back to index

Dr. Matthew Johnson: Psychedelics for Treating Mental Disorders | Huberman Lab Podcast #38



link |
00:00:00.000
Welcome to the Huberman Lab Podcast,
link |
00:00:02.240
where we discuss science and science-based tools
link |
00:00:04.880
for everyday life.
link |
00:00:09.320
I'm Andrew Huberman,
link |
00:00:10.320
and I'm a professor of neurobiology and ophthalmology
link |
00:00:13.000
at Stanford School of Medicine.
link |
00:00:15.040
Today, I have the pleasure of introducing
link |
00:00:16.700
Dr. Matthew Johnson.
link |
00:00:18.720
Dr. Johnson is a professor of psychiatry
link |
00:00:20.800
at Johns Hopkins School of Medicine,
link |
00:00:22.940
where he also directs the Center for Psychedelic
link |
00:00:25.160
and Consciousness Research.
link |
00:00:27.280
As many of you know,
link |
00:00:28.520
there's extreme excitement about the use of psychedelics
link |
00:00:31.360
for the treatment of various disorders of the mind.
link |
00:00:33.980
Dr. Johnson's laboratory is among the premier laboratories
link |
00:00:37.000
in the world understanding how these compounds work,
link |
00:00:40.240
how things like psilocybin and LSD and related compounds
link |
00:00:44.280
allow neural circuitry in the brain to be shaped and change
link |
00:00:47.800
such that people can combat diseases like depression
link |
00:00:51.600
or trauma or other disorders of the mind
link |
00:00:53.960
that cause tremendous suffering.
link |
00:00:55.840
Dr. Johnson is also an expert in understanding
link |
00:00:58.120
how different types of drugs impact
link |
00:01:00.120
different types of human behaviors,
link |
00:01:02.040
such as sexual behavior, risk-taking, and crime.
link |
00:01:05.600
Dr. Johnson and his work have also been featured prominently
link |
00:01:08.520
in the popular press,
link |
00:01:10.000
such as articles in the New York Times
link |
00:01:12.080
and Michael Pollan's book, How to Change Your Mind,
link |
00:01:14.200
and in a feature in 60 Minutes about psychedelics
link |
00:01:16.960
and the new emerging science of psychedelic therapies
link |
00:01:20.080
for treating mental disorders.
link |
00:01:22.400
During the course of today's conversation,
link |
00:01:24.520
Dr. Johnson and I talk about psychedelics
link |
00:01:27.280
at the level of what's called microdosing,
link |
00:01:29.800
whether or not it is useful for the treatment
link |
00:01:31.880
of any mental disorders.
link |
00:01:33.480
We also talk about more typical macrodosing,
link |
00:01:35.960
what those macrodoses entail,
link |
00:01:37.720
and he walks us through what an experiment
link |
00:01:41.000
of a patient taking psychedelics
link |
00:01:42.600
for the treatment of depression looks like
link |
00:01:44.460
in his laboratory from start to finish.
link |
00:01:47.040
The conversation was an absolutely fascinating one
link |
00:01:49.740
for me to partake in.
link |
00:01:51.120
I learned so much about the past, present, and future
link |
00:01:54.800
of psychedelic treatments and compounds.
link |
00:01:57.160
And indeed, I hope to have Dr. Johnson
link |
00:01:58.800
on this podcast again in the not too distant future
link |
00:02:01.840
so that we can talk about other compounds
link |
00:02:04.160
that powerfully impact the mind and human behavior,
link |
00:02:07.280
and perhaps can also be used to treat various diseases.
link |
00:02:10.660
Before we begin, I'd like to emphasize
link |
00:02:12.520
that this podcast is separate
link |
00:02:13.780
from my teaching and research roles at Stanford.
link |
00:02:16.200
It is, however, part of my desire and effort
link |
00:02:18.400
to bring zero cost to consumer information about science
link |
00:02:21.160
and science-related tools to the general public.
link |
00:02:23.920
In keeping with that theme,
link |
00:02:25.000
I'd like to thank the sponsors of today's podcast.
link |
00:02:27.840
Our first sponsor is Athletic Greens.
link |
00:02:30.240
Athletic Greens is an all-in-one
link |
00:02:32.000
vitamin mineral probiotic drink.
link |
00:02:34.400
I've been taking Athletic Greens since 2012,
link |
00:02:37.040
and so I'm delighted that they're sponsoring the podcast.
link |
00:02:39.800
The reason I started taking Athletic Greens,
link |
00:02:41.720
and the reason I still take Athletic Greens
link |
00:02:43.560
once or twice a day, every day,
link |
00:02:45.480
is because it covers my foundational nutritional needs.
link |
00:02:48.800
It has the vitamins I need, the minerals I need,
link |
00:02:50.760
and the probiotics are important to me
link |
00:02:52.920
because there is now so much data
link |
00:02:55.120
about the importance of the so-called gut microbiome,
link |
00:02:57.760
maintaining healthy gut bacteria,
link |
00:03:00.000
and the ways in which those gut bacteria
link |
00:03:01.840
impact things like inflammation
link |
00:03:03.800
and keeping inflammation down in the brain and body,
link |
00:03:06.460
as well as supporting things like quality mood,
link |
00:03:08.800
endocrine function, metabolic function,
link |
00:03:10.520
just so many factors.
link |
00:03:11.960
The great thing about Athletic Greens
link |
00:03:13.600
is that it also tastes very good.
link |
00:03:14.960
I mix mine with water, a little bit of lemon juice,
link |
00:03:16.840
and as I mentioned, I drink that once or twice a day.
link |
00:03:20.360
If you'd like to try Athletic Greens,
link |
00:03:21.760
you can go to athleticgreens.com slash Huberman,
link |
00:03:24.800
and if you do that, you'll get the Athletic Greens,
link |
00:03:27.100
plus you'll get five free travel packs.
link |
00:03:29.720
The travel packs make it very easy
link |
00:03:31.080
to mix up Athletic Greens when you're on the road,
link |
00:03:33.160
in the car, on the plane, et cetera,
link |
00:03:35.040
and you'll get a year supply of vitamin D3, K2.
link |
00:03:38.640
There's now a lot of evidence that vitamin D3 and K2
link |
00:03:41.080
are important for various aspects of metabolic health,
link |
00:03:44.000
cardiac health, and so forth.
link |
00:03:45.640
So once again, that's athleticgreens.com slash Huberman
link |
00:03:49.060
to get Athletic Greens, the five free travel packs,
link |
00:03:51.740
and your year supply of vitamin D3 and K2.
link |
00:03:54.880
Today's podcast is also brought to us by Inside Tracker.
link |
00:03:58.380
Inside Tracker is a personalized nutrition platform
link |
00:04:00.840
that analyzes data from your blood and DNA
link |
00:04:03.400
to help you better understand your body
link |
00:04:05.280
and help you reach your health goals.
link |
00:04:07.360
I've long been a believer in getting regular blood work done
link |
00:04:10.360
and now with the advent of quality DNA tests,
link |
00:04:12.800
you can get a lot of information about your genetics
link |
00:04:15.280
and how that also impacts your immediate
link |
00:04:17.700
and long-term health.
link |
00:04:19.120
The reason I'm such a fan of getting blood work done
link |
00:04:21.320
is that it is really the only way to understand
link |
00:04:23.800
what's going on in your system at a level
link |
00:04:25.960
that can really inform your decisions
link |
00:04:27.820
about your immediate and long-term health.
link |
00:04:30.440
The problem with a lot of blood and DNA tests, however,
link |
00:04:33.120
is that you get numbers back about your hormones
link |
00:04:35.400
and your metabolic factors, et cetera,
link |
00:04:36.940
but you don't know what to do with that information.
link |
00:04:39.080
With Inside Tracker, they have a very easy to use dashboard
link |
00:04:42.400
that gives you that information
link |
00:04:43.800
and then gives you some suggestions and directives
link |
00:04:46.400
about things you could change about your nutrition,
link |
00:04:48.680
about your exercise and other lifestyle factors
link |
00:04:50.880
that can help you move those numbers in the direction
link |
00:04:53.320
that's best for you and for your health.
link |
00:04:55.640
If you'd like to try Inside Tracker,
link |
00:04:57.100
you can go to insidetracker.com slash Huberman
link |
00:05:00.360
to get 25% off any of Inside Tracker's plans.
link |
00:05:03.160
Just use the code Huberman at checkout.
link |
00:05:05.760
Today's podcast is also brought to us by Belcampo.
link |
00:05:08.840
Belcampo is a regenerative farm in Northern California
link |
00:05:11.500
that raises organic, grass-fed
link |
00:05:13.400
and finished certified humane meats.
link |
00:05:16.120
I eat meat about once a day.
link |
00:05:17.760
In general, my lunch or my breakfast
link |
00:05:20.280
consists of some meat
link |
00:05:21.880
and that meat has to be a very high quality.
link |
00:05:23.640
And generally I'll eat some vegetable as well.
link |
00:05:25.640
And then I tend to eat pastas and rice
link |
00:05:27.660
and things of that sort later in the day or in the evening
link |
00:05:30.240
in order to facilitate the transition to sleep.
link |
00:05:32.720
So I'm eating meat about once a day.
link |
00:05:34.800
And I always insist that the meat that I eat
link |
00:05:37.320
be of the very highest quality
link |
00:05:38.840
and that the animals were raised and maintained humanely.
link |
00:05:42.260
While conventionally raised animals
link |
00:05:43.680
are confined to feed lots
link |
00:05:44.840
and eat a diet of inflammatory grains,
link |
00:05:46.960
Belcampo's animals graze on open pastures
link |
00:05:49.280
and seasonal grasses,
link |
00:05:50.640
resulting in meat that's higher in nutrients
link |
00:05:52.440
and healthy fats.
link |
00:05:54.000
In addition, they raise their animals
link |
00:05:55.480
in a way that's not just better for our health,
link |
00:05:57.560
but also has a positive impact on the environment.
link |
00:06:00.340
They practice regenerative agriculture,
link |
00:06:02.000
which means the meat is climate positive
link |
00:06:04.100
and carbon negative.
link |
00:06:05.320
So you can feel good about what you're eating
link |
00:06:06.880
at the environmental level and for sake of your health.
link |
00:06:09.960
You can order Belcampo's sustainably raised meats
link |
00:06:12.120
to be delivered to you by using my code Huberman
link |
00:06:14.600
at belcampo.com slash Huberman
link |
00:06:17.100
and entering my code Huberman to get 20% off
link |
00:06:20.040
your first time order.
link |
00:06:21.760
I'm partial to the ribeyes or the New York steaks.
link |
00:06:24.640
So on one day I might have a ribeye,
link |
00:06:26.040
the next day I might have a New York steak.
link |
00:06:27.560
I also really like the meatballs.
link |
00:06:29.240
I'm a particular fan of the meatballs.
link |
00:06:31.160
So again, that's belcampo.com slash Huberman
link |
00:06:34.520
and enter the code Huberman at checkout
link |
00:06:36.760
to get 20% off your order.
link |
00:06:39.120
And now my conversation with Dr. Matthew Johnson.
link |
00:06:42.580
Well, Matthew, I've been looking forward
link |
00:06:43.800
to this for a long time.
link |
00:06:44.960
I'm a huge fan of your scientific work
link |
00:06:48.440
and I'm eager to learn from you.
link |
00:06:50.600
Likewise, big fan and happy to do this with you.
link |
00:06:53.600
Great, well, thank you.
link |
00:06:55.340
My first question is a very basic one,
link |
00:06:57.280
which is what is a psychedelic?
link |
00:07:00.080
We hear this term all the time,
link |
00:07:01.440
but what qualifies a substance as a psychedelic?
link |
00:07:05.880
Nomenclature is a real challenge
link |
00:07:09.240
in this area of psychedelics.
link |
00:07:10.760
So starting with the word psychedelic,
link |
00:07:12.780
it just, if you're a pharmacologist,
link |
00:07:16.000
it's not very satisfying
link |
00:07:18.040
because that term really spans
link |
00:07:21.160
different pharmacological classes.
link |
00:07:23.440
In other words, if you're really concerned
link |
00:07:24.920
about receptor effects and the basic effects of a compound,
link |
00:07:29.080
it spans several classes of compounds.
link |
00:07:32.680
But overall, so it's really more of a cultural term
link |
00:07:37.080
or it does have a relationship to drug effects,
link |
00:07:42.080
but it's at a very high level.
link |
00:07:44.880
So all of the so-called psychedelics
link |
00:07:47.020
across these distinct classes that I can talk more about,
link |
00:07:54.160
the way I put it is they all have the ability
link |
00:07:56.480
to profoundly alter one's sense of reality.
link |
00:08:00.520
And that can mean many things.
link |
00:08:02.080
Part of that is profoundly altering the sense of self
link |
00:08:05.560
acutely, so when someone's on the psychedelic.
link |
00:08:09.560
So the different classes that can be,
link |
00:08:13.160
the specific pharmacological classes
link |
00:08:15.640
that can be called a psychedelic
link |
00:08:17.640
are one, what are called the classic psychedelics.
link |
00:08:21.200
So in the literature, you'll see that term.
link |
00:08:23.080
And hallucinogen and psychedelic
link |
00:08:25.960
are all have traditionally been used synonymously.
link |
00:08:29.640
I think there was a little of a tendency
link |
00:08:31.320
to stay away from psychedelics as the baggage,
link |
00:08:33.380
but there's been a return to that in the last several years.
link |
00:08:36.820
But the classic psychedelics or classic hallucinogens
link |
00:08:39.440
are things like LSD, psilocybin,
link |
00:08:44.160
which is in so-called magic mushrooms.
link |
00:08:47.160
It's in over 200 species that we know of so far
link |
00:08:50.120
of mushrooms, dimethyltryptamine or DMT,
link |
00:08:53.800
which is in dozens and dozens of plants,
link |
00:08:58.080
mescaline, which is in the peyote cacti
link |
00:09:01.000
and some other cacti like San Pedro.
link |
00:09:03.720
And even amongst these classic psychedelics,
link |
00:09:06.460
there are two structural classes.
link |
00:09:10.860
So that's the chemistry.
link |
00:09:11.820
There's the tryptamine-based compounds
link |
00:09:13.960
like psilocybin and DMT.
link |
00:09:16.180
And then there's the phenethylamine-based compounds.
link |
00:09:19.260
So these are the two basic building blocks
link |
00:09:23.020
that you're starting from,
link |
00:09:24.300
either a tryptamine structure or a phenethylamine structure.
link |
00:09:27.980
But that's just the chemistry.
link |
00:09:29.660
All of the, what's more important,
link |
00:09:32.260
or at least to someone like me,
link |
00:09:34.620
are the receptor effects.
link |
00:09:35.980
And then ultimately that's going to have a relationship
link |
00:09:38.060
to the behavioral and subjective effects.
link |
00:09:39.980
So all of these classic psychedelics serve as agonists
link |
00:09:43.460
or partial agonists at the serotonin 2A receptor,
link |
00:09:47.100
so subtype of serotonin receptor.
link |
00:09:49.860
Then you have these other classes of compounds
link |
00:09:54.500
that you could call psychedelic.
link |
00:09:56.660
Another big one would be the NMDA antagonist.
link |
00:09:59.240
So this would include ketamine, PCP, and dextromethorphan,
link |
00:10:03.460
something I've done some research with,
link |
00:10:04.900
which folks might recognize from like robo-tripping,
link |
00:10:07.740
guzzling, like, you know, call syrup,
link |
00:10:11.740
which is something kind of like high school kids
link |
00:10:13.840
are known to do and they can't get ahold of real drugs,
link |
00:10:16.060
that type of thing.
link |
00:10:17.380
So a large overlap in the types of subjective effects
link |
00:10:23.020
that you get from those compounds
link |
00:10:24.580
compared to the 2A agonist classic psychedelics.
link |
00:10:29.100
But then you have, and by the way,
link |
00:10:31.500
this description, this framework I'm describing,
link |
00:10:33.900
not everyone will agree.
link |
00:10:35.340
Some people will say,
link |
00:10:36.380
no, psychedelic only means classic psychedelic.
link |
00:10:40.040
So there's different opinions here.
link |
00:10:41.540
But you have, gosh, salvinorin A,
link |
00:10:43.860
which is a kappa opioid agonist, which again-
link |
00:10:48.340
Where does that come from?
link |
00:10:49.620
Salvia divinorum.
link |
00:10:51.020
It's a plant that became 20 years ago.
link |
00:10:53.180
It sort of popped onto the legal high scene.
link |
00:10:56.100
And there's a long history of this.
link |
00:10:58.540
Predating the internet, going back to like the stuff
link |
00:11:00.880
that went good or in the back of High Times Magazine.
link |
00:11:03.900
And most of this stuff like never worked, you know?
link |
00:11:06.260
It's like, smoke enough of anything,
link |
00:11:07.980
maybe you get a little bit lightheaded.
link |
00:11:09.740
But this is one of those things that popped around
link |
00:11:12.300
20 years ago when it quickly got the reputation of like,
link |
00:11:15.020
holy shit, this stuff actually works
link |
00:11:17.260
and works really strongly.
link |
00:11:19.420
And these smoked extracts particularly,
link |
00:11:21.520
people have these reality altering experiences
link |
00:11:25.620
on par with smoked DMT, the classic psychedelic.
link |
00:11:29.500
So often, and we did the first blinded,
link |
00:11:32.300
controlled human research with salvinorin A.
link |
00:11:34.300
So lots of entity contact.
link |
00:11:37.020
So feeling that you, in the experience of one,
link |
00:11:39.800
is actually interacting with autonomous beings,
link |
00:11:43.460
that type of thing.
link |
00:11:44.980
And then you have another big one,
link |
00:11:46.820
I probably should have mentioned even before the,
link |
00:11:48.620
you know, salvinorin A, but you have MDMA,
link |
00:11:51.820
which really stands in a class by itself.
link |
00:11:53.900
So it's been called an entactogen and-
link |
00:11:57.260
What does that mean?
link |
00:11:58.800
It means like, touching within.
link |
00:12:01.820
It sort of eludes the idea that it can really put someone
link |
00:12:04.860
in touch with their emotions.
link |
00:12:07.460
It's also been called an empathogen,
link |
00:12:09.500
meaning can it can afford empathy.
link |
00:12:12.660
But I think entactogen is probably,
link |
00:12:14.240
that's the term that I tend to focus on.
link |
00:12:17.220
And I know I'm not telling you anything you don't know,
link |
00:12:19.780
but for the viewers, the primary mechanism of MDMA
link |
00:12:25.620
is serotonin release.
link |
00:12:27.920
And to a degree, other monoamine release,
link |
00:12:31.060
dopamine, serotonin.
link |
00:12:32.780
And so structurally, that's also in the phenethylamine class
link |
00:12:37.620
which contains mescaline, the classic psychedelic,
link |
00:12:42.140
but also amphetamine.
link |
00:12:43.660
So just like Adderall is in that phenethylamine class.
link |
00:12:49.380
And so this is another example
link |
00:12:50.540
where chemistry doesn't dictate.
link |
00:12:52.060
I mean, you can tweak a molecule,
link |
00:12:53.940
it might have that same basic structure,
link |
00:12:56.620
but now you've profoundly changed the way
link |
00:12:58.300
it interacts with the receptor.
link |
00:12:59.540
So MDMA does not exert its actions
link |
00:13:05.540
by, I like to say, by mimicking the baseball,
link |
00:13:11.060
entering the postsynaptic receptor side,
link |
00:13:16.380
acting as an agonist.
link |
00:13:17.480
So mimicking the endogenous neurotransmitter serotonin,
link |
00:13:23.100
like the classic psychedelics do,
link |
00:13:25.180
MDMA works on the pitcher side
link |
00:13:27.380
of just basically throwing out more of the natural,
link |
00:13:30.900
the endogenous.
link |
00:13:31.740
Dumping more serotonin.
link |
00:13:32.580
Dumping more serotonin, flooding the synapse.
link |
00:13:35.940
So I get the impression that the psychedelic space
link |
00:13:39.500
is a enormous cloud of partially overlapping compounds.
link |
00:13:43.460
Right.
link |
00:13:44.300
Meaning some are impacting the serotonin system
link |
00:13:46.660
more than the dopamine system.
link |
00:13:47.900
Others are impacting the dopamine system
link |
00:13:50.180
more than the serotonin system.
link |
00:13:52.840
Given that the definition of a psychedelic
link |
00:13:55.100
is that it profoundly alters sense of self,
link |
00:13:59.180
at least that's included as a partial definition.
link |
00:14:03.180
Can we break that down into a couple of subcategories?
link |
00:14:06.500
So for instance, hallucinating, either auditory or visual.
link |
00:14:12.260
Synesthesia, perceptual blending,
link |
00:14:14.840
the sense that you can hear colors and see sounds,
link |
00:14:19.980
for instance, a common report of people
link |
00:14:22.660
that take psychedelics in sufficiently high doses.
link |
00:14:26.480
So hallucinating, synesthesia,
link |
00:14:28.880
and then in terms of sense of self,
link |
00:14:32.080
you know, as a neuroscientist, I think,
link |
00:14:34.020
okay, what does it mean to alter a sense of reality?
link |
00:14:36.800
Really what the brain does in a very coarse way
link |
00:14:41.900
is to try and figure out what's happening in space,
link |
00:14:45.060
physical space, and that physical space could be within us
link |
00:14:47.740
or outside us, and what's happening in time.
link |
00:14:50.060
Right.
link |
00:14:50.900
And as a vision scientist, the simplest explanation
link |
00:14:54.100
is when I move my hand from one location to another location,
link |
00:14:57.180
it's measuring the space,
link |
00:14:58.820
the location of my hand in space over time.
link |
00:15:01.260
And then you get a rate and a speed
link |
00:15:03.220
and all that kind of stuff, right?
link |
00:15:04.420
Yeah.
link |
00:15:05.880
That gets more complicated
link |
00:15:06.820
as you get into the emotional realm.
link |
00:15:09.860
But is it fair to say that psychedelics
link |
00:15:12.060
are impacting the space time analysis
link |
00:15:15.780
that the brain is performing
link |
00:15:16.980
and thereby creating hallucinations
link |
00:15:19.620
and thereby altering, you know, the blending of senses?
link |
00:15:25.940
Is it fair to say that?
link |
00:15:28.500
I think it's fair to explore that area.
link |
00:15:31.140
And here's what I'm thinking.
link |
00:15:32.620
The clearly there is a changed relationship,
link |
00:15:36.600
certainly at the right dose of orientation and space time.
link |
00:15:42.080
I think as a, you know, I'm primarily a behaviorist
link |
00:15:46.100
and in terms of human behavioral pharmacology,
link |
00:15:49.400
I always go to comparative pharmacology.
link |
00:15:51.620
Okay, what can we say that is it truly unique
link |
00:15:54.220
about the classic psychedelic or psychedelics in general?
link |
00:15:57.420
So with that description, I'm thinking, okay,
link |
00:16:00.260
alcohol can really screw up your, you know,
link |
00:16:03.140
time-space orientation.
link |
00:16:05.300
And proprioception, your balance.
link |
00:16:06.140
Proprioception.
link |
00:16:06.980
Your vestibular, yeah.
link |
00:16:07.820
You know, and in many ways,
link |
00:16:10.100
and sort of in those gross motorways, like far worse,
link |
00:16:12.980
you know, of course everything's dose dependent,
link |
00:16:14.600
but in the classic psychedelics, you know,
link |
00:16:16.220
obviously the benzodiazepines being very similar alcohol,
link |
00:16:18.660
same thing.
link |
00:16:19.500
So, you know, I'd want to, you know,
link |
00:16:22.860
dig in a little more in terms of like,
link |
00:16:25.140
maybe there's something more specific we could say
link |
00:16:27.380
about that relationship to time and space
link |
00:16:31.620
that the psychedelics are tinkering with,
link |
00:16:33.740
but I'm not sure.
link |
00:16:34.660
It's an interesting hypothesis that the idea
link |
00:16:36.760
that that's a mediator, that that's something,
link |
00:16:39.020
that there's something fundamental about changing that,
link |
00:16:42.360
the representation in time and space.
link |
00:16:45.980
There might be something to that.
link |
00:16:49.200
I mean, I think of these as psychedelics
link |
00:16:51.740
as profoundly altering models, you know,
link |
00:16:55.720
we're all, you know, we're prediction machines
link |
00:16:58.780
and that's large, so much of that is top-down
link |
00:17:02.640
and psychedelics have a good way of, you know,
link |
00:17:08.240
loosely speaking, dissolving those models.
link |
00:17:11.520
And one of the reality-
link |
00:17:13.360
Can you give us an example of one of like a model,
link |
00:17:15.520
like I know that when I throw a ball in the air,
link |
00:17:18.800
it falls down, not up.
link |
00:17:21.320
That's a prediction that I learned as a child
link |
00:17:23.960
that I did not come into the world with a brain
link |
00:17:27.400
that knew that relationship between objects and gravity.
link |
00:17:32.680
But one of the first things that a child learns
link |
00:17:36.260
is the relationship between objects and gravity
link |
00:17:39.360
and their trajectories.
link |
00:17:40.320
Yeah, and with a four-year-old, I mean,
link |
00:17:42.200
I saw that at earlier ages,
link |
00:17:44.200
like that experimentation of like,
link |
00:17:46.160
oh yeah, that's what happens, you know?
link |
00:17:48.400
Right, so if he were to throw a ball,
link |
00:17:50.600
if your child were to throw a ball
link |
00:17:52.160
and it went up into the sky,
link |
00:17:54.020
that would be absolutely mind-blowing.
link |
00:17:57.220
It would be for an adult too.
link |
00:17:58.480
It'd be a pretty psychedelic experience probably.
link |
00:18:01.100
Right, and so there's a rule there, you're saying,
link |
00:18:04.400
there's a kind of a prediction,
link |
00:18:07.360
there's a rule that underlies a prediction
link |
00:18:09.920
that when that rule is violated,
link |
00:18:13.200
all of a sudden the circuit, presumably,
link |
00:18:14.840
for that prediction, it doesn't have a mind of its own,
link |
00:18:18.040
but somehow it creates a surprise element
link |
00:18:20.440
or a recognition element.
link |
00:18:22.800
And it's not filtered out, you know?
link |
00:18:27.000
And this might sound extreme, but there are these cases,
link |
00:18:30.020
it was overblown in sort of the propaganda
link |
00:18:32.680
of the late 60s, early 70s,
link |
00:18:34.460
but there are credible cases of people,
link |
00:18:37.440
I think it's very atypical,
link |
00:18:39.120
of sounds like they really thought they could fly.
link |
00:18:42.480
And jump out of a window.
link |
00:18:46.120
Now, far more people every year fall,
link |
00:18:51.120
I mean, who knows, they fall and die from height
link |
00:18:55.360
because they're drunk, so this is extremely rare.
link |
00:18:59.040
But there are some pretty convincing cases.
link |
00:19:03.260
There was one research volunteer in our studies
link |
00:19:06.040
that she looked like she was, in one of our studies,
link |
00:19:11.040
like she was trying to dive through a painting on the wall.
link |
00:19:14.060
She was fine, but she, reviewing the video,
link |
00:19:18.100
it looked like she really thought
link |
00:19:21.400
that she was going to go through that painting
link |
00:19:23.960
and who knows, enter the other dimension.
link |
00:19:28.240
Yeah, so they're violating these predictions.
link |
00:19:31.560
Yeah, the reason I ask it, the question the way I did,
link |
00:19:34.860
is because given the enormous cloud of different substances
link |
00:19:38.480
and given the range of previous experiences
link |
00:19:41.520
that people show up to a psychedelic experience with,
link |
00:19:46.040
I feel like the ability to extract
link |
00:19:47.800
some universal themes is useful,
link |
00:19:50.200
especially for people who haven't done them before, right?
link |
00:19:52.640
Who might not have an understanding
link |
00:19:54.560
of what their effects are like.
link |
00:19:56.520
Can we just briefly touch on the serotonin system
link |
00:20:01.800
and the dopamine system?
link |
00:20:03.000
I want to acknowledge it, as you already know,
link |
00:20:05.880
that there are many neuromodulator systems in the body.
link |
00:20:08.440
And, you know, the opioid systems, cannabinoid systems,
link |
00:20:10.860
but there's something so profound
link |
00:20:13.320
about the serotonin system and the dopamine system,
link |
00:20:15.740
because the way I define a neuromodulator is,
link |
00:20:19.400
it's a modulator, it changes the way
link |
00:20:20.920
that other circuits behave.
link |
00:20:22.680
And essentially it increases the probability
link |
00:20:25.480
that certain circuits will be active
link |
00:20:26.840
and decreases the probability
link |
00:20:27.900
that other circuits will be active, in a general sense.
link |
00:20:31.480
So, compounds like LSD,
link |
00:20:34.560
lysergic acid, diethylamide, and psilocybin,
link |
00:20:38.400
my understanding is that they primarily
link |
00:20:41.920
target the serotonin system.
link |
00:20:44.980
How do they do that at a kind of general level?
link |
00:20:48.440
And why would increasing the activity
link |
00:20:51.240
of a particular serotonin receptor
link |
00:20:53.100
or batch of serotonin receptors
link |
00:20:55.120
lead to these profoundly different experiences
link |
00:20:58.360
that we're calling model challenges,
link |
00:21:02.600
challenging pre-existing models and predictions?
link |
00:21:05.040
I mean, at the end of the day, it's a chemical
link |
00:21:07.560
and these receptors are scattered around the brain
link |
00:21:09.800
with billions of other receptors.
link |
00:21:14.060
What do we think is going on in a general sense?
link |
00:21:17.160
Yeah, yeah.
link |
00:21:18.000
And this is really the area of active exploration
link |
00:21:21.200
and we don't have great answers.
link |
00:21:22.680
We know a good amount
link |
00:21:24.320
about the receptor level pharmacology,
link |
00:21:26.380
some things about post receptor signaling pathways.
link |
00:21:29.840
In other words, just fitting into the receptor,
link |
00:21:32.520
clearly serotonin itself is not psychedelic,
link |
00:21:36.280
or else we'd be tripping all of us all the time.
link |
00:21:38.320
Because when I eat a bagel,
link |
00:21:39.280
I get serotonin release, right?
link |
00:21:41.360
I mean, there's turkey, I mean, there's triptophan, right?
link |
00:21:45.160
My understanding of serotonin is that in very broad strokes,
link |
00:21:49.040
that it generally leads to a state of being fairly,
link |
00:21:53.000
it pushes the mind and body towards a state of contentment
link |
00:21:56.440
within the immediate experience.
link |
00:21:59.560
Whereas the dopamine system really places us
link |
00:22:02.000
into an external view of what's out there in the world
link |
00:22:05.280
and what's possible.
link |
00:22:06.280
Yeah, we need to do something.
link |
00:22:08.240
I mean, that's consistent with my understanding.
link |
00:22:11.540
And I'll certainly not, in terms of,
link |
00:22:14.480
I don't primarily identify as a neuroscientist,
link |
00:22:17.800
definitely tell the viewers
link |
00:22:19.560
that we're far more in your domain here than mine,
link |
00:22:23.140
but in terms of how psychedelics and other drugs
link |
00:22:25.960
interface at the neuroscience level.
link |
00:22:28.320
Well, feel free to explain it at the experiential level.
link |
00:22:31.360
I mean, it doesn't have,
link |
00:22:32.200
I think there probably are some audience members
link |
00:22:35.000
that are interested in, is it the 5-H2C?
link |
00:22:36.840
Is it the layer five neurons and cortex?
link |
00:22:39.120
That conversation we could hold,
link |
00:22:40.520
and that's an interesting conversation.
link |
00:22:41.800
But just in terms of the experience of serotonergic
link |
00:22:46.000
versus dopaminergic drugs,
link |
00:22:48.640
they do seem to create distinct classes of experience.
link |
00:22:54.340
So I think that's the appropriate level
link |
00:22:57.020
for us to discuss them.
link |
00:22:58.160
And in terms of how they, and I'd like to explore the biology
link |
00:23:01.200
a little bit here and tell you sort of what's known
link |
00:23:03.400
and what some of the ideas are.
link |
00:23:06.440
You have this path, as you know,
link |
00:23:09.460
these are levels of analysis,
link |
00:23:11.040
and it's not which one is going on.
link |
00:23:13.120
It's almost like, for the particular question,
link |
00:23:15.240
which level of analysis is most appropriate?
link |
00:23:17.760
Is a question best addressed by the biology,
link |
00:23:21.120
the chemistry, or the physics?
link |
00:23:23.400
That's how I think of receptor level,
link |
00:23:25.160
post-receptor signaling, downstream effects
link |
00:23:27.600
on other neurotransmitters,
link |
00:23:29.440
and then activation level effects,
link |
00:23:32.880
and then coordination of activation.
link |
00:23:35.760
So you've got the, clearly with the classic psychedelics,
link |
00:23:39.380
the 2A activation, we do know
link |
00:23:43.400
that there are downstream effects
link |
00:23:44.800
in terms of increasing glutamate transmission.
link |
00:23:47.960
So this is likely a commonality why ketamine
link |
00:23:52.240
is very psychedelic in a slightly different way.
link |
00:23:54.320
But-
link |
00:23:55.140
Do people hallucinate on ketamine?
link |
00:23:55.980
Yes, yes, and it's more dissociative,
link |
00:23:58.160
so someone is more likely to sort of
link |
00:24:01.200
be less behaviorally active.
link |
00:24:03.160
If they have a really high dose, they go into a K hole,
link |
00:24:05.240
and if they go in a really high dose,
link |
00:24:06.700
like you get into surgery, you're just unconscious.
link |
00:24:09.080
Yeah, a K hole.
link |
00:24:09.920
Not an A hole, but a K hole.
link |
00:24:10.760
A K hole, yeah, it's very different.
link |
00:24:14.600
The K hole, and ketamine's interesting
link |
00:24:16.320
because people can take kind of bumps
link |
00:24:17.800
and kind of dance on it
link |
00:24:19.000
with the sort of an alcohol level strength of effect,
link |
00:24:22.200
and that's sort of the classic kind of raving use of it.
link |
00:24:25.900
But then those folks want to titrate their dose
link |
00:24:28.780
because if they do more of like a line,
link |
00:24:31.120
you get up to like 75, 100 milligrams,
link |
00:24:33.620
then you're talking about, you know,
link |
00:24:37.160
if you're on the dance floor, you're on the floor,
link |
00:24:39.680
and your friends are trying to make sure
link |
00:24:41.360
people aren't stepping on you.
link |
00:24:42.560
So that's like-
link |
00:24:43.400
Yeah, why would somebody want to take
link |
00:24:45.300
a dissociative anesthetic?
link |
00:24:47.400
Like to me, it's completely mysterious
link |
00:24:49.920
as to why someone would want to dissociate from their body.
link |
00:24:53.540
People claim that these NMDA antagonist psychedelics
link |
00:24:58.780
are extremely insightful, you know,
link |
00:25:00.540
in a very similar way to the experiences
link |
00:25:03.300
with the classic psychedelics.
link |
00:25:05.240
And ketamine is now legal for therapeutic use, right?
link |
00:25:07.320
Right, right.
link |
00:25:08.160
Spravato, the intranasal form marketed by Janssen,
link |
00:25:13.600
which is S-ketamine, and it's one of the-
link |
00:25:15.960
Yeah, it's prescription, and-
link |
00:25:18.480
So people are taking in the nasal spray.
link |
00:25:20.760
Yeah.
link |
00:25:21.600
And then are they undergoing talk therapy
link |
00:25:23.200
while they're doing this?
link |
00:25:24.080
Typically not.
link |
00:25:25.040
So this is very interesting,
link |
00:25:26.800
and there's so much work that needs to be done.
link |
00:25:29.560
It's not treated as psychedelic therapy.
link |
00:25:32.300
And by that, psychedelic therapy, I mean,
link |
00:25:35.180
you tell the person they're going to have
link |
00:25:36.440
an altered experience.
link |
00:25:38.160
You tell them to pay attention to that experience,
link |
00:25:41.480
that they might learn something from that experience.
link |
00:25:43.320
And afterwards, you discuss that experience.
link |
00:25:45.760
With Spravato, the model is-
link |
00:25:48.960
Spravato is?
link |
00:25:49.860
Is S-ketamine.
link |
00:25:50.960
Okay.
link |
00:25:51.800
That's the, yeah, the spray form of ketamine.
link |
00:25:54.440
It's been FDA approved for treatment-resistant depression,
link |
00:25:57.920
but you'll probably feel different.
link |
00:26:00.520
Ignore that.
link |
00:26:01.560
That's a side effect.
link |
00:26:03.040
That's an adverse effect.
link |
00:26:05.260
Just ignore it.
link |
00:26:06.920
We don't think that has anything to do with the way it works,
link |
00:26:09.880
but just get this thing.
link |
00:26:10.960
It's a direct sort of chemotherapeutic effect in a sense.
link |
00:26:15.080
It's not facilitating a learning process.
link |
00:26:19.320
Now, there's older work.
link |
00:26:21.040
There was a guy, Krupitsky, in Russia
link |
00:26:23.100
that did extensive work with higher doses of ketamine.
link |
00:26:27.040
I should say Spravato at the prescribed doses
link |
00:26:30.040
isn't very, it's a pretty low dose.
link |
00:26:32.600
It's in the mild psychedelic range, but it's not very strong.
link |
00:26:36.660
But this older work that happened in the 90s
link |
00:26:39.220
and early 2000s in Russia,
link |
00:26:42.060
they were using very high doses
link |
00:26:43.360
and treating it like a psychedelic,
link |
00:26:45.340
treating it as if it was a psychedelic therapy.
link |
00:26:48.220
In other words, telling people,
link |
00:26:49.600
you're going to have this experience.
link |
00:26:50.800
It's going to, you know,
link |
00:26:52.320
we're hoping you learn something from it.
link |
00:26:54.080
We're going to help you through it.
link |
00:26:54.960
We're going to discuss it afterwards.
link |
00:26:56.360
And they found incredibly high rates of success
link |
00:26:58.840
in some pretty well-controlled trials
link |
00:27:00.420
for both heroin addiction and alcohol addiction.
link |
00:27:04.860
So I think a whole lot of work needs to be done now.
link |
00:27:07.620
And you see some of the ketamine clinics
link |
00:27:09.320
that are using ketamine off-label,
link |
00:27:10.900
a lot of them are treating it like psychedelic therapy.
link |
00:27:13.960
There's essentially no research at this point on that.
link |
00:27:16.700
Do you get better results?
link |
00:27:19.060
Straight abusive Spervado,
link |
00:27:22.100
there's some good variability,
link |
00:27:23.440
but its antidepressant effects last about a week.
link |
00:27:26.940
But they kick in immediately.
link |
00:27:28.500
Now, a week is a long time for like most psychiatric drugs.
link |
00:27:32.900
Like you take it every day.
link |
00:27:34.900
So that's amazing, but it's still just a week.
link |
00:27:37.000
We're seeing effects a year or more later
link |
00:27:40.620
with psilocybin and some of the classic psychedelics.
link |
00:27:44.460
That could be a pharmacological difference,
link |
00:27:46.460
or it could be that they get a lot more mileage
link |
00:27:49.140
out of ketamine if they treated it like psychedelic therapy.
link |
00:27:53.340
And so that's some-
link |
00:27:54.180
What would that look like?
link |
00:27:56.020
Really just like our psilocybin sessions,
link |
00:27:59.380
which I know I haven't described,
link |
00:28:00.900
but briefly you have anywhere from four to eight hours
link |
00:28:03.940
of preparation, getting to know the people
link |
00:28:05.940
who are going to be the guides
link |
00:28:06.980
or the therapists in the room.
link |
00:28:08.140
Yeah, maybe you could walk us through this.
link |
00:28:10.420
So let's say I were to come to one of your clinical trials,
link |
00:28:14.460
because these are clinical trials, right?
link |
00:28:16.540
At your lab at Hopkins.
link |
00:28:18.100
And would I need to be depressed
link |
00:28:19.920
or could I just be somebody
link |
00:28:20.860
who wanted to explore psychedelics?
link |
00:28:22.740
We've had studies for all of these
link |
00:28:25.620
and a number of other disorders.
link |
00:28:27.260
So healthy normal studies,
link |
00:28:28.900
the code for not a problem to fix,
link |
00:28:31.380
but we're all here.
link |
00:28:32.220
That's what's amazing about psychedelics though,
link |
00:28:34.260
because if you administer them under this model
link |
00:28:37.340
and you develop a relationship
link |
00:28:38.620
and give a high dose of psychedelic,
link |
00:28:40.140
you can be a healthy normal without a diagnosable issue.
link |
00:28:42.700
But man, we're all human
link |
00:28:44.640
and the issues seem to come to the surface.
link |
00:28:47.100
So, but we've done work with smoking cessation.
link |
00:28:50.180
So people trying to quit tobacco
link |
00:28:51.780
and haven't been successful.
link |
00:28:52.620
So a variety of reasons.
link |
00:28:54.260
So maybe I'll just ask some very simple questions
link |
00:28:57.060
that would kind of step us through the process.
link |
00:28:58.580
So let's say I were to sign up for one of these trials
link |
00:29:01.100
and I qualified for one of these trials.
link |
00:29:03.220
I'd show up, you said I would do several hours in advance
link |
00:29:06.040
of getting to know the team
link |
00:29:07.140
that would be present during this psychedelic journey.
link |
00:29:11.100
First there's screening.
link |
00:29:12.160
So it's kind of like a couple of days of both psychiatric,
link |
00:29:15.580
like structured psychiatric interviews
link |
00:29:17.900
about your whole, your past and symptoms
link |
00:29:20.780
across the DSM, the psychiatric Bible
link |
00:29:23.740
to see if you might have various disorders
link |
00:29:25.980
that could disqualify you.
link |
00:29:28.380
Like the main ones being the psychotic disorders,
link |
00:29:30.860
schizophrenia, and also including bipolar.
link |
00:29:34.300
So the manic side of bipolar.
link |
00:29:36.780
So after that, and also cardiovascular screening,
link |
00:29:39.580
heart disease, after that screening,
link |
00:29:41.140
then the preparation where you get,
link |
00:29:42.700
you're both, you develop a therapeutic rapport
link |
00:29:46.140
with the people who are going to be in the room with you,
link |
00:29:48.300
your guides, but you're also then didactically
link |
00:29:52.620
sort of explained about what the psychedelic could be like.
link |
00:29:56.480
And that's kind of a laundry list
link |
00:29:58.200
because they're more known by their variability
link |
00:30:00.980
than it's going to, it's not like cocaine.
link |
00:30:03.260
Like you're going to feel stimulated.
link |
00:30:05.380
You're going to feel like you can do any,
link |
00:30:07.980
it's like, or alcohol.
link |
00:30:09.500
You're probably going to feel more relaxed.
link |
00:30:11.300
It's like, I call them uppers, downers, and all-arounders,
link |
00:30:15.060
and the psychedelics are all-arounders.
link |
00:30:16.780
It's like, yeah, you could be,
link |
00:30:18.800
you could have the most beautiful experience of your life
link |
00:30:22.660
or the most terrifying experience of your life.
link |
00:30:24.800
So it's this kind of laundry list
link |
00:30:26.060
of like the things that could happen.
link |
00:30:27.180
So there's no surprises.
link |
00:30:29.620
I think it's so important for people to hear
link |
00:30:31.260
because the all-arounders, they,
link |
00:30:34.900
you really can't predict how somebody
link |
00:30:36.500
is going to react internally.
link |
00:30:38.540
Right.
link |
00:30:39.940
I want to just briefly touch on something
link |
00:30:42.620
because we left that topic,
link |
00:30:44.420
but it occurred to me that a lot of these effects
link |
00:30:48.560
of psychedelics and how they function, et cetera,
link |
00:30:50.860
is still very mysterious.
link |
00:30:52.040
But then I recall to mind
link |
00:30:54.300
that how most prescription antidepressants work
link |
00:30:57.160
is also very mysterious.
link |
00:30:58.880
They increase serotonin or dopamine or epinephrine, et cetera,
link |
00:31:02.140
but why they take weeks on end,
link |
00:31:04.120
several weeks to kick in, et cetera, is also mysterious.
link |
00:31:06.740
But going back to the experience
link |
00:31:09.580
of coming to your laboratory.
link |
00:31:11.180
Okay, so let's say that somebody passes
link |
00:31:13.700
all the prerequisites and it's the day.
link |
00:31:19.300
Comes the day that they're going to have this experience.
link |
00:31:22.420
Are they eating mushrooms like you hear about
link |
00:31:26.780
or are they taking it in capsule form?
link |
00:31:29.140
And what sorts of doses are you prescribing?
link |
00:31:32.460
Is there a dose response curve?
link |
00:31:34.100
Yeah. And then secondary to that,
link |
00:31:37.480
I'd like to talk about microdose versus macrodose.
link |
00:31:40.280
So how do they get this stuff into,
link |
00:31:42.100
how do people receive it
link |
00:31:44.720
and how do they get it into their body?
link |
00:31:46.080
So they receive pure psilocybin.
link |
00:31:48.200
So the mushroom, and there are many species,
link |
00:31:51.240
the most private, people have taken mushrooms
link |
00:31:53.140
in the United States.
link |
00:31:54.080
It's most likely psilocybe cubensis.
link |
00:31:57.680
They're easy to grow.
link |
00:31:58.600
They grow in cow patties.
link |
00:31:59.880
It's easy for any body to grow them in their closet.
link |
00:32:02.760
It doesn't take a 1,000-watt light like cannabis.
link |
00:32:05.600
It takes like a little 10-watt light bulb
link |
00:32:08.680
and a Tupperware bin.
link |
00:32:09.640
So those are the types of mushrooms
link |
00:32:12.320
that people typically take.
link |
00:32:13.280
We're not administering those.
link |
00:32:14.920
Psilocybin is the compound.
link |
00:32:17.380
You could draw a molecule, psilocybin,
link |
00:32:19.920
again, based on the tryptamine structure.
link |
00:32:22.360
That's a single molecular entity.
link |
00:32:24.760
So it's a white powder.
link |
00:32:26.080
Does it look like serotonin molecularly?
link |
00:32:28.480
Yes, yes, yes.
link |
00:32:30.440
So if I were to show people
link |
00:32:32.000
the chemical structure of serotonin,
link |
00:32:33.440
the chemical structure of psilocybin,
link |
00:32:35.160
it would look quite similar.
link |
00:32:36.560
Right, right.
link |
00:32:37.400
So they're basically taking serotonin.
link |
00:32:41.080
A modified version of serotonin, which makes sense.
link |
00:32:43.840
But then again, this repeated theme of the chemistry
link |
00:32:47.660
doesn't always neatly line up
link |
00:32:49.380
because like mescaline looks more like dopamine
link |
00:32:54.340
than it does like serotonin,
link |
00:32:55.780
but yet at the receptor activation level,
link |
00:32:58.980
the pharmacological effect,
link |
00:33:01.640
those are similar.
link |
00:33:03.160
But yeah, and what it does at the receptor
link |
00:33:06.360
is it's hitting the same switch,
link |
00:33:09.000
but then having an alternate response at the receptor level.
link |
00:33:14.040
So for people that don't necessarily understand
link |
00:33:15.680
the relationship between what we call ligand,
link |
00:33:17.640
the thing that parks in the receptor,
link |
00:33:19.400
and the receptor is the parking spot,
link |
00:33:21.240
one of the reasons that you can get such a variety
link |
00:33:24.320
of effects from different compounds is,
link |
00:33:26.840
for instance, serotonin might affect a certain pathway
link |
00:33:30.480
at a particular rate,
link |
00:33:32.080
and psilocybin might trigger activation
link |
00:33:35.460
of different components of that pathway at different rates,
link |
00:33:37.560
and so you can get vastly different experiences
link |
00:33:40.320
from two things that look chemically similar.
link |
00:33:42.640
This is also a good reason why people shouldn't just assume
link |
00:33:47.800
that they can cowboy their own chemistry, right?
link |
00:33:50.820
That what you see on paper and what you can mix up
link |
00:33:53.440
in a vial is often vastly different than what you predict.
link |
00:33:58.240
Right.
link |
00:33:59.120
And there's a dose effect curve that's really interesting.
link |
00:34:01.680
Some of our early work with psilocybin in healthy normals
link |
00:34:06.380
looked at a true placebo plus four active doses,
link |
00:34:10.000
five, 10, 20, and 30 milligrams of psilocybin.
link |
00:34:13.320
Body weight adjusted,
link |
00:34:14.740
so those milligrams per 70 kilograms of body weight.
link |
00:34:18.840
We've recently published a paper in our newer trials
link |
00:34:21.540
where we're dropping the body weight adjustment
link |
00:34:23.680
because we're going across hundreds of volunteers.
link |
00:34:26.080
We've kind of figured out that you shouldn't really be,
link |
00:34:29.440
you don't need to be adjusting by body weight.
link |
00:34:32.080
Interesting.
link |
00:34:32.920
So, yeah.
link |
00:34:33.760
Well, brain size doesn't vary that much between individuals.
link |
00:34:37.240
Yeah, yeah.
link |
00:34:38.320
And, you know, at the end, this is a brain effect, mostly.
link |
00:34:43.000
Probably body as well.
link |
00:34:44.880
Okay, so the person ingests the powder or capsule?
link |
00:34:48.160
In a little pill.
link |
00:34:49.120
Okay.
link |
00:34:49.960
Yeah, and it doesn't take 30 milligrams as a small.
link |
00:34:52.220
You could fit it into a tiny little capsule,
link |
00:34:54.940
and it'll take about a half hour,
link |
00:34:57.160
but anywhere from 15 minutes to an hour to kick in.
link |
00:35:00.400
And you said the dose range was?
link |
00:35:03.900
Most of our studies are looking at
link |
00:35:06.580
where we want a psychedelic effect
link |
00:35:08.760
are in the 20 to 30 milligram range.
link |
00:35:12.740
Again, because we have adjusted by body weight
link |
00:35:15.200
and the average American is over 70 kilograms,
link |
00:35:18.200
about 150 pounds.
link |
00:35:19.400
Like people, and in fact, have gotten more like 40, 45
link |
00:35:23.880
in a lot of cases.
link |
00:35:25.280
But it's still a small pill.
link |
00:35:29.860
The session day itself is not full of,
link |
00:35:32.640
for most of our studies, is not full of tasks.
link |
00:35:34.840
We really want to look at the therapeutic response.
link |
00:35:37.560
Obviously, if it's a therapeutic study,
link |
00:35:39.440
we want it to be a meaningful experience.
link |
00:35:41.640
And research has found, not surprisingly,
link |
00:35:44.440
that you get a less meaningful experience
link |
00:35:46.480
when you're in an FMRI
link |
00:35:48.880
or when you're doing a lot of cognitive tasks.
link |
00:35:51.180
We've done some research of that type, for sure,
link |
00:35:57.280
and plenty of colleagues have.
link |
00:35:59.080
But when you're in a therapeutic study,
link |
00:36:00.760
or if you're trying to understand the therapeutic effects,
link |
00:36:02.840
you have to recognize there's this trade-off
link |
00:36:05.960
of what you can do.
link |
00:36:06.800
So our typical therapeutic model,
link |
00:36:08.560
which again, isn't just limited necessarily
link |
00:36:10.900
to the therapeutic studies
link |
00:36:12.120
where we're trying to treat a specific disorder,
link |
00:36:14.440
is to have that preparation
link |
00:36:17.940
so the person feels very comfortable with their guides.
link |
00:36:21.280
I mean, ultimately, what I tell people is like,
link |
00:36:25.680
any emotional response, it's all welcome.
link |
00:36:28.200
I mean, you could be crying like a baby hysterically.
link |
00:36:33.040
Like, that's what you should be doing
link |
00:36:34.560
if that's what you feel like.
link |
00:36:35.720
And so in a lot of ways,
link |
00:36:36.960
sometimes people with psychedelic experience on their own,
link |
00:36:41.800
it can be harder to train them in this model
link |
00:36:44.040
because in the real world,
link |
00:36:45.880
people with psychedelic experience,
link |
00:36:47.160
a lot of times the rule is, you know, hold your shit.
link |
00:36:48.960
So several friends go to a party,
link |
00:36:51.720
they split a bag of mushrooms.
link |
00:36:53.100
It's like, you know, there's a social pressure
link |
00:36:55.520
for good reason not to be the guy, you know,
link |
00:36:58.760
in the corner of the room
link |
00:37:00.920
where everyone's trying to just have a good time, relax,
link |
00:37:02.920
like crying about your mother.
link |
00:37:04.580
Your other friends are, they're having an experience too,
link |
00:37:07.080
and you're being a drama king and blah, blah, blah.
link |
00:37:09.600
And so like, yeah, compose yourself, hold your-
link |
00:37:12.160
You're doing, I mean, you're doing therapy for people.
link |
00:37:14.600
It's not just about the experience.
link |
00:37:17.360
Right, and the experience itself is very much shaped
link |
00:37:19.920
by that container, by the environment,
link |
00:37:23.360
and the degree to which one allows it to happen.
link |
00:37:26.280
Like one should let go of control.
link |
00:37:29.240
Yeah, let's talk about the letting go of control.
link |
00:37:32.140
And then as we march through this hypothetical experience
link |
00:37:36.440
that does take place in your lab,
link |
00:37:38.480
so we're using a sort of generic case example, if you will.
link |
00:37:42.320
The letting go of control is an interesting feature,
link |
00:37:45.560
actually, because one of the common themes
link |
00:37:47.800
of good psychoanalysis or psychotherapy of any kind
link |
00:37:51.340
is that there's a trust built between the patient
link |
00:37:54.240
and the analyst, and that relationship becomes a template
link |
00:37:58.620
for trust more generally and trust in oneself.
link |
00:38:01.760
It's actually the end goal of good psychoanalysis
link |
00:38:04.680
is that the patient actually, one of the end goals
link |
00:38:07.080
is that they develop an empathy for themselves,
link |
00:38:09.360
which almost sounds like an oxymoron,
link |
00:38:11.240
but if you spend a little time with that statement,
link |
00:38:13.560
it actually pans out.
link |
00:38:15.120
So the psychedelic experience is one in which chemically
link |
00:38:21.000
you're under a new set of conditions, right?
link |
00:38:26.400
Coarsely, space and time are altered in some way,
link |
00:38:29.960
sense of self.
link |
00:38:31.560
For instance, I might be going to a strongly
link |
00:38:33.800
interoceptive mode where I'm focusing on everything
link |
00:38:36.620
within the confines of my skin,
link |
00:38:37.920
whereas normally we're sort of interacting in space
link |
00:38:40.320
and pens and conversation, and I'm sort of,
link |
00:38:42.520
if I had, occasionally I'll pay attention to my breathing,
link |
00:38:45.040
but I'm sort of dilating and contracting my focus
link |
00:38:47.960
for different things all the time.
link |
00:38:50.320
The letting go of control, it seems to me,
link |
00:38:53.660
could be sort of the expansion of one perceptual bubble
link |
00:38:57.520
to the point where you're not actually worried
link |
00:39:01.240
that that perceptual bubble is going to pop or that,
link |
00:39:03.600
meaning you're not worried about what people think of you.
link |
00:39:06.960
You're not worried whether or not your brain
link |
00:39:09.640
is going to explode,
link |
00:39:10.520
even though a thought could feel enormous.
link |
00:39:13.720
If I keep going like this, it almost sounds psychedelic,
link |
00:39:15.920
but that's the idea here.
link |
00:39:18.040
Or if I'm paying attention, for instance,
link |
00:39:19.760
to some somatic experience,
link |
00:39:21.680
like the coursing of waves of heat through my body,
link |
00:39:26.620
that I'm not suddenly saying, you know, is that weird?
link |
00:39:30.520
I'm actually just going deeper and deeper into it.
link |
00:39:32.800
So it's essentially expanding our perceptual phenomenon.
link |
00:39:35.720
How do you convince people to go further
link |
00:39:39.200
and further down that path?
link |
00:39:40.660
What do you think allows them to do that?
link |
00:39:42.220
Because I think that, to me,
link |
00:39:44.080
is one of the more unusual aspects to psychedelics
link |
00:39:47.940
is that normally the social pressure,
link |
00:39:51.000
but also just our internal pressure from our own brain
link |
00:39:54.420
is pay attention to many things at once, not just one.
link |
00:39:59.000
Is that-
link |
00:39:59.840
Especially these days.
link |
00:40:00.660
Yeah, multitask.
link |
00:40:02.120
Multitask, and the more that we focus on one thing,
link |
00:40:05.480
the more bizarre that thing actually can appear to us, right?
link |
00:40:08.420
Right.
link |
00:40:09.260
I mean, even if it's the tip of your finger
link |
00:40:10.420
and you're not taking any psychedelics,
link |
00:40:11.660
you spend a long enough looking at the tip of your finger,
link |
00:40:13.420
you will notice some very weird things, right?
link |
00:40:16.940
I think of that as the classic psychedelic effect
link |
00:40:19.260
or one classic effect,
link |
00:40:21.540
and one I've used many times of this example
link |
00:40:24.700
of why people shouldn't necessarily, you know,
link |
00:40:28.300
these aren't,
link |
00:40:31.380
one should be judicious
link |
00:40:32.940
in putting themselves in these circumstances.
link |
00:40:35.140
Someone could be, you know,
link |
00:40:37.420
having a very strong psilocybin experience
link |
00:40:40.480
and they're trying to navigate their way in Manhattan,
link |
00:40:43.660
crossing the street,
link |
00:40:44.620
and they might be staring into the hand and realize,
link |
00:40:47.380
like that's, their hand is the most amazing miracle.
link |
00:40:50.740
Like the entire universe has essentially conspired
link |
00:40:53.500
to come to this one point
link |
00:40:55.340
to make this absolutely breathtaking.
link |
00:40:57.600
It's almost like, I think of the simplest form of,
link |
00:41:00.680
well, we know that the simplest form of learning
link |
00:41:02.180
is habituation.
link |
00:41:03.020
Simply keep applying stimuli
link |
00:41:04.620
and there's less response.
link |
00:41:05.460
Like, this is what organisms do.
link |
00:41:07.340
This is what we have to do.
link |
00:41:08.620
And it's like, there's this dishabituation component
link |
00:41:11.580
that like-
link |
00:41:12.420
Dishabituation.
link |
00:41:13.240
Yes, like we wouldn't be able to get through life
link |
00:41:14.800
if we wouldn't be able to cross that street
link |
00:41:16.500
if we were like, oh, like this is a miracle.
link |
00:41:19.860
Well, I'm so glad you,
link |
00:41:21.260
no, I'm so glad you brought this up.
link |
00:41:22.700
I mean, here I'm reflecting my bias as a vision scientist,
link |
00:41:25.180
but most people don't realize this,
link |
00:41:26.740
but if you look at something long enough,
link |
00:41:28.200
it eventually disappears.
link |
00:41:30.460
It doesn't actually disappear,
link |
00:41:31.500
but perceptually it disappears.
link |
00:41:33.020
You have these little microsaccades that ensure
link |
00:41:35.040
that it doesn't.
link |
00:41:36.100
But most of us don't look at any one thing for very long.
link |
00:41:39.820
The brain's default is to perceptually jump around
link |
00:41:43.900
like crazy with the visual system,
link |
00:41:45.740
with the auditory system.
link |
00:41:47.120
We all, ADD, people talk about ADD a lot,
link |
00:41:50.500
is sort of baked into our underlying networks at some level.
link |
00:41:53.620
And then we can force attention.
link |
00:41:56.000
But it sounds like in psychedelics,
link |
00:41:57.960
one of the primary goals therapeutically
link |
00:41:59.820
is to really drill into one of these perceptual bubbles
link |
00:42:03.580
and expand that bubble.
link |
00:42:04.860
And the safety it seems is the safety,
link |
00:42:08.340
it's sort of like a permission to do that
link |
00:42:11.260
without worrying that something's going to happen.
link |
00:42:14.140
Right, because I've had people there on the couch.
link |
00:42:18.560
Yeah, I remember one lady said,
link |
00:42:20.100
this is probably 13, 14 years ago,
link |
00:42:23.440
said, Matt, tell me again, I can't die.
link |
00:42:26.420
I feel like my heart is going to rip through my chest.
link |
00:42:29.220
I mean, she was feeling her.
link |
00:42:30.420
And I should say, typically,
link |
00:42:32.300
cardiovascular response is modest.
link |
00:42:34.700
The pulse and blood pressure go up somewhat.
link |
00:42:38.420
It can be dangerous for people
link |
00:42:39.720
if they're at severe heart risk,
link |
00:42:41.100
and we do monitor.
link |
00:42:41.940
Are you monitoring this the whole time?
link |
00:42:42.760
We do, yeah.
link |
00:42:43.600
So they're plugged into a variety of devices.
link |
00:42:45.460
Yeah, so every half hour or so,
link |
00:42:47.140
we take their own protocol,
link |
00:42:48.820
and we space it out a little further,
link |
00:42:51.300
further into the time course.
link |
00:42:52.740
But we take their blood pressure and their pulse.
link |
00:42:55.100
And if it goes over a certain level, we have a protocol.
link |
00:42:57.340
And we've had to do this only a few times.
link |
00:42:58.620
But the physician comes in,
link |
00:43:00.300
gives them a little nitroglycerin under the tongue,
link |
00:43:02.600
and knocks the blood pressure down a little bit,
link |
00:43:04.820
doesn't affect the experience.
link |
00:43:05.980
So we have it all in place,
link |
00:43:07.320
even though they'd probably be fine
link |
00:43:08.420
out of an abundance of caution.
link |
00:43:09.940
Sure.
link |
00:43:11.780
But yeah, but someone can feel that,
link |
00:43:15.020
my God, I'm going to die.
link |
00:43:16.260
Like, I have never felt my heart beat like this before.
link |
00:43:21.180
And the experience of the breath
link |
00:43:23.260
can be just absolutely fantastic.
link |
00:43:27.820
This sort of, and the breath is obviously interesting
link |
00:43:29.900
because it's this automatic control,
link |
00:43:33.220
but it can also be voluntary.
link |
00:43:35.100
So people can get into a sense of like,
link |
00:43:37.180
my God, what if I forget, what if I forget?
link |
00:43:38.780
It sounds silly,
link |
00:43:39.620
like a stoner movie. What if I forget to breathe?
link |
00:43:40.820
Exactly.
link |
00:43:42.060
But people, that can be so compelling.
link |
00:43:45.500
And so one of the reasons,
link |
00:43:46.340
and get back to one of your questions,
link |
00:43:47.820
it's like, what do we do to kind of allow them
link |
00:43:50.780
to go further into these bubbles?
link |
00:43:52.540
It's like, one is wearing the eye shades.
link |
00:43:56.100
We don't call them blindfolds
link |
00:43:57.740
because that has a negative connotation like being kidnapped.
link |
00:44:00.300
And they're probably seeing a lot in there anyway.
link |
00:44:02.140
So blind isn't the appropriate word.
link |
00:44:03.820
Right, right.
link |
00:44:05.260
I've never thought of it.
link |
00:44:06.100
These should be like inner sight shades.
link |
00:44:09.260
But when you close the eyes,
link |
00:44:10.500
the levels of activity in the retina actually are maintained.
link |
00:44:14.100
It's just spontaneous activity.
link |
00:44:16.100
And it seems,
link |
00:44:16.940
and I'd be curious about your thoughts on this.
link |
00:44:20.500
But the way I describe it is that the mind's eye,
link |
00:44:25.500
meaning this kind of loose term we use,
link |
00:44:28.300
can be on rocket boosters.
link |
00:44:29.820
So a lot of times, for some people,
link |
00:44:31.980
like a compound like psilocybin,
link |
00:44:33.260
for some people, there's no perceptual effect.
link |
00:44:37.340
Like if they're looking at this room,
link |
00:44:38.500
it would pretty much look the same.
link |
00:44:40.660
Sometimes folks say,
link |
00:44:41.500
yeah, things seem a little bit brighter.
link |
00:44:42.860
Now, some people will say,
link |
00:44:44.300
oh my God, there's waves.
link |
00:44:45.660
That wall is waving and these curtains are, you know.
link |
00:44:48.780
On these compounds,
link |
00:44:49.660
people don't typically see pink elephants.
link |
00:44:51.380
You do actually get that in another class.
link |
00:44:53.220
I didn't mention the anticholinergics,
link |
00:44:56.540
sort of like atropine and scopolamine, those drugs.
link |
00:44:59.220
Those are the true hallucinations
link |
00:45:01.140
where you thought you were having a conversation
link |
00:45:03.220
with someone who was never there.
link |
00:45:06.980
We will definitely get to those.
link |
00:45:08.100
But the reason I kind of cringe and say,
link |
00:45:10.220
oh my, when you talked about those,
link |
00:45:11.780
is that knowing a little bit
link |
00:45:14.220
about the pharmacology of acetylcholine,
link |
00:45:16.540
the idea of manipulating that system,
link |
00:45:19.900
to me, sounds very uncomfortable.
link |
00:45:22.420
Because like the whole idea of, well, witches and flying,
link |
00:45:26.900
there was a whole history there, you know,
link |
00:45:28.620
hundreds of years ago, so-called witches,
link |
00:45:31.100
taking these agents and then thinking
link |
00:45:33.900
they were flying around on broomsticks
link |
00:45:35.620
and things of that sort.
link |
00:45:36.540
And there's a lot of mythology around the broomsticks.
link |
00:45:38.580
It's complicated, but that sounds very unpleasant.
link |
00:45:41.500
One thing about the serotonergic,
link |
00:45:43.820
let's just, with psilocybin.
link |
00:45:46.020
So there's an expansion
link |
00:45:50.420
of a particular fairly narrow percept.
link |
00:45:53.940
It could be sound, could be an emotion, could be sadness,
link |
00:45:56.460
could be a historical event or a fear of the future.
link |
00:46:00.940
And you've mentioned before that there's something
link |
00:46:04.180
to be learned in that experience.
link |
00:46:06.580
There's something about going into that experience
link |
00:46:09.020
in an undeterred way that allows somebody
link |
00:46:16.500
to bring something back into more standard reality.
link |
00:46:22.340
Given the huge variety of experiences
link |
00:46:25.060
that people have on psychedelics,
link |
00:46:26.500
given the huge variety of humans that are out there,
link |
00:46:30.460
but what are now very clear therapeutic effects
link |
00:46:33.260
in the realm of depression,
link |
00:46:35.140
what do you think is the value of going into this
link |
00:46:39.740
fairly restricted perceptual bubble,
link |
00:46:42.020
what we are calling letting go or giving up control?
link |
00:46:45.320
Because if the experiences are many,
link |
00:46:47.840
but the value of what one exports from that experience
link |
00:46:51.720
is kind of similar across individuals,
link |
00:46:54.580
that raises all sorts of interesting questions.
link |
00:46:56.820
And this is not a philosophy discussion.
link |
00:46:58.940
We're talking about biology and psychology here.
link |
00:47:01.940
So let's say I decide I'm going to focus on the tip
link |
00:47:05.420
of my pen.
link |
00:47:06.260
I mean, in a psychedelic state,
link |
00:47:07.780
I could fall in love with this pen.
link |
00:47:09.120
I do happen to like these Pilot V5s and V7s very much,
link |
00:47:12.260
but I could feel real love for the pen, right?
link |
00:47:16.200
That's not an unreasonable thing to expect
link |
00:47:18.740
in a psychedelic journey.
link |
00:47:20.180
And in the context of your laboratory model,
link |
00:47:22.940
which I think is a great one,
link |
00:47:24.380
that experience would be just as valid
link |
00:47:26.880
as me going into the experience of some of the deep friction
link |
00:47:30.340
that I might have with a family member
link |
00:47:32.180
over my entire lifespan.
link |
00:47:34.080
And yet the export from that,
link |
00:47:36.780
those two vastly different experiences
link |
00:47:39.900
is one of feeling a better relationship
link |
00:47:42.360
to the world and to oneself.
link |
00:47:43.920
So what does this tell us about-
link |
00:47:44.760
Like how can the pen and the processing
link |
00:47:46.940
your childhood trauma both lead to?
link |
00:47:49.200
Right.
link |
00:47:50.040
So what does this, I mean, at that level,
link |
00:47:53.180
it raises this question like, first of all, how, why,
link |
00:47:57.980
I mean, or just what are your thoughts on that?
link |
00:48:00.060
So this is definitely in the,
link |
00:48:02.080
this is in the terrain we're figuring out, you know?
link |
00:48:04.760
So there's no, educated speculation
link |
00:48:07.060
is the best I can provide.
link |
00:48:08.660
But I think the best, the most,
link |
00:48:14.540
I think the common denominator
link |
00:48:16.860
are persisting changes in self-representation.
link |
00:48:20.900
Okay, tell me more about self-representation.
link |
00:48:23.100
That's the way one holds the sense of self,
link |
00:48:27.660
the fundamental relationship of a person in the world.
link |
00:48:31.920
I mentioned earlier that these experience
link |
00:48:34.780
seems to alter the models we hold of reality.
link |
00:48:37.500
And I think that the self is the biggest model,
link |
00:48:39.540
that I am a thing that's separate from other things.
link |
00:48:42.300
And that's, I am defined by certain,
link |
00:48:46.420
I have a certain personality and I'm a smoker
link |
00:48:49.260
that's having a hard time quitting,
link |
00:48:50.520
or I'm a depressed person that, you know,
link |
00:48:53.540
views myself as a failure and all of these things.
link |
00:48:55.580
Those are models too.
link |
00:48:56.820
And I think, I think that change in self-representation
link |
00:49:01.420
may be an end point for these different experiences.
link |
00:49:04.020
I mean, maybe the falling in love with the pen,
link |
00:49:06.940
the whole idea that you're,
link |
00:49:09.220
especially in contemplation afterwards,
link |
00:49:10.920
and obviously I'm speculating here,
link |
00:49:12.300
but the whole idea that you could
link |
00:49:14.580
have such a deep connection with this random,
link |
00:49:18.060
obviously random aspect of the universe
link |
00:49:21.700
could potentially lead to this, you know,
link |
00:49:24.620
transformed understanding of the self and like,
link |
00:49:27.580
the pen may be a proxy for the miracle of reality,
link |
00:49:31.580
in a way that relies nothing on,
link |
00:49:34.260
on no supernatural thinking, you know,
link |
00:49:36.620
you can be a hard atheist and take this,
link |
00:49:38.940
ultimately, oh my God, like that,
link |
00:49:40.820
just like the pen, this is, you know,
link |
00:49:43.220
this is amazing, the fact that we exist.
link |
00:49:45.580
And so there could be an extrapolation chair
link |
00:49:48.040
and you use the pen, but I think it sounds so similar
link |
00:49:50.500
to Aldous Huxley's classic description
link |
00:49:52.940
on the doors of perception of the chair and the drapes.
link |
00:49:55.860
Like he took 500 milligrams of mescaline.
link |
00:49:59.220
He was just like-
link |
00:50:00.060
Is that a high dose of mescaline?
link |
00:50:01.140
Yeah, yeah.
link |
00:50:02.140
And that's, you know, that's a heroic dose for sure.
link |
00:50:06.460
And he just going off on the chairiness of the chair,
link |
00:50:09.280
like this chair is exuding the quality of being a chair.
link |
00:50:13.260
So this is this expansion of the perceptual bubble,
link |
00:50:16.120
a narrow, a narrow percept that then grows
link |
00:50:19.980
within the confines of that narrow percept.
link |
00:50:23.100
Yeah.
link |
00:50:23.980
So sense of self is a very interesting phenomenon.
link |
00:50:27.100
And if we could dissect it a little bit,
link |
00:50:29.940
there's the somatic sense of self.
link |
00:50:31.640
So the ability to literally feel the self
link |
00:50:34.620
into this process we call interoception.
link |
00:50:36.780
And then there's the title of the self, the I am blank.
link |
00:50:41.020
Yeah.
link |
00:50:41.860
And I noticed you said that several times.
link |
00:50:42.740
It's intriguing to me, I have a good friend.
link |
00:50:44.900
I don't think I can or should mention his name,
link |
00:50:47.620
but he had a very long and successful career
link |
00:50:51.140
within one of the more elite teams
link |
00:50:52.700
and within the SEAL teams.
link |
00:50:53.980
And he's a fairly philosophical guy,
link |
00:50:57.860
also very practical guy,
link |
00:50:59.460
but he has said many times to me
link |
00:51:03.700
that the most powerful words in any language are I am,
link |
00:51:08.820
because whatever follows that,
link |
00:51:10.860
tends, if you repeat it enough,
link |
00:51:12.580
tends to have this kind of feedback effect
link |
00:51:15.380
on how you are in the world.
link |
00:51:17.820
And the first pass, it sounded to me a little bit
link |
00:51:21.460
like kind of like internet psychology type thing,
link |
00:51:24.940
like the secret or something to say,
link |
00:51:26.260
which frankly I'm just not particularly.
link |
00:51:28.500
Yeah, so if you kind of like the whole fake it
link |
00:51:30.920
till you make it,
link |
00:51:31.760
like I don't actually subscribe to any of that.
link |
00:51:34.460
But in dissecting that a little bit further with him,
link |
00:51:36.660
I came to realize that these words I am are very powerful.
link |
00:51:41.080
I don't think you reprogram your brain just by saying them,
link |
00:51:43.660
but how one defines themselves internally,
link |
00:51:49.700
not just to other people,
link |
00:51:51.260
but how one psychologically and by default
link |
00:51:54.300
defines themselves, I think is a very powerful,
link |
00:51:57.220
like and depressed people,
link |
00:51:59.940
as well as happy people seem to define themselves
link |
00:52:02.020
in terms of these categories of emotional states.
link |
00:52:04.780
So I think it's so interesting that letting go
link |
00:52:09.060
and going into this perceptual bubble,
link |
00:52:10.960
which is facilitated by obviously a really wonderful team
link |
00:52:14.540
of therapists, but also the serotonergic agent
link |
00:52:17.780
allows us to potentially reshape the perception of self.
link |
00:52:22.960
That's a tremendous feat of neuroplasticity.
link |
00:52:26.420
Right, and I think certainly more work needs to be done.
link |
00:52:30.700
This is the horizon.
link |
00:52:33.020
And I should credit Chris Lethaby, a philosopher
link |
00:52:36.820
in Australia who has a forthcoming book.
link |
00:52:40.220
It might be out right about now or soon,
link |
00:52:42.660
within the coming months, Psychedelics and Philosophy.
link |
00:52:47.260
That's the title of the book.
link |
00:52:49.340
It might be Psychedelic Philosophy.
link |
00:52:51.100
It's really close.
link |
00:52:51.940
Chris Lethaby, we'll put a link to it.
link |
00:52:53.780
Right, and so his conclusion in this,
link |
00:52:56.300
it's a really great book and he really plays with the idea.
link |
00:52:59.580
It's like psychedelic experiences come along
link |
00:53:01.480
with a lot of supernatural stuff, experience.
link |
00:53:05.460
It can certainly go along with that,
link |
00:53:06.940
but the idea is like, can these experiences
link |
00:53:09.820
and including those therapeutic effects
link |
00:53:11.380
be explained from a naturalist point of view?
link |
00:53:14.900
And his conclusion is that the changes
link |
00:53:18.180
in self-representation may be the commonality.
link |
00:53:20.820
Now that could go along with plant spirits
link |
00:53:23.820
and the Buddha and chakras and whatever your model,
link |
00:53:28.700
you know, system in Jesus, all of that,
link |
00:53:32.140
but it could also be completely devoid
link |
00:53:34.940
of any supernatural, any religious.
link |
00:53:37.460
And we do, in fact, see all of these varieties.
link |
00:53:41.860
So I think there's something about this change
link |
00:53:43.900
in sense of self.
link |
00:53:45.780
There seems to be something on the identity level,
link |
00:53:48.140
both with, I think, of the work we did
link |
00:53:49.940
with cancer patients who had substantial depression
link |
00:53:52.260
and anxiety because of their cancer,
link |
00:53:53.940
and also our work with people
link |
00:53:55.020
trying to quit cigarette smoking.
link |
00:53:57.540
I mean, there's this real,
link |
00:54:00.780
there seems to be, when it really works,
link |
00:54:02.520
this change in how people view themselves,
link |
00:54:06.340
like with smoking, like really stepping out of this model,
link |
00:54:11.540
like I'm a smoker, it's tough to quit smoking cigarettes,
link |
00:54:15.620
I can't do it, I failed a bunch of times.
link |
00:54:18.420
I remember one participant during the session,
link |
00:54:20.780
but he held onto this afterwards, said,
link |
00:54:22.580
my God, it's like, I can really just decide,
link |
00:54:26.780
like flicking off a bucket, I can decide not to smoke.
link |
00:54:29.420
And it's, I call these duh experiences with psychedelics
link |
00:54:32.420
because people often, like in the cancer study,
link |
00:54:34.820
they say, I'm causing most of my own suffering.
link |
00:54:38.160
Like I can follow my appointments, I can do everything,
link |
00:54:40.820
but I can still plan for the vacation,
link |
00:54:42.020
I'm not getting outside in the sunshine,
link |
00:54:44.860
I'm not playing with my grandkids, I'm choosing to do that.
link |
00:54:47.660
And it's like, they told themselves that before,
link |
00:54:50.020
and the smoker has told themselves a million times,
link |
00:54:52.900
I can, so it sounds, when it comes out of their mouths,
link |
00:54:56.140
and folks will say, this is part of the ineffability
link |
00:54:58.340
of a psychedelic experience, folks say,
link |
00:55:00.080
I know this sounds like bullshit, and this sounds like,
link |
00:55:02.340
but my God, I could just decide.
link |
00:55:05.420
Like, they're feeling this gravity of agency,
link |
00:55:08.980
which I think is interesting,
link |
00:55:10.100
because regardless of the debates
link |
00:55:13.980
on the reality of free will,
link |
00:55:15.660
I think the philosophy of that,
link |
00:55:18.300
whether it's ultimately free will, like pure agency,
link |
00:55:22.180
if that exists, which I'm skeptical of,
link |
00:55:24.320
or just the idea that clearly we have a sense of agency,
link |
00:55:28.600
there's something there,
link |
00:55:30.360
whether it's the sense of agency even,
link |
00:55:32.840
that is the human being has,
link |
00:55:35.540
and that seems to be at times fundamentally like supercharged
link |
00:55:41.480
from a psychedelic experience, this idea like,
link |
00:55:44.180
I'm just going to make a decision.
link |
00:55:46.740
Like normally, like you tell a depressed person,
link |
00:55:48.620
like, don't think of yourself that way,
link |
00:55:50.300
you're not a failure, look at all the, it's just, yeah,
link |
00:55:52.460
it's like, and you can actually, in one of these states,
link |
00:55:55.700
have an experience where you realize like, my God,
link |
00:55:57.880
just like using MDMA to treat PTSD,
link |
00:56:00.460
and we're going to be starting work with psilocybin
link |
00:56:02.020
to treat PTSD,
link |
00:56:03.100
someone could really reprocess their trauma
link |
00:56:06.740
in a way that like has lasting effects,
link |
00:56:09.740
and clearly there's probably something, you know,
link |
00:56:11.640
reconsolidation of those memories,
link |
00:56:14.060
they are altered, you know,
link |
00:56:17.060
very consistent with our understanding
link |
00:56:19.260
of the way memory works.
link |
00:56:20.360
So the whole idea, people can actually, in a few hours,
link |
00:56:24.740
have such a profound experience
link |
00:56:26.440
that they decide to make these changes in who they are,
link |
00:56:31.100
and it sticks.
link |
00:56:32.620
There seems to be something like that.
link |
00:56:34.340
And that's profound.
link |
00:56:35.460
I mean, I think a few moments ago,
link |
00:56:38.680
I made some semi-disparaging statements
link |
00:56:41.400
about things like the secret and affirmations,
link |
00:56:43.860
and the reason I do that with a nod to the fact
link |
00:56:48.700
that the people who are putting those ideas forward
link |
00:56:51.460
are well-intentioned people
link |
00:56:53.100
is that the neural networks of the brain put language last.
link |
00:56:59.660
We tell stories, you know, and stories are very powerful,
link |
00:57:03.060
but I think one of the most cruel aspects
link |
00:57:07.680
of the whole self-help literature in popular psychology
link |
00:57:11.900
is this idea that everything you say,
link |
00:57:13.880
your brain and body hear it.
link |
00:57:15.820
That's actually a very unkind or even cruel thing
link |
00:57:19.260
for people who are depressed or anxious to hear,
link |
00:57:22.060
because if they hear that and believe that,
link |
00:57:24.060
and I want to be clear, I don't think it's true,
link |
00:57:26.260
that they think that it's very hard to control thoughts.
link |
00:57:30.600
Is it very hard to control thoughts?
link |
00:57:32.500
So if somebody says, you know, I can't,
link |
00:57:35.240
and then somebody says, well, no,
link |
00:57:36.540
every time you say you can't,
link |
00:57:37.700
your brain hears that and it reinforces it,
link |
00:57:39.500
that's a very treacherous place to live.
link |
00:57:42.760
And language is powerful, but neural networks, the brain,
link |
00:57:48.980
and the networks that underlie emotionality and perception
link |
00:57:51.880
and sense of self, they don't change in response to language.
link |
00:57:56.020
They change in response to experience.
link |
00:57:59.240
And it just fundamentally, you need,
link |
00:58:01.660
there are some prerequisites.
link |
00:58:02.700
You need certain neuromodulators present,
link |
00:58:04.660
like serotonin or dopamine.
link |
00:58:06.500
You need them to be at sufficient levels.
link |
00:58:08.260
You don't need a drug necessarily to do it.
link |
00:58:09.900
You could, you know, you give a kid a kitten or a puppy,
link |
00:58:13.540
their first kitten or puppy,
link |
00:58:14.820
and the levels of dopamine and serotonin,
link |
00:58:17.740
I've never measured them,
link |
00:58:18.580
but we can be pretty sure that they are higher
link |
00:58:20.620
than baseline and that experience will reshape them, right?
link |
00:58:24.940
Likewise with an adult in certain circumstances.
link |
00:58:28.280
So I think I'm fascinated by this idea
link |
00:58:31.420
that a somatic and a perceptual experience,
link |
00:58:35.900
but a real experience of the sort that you're describing
link |
00:58:39.400
is what allows us to reshape our neural circuitry
link |
00:58:41.900
and to feel differently about ourselves.
link |
00:58:43.780
And I know there's been really tremendous success
link |
00:58:48.700
in many individuals of alleviating depression,
link |
00:58:52.460
of treating trauma with these different compounds.
link |
00:58:55.140
I want to step from the experience
link |
00:58:59.200
under the effects of the psychedelic.
link |
00:59:01.600
So the person there with your team,
link |
00:59:03.300
they go into this expanded perceptual bubble.
link |
00:59:05.860
If things go well,
link |
00:59:08.020
they're able to do that to a really deep degree.
link |
00:59:10.040
Maybe it's the relive trauma.
link |
00:59:12.360
Maybe it's the beauty of their ability
link |
00:59:14.580
to connect to things in the world.
link |
00:59:16.920
And I want to talk about the transition out of that state
link |
00:59:19.900
and then the export into life,
link |
00:59:21.980
because this is really where the power of psychedelics
link |
00:59:24.340
seems to be in the therapeutic sense
link |
00:59:26.460
is the ability to learn, truly learn from that experience
link |
00:59:29.560
so that the learning becomes the default,
link |
00:59:31.880
that one doesn't have to remind themselves,
link |
00:59:33.320
oh, I am, you know, they don't have to do an affirmation.
link |
00:59:35.940
I am a happy person.
link |
00:59:37.080
I am a happy, you know, I always think of Bart Simpson
link |
00:59:38.940
like writing on the chalkboard, right?
link |
00:59:40.580
Didn't work for him.
link |
00:59:41.420
Doesn't work for this other stuff too.
link |
00:59:43.300
But so as they transition out of this state,
link |
00:59:46.380
I know that there's a kind of a heightened,
link |
00:59:47.740
there's a so-called peak
link |
00:59:49.380
where everything seems to be kind of cascading in
link |
00:59:51.800
at such a level that the person just,
link |
00:59:55.820
they can't really turn it off at that point.
link |
00:59:57.620
It would be challenging.
link |
00:59:59.880
And then they start to exit the effects of the drug.
link |
01:00:05.180
Are those transition zones, are those valuable,
link |
01:00:08.200
much like is the transition
link |
01:00:09.940
between a dream and the waking state valuable?
link |
01:00:12.820
Because you're in a sort of mishmash of altered reality
link |
01:00:16.540
and new reality.
link |
01:00:18.340
What do you do to guide people through the,
link |
01:00:22.940
out the tunnel as they exit the tunnel?
link |
01:00:25.220
And I have to say,
link |
01:00:26.100
like this is where we need more experimentation.
link |
01:00:30.180
Really the clinical model goes back
link |
01:00:32.400
to literally the late 1950s.
link |
01:00:35.940
And there's been virtually no experimentation on,
link |
01:00:39.400
let's say, you know, randomize people to,
link |
01:00:42.020
we're going to talk more during the latter half
link |
01:00:44.020
of the session versus not,
link |
01:00:46.060
versus we have them write an essay
link |
01:00:48.580
after their session versus not,
link |
01:00:50.140
versus we have this amount of integration.
link |
01:00:52.340
What's the discussion?
link |
01:00:53.500
In your studies, are they writing or talking
link |
01:00:55.940
as they're doing it?
link |
01:00:56.780
And it's called very loosey-goosey term integration,
link |
01:01:00.620
but for us means as they're coming back from the experience
link |
01:01:06.060
to sort of five, six hours in,
link |
01:01:08.060
so this is the afternoon,
link |
01:01:09.180
they've been dosed around nine o'clock,
link |
01:01:10.640
so this is like four o'clock or so.
link |
01:01:13.140
Just some initial,
link |
01:01:13.980
tell us about the experience.
link |
01:01:15.380
Do you want to not unpacking it totally,
link |
01:01:17.300
but kind of initially just have a little bit discussion
link |
01:01:19.460
before they go home.
link |
01:01:20.300
So there's a little bit of that,
link |
01:01:21.820
but then that night their homework is to write something.
link |
01:01:25.460
So it could be, you know, a few bullet points.
link |
01:01:27.700
It could be, you know, 20 pages
link |
01:01:30.420
and we get everything, you know, in that range,
link |
01:01:33.980
but, you know, try not to be self-critical.
link |
01:01:36.900
It's not great at like, this is just to process.
link |
01:01:39.720
And for a point of discussion the next day.
link |
01:01:41.560
So they write something, they come in the next day
link |
01:01:44.000
for a one to two hour,
link |
01:01:45.940
depending on the study, integration session.
link |
01:01:48.140
Basically, let's discuss your experience
link |
01:01:51.360
and depending on what study it's in,
link |
01:01:53.440
like what might that mean for your dealing with cancer?
link |
01:01:57.160
What might that mean for your smoking?
link |
01:02:00.460
Or becoming a non-smoker?
link |
01:02:02.460
So you encourage them to simply take it seriously.
link |
01:02:04.940
And I think this is, again,
link |
01:02:06.380
is sort of one of the points
link |
01:02:08.380
that could be the antithesis
link |
01:02:09.840
of what some just kind of social users use.
link |
01:02:13.860
I mean, this was written about by Houston Smith,
link |
01:02:17.260
the scholar of religion,
link |
01:02:18.300
in terms of these mystical experiences
link |
01:02:20.780
that can happen from psychedelics
link |
01:02:22.180
and how a lot of times the attribution
link |
01:02:24.860
to a drug effect is dismissed.
link |
01:02:26.740
Like even if one has this, you know,
link |
01:02:30.540
this sense of being one with the universe
link |
01:02:32.120
and it totally like shakes their soul, so to speak,
link |
01:02:34.900
you know, but the next day their friends are like,
link |
01:02:36.600
ah, dude, you were screwed up.
link |
01:02:38.820
Too much acid for you, woo.
link |
01:02:40.740
You know, like, man, next time
link |
01:02:42.380
you needed to have a few more beers to like bring that down.
link |
01:02:44.940
You know, like this sort of like, you know,
link |
01:02:48.460
social, you know, reinforcement
link |
01:02:50.960
for dismissing the experience.
link |
01:02:52.860
Oh God, you're talking out of your head, man.
link |
01:02:55.040
Like, you know, even if it's, you know, good natured,
link |
01:02:58.180
but it's this dismissal, it's not like, you know,
link |
01:03:01.820
what you want to do, you know,
link |
01:03:03.620
is like, tell me more about that.
link |
01:03:05.300
You know, you were crying at one point,
link |
01:03:07.040
like in talking about your mom, let's talk about that.
link |
01:03:10.300
What was that like?
link |
01:03:11.140
Do you remember that?
link |
01:03:13.380
Are you doing that follow-up
link |
01:03:14.740
or they're encouraged to do that in their own life
link |
01:03:16.660
with the various people in their life?
link |
01:03:18.060
Both, so we do that explicitly in the follow-up
link |
01:03:20.900
where we have these discussions.
link |
01:03:22.260
And I, depending on what the situation is,
link |
01:03:26.540
you might encourage the person to kind of follow up.
link |
01:03:29.780
It's really, the basics of it is supportive therapy.
link |
01:03:35.920
It's non-structured.
link |
01:03:37.380
It's, you know, use all the, you know, reflective listening
link |
01:03:40.140
and the sort of the humanistic psychology thing,
link |
01:03:42.540
you know, unconditional positive regard for the person.
link |
01:03:45.220
But, you know, I think if, you know,
link |
01:03:48.940
if someone feels inclined to, you know,
link |
01:03:51.660
apologize to their sibling about something,
link |
01:03:56.940
it's like, yeah, go ahead and call them up.
link |
01:03:58.440
When it, with something big, like a relationship change,
link |
01:04:01.160
I'd be like, sit on that two weeks.
link |
01:04:04.140
Don't make any big, don't end any relationship.
link |
01:04:06.540
Don't quit your job.
link |
01:04:07.580
Don't make any big-
link |
01:04:08.580
Do you also tell them not to start any relationships?
link |
01:04:13.820
I don't remember that ever coming up.
link |
01:04:15.740
Interesting.
link |
01:04:16.580
But if it-
link |
01:04:17.420
I'm not Joey.
link |
01:04:18.240
I was just wondering, you know, but it makes sense
link |
01:04:19.880
why you move on.
link |
01:04:20.720
Like if they're dating and they're thinking like,
link |
01:04:21.840
ah, it might be time to take it to the next level.
link |
01:04:24.260
Should I ask this girl to marry me?
link |
01:04:26.260
If it did come up, I would say there too.
link |
01:04:29.260
Why don't you sit on that a week or two
link |
01:04:30.580
and let your sober mind-
link |
01:04:32.420
Don't get a puppy.
link |
01:04:33.420
Certainly don't get four puppies until you're-
link |
01:04:36.180
I have a question about flashbacks.
link |
01:04:40.240
Uh-huh.
link |
01:04:41.080
You know, one of the kind of things you hear is,
link |
01:04:43.700
you know, flashbacks and that people,
link |
01:04:46.020
do people get flashbacks?
link |
01:04:47.620
And if so, what is the basis of flashbacks?
link |
01:04:49.700
The on the street lore about this
link |
01:04:54.700
is that somehow some of the compound gets stored
link |
01:04:58.380
in body fat tissues and then released later.
link |
01:05:00.460
Like is that complete nonsense?
link |
01:05:02.900
No evidence for that.
link |
01:05:04.280
So probably complete nonsense.
link |
01:05:06.460
Flashbacks are nonsense or the storage in body fat
link |
01:05:08.920
is complete nonsense?
link |
01:05:09.760
The storage in body fat.
link |
01:05:11.020
So to answer whether flashbacks are complete nonsense,
link |
01:05:14.340
we have to define it.
link |
01:05:15.420
So I really think these are multiple constructs
link |
01:05:17.660
that are going on.
link |
01:05:18.480
It's not the same thing that fall under that term.
link |
01:05:21.620
There is a phenomenon that appears real
link |
01:05:25.460
that's called hallucinogen persisting perceptual disorder.
link |
01:05:28.420
It's in the DSM.
link |
01:05:30.420
A certain number of people,
link |
01:05:32.300
very small number of people percentage wise
link |
01:05:35.760
who have used psychedelics
link |
01:05:37.100
will have these persisting perceptual disorders.
link |
01:05:40.140
Like they'll see halos around things.
link |
01:05:41.760
They'll see some trails, like, you know,
link |
01:05:44.120
like the after images following an object in motion.
link |
01:05:49.500
They'll see distortions in color.
link |
01:05:51.300
And it'll be like anything else
link |
01:05:53.420
that's a disorder in the DSM.
link |
01:05:55.660
It has to be clinically distressing
link |
01:05:57.180
and it has to be persisting over some number of months.
link |
01:06:01.340
And so very rare, very mysterious.
link |
01:06:04.900
Some of the keys to that are amazingly,
link |
01:06:08.440
it's never been seen in the thousands of participants
link |
01:06:11.460
either from the older era,
link |
01:06:12.700
from the late fifties to the early seventies,
link |
01:06:15.580
people in psychedelic studies with LSD, psilocybin, masculine
link |
01:06:18.460
and it's never been seen in the modern era.
link |
01:06:20.140
Again, now with thousands of participants
link |
01:06:22.700
at a number of centers like ours throughout the world.
link |
01:06:26.540
So it seems to be something that is
link |
01:06:30.500
for some reason happening in illicit use.
link |
01:06:33.860
So that brings in, okay, is there polypharmacology?
link |
01:06:38.260
You know, like, cause you're drinking during it.
link |
01:06:39.940
Did you take what you thought you'd do?
link |
01:06:40.940
Yeah, what's the dose, what's the purity?
link |
01:06:43.460
But then also what I think is actually even more so
link |
01:06:46.660
than that what's likely going on
link |
01:06:48.100
is some sort of very rare neurological susceptibility.
link |
01:06:51.020
There is one paper that is a case series
link |
01:06:55.420
of individuals reporting these symptoms
link |
01:06:57.180
and they didn't limit it to just people
link |
01:06:59.900
who had had hallucinogen history.
link |
01:07:02.620
And the amazing thing about this is that
link |
01:07:05.700
a number of people seem to have straight up HPPD diagnosis.
link |
01:07:10.620
What is HPPD?
link |
01:07:11.780
Hallucinogen persisting perceptual disorder
link |
01:07:14.060
who have never taken a psychedelic.
link |
01:07:16.040
So it's often prompted by alcohol,
link |
01:07:20.940
benzodiazepines, cannabis, even tobacco.
link |
01:07:25.660
And I believe in one individual,
link |
01:07:29.460
no lifetime history of any,
link |
01:07:31.180
it wasn't preceded by any of those substance use.
link |
01:07:35.860
So I think of it like the precipitation exacerbation
link |
01:07:41.300
of psychotic disorders.
link |
01:07:42.660
It seems pretty clear through observation
link |
01:07:44.740
that some people with either predisposition
link |
01:07:47.940
or active psychotic disease
link |
01:07:49.860
that this can destabilize them.
link |
01:07:52.640
The same way that a life experience
link |
01:07:54.300
can destabilize those person more easily,
link |
01:07:56.380
I think of it like that there's probably
link |
01:07:57.640
some pretty rare neurological susceptibility.
link |
01:08:00.660
We have tended, going this goes back to the 80s,
link |
01:08:05.020
clinical practice, it ended up in the DSM
link |
01:08:07.540
focused on hallucinogen because I relate it
link |
01:08:11.440
to the psychology of xenophobia.
link |
01:08:13.820
It's always the weird other thing that gets the attribution.
link |
01:08:16.780
You don't attribute to the thing like,
link |
01:08:19.080
oh yeah, did you smoke cigarettes?
link |
01:08:20.620
Did you drink?
link |
01:08:21.460
It's like, well, yeah, but I see lots of people drinking
link |
01:08:23.660
and not ending up with this.
link |
01:08:25.020
Like you take a crazy like drug
link |
01:08:29.140
and you can get people to believe all sorts of crazy stuff.
link |
01:08:32.220
The biggest example of that is the cathinone derivatives,
link |
01:08:35.420
so-called bath salts.
link |
01:08:36.900
And if you remember several years back,
link |
01:08:39.140
the guy in Florida that ate the other guy's face,
link |
01:08:42.820
there was a homeless guy that like literally
link |
01:08:44.980
ate part of someone's face off, like yeah.
link |
01:08:47.340
It's one of the crazies.
link |
01:08:48.180
While the person was alive.
link |
01:08:49.020
While the person was alive.
link |
01:08:50.500
And all it took was one sheriff's deputy to say,
link |
01:08:53.740
well, I don't know, but I bet it was
link |
01:08:55.860
some of that bath salts stuff that's been going on.
link |
01:08:58.500
The only thing-
link |
01:08:59.340
What was it?
link |
01:09:00.700
The only thing in his system-
link |
01:09:01.660
Maybe we can set the record straight for people.
link |
01:09:03.540
What was the, why would he say bath salts?
link |
01:09:06.700
And was it bath salts?
link |
01:09:08.420
It wasn't.
link |
01:09:09.620
And so the only thing in his talks was cannabis,
link |
01:09:12.420
which we all know,
link |
01:09:14.540
typically people don't eat people's faces off
link |
01:09:16.580
after they get stuff-
link |
01:09:17.420
Makes you hungrier, but not that hungry.
link |
01:09:19.180
Right, right.
link |
01:09:20.100
So it's just an example of the xenophobia.
link |
01:09:22.860
Like today, if you get on Google Images
link |
01:09:24.900
and look up bath salts,
link |
01:09:26.500
one of the most common images you'll see
link |
01:09:29.140
is this poor guy's face being eaten off.
link |
01:09:31.420
So we're just so ready to latch on,
link |
01:09:33.540
just like the people of another culture
link |
01:09:36.140
that we don't know of.
link |
01:09:36.980
It's very easy to assign attribution to a class
link |
01:09:41.980
that you're very unfamiliar with.
link |
01:09:43.300
So I think the psychedelics got that attribution
link |
01:09:46.460
with this very rare neurological susceptibility,
link |
01:09:50.100
the way that alcohol didn't.
link |
01:09:51.540
So I think it's not specific to psychedelics,
link |
01:09:54.780
but we don't really know.
link |
01:09:56.980
But we look at it,
link |
01:09:58.060
and our research have never seen an example of it.
link |
01:10:00.340
But flashbacks can mean a number of other things.
link |
01:10:03.420
I think the most common thing people experience
link |
01:10:05.300
is what we call state-dependent learning.
link |
01:10:08.580
It's returning yourself to a similar context
link |
01:10:12.220
can bring back the same thoughts
link |
01:10:13.940
and emotions as the experience.
link |
01:10:15.860
So someone used mushrooms a week ago.
link |
01:10:18.780
Now they do something like they smoke some cannabis,
link |
01:10:22.380
or they take a warm bath,
link |
01:10:27.220
or they're simply relaxed
link |
01:10:29.100
and it seems to come out of the blue,
link |
01:10:30.580
and all of a sudden these,
link |
01:10:31.940
or they follow a thought trail
link |
01:10:33.980
that reminds them of their,
link |
01:10:35.780
and they find themselves in that same experience again.
link |
01:10:39.900
I think that's more state-dependent learning.
link |
01:10:42.020
It's not the distressing component that is in,
link |
01:10:45.420
and it's typically not perceptual.
link |
01:10:47.420
And then another class
link |
01:10:49.540
are just sort of perceptual anomalies
link |
01:10:53.580
within a day or two following the experience,
link |
01:10:56.780
which is not HPPD.
link |
01:10:58.540
Most people have joked that this is a free trip.
link |
01:11:01.660
Like you might see a few trails or halos the day afterwards.
link |
01:11:04.980
It doesn't last longer than that.
link |
01:11:07.620
And it doesn't screw you up.
link |
01:11:09.340
It's kind of fun.
link |
01:11:10.180
Like, oh yeah, I'm still seeing some trails.
link |
01:11:11.580
Most people will say.
link |
01:11:13.420
So it could mean any of those things.
link |
01:11:15.380
Flashback is, yeah.
link |
01:11:17.020
Interesting.
link |
01:11:17.860
No, I appreciate you clarifying that.
link |
01:11:20.220
I mean, one very common misconception
link |
01:11:23.660
about neuroplasticity is that it's an event
link |
01:11:26.340
and it's not an event, it's a process.
link |
01:11:28.860
And we have no understanding
link |
01:11:31.620
of the duration of that process.
link |
01:11:33.780
However, the experience of any drug
link |
01:11:37.460
or any life experience, right,
link |
01:11:39.420
even if it's a trauma or a wonderful experience
link |
01:11:41.980
or a psychedelic experience, doesn't matter,
link |
01:11:44.340
sets in motion a series of dominoes that fall.
link |
01:11:47.980
And it's the falling of those dominoes
link |
01:11:49.540
that we call neuroplasticity.
link |
01:11:51.020
I mean, the reshaping of neural circuits could take years.
link |
01:11:54.140
We don't know.
link |
01:11:55.100
It's the trigger and then there's the actual change.
link |
01:11:58.100
And so I think that some of what you described
link |
01:12:00.500
could be literally the reordering of circuitry,
link |
01:12:03.740
that in some individuals might extend longer than others.
link |
01:12:07.860
And there is one phenomenon
link |
01:12:10.340
that I've been told people experience.
link |
01:12:14.380
And I'm wondering whether or not
link |
01:12:15.420
any of the patients you've worked with
link |
01:12:17.580
or people in your trials have reported this.
link |
01:12:21.540
I've never done ayahuasca,
link |
01:12:24.220
which I'm assuming has some overlap
link |
01:12:25.900
with the serotonin system.
link |
01:12:27.020
Probably hits a variety of systems.
link |
01:12:28.060
So it's DMT, the active, yeah, it's orally active.
link |
01:12:30.940
That's right.
link |
01:12:31.780
MAO inhibitors that allow the DMT
link |
01:12:33.340
to be orally.
link |
01:12:34.180
Right, I should have recalled that, absolutely.
link |
01:12:37.580
Well, I've never done it,
link |
01:12:38.420
but a number of people I know that have done ayahuasca
link |
01:12:41.700
as well as people I know who have done MDMA
link |
01:12:44.780
report an increased sense of what are sometimes called ASMR,
link |
01:12:49.100
or these autonomic sensory meridian reflexes, which is,
link |
01:12:52.980
and it's interesting,
link |
01:12:53.820
a lot of people have these naturally and they hide these.
link |
01:12:57.900
It's actually something
link |
01:12:58.980
that many people keep hidden to themselves.
link |
01:13:01.180
I'll just ask you if you can do it.
link |
01:13:03.700
So some people are able to pass a,
link |
01:13:06.620
like a shiver down their spine
link |
01:13:08.460
or up their spine consciously.
link |
01:13:10.500
You know, like you can kind of,
link |
01:13:11.900
like I'm able to actually pass a shiver up my spine.
link |
01:13:14.500
I actually learned how to do this when I was a kid
link |
01:13:15.980
on a hot day.
link |
01:13:16.820
I was standing on a field in sports camp
link |
01:13:18.260
and I was like, it's really hot here.
link |
01:13:19.420
And I could actually create like a cooling,
link |
01:13:22.540
cooled perception.
link |
01:13:24.220
Some people, I told someone this once
link |
01:13:26.140
and then this led to a discussion of, oh, I can do it.
link |
01:13:28.340
But I always hid that from people
link |
01:13:29.500
because it's actually somewhat pleasurable.
link |
01:13:31.620
And this is a well-known phenomenon, ASMR.
link |
01:13:35.260
And some people I know who have taken MDMA therapeutically
link |
01:13:38.980
or ayahuasca will report that they feel great relief
link |
01:13:44.180
from this.
link |
01:13:45.020
They can generate these autonomic reflexes
link |
01:13:47.180
through their body more readily.
link |
01:13:49.220
Probably, I'm guessing,
link |
01:13:50.700
because they were able to tune into a kind of deeper sense
link |
01:13:53.900
of somatic self.
link |
01:13:55.260
Now on the internet, ASMR, if you look it up,
link |
01:13:57.980
it's a little bit like the bath salt thing,
link |
01:13:59.420
but in the other direction.
link |
01:14:00.460
Like there were people that pay,
link |
01:14:03.340
let's just say there are accounts on YouTube
link |
01:14:04.980
that have many, many millions of viewers
link |
01:14:07.700
of people that will whisper to them about,
link |
01:14:11.580
like for instance, there's people that will go listen to,
link |
01:14:15.420
it seems to be women in particular,
link |
01:14:16.940
whispering about like car mechanics or something
link |
01:14:19.900
or about, or scratching.
link |
01:14:21.580
So there are certain sounds will do this,
link |
01:14:23.500
whispering, tapping, finger tapping,
link |
01:14:25.820
and people experience immense pleasure from it.
link |
01:14:28.100
It's not really sexual pleasure,
link |
01:14:29.540
but it's this kind of deep core of the body.
link |
01:14:32.420
It's the autonomic nervous system
link |
01:14:34.180
down the corner of the spine.
link |
01:14:35.020
Probably what a certain number of people
link |
01:14:36.260
would call Kundalini,
link |
01:14:37.780
which is another one scientifically who, yeah.
link |
01:14:40.340
That's right.
link |
01:14:41.180
People who do long duration Kundalini breathing sessions,
link |
01:14:44.380
many of them will report later feeling
link |
01:14:46.700
as if their perception of self is outside of their head,
link |
01:14:50.980
that they're literally walking.
link |
01:14:52.660
It's very uncomfortable for them
link |
01:14:54.420
that they feel like they're walking around
link |
01:14:56.060
with their sense of self extended beyond the body.
link |
01:14:59.380
And this is a clinically described neurologic phenomenon.
link |
01:15:02.380
Have any studies been done?
link |
01:15:03.500
I would imagine that person might actually like,
link |
01:15:05.900
would they duck?
link |
01:15:07.420
Oh, what?
link |
01:15:08.260
Like that would be an interesting experiment.
link |
01:15:09.100
That would be the kind of thing my lab
link |
01:15:10.260
would want to get into.
link |
01:15:11.100
Yeah, their body could clear,
link |
01:15:12.700
but their projection wouldn't.
link |
01:15:15.460
Yeah, the sense of self.
link |
01:15:16.660
I mean, there's a well-known phenomenon.
link |
01:15:18.380
It's very, in a few individuals,
link |
01:15:20.660
very sad where people actually avidly seek out
link |
01:15:24.020
amputation of their limbs
link |
01:15:25.220
because their limbs they feel don't belong to their body.
link |
01:15:27.620
Oh yeah.
link |
01:15:28.460
This is a very sad and fortunately very rare,
link |
01:15:31.020
but also very sad condition.
link |
01:15:32.620
Anyway, I think that the core of this conversation
link |
01:15:36.660
that we're drilling into is this notion
link |
01:15:38.900
of reordering the self.
link |
01:15:40.860
And it's a relief to me to know that flashbacks
link |
01:15:43.700
are not something that is kind of, forgive the term,
link |
01:15:47.860
baked in to the psychedelic experience.
link |
01:15:51.860
And I suppose that's a good segue
link |
01:15:53.340
to ask about other sorts of drugs.
link |
01:15:56.420
Having said baked in,
link |
01:15:57.300
the temptation is to go to marijuana or cannabis,
link |
01:16:00.620
but if we could, I'd like to just ask about
link |
01:16:04.420
some of the more dopaminergic compounds,
link |
01:16:06.900
in particular MDMA.
link |
01:16:08.340
Yeah.
link |
01:16:09.260
My understanding is that MDMA
link |
01:16:11.540
is a purely synthetic compound,
link |
01:16:14.180
that you're not going to find MDMA in nature.
link |
01:16:16.860
So far.
link |
01:16:17.980
So far.
link |
01:16:18.820
DMT was first synthesized in the lab
link |
01:16:20.780
and then we thought it didn't exist in nature
link |
01:16:23.100
and then like Richard Schultes
link |
01:16:25.420
found it like everywhere in South America.
link |
01:16:28.660
Who knows?
link |
01:16:29.500
A plan out there might be making MDMA,
link |
01:16:31.060
but as far as we know now, no.
link |
01:16:33.020
Right.
link |
01:16:33.860
And we'll talk about DMT and its sources within the body,
link |
01:16:35.700
but MDMA could exist elsewhere,
link |
01:16:40.940
but has been synthesized.
link |
01:16:42.140
And my understanding is that MDMA
link |
01:16:44.740
leads to very robust increases
link |
01:16:47.380
in both dopamine and serotonin simultaneously,
link |
01:16:50.620
which from a neural network's perspective
link |
01:16:55.100
is a very unusual situation, right?
link |
01:16:57.660
Normally, because dopamine puts us in this exteroceptive,
link |
01:17:00.820
looking outside ourselves,
link |
01:17:01.900
seeking things in the world beyond the skin, our own skin,
link |
01:17:05.980
and dopamine, excuse me, serotonin tends to focus us inward.
link |
01:17:09.700
Those are almost mutually exclusive
link |
01:17:11.620
kind of neurochemical states,
link |
01:17:13.540
although they're always at different levels.
link |
01:17:15.140
So why would it be that having this increased dopamine
link |
01:17:20.780
and increased serotonin would provide an experience
link |
01:17:25.060
that is beneficial?
link |
01:17:26.540
And how do you, to the extent that you can describe it,
link |
01:17:29.580
how do you think that experience differs
link |
01:17:31.580
from the sorts of experiences that people have on psilocybin
link |
01:17:34.100
or more serotonergic agents?
link |
01:17:36.580
Just broadly speaking.
link |
01:17:37.940
Yeah, yeah.
link |
01:17:39.340
In terms of that balance,
link |
01:17:41.260
in terms of the effects generally on serotonin and dopamine,
link |
01:17:46.260
I can only speculate,
link |
01:17:49.060
like sort of is that dopaminergic component necessary
link |
01:17:53.740
for, let's say we know that the amygdala
link |
01:17:56.740
is less reactive under acute effects,
link |
01:17:59.580
and that may play a role in,
link |
01:18:03.460
there's less sort of control from the amygdala
link |
01:18:07.140
in terms of like one's experience of memory.
link |
01:18:10.100
So it may be part of this sort of reprocessing,
link |
01:18:13.100
this reconsolidation of these memories in a different way
link |
01:18:15.740
where the amygdala is not like going crazy,
link |
01:18:17.900
saying freak out, like fight or flight.
link |
01:18:20.380
Well, I should have said,
link |
01:18:21.580
it seems like MDMA is being used clinically anyway,
link |
01:18:25.180
mainly for trauma, not just for depression.
link |
01:18:30.860
Although part of that, we really don't know,
link |
01:18:33.740
and maybe that MDMA is great for depression
link |
01:18:36.380
and some of these other, and it may be that,
link |
01:18:38.060
and I'm going to be looking at this soon,
link |
01:18:39.300
that psilocybin is great for treating PTSD.
link |
01:18:42.100
A lot of underground therapists say that,
link |
01:18:44.780
underground psychedelic therapists.
link |
01:18:46.260
So we don't really know yet which people doing illegal,
link |
01:18:51.100
but more like a professional therapist would,
link |
01:18:54.420
it's just illegal.
link |
01:18:55.500
And this is a kind of a growing thing.
link |
01:18:59.340
So we don't really know which,
link |
01:19:02.100
it's speculating, but it may be that MDMA
link |
01:19:06.620
for a broader number of people is better for trauma
link |
01:19:11.980
because the chances of having
link |
01:19:14.300
an extremely challenging experience,
link |
01:19:16.140
what I call the bad trip, like really freaking out,
link |
01:19:20.860
is much lower with MDMA.
link |
01:19:22.500
People can have bad trips,
link |
01:19:23.740
but they're of a different nature.
link |
01:19:25.420
It's not sort of like freaking out
link |
01:19:28.500
because all of reality is sort of shattering
link |
01:19:31.100
and it's less of this,
link |
01:19:33.340
it can take so many forms with the classic psychedelics,
link |
01:19:36.340
but typically you'll hear something like,
link |
01:19:40.220
I didn't know it was going to be like this,
link |
01:19:42.740
no matter how hard you tried to prepare them,
link |
01:19:44.940
that like, this is like, get me off this drive.
link |
01:19:49.060
You're talking about LSD or psilocybin.
link |
01:19:50.380
LSD, psilocybin, IY, yeah, yeah.
link |
01:19:53.500
And just the sense of like, I'm going insane.
link |
01:19:56.660
This is so far beyond anything I've ever experienced
link |
01:20:00.420
and it's scaring the shit out of me.
link |
01:20:03.300
How often does that happen?
link |
01:20:04.140
I don't have a toe hold on anything,
link |
01:20:05.940
even that I exist as an entity.
link |
01:20:09.340
And that can be really, I think, frankly, experientially,
link |
01:20:12.460
that's kind of the gateway
link |
01:20:13.620
to both the transcendental mystical experiences,
link |
01:20:17.780
the sense of unity with all things,
link |
01:20:21.140
which we know our data suggests
link |
01:20:22.700
is related to long-term positive outcomes.
link |
01:20:27.140
Wait, I want to make sure I understand.
link |
01:20:28.340
So you're saying the bad trip
link |
01:20:29.540
can be related to the transcendental experience?
link |
01:20:31.740
Right, I think those are both speculating,
link |
01:20:34.100
but you have to pass through this sort of like,
link |
01:20:39.020
reality shattering, including your sense of self.
link |
01:20:42.380
And one can handle that in one of two ways.
link |
01:20:45.380
You can either completely surrender to it
link |
01:20:48.180
or you can try to hang on.
link |
01:20:49.940
And if you try to hang on,
link |
01:20:50.940
it's going to be more like a bad trip.
link |
01:20:52.660
So again, I wish there was more
link |
01:20:54.220
and hopefully there will be more experimentation.
link |
01:20:56.220
There's a lot going on here in the black box
link |
01:20:58.420
in terms of the operant behavior
link |
01:21:00.620
of how you are within yourself,
link |
01:21:04.300
choosing to handle, like letting go.
link |
01:21:07.260
And eventually we'll be able to see this in real time
link |
01:21:09.780
with brain imaging.
link |
01:21:10.740
Ah, there they are surrendering to the psychedelic experience.
link |
01:21:13.660
Here they are trying to hold on, but we're not there yet.
link |
01:21:17.340
But I think through clinical observation,
link |
01:21:19.820
it seems pretty clear that something like that is going on.
link |
01:21:23.300
And certain drugs like DMT, smoke DMT, can be so strong.
link |
01:21:26.620
The reason I think that can be so extraordinary,
link |
01:21:30.580
you can compare to the others,
link |
01:21:31.420
because it like forces people.
link |
01:21:32.940
Like there is no choice to hang out in it.
link |
01:21:34.220
I've never done it.
link |
01:21:35.060
I was told that DMT is like a high-speed locomotive
link |
01:21:39.020
into the psychedelic experience
link |
01:21:40.740
and out of the psychedelic experience.
link |
01:21:43.180
And there's no ability to hold on to the self
link |
01:21:46.500
while you're in the kind of peak phase.
link |
01:21:48.820
Is that correct?
link |
01:21:49.660
A lot of people say that,
link |
01:21:50.740
but Terrence McKenna,
link |
01:21:52.940
who is kind of the classic bard on DMT effects,
link |
01:21:55.980
he would say the sense of self was intact,
link |
01:21:59.620
but everything else, the sensorium and what you navigated,
link |
01:22:03.460
what you oriented towards,
link |
01:22:05.580
everything else changed basically.
link |
01:22:07.580
But it's hard to, when everything's changing,
link |
01:22:09.260
it's hard to say like, what is the self that's changing?
link |
01:22:11.620
What is the rest of the world?
link |
01:22:12.980
Well, and language is totally deficient
link |
01:22:15.180
to describe experience anyway, much less on a psychedelic.
link |
01:22:19.740
What is McKenna's background?
link |
01:22:21.500
Like what is his qualification for being this,
link |
01:22:24.580
as you referred, this bard of DMT?
link |
01:22:27.380
And we're talking about Terrence
link |
01:22:28.780
and there's also the brother Dennis,
link |
01:22:31.260
whom I know who's-
link |
01:22:33.300
Can only imagine what Thanksgiving dinner is like
link |
01:22:35.460
at their house. Terrence passed away
link |
01:22:37.420
years, a couple of decades ago now,
link |
01:22:39.420
but he's sort of the one who's known as being a bard
link |
01:22:42.420
and you can find hundreds, if not thousands of hours of him
link |
01:22:46.580
on the lecture circuit in the eighties and nineties
link |
01:22:48.860
on YouTube.
link |
01:22:49.860
But his background was really, oh gosh,
link |
01:22:52.500
I don't recall what his college degree was in,
link |
01:22:54.500
but he basically, when he was like 19,
link |
01:22:57.620
he traveled to South America
link |
01:22:59.820
and actually on the initial trip with his brother
link |
01:23:03.100
who was even younger than him, with some other friends
link |
01:23:06.300
and just in search for a DMT snuff
link |
01:23:11.140
that they had read about in the Harvard archives
link |
01:23:14.020
from the work of Schultes from a generation before,
link |
01:23:17.980
but they had discovered all of these mushrooms growing
link |
01:23:22.660
that down there, the psilocybin mushrooms,
link |
01:23:24.980
what they recognized and just took a lot of mushrooms and-
link |
01:23:29.780
And talked about it.
link |
01:23:30.660
Talked about it.
link |
01:23:31.500
And Terrence was basically a very intelligent,
link |
01:23:33.500
very well-read and literature and culture person
link |
01:23:38.300
that could be, he was sort of the next generation's
link |
01:23:41.700
Tim Leary, someone who could really speak,
link |
01:23:44.860
get a little closer to the magnitude
link |
01:23:47.420
of what the psychedelic experience was like for people.
link |
01:23:50.300
And he served, like Leary, somewhat of an advocate.
link |
01:23:53.740
I mean, he would tell people, folks,
link |
01:23:56.300
you could see the equivalent of a UFO landing
link |
01:23:59.420
on the White House lawn.
link |
01:24:00.860
Like it's right there.
link |
01:24:02.620
It'll take five minutes.
link |
01:24:03.900
It'll shake everything in your reality.
link |
01:24:06.900
He would sort of goad people into doing it.
link |
01:24:08.980
Well, certainly science and clinical medicine
link |
01:24:11.580
are just but two lenses with which to explore
link |
01:24:15.180
these things in life.
link |
01:24:16.300
But part of the reason I ask is I feel like, you know,
link |
01:24:21.900
in the world of health and fitness,
link |
01:24:25.540
you have this very extreme condition
link |
01:24:28.220
of like Arnold Schwarzenegger's and bodybuilders
link |
01:24:30.980
who have like 2% body fat and they look like,
link |
01:24:33.500
to most people, they look kind of freakish,
link |
01:24:36.180
especially now, right?
link |
01:24:37.180
Oh, especially now.
link |
01:24:38.140
Especially now.
link |
01:24:38.980
Yeah.
link |
01:24:39.820
And yeah.
link |
01:24:40.640
Made Arnold look like regular.
link |
01:24:42.260
Exactly.
link |
01:24:43.100
Back in his day, yeah.
link |
01:24:43.940
And you have contortionists who can put themselves
link |
01:24:46.700
into a small box and wrap themselves into a pretzel.
link |
01:24:49.380
But from those two very extreme subculture practices
link |
01:24:54.940
that, I don't know anything about contortionism really,
link |
01:24:57.780
but except that they get really bendy,
link |
01:25:00.740
but it was a community that included lifestyle practices
link |
01:25:04.540
and nutritional practices and then drug practices.
link |
01:25:06.800
From those very extreme subcultures,
link |
01:25:09.260
there's been an export, which is that, you know,
link |
01:25:12.660
weight training is healthy, right?
link |
01:25:14.240
The general public has done that.
link |
01:25:15.620
Or that yoga is healthy.
link |
01:25:17.180
So contortionism to yoga, et cetera.
link |
01:25:20.220
And I feel like a similar thing is happening
link |
01:25:22.340
in the realm of psychedelics where it was Leary
link |
01:25:27.900
and Huxley.
link |
01:25:29.100
I mean, like I'm from the Bay Area.
link |
01:25:30.980
I'm not far from the Menlo Park VA
link |
01:25:32.700
where One Flew Over the Cuckoos is basically based on, right?
link |
01:25:35.340
Ken Kesey and those guys.
link |
01:25:36.420
And you know, there has been an attempt
link |
01:25:39.820
at creating this movement toward openness about psychedelics
link |
01:25:45.100
and their positive effects.
link |
01:25:46.740
This has happened before.
link |
01:25:48.460
The difference is that now there are people like you
link |
01:25:50.420
inside the walls of the university
link |
01:25:52.220
or publishing peer reviewed studies and things of that sort.
link |
01:25:54.980
The reason I asked about McKenna was, you know,
link |
01:25:56.900
it seems like McKenna and his brother are,
link |
01:26:00.780
but you know, just two of many people,
link |
01:26:05.100
Michael Pollan, et cetera,
link |
01:26:06.300
who have no real formal training in biology or psychology.
link |
01:26:12.620
The other guys who were at universities lost their jobs.
link |
01:26:15.660
They were actually removed from places like Harvard
link |
01:26:18.060
and other universities for their kind
link |
01:26:20.340
of cavalier explorations, right?
link |
01:26:22.980
And now things are kind of returning.
link |
01:26:25.020
So in the same way that bodybuilding led to weight training
link |
01:26:27.620
in every corner gym, you know, men, women, and children,
link |
01:26:32.140
and contortionism is one extreme,
link |
01:26:34.400
but people generally think that yoga is a pretty
link |
01:26:36.600
healthy practice, right?
link |
01:26:38.180
These are matter of degrees, right?
link |
01:26:40.160
And now here you are inside the walls
link |
01:26:44.660
of a very highly respected university, Johns Hopkins.
link |
01:26:47.900
You're on the medical school side of the undergrad.
link |
01:26:49.780
So in the med school, which is, you know,
link |
01:26:54.180
a serious health institution.
link |
01:27:00.100
You know, the question is to me, you know,
link |
01:27:03.820
what are the valuable exports, right?
link |
01:27:07.140
And where does the extreme lie?
link |
01:27:09.100
I mean, clearly there's a problem
link |
01:27:11.820
with tinkering with reality through pharmacology.
link |
01:27:17.220
And there's a benefit, it sounds like,
link |
01:27:19.180
to tinkering with reality through pharmacology.
link |
01:27:23.060
And what's so striking to me is this,
link |
01:27:25.660
is the elements of atypical experience,
link |
01:27:29.340
atypical representation of the self.
link |
01:27:31.540
So for the average person, right?
link |
01:27:37.300
Or for kids that are hearing this,
link |
01:27:38.900
kids that are in their teens, right?
link |
01:27:40.660
What are the, I want to talk about,
link |
01:27:42.660
what are the dangers of psychedelics?
link |
01:27:44.860
This is something you don't hear a lot about these days,
link |
01:27:46.580
and it's not because I'm anti-psychedelic at all,
link |
01:27:48.940
but what are the dangers, right?
link |
01:27:50.500
If a kid or adult has a predisposition toward,
link |
01:27:54.540
let's say psychotic thinking, right?
link |
01:27:59.540
Or auditory hallucinations,
link |
01:28:02.380
or is on the Asperger's side of the autism spectrum,
link |
01:28:07.820
is there an increased risk of bringing the mind
link |
01:28:10.500
into these states?
link |
01:28:11.620
Because it sounds like a very labile situation.
link |
01:28:14.820
So could we talk a little bit about that?
link |
01:28:16.700
And are there classes of these different drugs,
link |
01:28:18.900
whether or not it be MDMA, LSD, or DMT,
link |
01:28:21.260
that you think are particularly sharp blades
link |
01:28:24.780
and therefore need to be wielded particularly carefully?
link |
01:28:28.500
Yeah, so these can be profoundly destabilizing experiences
link |
01:28:35.300
and ones that ideally are had in a safe container,
link |
01:28:43.340
sort of where someone, what are the relevant dangers
link |
01:28:47.860
and what can we do to mitigate those?
link |
01:28:49.700
So there's two biggies.
link |
01:28:54.340
One, and I've already mentioned,
link |
01:28:55.860
it's people with very severe psychiatric illness,
link |
01:29:00.220
not depression, not anxiety.
link |
01:29:02.940
I'm talking about psychotic disorders like schizophrenia
link |
01:29:06.660
or mania as part of bipolar disorder.
link |
01:29:10.180
So, and diagnostically, this has shifted.
link |
01:29:13.100
So it's a little hard to say how many people today
link |
01:29:15.140
with bipolar would have been labeled as schizophrenia
link |
01:29:17.100
back in the 60s when some of this early research
link |
01:29:20.900
or just clinical observation was done.
link |
01:29:23.220
So it seems very clear that folks with a predisposition
link |
01:29:27.380
or active disease, they could be destabilized.
link |
01:29:29.580
And so some of the cases that we know of,
link |
01:29:31.660
I always think of Sid Barrett,
link |
01:29:33.460
the first singer of Pink Floyd, seems pretty clear,
link |
01:29:38.900
although I think the family-
link |
01:29:39.740
I don't know what happened there.
link |
01:29:41.220
I should be, sorry, Pink Floyd fans.
link |
01:29:43.140
I've never, the songs are just really long.
link |
01:29:45.300
Yeah, you're more of a punk guy, right?
link |
01:29:46.940
Yeah.
link |
01:29:48.780
So I've got my foot in a lot of worlds,
link |
01:29:50.980
definitely in part in the Floyd world,
link |
01:29:53.420
but he basically went crazy early on.
link |
01:29:57.820
He, it seemed, I don't think his family ever admitted it,
link |
01:30:00.700
but he developed schizophrenia, classic pattern.
link |
01:30:04.500
And he was doing a lot of LSD.
link |
01:30:08.580
But like a lot of these cases,
link |
01:30:11.540
it looked like he was showing all of the signs
link |
01:30:14.300
of some hints that he had that susceptibility before.
link |
01:30:23.540
And often this is hard to disentangle what causes what,
link |
01:30:26.420
because when do people typically, not always, but develop,
link |
01:30:30.500
when's the modal period for first break?
link |
01:30:32.380
It's adolescence, early adulthood, yeah.
link |
01:30:34.580
And when do people start playing with drugs?
link |
01:30:37.260
Same exact time period.
link |
01:30:39.780
So it can be hard to disentangle, but it seems pretty clear.
link |
01:30:43.300
Now I should also say, there are cases of folks
link |
01:30:45.980
with schizophrenia that say psychedelics have helped them.
link |
01:30:48.700
There's anecdotes for everything.
link |
01:30:50.300
Do the people around those schizophrenics
link |
01:30:52.060
say it's helped them?
link |
01:30:52.900
I don't know.
link |
01:30:53.740
Because when schizophrenics say things, you have to,
link |
01:30:55.820
I mean, with all due compassion and respect
link |
01:30:58.780
for schizophrenia, it's a disorder of thinking.
link |
01:31:01.740
So if they're saying it helped them.
link |
01:31:03.700
Yeah, can you trust them?
link |
01:31:04.860
Yeah.
link |
01:31:05.700
I wouldn't be surprised if there was some kernel of truth
link |
01:31:08.740
in some cases, but they're just so,
link |
01:31:11.140
it seems very clear that the other side is there too.
link |
01:31:14.860
And that there ever is a therapeutic potential there
link |
01:31:17.900
for those disorders,
link |
01:31:19.020
that shouldn't be the first thing on our list.
link |
01:31:21.460
We need to learn a lot more because of the level of risk
link |
01:31:24.460
before we start doing research to see if,
link |
01:31:27.380
you know, psilocybin can help with schizophrenia.
link |
01:31:29.860
Like, I don't think that that may never be the case,
link |
01:31:32.060
but even if it is, you'd have to be even more cautious
link |
01:31:35.180
and figure some more things out first
link |
01:31:37.860
with some of these other disorders.
link |
01:31:39.540
What about bipolar disorder?
link |
01:31:41.900
Can it be exacerbated by these compounds?
link |
01:31:44.180
Yeah, and it may be that sort of the manifestation
link |
01:31:50.260
of people having prolonged psychiatric issues
link |
01:31:53.100
after a psychedelic experience, as atypical as that is,
link |
01:31:58.820
when that happens, it may be that might be more
link |
01:32:02.100
like a manic episode than a psychotic episode,
link |
01:32:05.060
and that can be a blurry line.
link |
01:32:06.860
And it's, the folklore is that, you know,
link |
01:32:10.900
people go on a trip and they never come back.
link |
01:32:12.900
That's clearly not the case because, you know,
link |
01:32:15.340
the drug is metabolized like for anyone else,
link |
01:32:17.660
and the next day there's not, you know,
link |
01:32:19.100
it's virtually nothing in the system.
link |
01:32:19.940
But it reshapes circuitry, I mean.
link |
01:32:21.820
Right, and there's still, and I really do think, you know,
link |
01:32:24.180
much like the positive, you know, long-term effects that,
link |
01:32:28.660
you know, this class of problems is related to like the,
link |
01:32:33.220
to the experience and the destabilization
link |
01:32:38.100
that can happen from that experience,
link |
01:32:42.020
if it's not in the right container.
link |
01:32:44.700
And again, like these people are susceptible to, you know,
link |
01:32:47.900
some people with that psychotic predisposition,
link |
01:32:50.780
they lucky to be born to a great family, stable environment.
link |
01:32:55.100
They maybe never have a full break or the one that they have
link |
01:32:57.660
is not nearly as bad as what, you know,
link |
01:33:00.220
someone who's homeless and is coming from all kinds
link |
01:33:04.060
of early childhood trauma.
link |
01:33:05.340
Like the disease is probably going to be far worse, you know.
link |
01:33:08.860
So, you know, having a psychedelic experience
link |
01:33:12.660
is like one of those destabilizing experiences, you know.
link |
01:33:16.100
So, now fortunately it's really easy
link |
01:33:19.020
to identify those people.
link |
01:33:20.500
And we even err on the side of extreme caution
link |
01:33:23.500
by eliminating people with like, say,
link |
01:33:25.220
a first degree relative.
link |
01:33:26.260
In some studies, even a second degree relative.
link |
01:33:28.620
Given the heritability, there's some increased chance
link |
01:33:31.380
if your brother or your...
link |
01:33:33.020
Yeah.
link |
01:33:34.780
So, in an abundance of caution, even eliminating that.
link |
01:33:38.580
I think eventually if it's approved for use,
link |
01:33:41.780
FDA use, that we could dial back on that as we learn more.
link |
01:33:45.420
I think it's, again, overly cautious, which is-
link |
01:33:49.180
But you're doing an early stage clinical trial.
link |
01:33:50.660
Yeah, it's the appropriate place
link |
01:33:52.300
to start at this point in time.
link |
01:33:53.620
But, you know, if you give a skid
link |
01:33:56.260
or another structured psychiatric interview
link |
01:33:58.260
with a clinician sitting down with this person
link |
01:34:00.060
for a few hours to delve into their history.
link |
01:34:02.380
And like, you can very reliably determine
link |
01:34:05.140
if this person has either, you know,
link |
01:34:07.660
a psychotic disorder or bipolar disorder
link |
01:34:10.100
or a strong predisposition.
link |
01:34:12.140
So, that's, you know, that you can screen for that.
link |
01:34:14.420
And that's how you address that.
link |
01:34:15.860
The far more likely danger is the bad trip.
link |
01:34:18.820
Anyone can have this.
link |
01:34:20.180
The most psychologically healthy person
link |
01:34:21.940
in the world, probably.
link |
01:34:23.700
You jack the dose high enough,
link |
01:34:25.060
and especially in a less than an ideal environment,
link |
01:34:29.180
you can have a bad trip.
link |
01:34:30.580
You even get it in an ideal environment like ours,
link |
01:34:33.620
at a high dose of around 30 milligrams of psilocybin.
link |
01:34:37.260
After, you know, the best preparation we can provide,
link |
01:34:39.980
about a third of people will say,
link |
01:34:42.060
essentially, at some point they have a bad trip, you know.
link |
01:34:45.140
At some point within the entire journey.
link |
01:34:47.340
Right, now they could have
link |
01:34:48.860
one of the most beautiful experiences of their life,
link |
01:34:50.980
sometimes, like a couple minutes later.
link |
01:34:53.460
But at some point, they had a sense of strong anxiety,
link |
01:34:56.180
fear, losing their mind, feeling trapped,
link |
01:34:59.620
something like that.
link |
01:35:01.380
Now, typically when people have that in the, you know,
link |
01:35:04.540
when they're just taking on their own,
link |
01:35:06.660
like a lot of things, they're fine.
link |
01:35:08.180
They get through it.
link |
01:35:09.020
You know, they're more likely to be better off
link |
01:35:11.100
if they're not having to navigate the streets of Manhattan.
link |
01:35:14.260
That, you know, or, and if they're with, you know,
link |
01:35:17.340
other people with friends,
link |
01:35:19.500
better that those friends aren't also dealing
link |
01:35:21.580
with their own psychedelic experience,
link |
01:35:22.980
but probably having some friend of any type,
link |
01:35:25.340
but whether they're on there is better than having nothing.
link |
01:35:27.260
So very dependent on context.
link |
01:35:30.260
And so the tough thing here that,
link |
01:35:32.740
that in conveying to the public is that
link |
01:35:36.820
a lot of folks will say,
link |
01:35:38.380
man, I've taken psychedelics hundreds of times,
link |
01:35:41.060
and this is like your fear-mongering,
link |
01:35:43.780
and, you know, there's no, you know,
link |
01:35:46.500
you're exaggerating the danger there.
link |
01:35:48.300
So I want to say it is atypical,
link |
01:35:50.820
but sometimes, and I have a file folder
link |
01:35:53.500
that grows larger every year of these cases,
link |
01:35:57.700
either in the medical literature or from the news
link |
01:36:00.020
of people that freak out on a psychedelic
link |
01:36:02.180
and they get hurt or they die.
link |
01:36:04.740
They run into traffic.
link |
01:36:06.500
They fall from a height,
link |
01:36:08.580
whether they thought they could fly
link |
01:36:10.060
or whether they just fell like they,
link |
01:36:12.220
you can do when you're drunk
link |
01:36:13.580
or you're intoxicated on any substance.
link |
01:36:16.140
Sometimes that's unclear.
link |
01:36:18.700
Or gosh, one of the craziest cases was a kid,
link |
01:36:22.780
like an 18 year old or so in Oregon several years back
link |
01:36:26.460
that just, he even wrote about,
link |
01:36:28.420
I want to take the biggest, he had done mushrooms before.
link |
01:36:30.300
I want to take a heroic dose,
link |
01:36:32.380
the biggest dose I've ever taken.
link |
01:36:33.580
He ended up just totally out of it,
link |
01:36:35.620
ended up in a neighbor's house.
link |
01:36:37.020
He was just totally disoriented,
link |
01:36:38.540
disconnected from reality,
link |
01:36:39.540
and the cops ended up killing him.
link |
01:36:41.620
And it was just tragic,
link |
01:36:42.700
obviously an overuse of force in that case,
link |
01:36:45.300
because he was actually naked at the time,
link |
01:36:46.780
this naked like 120 pound, I think,
link |
01:36:49.980
as a recalled kid that ended up dying.
link |
01:36:52.340
Well, it's analogous to the reason I use the examples
link |
01:36:55.060
of like bodybuilding culture.
link |
01:36:56.260
I mean, people there have taken excessive amounts
link |
01:36:58.620
of antibiotics and diuretics and died.
link |
01:37:00.980
Then the contortionist culture,
link |
01:37:02.460
people have put themselves in a little plexiglass boxes
link |
01:37:04.820
to do, at the extremes, you're going to get deaths.
link |
01:37:09.660
And at the extremes,
link |
01:37:11.140
and one of the extremes is the sheer number of people
link |
01:37:14.220
with different biological makeups taking the same drug.
link |
01:37:18.500
And so you can create extremes through numbers.
link |
01:37:20.340
You can take extreme,
link |
01:37:21.380
you create extremes through dosage, right?
link |
01:37:23.980
It seems.
link |
01:37:25.620
Well, this is why I'm such a fan of the fact
link |
01:37:28.060
that people like yourself are doing clinical trials
link |
01:37:30.500
inside the walls of universities.
link |
01:37:33.820
Not because I think that psychedelics only have utility
link |
01:37:39.260
in those environments,
link |
01:37:40.220
but because it's so important toward creating
link |
01:37:42.780
their transition to legality
link |
01:37:45.660
and to understand what legality means
link |
01:37:48.100
for a compound like this, right?
link |
01:37:50.020
What model?
link |
01:37:51.020
Right, I mean, again,
link |
01:37:52.300
we'll stay with the anabolic steroids.
link |
01:37:54.180
There's now testosterone and estrogen replacement therapy.
link |
01:37:56.780
Hormone replacement therapy is a common
link |
01:37:59.460
medically approved practice,
link |
01:38:00.700
but that's vastly different
link |
01:38:01.740
than people taking their own stuff or diet
link |
01:38:04.380
or deciding how much they need to take, right?
link |
01:38:06.820
Like we said, there's yoga and there's contortionism
link |
01:38:09.500
in a plexiglass box and thinking of Houdini or something.
link |
01:38:12.940
So these are a matter of degrees.
link |
01:38:15.900
Speaking of dosage,
link |
01:38:16.940
I definitely want to ask you about microdose
link |
01:38:20.300
versus standard or macrodose.
link |
01:38:24.420
Tell me that I'm wrong,
link |
01:38:26.500
but I'm always a little bit,
link |
01:38:30.500
I sort of, a little,
link |
01:38:32.180
I'm micro cynical, if you will,
link |
01:38:34.900
about this term microdose.
link |
01:38:36.580
And the reason is that many people that I know
link |
01:38:39.580
who talk about microdosing
link |
01:38:42.860
are taking dosages of compounds that work at,
link |
01:38:46.180
that are very powerful at microgram levels.
link |
01:38:50.300
So the word micro,
link |
01:38:51.620
I think can be a little bit confusing to people
link |
01:38:53.500
because microdose implies less than something.
link |
01:38:57.860
It's a mini dose, right?
link |
01:38:59.620
And yet some of these compounds
link |
01:39:02.060
are tremendously powerful at microgram concentrations.
link |
01:39:06.620
So what it constitutes a microdose
link |
01:39:10.300
and what is the value of so-called microdosing, if any,
link |
01:39:14.220
and how does it differ from standard
link |
01:39:17.980
or what I can only assume is called macrodosing?
link |
01:39:20.620
Yeah.
link |
01:39:21.460
And so LSD would be the prototypical example
link |
01:39:24.460
of that super potent compound.
link |
01:39:27.180
What size dosage of LSD will lead to hallucinations
link |
01:39:31.940
and kind of standard?
link |
01:39:32.780
So sort of the entry point for psychedelic type effects,
link |
01:39:37.100
which may not involve hallucination.
link |
01:39:38.740
Actually, most classic psychedelics
link |
01:39:40.780
don't lead to true hallucinations
link |
01:39:42.740
as defined in psychiatry.
link |
01:39:44.300
You know, thinking you're talking to the person
link |
01:39:46.660
that's not there, seeing the pink elephant.
link |
01:39:48.180
No, it's more like tracers and things like that.
link |
01:39:50.740
Right, and some people never get that
link |
01:39:53.860
even at a very high dose.
link |
01:39:55.140
So I think more broadly in terms of the psychedelic effects,
link |
01:39:58.700
which isn't just perceptual,
link |
01:40:00.140
unless we get into the level of,
link |
01:40:01.900
as you were alluding to earlier,
link |
01:40:03.620
a broader definition of perception,
link |
01:40:05.700
like one's models of the world, the model of the self,
link |
01:40:09.380
you can consider all of that perception
link |
01:40:12.060
in terms of truly not sensation, but perception,
link |
01:40:15.340
the construction of putting together reality.
link |
01:40:18.860
So yeah, yeah, yeah.
link |
01:40:21.620
So the psychedelic effects are typically considered
link |
01:40:25.260
to start for LSD around 100 micrograms.
link |
01:40:27.060
So a 10th of a milligram is 100 micrograms.
link |
01:40:31.100
So someone taking 100 micrograms of LSD,
link |
01:40:35.980
nowadays people might mistakenly refer to that
link |
01:40:38.300
as a microdose because it's micrograms,
link |
01:40:40.340
but that's actually a macrodose of LSD.
link |
01:40:43.100
Right, and that's one of the most common mistakes
link |
01:40:45.860
or situations that people get into with microdosing
link |
01:40:49.220
is they intend it to be a microdose,
link |
01:40:50.780
but it ends up being a full-blown dose.
link |
01:40:54.100
Now, people do, when they're working with LSD
link |
01:40:57.220
and they're microdosing, they'll shoot for something
link |
01:40:58.940
like say 10 milligrams, something in that range,
link |
01:41:03.900
10, 20 milligrams of LSD.
link |
01:41:06.020
So a 10th, a fifth, something of kind of
link |
01:41:09.500
your entry-level psychedelic dose.
link |
01:41:12.420
People's ability on the street to do this,
link |
01:41:15.700
say the street as if they're on the corner,
link |
01:41:17.300
but anyway, like outside of the medical profession
link |
01:41:19.420
to do this, it varies as you can imagine.
link |
01:41:21.260
And they're not measuring purity and molarity
link |
01:41:22.900
or things like that, typically.
link |
01:41:24.060
And there's ways to do it.
link |
01:41:25.300
So even if you don't ultimately know the dose
link |
01:41:27.180
that's in like the blotter paper of acid,
link |
01:41:29.900
one could at least get a sense of like,
link |
01:41:31.500
yeah, having one of those tabs is one of those hits
link |
01:41:35.300
is a psychedelic experience.
link |
01:41:37.260
They could do something like put it in water,
link |
01:41:39.220
it's 100% aqueous soluble.
link |
01:41:41.580
You could make sure it all gets into solution
link |
01:41:44.540
and then volumetrically measure.
link |
01:41:46.100
It's gonna be homogeneously distributed
link |
01:41:48.220
so you can take 1 10th of that volume of water
link |
01:41:51.060
after it's fully dissolved.
link |
01:41:52.820
That whatever you started with,
link |
01:41:54.060
you're gonna have a 10th of that dose.
link |
01:41:55.260
So the people that are more sophisticated
link |
01:41:57.340
will do things like that.
link |
01:41:58.700
And when they're working with mushrooms,
link |
01:42:00.420
they'll grow a bunch of mushrooms
link |
01:42:01.500
and then they'll say, put it in a coffee grinder.
link |
01:42:03.700
I'm not telling people to do this, by the way,
link |
01:42:05.660
I'm just describing, so don't do this at home,
link |
01:42:07.580
but like grind it all up so it's homogenous.
link |
01:42:10.060
Because you can have like,
link |
01:42:11.540
sort of taking two caps and a stem,
link |
01:42:14.700
hey, this two caps and a stem that this buddy takes
link |
01:42:18.300
has a different potency than this two caps and a stem
link |
01:42:20.740
that the other buddy takes.
link |
01:42:21.780
So people that are kind of in the know
link |
01:42:24.260
will grind it all up into a homogenous powder
link |
01:42:26.860
and they'll pack it into whatever size capsule
link |
01:42:29.140
and they'll know that.
link |
01:42:30.020
And again, even if they don't have,
link |
01:42:31.860
sometimes they might have a buddy
link |
01:42:32.980
that'll sneak it into the HPLC at their job or whatever,
link |
01:42:36.380
if they have-
link |
01:42:37.220
Not your lab.
link |
01:42:38.060
Not my lab, that's never happened.
link |
01:42:39.260
Yeah, seriously, never happened.
link |
01:42:40.500
But they'll at least know that,
link |
01:42:43.340
hey, I've got a sense of what two capsules do.
link |
01:42:46.740
I've got a sense of what five capsules do.
link |
01:42:49.340
But in reality, like that's not what people do.
link |
01:42:53.460
They'll take a piece of blotter paper
link |
01:42:55.540
and they get a tiny little pair of scissors,
link |
01:42:58.300
a Swiss army knife pair of scissors,
link |
01:42:59.860
and they'll cut up the tab of acid,
link |
01:43:02.100
which is like a quarter inch square or something.
link |
01:43:05.260
And they'll cut it up in 10 little pieces.
link |
01:43:07.460
And it's like, you have no idea
link |
01:43:09.500
like if it's equally distributed in that media.
link |
01:43:12.220
Yeah, and we can chuckle about it.
link |
01:43:13.900
And, but to me, one of the reasons
link |
01:43:17.580
why this experiment around psychedelics,
link |
01:43:19.980
this cultural experiment and this legal experiment,
link |
01:43:24.300
we're seeing this now,
link |
01:43:25.420
but this was all attempted once before in the 60s and 70s.
link |
01:43:29.860
The difference was it was all out in the street.
link |
01:43:32.540
The people in universities who were dabbling with this stuff,
link |
01:43:36.300
most of them lost their jobs
link |
01:43:37.700
or were asked to leave through-
link |
01:43:40.140
They lost their funding for this research minimally
link |
01:43:42.220
and they had to move on to other topics.
link |
01:43:43.580
That's right.
link |
01:43:44.420
So these are precarious times.
link |
01:43:45.700
I mean, we're at a key moment where everyone assumes
link |
01:43:50.540
that this is all going to be legal in a few years.
link |
01:43:52.700
But I think that that's a premature assumption, frankly.
link |
01:43:56.260
But, and let's touch on the legality
link |
01:44:00.780
and some of the things that are happening now.
link |
01:44:02.540
But what is microdosing psilocybin
link |
01:44:06.540
versus the sorts of dosages that you described before
link |
01:44:09.980
in the 10 to 40 milligram range?
link |
01:44:12.540
I've heard of people taking one or two milligrams
link |
01:44:16.820
of psilocybin every day as a way to quote, unquote,
link |
01:44:20.340
and for those listening,
link |
01:44:21.180
I'm just making air quotes with my fingers,
link |
01:44:23.100
increase plasticity,
link |
01:44:24.340
which is a term that I personally loathe
link |
01:44:26.740
because what does that mean?
link |
01:44:28.140
I mean, you don't really want your brain to be plastic
link |
01:44:30.380
because you need to maintain your ability
link |
01:44:33.860
to make predictions.
link |
01:44:34.900
Yeah, I mean-
link |
01:44:35.740
Ordering chaos, like prediction.
link |
01:44:38.300
You need models of the world.
link |
01:44:40.060
You need heuristics.
link |
01:44:41.260
Plasticity is never the goal or be it plasticity
link |
01:44:44.420
is never the goal.
link |
01:44:45.660
The goal-directed plasticity is the goal, right?
link |
01:44:48.940
Learning a language, reshaping your experience to a trauma,
link |
01:44:53.140
altering the perception of self.
link |
01:44:54.820
But plasticity is a process like-
link |
01:44:58.340
Yeah, schizophrenia is a lot of plasticity.
link |
01:45:01.260
Exactly, right, right.
link |
01:45:02.620
It might even be, there's one theory
link |
01:45:04.220
that it's extreme ongoing plasticity
link |
01:45:06.460
and that's why people never create
link |
01:45:08.100
stable representations of anything.
link |
01:45:10.020
That's kind of a minority view out there,
link |
01:45:13.540
but so what's the business with microdosing
link |
01:45:17.020
and is there any clinical evidence
link |
01:45:19.060
or peer-reviewed published evidence
link |
01:45:20.660
that it works, quote unquote,
link |
01:45:22.300
to make people feel better about anything?
link |
01:45:24.780
So microdosing is the aim of taking,
link |
01:45:30.580
again, something around a 10th of what would be
link |
01:45:33.580
sort of an entry-level psychedelic dose
link |
01:45:35.620
for whatever compound.
link |
01:45:36.780
So like, yeah, with psilocybin,
link |
01:45:39.460
usually people, almost never do people have
link |
01:45:42.020
like pure psilocybin.
link |
01:45:43.060
Like one milligram of psilocybin
link |
01:45:44.860
would be in the range of a microdose.
link |
01:45:46.140
More likely people are going to have mushrooms.
link |
01:45:48.340
So like something like a half of a gram of mushroom.
link |
01:45:53.180
I know people that are doing this every day.
link |
01:45:55.500
They're doing these every day.
link |
01:45:56.540
It's like in their, like the same way that I take,
link |
01:45:59.180
like I'm personally,
link |
01:46:00.540
I'm not recommending other people do this,
link |
01:46:02.140
but I take some, I'm a fan of LCL carnitine lately.
link |
01:46:05.300
I've been kind of experimenting with that a little bit,
link |
01:46:07.020
which is not a psychedelic compound.
link |
01:46:08.900
I take it every day.
link |
01:46:09.860
And they're taking their psilocybin every day.
link |
01:46:12.540
That's their supplement.
link |
01:46:13.460
Yeah.
link |
01:46:15.420
So yeah, the claims are, and there are a number of them,
link |
01:46:19.180
there's two general ones.
link |
01:46:20.500
One is sort of acting in place of the ADHD treating drugs.
link |
01:46:25.980
So the psychomotor stimulants.
link |
01:46:27.180
So like a better version of Adderall.
link |
01:46:29.700
The other claims are essentially a better version
link |
01:46:32.700
of the traditional antidepressants,
link |
01:46:35.860
a better version of Prozac.
link |
01:46:37.620
So people are taking both for attention deficit
link |
01:46:39.860
and for depression.
link |
01:46:41.820
Yeah, and the aspects of those disorders
link |
01:46:44.940
that we all have a degree of,
link |
01:46:48.060
just like amphetamine is going to increase the focus
link |
01:46:50.980
at the right dose of anyone who takes amphetamine,
link |
01:46:53.420
pretty much, whether you're ADHD diagnosed or not,
link |
01:46:57.860
the idea is that there may not be necessarily a clear divide
link |
01:47:02.660
between the therapeutic need and positive psychology,
link |
01:47:07.380
even improving mood and focus.
link |
01:47:11.340
So it's not necessarily correcting ADHD,
link |
01:47:15.020
but improving focus to supercharge your life.
link |
01:47:19.180
And so those are the claims.
link |
01:47:23.340
So none of the peer reviewed studies
link |
01:47:25.660
that have much credibility,
link |
01:47:29.900
none of them have shown a benefit.
link |
01:47:32.620
And they've tried.
link |
01:47:33.460
Now there's only at this point four or five studies that,
link |
01:47:36.580
and I think for things like this,
link |
01:47:39.020
you really need double-blind research because the effects,
link |
01:47:43.180
I mean, there was one study done in Amsterdam
link |
01:47:45.340
where people knew they were taking psilocybin truffles,
link |
01:47:48.140
basically same as mushrooms,
link |
01:47:49.260
more like the roots of the mycelia.
link |
01:47:50.860
Microdosing them.
link |
01:47:52.140
Well, taking what would be considered a microdose
link |
01:47:56.940
and then doing some cognitive measures before and after.
link |
01:48:01.220
And the types of things that,
link |
01:48:02.340
like a lot of cognitive measures
link |
01:48:03.380
are measured on the order of reaction time
link |
01:48:06.020
in milliseconds.
link |
01:48:06.860
I mean, and the types of effects you get,
link |
01:48:08.820
as you could imagine,
link |
01:48:09.700
are ones that you would totally expect could be there
link |
01:48:13.740
from either a practice effect or an expectancy effect,
link |
01:48:18.460
a placebo effect.
link |
01:48:19.500
So for something like these claimed,
link |
01:48:23.620
you can imagine a sort of an increased focus,
link |
01:48:26.780
enhancement of cognition.
link |
01:48:29.420
These are gonna be more subtle effects
link |
01:48:32.060
that you really need a good placebo control for.
link |
01:48:36.660
The handful of studies that have done that have shown,
link |
01:48:40.700
they've ranged from finding no effect whatsoever
link |
01:48:43.140
to just a little bit of impairment,
link |
01:48:44.940
like impairing someone's ability to do time estimation
link |
01:48:48.860
and production tasks.
link |
01:48:49.940
So you want an accurate sense of time,
link |
01:48:52.500
at least if you're navigating in the real world.
link |
01:48:54.820
It's different if you're on the couch on a heroic dose
link |
01:48:57.620
for therapeutic reasons where you're safe,
link |
01:48:59.380
but if you're crossing the street,
link |
01:49:01.020
if you're in your work life,
link |
01:49:03.860
which is the way people are claiming to use it,
link |
01:49:06.700
it helps them be a better CEO.
link |
01:49:08.740
Like you want an accurate sense of time.
link |
01:49:10.580
So if anything, the data suggests
link |
01:49:12.180
that it makes it a little bit less accurate.
link |
01:49:14.820
And there's evidence that someone feels a little bit
link |
01:49:19.040
impaired and they feel a little bit high.
link |
01:49:22.540
So in terms of, you call that abuse liability in research,
link |
01:49:26.380
not surprising, you take a little bit of a drug
link |
01:49:28.900
that can result in some type of a high
link |
01:49:31.340
and you take a little tiny bit of it,
link |
01:49:32.500
you'll feel a little bit high.
link |
01:49:34.440
So, you know, none of the,
link |
01:49:37.660
so far, no studies have shown any increase in creativity,
link |
01:49:44.260
enhancement of any form of cognition
link |
01:49:47.160
or a sustained improvement in mood.
link |
01:49:50.660
Now, no studies have actually looked
link |
01:49:53.860
at the system of microdosing
link |
01:49:57.820
that the aficionados are claiming.
link |
01:49:59.860
And there's a couple of models out there,
link |
01:50:02.020
but folks like Paul Stamets and others,
link |
01:50:05.460
they'll have particular formulas.
link |
01:50:06.940
They're like, you need to take it one day
link |
01:50:09.020
and then take so many days off and take it every four days.
link |
01:50:11.820
And I don't want to get into whose model is what,
link |
01:50:13.740
but it's always something like that.
link |
01:50:14.980
Some pattern of use, usually not every day.
link |
01:50:18.620
And the claim is that it's not just, you know,
link |
01:50:21.780
sometimes people get benefit that first time
link |
01:50:23.940
when they take it, but they really say,
link |
01:50:26.280
you need to be on it for a while.
link |
01:50:27.940
Like a few weeks in, you may start to notice
link |
01:50:29.800
through this pattern of using it.
link |
01:50:32.620
And you're feeling the benefits on those off days,
link |
01:50:35.460
like the three or two days in between your active doses.
link |
01:50:40.620
So those are the claims.
link |
01:50:41.600
Again, we don't know that there's any truth to that working,
link |
01:50:44.220
but studies have not been done to model that.
link |
01:50:47.840
So that's a big caveat.
link |
01:50:49.340
We as a field, I say we as the scientific field,
link |
01:50:53.500
have not done the studies to really model, you know,
link |
01:50:57.420
what the real aficionados are claiming, you know,
link |
01:51:00.820
where the therapeutic benefits come from.
link |
01:51:03.740
That said, it's almost assuredly
link |
01:51:06.480
there's a good amount of placebo there.
link |
01:51:08.460
But the caveat to that is like almost everything
link |
01:51:11.620
in medicine or therapeutics,
link |
01:51:13.500
there's, it's going to have some degree of placebo there.
link |
01:51:16.380
Belief effects are, I have a colleague at Stanford,
link |
01:51:19.940
Aaliyah Crum, who has published really beautiful work
link |
01:51:22.380
on belief effects that show that essentially
link |
01:51:26.580
you give the same milkshake to two people,
link |
01:51:28.480
you, or two groups of people,
link |
01:51:30.360
you tell them that one contains a lot of nutrients,
link |
01:51:32.860
the other is a low calorie shake.
link |
01:51:34.100
They're, the insulin response.
link |
01:51:36.100
Amazing.
link |
01:51:37.060
Varies dramatically between the two or two groups
link |
01:51:40.500
rather doing equivalent amounts of physical movement.
link |
01:51:45.060
And you tell one group that it's going to be good for them
link |
01:51:46.940
and help them lose weight.
link |
01:51:47.860
And they lose on average eight to 12 pounds more
link |
01:51:50.080
doing the exact same patterns of movement.
link |
01:51:53.220
So, and I think that these belief effects boil down
link |
01:51:55.420
to all sorts of kind of network-wide neuromodulation,
link |
01:51:58.540
things of that sort.
link |
01:51:59.380
And then the work at Harvard suggesting
link |
01:52:01.060
that even if you don't have deception,
link |
01:52:03.160
you give a placebo and say, this is a sugar pill.
link |
01:52:05.580
Right.
link |
01:52:06.420
You know, tell them that.
link |
01:52:07.980
And they could still treat things.
link |
01:52:09.180
I think irritable bowel was the first thing they looked at.
link |
01:52:11.740
Right.
link |
01:52:12.580
And so there's a huge, so there's a reality there.
link |
01:52:14.940
Right.
link |
01:52:15.940
There's a necessity in developing drugs
link |
01:52:17.520
to make sure it's not only that,
link |
01:52:19.060
but in the actual practice of medicine,
link |
01:52:21.740
hopefully what you're always getting
link |
01:52:23.100
is some underlying direct efficacy
link |
01:52:25.140
plus the placebo that it enhances at.
link |
01:52:27.940
Now, it could be that this is, the real question is,
link |
01:52:31.380
is the microdosing, are those claims 100% placebo
link |
01:52:35.500
or are they only part placebo and part real,
link |
01:52:39.480
you know, quote unquote effect.
link |
01:52:41.240
My bet is, and this is totally based on anecdotes
link |
01:52:45.100
that I think there is probably a reality
link |
01:52:47.740
to the antidepressant effects.
link |
01:52:49.300
I find that more intriguing
link |
01:52:51.300
because of the suffering with depression.
link |
01:52:53.140
Right.
link |
01:52:53.980
Even if it's, it wouldn't be as interesting
link |
01:52:56.200
as I think what we're doing with high dose psilocybin
link |
01:52:59.180
or psychedelics to treat depression.
link |
01:53:01.740
It would be, if this is developed and there's a reality,
link |
01:53:04.260
it would be more like a better, you know,
link |
01:53:06.820
perhaps a better SSRI, a better Prozac.
link |
01:53:10.060
Which are similar.
link |
01:53:10.900
That being said, we need more tools
link |
01:53:11.740
than fewer tools in the toolbox.
link |
01:53:14.100
And it shouldn't be that surprise.
link |
01:53:15.860
Like even before, going back to the tricyclics
link |
01:53:19.420
and the MAO inhibitors, going back to the fifties,
link |
01:53:22.100
like augmenting extracellular serotonin
link |
01:53:25.340
in one way or another, for many people,
link |
01:53:28.980
leads to a reduction in depressive symptoms.
link |
01:53:31.340
It wouldn't be that crazy for chronically stimulating
link |
01:53:34.580
a subtype of serotonin receptor
link |
01:53:37.020
that you have an antidepressant effect.
link |
01:53:38.860
So I think if I had put my bets on it,
link |
01:53:41.300
that if there's anything real, it is in that category.
link |
01:53:44.460
Although I'm very open to like, maybe there is something
link |
01:53:46.460
to the creativity, to the, you know, improved cognition,
link |
01:53:50.980
which covers many domains in and of itself.
link |
01:53:53.900
But my greatest hopes are on the antidepressant effects.
link |
01:54:00.540
That said, in the big picture,
link |
01:54:02.140
I think all of the most interesting thing
link |
01:54:04.180
about psychedelics are the heroic doses.
link |
01:54:06.580
I mean, the idea that you can give something
link |
01:54:08.260
one, two, three times, and you see improvements
link |
01:54:10.580
in depression months later and in addiction,
link |
01:54:14.820
you know, over a year later and with these, you know,
link |
01:54:17.500
people dealing with potentially terminal illness.
link |
01:54:20.100
I mean, it's, I mean, I'm interested in big effects
link |
01:54:23.860
and I don't think you're ever going to get
link |
01:54:25.140
the really big effects.
link |
01:54:26.620
There's also some concern that almost all of these
link |
01:54:30.180
common, the more common psychedelics, even counting MDMA,
link |
01:54:34.060
they have serotonin 2B agonist effects.
link |
01:54:37.300
And agonizing serotonin 2B has been shown to lead
link |
01:54:42.660
to heart valve formation problems, morphology issues.
link |
01:54:48.500
So valvulopathy.
link |
01:54:50.620
And so this is why Fen-Phen was pulled from the market.
link |
01:54:53.460
The diet drug.
link |
01:54:54.580
Yes.
link |
01:54:55.420
Very effective diet drug.
link |
01:54:56.260
Right, right.
link |
01:54:57.100
And it was the portion of that combination
link |
01:54:59.740
that had the serotonin 2B activity that was the problem.
link |
01:55:04.740
And so we don't know.
link |
01:55:07.180
So all of the toxicologists I've ever spoken to about this
link |
01:55:10.980
would, you know, say, and cardiologists say like,
link |
01:55:13.260
look, hey, if there was some concern there,
link |
01:55:16.380
it's not applicable to the whole idea
link |
01:55:18.340
of you taking something a few times therapeutically
link |
01:55:20.900
within a lifetime.
link |
01:55:21.900
But the idea of taking something like, you know,
link |
01:55:26.140
twice a week for years.
link |
01:55:28.940
I mean, even the hippies back in the sixties
link |
01:55:31.220
weren't doing that, right?
link |
01:55:32.380
Like there's not even these natural,
link |
01:55:33.860
and even if there was some heart valve disease problem
link |
01:55:39.860
that stemmed from psychedelic use,
link |
01:55:42.660
who's connecting those dots?
link |
01:55:44.300
That's not showing up in the clinical charts
link |
01:55:46.300
for anyone to figure out.
link |
01:55:47.260
So there is, and just theoretically,
link |
01:55:49.740
there is more of a concern.
link |
01:55:51.940
If something's going to happen with heart valves,
link |
01:55:55.220
it's more likely that those issues would arise
link |
01:55:58.900
when someone's taking these things like, yeah,
link |
01:56:00.500
let's say twice a week for the next five years.
link |
01:56:04.220
And so I do want to throw that out to people
link |
01:56:05.940
to really consider.
link |
01:56:07.020
Right, yeah, it's something I hadn't heard before
link |
01:56:08.740
that in micro sounds safer,
link |
01:56:11.180
micro dosing as opposed to heroic or macro dosing.
link |
01:56:14.260
And yet, unless, and in the context of your lab
link |
01:56:18.140
and other labs doing similar work,
link |
01:56:20.940
you've got this people checking blood pressure,
link |
01:56:23.340
you've got people that are really monitoring
link |
01:56:25.060
your psychological and physical safety.
link |
01:56:27.300
When people are out there micro dosing,
link |
01:56:28.860
it sounds like there's the potential,
link |
01:56:30.900
either through this serotonin 5-H2B receptor
link |
01:56:35.420
or other mechanism that maybe there could be
link |
01:56:37.540
some kind of cumulative negative effects.
link |
01:56:41.540
And I think that's a really important consideration.
link |
01:56:44.340
So I'm glad you brought it up.
link |
01:56:46.260
What about kids?
link |
01:56:47.540
So the brain is very plastic early in life.
link |
01:56:50.700
It becomes less plastic as we age,
link |
01:56:53.460
although it maintains some degree of plasticity
link |
01:56:56.140
throughout the lifespan.
link |
01:56:57.660
The year 25, not the year 25,
link |
01:57:01.660
but rather the age 25 years is sort of an inflection point
link |
01:57:06.900
where the rigidity of the nervous system
link |
01:57:10.420
seems to really take off.
link |
01:57:11.620
Of course, people don't wake up on their 25th birthday
link |
01:57:14.060
and find they have no neuroplasticity,
link |
01:57:16.300
whereas the day before they had a lot,
link |
01:57:17.740
these are, it's plus or minus, whatever it is,
link |
01:57:20.580
a year or two, but depends on the individual.
link |
01:57:23.700
However, the young brain is very plastic.
link |
01:57:30.660
And I could imagine there could be great risks,
link |
01:57:35.980
who knows, maybe even benefits,
link |
01:57:37.420
but I'm certainly not thinking about those.
link |
01:57:40.020
I'm mainly thinking about the risks
link |
01:57:42.620
for young people taking psychedelics.
link |
01:57:46.220
Are there any trials looking at people in clinical trials
link |
01:57:49.940
this would be under the age of 18?
link |
01:57:51.300
Has anyone explored this in a rigorous way?
link |
01:57:54.420
Given the potential to exacerbate psychotic symptoms
link |
01:57:57.660
and bipolar symptoms in some people,
link |
01:58:00.980
is there heightened risk of that?
link |
01:58:03.300
What's the story with age of use and psychedelics
link |
01:58:06.340
for therapeutic purposes?
link |
01:58:07.540
There's no formal research,
link |
01:58:10.060
although there's a very high chance that there will be.
link |
01:58:13.060
And so this is one of the very interesting things
link |
01:58:14.820
folks may not realize or appreciate
link |
01:58:17.420
about the FDA approval process.
link |
01:58:19.580
So the FDA already in multiple instances
link |
01:58:22.140
has signaled that they want to see those studies before.
link |
01:58:26.860
Well, not before it's approved necessarily for adults,
link |
01:58:32.780
but they're going to eventually want to see it.
link |
01:58:34.380
In fact, so the MAPS group that's developing MDMA for PTSD,
link |
01:58:38.260
they've already signaled
link |
01:58:41.460
that that's kind of on the list of interest.
link |
01:58:44.900
And there's even some incentives in the FDA pathways
link |
01:58:50.020
for incentivizing folks to explore
link |
01:58:53.500
that use in young people.
link |
01:58:55.780
I know in some of the work that I helped with
link |
01:58:57.780
in pushing psilocybin into phase 2B clinical research,
link |
01:59:05.020
the FDA said, well, why can't you give this to kids?
link |
01:59:09.540
It's like, are you aware that depression
link |
01:59:12.780
is a problem with adolescents?
link |
01:59:17.020
And it's really interesting
link |
01:59:18.300
because this FDA is very concerned about pseudospecificity.
link |
01:59:23.060
The idea that you put out a drug and say,
link |
01:59:26.020
oh, this is good for men, but not women.
link |
01:59:28.820
This is good for black folks, but not white folks.
link |
01:59:31.580
And now sometimes there's a very good rationale for that.
link |
01:59:34.660
Like when we're talking about hormones
link |
01:59:36.700
and for a specific, for men versus women.
link |
01:59:40.460
And there's certain issues,
link |
01:59:45.180
certain disease say it's like maybe sickle cell anemia
link |
01:59:47.780
that's more relevant to-
link |
01:59:48.620
It tastes excellent.
link |
01:59:49.460
Yeah, exactly.
link |
01:59:51.020
But absent of something that they're very concerned
link |
01:59:53.940
about saying, oh, this is for this type of person,
link |
01:59:56.740
but not that type of person.
link |
01:59:57.980
So age is one of those things.
link |
01:59:59.580
And also this recognition,
link |
02:00:01.900
much like the emphasis at NIH with rodent studies
link |
02:00:06.380
and human studies that like,
link |
02:00:07.300
you can't just say you're studying men
link |
02:00:08.780
or just you need a rationale if you're only-
link |
02:00:11.700
Yeah, to be clear to people, it's a recent switch,
link |
02:00:15.340
but there's a stipulation in every federally funded grant
link |
02:00:19.820
that both sexes, we don't refer to gender
link |
02:00:22.820
in scientific studies, unless it's a study of gender per se.
link |
02:00:26.460
We refer to sex, meaning biological sex.
link |
02:00:28.860
So that there's a stipulation that in order to receive
link |
02:00:32.180
and continue to receive funding,
link |
02:00:33.460
you have to do studies on both males and females
link |
02:00:37.680
of that species, including humans.
link |
02:00:39.860
And at least, even if you're not powered for it,
link |
02:00:42.040
at least looking at that in exploratory analysis,
link |
02:00:44.660
like as a grant reviewer, I'm charged with looking at,
link |
02:00:48.260
did they address like sex
link |
02:00:49.720
as a biologically relevant variable?
link |
02:00:51.780
Right, does the same drug have different effects
link |
02:00:55.420
in males versus females?
link |
02:00:56.740
Right, and you can at least look at the trends,
link |
02:00:58.700
even again, if you're underpowered
link |
02:01:00.140
to look at those between subject type effects.
link |
02:01:02.940
Which is a great shift that didn't exist
link |
02:01:04.980
in 10 years ago, sounds like we're both on grants panels.
link |
02:01:10.500
As study section members, you didn't have to do that.
link |
02:01:12.500
Now it's an important biological variable.
link |
02:01:14.560
If you don't look at that,
link |
02:01:16.180
you essentially won't get your funding.
link |
02:01:18.600
And age is a similar thing.
link |
02:01:19.960
So it's the whole idea like,
link |
02:01:21.180
man, if something could help kids, like what's the rationale?
link |
02:01:23.940
So I think there's going to be,
link |
02:01:24.960
now obviously you're going to have in those studies
link |
02:01:28.420
at least just as much, probably more,
link |
02:01:31.020
it should be more of a cautionary approach.
link |
02:01:34.720
It's probably going to be,
link |
02:01:37.260
would certainly whatever disease states are looked at
link |
02:01:39.260
are going to have to be probably treatment resistant,
link |
02:01:41.320
at least as a first step.
link |
02:01:42.440
You know, hey-
link |
02:01:43.280
Suicidal depression.
link |
02:01:44.100
Yeah, yeah, and so all of that in the mix,
link |
02:01:46.660
but hey, you know, if this stuff really helps people,
link |
02:01:51.060
you know, that are 25 or 30,
link |
02:01:54.140
like what's the rationale that it won't help a younger person?
link |
02:01:57.740
You know, and there's these generic kind of concerns
link |
02:02:00.100
about the developing nervous system
link |
02:02:02.720
is more susceptible to problem.
link |
02:02:05.300
I mean, it cuts both ways
link |
02:02:06.460
because it's also more plastic generally and adaptable
link |
02:02:10.060
and maybe resilient to injury in certain ways.
link |
02:02:12.700
But, you know, you hear the rhetoric
link |
02:02:14.260
about kids, their brains and drugs,
link |
02:02:16.280
and it's like the developing brain is a special concern.
link |
02:02:20.740
So yeah, but I think we're going to be
link |
02:02:22.140
seeing research eventually.
link |
02:02:23.800
That's interesting.
link |
02:02:24.720
I went to the high school that is infamous, sadly,
link |
02:02:29.720
Gunn High School, for having the highest degree,
link |
02:02:33.340
at least at one point, of suicide rate.
link |
02:02:36.100
Wow.
link |
02:02:36.940
And a very large number of suicides.
link |
02:02:39.020
This was written up in the Times and elsewhere.
link |
02:02:41.440
Is it a very academically successful school?
link |
02:02:44.020
It's a very academically-
link |
02:02:44.860
So there's a lot of high pressure.
link |
02:02:45.900
Yeah, very academically demanding school
link |
02:02:47.900
to the point where they've restricted,
link |
02:02:50.220
the kids will meet often at 6.30 a.m. or 6 a.m. before school
link |
02:02:54.400
for study groups and things of that sort.
link |
02:02:56.420
So some of it may relate to that.
link |
02:02:58.620
But I have to say that even prior
link |
02:03:00.160
to all that academic pressure,
link |
02:03:03.240
when I went there, the pressure wasn't like that.
link |
02:03:06.680
You know, we had an unusual number of suicides
link |
02:03:10.660
for whatever reason.
link |
02:03:11.800
And, you know, and so the idea of kids being prescribed,
link |
02:03:17.180
and I want to emphasize prescribed, not just using,
link |
02:03:19.340
but prescribed psychedelics for therapeutic purposes,
link |
02:03:22.120
I think might make some people balk.
link |
02:03:24.560
But the idea of kids killing themselves
link |
02:03:29.460
should also make people balk.
link |
02:03:30.780
And so I'm relieved to hear that there's going to be
link |
02:03:34.180
a rational, scientific, safe,
link |
02:03:37.380
clinical trial-based exploration of this.
link |
02:03:41.880
I want to ask you about the current status
link |
02:03:45.380
of these drugs and compounds.
link |
02:03:47.000
I'm pretty active on social media,
link |
02:03:51.260
more so on Instagram than on Twitter.
link |
02:03:53.260
But as I have been on Twitter a little bit more recently,
link |
02:03:57.280
I've noticed that there's a lot of dialogue
link |
02:04:00.700
around your account and other people's accounts
link |
02:04:02.560
around a couple of themes related to psychedelics.
link |
02:04:04.780
First of all, what is the status of the transition
link |
02:04:08.420
to legality for prescription purposes?
link |
02:04:11.980
So medical doctors, MDs,
link |
02:04:14.500
prescribing it legally for therapeutic purposes.
link |
02:04:17.980
That's the first question.
link |
02:04:19.060
The second question is what is the status
link |
02:04:22.080
as it relates to possession and criminal charges?
link |
02:04:25.580
So for a long time, I lived in Oakland,
link |
02:04:28.740
where we were one day told not too long ago,
link |
02:04:32.060
it is now quote-unquote decriminalized is what I was told.
link |
02:04:35.220
I double-check people.
link |
02:04:37.300
But what does that mean?
link |
02:04:38.820
And then the other issue and the third question,
link |
02:04:41.780
and we can parse these one by one,
link |
02:04:43.480
is this issue of, let's just say I'm aware
link |
02:04:46.980
of a lot of investor dollars going into companies
link |
02:04:50.340
that are essentially companies focused on psychedelics
link |
02:04:55.680
as therapeutics or psychedelics generally.
link |
02:04:58.800
I have to assume that they are investing in anticipation
link |
02:05:02.220
of a shift in the legal status.
link |
02:05:05.520
And there's a lot of interest now,
link |
02:05:07.620
like will psilocybin become a taxable thing
link |
02:05:11.500
just like marijuana?
link |
02:05:12.380
So let's start with the question of like,
link |
02:05:14.360
what is going on in the US legally?
link |
02:05:18.060
Is it illegal to possess and sell and use these compounds?
link |
02:05:24.420
My understanding is you can still go to jail
link |
02:05:26.500
for having these compounds in your possession
link |
02:05:30.260
or for selling.
link |
02:05:31.100
Right, so even though the legal landscape
link |
02:05:35.580
is very different than with cannabis,
link |
02:05:38.260
there are some similarities.
link |
02:05:39.700
So one of the similarities is that regardless
link |
02:05:42.080
of what local municipal, whether city or state
link |
02:05:45.800
is decriminalized, and that word itself can mean many things.
link |
02:05:50.580
So the devil, some forms of decriminalization
link |
02:05:53.820
is close to what folks would call legalization
link |
02:05:56.820
and others are like pretty weak,
link |
02:05:59.260
just saying we suggest that the police
link |
02:06:01.780
make it their lowest law enforcement priority,
link |
02:06:03.860
that type of thing.
link |
02:06:04.700
So they can choose.
link |
02:06:05.540
Turn the other kind of thing.
link |
02:06:06.380
Right, but even the cops can still choose to.
link |
02:06:09.200
But someone could get pulled over for one thing searched
link |
02:06:12.260
and then by definition, if it's illegal and they find it,
link |
02:06:15.300
then they have to do something about it.
link |
02:06:17.940
And that'll probably be determined
link |
02:06:19.560
by both judicial precedent.
link |
02:06:22.460
Is it going to be thrown out?
link |
02:06:23.600
And just the local prosecutor,
link |
02:06:25.940
even before, are they going to choose,
link |
02:06:27.520
even at post arrest are going to pursue
link |
02:06:30.100
to really go after those charges,
link |
02:06:31.940
make those charges stick.
link |
02:06:33.700
So I think that's still in play
link |
02:06:34.900
and is going to depend on the municipality.
link |
02:06:36.420
But like cannabis, federally,
link |
02:06:38.960
these are all schedule one compounds.
link |
02:06:40.620
Which means they're illegal.
link |
02:06:41.860
Which means they're illegal.
link |
02:06:43.860
The caveat to that, just as has always been the case
link |
02:06:46.140
since Prop 215 in California with cannabis in 96,
link |
02:06:49.340
is that, hey, 99% of drug enforcement
link |
02:06:54.180
is done at the local and state level.
link |
02:06:55.720
The DEA, which is the federal level of law enforcement,
link |
02:06:59.580
is a tiny fraction of the arrests.
link |
02:07:02.740
I mean, most people that are arrested for any drug
link |
02:07:04.860
are done by local or state level authorities.
link |
02:07:10.360
But it's still technically illegal.
link |
02:07:13.180
And so you can, and they could potentially,
link |
02:07:15.980
and depending on the ambiguity of local law,
link |
02:07:18.420
even those local officials could charge you
link |
02:07:20.140
with a federal crime.
link |
02:07:22.780
And theoretically, the feds could always come in.
link |
02:07:27.100
Now, although you'll, again, a similar case
link |
02:07:30.980
with the whole cannabis history,
link |
02:07:33.380
it was the feds came in in the early days,
link |
02:07:36.960
but the folks that were basically highly visible.
link |
02:07:39.820
They went after Tommy Chong for selling bongs.
link |
02:07:42.620
But I remember him being on The Tonight Show one time,
link |
02:07:45.420
and I think it was back in the Jay Leno days,
link |
02:07:47.340
he says, but oh, along the Santa Monica boardwalk,
link |
02:07:50.220
like every shop sells bongs.
link |
02:07:51.580
How did you go to prison for a half year for bongs?
link |
02:07:53.720
It's because he was, and they're-
link |
02:07:55.220
Because he was famous.
link |
02:07:56.060
Because he was Tommy Chong.
link |
02:07:57.820
And there was some high profile cannabis groups
link |
02:08:02.340
that were distributing it and they were very vocal.
link |
02:08:04.500
Those were the ones rated by the DEA in the early days,
link |
02:08:06.900
not the ones kind of keeping to themselves,
link |
02:08:08.920
keeping it quiet and just doing their thing.
link |
02:08:10.540
So there's always the potential for selective enforcement.
link |
02:08:14.600
And so, and like this initiative in Oregon,
link |
02:08:17.260
which is a state level legalization of psilocybin therapy,
link |
02:08:22.480
which is really interesting.
link |
02:08:24.160
Part of their plan for two years is to figure out
link |
02:08:26.620
how to integrate with the federal level.
link |
02:08:30.300
And I don't know how that's going to go
link |
02:08:32.100
because unless you rewrite the Controlled Substances Act,
link |
02:08:36.020
it seems like the best you're going to get
link |
02:08:37.460
is a tolerance from the federal government.
link |
02:08:42.940
And that could be very, hey, you change administrations.
link |
02:08:48.060
And this is psilocybin by a prescription
link |
02:08:51.020
from a medical doctor, or you're talking about therapists
link |
02:08:55.620
who have master's degrees or PhDs or self-appointed coaches
link |
02:09:00.260
or something like that, administering psilocybin,
link |
02:09:04.460
but without any oversight.
link |
02:09:06.740
So this is all getting figured out in the Oregon case.
link |
02:09:09.480
And again, there's that two-year period of like,
link |
02:09:11.480
basically we're going to figure this out.
link |
02:09:13.100
And so there's-
link |
02:09:13.940
What is it with Oregon?
link |
02:09:15.420
They're ahead with a lot of, you know, euthanasia.
link |
02:09:18.220
I love the state of Oregon.
link |
02:09:19.580
But it's interesting how you have these pockets.
link |
02:09:22.540
Oregon, Vermont seems to be one.
link |
02:09:24.720
You know, you've got these kind of pockets
link |
02:09:26.540
where people are experimental with plant compounds.
link |
02:09:30.720
They seem to be green, woodsy areas for,
link |
02:09:33.420
at least in my mind, but there's sort of a culture
link |
02:09:35.900
around plants and the use of plants as therapeutics.
link |
02:09:39.240
And combine that with the West,
link |
02:09:41.060
just more geographically of more of the anti-federalism,
link |
02:09:46.740
the anti, I mean, the Oregon ranchers from several years ago
link |
02:09:49.580
that held up the, you know, the whatever wildlife place,
link |
02:09:53.820
you know, and that was a big showdown with the feds,
link |
02:09:55.780
you know, and the, you know, just kind of the West
link |
02:09:59.060
is kind of known for, you know, more of those issues.
link |
02:10:02.280
So you combine the two,
link |
02:10:03.500
the hippie dippie, California, Oregon vibe,
link |
02:10:05.820
with the kind of anti-
link |
02:10:06.660
Although I would argue it's becoming less hippie dippie
link |
02:10:08.660
than, although it was,
link |
02:10:11.300
that there's always been a tradition,
link |
02:10:13.140
not just in the culture around drugs,
link |
02:10:15.460
but certainly in academia and in tech, et cetera,
link |
02:10:18.380
that the West has been a place
link |
02:10:21.540
where people have tried to throw off traditionalism
link |
02:10:25.180
and kind of lineage and like who your parents are,
link |
02:10:28.700
what school you went to, and the past
link |
02:10:32.820
as a determinant of what's next
link |
02:10:34.980
and exciting about the future.
link |
02:10:36.720
Whereas, and here we are an East Coast institution guy
link |
02:10:39.700
and a West Coast institution guy.
link |
02:10:42.260
I think that it's this idea of kind of innovation
link |
02:10:46.140
and the future versus do we stay grounded
link |
02:10:49.120
in history and tradition.
link |
02:10:51.620
And of course there are great institutions on both sides.
link |
02:10:53.860
What's interesting is that Hopkins,
link |
02:10:56.260
Johns Hopkins Medical School,
link |
02:10:57.900
I think of as a real like East Coast academic institution.
link |
02:11:02.000
It is on the East Coast, but here you are
link |
02:11:05.940
doing these very pioneering and important
link |
02:11:09.320
and exploratory studies in a,
link |
02:11:12.820
certainly not a hippie dippie environment.
link |
02:11:14.960
Right, oh yeah.
link |
02:11:15.980
Very conservative psychiatry department,
link |
02:11:17.980
even amongst psychiatry departments.
link |
02:11:19.580
And as a psychologist in a psychiatry department,
link |
02:11:21.940
psychiatry is certainly more conservative than psychology,
link |
02:11:25.160
even within academics.
link |
02:11:26.320
But even amongst psychiatry departments,
link |
02:11:28.260
it's a very conservative department.
link |
02:11:30.700
So we've got the law at the federal level.
link |
02:11:32.960
We've got the law at the state and local level.
link |
02:11:35.820
And then we've got this question
link |
02:11:37.740
of whether or not it's going to be physicians.
link |
02:11:40.560
So MDs, people with PhDs or master's degrees,
link |
02:11:44.220
or whether or not it will be kind of a free-for-all
link |
02:11:47.580
for consumption.
link |
02:11:48.740
And the life coaches.
link |
02:11:49.780
The life coaches and the general public.
link |
02:11:52.220
I mean, cannabis, I'm not a pot smoker.
link |
02:11:55.860
It's never appealed to me.
link |
02:11:57.640
That's just me and my pharmacology.
link |
02:11:59.900
But you can buy cannabis most places in the U.S.
link |
02:12:05.960
without a ton of risk, it seems, right?
link |
02:12:10.440
Are we going to see a time in which
link |
02:12:12.680
you can essentially go into a shop
link |
02:12:15.880
on Abbot Kinney Boulevard in Venice, California?
link |
02:12:19.540
And right now you can go buy marijuana
link |
02:12:21.580
if you have a marijuana carta.
link |
02:12:23.300
That's my understanding.
link |
02:12:24.200
I see a lot of people going in and out of these stores.
link |
02:12:27.100
The police certainly have no problem with it.
link |
02:12:28.820
Is there going to come a time
link |
02:12:29.880
where people can just go buy psilocybin?
link |
02:12:32.660
Do you think-
link |
02:12:33.500
Like they do in Amsterdam and have for a long time.
link |
02:12:35.340
Do you think that time is coming?
link |
02:12:39.020
I think so at a certain point.
link |
02:12:42.920
And I don't know how long.
link |
02:12:48.660
It's hard to imagine our current level
link |
02:12:52.060
of drug criminalization holding up for,
link |
02:12:57.060
and I'm thinking like large spans of time,
link |
02:12:58.940
like really in a hundred years
link |
02:13:00.360
are we going to be doing this 500 years?
link |
02:13:02.200
Like how could that?
link |
02:13:03.040
It's not going to be sustainable.
link |
02:13:04.580
But in five years, for instance.
link |
02:13:06.140
So I don't think so in the United States.
link |
02:13:09.720
I do think eventually you're going to see something like that
link |
02:13:13.680
because there's going to be no way.
link |
02:13:15.080
And I think we're going to,
link |
02:13:16.660
I hope that we're going to eventually come so strongly.
link |
02:13:21.420
We're going to move on from this model of criminalizing drugs
link |
02:13:25.500
that we're really going to focus on regulating drugs
link |
02:13:28.180
at the right level for that drug.
link |
02:13:29.620
And I like the word regulation better than legalization.
link |
02:13:33.280
So, I mean, I could imagine what one day regulation,
link |
02:13:36.700
smart regulation might mean for psychedelics.
link |
02:13:38.980
Maybe it could mean that there will be,
link |
02:13:41.640
whether or not you have a diagnosis of a problem,
link |
02:13:44.800
it may be that even for personal exploration,
link |
02:13:47.000
you can do this legally,
link |
02:13:48.600
but you first have to maybe take a court, get a drive.
link |
02:13:51.420
And this has been, I'm not the first to say this,
link |
02:13:52.980
but get equivalent of a driver's license.
link |
02:13:55.200
You have to go to get some sort of training.
link |
02:13:58.040
Maybe your first number of experiences
link |
02:14:00.700
need to be with trained guides who can facilitate it.
link |
02:14:05.060
And then the public health information
link |
02:14:06.880
for anyone using this that this is what riskier use is.
link |
02:14:10.760
All use is going to have risk.
link |
02:14:12.040
This is what riskier use is.
link |
02:14:13.260
This is less risky use.
link |
02:14:14.700
These are the factors.
link |
02:14:16.200
So I think eventually we're going to be getting for any,
link |
02:14:18.100
but I would say the same thing for like methamphetamine
link |
02:14:20.900
and heroin and cocaine, like all of these drugs,
link |
02:14:24.740
it's hard to imagine the current approach
link |
02:14:27.120
of just feeding a black market
link |
02:14:29.560
and really exacerbating a lot of the harms from drugs.
link |
02:14:34.240
You know, that happens under the current model.
link |
02:14:36.440
It's hard to imagine that maintaining.
link |
02:14:38.120
That isn't to say, I think it should be
link |
02:14:40.760
in all of the 7-Elevens, you know,
link |
02:14:42.560
sold to kids at the other extreme.
link |
02:14:44.400
I would hope not.
link |
02:14:45.720
But I do think it's probably not going to be soon
link |
02:14:48.180
in the United States.
link |
02:14:50.060
I do want to make the major point that
link |
02:14:52.380
even if psychedelics had never been made illegal,
link |
02:14:55.280
I think the trajectory of the medical research right now
link |
02:14:59.000
would still need to happen.
link |
02:15:00.700
If it's effective as an antidepressant,
link |
02:15:03.880
like we need it to be, you know,
link |
02:15:06.840
there's all the evidence suggesting that
link |
02:15:09.200
whatever disorder we're talking about,
link |
02:15:10.500
the efficacy is going to be increased
link |
02:15:12.160
and the risks are going to be mitigated drastically
link |
02:15:16.020
in the types of models we're talking about
link |
02:15:18.120
with the screening, with the preparation,
link |
02:15:20.480
with the integration of cognitive behavioral therapy
link |
02:15:22.720
or what have you,
link |
02:15:23.560
depending on the disorder you're treating,
link |
02:15:25.440
with the integration afterwards with the professionals.
link |
02:15:28.520
So we would be doing it anyway.
link |
02:15:32.580
So it's not like this versus that.
link |
02:15:34.360
So I don't see it as a race between the decriminalization
link |
02:15:37.080
or legalization of these compounds
link |
02:15:38.840
versus their medical development.
link |
02:15:40.360
Some people who are psychedelic fans
link |
02:15:43.480
get all into a bunch about the medical development.
link |
02:15:47.360
They say, you guys want to like, you want to keep it only
link |
02:15:50.760
for your medical research and I retire
link |
02:15:54.000
and you want to be in control of it as academics.
link |
02:15:57.360
And my take is I didn't make it illegal for anyone.
link |
02:16:00.800
We're only moving the needle in one direction.
link |
02:16:03.340
And again, even if it was already illegal,
link |
02:16:05.640
and I've done plenty of survey research of people reporting,
link |
02:16:09.160
they took mushrooms for fun or for personal exploration.
link |
02:16:12.220
And they said, my God, why am I smoking?
link |
02:16:14.800
And they quit smoking 20 years because of it,
link |
02:16:16.720
or it's helped with their depression,
link |
02:16:18.260
or it's helped with them overcoming alcoholism
link |
02:16:20.300
or these different.
link |
02:16:21.140
Sometimes that happens out of the blue
link |
02:16:22.920
when people use psychedelics.
link |
02:16:24.600
Nonetheless, obviously the efficacy rates
link |
02:16:27.680
are going to be higher when you bring it
link |
02:16:29.220
into these medical models and it's going to be safer.
link |
02:16:31.820
So we need to be pushing that.
link |
02:16:34.840
And my best guess is that MDMA is going to be approved
link |
02:16:38.260
within the next three years.
link |
02:16:39.820
And for prescription by a physician.
link |
02:16:42.040
Yes, and not just take two and call me in the morning,
link |
02:16:46.160
but in the clinics,
link |
02:16:47.200
the way that those PTSD trials are being run.
link |
02:16:50.080
So the MDMA would be approved for PTSD
link |
02:16:52.960
and every disorder needs to be looked at separately.
link |
02:16:55.100
And it's going to only be approved for those things.
link |
02:16:56.920
Now, there's going to be questions about-
link |
02:16:57.760
Right, because approved and legalized and regulated are,
link |
02:17:00.760
you know, now we're getting into the nuance.
link |
02:17:02.600
I think when people hear it's going to be approved
link |
02:17:04.400
in two years, they think that they'll be able to buy
link |
02:17:07.540
and sell and use MDMA without legal consequences.
link |
02:17:10.000
And I do not think that's going to be the situation.
link |
02:17:12.480
It's not the way it is.
link |
02:17:13.480
And I will say that I think the quote unquote,
link |
02:17:18.280
psychedelic community, I mean,
link |
02:17:20.120
they've been doing what they want to
link |
02:17:21.840
and will carry on doing what they want to anyway, right?
link |
02:17:25.840
It's not like the legal status has prevented them
link |
02:17:29.160
from doing what they're doing.
link |
02:17:30.800
In fact, unlike Lee Erie and Timothy Leary and Huxley
link |
02:17:36.080
and, you know, and some of the others that were very vocal
link |
02:17:38.720
and lost their jobs and some of them even went to jail,
link |
02:17:41.020
et cetera.
link |
02:17:41.920
I mean, you've got a lot of public figures now
link |
02:17:43.980
like McKenna and others who are just basically out there
link |
02:17:46.000
talking about psychedelics.
link |
02:17:48.000
Michael Pollan, who is more of a writer,
link |
02:17:50.140
foodie guy gone psychedelic dabbler, writer guy.
link |
02:17:54.360
I know he's kind of a polymath,
link |
02:17:55.920
but you know, the legal status didn't seem to hinder their,
link |
02:18:01.840
at least online career.
link |
02:18:02.920
So I don't know, I haven't looked at their bank accounts,
link |
02:18:05.260
but I'm imagining they're doing just fine, right?
link |
02:18:08.040
So the fact that the work is happening inside
link |
02:18:10.840
of big institutions, I think it's important
link |
02:18:13.920
that you point out, and I'm just trying to underscore
link |
02:18:16.100
that that's in no way antagonistic
link |
02:18:19.900
to what people are doing.
link |
02:18:20.880
It's in support of a different sort of mission,
link |
02:18:23.800
which is to explore the validity in different contexts
link |
02:18:26.800
in a really controlled way,
link |
02:18:28.920
which I really, you know,
link |
02:18:31.080
I think it's a really important mission.
link |
02:18:34.900
I want to make sure that I ask you
link |
02:18:36.400
about the other really important mission
link |
02:18:38.480
that you're involved in with respect to psychedelics,
link |
02:18:40.540
which is not about depression per se,
link |
02:18:43.680
but is about a neurologic injury or head injury.
link |
02:18:47.760
I realize it's early days for this,
link |
02:18:49.460
but I think there's a lot of concussion out there, sadly.
link |
02:18:54.220
There's a lot of TBI, traumatic brain injury,
link |
02:18:57.000
not just from sports.
link |
02:18:58.060
I think people sometimes forget that it's not,
link |
02:19:00.400
the major source of traumatic head injury is not football,
link |
02:19:04.280
it's not hockey, it's not boxing,
link |
02:19:07.000
it's not any of that stuff.
link |
02:19:08.520
It's construction workers and it's people,
link |
02:19:10.920
I mean, if you've ever seen the helmets
link |
02:19:12.180
that construction workers wear, I mean-
link |
02:19:14.040
The jackhammer, oh my God.
link |
02:19:15.600
The jackhammer that- How could that not be just like-
link |
02:19:17.240
Yeah, I have a colleague that works on this
link |
02:19:19.000
in bioengineering and when you look at the,
link |
02:19:20.960
you know, we always think sports,
link |
02:19:22.660
but there are many people who make a living