Peter Hendricks, PhD. November 2023

November 22, 2023

Information

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.

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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.