- 35:05dependence on other substances,
- 35:07with the exception of tobacco,
- 35:09if we had excluded people who are
- 35:11also smoking cigarettes that this
- 35:12would have been impossible to do.
- 35:14So we allowed tobacco use.
- 35:16We allowed alcohol abuse but not
- 35:18dependence and alcohol use among those
- 35:21who use cocaine is very prevalent.
- 35:23And it's you probably know again
- 35:25that when you when you drink and
- 35:27use cocaine at the same time,
- 35:28there's a unique byproduct that sort
- 35:31of extends the the effects of cocaine.
- 35:34And not all of those who use
- 35:35cocaine are aware of this,
- 35:36but you basically get more bang
- 35:38for your buck when you drink and
- 35:39use cocaine at the same time.
- 35:40So there's a fair amount of drinking here,
- 35:42but we would have excluded anybody with
- 35:46an independent alcohol dependence diagnosis.
- 35:48A lot of people use cannabis,
- 35:51but no one met criteria for dependence.
- 35:53And so we also allowed abuse on cannabis.
- 35:59How about other psychiatric diagnosis?
- 36:01How about bipolar or, you know,
- 36:04history of psychosis or other things?
- 36:06Did you rule those out? Yeah.
- 36:08So anybody, that's a great question.
- 36:09Anybody with the first or second degree
- 36:11relative with the history of bipolar
- 36:12disorders or psychotic disorders would
- 36:14have been excluded from the study
- 36:18that that can be difficult to assess
- 36:20sometimes because I learned in in
- 36:22this part of the world the term
- 36:25schizophrenia is sometimes used
- 36:26just to refer to you know a parent
- 36:28who is kind of irritable and Moody.
- 36:31So we were we were careful not
- 36:33to include anybody who had first
- 36:35or second degree relatives with
- 36:36psychotic or bipolar disorders.
- 36:38And we don't really know
- 36:40what psychedelics might do.
- 36:41I mean I I actually think that
- 36:43concerns around hypomanic or
- 36:44manic episodes are real.
- 36:46I'm not as concerned now about the
- 36:48impact on psychotic disorders and
- 36:50I think even there could be a a
- 36:52future in studying psychedelics
- 36:53for psychotic disorders.
- 36:55But to be very safe in the study
- 36:56we excluded those people.
- 37:00OK, I'll keep going here.
- 37:01So just to give you a general
- 37:03overview this this is just the
- 37:041st 10 people you know our our
- 37:06demographics will change it.
- 37:07But, but I mean generally speaking
- 37:10our participants were were
- 37:11economically disadvantaged folks,
- 37:13some were homeless,
- 37:15many were unemployed and the
- 37:17majority of our sample was African
- 37:19American and that just reflects
- 37:20the population of Birmingham,
- 37:22that's over 70% African American.
- 37:25So we administered the challenging
- 37:28experience questionnaire after psilocybin
- 37:31sessions and this was a questionnaire that
- 37:34was ultimately developed by Fred Baird.
- 37:38But based on some older
- 37:40questionnaires from the 60s,
- 37:41I think Walter Panke and colleagues
- 37:42may have developed a number of these
- 37:44questions that get at some of the more
- 37:46difficult experiences that people
- 37:47can have with the psychedelic. Now,
- 37:49to give you a sense of what these might mean,
- 37:51there were adjectival anchors at
- 37:53each number and zero the the anchor.
- 37:55There would have been none.
- 37:56One would have been so slight I cannot tell.
- 38:00Two would have been mild,
- 38:013 was moderate, 4 was very strong,
- 38:04and five was extreme.
- 38:05So although your eyes might tell you
- 38:08here that there were indeed differences
- 38:11between psilocybin and placebo,
- 38:12just note that even for,
- 38:13say, fear, the fear scale,
- 38:15where we saw the strongest mean score,
- 38:19folks were essentially saying that
- 38:21their mean fear was somewhere between
- 38:23so slight I cannot tell and mild.
- 38:25I do think it's important to note here,
- 38:28though, that, you know,
- 38:30one could have a few moments
- 38:32of rather intense fear followed
- 38:34by maybe hours of bliss.
- 38:36And so when we asked them at the end
- 38:38of their experience, were you afraid?
- 38:41If they're.
- 38:42Even though we tell them to
- 38:43answer based on how they may have
- 38:45felt at any one period of time,
- 38:47they've had a rather blissful experience.
- 38:48It might be common for them to
- 38:50downplay the degree to which they
- 38:52might have been afraid at one point.
- 38:54And I, as an analogy,
- 38:55I often use this story of when I took my
- 38:58my daughter, now 12, she has no idea.
- 39:01I use this analogy.
- 39:01I don't know how she'd feel.
- 39:02I'll have to ask her tonight.
- 39:03But when she was 10,
- 39:05I I took her to her first roller
- 39:07coaster and she was really excited.
- 39:08We're waiting in line and we,
- 39:09we got the,
- 39:10the,
- 39:10the car and we were strapped in and
- 39:12she was talking about how excited she
- 39:13was to be doing this for the first time.
- 39:15And then when we started climbing the hill,
- 39:17she said, Oh no.
- 39:18All right, Daddy, tell him to stop the ride,
- 39:20take it back.
- 39:21I'm getting off,
- 39:21I'm not doing this.
- 39:23And I said obviously there's
- 39:24there's no way off this unless
- 39:26we see this ride through the end.
- 39:28And she was a little upset.
- 39:30But once the ride began,
- 39:31she had a great time and by the end
- 39:32she was saying let's do it again.
- 39:34And I was like, well,
- 39:35you were a little scared there at the
- 39:36at the beginning and she was like,
- 39:37no, I wasn't. I was fine.
- 39:39I don't know what you're talking about.
- 39:40Issues kind of downplaying it.
- 39:42I think that's a pretty good
- 39:43analogy for how this experience
- 39:44can be for many people.
- 39:45There's some fear at the beginning,
- 39:47sometimes an expression to to
- 39:49stop the experience altogether.
- 39:50But after that initial period of fear
- 39:53passes, there's awe and wonder
- 39:56and bliss, and at the end they
- 39:58might say it wasn't so bad.
- 39:59But I think these these scores probably
- 40:01underestimate at least how they may
- 40:03have felt for a period of time. Did
- 40:06they have previous experience
- 40:08with psychedelics? I'm
- 40:09sorry, could you repeat the question? Did
- 40:11they have, did they, did they have
- 40:13previous experience with psychedelics
- 40:14or was it their first time?
- 40:17So we required that our participants
- 40:19would have not used a psychedelic
- 40:21before or that would have been three
- 40:23years since their prior experience.
- 40:24And the idea here is if they had recently
- 40:26had a large dose of a psychedelic that
- 40:28they'd be easily able to tell whether
- 40:30they received the active drug or not.
- 40:32But also, if if someone had said, yeah,
- 40:34you know, just last month I took 500
- 40:37micrograms of LSD and I'm still using
- 40:39cocaine every day, we might think,
- 40:40well just from the beginning.
- 40:41There's reason to think this
- 40:42person might not be a responder,
- 40:44even though I do think that pairing in
- 40:47the psychotherapeutic context is much
- 40:50different than than naturalistic use.
- 40:52I'd have to take a look at the data,
- 40:53but like almost all of our participants had
- 40:56no prior experience with the psychedelic.
- 40:58And those who did may have,
- 40:59you know, at age 50 had said, yeah,
- 41:01when I was when I was a teenager,
- 41:03somebody passed around microdots.
- 41:04And what do I remember from that experience?
- 41:07We all kind of laughed and you know,
- 41:09the colors were bright and vibrant.
- 41:10But that's all I remember.
- 41:12So they were for the most part
- 41:14naive and most I will say, you know,
- 41:16anecdotally,
- 41:16most of the folks thought the
- 41:17idea sounded crazy, right?
- 41:19They'd say you're going to help me
- 41:21stop getting high by getting me high.
- 41:22I'm not so sure about this,
- 41:24but hey I've tried everything at this point,
- 41:25so I'll move forward.
- 41:27So here we have the Mystical
- 41:29Experience Questionnaire and we
- 41:30generally think these these are the
- 41:32sort of experiences we want people
- 41:33to have and the the adjectival
- 41:35anchors are the same as with the the
- 41:37challenging experience questionnaire.
- 41:38SO4 is very strong,
- 41:40five is extreme and you'll see here we we
- 41:44didn't conduct any inferential statistics,
- 41:46but I think your your eyes will probably
- 41:48give you a sense of what's happening.
- 41:51Their psilocybin appears to do as
- 41:55advertised. I I would say here.
- 41:59So we always we ask folks the same
- 42:01sort of questions they did at Hopkins.
- 42:03You know how spiritually significant
- 42:05was this experience for you?
- 42:07And let's see, of the six people in
- 42:10the 1st 10 who received psilocybin,
- 42:123 said it was the single most spiritually
- 42:15significant experience of their lives.
- 42:17The the next response option
- 42:18is it's in the top five.
- 42:20One person indicated that that is
- 42:22where psilocybin landed for them.
- 42:24Among those who received the placebo.
- 42:25No one endorsed either of those responses.
- 42:29And follow me here,
- 42:30there's a lot going on and I realize
- 42:32it's it's probably not labeled ideally,
- 42:34but I'll I'll walk you through.
- 42:36So when we first see our participants,
- 42:38they're using about half the time on average.
- 42:43There's a lot of variability.
- 42:47You know,
- 42:47the limiting factor really appears
- 42:49to be finances, right?
- 42:50They might use more if they had
- 42:52money to use and this would be
- 42:56during the before we've started any
- 42:59kind of behavioral intervention.
- 43:01But while they're a participant in the study,
- 43:02we see that they already begin to
- 43:05reduce their percentage of use.
- 43:06They already begin to use,
- 43:08reduce cocaine use and that's a fairly
- 43:09common finding in clinical trials.
- 43:11People begin to change before
- 43:12you ask them to.
- 43:13Now during the preparation process we
- 43:16see further reduction in cocaine use.
- 43:19But this is what I want you to look at here.
- 43:20This is the period of time from Drug
- 43:23Administration DA through end of
- 43:24treatment and in this first again 10,
- 43:26these first 10 participants,
- 43:29we see that everybody who was administered
- 43:32psilocybin reported 100% abstinence
- 43:34and that's why there's there's no,
- 43:36there are no error bars there.
- 43:38The the folks who received
- 43:40placebo are doing pretty well too.
- 43:42There's a little bit of a dip from end
- 43:44of treatment through 90 day follow up,
- 43:47although between 90 day to 108 day follow up.
- 43:51Those who received psilocybin again
- 43:53report complete abstinence whereas
- 43:55those who received the placebo reported
- 43:58abstinence about 85% of the time.
- 44:01I I would just interpret these
- 44:03very cautiously again because we'll
- 44:05have the full data set on the 40
- 44:07shortly and these are the 1st 10.
- 44:08And and you know I conducted some
- 44:11inferential statistics here,
- 44:12though I should not have because
- 44:14this is just the 1st 10.
- 44:15But if you are interested,
- 44:17the effect sizes look large.
- 44:19I can't imagine they'll be that large
- 44:20at the end but there there seems to
- 44:22be a signal here that looks promising.
- 44:26So OK, I came up with the video here.
- 44:29It's a little silly,
- 44:30but I I want to discuss briefly what
- 44:31I think might be going on and I
- 44:33need to credit my doctoral student
- 44:35Haley Durant for helping me come
- 44:37up with this and the general idea.
- 44:38So our our thought here and we we
- 44:42outline this in a very long paper in
- 44:45pharmacologic reviews would suggest
- 44:46that for most mental health conditions
- 44:48there is a rather pathological degree
- 44:51of self focus that your your your sort
- 44:56of field of of attention is narrow and
- 44:59in the case of someone using cocaine
- 45:02there might very frequently be this
- 45:04focus on where can I obtain the drug.
- 45:07How can I obtain money to obtain the drug.
- 45:08I have an urge.
- 45:09I have these withdrawal symptoms
- 45:11how can I make them go away.
- 45:12I want to use what am I going to use how
- 45:15am I going to use and so your your your
- 45:18attentional scope can be very narrow.
- 45:21We believe that for for reasons we
- 45:24don't yet completely understand,
- 45:25when one in just ingest A psychedelic
- 45:28that attentional scope is broadened
- 45:30and there is a a an experience of
- 45:33reduced self focus paired with
- 45:35hyper associative thinking.
- 45:37So in other words,
- 45:39one's very narrow laser focus is broadened
- 45:43to a a much wider attentional scope.
- 45:45And it's in in these experiences that
- 45:48people can have insights that that
- 45:50may prove to be beneficial to them.
- 45:55And where this sort of pathological
- 45:57self focus there's there's almost this
- 45:59experience of liberation from this,
- 46:01from this self focus and and
- 46:03insights that might lead in fact
- 46:05to more adaptive behavior change.
- 46:06So here we've come up with a a humorous
- 46:08video that hopefully you'll follow.
- 46:10We'll see how it goes.
- 46:13So this, this young boy here
- 46:14is fixated on a family,
- 46:33right? So I'll have to work on this a bit.
- 46:36But you'll see here in the bottom corner,
- 46:38there's still this young child
- 46:39and the fly that was there before.
- 46:41And this is Salvador Dali's
- 46:44hallucinogenic torador.
- 46:46I went to Graduate School at the
- 46:47University of South Florida.
- 46:48Not many people know,
- 46:49but the USF owns many of his masterpieces.
- 46:51So I could as a graduate student
- 46:53and enjoy his is masterpieces
- 46:55for nothing with my student ID.
- 46:57But I often think of of this as
- 46:58as maybe one way of capturing
- 47:00the psychedelic experience.
- 47:01Your your intentional focus is very narrow.
- 47:03It's first just this child
- 47:05child focused on this fly.
- 47:07But in the in the wake of a
- 47:08of a psychedelic experience,
- 47:09suddenly the intentional focus is
- 47:12is broadened tremendously and one
- 47:16forgets about themselves altogether in
- 47:19the in the midst of this information
- 47:22rich environment that can lead to insight.
- 47:25So people sometimes use the term
- 47:27ego dissolution and I think there's
- 47:29something to that to a degree and
- 47:31that your yourself focus has reduced
- 47:33substantially.
- 47:34But there's more to it than that.
- 47:35There's also self presence,
- 47:37which means that this is a term from
- 47:39the the schizophrenia literature.
- 47:40Some of you might be familiar with this,
- 47:42but that one is very present and
- 47:44aware of an experience that has
- 47:46very little to do with them.
- 47:47And if it were just ego dissolution,
- 47:49I could say let's all drink a a pint
- 47:51or or gallon of vodka tonight and we'll all,
- 47:54you know be unaware of our existence.
- 47:56That alone is not going to be the trick.
- 47:58There needs to be also some self
- 48:00presence and I think meaning
- 48:02and salience to the experience.
- 48:04So that's our thinking for now,
- 48:05that in essence those who are struggling
- 48:07with substance use disorders have
- 48:09these experiences that sort of take
- 48:11them out of that rut of self focus on,
- 48:13you know,
- 48:14craving an urge and often lead to
- 48:17insights around the the the impact
- 48:19of their substance use on those they
- 48:22love or maybe some novel problem
- 48:26solving solutions that they might
- 48:29generate from their experience
- 48:31or or maybe something else.
- 48:32I don't know.
- 48:33We we need to figure that out as
- 48:36the field goes forward.
- 48:37Oh, you don't need to see that again.
- 48:38OK,
- 48:39so here's here's a little explanation
- 48:41of that that theory and I think
- 48:43I've generally gone over this.
- 48:45Now one thing we would say is it's
- 48:48likely that psychosis represents a hyper
- 48:50associative style of thinking as well.
- 48:53But the difference here is that
- 48:55that self focus remains very high.
- 48:57So someone might have some very novel ideas,
- 48:59but they tend to be self referential
- 49:01and that seems to not be helpful.
- 49:03So we we do think that hyper
- 49:05associative thinking is really
- 49:06important in the case of psychedelics,
- 49:08but it's crucial that that be paired
- 49:10with low self focus and that's what
- 49:11leads to many of these beneficial
- 49:13outcomes that we've seen with psychedelics,
- 49:15whereas high self focus can lead
- 49:16to a number of the outcomes that we
- 49:18tend to see with psychotic disorders.
- 49:23Let's see many of you have probably
- 49:25seen this and thought about this
- 49:27and I often think about this.
- 49:28I just want to, before we
- 49:29open the field to questions,
- 49:31I wanted to mention a few things about this.
- 49:33You know, I do. I do think we're
- 49:35at somewhere in this process,
- 49:36depending on where you are.
- 49:37There's been a lot of hype
- 49:39around psychedelics and I'm
- 49:40really excited about them.
- 49:42But you know,
- 49:43I'm under no illusions that
- 49:45they're without risk and that
- 49:48we might not see some very
- 49:50negative headlines in the future.
- 49:52We've already seen a few probably.
- 49:53You saw this this story about a
- 49:56an aviator who tried to down a
- 49:59commercial airplane and said that
- 50:00he was experiencing some difficulty
- 50:02after a psilocybin experience.
- 50:03That might be true.
- 50:04And I think it's very clear that these
- 50:07experiences can be really unsettling,
- 50:09especially I think without very
- 50:12careful mental health care that's
- 50:14paired with the experience.
- 50:15So I'm a little worried about
- 50:17these state level initiatives.
- 50:19I mean I I think people should be
- 50:20free to do what they want to do.
- 50:21But I I also am not in the place where
- 50:23I would promote psychedelic use and
- 50:24I think we're going to see some harms.
- 50:26And I'm I'm,
- 50:27I'm worried about what that might portend,
- 50:29especially around maybe political support
- 50:31for the commercialization of these drugs.
- 50:33But I I clearly think that the
- 50:36sort of guardrails that we've
- 50:37built up in these clinical trials
- 50:38are crucial and I wouldn't want
- 50:40to do this work without a team
- 50:42of licensed mental health care
- 50:43professionals working with me.
- 50:47So like why is media hype
- 50:49I think so dangerous?
- 50:51Well, you know, we see this and
- 50:53any psychiatrist or people in drug
- 50:54development here would know that
- 50:56there have been a number of drugs
- 50:58that have been labeled game changers.
- 51:00The media has sort of hyped up these,
- 51:02these medications from new novel
- 51:06antipsychotics to anxiolytics.
- 51:08And you know typically the sort of
- 51:10effect sizes we see in clinical trials
- 51:11just don't pan out in the real world.
- 51:13And the media has a way of hyping things
- 51:16up and sort of knocking you down and
- 51:18things don't go quite as planned and you
- 51:20know adverse outcomes when they occur.
- 51:22It's not a matter of if, but when,
- 51:24even in carefully controlled clinical
- 51:26settings will likely be hammered to death.
- 51:28And a very tragic example from the
- 51:30older days would be Art Linkletter who
- 51:32is a famous television personality.
- 51:34His daughter committed suicide and
- 51:36you know there there seems to be
- 51:38some evidence that she had an LSD
- 51:40experience that really unsettled her
- 51:41and it could very well have been
- 51:43that it contributed to her death.
- 51:45And I can only imagine how painful
- 51:46that was for him as a father.
- 51:48And he really dedicated the rest
- 51:50of his life to to being like a a,
- 51:52a sort of drug warrior, anti drug crusader.
- 51:55And some of the ideas that we have
- 51:57around psychedelics and self harm
- 51:59are formed in part by what happened
- 52:01here with Art Linkletter.
- 52:02But if you saw the outcomes of the
- 52:04Compass study you'll see that there are
- 52:05some people who might be at risk of
- 52:08self harm after a psychedelic experience.
- 52:09And we know that there are interventions
- 52:11that we provide today that can certainly
- 52:13make things worse before they get better.
- 52:15So I I would say for one,
- 52:17we need to be really clear with the
- 52:19general public and media that these
- 52:20are not substances without risk,
- 52:22they can be really intense and that
- 52:24they're not for everybody and some
- 52:27people could certainly be harmed.
- 52:29And so I would say like there's important,
- 52:31important to be really transparent from
- 52:34transparent from the beginning and
- 52:35provide a realistic picture of the benefits.
- 52:38So we're about to start data collection,
- 52:40thank goodness on a Nida funded trial
- 52:42of psilocybin for smoking cessation.
- 52:44And to put things in perspective
- 52:46then our current smoking cessation
- 52:48success rates are 20 to 30% or so,
- 52:51maybe lower outside of clinical trials.
- 52:53If we double this rate,
- 52:54it would be a boon for public health.
- 52:56I'd be really excited,
- 52:57but that would mean that the treatment
- 52:59would not be effective for maybe
- 53:0140 to 60% of the smokers.
- 53:03So if I started a smoking cessation clinic
- 53:05providing providing psilocybin in the future,
- 53:07it might very well be that the
- 53:09majority of my patients would not quit
- 53:11smoking and they'd leave thinking,
- 53:12well wait a second,
- 53:13I thought Michael Pollan said
- 53:14that's how you change your mind.
- 53:16So what in the world were they talking about?
- 53:18I think we would have to be clear
- 53:20from the beginning that maybe we're
- 53:21taking our treatments from from being
- 53:23not very good to and not so bad.
- 53:25I I don't know how to award this,
- 53:27but I want to be really clear And I
- 53:29think it's also important that we be
- 53:31very clear about the risks now so as
- 53:34that to prevent the public from feeling
- 53:36like they were you know bamboozled
- 53:38and that we're only talking about
- 53:40how great psychedelics might be.
- 53:42And I'll just say is this last point,
- 53:43I think you know when we when and if
- 53:46psilocybin is approved for clinical use,
- 53:48I think training and maintaining
- 53:51fidelity are crucial.
- 53:52And this is a, you know,
- 53:53drill Sergeant from Full Metal Jacket.
- 53:58You know, I think we've got to be really,
- 54:00really careful here.
- 54:01And I'm concerned about what's
- 54:03happening in some of these states
- 54:05where it's hard to see exactly what,
- 54:07what if any protocols might be there
- 54:10to ensure safety and and fidelity
- 54:13that whatever the true protocol
- 54:14might be and to ensure that,
- 54:16you know,
- 54:16competent licensed mental health
- 54:18care professionals are involved in
- 54:20the administration of these drugs.
- 54:22And I think already like my friend
- 54:24Matt Johnson has drawn attention to
- 54:26concerns around the the the ways in
- 54:29which boundaries are are crossed.
- 54:30And those of us who are,
- 54:31are a clinicians, psychologists,
- 54:34social workers,
- 54:35psychiatrists know that there are a number
- 54:36of boundary issues already in what we do.
- 54:38And it seems that with psychedelics,
- 54:40those issues are just amplified even further.
- 54:42And so we we've got to be really careful
- 54:44in how we do what we do and ensure
- 54:47that we we maintain those boundaries.
- 54:48And I think in,
- 54:49in Matt's case,
- 54:50he's even concerned about the development
- 54:51of cults that might might appear
- 54:53and and yeah, that might happen.
- 54:55You know,
- 54:55psychedelics are really interesting
- 54:56drugs and they can,
- 54:58they can really change the way we think
- 55:00and lead sometimes to some rather
- 55:02grandiose and delusional thought patterns.
- 55:03So I,
- 55:04I would conclude then by saying I'm really
- 55:06excited about what the future brings here,
- 55:08but I really think it's crucial we
- 55:10do this in a really careful way.
- 55:12I think that's my last slide.
- 55:13No.
- 55:14OK.
- 55:14Well I guess my my last slide
- 55:16then has to do with my,
- 55:17my concerns around availability and I
- 55:19work with very low income people and
- 55:21people in the the criminal justice system.
- 55:23And you know we we have an Ischetamine
- 55:26clinic at UAB and and I think
- 55:27it could be doing a lot better,
- 55:29but it seems like Ischetamine
- 55:31could have done better had there
- 55:33been conversations with managed
- 55:34care well before it was you know
- 55:36it was it was available on market.
- 55:38So I think we need to really think
- 55:40about partnering with practices and
- 55:41come up with a come up with a business
- 55:43model that makes sense because if we
- 55:44don't have a viable business model,
- 55:46these psychedelics just won't be taken up.
- 55:48And you know there's going
- 55:49to be some resistance here
- 55:51because psychedelic paradigms
- 55:52are likely very expensive.
- 55:53I think that's my last slide.
- 55:55Yes, I was right.
- 55:55So with that I'll stop,
- 55:56stop sharing and and happy to
- 55:58answer any questions anybody has.
- 56:03Thank you so much, Peter, for that,
- 56:05both the overview and then peek at
- 56:07your own data, exciting early results.
- 56:09We look forward to seeing the full status.
- 56:11You have some time for questions
- 56:13and I see your hand. Matthias,
- 56:17Hello, thanks a lot for interesting talk.
- 56:20I have a question about the rationales
- 56:23on the neuroscientific level behind
- 56:25using psilocybin in cocaine dependence.
- 56:29We know that, you know,
- 56:32a lot of addictions including cocaine
- 56:35dependence are related mostly to the
- 56:38alternations in their dopaminergic
- 56:40circuit and psilocybin selectively
- 56:42interacting with the serotonin circuit.
- 56:45So how would it work on
- 56:47the on the brain level,
- 56:50I don't think we know.
- 56:51I mean I think you could say
- 56:53that it's probably disrupting
- 56:54the reward system in some way.
- 56:56It's probably disrupting the reward pathway.
- 56:58I mean I should say that I'm a
- 57:00clinical psychologist so I don't
- 57:01I don't really want to get into to
- 57:03that because I I'm probably you know
- 57:05speaking outside of my my wheelhouse.
- 57:07But I I mean I just think it's fair to
- 57:09know that we fair to say that we don't
- 57:11really know what's happening there.
- 57:12But for those of you who are interested
- 57:15maybe you we could get at a a better
- 57:17sense of what might be happening.
- 57:19But I think in general I would guess
- 57:21that that the the dopamine pathway,
- 57:23the reward system is somehow being disrupted.
- 57:30Maybe it is an interesting
- 57:31general question of whether the
- 57:33the treatment is going to reverse the
- 57:36original pathology or whether there's
- 57:39an interaction somewhere downstream,
- 57:41or whether the pathology sets up a
- 57:43feedback loop within the brain that
- 57:44evolves over time and the treatments
- 57:46interrupting that feedback like it.
- 57:47It's a it's a good hypothesis that the
- 57:49treatment is going to act on the dopamine
- 57:51system and reverse the original hypothesis,
- 57:52the original pathology.
- 57:53But it's not necessarily true.
- 57:55And it's sort of an interesting way
- 57:57to think about how treatments work in
- 57:58general is are they reversing pathology
- 58:00or are they or are they interacting
- 58:02at some downstream point to reverse
- 58:04consequences of the original pathology?
- 58:06Or are they allowing for some kind
- 58:08of new homeostasis that doesn't
- 58:10re achieve normality but rather
- 58:12compensates in some way to to achieve
- 58:14a a a new functional state?
- 58:16I don't, I don't know that there's
- 58:18any psychiatric condition where we
- 58:18know the answers to those questions,
- 58:20but it's an interesting way to
- 58:21frame the questions.
- 58:23I think so. And I think that question too,
- 58:25as to whether this opens up some sort of
- 58:27window of neuroplasticity in like the
- 58:29weeks that follow is really fascinating.
- 58:311. So I mean it could very well be
- 58:33that as Larry suggested back in
- 58:34the day that set and setting are
- 58:36crucial and it's not enough just to
- 58:39have an experience with the drug.
- 58:40It needs to be paired with the
- 58:41right sort of behavioral platform
- 58:43to really enact long term change.
- 58:45And I think there are a lot of questions
- 58:47that we can answer like that that we
- 58:48will answer in the years to come,
- 58:50but we just don't we know so little
- 58:51right now and it's it's so interesting
- 58:53because as many of you probably
- 58:55know we most drugs we we have some
- 58:57understanding of the mechanism first
- 58:58and then we evaluate the outcome.
- 58:59But here we're we're evaluating
- 59:01outcomes and and trying to figure out
- 59:03what the mechanism is as as we go.
- 59:05And that's likely because these drugs
- 59:07have been around for so long and humans
- 59:08have interacted with them for so long
- 59:10that we're kind of working in reverse.
- 59:13It's really fascinating to me,
- 59:14and I I would really like to know
- 59:15better what what's happening.
- 59:18To be fair, that's been true
- 59:19throughout the history of psychiatry,
- 59:20where we've discovered the drugs that
- 59:22have effects serendipitously and then
- 59:24work backwards to try to figure out why.
- 59:26Dream of a day where that won't
- 59:27be true for a new system.
- 59:28But that was true for lithium.
- 59:29It was true for tricyclics.
- 59:31It was true for antipsychotics.
- 59:34Yeah. And you
- 59:34know, I think in the case of like
- 59:37bupropion and smoking cessation,
- 59:39we still don't really know how it works.
- 59:40And it's been around for
- 59:41a pretty long time now.
- 59:47So one more question here.
- 59:50Yeah, actually there is plenty of
- 59:53evidence showing that this window of
- 59:56neuroplasticity is created by the psilocybin,
- 59:59mostly from the animal studies.
- 01:00:02But does it mean that if we have,
- 01:00:05let's say, in the treatment we
- 01:00:08have someone who's continue using
- 01:00:10cocaine or other drugs of abuse?
- 01:00:13We should stop using psilocybin for
- 01:00:17treating them because, you know,
- 01:00:20it may work against them if we create,
- 01:00:23if we enhance neuroplasticity, right.
- 01:00:26Could that actually somehow
- 01:00:28reinforce that behavior even further?
- 01:00:31That's a great, I mean,
- 01:00:32I I've thought about that many times over.
- 01:00:34Yeah. If if we see that people fall
- 01:00:36right back into their prior patterns
- 01:00:38that we somehow entrench that behavior.
- 01:00:40I I don't know,
- 01:00:45I don't I I I really don't know.
- 01:00:47I wish I had a good answer for you there.
- 01:00:49I think the like in in general I would say
- 01:00:51if if we're going to see an FDA indication
- 01:00:54for say treatment resistant depression,
- 01:00:56the big question I would have for my
- 01:00:59physician colleagues here is well like how
- 01:01:01are you going to use this in practice.
- 01:01:02So if someone comes to see you,
- 01:01:03they're depressed, you give them one dose,
- 01:01:05you don't really respond.
- 01:01:06And do you do this again?
- 01:01:08When do you increase the dose?
- 01:01:10Or maybe someone does respond nicely,
- 01:01:12but then maybe six months
- 01:01:13later they're saying they begin
- 01:01:14to feel depressed once more.
- 01:01:15What do you do in that case or in the case
- 01:01:17of let's say a substance use disorder,
- 01:01:19what do you do if someone doesn't seem
- 01:01:21to respond the first time around is
- 01:01:23right back to their prior pattern,
- 01:01:24you administer the drug again And if so,
- 01:01:26when and what dose?
- 01:01:27I think these are the most
- 01:01:28fascinating questions.
- 01:01:29And all I can really say for now is
- 01:01:31the studies that we're conducting are
- 01:01:33just very simple efficacy studies that
- 01:01:35are designed to really only show that
- 01:01:37the novel intervention in this case
- 01:01:38might have some impact on the outcome.
- 01:01:40But we also know there's a lot
- 01:01:42of variability and some people
- 01:01:43respond and some people don't.
- 01:01:44And, you know,
- 01:01:46I think we're only just beginning
- 01:01:48to understand how how these drugs
- 01:01:49work and under what circumstances
- 01:01:51they're beneficial and under what
- 01:01:52circumstances they might be harmful.
- 01:01:56Yeah, you know, I was thinking right
- 01:01:58now we have very small samples in all
- 01:02:01the trials and addictions, you know,
- 01:02:03like the study of Bogan Schultz
- 01:02:04in alcoholism disorder and so on.
- 01:02:07But if we know already that it
- 01:02:09works pretty well in depression
- 01:02:11treatment and all those disorders
- 01:02:13related to the serotonin system,
- 01:02:16maybe it just helps with comorbidity.
- 01:02:20And then, you know, if someone,
- 01:02:24there is a high comorbidity among those who
- 01:02:27are addicted mostly with the depression,
- 01:02:29anxiety disorders here.
- 01:02:31So if we help them with depression,
- 01:02:33then they can cope better
- 01:02:35with addiction and so on.
- 01:02:37So yeah, but it's hard to really
- 01:02:40test it without the big, big,
- 01:02:42big trials.
- 01:02:44And regarding the previous question,
- 01:02:46I think you know,
- 01:02:47without understanding the mechanism,
- 01:02:48we can't really formulate any,
- 01:02:52any guidelines for the treatment.
- 01:02:56Yeah, right. I I will say that you know the,
- 01:02:59the theory of addiction that
- 01:03:00I operate from is Tim Baker's
- 01:03:04theory of affective modulation.
- 01:03:07In other words, that the use of addictive
- 01:03:11drugs is motivated by the desire
- 01:03:13to escape or avoid negative affect.
- 01:03:15So in other words, it's a sort of
- 01:03:18maladaptive coping response to anger,
- 01:03:20irritability, sadness, anxiety.
- 01:03:21One would smoke or drink or use cocaine,
- 01:03:25whatever it might be,
- 01:03:26to deal with these emotions.
- 01:03:28And the key, of course,
- 01:03:29in sobriety is to find more adaptive
- 01:03:32ways of coping with those emotions.
- 01:03:34So if at the core of this is just,
- 01:03:37you know, more effective affect regulation,
- 01:03:41it would,
- 01:03:42it would make sense that there's
- 01:03:44a transdiagnostic mechanism here.
- 01:03:45Some people have suggested that there's
- 01:03:47something around experiential avoidance.
- 01:03:48So, you know,
- 01:03:49could be that people are just more
- 01:03:50willing to deal with these negative
- 01:03:51emotions rather than escape or avoid them.
- 01:03:53But again, I think I'd really like
- 01:03:55to understand better what they are.
- 01:03:57And sometimes I I I wonder if you know,
- 01:04:00we'll we'll answer those questions
- 01:04:01in my lifetime because these these
- 01:04:02things seem to take a very long
- 01:04:04time to get at
- 01:04:11Jenna. Yeah. I thank
- 01:04:13you so much for the talk by the
- 01:04:15way and apologies for my bad zoom
- 01:04:17etiquette upon entering the meeting.
- 01:04:18I hope it wasn't too much of A distraction.
- 01:04:21I was really curious about this idea
- 01:04:23that you were talking about about self
- 01:04:25reference and the kind of attentional scope.
- 01:04:27And I saw that you were doing MRI scans and
- 01:04:29I would assume that there's some sort of DMN,
- 01:04:31self reference kind of network
- 01:04:33stuff you're looking at.
- 01:04:34I was curious like if you're thinking
- 01:04:37or if you did anything or what you
- 01:04:39think about kind of like qualitative
- 01:04:40analysis of self reference and what's
- 01:04:43going on there during the experience,
- 01:04:45after the experience thinking
- 01:04:46about like the role of integration
- 01:04:48and psychedelic studies thus far.
- 01:04:50And obviously this kind of like you know,
- 01:04:53self reference rumination kind of
- 01:04:54stuff is is big and in terms of
- 01:04:56the transdiagnostic stuff as well.
- 01:04:58So not a super directed question,
- 01:05:00but I'm curious to hear you say
- 01:05:01a little bit more about that.
- 01:05:05Yeah. So getting that is not easy.
- 01:05:10We we did include the dispositional
- 01:05:13positive emotion scale which
- 01:05:15includes an awe subscale.
- 01:05:17So I really do think that awe might
- 01:05:19be at least playing a role in the
- 01:05:22acute effects with with the emotion
- 01:05:24awe being described as that that
- 01:05:27you experience in the presence of
- 01:05:29a a stimulus that's so large and
- 01:05:31outside of your understanding that
- 01:05:33that you you feel very small and
- 01:05:36you you you change the way you
- 01:05:37view reality in some way, right.
- 01:05:39So it's it's like seeing the night sky
- 01:05:41for the first time every star in the
- 01:05:43sky or seeing the ocean for the first time.
- 01:05:45It's just wow you were so absorbed by what's
- 01:05:50in front of you that you forget yourself.
- 01:05:52But you are again very present to
- 01:05:54the experience and that perhaps that
- 01:05:56experience can carry forward after
- 01:05:58the acute experience has ended.
- 01:06:01Meaning you were you were I might
- 01:06:03guess less likely to have a a more
- 01:06:05self oriented experience and and
- 01:06:07maybe there's a way that awe can
- 01:06:10build upon itself and people seek
- 01:06:12out experiences in which they again
- 01:06:14feel small and have moments of
- 01:06:17of wonder and and they feel some
- 01:06:20little sense of transcendence.
- 01:06:22And I think people can achieve these
- 01:06:25experiences in nature and religious
- 01:06:27observations and meditation.
- 01:06:28And so I mean to get at your question
- 01:06:30I think we might be able to capture
- 01:06:32if there's maybe a long term effect
- 01:06:35by determining if if generally awe as
- 01:06:37a dispositional emotion is something
- 01:06:39that is increased over time to to
- 01:06:42get though like qualitatively
- 01:06:43what people might say
- 01:06:49there. I I I think what's so
- 01:06:50interesting about the emotion, Oz,
- 01:06:52it appears to be a a uniquely social
- 01:06:54emotion that is one that's designed
- 01:06:56to encourage humans to think a
- 01:06:59little less about ourselves and more
- 01:07:01about the people in our collective.
- 01:07:03And I I feel that for many people,
- 01:07:06the experience, not all but for many,
- 01:07:08is characterized by this,
- 01:07:10this really difficult awareness that their
- 01:07:14drug use has harmed people they really love,
- 01:07:18like, and and this can be really upsetting.
- 01:07:21And this might in in fact be
- 01:07:24responsible for part of that challenge.
- 01:07:26People will realize I haven't talked to
- 01:07:29parents or siblings or children for years.
- 01:07:31I've ruined relationships.
- 01:07:33I've alienated, you know,
- 01:07:34family members because I've
- 01:07:36been so fixated on cocaine.
- 01:07:38And I just feel so awful, so awful.
- 01:07:41But you know what?
- 01:07:43I still have a chance to write
- 01:07:45things and I'm going forward
- 01:07:46going to try to be a much better,
- 01:07:48you know,
- 01:07:49spouse and sibling and parent
- 01:07:51and citizen of humanity.
- 01:07:53And so I think there might be some longer
- 01:07:55term impacts on altruistic behavior.
- 01:07:57We're trying to capture that also
- 01:07:59and maybe at the core of it is also
- 01:08:01the degree to which people are are
- 01:08:03more integrated with their community
- 01:08:05because in the extreme addiction can
- 01:08:07be just the state of complete isolation
- 01:08:09from those in in your environment.
- 01:08:12So we're trying to capture that that
- 01:08:13you know self report is limited.
- 01:08:15We we do some degree of qualitative research.
- 01:08:17I don't think of myself as a qualitative
- 01:08:19scientist but we we will have some
- 01:08:21qualitative data to try to capture that.
- 01:08:22And I I I think that will really
- 01:08:25reveal something at least to the I
- 01:08:26I do think people seem to be more
- 01:08:28aware of their their the people
- 01:08:30they love and how their behavior
- 01:08:31impacts those they love.
- 01:08:32And and you know it's again it's I may
- 01:08:34mention this but it's it seems very
- 01:08:36similar to the Ebenezer Scrooge experience.
- 01:08:38You're like oh man,
- 01:08:39I've been such a greedy miser that
- 01:08:41I've hurt people I really love.
- 01:08:43And that feels terrible.
- 01:08:44But I want to be better going forward.
- 01:08:48That was a little jumbled.
- 01:08:49But I hope that was helpful.
- 01:08:52All right.
- 01:08:55You
- 01:09:00know I I would teach undergraduates.
- 01:09:02So I'm I'm used to awkward silences.
- 01:09:04I can I can just sit here forever.
- 01:09:06But feel free. Any more questions,
- 01:09:09I'm happy to take
- 01:09:11Any final questions for Peter
- 01:09:12before we shut down for the day.
- 01:09:15Yeah, so I'm just wondering with you know
- 01:09:18such a broad portfolio of psychedelic
- 01:09:21substances why you chose psilocybin?
- 01:09:24I love that question,
- 01:09:28Few reasons, broad portfolio,
- 01:09:31broad portfolio, I don't know,
- 01:09:33I mean we need substantial enough data
- 01:09:36that the FDA would feel comfortable in
- 01:09:39our administering these drugs to people.
- 01:09:41So we need, you know,
- 01:09:42substantial animal data and and safety data.
- 01:09:48Yeah, there are a lot of substances
- 01:09:49in like T call or P call,
- 01:09:50but many of them have almost
- 01:09:52no data whatsoever that would
- 01:09:54satisfy the FDA's requirements.
- 01:09:55We do with psilocybin.
- 01:09:57We do, I think with mescaline and LSD.
- 01:10:00Mescaline and LSD last 10, maybe 14 hours.
- 01:10:04Psilocybin lasts 4 to 6.
- 01:10:05So if we want to fit in a a
- 01:10:07psilocybin session in a standard
- 01:10:09work day that can be done.
- 01:10:10We can't do that with LSD or mescaline.
- 01:10:12That's one thing I'm thinking.
- 01:10:14I think also early on there was
- 01:10:16this concern that if we were doing
- 01:10:18a study with LSD that, you know,
- 01:10:20too many people would recognize
- 01:10:21what we were doing.
- 01:10:22They'd they'd see we were doing
- 01:10:23a study with acid.
- 01:10:23It would sound crazy.
- 01:10:25We'd attract more attention than we
- 01:10:26wanted to from especially maybe like
- 01:10:28more conservative political figures.
- 01:10:30So if we chose psilocybin,
- 01:10:32you know, early on,
- 01:10:33most people never heard of it.
- 01:10:34Even a number of my physician colleagues
- 01:10:35here at UAB didn't know what it was.
- 01:10:37And I thought, well, that's good.
- 01:10:38I don't want people to know.
- 01:10:40So I think there's that too.
- 01:10:42But now we see the field is
- 01:10:44moving toward other compounds
- 01:10:45like 5 in the ODMT and the DMT.
- 01:10:47And the big advantage there is
- 01:10:49they're shorter acting and and
- 01:10:50might be more scalable and and
- 01:10:51I think that's that's a really
- 01:10:53important thing that we're doing.
- 01:10:54But early on,
- 01:10:55it was just that we had substantial data
- 01:10:57that would satisfy FDA requirements.
- 01:10:59We could give to the people and we
- 01:11:01could do it in a standard work day.
- 01:11:03Pretty much as simple as that.
- 01:11:07Well, thank you. Yeah,
- 01:11:11I should have mentioned too,
- 01:11:11before I started, You know,
- 01:11:12my my my grandparents lived in Branford and
- 01:11:15I grew up sailing in the Long Island Sound,
- 01:11:18and they never wanted to take me to New Haven
- 01:11:20because they thought it was so dangerous.
- 01:11:21So I've I've never actually been to
- 01:11:23New Haven, but I've been to Branford.
- 01:11:24And they they they died.
- 01:11:26They lived into their 90s.
- 01:11:28But, you know,
- 01:11:28I'm glad to be talking to a group at Yale.
- 01:11:31I kind of feel like it's a
- 01:11:33homecoming of some sort,
- 01:11:34even though I've never actually
- 01:11:35been to New Haven.
- 01:11:36Well,
- 01:11:36maybe next. Maybe next time we
- 01:11:38can have you up. Sure. Sure.
- 01:11:39In person. And it's much,
- 01:11:41it's much better now than it was when
- 01:11:44your grandparents were young. They
- 01:11:46were old grandparents from the South,
- 01:11:47and they thought everything
- 01:11:48was dangerous. So that's fine.
- 01:11:50Well, thank you so much as you you,
- 01:11:52as I said, you took a beautiful
- 01:11:54combination of of history, of some
- 01:11:55theory and then some exciting new data.
- 01:11:57So thank you for sharing this with us.
- 01:12:00Thank you and thank you
- 01:12:01everyone for being here.
- 01:12:02We look forward to seeing you all at
- 01:12:03our December meeting, which as I said,
- 01:12:05will be about the USUNA depression study,
- 01:12:06one of the biggest clinical trials
- 01:12:09that's been done in this space,
- 01:12:11#11 had a good presentation
- 01:12:12and a good conversation,
- 01:12:13then we'll see you then.
- 01:12:14Happy Thanksgiving.
- 01:12:18Thank you, Peter. Thank you.