Dr. Matthew Johnson: Psychedelics for Treating Mental Disorders

00:00:00.320 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.880 | I'm Andrew Huberman,

00:00:10.320 | and I'm a professor of neurobiology and ophthalmology

00:00:13.000 | at Stanford School of Medicine.

00:00:15.040 | Today, I have the pleasure of introducing

00:00:16.700 | Dr. Matthew Johnson.

00:00:18.720 | Dr. Johnson is a professor of psychiatry

00:00:20.800 | at Johns Hopkins School of Medicine,

00:00:22.940 | where he also directs the Center for Psychedelic

00:00:25.160 | and Consciousness Research.

00:00:27.280 | As many of you know,

00:00:28.520 | there's extreme excitement about the use of psychedelics

00:00:31.360 | for the treatment of various disorders of the mind.

00:00:33.980 | Dr. Johnson's laboratory is among the premier laboratories

00:00:37.000 | in the world understanding how these compounds work,

00:00:40.240 | how things like psilocybin and LSD and related compounds

00:00:44.280 | allow neural circuitry in the brain to be shaped and change

00:00:47.800 | such that people can combat diseases like depression

00:00:51.600 | or trauma or other disorders of the mind

00:00:53.960 | that cause tremendous suffering.

00:00:55.840 | Dr. Johnson is also an expert in understanding

00:00:58.120 | how different types of drugs impact

00:01:00.120 | different types of human behaviors,

00:01:02.040 | such as sexual behavior, risk-taking, and crime.

00:01:05.600 | Dr. Johnson and his work

00:01:06.960 | have also been featured prominently in the popular press,

00:01:10.000 | such as articles in the New York Times

00:01:12.080 | and Michael Pollan's book, "How to Change Your Mind,"

00:01:14.200 | and in a feature in "60 Minutes" about psychedelics

00:01:16.960 | and the new emerging science of psychedelic therapies

00:01:20.080 | for treating mental disorders.

00:01:22.400 | During the course of today's conversation,

00:01:24.520 | Dr. Johnson and I talk about psychedelics

00:01:27.280 | at the level of what's called microdosing,

00:01:29.800 | whether or not it is useful for the treatment

00:01:31.880 | of any mental disorders.

00:01:33.480 | We also talk about more typical macrodosing,

00:01:35.960 | what those macrodoses entail,

00:01:37.720 | and he walks us through what an experiment

00:01:41.000 | of a patient taking psychedelics

00:01:42.600 | for the treatment of depression looks like

00:01:44.460 | in his laboratory from start to finish.

00:01:47.040 | The conversation was an absolutely fascinating one

00:01:49.740 | for me to partake in.

00:01:51.120 | I learned so much about the past, present, and future

00:01:54.800 | of psychedelic treatments and compounds.

00:01:57.160 | And indeed, I hope to have Dr. Johnson on this podcast again

00:02:00.400 | in the not too distant future

00:02:01.840 | so that we can talk about other compounds

00:02:04.160 | that powerfully impact the mind and human behavior,

00:02:07.280 | and perhaps can also be used to treat various diseases.

00:02:10.660 | Before we begin, I'd like to emphasize

00:02:12.520 | that this podcast is separate

00:02:13.780 | from my teaching and research roles at Stanford.

00:02:16.200 | It is, however, part of my desire and effort

00:02:18.400 | to bring zero cost to consumer information about science

00:02:21.160 | and science-related tools to the general public.

00:02:23.920 | In keeping with that theme,

00:02:25.000 | I'd like to thank the sponsors of today's podcast.

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00:06:39.120 | And now my conversation with Dr. Matthew Johnson.

00:06:42.580 | Well, Matthew, I've been looking forward to this

00:06:44.100 | for a long time.

00:06:44.980 | I'm a huge fan of your scientific work

00:06:48.420 | and I'm eager to learn from you.

00:06:50.680 | - Likewise, big fan and happy to do this with you.

00:06:53.600 | - Great, well, thank you.

00:06:55.340 | My first question is a very basic one,

00:06:57.280 | which is what is a psychedelic?

00:07:00.080 | We hear this term all the time,

00:07:01.440 | but what qualifies a substance as a psychedelic?

00:07:05.880 | - Nomenclature is a real challenge

00:07:09.220 | in this area of psychedelics.

00:07:10.760 | So starting with the word psychedelic,

00:07:12.780 | it just, if you're a pharmacologist,

00:07:16.020 | it's not very satisfying because that term

00:07:18.900 | really spans different pharmacological classes.

00:07:23.460 | In other words, if you're really concerned

00:07:24.920 | about receptor effects and the basic effects of a compound,

00:07:29.100 | it spans several classes of compounds.

00:07:32.660 | But overall, so it's really more of a cultural term

00:07:37.100 | or it does have a relationship to drug effects,

00:07:42.660 | but it's at a very high level.

00:07:44.900 | So all of the so-called psychedelics

00:07:47.020 | across these distinct classes that I can talk more about,

00:07:52.020 | the way I put it is they all had the ability

00:07:56.500 | to profoundly alter one's sense of reality.

00:08:00.500 | And that can mean many things.

00:08:02.060 | Part of that is profoundly altering the sense of self

00:08:04.660 | acutely, so when someone's on the psychedelic.

00:08:09.560 | So the different classes that can be,

00:08:13.160 | the specific pharmacological classes

00:08:15.640 | that can be called a psychedelic

00:08:17.640 | are one, what are called the classic psychedelics.

00:08:21.200 | So in the literature, you'll see that term.

00:08:23.080 | And hallucinogen and psychedelic

00:08:25.960 | are all have traditionally been used synonymously.

00:08:29.640 | I think there was a little of a tendency

00:08:31.320 | to stay away from psychedelics as the baggage,

00:08:33.380 | but there's been a return to that in the last several years.

00:08:36.820 | But the classic psychedelics or classic hallucinogens

00:08:39.440 | are things like LSD, psilocybin,

00:08:44.180 | which is in so-called magic mushrooms,

00:08:47.140 | it's in over 200 species that we know of so far of mushrooms,

00:08:50.920 | dimethyltryptamine or DMT,

00:08:53.780 | which is in dozens and dozens of plants,

00:08:58.060 | mescaline, which is in the peyote cacti

00:09:00.980 | and some other cacti like San Pedro.

00:09:03.700 | And even amongst these classic psychedelics,

00:09:07.600 | there are two structural classes.

00:09:10.880 | So that's the chemistry.

00:09:11.840 | There's the tryptamine-based compounds

00:09:13.960 | like psilocybin and DMT,

00:09:16.160 | and then there's the phenethylamine-based compounds.

00:09:19.240 | So these are the basic two to basically building blocks

00:09:23.040 | that you're starting from,

00:09:24.280 | either a tryptamine structure or a phenethylamine structure.

00:09:27.980 | But that's just the chemistry.

00:09:29.640 | All of the, what's more important,

00:09:32.240 | or at least to someone like me, are the receptor effects.

00:09:35.980 | And then ultimately that's going to have a relationship

00:09:38.040 | to the behavioral and subjective effects.

00:09:39.980 | So all of these classic psychedelics serve as agonists

00:09:43.460 | or partial agonists at the serotonin 2A receptor,

00:09:47.100 | so subtype of serotonin receptor.

00:09:49.860 | Then you have these other classes of compounds

00:09:54.500 | that you could call psychedelic.

00:09:56.660 | Another big one would be the NMDA antagonist.

00:09:59.240 | So this would include ketamine, PCP, and dextromethorphan,

00:10:03.460 | something I've done some research with,

00:10:04.900 | which folks might recognize from like robo-tripping,

00:10:07.720 | guzzling, like, you know, call syrup,

00:10:11.740 | which is something kind of like high school kids

00:10:13.840 | are known to do when they can't get ahold of real drugs,

00:10:16.040 | that type of thing.

00:10:17.360 | So a large overlap in the types of subjective effects

00:10:22.360 | that you get from those compounds

00:10:24.560 | compared to the 2A agonist classic psychedelics.

00:10:29.080 | But then you have, and by the way, this description,

00:10:32.480 | this framework I'm describing,

00:10:33.880 | not everyone will agree.

00:10:35.300 | Some people will say,

00:10:36.340 | "No, psychedelic only means classic psychedelic."

00:10:40.000 | So there's different opinions here,

00:10:41.500 | but you have, gosh, salvinorin A,

00:10:43.820 | which is a kappa opioid agonist, which again-

00:10:48.300 | - Where does that come from?

00:10:49.580 | - Salvia divinorum.

00:10:50.980 | It's a plant that became 20 years ago.

00:10:53.140 | It sort of popped onto the legal high scene.

00:10:56.060 | And there's a long history of this.

00:10:58.500 | Predating the internet,

00:10:59.560 | going back to like the stuff one could order

00:11:01.340 | in the back of High Times Magazine.

00:11:03.720 | And most of this stuff like never worked.

00:11:05.620 | You know, it's like the smoke enough of anything,

00:11:07.820 | maybe you get a little bit lightheaded.

00:11:09.580 | But this is one of those things that popped around

00:11:12.140 | 20 years ago when it quickly got the reputation of like,

00:11:14.860 | holy shit, this stuff actually works

00:11:17.120 | and works really strongly.

00:11:19.260 | In these smoked extracts particularly,

00:11:21.380 | people have these reality altering experiences

00:11:25.480 | on par with smoked DMT, the classic psychedelic.

00:11:29.380 | So often, and we did the first

00:11:31.740 | blinded controlled human research with salvinorin A.

00:11:34.260 | So lots of entity contact.

00:11:37.000 | So feeling that you, in the experience of one

00:11:39.760 | is actually interacting with autonomous beings,

00:11:43.440 | that type of thing.

00:11:44.940 | And then you have another big one,

00:11:46.800 | probably should have mentioned even before the salvinorin A,

00:11:50.500 | but you have MDMA,

00:11:51.780 | which really stands in a class by itself.

00:11:53.860 | So it's been called an intactogen and-

00:11:57.240 | - What does that mean?

00:11:58.760 | - It means like touching within.

00:12:01.820 | It sort of eludes the idea that it can really put someone

00:12:04.860 | in touch with their emotions.

00:12:07.440 | It's also been called an empathogen,

00:12:09.500 | meaning it can afford empathy.

00:12:11.440 | But I think intactogen is probably,

00:12:14.240 | that's the term that I tend to focus on.

00:12:17.220 | And I know I'm not telling you anything you don't know,

00:12:19.760 | but for the viewers,

00:12:23.500 | the primary mechanism of MDMA is serotonin release.

00:12:27.920 | And to a degree, other monoamine release,

00:12:31.040 | dopamine, serotonin.

00:12:32.760 | And so structurally that's also in the phenethylamine class,

00:12:37.600 | which contains mescaline, the classic psychedelic,

00:12:42.120 | but also amphetamine.

00:12:43.640 | So just like Adderall is in that phenethylamine class.

00:12:48.640 | And so this is another example

00:12:50.520 | where chemistry doesn't dictate.

00:12:52.040 | I mean, you can tweak a molecule,

00:12:53.920 | it might have that same basic structure,

00:12:56.600 | but now you've profoundly changed the way it interacts

00:12:58.800 | with the receptor.

00:12:59.640 | So MDMA does not exert its actions

00:13:04.640 | by, I like to say, by mimicking the baseball,

00:13:10.520 | entering the postsynaptic receptor side,

00:13:16.060 | acting as an agonist.

00:13:17.480 | So mimicking the endogenous neurotransmitter serotonin,

00:13:22.480 | like the classic psychedelics do,

00:13:25.200 | MDMA works on the pitcher side

00:13:27.360 | of just basically throwing out

00:13:29.400 | more of the natural, the endogenous.

00:13:31.560 | - Dumping more serotonin.

00:13:32.400 | - Dumping more serotonin, flooding the synapse.

00:13:35.920 | - So I get the impression that the psychedelic space

00:13:39.500 | is a enormous cloud of partially overlapping compounds.

00:13:43.480 | - Right.

00:13:44.300 | - Meaning some are impacting the serotonin system

00:13:46.680 | more than the dopamine system.

00:13:47.920 | Others are impacting the dopamine system

00:13:50.180 | more than the serotonin system.

00:13:52.840 | - Given that the definition of a psychedelic

00:13:55.120 | is that it profoundly alters sense of self,

00:13:59.180 | at least that's included as a partial definition,

00:14:03.160 | can we break that down into a couple of subcategories?

00:14:06.500 | So for instance, hallucinating, either auditory or visual,

00:14:10.860 | synesthesia, perceptual blending,

00:14:14.840 | the sense that you can hear colors and see sounds,

00:14:19.980 | for instance, a common report of people that take psychedelics

00:14:23.780 | in sufficiently high doses.

00:14:26.480 | So hallucinating, synesthesia,

00:14:28.880 | and then in terms of sense of self,

00:14:32.080 | you know, as a neuroscientist, I think, okay,

00:14:34.200 | what does it mean to alter a sense of reality?

00:14:36.800 | Really what the brain does in a very coarse way

00:14:40.920 | is to try and figure out what's happening in space,

00:14:45.040 | physical space, and that physical space

00:14:47.120 | could be within us or outside us,

00:14:48.520 | and what's happening in time, right?

00:14:50.740 | And as a vision scientist, the simplest explanation

00:14:54.100 | is when I move my hand from one location to another location,

00:14:57.180 | it's measuring the space,

00:14:58.820 | the location of my hand in space over time,

00:15:01.260 | and then you get a rate and a speed

00:15:03.220 | and all that kind of stuff, right?

00:15:04.440 | - Yeah.

00:15:05.880 | - That gets more complicated

00:15:06.800 | as you get into the emotional realm.

00:15:09.860 | But is it fair to say that psychedelics are impacting

00:15:13.620 | the space time analysis that the brain is performing

00:15:16.980 | and thereby creating hallucinations

00:15:19.620 | and thereby altering, you know, the blending of senses?

00:15:24.620 | Is it fair to say that?

00:15:27.320 | - I think it's fair to explore that area.

00:15:31.140 | And here's what I'm thinking.

00:15:32.740 | Clearly there is a changed relationship,

00:15:36.600 | certainly at the right dose, of orientation in space time.

00:15:40.780 | I think as a, you know, I'm primarily a behaviorist,

00:15:46.100 | and in terms of human behavioral pharmacology,

00:15:49.380 | I always go to comparative pharmacology, okay?

00:15:51.940 | What can we say that is it truly unique

00:15:54.220 | about the classic psychedelic, or psychedelics in general?

00:15:57.420 | So with that description, I'm thinking, okay,

00:16:00.260 | alcohol can really screw up your, you know,

00:16:03.160 | time-space orientation.

00:16:05.260 | - And proprioception, your balance.

00:16:06.100 | - Proprioception. - Your vestibular, yeah.

00:16:07.860 | - You know, and in many ways,

00:16:10.100 | and sort of in those gross motorways, like far worse,

00:16:12.980 | you know, of course everything's dose dependent,

00:16:14.600 | but in the classic psychedelics, you know,

00:16:16.200 | obviously the benzodiazepines being very similar alcohol,

00:16:18.660 | same thing.

00:16:19.500 | So, you know, I'd want to, you know,

00:16:22.880 | dig in a little more in terms of like,

00:16:25.140 | maybe there's something more specific we could say

00:16:27.380 | about that relationship to time and space

00:16:31.580 | that the psychedelics are tinkering with.

00:16:33.740 | But I'm not sure.

00:16:34.660 | It's an interesting hypothesis that the idea

00:16:36.760 | that that's a mediator, that that's something,

00:16:39.020 | that there's something fundamental about changing that,

00:16:42.360 | the representation in time and space.

00:16:46.000 | There might be something to that.

00:16:49.220 | I mean, I think of these as psychedelics

00:16:51.740 | as profoundly altering models, you know.

00:16:55.720 | We're all, you know, we're prediction machines

00:16:58.780 | and that's large, so much of that is top-down

00:17:02.620 | and psychedelics have a good way of, you know,

00:17:07.620 | loosely speaking, dissolving those models.

00:17:11.540 | And one of, at the reality-

00:17:13.340 | - Can you give us an example of one of, like a model,

00:17:15.520 | like I know that when I throw a ball in the air,

00:17:18.780 | it falls down, not up.

00:17:20.220 | That's a prediction that I learned as a child

00:17:23.980 | that I did not come into the world with a brain

00:17:27.400 | that knew that relationship between objects and gravity.

00:17:32.400 | But one of the first things that a child learns

00:17:36.260 | is the relationship between objects and gravity

00:17:39.380 | and their trajectories.

00:17:40.340 | - Yeah, and with a four-year-old,

00:17:41.980 | I mean, I saw that at earlier ages,

00:17:44.180 | like that experimentation of like,

00:17:46.140 | oh yeah, that's what happens, you know.

00:17:48.420 | - Right, so if he were to throw a ball,

00:17:50.620 | if your child were to throw a ball

00:17:52.180 | and it went up into the sky,

00:17:54.020 | that would be absolutely mind-blowing.

00:17:57.220 | It would be for an adult too.

00:17:58.460 | - It'd be a pretty psychedelic experience probably.

00:18:01.100 | - Right, and so there's a rule there, you're saying,

00:18:04.400 | there's a kind of a prediction,

00:18:07.340 | there's a rule that underlies a prediction

00:18:09.940 | that when that rule is violated,

00:18:13.180 | all of a sudden the circuit,

00:18:14.340 | presumably for that prediction,

00:18:16.420 | like it doesn't have a mind of its own,

00:18:18.020 | but somehow it creates a surprise element

00:18:20.420 | or a recognition element.

00:18:22.780 | - And it's not filtered out, you know.

00:18:26.020 | And this might sound extreme, but there are these cases,

00:18:30.020 | it was overblown in sort of the propaganda

00:18:32.700 | of the late '60s, early '70s,

00:18:34.460 | but there are credible cases of people,

00:18:37.460 | and it's very atypical of,

00:18:40.180 | sounds like they really thought they could fly

00:18:42.460 | and jump out of a window.

00:18:46.140 | Now, far more people every year fall,

00:18:51.100 | I mean, who knows, they fall and die from height

00:18:55.380 | because they're drunk, so this is extremely rare.

00:18:59.060 | But there are some pretty convincing cases.

00:19:03.260 | There was one research volunteer in our studies

00:19:06.060 | that she looked like she was, in one of our studies,

00:19:11.060 | like she was trying to dive through a painting on the wall.

00:19:14.060 | She was fine, but she, reviewing the video,

00:19:18.100 | it looked like she really thought

00:19:21.420 | that she was going to go through that painting

00:19:23.980 | and who knows, into the other dimension.

00:19:28.260 | - Yeah, so they're violating these predictions.

00:19:30.660 | Yeah, the reason I ask it, the question the way I did,

00:19:34.860 | is because given the enormous cloud of different substances

00:19:38.460 | and given the range of previous experiences

00:19:41.500 | that people show up to a psychedelic experience with,

00:19:44.380 | I feel like the ability to extract some universal themes

00:19:49.340 | is useful, especially for people

00:19:50.900 | who haven't done them before, right?

00:19:52.620 | Who might not have an understanding

00:19:54.580 | of what their effects are like.

00:19:56.500 | Can we just briefly touch on the serotonin system

00:20:01.500 | and the dopamine system?

00:20:02.980 | I want to acknowledge that, as you already know,

00:20:05.900 | that there are many neuromodulator systems in the body

00:20:08.460 | and the opioid systems, cannabinoid systems,

00:20:10.860 | but there's something so profound

00:20:13.340 | about the serotonin system and the dopamine system

00:20:15.740 | because the way I define a neuromodulator

00:20:18.300 | is it's a modulator, it changes the way

00:20:20.920 | that other circuits behave.

00:20:22.660 | And essentially it increases the probability

00:20:25.480 | that certain circuits will be active

00:20:26.840 | and decreases the probability

00:20:27.900 | that other circuits will be active in a general sense.

00:20:31.480 | So compounds like LSD,

00:20:34.560 | lysergic acid, diethylamide, and psilocybin,

00:20:38.380 | my understanding is that they primarily target

00:20:42.440 | the serotonin system.

00:20:44.000 | How do they do that at a kind of general level?

00:20:48.440 | And why would increasing the activity

00:20:51.240 | of a particular serotonin receptor

00:20:53.100 | or batch of serotonin receptors

00:20:55.120 | lead to these profoundly different experiences

00:20:58.360 | that we're calling model challenges,

00:21:02.600 | challenging pre-existing models and predictions?

00:21:05.020 | I mean, at the end of the day, it's a chemical

00:21:07.560 | and these receptors are scattered around the brain

00:21:09.800 | with billions of other receptors.

00:21:12.100 | What do we think is going on in a general sense?

00:21:17.180 | - Yeah, yeah, and this is really the area

00:21:19.480 | of active exploration and we don't have great answers.

00:21:22.680 | We know a good amount about the receptor level pharmacology.

00:21:26.380 | Some things about post receptor signaling pathways.

00:21:29.820 | In other words, just fitting into the receptor.

00:21:32.540 | Clearly, serotonin itself is not psychedelic

00:21:36.300 | or else we'd be tripping all of us all the time.

00:21:38.340 | - 'Cause when I eat a bagel, I get serotonin release, right?

00:21:40.960 | - Uh-huh.

00:21:41.800 | - I mean, there's turkey, I mean, there's tryptophan, right?

00:21:45.180 | My understanding of serotonin is that in very broad strokes,

00:21:49.040 | that it generally leads to a state of being fairly,

00:21:53.000 | it pushes the mind and body towards a state

00:21:55.160 | of contentment within the immediate experience.

00:21:59.560 | Whereas the dopamine system really places us

00:22:02.000 | into an external view of what's out there in the world

00:22:05.280 | and what's possible.

00:22:06.280 | - Yeah.

00:22:07.120 | - Is that fair to say? - Need to do something.

00:22:08.240 | I mean, that's consistent with my understanding

00:22:11.540 | and I'll certainly not, in terms of,

00:22:14.480 | I don't primarily identify as a neuroscientist.

00:22:17.800 | Definitely tell the viewers that we're far more

00:22:20.920 | in your domain here than mine, but in terms

00:22:23.720 | of how psychedelics and other drugs, you know,

00:22:25.960 | interface at the neuroscience level.

00:22:28.360 | - Well, feel free to explain it at the experiential level.

00:22:31.360 | - Yeah.

00:22:32.200 | - I mean, it doesn't have, I think,

00:22:33.400 | there probably are some audience members

00:22:35.000 | that are interested in, is it the 5-H2C?

00:22:36.860 | Is it the layer five neurons and cortex?

00:22:39.140 | That conversation we could hold

00:22:40.520 | and that's an interesting conversation,

00:22:41.800 | but just in terms of the experience of serotonergic

00:22:46.000 | versus dopaminergic drugs.

00:22:48.640 | - Yeah.

00:22:49.480 | - They do seem to create distinct classes of experience.

00:22:54.360 | So I think that's the appropriate level

00:22:57.040 | for us to discuss them.

00:22:58.160 | - And in terms of how they, and I'd like to explore

00:23:00.520 | the biology a little bit here and tell you, like,

00:23:02.600 | sort of what's known and what some of the ideas are.

00:23:05.240 | - Please.

00:23:06.420 | - You know, have this path, you know, as you know,

00:23:08.820 | like, you know, these are levels of analysis

00:23:11.020 | and it's not which one is going on.

00:23:13.120 | It's almost like, for the particular question,

00:23:15.240 | which level of analysis is most appropriate?

00:23:17.760 | Is it, you know, is a question best addressed

00:23:20.120 | by the biology, the chemistry or the physics?

00:23:23.400 | That's how I think of like receptor level,

00:23:25.160 | post receptor signaling, downstream effects

00:23:27.600 | and other neurotransmitters,

00:23:29.440 | and then activation level effects

00:23:32.880 | and then coordination of activation.

00:23:35.760 | So you got the, clearly with the classic psychedelics,

00:23:39.380 | the 2A activation, we do know that there are downstream

00:23:44.320 | effects in terms of increasing glutamate transmission.

00:23:47.960 | So this is likely a commonality why, you know,

00:23:51.600 | ketamine is very psychedelic in a slightly different way.

00:23:54.320 | - Do people hallucinate on ketamine?

00:23:55.960 | - Yes, yes.

00:23:56.800 | And it's more dissociative, so someone is more likely

00:23:59.440 | to sort of be less behaviorally active.

00:24:03.160 | If they have a really high dose, they go into a K hole.

00:24:05.260 | And if they go in a really high dose,

00:24:06.700 | like you get into surgery, you're just unconscious.

00:24:09.080 | - Not an A hole, but a K hole.

00:24:10.720 | - A K hole, yeah, it's very different.

00:24:13.820 | The K hole, and ketamine is interesting

00:24:16.340 | because people can take kind of bumps

00:24:17.820 | and kind of dance on it with the sort of an alcohol level

00:24:20.940 | strength of effect, and that's sort of the classic

00:24:23.940 | kind of raving use of it.

00:24:25.900 | But then those folks want to titrate their dose

00:24:28.780 | because if they do more of like a line,

00:24:31.140 | you get up to like 75, 100 milligrams,

00:24:33.620 | then you're talking about, you know,

00:24:37.140 | if you're on the dance floor, you're on the floor

00:24:39.680 | and your friends are trying to make sure

00:24:41.380 | people aren't stepping on you.

00:24:42.560 | So that's like-

00:24:43.400 | - Yeah, why would somebody want to take

00:24:45.300 | a dissociative anesthetic?

00:24:47.400 | Like to me, it's completely mysterious

00:24:49.940 | as to why someone would want to dissociate from their body.

00:24:53.540 | - People claim that these NMDA antagonist psychedelics

00:24:58.540 | are extremely insightful in a very similar way

00:25:01.740 | to the experiences with the classic psychedelics, so-

00:25:05.220 | - And ketamine is now legal for therapeutic use.

00:25:07.300 | - Right, right, Spravato, the intranasal form,

00:25:12.320 | marketed by Janssen, which is esketamine-

00:25:14.580 | - It's prescription.

00:25:15.940 | - Yeah, it's prescription and-

00:25:18.460 | - So people are taking in the nasal spray?

00:25:20.740 | - Yeah.

00:25:21.580 | - And then are they undergoing talk therapy

00:25:23.220 | while they're doing this?

00:25:24.100 | - Typically not, so this is very interesting

00:25:26.820 | and there's so much work that needs to be done.

00:25:29.560 | It's not treated as psychedelic therapy.

00:25:32.300 | And by that psychedelic therapy, I mean,

00:25:35.180 | you tell the person they're going to have

00:25:36.460 | an altered experience.

00:25:38.140 | You tell them to pay attention to that experience,

00:25:41.500 | that they might learn something from that experience.

00:25:43.320 | And afterwards you discuss that experience.

00:25:45.740 | With Spravato, the model is-

00:25:48.940 | - Spravato is?

00:25:49.860 | - Is esketamine.

00:25:50.940 | - Okay.

00:25:51.780 | - It's the, yeah, the spray form of ketamine.

00:25:54.440 | It's been FDA approved for treatment-resistant depression,

00:25:57.920 | but you'll probably feel different, ignore that.

00:26:01.580 | That's a side effect.

00:26:03.020 | That's an adverse effect.

00:26:04.420 | Just ignore it.

00:26:06.940 | We don't think that has anything to do with the way it works

00:26:09.880 | but just get this thing.

00:26:11.180 | It's a direct sort of chemotherapeutic effect in a sense.

00:26:15.080 | It's not facilitating a learning process.

00:26:19.320 | Now there's older work.

00:26:21.020 | There was a guy Kripitsky in Russia

00:26:23.100 | that did extensive work with higher doses of ketamine.

00:26:27.040 | I should say Spravato at the prescribed doses

00:26:30.020 | isn't very, it's a pretty low dose.

00:26:32.620 | It's in the mild psychedelic range, but it's not very strong.

00:26:36.660 | But this older work that happened in the '90s

00:26:39.220 | and early 2000s in Russia,

00:26:42.060 | they were using very high doses

00:26:43.360 | and treating it like a psychedelic,

00:26:45.340 | treating it as if it was a psychedelic therapy.

00:26:48.220 | In other words, telling people,

00:26:49.580 | you're going to have this experience.

00:26:50.800 | It's going to, we're hoping you learn something from it.

00:26:54.080 | We're going to help you through it.

00:26:54.940 | We're going to discuss it afterwards.

00:26:56.380 | And they found incredibly high rates of success

00:26:58.840 | in some pretty well-controlled trials

00:27:00.420 | for both heroin addiction and alcohol addiction.

00:27:04.860 | So I think a whole lot of work needs to be done now.

00:27:07.620 | And you see some of the ketamine clinics

00:27:09.320 | that are using ketamine off-label,

00:27:10.900 | a lot of them are treating it like psychedelic therapy.

00:27:13.940 | There's essentially no research at this point on that.

00:27:16.700 | Do you get better results?

00:27:19.060 | Straight-abusive Spravato, there's some good variability,

00:27:23.420 | but its antidepressant effects last about a week.

00:27:26.940 | But they kick in immediately.

00:27:28.500 | Now, a week is a long time for like most psychiatric drugs.

00:27:32.900 | Like you take it every day.

00:27:34.900 | So that's amazing, but it's still just a week.

00:27:37.020 | We're seeing effects a year or more later

00:27:40.620 | with psilocybin and some of the classic psychedelics.

00:27:44.460 | That could be a pharmacological difference,

00:27:46.460 | or it could be that they get a lot more mileage

00:27:49.140 | out of ketamine if they treated it like psychedelic therapy.

00:27:53.340 | And so that's some-

00:27:54.180 | - What would that look like?

00:27:56.000 | - Really just like our psilocybin sessions,

00:27:59.380 | which I know I haven't described,

00:28:00.900 | but briefly you have anywhere from four to eight hours

00:28:03.940 | of preparation, getting to know the people

00:28:05.940 | who are going to be the guides or the therapists

00:28:07.740 | in the room with the person.

00:28:08.580 | - Yeah, maybe you could walk us through this.

00:28:10.420 | So let's say I were to come to one of your clinical trials,

00:28:14.460 | 'cause these are clinical trials, right?

00:28:15.900 | And in your lab at Hopkins.

00:28:18.080 | And would I need to be depressed

00:28:19.920 | or could I just be somebody who wanted

00:28:21.220 | to explore psychedelics?

00:28:22.740 | - We've had studies for all of these

00:28:25.860 | and a number of other disorders.

00:28:27.260 | So healthy normal studies,

00:28:28.900 | the code for not a problem to fix, but we're all here.

00:28:31.980 | That's what's amazing about psychedelics though,

00:28:34.260 | because if you administer them under this model

00:28:37.340 | and you develop a relationship

00:28:38.600 | and give a high dose of psychedelic,

00:28:40.140 | you can be a healthy normal without a diagnosable issue,

00:28:42.700 | but man, we're all human

00:28:44.640 | and the issues seem to come to the surface.

00:28:47.100 | So, but we've done work with smoking cessation.

00:28:50.180 | So people trying to quit tobacco

00:28:51.800 | and haven't been successful.

00:28:52.640 | - So a variety of reasons.

00:28:54.260 | So maybe I'll just ask some very simple questions

00:28:57.060 | that would kind of step us through the process.

00:28:58.600 | So let's say I were to sign up for one of these trials

00:29:01.100 | and I qualified for one of these trials.

00:29:03.220 | I'd show up, you said I would do several hours in advance

00:29:06.040 | of getting to know the team that would be present

00:29:09.100 | during this psychedelic journey.

00:29:11.140 | - First there's screening.

00:29:12.180 | So it's kind of like a couple of days of both psychiatric,

00:29:15.580 | like structured psychiatric interviews about your whole,

00:29:18.620 | your past and symptoms across the DSM,

00:29:22.720 | the psychiatric Bible to see if you might have

00:29:25.040 | various disorders that could disqualify you.

00:29:28.380 | Like the main ones being the psychotic disorders,

00:29:30.900 | schizophrenia, and also including bipolar.

00:29:34.300 | So the manic side of bipolar.

00:29:36.780 | So after that, and also cardiovascular screening,

00:29:39.580 | heart disease, after that screening,

00:29:41.140 | then the preparation where you get, you're both,

00:29:43.500 | you develop a therapeutic rapport

00:29:46.100 | with the people who are going to be in the room with you,

00:29:48.260 | your guides, but you're also then didactically

00:29:52.580 | sort of explained about what the psychedelic could be like.

00:29:56.460 | And that's kind of a laundry list

00:29:58.180 | because they're more known by their variability than,

00:30:01.740 | it's not like cocaine.

00:30:03.220 | Like you're going to feel stimulated.

00:30:05.340 | You're going to feel like, you can do any, it's like,

00:30:08.820 | or alcohol, you're probably going to feel more relaxed.

00:30:11.300 | It's like, I call them uppers, downers, and all arounders,

00:30:15.060 | and the psychedelics are all arounders.

00:30:16.780 | It's like, yeah, you could be,

00:30:18.800 | you could have the most beautiful experience of your life

00:30:22.660 | or the most terrifying experience of your life.

00:30:24.800 | So it's just kind of laundry list of like the things

00:30:26.700 | that could happen, so there's no surprises.

00:30:29.600 | - I think it's so important for people to hear

00:30:31.260 | because the all-arounders, they,

00:30:34.900 | you really can't predict how somebody

00:30:36.500 | is going to react internally.

00:30:38.660 | I want to just briefly touch on something

00:30:42.620 | because we left that topic, but it occurred to me

00:30:47.480 | that a lot of these effects of psychedelics

00:30:49.380 | and how they function, et cetera, is still very mysterious.

00:30:52.040 | But then I recall to mind that how most prescription

00:30:56.140 | antidepressants work is also very mysterious.

00:30:58.880 | They increase serotonin or dopamine or epinephrine, et cetera,

00:31:02.140 | but why they take weeks on end, you know,

00:31:04.100 | several weeks to kick in, et cetera, is also mysterious.

00:31:06.740 | But going back to the experience

00:31:09.860 | of coming to your laboratory, okay,

00:31:11.460 | so let's say that somebody passes all the prerequisites

00:31:14.940 | and it's the day.

00:31:18.820 | It comes the day that they're going to have this experience.

00:31:22.420 | Are they eating mushrooms like you hear about,

00:31:26.780 | or are they taking it in capsule form?

00:31:29.140 | And what sorts of doses are you prescribing?

00:31:32.460 | Is there a dose-response curve?

00:31:34.060 | And then secondary to that,

00:31:37.460 | I'd like to talk about microdose versus macrodose.

00:31:40.280 | So how do they get this stuff into,

00:31:42.100 | how do people receive it

00:31:44.720 | and how do they get it into their body?

00:31:45.900 | - So they receive pure psilocybin.

00:31:48.220 | So the mushroom, and there are many species,

00:31:51.240 | the most, if people have taken mushrooms

00:31:53.140 | in the United States, it's most likely psilocybe cubensis.

00:31:57.700 | They're easy to grow.

00:31:58.600 | They grow in cow patties.

00:31:59.880 | It's easy for anybody to grow them in their closet.

00:32:02.740 | It doesn't take a 1,000-watt light like cannabis.

00:32:05.580 | It takes like a little, you know,

00:32:07.600 | 10-watt light bulb and a Tupperware bin.

00:32:09.600 | So those are the types of mushrooms

00:32:12.300 | that people typically take.

00:32:13.240 | We're not administering those.

00:32:14.900 | Psilocybin is the compound.

00:32:17.340 | You could draw a molecule, psilocybin,

00:32:19.900 | again, based on the tryptamine structure.

00:32:22.080 | Like that's a single molecular entity.

00:32:24.720 | So it's a white powder.

00:32:26.040 | - Does it look like serotonin molecularly?

00:32:28.440 | - Yes, yes, yes.

00:32:30.040 | - So if I were to show people the chemical structure

00:32:32.800 | of serotonin and the chemical structure of psilocybin,

00:32:35.140 | it would look quite similar.

00:32:36.560 | - Right, right.

00:32:37.400 | - So they're basically taking serotonin.

00:32:39.600 | - A modified version of serotonin, which makes sense.

00:32:43.840 | But then again, this repeated theme of the chemistry

00:32:47.660 | doesn't always neatly line up

00:32:49.380 | because like mescaline looks more like dopamine

00:32:54.360 | than it does like serotonin,

00:32:55.780 | but yet at the receptor activation level,

00:32:58.980 | the pharmacological effect, those are similar.

00:33:03.160 | But yeah, I mean, and what it does at the receptor

00:33:06.360 | is an alternate, it's hitting the same switch,

00:33:09.000 | but then having an alternate response at the receptor level.

00:33:14.000 | - Yeah, so for people that don't necessarily understand

00:33:15.680 | the relationship between what we call ligand,

00:33:17.640 | the thing that parks in the receptor

00:33:19.400 | and the receptor is the parking spot,

00:33:21.240 | one of the reasons that you can get such a variety of effects

00:33:24.920 | from different compounds is, for instance,

00:33:27.860 | serotonin might affect a certain pathway

00:33:30.460 | at a particular rate and psilocybin might trigger activation

00:33:35.460 | of different components of that pathway at different rates.

00:33:37.560 | And so you can get vastly different experiences

00:33:40.320 | from two things that look chemically similar.

00:33:42.660 | This is also a good reason why people

00:33:46.260 | shouldn't just assume that they can

00:33:48.660 | cowboy their own chemistry, right?

00:33:50.820 | That what you see on paper and what you can mix up

00:33:53.440 | in a vial is often vastly different than what you predict.

00:33:58.260 | - Right, and there's a dose effect curve

00:34:00.480 | that's really interesting.

00:34:01.660 | Some of our early work with psilocybin in healthy normals

00:34:06.380 | looked at a true placebo plus four active doses,

00:34:09.980 | five, 10, 20, and 30 milligrams of psilocybin.

00:34:13.320 | Body weight adjusted, so, you know, those milligrams

00:34:16.520 | per 70 kilograms of body weight.

00:34:18.840 | We've recently published a paper in our newer trials

00:34:21.540 | where we're dropping the body weight adjustment

00:34:23.680 | 'cause our going across hundreds of volunteers,

00:34:26.100 | we've kind of figured out that you shouldn't really be,

00:34:29.440 | you don't need to be adjusting by body weight.

00:34:32.040 | - Interesting. - So, yeah.

00:34:33.740 | - Well, brain size doesn't vary that much

00:34:35.920 | between individuals.

00:34:37.240 | - Yeah, yeah.

00:34:38.240 | - And, you know, at the end, this is a brain effect, mostly.

00:34:43.000 | - Probably body as well.

00:34:44.880 | Okay, so the person ingests the powder or capsule?

00:34:48.320 | - In a little pill. - Okay.

00:34:49.440 | - Yeah, and it doesn't take 30 milligrams as a small,

00:34:52.220 | you could fit it into a tiny little capsule.

00:34:54.920 | And it'll take about a half hour,

00:34:57.160 | but anywhere from 15 minutes to an hour to kick in.

00:35:00.400 | - And you said the dose range was?

00:35:02.380 | - Most of our studies are looking at

00:35:06.560 | where we want a psychedelic effect

00:35:08.760 | are in the 20 to 30 milligram range.

00:35:12.740 | Again, because we have adjusted by body weight

00:35:15.200 | and the average American is over 70 kilograms,

00:35:18.200 | about 150 pounds.

00:35:19.400 | Like people, and in fact, have gotten more like 40, 45

00:35:23.880 | in a lot of cases, but it's still a small pill.

00:35:27.680 | The session day itself is not full of,

00:35:32.640 | for most of our studies, is not full of tasks.

00:35:34.840 | We really want to look at the therapeutic response.

00:35:37.560 | Obviously, if it's a therapeutic study,

00:35:39.440 | we want it to be a meaningful experience

00:35:41.640 | and research has found, not surprisingly,

00:35:44.420 | that you get a less meaningful experience

00:35:46.500 | when you're in an FMRI

00:35:48.880 | or when you're doing a lot of cognitive tasks.

00:35:51.180 | We've done some research of that type, for sure,

00:35:57.280 | and plenty of colleagues have,

00:35:59.080 | but when you're in a therapeutic study

00:36:00.740 | or if you're trying to understand the therapeutic effects,

00:36:02.840 | you have to recognize there's this trade-off

00:36:05.960 | of what you can do.

00:36:06.800 | So our typical therapeutic model,

00:36:08.560 | which again, isn't just limited necessarily

00:36:10.900 | to the therapeutic studies

00:36:12.120 | where we're trying to treat a specific disorder,

00:36:14.480 | is to have that preparation

00:36:17.940 | so the person feels very comfortable with their guides.

00:36:20.720 | I mean, ultimately, what I tell people is like,

00:36:25.680 | any emotional response, it's all welcome.

00:36:28.200 | I mean, you could be crying like a baby hysterically,

00:36:33.060 | like that's what you should be doing

00:36:34.560 | if that's what you feel like.

00:36:35.720 | And so, in a lot of ways,

00:36:36.940 | sometimes people with psychedelic experience on their own,

00:36:40.920 | it can be harder to train them in this model

00:36:44.040 | because in the real world,

00:36:45.880 | people with psychedelic experience,

00:36:47.160 | a lot of times the rule is, you know, hold your shit.

00:36:48.940 | So several friends go to a party,

00:36:51.720 | they split a bag of mushrooms.

00:36:53.100 | It's like, you know, there's a social pressure

00:36:55.520 | for good reason not to be the guy in the corner of the room

00:37:00.520 | where everyone's trying to just have a good time and relax,

00:37:02.900 | like crying about your mother.

00:37:04.580 | Your other friends are, they're having an experience too,

00:37:07.080 | and you're being a drama king and blah, blah, blah.

00:37:09.600 | And so like, yeah, compose yourself, hold your-

00:37:12.160 | - You're doing, I mean, you're doing therapy for people.

00:37:14.600 | This is, it's not just about the experience.

00:37:17.160 | - Right, and the experience itself is very much shaped

00:37:19.920 | by that container, by the environment,

00:37:23.340 | and the degree to which one allows it to happen.

00:37:26.280 | Like, one should let go of control.

00:37:29.240 | - Yeah, let's talk about the letting go of control.

00:37:32.140 | And then as we march through this hypothetical experience,

00:37:36.440 | that does take place in your lab,

00:37:37.780 | but we're using a sort of generic case example, if you will.

00:37:42.320 | The letting go of control is an interesting feature actually,

00:37:46.060 | because one of the common themes of good psychoanalysis

00:37:49.760 | or psychotherapy of any kind is that there's a trust built

00:37:53.060 | between the patient and the analyst,

00:37:55.660 | and that relationship becomes a template

00:37:58.620 | for trust more generally and trust in oneself.

00:38:01.760 | It's actually, the end goal of good psychoanalysis

00:38:04.700 | is that the patient actually, one of the end goals

00:38:07.080 | is that they develop an empathy for themselves,

00:38:09.380 | which almost sounds like an oxymoron,

00:38:11.240 | but if you spend a little time with that statement,

00:38:13.400 | it actually pans out.

00:38:15.120 | So the psychedelic experience is one in which chemically,

00:38:20.120 | you're under a new set of conditions, right?

00:38:25.840 | Let's coarsely, space and time are altered in some way,

00:38:29.960 | sense of self, for instance,

00:38:32.000 | I might be going to a strongly interoceptive mode

00:38:35.180 | where I'm focusing on everything

00:38:36.620 | within the confines of my skin,

00:38:37.920 | whereas normally we're sort of interacting in space

00:38:40.320 | and pens and conversation.

00:38:41.920 | And I'm sort of, if I had,

00:38:43.440 | occasionally I'll pay attention to my breathing,

00:38:45.040 | but I'm sort of dilating and contracting my focus

00:38:47.960 | for different things all the time.

00:38:50.320 | The letting go of control, it seems to me,

00:38:53.660 | could be sort of the expansion of one perceptual bubble

00:38:57.520 | to the point where you're not actually worried

00:39:01.240 | that that perceptual bubble is going to pop or that,

00:39:03.600 | meaning you're not worried about what people think of you.

00:39:06.960 | You're not worried whether or not your brain

00:39:09.640 | is going to explode,

00:39:10.520 | even though a thought could feel enormous.

00:39:12.680 | If I keep going like this, it almost sounds psychedelic,

00:39:15.920 | but that's the idea here.

00:39:18.040 | Or if I'm paying attention, for instance,

00:39:19.760 | to some somatic experience,

00:39:21.680 | like the coursing of waves of heat through my body,

00:39:26.600 | that I'm not suddenly saying, is that weird?

00:39:30.520 | I'm actually just going deeper and deeper into it.

00:39:32.800 | So it's essentially expanding our perceptual phenomenon.

00:39:35.720 | How do you convince people

00:39:38.440 | to go further and further down that path?

00:39:40.680 | What do you think allows them to do that?

00:39:42.220 | Because I think that to me

00:39:44.080 | is one of the more unusual aspects to psychedelics

00:39:47.940 | is that normally the social pressure,

00:39:51.000 | but also just our internal pressure from our own brain

00:39:54.420 | is pay attention to many things at once, not just one.

00:39:58.460 | - Especially these days.

00:40:00.600 | Yeah, multitask. - Exactly.

00:40:02.140 | Multitask and the more that we focus on one thing,

00:40:05.480 | the more bizarre that thing actually can appear to us, right?

00:40:08.420 | - Right.

00:40:09.260 | - I mean, even if it's the tip of your finger

00:40:10.420 | and you're not taking any psychedelics,

00:40:11.660 | you spent a long enough looking at the tip of your finger,

00:40:13.420 | you will notice some very weird things, right?

00:40:16.940 | - I think of that as the classic psychedelic effect

00:40:19.260 | or one classic effect

00:40:21.540 | and one I've used many times of this example

00:40:24.700 | of why people shouldn't necessarily, you know,

00:40:28.300 | these aren't,

00:40:29.140 | these, one should be judicious

00:40:32.940 | in putting themselves in these circumstances.

00:40:35.140 | Someone could be, you know,

00:40:37.420 | having a very strong psilocybin experience

00:40:40.480 | and they're trying to navigate their way in Manhattan

00:40:43.660 | crossing the street

00:40:44.620 | and they might be staring into the hand and realize,

00:40:47.380 | like that's, their hand is the most amazing miracle.

00:40:50.740 | Like the entire universe has essentially conspired

00:40:53.500 | to come to this one point

00:40:55.340 | to make this absolutely breathtaking.

00:40:57.600 | It's almost like, I think of the simplest form of,

00:41:00.680 | well, we know that the simplest form of learning

00:41:02.180 | is habituation.

00:41:03.020 | Simply keep applying stimuli and there's less response.

00:41:05.340 | Like this is what organisms do.

00:41:07.340 | This is what we have to do.

00:41:08.620 | And it's like, there's this dishabituation component.

00:41:11.580 | - Dishabituation.

00:41:12.780 | - Yes, like we wouldn't be able to get through life

00:41:14.800 | if we wouldn't be able to cross that street

00:41:16.500 | if we were like, oh, like this is a miracle.

00:41:19.860 | - Well, I'm so glad you brought this up.

00:41:22.700 | I mean, here, I'm reflecting my bias as a vision scientist,

00:41:25.180 | but most people don't realize this,

00:41:26.740 | but if you look at something long enough,

00:41:28.200 | it eventually disappears.

00:41:30.460 | It doesn't actually disappear,

00:41:31.500 | but perceptually it disappears.

00:41:33.020 | You have these little microsaccades

00:41:34.420 | that ensure that it doesn't,

00:41:36.100 | but most of us don't look at any one thing for very long.

00:41:39.860 | The brain's default is to perceptually jump around

00:41:43.900 | like crazy with the visual system, with the auditory system.

00:41:47.120 | We all, ADD, people talk about ADD a lot,

00:41:50.480 | is sort of baked into our underlying networks at some level.

00:41:53.600 | And then we can force attention.

00:41:56.000 | But it sounds like on psychedelics,

00:41:57.960 | one of the primary goals therapeutically

00:41:59.820 | is to really drill into one of these perceptual bubbles

00:42:03.580 | and expand that bubble.

00:42:04.860 | And the safety it seems is the safety,

00:42:08.340 | it's sort of like a permission to do that

00:42:11.280 | without worrying that something's going to happen.

00:42:14.120 | - Right, because I've had people there on the couch.

00:42:17.420 | Yeah, I remember one lady said,

00:42:20.100 | this is probably 13, 14 years ago,

00:42:23.420 | said, "Matt, tell me again, I can't die.

00:42:26.420 | I feel like my heart is going to rip through my chest."

00:42:29.220 | I mean, she was feeling her.

00:42:30.300 | And I should say, typically cardiovascular response

00:42:33.660 | is modest, the pulse and blood pressure go up somewhat.

00:42:38.420 | It can be dangerous for people

00:42:39.720 | if they're at severe heart risk.

00:42:41.100 | And we do monitoring this the whole time.

00:42:42.420 | - So they're plugged into a variety of devices?

00:42:45.480 | - Yeah, so every half hour or so we take their on protocol

00:42:48.840 | and we space it out a little further,

00:42:51.320 | further into the time course,

00:42:52.760 | but we take their blood pressure and their pulse.

00:42:55.120 | And if it goes over a certain level, we have a protocol.

00:42:57.360 | And we've had to do this only a few times,

00:42:58.640 | but the physician comes in,

00:43:00.360 | gives them a little nitroglycerin under the tongue

00:43:02.640 | and knocks the blood pressure down a little bit,

00:43:04.840 | doesn't affect the experience.

00:43:06.040 | So we have it all in place,

00:43:07.360 | even though they'd probably be fine

00:43:08.440 | out of an abundance of caution.

00:43:11.240 | But yeah, but someone can feel that,

00:43:15.020 | my God, I'm going to die.

00:43:16.240 | Like I have never felt my heart beat like this before.

00:43:21.200 | And like the experience of the breath can be just,

00:43:24.380 | you know, absolutely fantastic.

00:43:27.180 | And the breath is obviously interesting

00:43:29.900 | because it's this automatic control,

00:43:33.220 | but it can also be voluntary.

00:43:35.100 | So people can get into a sense of like,

00:43:37.140 | my God, what if I forget?

00:43:38.780 | It sounds silly like a stoner movie.

00:43:39.620 | - What if I forget to breathe?

00:43:40.860 | - Exactly.

00:43:42.060 | But people, that can be so compelling.

00:43:45.500 | And so one of the reasons,

00:43:46.500 | get back to one of your questions,

00:43:47.840 | it's like, what do we do to kind of allow them

00:43:50.800 | to go further into these bubbles?

00:43:52.540 | It's like, one is wearing the eye shades.

00:43:56.100 | We don't call them blindfolds

00:43:57.740 | 'cause that has a negative connotation like being kidnapped.

00:44:00.340 | - And they're probably seeing a lot in there anyway.

00:44:02.140 | So blind isn't the appropriate word.

00:44:03.820 | - Right, right.

00:44:05.260 | I've never thought of it.

00:44:06.100 | These should be like inner sight shades.

00:44:09.260 | But when you close the eyes, the levels of activity

00:44:11.940 | in the retina actually are maintained.

00:44:14.100 | It's just spontaneous activity.

00:44:16.120 | - And it seems, and I'd be curious

00:44:17.540 | about your thoughts on this.

00:44:19.060 | But the way I describe it is that the mind's eye,

00:44:25.480 | being this kind of loose term we use,

00:44:28.300 | can be on rocket boosters.

00:44:29.820 | So a lot of times, for some people,

00:44:31.980 | like a compound like psilocybin,

00:44:33.280 | for some people, there's no perceptual effect.

00:44:37.340 | Like if they're looking at this room,

00:44:38.500 | it would pretty much look the same.

00:44:40.680 | Sometimes folks say, "Yeah, things seem

00:44:42.180 | a little bit brighter."

00:44:43.020 | Now, some people will say, "Oh my God,

00:44:44.780 | there's waves, that wall is waving,

00:44:47.140 | and these curtains are..."

00:44:48.780 | On these compounds, people don't typically see pink elephants.

00:44:51.400 | You do actually get that in another class.

00:44:53.220 | I didn't mention the anticholinergics,

00:44:56.540 | sort of like atropine and scopolamine, those drugs.

00:44:59.220 | Those are the true hallucinations

00:45:01.140 | where you thought you were having a conversation

00:45:03.220 | with someone who was never there.

00:45:04.860 | - We will definitely get to those.

00:45:08.120 | But the reason I kind of cringe and say,

00:45:10.140 | "Oh my," when you talked about those,

00:45:11.780 | is that knowing a little bit about the pharmacology

00:45:15.180 | of acetylcholine, the idea of manipulating that system,

00:45:19.900 | to me, sounds very uncomfortable.

00:45:22.440 | Because like the whole idea of, well, witches and flying,

00:45:26.900 | there was a whole history there hundreds of years ago,

00:45:29.720 | so-called witches taking these agents

00:45:32.640 | and then thinking they were flying around on broomsticks

00:45:35.620 | and things of that sort.

00:45:36.660 | And there's a lot of mythology around the broomsticks.

00:45:38.580 | It's complicated, but that sounds very unpleasant.

00:45:41.500 | One thing about the serotonergic,

00:45:43.800 | let's just, with psilocybin,

00:45:46.040 | so there's an expansion of a particular,

00:45:51.360 | fairly narrow percept.

00:45:53.960 | It could be sound, it could be an emotion,

00:45:55.580 | it could be sadness, could be a historical event

00:45:58.640 | or a fear of the future.

00:46:00.020 | And you've mentioned before that there's something

00:46:04.180 | to be learned in that experience.

00:46:06.600 | There's something about going into that experience

00:46:09.020 | in an undeterred way that allows somebody

00:46:14.020 | to bring something back into more standard reality.

00:46:20.740 | Given the huge variety of experiences

00:46:25.060 | that people have on psychedelics,

00:46:26.500 | given the huge variety of humans that are out there,

00:46:29.160 | but what are now very clear therapeutic effects

00:46:33.260 | in the realm of depression,

00:46:35.140 | what do you think is the value

00:46:37.500 | of going into this fairly restricted perceptual bubble,

00:46:42.020 | what we are calling letting go or giving up control?

00:46:45.320 | Because if the experiences are many,

00:46:47.840 | but the value of what one exports from that experience

00:46:51.720 | is kind of similar across individuals,

00:46:54.580 | that raises all sorts of interesting questions.

00:46:56.800 | And this is not a philosophy discussion.

00:46:58.940 | We're talking about biology and psychology here.

00:47:01.940 | So let's say I decide I'm going to focus

00:47:05.040 | on the tip of my pen.

00:47:06.260 | I mean, in a psychedelic state,

00:47:07.780 | I could fall in love with this pen.

00:47:09.120 | I do happen to like these Pilot V5s and V7s very much,

00:47:12.260 | but I could feel real love for the pen, right?

00:47:16.200 | That's not an unreasonable thing

00:47:17.700 | to expect in a psychedelic journey.

00:47:20.180 | And in the context of your laboratory model,

00:47:22.940 | which I think is a great one,

00:47:24.380 | that experience would be just as valid

00:47:26.880 | as me going into the experience

00:47:28.580 | of some of the deep friction that I might have

00:47:31.200 | with a family member over my entire lifespan.

00:47:34.080 | And yet the export from that,

00:47:36.780 | those two vastly different experiences

00:47:39.900 | is one of feeling a better relationship

00:47:42.360 | to the world into oneself.

00:47:43.920 | So what does this tell us about-

00:47:44.760 | - Like how can the pen

00:47:45.620 | and the processing your childhood trauma both lead to?

00:47:49.200 | - Right.

00:47:50.040 | So what does this, I mean, at that level,

00:47:53.180 | it raises this question like, first of all, how, why?

00:47:57.980 | I mean, or just what are your thoughts on that?

00:48:00.060 | - So this is definitely in the,

00:48:02.080 | this is in the terrain we're figuring out, you know?

00:48:04.760 | So there's no, educated speculation

00:48:07.060 | is the best I can provide.

00:48:08.640 | But I think the best,

00:48:12.660 | I think the common denominator

00:48:16.860 | are persisting changes in self-representation.

00:48:20.900 | - Okay, tell me more about self-representation.

00:48:23.100 | - That's the way one holds the sense of self.

00:48:27.660 | The fundamental relationship of a person in the world.

00:48:31.920 | I mentioned earlier that these experience

00:48:34.780 | seems to alter the models we hold of reality.

00:48:37.500 | And I think that the self is the biggest model,

00:48:39.540 | that I am a thing that's separate from other things.

00:48:42.300 | And that's, I am defined by certain,

00:48:46.420 | I have a certain personality

00:48:47.860 | and I'm a smoker that's having a hard time quitting,

00:48:50.520 | or I'm a depressed person that, you know,

00:48:53.540 | views myself as a failure and all of these things.

00:48:55.580 | Those are models too.

00:48:56.820 | And I think that change in self-representation

00:49:01.420 | may be an end point for these different experiences.

00:49:04.020 | I mean, maybe the falling in love with the pen,

00:49:06.940 | the whole idea that you're,

00:49:08.260 | especially in contemplation afterwards,

00:49:10.920 | and obviously I'm speculating here,

00:49:12.300 | but the whole idea that you could

00:49:14.580 | have such a deep connection with this random,

00:49:18.060 | obviously random aspect of the universe

00:49:21.700 | could potentially lead to this, you know,

00:49:24.620 | transformed understanding of the self.

00:49:26.780 | And like the pen may be a proxy for the miracle of reality,

00:49:31.580 | in a way that relies nothing on no supernatural thinking.

00:49:36.260 | You know, you can be a hard atheist and take this,

00:49:38.940 | ultimately, oh my God, like that,

00:49:40.820 | just like the pen, this is, you know,

00:49:43.220 | this is amazing the fact that we exist.

00:49:45.580 | And so there could be an extrapolation chair

00:49:48.040 | and you use the pen, but I think it sounds so similar

00:49:50.500 | to Aldous Huxley's classic description

00:49:52.940 | on the doors of perception of the chair and the drapes.

00:49:55.860 | Like he took 500 milligrams of mescaline.

00:49:59.220 | He was just like-

00:50:00.060 | - Is that a high dose of mescaline?

00:50:01.140 | - Yeah, yeah.

00:50:02.140 | And that's a, you know, that's a heroic dose for sure.

00:50:06.460 | And he just going off on the chairiness of the chair,

00:50:09.280 | like this chair is exuding the quality of being a chair.

00:50:13.260 | - So this is this expansion of the perceptual bubble,

00:50:16.120 | a narrow, a narrow percept that then grows

00:50:19.980 | within the confines of that narrow percept.

00:50:23.080 | - Yeah.

00:50:23.980 | - So sense of self is a very interesting phenomenon.

00:50:27.100 | And if we could dissect it a little bit,

00:50:29.100 | there's the somatic sense of self.

00:50:31.640 | So the ability to literally feel the self

00:50:34.620 | into this process we call interoception.

00:50:36.780 | And then there's the title of the self, the I am blank.

00:50:41.020 | - Yeah.

00:50:41.860 | - And I noticed you said that several times.

00:50:42.740 | It's intriguing to me.

00:50:43.860 | I have a good friend.

00:50:44.900 | I don't think I can or should mention his name,

00:50:47.620 | but he had a very long and successful career

00:50:50.140 | within one of the more elite teams

00:50:52.700 | and within the SEAL teams.

00:50:53.980 | And he's a fairly philosophical guy,

00:50:57.860 | also very practical guy,

00:50:59.480 | but he has said many times to me

00:51:03.700 | that the most powerful words in any language are I am,

00:51:08.700 | because whatever follows that tends,

00:51:11.420 | if you repeat it enough,

00:51:12.580 | tends to have this kind of feedback effect

00:51:15.380 | on how you are in the world.

00:51:17.820 | And the first pass, it sounded to me a little bit

00:51:21.460 | like kind of like internet psychology type thing,

00:51:24.940 | like the secret or something,

00:51:26.300 | which frankly, I'm just not particularly.

00:51:28.500 | Yeah, so if you kind of like the whole fake it

00:51:30.920 | till you make it,

00:51:31.760 | like I don't actually subscribe to any of that.

00:51:34.460 | But in dissecting that a little bit further with him,

00:51:36.660 | I came to realize that these words I am are very powerful.

00:51:41.080 | I don't think you reprogram your brain just by saying them,

00:51:43.660 | but how one defines themselves internally,

00:51:48.660 | not just to other people,

00:51:51.260 | but how one psychologically and by default

00:51:54.300 | defines themselves, I think is a very powerful,

00:51:57.220 | like and depressed people,

00:51:59.940 | as well as happy people seem to define themselves

00:52:02.020 | in terms of these categories of emotional states.

00:52:04.780 | So I think it's so interesting that letting go

00:52:09.060 | and going into this perceptual bubble,

00:52:10.960 | which is facilitated by obviously a really wonderful team

00:52:14.560 | of therapists, but also the serotonergic agent,

00:52:17.780 | allows us to potentially reshape the perception of self.

00:52:22.780 | That's a tremendous feat of neuroplasticity.

00:52:26.420 | - Right, and I think certainly more work needs to be done.

00:52:30.720 | This is the horizon.

00:52:33.000 | And I should credit Chris Lethaby,

00:52:35.440 | a philosopher in Australia who has a forthcoming book.

00:52:40.220 | It might be out right about now or soon,

00:52:42.640 | within the coming months, "Psychodelics and Philosophy."

00:52:47.280 | - That's the title of the book?

00:52:49.300 | - It might be "Psychodelic Philosophy."

00:52:51.080 | It's really close.

00:52:51.920 | - Chris Lethaby, we'll put a link to it.

00:52:53.760 | - Right, and so his conclusion in this,

00:52:56.260 | it's a really great book and he really plays with the idea.

00:52:59.540 | It's like psychedelic experiences come along

00:53:01.440 | with a lot of supernatural stuff, experience.

00:53:05.400 | It can certainly go along with that,

00:53:06.900 | but the idea is like, can these experiences

00:53:09.760 | and including those therapeutic effects

00:53:11.360 | be explained from a naturalist point of view?

00:53:14.900 | And his conclusion is that the changes

00:53:18.200 | in self-representation may be the commonality.

00:53:20.820 | Now that could go along with plant spirits

00:53:23.820 | and the Buddha and chakras and whatever your model system,

00:53:28.820 | in Jesus, all of that, but it could also be completely devoid

00:53:34.800 | of any supernatural, any religious.

00:53:37.480 | And we do, in fact, see all of these varieties.

00:53:41.860 | So I think there's something about this change

00:53:43.920 | in sense of self.

00:53:45.760 | There seems to be something on the identity level,

00:53:48.160 | both with, I think, of the work we did with cancer patients

00:53:50.960 | who had substantial depression and anxiety

00:53:52.760 | because of their cancer, and also our work

00:53:54.640 | with people trying to quit cigarette smoking.

00:53:57.520 | I mean, there seems to be, when it really works,

00:54:02.520 | this change in how people view themselves,

00:54:06.360 | like with smoking, like really stepping out of this model,

00:54:11.360 | like I'm a smoker, it's tough to quit smoking cigarettes,

00:54:15.640 | I can't do it, I failed a bunch of times.

00:54:18.420 | I remember one participant during the session,

00:54:20.800 | but he held onto this afterwards, said,

00:54:22.680 | my God, it's like, I can really just decide,

00:54:26.800 | like flicking off a bucket, I can decide not to smoke.

00:54:29.400 | And I call these duh experiences with psychedelics

00:54:32.440 | 'cause people often, like in the cancer study,

00:54:34.800 | you say, I'm causing most of my own suffering.

00:54:38.160 | Like I can follow my appointments, I can do everything,

00:54:40.800 | but I can still plan for the vacation,

00:54:42.000 | I'm not getting outside in the sunshine,

00:54:44.880 | I'm not playing with my grandkids, I'm choosing to do that.

00:54:47.680 | And it's like, they told themselves that before,

00:54:50.020 | and the smoker has told themselves a million times,

00:54:52.920 | I can, so it sounds, when it comes out of their mouths,

00:54:56.160 | and folks will say, this is part of the ineffability

00:54:58.320 | of a psychedelic experience, folks say,

00:55:00.080 | I know this sounds like bullshit, and this sounds like,

00:55:02.360 | but my God, I could just sigh.

00:55:05.400 | Like they're feeling this gravity of agency,

00:55:09.000 | which I think is interesting 'cause regardless

00:55:12.000 | of the debates on the reality of free will,

00:55:15.660 | I think the philosophy of that,

00:55:18.320 | whether it's ultimately free will,

00:55:20.840 | like pure agency, if that exists, which I'm skeptical of,

00:55:24.320 | or just the idea that clearly we have a sense of agency,

00:55:28.600 | there's something there,

00:55:30.360 | whether it's the sense of agency even,

00:55:32.840 | that is the human being has,

00:55:35.520 | and that seems to be at times fundamentally like supercharged

00:55:40.520 | from a psychedelic experience, this idea like,

00:55:44.180 | I'm just gonna make a decision.

00:55:46.760 | Like normally, like you tell a depressed person,

00:55:48.620 | like don't think of yourself that way,

00:55:50.320 | you're not a failure, look at all that.

00:55:51.760 | It's just, yeah, it's like, and well,

00:55:53.560 | you can actually in one of these states have an experience

00:55:56.400 | where you realize like, my God,

00:55:57.880 | just like using MDMA to treat PTSD,

00:56:00.480 | and we're gonna be starting work

00:56:01.320 | with psilocybin to treat PTSD,

00:56:03.080 | someone could really reprocess their trauma

00:56:06.740 | in a way that like has lasting effects.

00:56:09.760 | And clearly there's probably something,

00:56:11.640 | reconsolidation of those memories.

00:56:13.500 | They are altered, very consistent with our understanding

00:56:19.280 | of the way memory works.

00:56:20.360 | So the whole idea, people can actually in a few hours

00:56:24.760 | have such a profound experience

00:56:26.440 | that they decide to make these changes in who they are,

00:56:31.100 | and it sticks.

00:56:32.620 | There seems to be something like that.

00:56:34.320 | - And that's profound.

00:56:35.480 | I mean, I think a few moments ago,

00:56:38.680 | I made some semi-disparaging statements

00:56:41.400 | about things like the secret and affirmations.

00:56:43.840 | And the reason I do that with a nod to the fact

00:56:48.680 | that the people who are putting those ideas forward

00:56:51.460 | are well-intentioned people is that the neural networks

00:56:55.720 | of the brain put language last.

00:56:59.660 | We tell stories, and stories are very powerful,

00:57:03.040 | but I think one of the most cruel aspects

00:57:07.680 | of the whole self-help literature in popular psychology

00:57:11.880 | is this idea that everything you say,

00:57:13.880 | your brain and body hear it.

00:57:15.820 | That's actually a very unkind or even cruel thing

00:57:19.240 | for people who are depressed or anxious to hear,

00:57:22.060 | because if they hear that and believe that,

00:57:24.080 | and I want to be clear, I don't think it's true,

00:57:26.280 | that they think that it's very hard to control thoughts.

00:57:30.600 | It's very hard to control thoughts.

00:57:32.520 | So if somebody says, I can't, and then somebody says,

00:57:36.240 | well, no, every time you say you can't,

00:57:37.700 | your brain hears that and it reinforces it,

00:57:39.480 | that's a very treacherous place to live.

00:57:41.760 | And language is powerful, but neural networks,

00:57:47.480 | the brain and the networks that underlie emotionality

00:57:51.080 | and perception and sense of self,

00:57:53.160 | they don't change in response to language.

00:57:56.020 | They change in response to experience.

00:57:59.240 | And it just fundamentally, you need,

00:58:01.660 | there are some prerequisites.

00:58:02.720 | You need certain neuromodulators present,

00:58:04.640 | like serotonin or dopamine.

00:58:06.480 | You need them to be at sufficient levels.

00:58:08.240 | You don't need a drug necessarily do it.

00:58:09.900 | You could, you know, you give a kid a kitten or a puppy,

00:58:13.560 | their first kitten or puppy,

00:58:14.840 | and the levels of dopamine and serotonin,

00:58:17.740 | I've never measured them,

00:58:18.580 | but we can be pretty sure

00:58:19.520 | that they are higher than baseline.

00:58:21.840 | And that experience will reshape them, right?

00:58:24.500 | - Yeah.

00:58:25.340 | - Likewise with an adult in a certain circumstances.

00:58:28.280 | So I think I'm fascinated by this idea

00:58:31.400 | that a somatic and a perceptual experience,

00:58:35.900 | but a real experience of the sort that you're describing

00:58:39.400 | is what allows us to reshape our neural circuitry

00:58:41.920 | and to feel differently about ourselves.

00:58:43.780 | And I know there's been really tremendous success

00:58:48.680 | in many individuals of alleviating depression,

00:58:52.420 | of treating trauma with these different compounds.

00:58:55.140 | I want to step from the experience

00:58:59.200 | under the effects of the psychedelic.

00:59:01.600 | So the person there with your team,

00:59:03.300 | they go into this expanded perceptual bubble.

00:59:06.160 | If things go well,

00:59:08.000 | they're able to do that to a really deep degree.

00:59:10.040 | Maybe it's the relive trauma.

00:59:12.360 | Maybe it's the beauty of their ability

00:59:14.600 | to connect to things in the world.

00:59:16.920 | And now I want to talk about the transition out of that state

00:59:19.880 | and then the export into life,

00:59:21.980 | because this is really where the power of psychedelics

00:59:24.360 | seems to be in the therapeutic sense,

00:59:26.480 | is the ability to truly learn from that experience

00:59:29.560 | so that the learning becomes the default,

00:59:31.880 | that one doesn't have to remind themselves,

00:59:33.320 | oh, I am, they don't have to do an affirmation.

00:59:35.940 | I am a happy person.

00:59:37.080 | I am a happy, you know, I was saying a Bart Simpson,

00:59:38.940 | like writing on the chalkboard, right?

00:59:40.600 | Didn't work for him.

00:59:41.440 | Doesn't work for this other stuff too.

00:59:43.300 | But so as they transition out of this state,

00:59:46.400 | I know that there's a kind of a heightened,

00:59:47.760 | there's a so-called peak where everything seems

00:59:50.440 | to be kind of cascading in at such a level

00:59:52.640 | that the person just,

00:59:55.800 | they can't really turn it off at that point.

00:59:57.640 | It would be challenging.

00:59:58.840 | And then they start to exit the effects of the drug.

01:00:04.880 | Are those transition zones, are those valuable,

01:00:08.200 | much like is the transition between a dream

01:00:10.800 | and the waking state valuable?

01:00:12.800 | Because you're in a sort of mishmash of altered reality

01:00:16.520 | and new reality.

01:00:18.360 | - Right.

01:00:19.200 | - What do you do to guide people through the,

01:00:21.480 | out the tunnel as they exit the tunnel?

01:00:25.200 | - And I have to say like,

01:00:26.320 | this is where we need more experimentation.

01:00:30.200 | Really the clinical model goes back

01:00:32.400 | to literally the late 1950s.

01:00:35.960 | And there's been virtually no experimentation on,

01:00:39.400 | let's say, you know, randomized people to,

01:00:42.000 | we're going to talk more during the latter half

01:00:44.040 | of the session versus not, versus we have them, you know,

01:00:47.640 | write an essay after their session versus not,

01:00:50.160 | versus we had this amount of integration.

01:00:52.320 | What's the discussion?

01:00:53.160 | - In your studies, are they writing or talking

01:00:55.960 | as they're doing it?

01:00:56.800 | - And it's called, you know, very loosey-goosey,

01:00:59.160 | you know, term integration.

01:01:00.600 | But for us means as they're coming back from the experience

01:01:05.600 | to sort of five, six hours in, you know,

01:01:08.040 | so this is the afternoon,

01:01:09.160 | they've been dosed around nine o'clock.

01:01:10.640 | So this is like four o'clock or so.

01:01:13.120 | Just some initial, tell us about the experience.

01:01:15.400 | Do you want to, not unpacking it totally,

01:01:17.320 | but kind of initially just have a little bit discussion

01:01:19.440 | before they go home.

01:01:20.280 | So there's a little bit of that.

01:01:21.800 | But then that night, their homework is to write something.

01:01:25.440 | So it could be, you know, a few bullet points.

01:01:27.720 | It could be, you know, 20 pages and we get everything,

01:01:31.640 | you know, in that range.

01:01:34.000 | But, you know, try not to be self-critical.

01:01:36.880 | It's not great at like, this is just to process

01:01:39.720 | and for a point of discussion the next day.

01:01:41.560 | So they write something, they come in the next day

01:01:44.000 | for a one to two hour,

01:01:45.940 | depending on the study, integration session.

01:01:48.140 | Basically, let's discuss your experience

01:01:51.360 | and depending on what study it's in,

01:01:53.440 | like what might that mean for you're dealing with cancer?

01:01:57.160 | What might that mean for your smoking?

01:01:59.460 | Or becoming a non-smoker?

01:02:02.440 | So you encourage them to simply take it seriously.

01:02:04.960 | And I think this is, again,

01:02:06.400 | is sort of one of the points that could be the antithesis

01:02:09.840 | of what some just kind of social users use.

01:02:13.880 | I mean, this was written about by Houston Smith,

01:02:17.240 | the scholar of religion,

01:02:18.300 | in terms of these mystical experiences

01:02:20.780 | that can happen from psychedelics

01:02:22.200 | and how a lot of times the attribution

01:02:24.880 | to a drug effect is dismissed.

01:02:26.720 | Like even if one has this, you know,

01:02:30.540 | this sense of being one with the universe

01:02:32.120 | and it totally like shakes their soul, so to speak,

01:02:34.900 | you know, but the next day their friends are like,

01:02:36.600 | "Oh dude, you were screwed up.

01:02:38.820 | Too much acid for you, woo!"

01:02:40.740 | You know, like, "Man, next time you needed

01:02:42.720 | to have a few more beers to like bring that down."

01:02:44.940 | You know, like this sort of like, you know,

01:02:48.460 | social, you know, reinforcement

01:02:50.960 | for dismissing the experience.

01:02:52.780 | "Oh God, you're talking out of your head, man."

01:02:55.040 | Like, you know, even if it's, you know, good-natured,

01:02:58.180 | but it's this dismissal.

01:02:59.400 | It's not like, you know, what you want to do, you know,

01:03:03.620 | is like, "Tell me more about that.

01:03:05.300 | You know, you were crying at one point,

01:03:07.040 | like in talking about your mom.

01:03:09.360 | Let's talk about that.

01:03:10.300 | What was that like?

01:03:11.140 | Do you remember that?"

01:03:12.040 | - So are you doing that follow-up

01:03:14.740 | or are they encouraged to do that in their own life

01:03:16.640 | with the various people in their life?

01:03:18.080 | - Both, so we do that explicitly in the follow-up

01:03:20.900 | where we have these discussions.

01:03:22.260 | And I, depending on what the situation is,

01:03:26.540 | you might encourage the person to kind of follow up.

01:03:29.780 | It's really, the basics of it is supportive therapy.

01:03:34.780 | It's non-structured.

01:03:37.380 | It's, you know, use all the, you know, reflective listening

01:03:40.140 | and the sort of the humanistic psychology thing,

01:03:42.540 | you know, unconditional positive regard for the person.

01:03:45.220 | But, you know, I think if, you know,

01:03:48.940 | if someone feels inclined to, you know,

01:03:51.660 | apologize to their sibling about something,

01:03:56.660 | it's like, "Yeah, go ahead and call them up."

01:03:58.440 | When it, with something big, like a relationship change,

01:04:01.160 | I'd be like, "Sit on that two weeks.

01:04:04.160 | Don't make any big, don't end any relationship.

01:04:06.540 | Don't quit your job.

01:04:07.560 | Don't make any big-"

01:04:08.560 | - Do you also tell them not to start any relationships?

01:04:11.300 | - I don't remember that ever coming up.

01:04:15.660 | - Interesting, I'm not Joey.

01:04:17.820 | I was just wondering, you know, but it makes sense

01:04:19.880 | why you move on.

01:04:20.720 | - Like if they're dating and they're thinking like,

01:04:21.760 | "Ah, it might be time to take it to the next level.

01:04:24.240 | Should I ask this girl to marry me?"

01:04:26.260 | If it did come up, I would say there too.

01:04:29.260 | Why don't you sit on that a week or two

01:04:30.780 | and let your sober mind- - Yeah, don't get a puppy.

01:04:32.440 | Don't get a puppy.

01:04:33.420 | Certainly don't get four puppies until you're...

01:04:36.180 | I have a question about flashbacks.

01:04:40.240 | - Uh-huh.

01:04:41.080 | - You know, one of the kind of things you hear is,

01:04:43.700 | you know, flashbacks and that people,

01:04:46.020 | do people get flashbacks?

01:04:47.620 | And if so, what is the basis of flashbacks?

01:04:49.700 | The on the street lore about this

01:04:55.020 | is that somehow some of the compound gets stored

01:04:58.380 | in body fat tissues and then released later,

01:05:00.460 | like is that complete nonsense?

01:05:02.900 | - No evidence for that.

01:05:04.280 | So probably complete nonsense.

01:05:06.460 | - Flashbacks are nonsense or the storage in body fat

01:05:08.900 | is complete nonsense?

01:05:09.740 | - The storage in body fat.

01:05:11.020 | So to answer whether flashbacks are complete nonsense,

01:05:14.340 | we have to define it.

01:05:15.420 | So I really think these are multiple constructs

01:05:17.660 | that are going on.

01:05:18.480 | It's not the same thing that fall under that term.

01:05:21.620 | There is a phenomenon that appears real

01:05:25.460 | that's called hallucinogen persisting perceptual disorder.

01:05:28.420 | It's in the DSM.

01:05:30.420 | A certain number of people,

01:05:32.300 | very small number of people percentage wise

01:05:35.760 | who have used psychedelics

01:05:37.100 | will have these persisting perceptual disorders.

01:05:40.140 | Like they'll see halos around things.

01:05:41.760 | They'll see some trails, like, you know,

01:05:44.120 | like the after images following an object in motion.

01:05:47.420 | They'll see distortions in color.

01:05:51.300 | And it'll be like anything else

01:05:53.420 | that's a disorder in the DSM.

01:05:55.660 | It has to be clinically distressing

01:05:57.180 | and it has to be persisting over some number of months.

01:06:01.340 | And so very rare, very mysterious.

01:06:04.900 | Some of the keys to that are amazingly,

01:06:08.440 | it's never been seen in the thousands of participants

01:06:11.460 | either from the older era,

01:06:12.700 | from the late fifties to the early seventies,

01:06:15.580 | people in psychedelic studies with LSD, psilocybin, masculine

01:06:18.460 | and it's never been seen in the modern era.

01:06:20.140 | Again, now with thousands of participants

01:06:22.720 | at a number of centers like ours throughout the world.

01:06:26.540 | So it seems to be something that is

01:06:30.500 | for some reason happening in illicit use.

01:06:33.860 | So that brings in, okay, is there polypharmacology?

01:06:38.260 | You know, like, cause you're drinking during it.

01:06:39.940 | - Did you take what you thought you'd do?

01:06:40.940 | - Yeah, what's the dose, what's the purity?

01:06:43.460 | But then also what I think is actually even more so

01:06:46.660 | than that what's likely going on

01:06:48.100 | is some sort of very rare neurological susceptibility.

01:06:51.020 | There is one paper that is a case series

01:06:55.420 | of individuals reporting these symptoms

01:06:57.180 | and they didn't limit it to just people

01:06:59.900 | who had had hallucinogen history.

01:07:02.620 | And the amazing thing about this is that

01:07:05.700 | a number of people seem to have straight up HPPD diagnosis.

01:07:10.660 | - What is HPPD?

01:07:11.780 | - Hallucinogen persisting perceptual disorder

01:07:14.060 | who have never taken a psychedelic.

01:07:16.040 | So it's often prompted by alcohol, benzodiazepines,

01:07:21.040 | cannabis, even tobacco.

01:07:25.660 | And I believe in one individual,

01:07:29.460 | no lifetime history of any,

01:07:31.180 | it wasn't preceded by any of those, you know, substance uses.

01:07:36.020 | So I think of it like the precipitation exacerbation

01:07:41.020 | of psychotic disorders.

01:07:42.660 | It seems pretty clear through observation

01:07:44.740 | that some people with either predisposition

01:07:47.920 | or active psychotic disease,

01:07:49.860 | that this can destabilize them.

01:07:51.720 | A psychedelic, the same way that a life experience

01:07:54.300 | can destabilize those person more easily.

01:07:56.360 | I think of it like that there's probably

01:07:57.640 | some pretty rare neurological susceptibility.

01:08:00.680 | We have tended going, this goes back to the '80s,

01:08:03.580 | you know, clinical practice.

01:08:06.180 | It ended up in the DSM focused on hallucinogen

01:08:08.760 | because I relate it to the psychology of xenophobia.

01:08:13.820 | It's always the weird other thing that gets the attribution.

01:08:16.780 | You don't attribute to the thing like,

01:08:19.080 | oh yeah, did you smoke cigarettes?

01:08:20.620 | Did you drink?

01:08:21.460 | It's like, well, yeah, but I see lots of people drinking

01:08:23.660 | and not ending up with this.

01:08:25.020 | Like you take a crazy like drug

01:08:29.120 | and you can get people to believe all sorts of crazy stuff.

01:08:32.220 | The biggest example of that is the cathinone derivative,

01:08:35.380 | so-called bath salts.

01:08:36.900 | And if you remember several years back,

01:08:39.140 | the guy in Florida that ate the other guy's face,

01:08:42.820 | there was a homeless guy that like literally

01:08:45.000 | ate part of someone's face off.

01:08:46.660 | Like, yeah, it's one of the crazies.

01:08:47.500 | - While the person was alive.

01:08:48.900 | - While the person was alive.

01:08:50.540 | And all it took was one sheriff's deputy to say,

01:08:53.780 | well, I don't know,

01:08:54.620 | but I bet it was some of that bath salts stuff

01:08:57.680 | that's been going on.

01:08:58.520 | The only thing-

01:08:59.360 | - What was it?

01:09:00.740 | - The only thing in his system-

01:09:01.700 | - Maybe we can set the record straight for people.

01:09:03.580 | What was the, why would he say bath salts?

01:09:06.740 | And was it bath salts?

01:09:08.420 | - It wasn't.

01:09:09.660 | And so the only thing in his talks was cannabis,

01:09:12.460 | which we all know,

01:09:14.580 | typically people don't eat people's faces off

01:09:16.620 | after they get stef-

01:09:17.460 | - Makes you hungrier, but not that hungry.

01:09:19.220 | - Right, right.

01:09:20.140 | So it's just an example of the xenophobia.

01:09:22.900 | Like today, if you get on Google images and look up,

01:09:25.860 | bath salts, one of the most common images you'll see

01:09:29.180 | is this poor guy's face being eaten off.

01:09:31.460 | So we're just so ready to latch on,

01:09:33.580 | just like the people of another culture

01:09:36.180 | that we don't know of.

01:09:37.020 | It's very easy to assign attribution to a class

01:09:42.300 | that you're very unfamiliar with.

01:09:43.620 | So I think they, the psychedelics got that attribution

01:09:46.780 | with this very rare neurological susceptibility,

01:09:50.420 | the way that alcohol didn't.

01:09:51.860 | So I think it's not specific to psychedelics,

01:09:55.080 | but we don't really know.

01:09:56.940 | We need, but we look at it and our research

01:09:59.020 | have never seen an example of it.

01:10:00.640 | But flashbacks can mean a number of other things.

01:10:03.740 | I think the most common thing people experience

01:10:05.620 | is what we call state dependent learning.

01:10:08.900 | It's returning yourself to a similar context

01:10:12.260 | can bring back the same thoughts and emotions

01:10:15.220 | as the experience.

01:10:16.060 | So someone used mushrooms a week ago,

01:10:18.820 | now they do something like they smoke some cannabis

01:10:22.420 | or they take a warm bath or they're simply like relaxed

01:10:27.420 | and it seems to come out of the blue

01:10:30.600 | and all of a sudden these,

01:10:31.980 | or they follow a thought trail that takes them,

01:10:34.740 | that reminds them of their,

01:10:35.820 | and they find themselves in that same experience again.

01:10:39.940 | I think that's more state dependent learning.

01:10:42.060 | It's not the distressing component that is in

01:10:45.480 | and it's typically not perceptual.

01:10:47.480 | And then another class are just sort of perceptual anomalies

01:10:52.480 | within a day or two following the experience,

01:10:56.840 | which is not HPPD.

01:10:58.580 | Most people have joked that this is a free trip.

01:11:01.720 | Like you might see a few trails or halos the day afterwards.

01:11:05.020 | It doesn't last longer than that.

01:11:07.620 | And it doesn't screw you up.

01:11:09.340 | It's kind of fun.

01:11:10.160 | Like, oh yeah, I'm still seeing some trail.

01:11:11.580 | Most people will say.

01:11:13.420 | So it could mean any of those things.

01:11:15.180 | So flashback is, yeah.

01:11:17.060 | - Interesting.

01:11:17.900 | No, I appreciate you clarifying that.

01:11:20.220 | I mean, one very common misconception about neuroplasticity

01:11:24.980 | is that it's an event and it's not an event, it's a process.

01:11:28.860 | And we have no understanding of the duration

01:11:32.320 | of that process.

01:11:33.780 | However, the experience of any drug or any life experience,

01:11:38.780 | even if it's a trauma or a wonderful experience

01:11:41.980 | or a psychedelic experience, doesn't matter.

01:11:44.360 | Sets in motion a series of dominoes that fall.

01:11:47.980 | And it's the falling of those dominoes

01:11:49.540 | that we call neuroplasticity.

01:11:51.020 | I mean, the reshaping of neural circuits could take years.

01:11:54.140 | We don't know.

01:11:55.080 | It's the trigger and then there's the actual change.

01:11:58.100 | And so I think that some of what you described

01:12:00.500 | could be literally the reordering of circuitry,

01:12:03.740 | that in some individuals might extend longer than others.

01:12:06.540 | And there is one phenomenon

01:12:10.340 | that I've been told people experience.

01:12:14.380 | And I'm wondering whether or not any of the patients

01:12:16.620 | you've worked with or people in your trials

01:12:19.280 | have reported this.

01:12:20.560 | I've never done ayahuasca,

01:12:23.100 | which I'm assuming has some overlap

01:12:25.900 | with the serotonin system.

01:12:27.020 | Probably hits a variety of systems.

01:12:28.100 | - So it's DMT, the active. - The DMT system.

01:12:29.860 | - Yeah, it's orally active. - Right, excuse me.

01:12:30.940 | That's right.

01:12:31.760 | - MAO inhibitors that allow the DMT

01:12:33.340 | to be orally.

01:12:34.180 | - Right, I should have recalled that, absolutely.

01:12:37.580 | Well, I've never done it,

01:12:38.420 | but a number of people I know that have done ayahuasca

01:12:41.700 | as well as people I know who have done MDMA

01:12:44.760 | report an increased sense of what are sometimes called ASMR,

01:12:49.140 | these autonomic sensory meridian reflexes, which is,

01:12:53.000 | and it's interesting,

01:12:53.840 | a lot of people have these naturally and they hide these.

01:12:57.880 | It's actually something that many people

01:12:59.680 | keep hidden to themselves.

01:13:02.300 | I'll just ask you if you can do it.

01:13:03.700 | So some people are able to pass a,

01:13:06.620 | like a shiver down their spine

01:13:08.440 | or up their spine consciously.

01:13:10.460 | You know, like you can kind of,

01:13:11.900 | I'm able to actually pass a shiver up my spine.

01:13:14.480 | I actually learned how to do this when I was a kid

01:13:15.980 | on a hot day.

01:13:16.820 | I was standing on a field in sports camp

01:13:18.300 | and I was like, it's really hot here.

01:13:19.420 | And I could actually create like a cooled perception.

01:13:24.220 | Some people, I've told someone this once

01:13:26.140 | and then this led to a discussion of,

01:13:27.660 | oh, I can do it, but I always hid that from people.

01:13:29.520 | 'Cause it's actually somewhat pleasurable.

01:13:31.580 | And this is a well-known phenomenon, ASMR.

01:13:35.260 | And some people I know who have taken MDMA therapeutically

01:13:39.000 | or ayahuasca will report that they feel great relief

01:13:44.000 | from this, they can generate these autonomic reflexes

01:13:47.180 | through their body more readily.

01:13:49.220 | Probably, I'm guessing, because they were able to tune in

01:13:52.700 | to a kind of deeper sense of somatic self.

01:13:55.280 | Now on the internet, ASMR, if you look it up,

01:13:57.980 | it's a little bit like the bath salt thing,

01:13:59.420 | but in the other direction,

01:14:00.460 | like there were people that pay,

01:14:02.200 | let's just say there are accounts on YouTube

01:14:05.000 | that have many, many millions of viewers

01:14:07.700 | of people that will whisper to them about,

01:14:11.580 | like for instance, there's people that will go listen to,

01:14:15.420 | it seems to be women in particular,

01:14:16.940 | whispering about like car mechanics or something

01:14:19.900 | or about, or scratching.

01:14:21.580 | So there are certain sounds will do this,

01:14:23.500 | whispering, tapping, finger tapping,

01:14:25.820 | and people experience immense pleasure from it.

01:14:28.120 | It's not really sexual pleasure,

01:14:29.540 | but it's this kind of deep core of the body.

01:14:32.520 | It's the autonomic nervous system

01:14:34.180 | down the core of the spine.

01:14:35.020 | - Probably what a certain number of people

01:14:36.260 | would call Kundalini, which is another one,

01:14:39.020 | scientifically who, yeah.

01:14:40.340 | - That's right, and people who do long duration

01:14:42.660 | Kundalini breathing sessions,

01:14:44.360 | many of them will report later feeling as if

01:14:47.140 | their perception of self is outside of their head,

01:14:50.980 | that they're literally walking,

01:14:52.660 | it's very uncomfortable for them,

01:14:54.420 | that they feel like they're walking around

01:14:56.040 | with their sense of self extended beyond the body.

01:14:59.380 | And this is a clinically described neurologic phenomenon.

01:15:02.460 | - Have any studies been done?

01:15:03.480 | I would imagine that person might actually like,

01:15:05.900 | would they duck?

01:15:07.420 | - Oh, what?

01:15:08.260 | - Like that would be an interesting experiment.

01:15:09.300 | - That would be the kind of thing my lab

01:15:10.260 | would want to get into.

01:15:11.420 | - Yeah, their body could clear,

01:15:12.680 | but their projection wouldn't.

01:15:15.460 | - Yeah, the sense of self,

01:15:16.660 | I mean, there's a well-known phenomenon.

01:15:18.380 | It's very, in a few individuals, very sad,

01:15:21.180 | where people actually avidly seek out

01:15:24.020 | amputation of their limbs

01:15:25.220 | because their limbs they feel don't belong to their body.

01:15:27.620 | - Oh yeah.

01:15:28.460 | - So it's very, very sad and fortunately very rare,

01:15:31.020 | but also very sad condition.

01:15:32.640 | Anyway, I think that the core of this conversation

01:15:36.660 | that we're drilling into is this notion

01:15:38.900 | of reordering the self.

01:15:40.580 | And it's a relief to me to know that flashbacks

01:15:43.700 | are not something that is kind of, forgive the term,

01:15:47.860 | baked in to the psychedelic experience.

01:15:51.860 | And I suppose that's a good segue

01:15:53.320 | to ask about other sorts of drugs.

01:15:56.420 | Having said baked in,

01:15:57.300 | the temptation is to go to marijuana or cannabis,

01:16:00.620 | but if we could, I'd like to just ask

01:16:04.260 | about some of the more dopaminergic compounds,

01:16:06.900 | in particular MDMA.

01:16:08.340 | - Yeah.

01:16:09.260 | - My understanding is that MDMA

01:16:11.540 | is a purely synthetic compound,

01:16:14.180 | that you're not going to find MDMA in nature.

01:16:16.860 | - So far.

01:16:17.980 | - So far.

01:16:18.820 | - DMT was first synthesized in the lab

01:16:20.780 | and then we thought it didn't exist in nature.

01:16:23.100 | And then like Richard Schultes found it like everywhere.

01:16:27.180 | - In South America.

01:16:28.660 | Who knows, a plant out there might be making MDMA,

01:16:31.060 | but as far as we know now, no.

01:16:33.040 | - Right, and we'll talk about DMT

01:16:34.260 | and its sources within the body.

01:16:35.720 | But MDMA could exist elsewhere, but has been synthesized.

01:16:40.720 | And my understanding is that MDMA

01:16:44.740 | leads to very robust increases

01:16:47.420 | in both dopamine and serotonin simultaneously,

01:16:50.660 | which from a neural network's perspective

01:16:55.100 | is a very unusual situation, right?

01:16:57.660 | Normally, because dopamine puts us in this exteroceptive,

01:17:00.820 | looking outside ourselves,

01:17:01.900 | seeking things in the world beyond the skin, our own skin,

01:17:06.000 | and dopamine, excuse me, serotonin tends to focus us inward.

01:17:09.700 | Those are almost mutually exclusive

01:17:11.620 | kind of neurochemical states,

01:17:13.540 | although they're always at different levels.

01:17:15.140 | So why would it be that having this increased dopamine

01:17:20.140 | and increased serotonin would provide an experience

01:17:25.060 | that is beneficial?

01:17:26.540 | And how do you, to the extent that you can describe it,

01:17:29.580 | how do you think that experience differs

01:17:31.580 | from the sorts of experiences that people have on psilocybin

01:17:34.100 | or more serotonergic agents, just broadly speaking?

01:17:37.960 | - Yeah, yeah.

01:17:39.340 | In terms of the effects generally on serotonin and dopamine,

01:17:44.340 | I can only speculate,

01:17:49.060 | like sort of is that dopaminergic component necessary

01:17:53.740 | for let's say we know that the amygdala

01:17:56.780 | is less reactive under acute effects,

01:17:59.580 | and that may play a role in,

01:18:02.320 | there's less sort of a control from the amygdala

01:18:07.140 | in terms of like one's experience of memory.

01:18:10.080 | So it may be part of this sort of reprocessing,

01:18:13.080 | this reconsolidation of these memories in a different way

01:18:15.720 | where the amygdala is not like going crazy,

01:18:17.880 | saying freak out, like fight or flight.

01:18:20.380 | - Well, I should have said,

01:18:21.580 | it seems like MDMA is being used clinically anyway,

01:18:25.180 | mainly for trauma, not just for depression.

01:18:29.140 | - Although part of that, we really don't know,

01:18:33.740 | and maybe that MDMA is great for depression

01:18:36.380 | and some of these other, and it may be that,

01:18:38.060 | and I'm going to be looking at this soon,

01:18:39.300 | that psilocybin is great for treating PTSD.

01:18:42.060 | A lot of underground therapists say that,

01:18:44.780 | underground psychedelic therapists.

01:18:46.260 | So we don't really know yet which people doing illegal,

01:18:51.100 | but more like a professional therapist would,

01:18:54.380 | it's just illegal, and this is a kind of a growing thing.

01:18:59.340 | So we don't really know which, it's speculating,

01:19:03.820 | but it may be that MDMA for a broader number of people

01:19:08.820 | is better for trauma because the chances

01:19:13.760 | of having an extremely challenging experience,

01:19:16.100 | what I call the bad trip, like really freaking out,

01:19:20.800 | is much lower with MDMA.

01:19:22.460 | People can have bad trips,

01:19:23.700 | but they're of a different nature.

01:19:25.400 | It's not sort of like freaking out

01:19:28.460 | because all of reality is sort of shattering,

01:19:31.060 | and it's less of this, it can take so many forms

01:19:34.500 | with the classic psychedelics,

01:19:36.300 | but like typically you'll hear something like,

01:19:40.260 | I didn't know it was going to be like this,

01:19:42.700 | no matter how hard you tried to prepare them,

01:19:44.920 | that like, this is like, get me off this drive.

01:19:49.020 | - You're talking about LSD or psilocybin?

01:19:50.260 | - Psilocybin, yeah, yeah.

01:19:53.480 | And just the sense of like, I'm going insane,

01:19:56.660 | this is so far beyond anything I've ever experienced,

01:20:00.400 | and it's scaring the shit out of me.

01:20:02.420 | I don't have a toehold on anything,

01:20:05.940 | even that I exist as an entity.

01:20:09.340 | And that can be really, I think, frankly, experientially,

01:20:12.460 | that's kind of the gateway

01:20:13.620 | to both the transcendental mystical experiences,

01:20:17.780 | the sense of unity with all things,

01:20:21.140 | which we know, our data suggests,

01:20:22.700 | is related to long-term positive outcomes.

01:20:27.140 | - Wait, I want to make sure I understand.

01:20:28.340 | So you're saying the bad trip

01:20:29.540 | can be related to the transcendental experience?

01:20:31.700 | - Right, I think those are both speculating,

01:20:34.100 | but you have to pass through this sort of like,

01:20:37.920 | reality shattering, including your sense of self.

01:20:42.380 | And one can handle that in one of two ways.

01:20:45.380 | You can either completely surrender to it,

01:20:48.180 | or you can try to hang on.

01:20:49.940 | And if you try to hang on,

01:20:50.960 | it's going to be more like a bad trip.

01:20:52.660 | So again, I wish there was more,

01:20:54.220 | and hopefully there will be more experimentation.

01:20:56.240 | There's a lot going on here in the black box

01:20:58.420 | in terms of the operant behavior

01:21:00.620 | of how you are within yourself,

01:21:04.320 | choosing to handle, like letting go.

01:21:07.260 | And eventually, we'll be able to see this in real time

01:21:09.780 | with brain imaging, ah, there they are surrendering

01:21:12.380 | to the psychedelic experience.

01:21:13.660 | Here they are trying to hold on, but we're not there yet.

01:21:17.360 | But I think through clinical observation,

01:21:19.820 | it seems pretty clear that something like that is going on.

01:21:23.300 | And certain drugs like DMT, smoked DMT, can be so strong.

01:21:26.640 | The reason I think that can be so extraordinary,

01:21:30.540 | you can compare to the others,

01:21:31.380 | 'cause it like forces people.

01:21:32.940 | Like there is no choice to hang out in it.

01:21:34.780 | - I've never done it.

01:21:35.620 | I was told that DMT is like a high-speed locomotive

01:21:39.020 | into the psychedelic experience

01:21:40.740 | and out of the psychedelic experience.

01:21:43.180 | And there's no ability to hold on to the self

01:21:46.500 | while you're in the kind of peak phase.

01:21:48.820 | Is that correct?

01:21:49.660 | - A lot of people say that, but Terrence McKenna,

01:21:52.940 | who is kind of the classic bard on DMT effects,

01:21:55.980 | he would say the sense of self was intact,

01:21:59.620 | but everything else, the sensorium and what you navigated,

01:22:03.460 | what you oriented towards,

01:22:05.580 | everything else changed basically.

01:22:07.560 | But it's hard to, when everything's changing,

01:22:09.260 | it's hard to say like, what is the self that's changing?

01:22:11.600 | What is the rest of the world?

01:22:12.960 | - Well, and language is totally deficient

01:22:15.180 | to describe experience any way, much less on a psychedelic.

01:22:19.740 | What is McKenna's background?

01:22:21.500 | Like, what is his qualification for being this,

01:22:24.580 | as you referred, this bard of DMT?

01:22:27.020 | - So, and we're talking about Terrence,

01:22:28.780 | and there's also the brother Dennis, whom I know who's-

01:22:33.260 | - Can only imagine what Thanksgiving dinner is like

01:22:35.460 | at their house. - Terrence passed away

01:22:37.440 | years, a couple of decades ago now.

01:22:39.440 | But he's sort of the one who's known as being a bard,

01:22:42.420 | and you can find hundreds, if not thousands of hours of him

01:22:46.580 | on the lecture circuit in the '80s and '90s on YouTube.

01:22:49.860 | But his background was really, oh gosh,

01:22:52.500 | I don't recall what his college degree was in,

01:22:54.500 | but he basically, when he was like 19,

01:22:57.620 | he traveled to South America,

01:22:59.840 | and actually on the initial trip with his brother,

01:23:03.120 | who was even younger than him, with some other friends,

01:23:06.300 | and just in search for a DMT snub

01:23:11.140 | that they had read about in the Harvard archives

01:23:14.040 | from the work of Schultes from a generation before,

01:23:17.980 | but they had discovered all of these mushrooms growing

01:23:22.680 | that down there, the psilocybin mushrooms,

01:23:25.020 | what they recognized, and just took a lot of mushrooms,

01:23:27.880 | and- - And talked about it.

01:23:30.700 | - Talked about it.

01:23:31.540 | Terrence was basically a very intelligent,

01:23:33.520 | very well-read and literature and culture person

01:23:38.300 | that could be, he was sort of the next generation's

01:23:41.740 | Tim Leary, someone who could really speak,

01:23:44.900 | get a little closer to the magnitude

01:23:47.460 | of what the psychedelic experience was like for people.

01:23:50.340 | And he served, like Leary, somewhat of an advocate.

01:23:53.780 | I mean, he would tell people, folks, you could see

01:23:57.580 | the equivalent of a UFO landing on the White House lawn,

01:24:00.900 | like it's right there, it'll take five minutes,

01:24:03.960 | it'll shake everything in your reality.

01:24:06.940 | He would sort of goad people into doing it.

01:24:09.020 | - Well, certainly science and clinical medicine

01:24:11.640 | are just but two lenses with which to explore

01:24:15.220 | these things in life.

01:24:16.340 | But part of the reason I ask is I feel like,

01:24:19.320 | in the world of health and fitness,

01:24:24.200 | you have this very extreme condition

01:24:28.220 | of like Arnold Schwarzenegger's and bodybuilders

01:24:30.980 | who have like 2% body fat, and they look like,

01:24:33.500 | to most people, they look kind of freakish,

01:24:36.180 | especially now, right?

01:24:37.200 | - Oh, especially now.

01:24:38.140 | - Especially now.

01:24:38.980 | - Yeah. - And yeah.

01:24:39.820 | - Made Arnold look like regular.

01:24:42.260 | - Exactly. - Back in his day, yeah.

01:24:43.740 | - Yeah, and you have contortionists

01:24:45.660 | who can put themselves into a small box

01:24:47.660 | and wrap themselves into a pretzel.

01:24:49.380 | But from those two very extreme subculture practices

01:24:53.580 | that, I don't know anything about contortionism, really,

01:24:57.780 | but, except that they get really bendy,

01:25:00.780 | but it was a community that included lifestyle practices

01:25:04.540 | and nutritional practices and then drug practices.

01:25:06.800 | From those very extreme subcultures,

01:25:09.260 | there's been an export, which is that,

01:25:11.320 | weight training is healthy, right?

01:25:14.240 | The general public has done that, or that yoga is healthy.

01:25:17.200 | So contortionism to yoga, et cetera.

01:25:20.220 | And I feel like a similar thing is happening

01:25:22.320 | in the realm of psychedelics,

01:25:23.780 | where it was Leary and Huxley.

01:25:28.780 | I mean, I'm from the Bay Area.

01:25:30.980 | I'm not far from the Menlo Park VA,

01:25:32.700 | where One Flew Over the Cuckoos is basically based on, right?

01:25:35.340 | Ken Kesey and those guys.

01:25:36.420 | And there has been an attempt at creating this movement

01:25:41.420 | toward openness about psychedelics

01:25:45.100 | and their positive effects.

01:25:46.740 | This has happened before.

01:25:48.460 | The difference is that now there are people like you

01:25:50.420 | inside the walls of the university

01:25:52.220 | or publishing peer-reviewed studies and things of that sort.

01:25:54.980 | The reason I asked about McKenna was,

01:25:56.900 | it seems like McKenna and his brother are,

01:26:00.780 | but just two of many people, Michael Pollan, et cetera,

01:26:05.780 | who have no real formal training in biology or psychology,

01:26:11.280 | the other guys who were at universities lost their jobs.

01:26:15.660 | They were actually removed from places like Harvard

01:26:18.040 | and other universities for their kind of

01:26:20.380 | cavalier explorations, right?

01:26:22.980 | And now things are kind of returning.

01:26:25.020 | So in the same way that bodybuilding led to weight training

01:26:27.620 | in every corner gym, men, women, and children,

01:26:31.140 | and contortionism is one extreme,

01:26:34.400 | but people generally think that yoga

01:26:36.020 | is a pretty healthy practice, right?

01:26:38.220 | These are matter of degrees, right?

01:26:40.180 | And now here you are inside the walls

01:26:44.660 | of a very highly respected university, Johns Hopkins.

01:26:47.900 | You're on the medical school side of the undergrad.

01:26:49.780 | So in the med school, which is a serious health institution,

01:26:54.780 | the question is to me, what are the valuable exports, right?

01:26:59.780 | And where does the extreme lie?

01:27:05.660 | I mean, clearly there's a problem

01:27:08.140 | with tinkering with reality through pharmacology,

01:27:13.140 | and there's a benefit, it sounds like,

01:27:15.580 | to tinkering with reality through pharmacology.

01:27:19.540 | And what's so striking to me is that

01:27:22.260 | this is the elements of atypical experience,

01:27:26.180 | atypical representation of the self.

01:27:28.340 | So for the average person, right,

01:27:34.340 | or for kids that are hearing this,

01:27:35.820 | kids that are in their teens, right?

01:27:37.820 | - Yeah.

01:27:38.660 | - I want to talk about what are the dangers of psychedelics?

01:27:41.820 | This is something you don't hear a lot about these days,

01:27:43.580 | and it's not because I'm anti-psychedelic at all,

01:27:45.980 | but what are the dangers, right?

01:27:47.540 | If a kid or a child, if a child is anti-psychedelic,

01:27:51.700 | a kid or adult has a predisposition toward, let's say,

01:27:55.460 | psychotic thinking, right?

01:27:59.860 | Or auditory hallucinations, or is on the Asperger's side

01:28:04.860 | of the autism spectrum.

01:28:07.820 | Is there an increased risk of bringing the mind

01:28:10.500 | into these states?

01:28:11.620 | 'Cause it sounds like a very labile situation.

01:28:14.820 | So could we talk a little bit about that,

01:28:16.700 | and are there classes of these different drugs,

01:28:18.900 | whether or not it be MDMA, LSD, or DMT that are,

01:28:22.380 | that you think are particularly sharp blades

01:28:24.780 | and therefore need to be wielded particularly carefully?

01:28:28.500 | - Yeah, so these can be profoundly destabilizing

01:28:33.460 | experiences and ones that, you know,

01:28:36.940 | ideally are had in a safe container, you know,

01:28:41.940 | sort of where someone, you know,

01:28:46.420 | what are the relevant dangers and what can we do

01:28:48.540 | to mitigate those?

01:28:49.700 | So there's two biggies.

01:28:52.860 | One, and I've already mentioned,

01:28:55.860 | it's people with very severe psychiatric illness,

01:29:00.220 | not depression, not anxiety.

01:29:02.940 | I'm talking about psychotic disorders like schizophrenia

01:29:06.660 | or mania as part of bipolar disorder.

01:29:10.180 | So, and diagnostically, this has shifted.

01:29:13.100 | So it's a little hard to say how many people today

01:29:15.140 | with bipolar would have been labeled as schizophrenia

01:29:17.100 | back in the '60s when some of this early research

01:29:20.900 | or just clinical observation was done.

01:29:23.220 | So it seems very clear that folks with a predisposition

01:29:27.380 | or active disease, they could be destabilized.

01:29:29.580 | And so some of the cases that we know of,

01:29:31.660 | I always think of Sid Barrett, the first singer of Pink Floyd

01:29:35.220 | seems pretty clear, although I think the family-

01:29:39.540 | - I don't know what happened there.

01:29:41.220 | I should be, sorry, Pink Floyd fans, I've never,

01:29:43.580 | the songs are just really long.

01:29:45.300 | - Yeah, you're more of a punk guy, right?

01:29:46.940 | - Yeah.

01:29:47.780 | So I've got my foot in a lot of worlds,

01:29:50.980 | definitely in part in the Floyd world,

01:29:53.420 | but he basically went crazy early on.

01:29:58.420 | It seemed, I don't think his family ever admitted it,

01:30:00.700 | but he developed schizophrenia, classic pattern.

01:30:04.500 | And he was doing a lot of LSD.

01:30:07.480 | But like a lot of these cases,

01:30:11.500 | it looked like he was showing all of the signs

01:30:14.300 | of some hints that he had that susceptibility before.

01:30:19.300 | And often this is hard to disentangle what causes what,

01:30:26.420 | because when do people typically, not always, but develop,

01:30:30.500 | when's the modal period for first break,

01:30:32.380 | it's adolescence, early adulthood, yeah.

01:30:34.580 | And when do people start playing with drugs?

01:30:37.260 | Same exact time period.

01:30:39.780 | So it can be hard to disentangle, but it seems pretty clear.

01:30:43.300 | Now I should also say, there are cases of folks

01:30:45.980 | with schizophrenia that say psychedelics have helped them.

01:30:48.700 | There's anecdotes for everything.

01:30:50.300 | - Do the people around those schizophrenics

01:30:52.060 | say it's helped them?

01:30:52.900 | - I don't know.

01:30:53.740 | - 'Cause when schizophrenics say things, you have to,

01:30:56.340 | I mean, with all due compassion and respect

01:30:58.780 | for schizophrenia, it's a disorder of thinking.

01:31:01.720 | So if they're saying it helped them.

01:31:03.700 | - Yeah, can you trust them?

01:31:04.860 | Yeah.

01:31:05.700 | I wouldn't be surprised if there was some kernel of truth

01:31:08.740 | in some cases, but they're just so,

01:31:11.620 | it seems very clear that the other side is there too,

01:31:14.860 | and that there ever is a therapeutic potential there

01:31:17.900 | for those disorders, that shouldn't be the first thing

01:31:20.980 | on our list, and we need to learn a lot more

01:31:23.140 | because of the level of risk before we start doing research

01:31:26.340 | to see if, you know, psilocybin can help with schizophrenia.

01:31:29.860 | Like, I don't think that that may never be the case,

01:31:32.080 | but even if it is, you'd have to be even more cautious

01:31:35.180 | and figure some more things out first

01:31:37.860 | with some of these other disorders.

01:31:39.540 | - What about bipolar, bipolar disorder?

01:31:41.900 | Can it be exacerbated by these compounds?

01:31:44.180 | - Yeah, and it may be that sort of the manifestation

01:31:49.180 | of people having prolonged psychiatric issues

01:31:53.100 | after a psychedelic experience, as atypical as that is,

01:31:58.100 | when that happens, it may be that might be more

01:32:02.080 | like a manic episode than a psychotic episode,

01:32:05.060 | and that can be a blurry line.

01:32:06.840 | And it's, the folklore is that, you know,

01:32:10.880 | people go on a trip and they never come back.

01:32:12.880 | That's clearly not the case because, you know,

01:32:15.320 | the drug is metabolized, like for anyone else,

01:32:17.640 | and the next day there's not, you know,

01:32:19.160 | there's virtually nothing in the system.

01:32:20.000 | - But it reshapes circuitry, I mean.

01:32:21.800 | - Right, and there's still, and I really do think, you know,

01:32:24.180 | much like the positive, you know, long-term effects that,

01:32:28.660 | you know, this class of problems is related to, like,

01:32:32.520 | the, to the experience and the destabilization

01:32:37.520 | that can happen from that experience,

01:32:42.040 | if it's not in that, in the right container.

01:32:44.700 | And again, like these people are susceptible to, you know,

01:32:47.920 | some people with that psychotic predisposition,

01:32:50.800 | they lucky to be born to a great family,

01:32:53.880 | stable environment, they maybe never have a full break,

01:32:56.680 | or the one that they have is not nearly as bad as what,

01:32:59.960 | you know, someone that is, who's homeless

01:33:02.920 | and is coming from all kinds of early childhood trauma,

01:33:05.320 | like the disease is probably going to be far worse, you know?

01:33:08.840 | So, you know, having a psychedelic experience

01:33:12.640 | is like one of those destabilizing experiences, you know?

01:33:16.080 | So exclude, now, fortunately,

01:33:18.280 | it's really easy to identify those people.

01:33:20.480 | And we even err on the side of extreme caution

01:33:23.480 | by eliminating people with like, say,

01:33:25.200 | a first degree relative, in some studies,

01:33:26.820 | even a second degree relative,

01:33:28.620 | given the heritability, there's some increased chance

01:33:31.400 | if your brother or your, yeah.

01:33:33.520 | So in an abundance of caution, even eliminating that.

01:33:38.580 | I think eventually, if it's approved for use, FDA use,

01:33:43.160 | we could dial back on that as we learn more.

01:33:45.420 | I think it's, again, overly cautious, which is-

01:33:49.200 | - But you're doing an early stage clinical trial.

01:33:50.620 | - Yeah, it's the appropriate place to start

01:33:52.640 | at this point in time.

01:33:53.600 | But, you know, if you give a skid

01:33:56.260 | or another structured psychiatric interview

01:33:58.260 | with a clinician sitting down with this person

01:34:00.080 | for a few hours to delve into their history.

01:34:02.360 | And like, you can very reliably determine

01:34:05.140 | if this person has either, you know,

01:34:07.680 | a psychotic disorder or bipolar disorder

01:34:10.120 | or a strong predisposition.

01:34:12.120 | So that's, you know, that you can screen for that.

01:34:14.400 | And that's how you address that.

01:34:15.880 | The far more likely danger is the bad trip.

01:34:18.800 | Anyone can have this.

01:34:20.180 | The most psychologically healthy person

01:34:21.960 | in the world, probably.

01:34:23.720 | You jack the dose high enough.

01:34:25.080 | And especially in a less than an ideal environment,

01:34:29.180 | you can have a bad trip.

01:34:30.580 | You even get it in an ideal environment like ours

01:34:33.620 | at a high dose of around 30 milligrams of psilocybin.

01:34:37.260 | After, you know, the best preparation we can provide,

01:34:39.980 | about a third of people will say,

01:34:42.060 | essentially at some point they have a bad trip, you know?

01:34:45.140 | - At some point within the entire journey.

01:34:47.340 | - Right, now they could have

01:34:48.860 | one of the most beautiful experiences of their life,

01:34:50.980 | sometimes like a couple minutes later.

01:34:53.460 | But at some point they had a sense of strong anxiety,

01:34:56.160 | fear, losing their mind, feeling trapped,

01:34:59.600 | something like that.

01:35:01.360 | Now, typically when people have that in the, you know,

01:35:04.520 | when they're just taking on their own,

01:35:06.660 | like a lot of things, they're fine.

01:35:08.180 | They get through it.

01:35:09.020 | You know, they're more likely to be better off

01:35:11.100 | if they're not having to navigate the streets of Manhattan,

01:35:14.260 | that, you know, or, and if they're with, you know,

01:35:17.340 | other people with friends,

01:35:19.480 | better that those friends aren't also dealing

01:35:21.600 | with their own psychedelic experience,

01:35:22.980 | but probably having some friend of any type,

01:35:25.340 | but whatever they're on there is better than having nothing.

01:35:27.260 | So very dependent on context.

01:35:30.260 | And so the tough thing here that,

01:35:32.740 | that in conveying to the public is that

01:35:35.700 | a lot of folks will say,

01:35:38.380 | man, I've taken psychedelics hundreds of times,

01:35:41.060 | and this is like your fear-mongering and, you know,

01:35:45.460 | there's no, you know, you're exaggerating the danger there.

01:35:48.300 | So I want to say it is atypical, but sometimes,

01:35:52.340 | and I have a file folder that grows larger every year

01:35:56.220 | of these cases, either in the medical literature

01:35:58.940 | or from the news of people that freak out on a psychedelic

01:36:02.140 | and they get hurt or they die.

01:36:04.700 | They run into traffic.

01:36:06.460 | They fall from a height, whether they thought they could fly

01:36:10.020 | or whether they just fell like you can do when you're drunk

01:36:13.540 | or you're intoxicated on any substance.

01:36:16.120 | Sometimes that's unclear.

01:36:18.660 | Or gosh, one of the craziest cases was a kid,

01:36:22.780 | like an 18-year-old or so in Oregon several years back

01:36:26.460 | that just, he even wrote about,

01:36:28.420 | I want to take the biggest, he had done mushrooms before.

01:36:30.300 | I want to take a heroic dose,

01:36:32.360 | the biggest dose I've ever taken.

01:36:33.580 | He ended up just totally out of it,

01:36:35.620 | ended up in a neighbor's house.

01:36:37.020 | He was just totally disoriented, disconnected from reality,

01:36:39.540 | and the cops ended up killing him.

01:36:41.580 | And it was just tragic,

01:36:42.700 | obviously an overuse of force in that case,

01:36:45.300 | 'cause he was actually naked at the time,

01:36:46.780 | this naked like 120-pound, I think,

01:36:49.980 | as a recalled kid that ended up dying.

01:36:52.340 | - Well, it's analogous to the reason I use the examples

01:36:55.060 | of like bodybuilding culture.

01:36:56.280 | I mean, people there have taken excessive amounts

01:36:58.620 | of antibiotics and diuretics and died.

01:37:00.980 | Then the contortionist culture,

01:37:02.460 | people have put themselves in a little plexiglass boxes

01:37:04.820 | to do, at the extremes, you're going to get deaths.

01:37:09.660 | And at the extremes, and one of the extremes

01:37:12.620 | is the sheer number of people

01:37:14.220 | with different biological makeups taking the same drug.

01:37:18.500 | And so you can create extremes through numbers.

01:37:20.340 | You can create extremes through dosage, right?

01:37:24.000 | It seems, well, this is why I'm such a fan of the fact

01:37:28.060 | that people like yourself are doing clinical trials

01:37:30.500 | inside the walls of universities.

01:37:33.820 | Not because I think that psychedelics only have utility

01:37:38.820 | in those environments, but because it's so important

01:37:41.600 | toward creating their transition to legality

01:37:45.640 | and to understand what legality means

01:37:48.120 | for a compound like this, right?

01:37:50.040 | - What model?

01:37:51.000 | - Right, I mean, again,

01:37:52.280 | we'll stay with the anabolic steroids.

01:37:54.200 | There's now testosterone and estrogen replacement therapy.

01:37:56.800 | Hormone replacement therapy

01:37:57.920 | is a common medically approved practice,

01:38:00.720 | but that's vastly different than people

01:38:02.520 | taking their own stuff for diet

01:38:04.400 | or deciding how much they need to take, right?

01:38:06.840 | Like we said, there's yoga and there's contortionism

01:38:09.480 | in a plexiglass box and thinking of Houdini or something.

01:38:12.920 | So these are a matter of degrees.

01:38:15.880 | Speaking of dosage, I definitely want to ask you

01:38:18.680 | about microdose versus standard or macro dose.

01:38:22.880 | Tell me that I'm wrong, but I'm always a little bit,

01:38:29.020 | I'm micro cynical, if you will, about this term microdose.

01:38:36.600 | And the reason is that many people that I know

01:38:39.560 | who talk about microdosing are taking dosages of compounds

01:38:44.560 | that are very powerful at microgram levels.

01:38:50.280 | So the word micro, I think,

01:38:51.900 | can be a little bit confusing to people

01:38:53.500 | because microdose implies less than something.

01:38:57.880 | It's a mini dose, right?

01:38:59.640 | And yet some of these compounds are tremendously powerful

01:39:04.240 | at microgram concentrations.

01:39:06.620 | So what it constitutes a microdose

01:39:10.320 | and what is the value of so-called microdosing, if any,

01:39:14.220 | and how does it differ from standard

01:39:17.980 | or what I can only assume is called macrodosing?

01:39:20.640 | - Yeah, and so LSD would be the prototypical example

01:39:24.480 | of that super potent compound.

01:39:27.200 | - What size dosage of LSD will lead to hallucinations

01:39:31.960 | and kind of standard-

01:39:32.780 | - Sort of the entry point for psychedelic type effects,

01:39:37.080 | which may not involve hallucinations.

01:39:38.760 | Actually, most classic psychedelics

01:39:40.800 | don't lead to true hallucinations

01:39:42.740 | as defined in psychiatry.

01:39:44.300 | You know, thinking you're talking to the person

01:39:46.660 | that's not there, seeing the pink elephant.

01:39:48.200 | - No, it's more like tracers and things like that.

01:39:50.780 | - Right, and some people never get that

01:39:53.880 | even at a very high dose.

01:39:55.160 | So I think more broadly in terms of the psychedelic effects,

01:39:58.680 | which isn't just perceptual,

01:40:00.140 | unless we get into the level, as you were alluding to,

01:40:02.720 | earlier, a broader definition of perception,

01:40:05.680 | like one's models of the world, the model of the self.

01:40:09.340 | You can consider all of that perception

01:40:12.020 | in terms of truly not sensation, but perception,

01:40:15.280 | the construction of putting together reality.

01:40:18.800 | So yeah, yeah, yeah.

01:40:21.560 | So the psychedelic effects are typically considered

01:40:25.240 | to start for LSD around 100 micrograms.

01:40:27.020 | So a 10th of a milligram is 100 micrograms.

01:40:30.800 | - Right, so someone taking 100 micrograms of LSD,

01:40:34.480 | nowadays, people might mistakenly refer to that

01:40:38.300 | as a microdose because it's micrograms,

01:40:40.340 | but that's actually a macrodose of LSD.

01:40:43.100 | - Right, and that's one of the most common mistakes

01:40:45.880 | or situations that people get into with microdosing

01:40:49.240 | is they intend it to be a microdose,

01:40:50.780 | but it ends up being a full-blown dose.

01:40:54.120 | Now, people do, when they're working with LSD

01:40:57.240 | and they're microdosing,

01:40:58.100 | they'll shoot for something like, say, 10.

01:41:01.040 | milligrams, something in that range,

01:41:03.920 | 10, 20 milligrams of LSD.

01:41:06.000 | So a 10th, a fifth, something of kind of

01:41:09.500 | your entry-level psychedelic dose.

01:41:12.400 | People's ability on the street to do this,

01:41:15.480 | yeah, I say the street as if they're on the corner,

01:41:17.300 | but anyway, like outside of the medical profession

01:41:19.440 | to do this, it varies as you can imagine.

01:41:21.020 | - And they're not measuring purity or molarity

01:41:22.900 | or things like that, typically.

01:41:24.080 | - And there's ways to do it.

01:41:25.280 | So even if you don't ultimately know the dose

01:41:27.200 | that's in the blot or paper of acid,

01:41:29.920 | one could at least get a sense of like,

01:41:31.520 | yeah, having one of those tabs is,

01:41:34.440 | one of those hits is a psychedelic experience.

01:41:37.240 | They could do something like put it in water,

01:41:39.240 | it's 100% aqueous soluble.

01:41:41.560 | You could make sure it all gets into solution

01:41:44.520 | and then volumetrically measure.

01:41:46.100 | It's gonna be homogeneously distributed.

01:41:48.200 | So you can take 1/10 of that volume of water

01:41:51.040 | after it's fully dissolved.

01:41:52.820 | That whatever you started with,

01:41:54.040 | you're gonna have a 10th of that dose.

01:41:55.280 | So the people that are more sophisticated

01:41:57.360 | will do things like that.

01:41:58.680 | And when they're working with mushrooms,

01:42:00.440 | they'll grow a bunch of mushrooms

01:42:01.500 | and then they'll say, put it in a coffee grinder.

01:42:03.720 | I'm not telling people to do this, by the way,

01:42:05.660 | I'm just describing, so don't do this at home,

01:42:07.600 | but like grind it all up so it's homogenous.

01:42:10.040 | 'Cause you can have like,

01:42:11.520 | sort of taking two caps and a stem,

01:42:14.680 | hey, this two caps and a stem that this buddy takes

01:42:18.300 | has a different potency than this two caps and a stem

01:42:20.740 | that the other buddy takes.

01:42:21.800 | So people that are kind of in the know

01:42:24.240 | will grind it all up into a homogenous powder

01:42:26.800 | and they'll pack it into whatever size capsule

01:42:29.120 | and they'll know that.

01:42:30.000 | And again, even if they don't have,

01:42:31.800 | sometimes they might have a buddy

01:42:32.920 | that'll sneak it into the HPLC at their job or whatever,

01:42:36.360 | if they have-- - Not your lab.

01:42:37.760 | - Not my lab, that's never happened.

01:42:39.200 | Yeah, seriously, never happened.

01:42:40.440 | But they'll at least know that,

01:42:43.320 | hey, I've got a sense of what two capsules do.

01:42:46.700 | I've got a sense of what five capsules do.

01:42:49.320 | But in reality, like that's not what people do.

01:42:53.960 | They'll take a piece of blotter paper

01:42:55.500 | and they get a tiny little pair of scissors,

01:42:58.260 | a Swiss army knife pair of scissors,

01:42:59.820 | and they'll cut up the tab of acid,

01:43:02.060 | which is like, you know, a quarter inch square or something.

01:43:05.220 | And they'll cut it up in 10 little pieces.

01:43:07.420 | And it's like, you have no idea

01:43:09.460 | like if it's equally distributed in that media.

01:43:12.160 | - Yeah, and we can chuckle about it.

01:43:13.840 | And, but to me, one of the reasons why this experiment

01:43:18.840 | around psychedelics, this cultural experiment

01:43:21.160 | and this legal experiment, we're seeing this now,

01:43:25.420 | but this was all attempted once before in the 60s and 70s.

01:43:29.860 | The difference was it was all out in the street.

01:43:32.560 | The people in universities who were dabbling with this stuff

01:43:35.920 | lost, most of them lost their jobs

01:43:37.680 | or were asked to leave through, you know.

01:43:40.160 | - They lost their funding for this research minimally

01:43:42.240 | and they had to move on to other topics.

01:43:43.600 | - That's right, so these are precarious times.

01:43:45.720 | I mean, we're at a key moment where everyone assumes

01:43:50.520 | that this is all going to be legal in a few years.

01:43:52.700 | But I think that that's a premature assumption.

01:43:55.360 | - Yeah. - Frankly.

01:43:56.260 | But, and let's touch on the legality

01:44:00.780 | and some of the things that are happening now.

01:44:02.540 | But what is microdosing psilocybin

01:44:06.540 | versus the sorts of dosages that you described before

01:44:09.980 | in the 10 to 40 milligram range?

01:44:12.560 | I've heard of people taking one or two milligrams

01:44:16.820 | of psilocybin every day as a way to quote unquote,

01:44:20.360 | and for those listening, I'm just making air quotes

01:44:22.200 | with my fingers, increase plasticity,

01:44:24.340 | which is a term that I personally loathe

01:44:26.740 | because what does that mean?

01:44:28.140 | I mean, you don't really want your brain to be plastic

01:44:30.400 | because you need to make,

01:44:32.520 | you need to maintain your ability to make predictions.

01:44:34.900 | Yeah, I mean, plasticity- - Ordering chaos,

01:44:36.700 | like prediction, you need models of the world.

01:44:40.080 | You need heuristics, like.

01:44:41.240 | - Plasticity is never the goal,

01:44:43.400 | or plasticity is never the goal.

01:44:45.660 | The goal-directed plasticity is the goal, right?

01:44:48.940 | Learning a language, reshaping your experience to a trauma,

01:44:53.140 | altering the perception of self,

01:44:54.820 | but plasticity is a process, like-

01:44:58.340 | - Yeah, schizophrenia is a lot of plasticity.

01:45:01.260 | - Exactly, right, right, and it might even be,

01:45:03.620 | there's one theory that it's extreme ongoing plasticity

01:45:06.420 | and that's why people never create

01:45:08.100 | stable representations of anything.

01:45:10.020 | That's a kind of a minority view out there,

01:45:13.640 | but so what's the business with microdosing

01:45:17.100 | and is there any clinical evidence

01:45:19.140 | or peer-reviewed published evidence that it works,

01:45:21.780 | quote, unquote, to make people feel better about anything?

01:45:24.860 | - So microdosing is the aim of taking,

01:45:29.860 | again, something around a 10th of what would be

01:45:33.700 | sort of an entry-level psychedelic dose

01:45:35.700 | for whatever compound, so like, yeah, with psilocybin,

01:45:39.540 | usually people, almost never do people have

01:45:42.020 | like pure psilocybin, like one milligram of psilocybin

01:45:44.860 | would be in the range of a microdose.

01:45:46.140 | More likely, people are going to have mushrooms,

01:45:48.320 | so like something like a half of a gram of mushroom.

01:45:53.200 | - I know people that are doing this every day.

01:45:55.500 | They're doing this every day, it's like in their,

01:45:57.300 | like the same way that I take, like I'm personally,

01:46:00.560 | I'm not recommending other people do this,

01:46:02.120 | but I take some, I'm a fan of LCL carnitine lately.

01:46:05.320 | I've been kind of experimenting with that a little bit,

01:46:07.000 | which is not a psychedelic compound.

01:46:08.880 | I take it every day and they're taking their psilocybin

01:46:12.160 | every day, that's their supplement, so.

01:46:15.440 | - So yeah, the claims are, and there are a number of them,

01:46:19.180 | there's two general ones.

01:46:20.500 | One is sort of acting in place of the ADHD treating drugs,

01:46:25.500 | so the psychomotor stimulant,

01:46:27.160 | so like a better version of Adderall.

01:46:29.700 | The other claims are essentially a better version

01:46:32.700 | of the traditional antidepressants,

01:46:35.840 | a better version of Prozac.

01:46:37.640 | - So people are taking both for attention deficit

01:46:39.860 | and for depression.

01:46:41.800 | - Yeah, and the aspects of those disorders

01:46:44.940 | that we all have a degree of,

01:46:48.080 | just like amphetamine is gonna increase the focus

01:46:51.000 | at the right dose of anyone who takes amphetamine

01:46:53.440 | pretty much, whether you're ADHD diagnosed or not,

01:46:57.860 | the idea is that there may not be necessarily

01:47:01.600 | a clear divide between the therapeutic need

01:47:04.880 | and positive psychology, even improving mood and focus,

01:47:11.320 | so it's not necessarily correcting ADHD,

01:47:15.020 | but improving focus to supercharge your life.

01:47:19.180 | And so those are the claims.

01:47:20.660 | So none of the peer-reviewed studies

01:47:25.660 | that have much credibility,

01:47:28.400 | none of them have shown a benefit and they've tried.

01:47:33.260 | Now there's only at this point four or five studies that,

01:47:36.580 | and I think for things like this,

01:47:39.020 | you really need double-blind research 'cause the effects,

01:47:43.200 | I mean, there was one study done in Amsterdam

01:47:45.340 | where people knew they were taking psilocybin truffles,

01:47:48.140 | basically same as mushrooms,

01:47:49.200 | they're more like the roots of the mycelia.

01:47:50.840 | - Microdosing them.

01:47:52.120 | - Well, taking what would be considered a microdose

01:47:56.940 | and then doing some cognitive measures before and after.

01:48:01.200 | And the types of things that,

01:48:02.340 | like a lot of cognitive measures are measured

01:48:04.200 | on the order of reaction time in milliseconds.

01:48:06.820 | I mean, and the types of effects you get

01:48:08.800 | as you could imagine are ones that like would be,

01:48:12.060 | you would totally expect could be there

01:48:13.720 | from either a practice effect or an expectancy effect,

01:48:18.420 | a placebo effect.

01:48:19.480 | So for something like these claimed,

01:48:22.700 | you can imagine a sort of an increased focus,

01:48:26.760 | enhancement of cognition.

01:48:28.440 | These are like gonna be more subtle effects

01:48:32.000 | that you really need a good placebo control for.

01:48:36.640 | The handful of studies that have done that have shown,

01:48:40.680 | they've ranged from finding no effect whatsoever

01:48:43.120 | to just a little bit of impairment,

01:48:44.900 | like impairing someone's ability

01:48:46.840 | to do time estimation and production tasks.

01:48:49.920 | So you want an accurate sense of time,

01:48:52.460 | at least if you're navigating in the real world.

01:48:54.800 | It's different if you're on the couch on a heroic dose

01:48:57.600 | for therapeutic reasons where you're safe,

01:48:59.340 | but if you're crossing the street,

01:49:00.960 | if you're getting in your work life,

01:49:03.840 | which is the way people are claiming to use it,

01:49:06.680 | it helps them be a better CEO,

01:49:08.720 | like you want an accurate sense of time.

01:49:10.520 | So if anything, the data suggests

01:49:12.120 | that it makes it a little bit less accurate.

01:49:14.760 | And there's evidence that someone feels a little bit

01:49:19.000 | impaired and they feel a little bit high.

01:49:22.520 | So in terms of, you call that abuse liability in research,

01:49:26.360 | not surprising, you take a little bit of a drug

01:49:28.880 | that can result in some type of a high

01:49:31.280 | and you take a little tiny bit of it,

01:49:32.460 | you'll feel a little bit high.

01:49:34.400 | So none of the, so far,

01:49:38.800 | no studies have shown any increase in creativity,

01:49:43.800 | enhancement of any form of cognition

01:49:47.120 | or a sustained improvement in mood.

01:49:50.620 | Now, no studies have actually looked

01:49:53.840 | at the system of microdosing

01:49:57.800 | that the aficionados are claiming.

01:49:59.840 | And there's a couple of models out there,

01:50:02.000 | but folks like Paul Stamets and others,

01:50:05.420 | they'll have particular formulas.

01:50:06.880 | They're like, you need to take it one day

01:50:09.000 | and then take so many days off and take it every four days.

01:50:11.780 | And I don't want to get into whose model is what,

01:50:13.700 | but it's always something like that,

01:50:14.960 | some pattern of use, usually not every day.

01:50:18.580 | And the claim is that it's not just,

01:50:21.740 | sometimes people get benefit that first time

01:50:23.920 | when they take it,

01:50:25.040 | but they really say you need to be on it for a while.

01:50:27.920 | Like a few weeks in, you may start to notice

01:50:29.760 | through this pattern of using it.

01:50:32.600 | And you're feeling the benefits on those off days,

01:50:35.440 | like the three or two days in between your active doses.

01:50:40.440 | So those are the claims.

01:50:41.560 | Again, we don't know that there's any truth to that working,

01:50:44.180 | but studies have not been done to model that.

01:50:47.800 | So that's a big caveat.

01:50:49.300 | We as a field, I say we as the scientific field,

01:50:53.440 | have not done the studies to really model

01:50:57.400 | what the real aficionados are claiming,

01:50:59.840 | where the therapeutic benefits come from.

01:51:03.720 | That said, it's almost assuredly

01:51:06.480 | there's a good amount of placebo there.

01:51:08.440 | But the caveat to that is like almost everything

01:51:11.600 | in medicine or therapeutics,

01:51:13.480 | there's, it's going to have some degree of placebo there.

01:51:16.360 | - Belief effects are, I have a colleague at Stanford,

01:51:19.920 | Alia Crum, who has published really beautiful work

01:51:22.380 | on belief effects that show that essentially

01:51:26.600 | you give the same milkshake to two people,

01:51:28.480 | you, or two groups of people,

01:51:30.360 | you tell them that one contains a lot of nutrients,

01:51:32.840 | the other is a low calorie shake.

01:51:34.100 | The insulin response.

01:51:36.080 | - Amazing.

01:51:37.040 | - Varies dramatically between the two,

01:51:39.120 | or two groups rather doing equivalent amounts

01:51:42.380 | of physical movement.

01:51:45.040 | And you tell one group that it's going to be good for them

01:51:46.940 | and help them lose weight.

01:51:47.840 | And they lose on average eight to 12 pounds more

01:51:50.080 | doing the exact same patterns of movement.

01:51:53.200 | So, and I think that these belief effects boil down

01:51:55.440 | to all sorts of kind of network-wide neuromodulation,

01:51:58.560 | things of that sort.

01:51:59.400 | - And then the work at Harvard suggesting

01:52:01.040 | that even if you don't have deception,

01:52:03.160 | you give a placebo and say, this is a sugar pill.

01:52:05.600 | - Right.

01:52:06.440 | - You know, tell them that.

01:52:08.000 | And they could still treat things.

01:52:09.180 | I think irritable bowel was the first thing they looked at.

01:52:11.720 | - Right.

01:52:12.560 | - And so there's a huge, so there's a reality there.

01:52:14.920 | - Right.

01:52:15.960 | - There's a necessity in developing drugs

01:52:17.520 | to make sure it's not only that,

01:52:19.080 | but in the actual practice of medicine,

01:52:21.720 | hopefully what you're always getting

01:52:23.080 | is some underlying direct efficacy plus the placebo

01:52:26.800 | that it enhances at.

01:52:27.920 | Now, it could be that this is, the real question is,

01:52:31.360 | is the microdosing, are those claims 100% placebo

01:52:35.520 | or are they only part placebo and part real,

01:52:39.480 | you know, quote unquote effect.

01:52:41.240 | My bet is, and this is totally based on anecdotes

01:52:45.080 | that I think there is probably a reality

01:52:47.720 | to the antidepressant effects.

01:52:49.320 | I find that more intriguing

01:52:50.880 | because of the suffering with depression.

01:52:53.160 | - Right.

01:52:54.000 | - Even if it's, it wouldn't be as interesting

01:52:56.200 | as I think what we're doing with high dose psilocybin

01:52:59.160 | or psychedelics to treat depression.

01:53:01.760 | It would be, if this is developed and there's a reality,

01:53:04.260 | it would be more like a better, you know,

01:53:06.800 | perhaps a better SSRI, a better Prozac.

01:53:10.080 | - Which are similar.

01:53:10.920 | - That being said, we need more tools

01:53:11.760 | than fewer tools in the toolbox.

01:53:14.080 | And it shouldn't be that surprise.

01:53:15.860 | Like even before the, going back to the tricyclics

01:53:19.400 | and the MAO inhibitors going back to the fifties,

01:53:22.080 | like augmenting extracellular serotonin

01:53:25.320 | in one way or another, for many people,

01:53:28.960 | leads to a reduction in depressive symptoms.

01:53:31.320 | It wouldn't be that crazy for chronically stimulating

01:53:34.560 | a subtype of serotonin receptor

01:53:36.980 | that you have an antidepressant effect.

01:53:38.800 | So I think if I had put my bets on it,

01:53:41.260 | that there's, if there's anything real,

01:53:42.880 | it is in that category.

01:53:44.440 | Although I'm very open to like,

01:53:45.560 | maybe there is something to the creativity,

01:53:48.120 | to the, you know, improved cognition,

01:53:50.960 | which covers many domains in and of itself.

01:53:53.860 | But my greatest hopes are on the antidepressant effects.

01:53:58.860 | That said, in the big picture,

01:54:02.120 | I think all of the most interesting thing

01:54:04.160 | about psychedelics are the heroic doses.

01:54:06.560 | I mean, the idea that you can give something

01:54:08.240 | one, two, three times,

01:54:09.520 | and you see improvements in depression months later

01:54:12.840 | and in addiction, you know, over a year later.

01:54:16.280 | And with these people dealing

01:54:18.120 | with potentially terminal illness,

01:54:20.080 | I mean, I'm interested in big effects.

01:54:23.820 | And I don't think you're ever going to get

01:54:25.120 | the really big effects.

01:54:26.600 | There's also some concern

01:54:28.640 | that almost all of these common psych,

01:54:31.000 | the more common psychedelics, even counting MDMA,

01:54:34.020 | they have serotonin 2B agonist effects.

01:54:37.280 | And agonizing serotonin 2B has been shown

01:54:42.120 | to lead to heart valve formation problems,

01:54:47.120 | morphology issues, so valvulopathy.

01:54:50.600 | And so this is why Fen-Phen was pulled from the market.

01:54:53.480 | - The diet drug.

01:54:54.580 | - Yes.

01:54:55.420 | - Very effective diet drug.

01:54:56.240 | - Right, right.

01:54:57.080 | And it was the portion of that combination

01:54:59.720 | that had the serotonin 2B activity that was the problem.

01:55:04.720 | And so we don't know.

01:55:07.200 | So all of the toxicologists I've ever spoken to about this

01:55:10.960 | would say, and cardiologists say like, look, hey,

01:55:14.560 | if there was some concern there,

01:55:16.360 | it's not applicable to the whole idea

01:55:18.360 | of you taking something a few times therapeutically

01:55:20.920 | within a lifetime.

01:55:21.900 | But the idea of taking something like twice a week for years,

01:55:26.900 | I mean, even the hippies back in the '60s

01:55:31.220 | weren't doing that, right?

01:55:32.380 | Like there's not even these natural,

01:55:33.840 | and even if there was some heart valve disease problem

01:55:39.880 | that stemmed from psychedelic use,

01:55:42.680 | who's connecting those dots?

01:55:44.320 | That's not showing up in the clinical charts

01:55:46.300 | for anyone to figure out.

01:55:47.260 | So there is, and just theoretically,

01:55:49.760 | there is more of a concern.

01:55:51.960 | If something's going to happen with heart valves,

01:55:55.220 | it's more likely that those issues would arise

01:55:58.900 | when someone's taking these things like, yeah,

01:56:00.520 | let's say twice a week for the next five years.

01:56:04.200 | And so I do want to throw that out to people

01:56:05.920 | to really consider.

01:56:07.040 | - Right, yeah, it's something I hadn't heard before

01:56:08.720 | that in micro sounds safer, micro dosing

01:56:12.000 | as opposed to heroic or macro dosing.

01:56:14.240 | And yet, unless, and in the context of your lab

01:56:18.120 | and other labs doing similar work,

01:56:20.960 | you've got this people checking blood pressure,

01:56:23.360 | you've got people that are really monitoring

01:56:25.040 | your psychological and physical safety.

01:56:27.280 | When people are out there micro dosing,

01:56:28.840 | it sounds like there's the potential

01:56:30.880 | either through this serotonin 5-HT-2B receptor

01:56:35.400 | or other mechanism that maybe there could be

01:56:37.540 | some kind of cumulative negative effects.

01:56:40.080 | And I think that's a really important consideration.

01:56:44.340 | So I'm glad you brought it up.

01:56:46.240 | What about kids?

01:56:47.540 | So the brain is very plastic early in life.

01:56:50.700 | It becomes less plastic as we age,

01:56:53.440 | although it maintains some degree of plasticity

01:56:56.120 | throughout the lifespan.

01:56:57.640 | The year 25, not the year 25, but rather the age 25 years

01:57:04.400 | is sort of an inflection point where the rigidity

01:57:09.200 | of the nervous system seems to really take off.

01:57:11.620 | Of course, people don't wake up on their 25th birthday

01:57:14.060 | and find they have no neuroplasticity,

01:57:16.300 | whereas the day before they had a lot.

01:57:17.760 | These are, it's plus or minus, whatever it is, a year or two,

01:57:21.620 | but depends on the individual.

01:57:23.700 | However, the young brain is very plastic

01:57:30.660 | and I could imagine there could be great risks.

01:57:35.660 | Who knows, maybe even benefits,

01:57:37.420 | but I'm certainly not thinking about those.

01:57:40.040 | I'm mainly thinking about the risks

01:57:42.620 | for young people taking psychedelics.

01:57:46.220 | Are there any trials looking at people in clinical trials

01:57:49.960 | this would be under the age of 18?

01:57:51.300 | Has anyone explored this in a rigorous way,

01:57:54.420 | given the potential to exacerbate psychotic symptoms

01:57:57.660 | and bipolar symptoms in some people?

01:58:00.180 | Is there a heightened risk of that?

01:58:03.320 | What's the story with age of use in psychedelics

01:58:06.340 | for therapeutic purposes?

01:58:07.540 | - There's no formal research,

01:58:10.060 | although there's a very high chance that there will be.

01:58:13.080 | And so this is one of the very interesting things

01:58:14.820 | folks may not realize or appreciate

01:58:17.420 | about the FDA approval process.

01:58:19.600 | So the FDA already in multiple instances has signaled

01:58:23.260 | that they want to see those studies.

01:58:25.900 | - Before?

01:58:26.860 | - Well, not before it's approved as necessarily

01:58:29.940 | as for adults, but they're going to eventually want to see

01:58:34.340 | in fact, so the MAPS group that's developing MDMA for PTSD,

01:58:38.260 | they've already signaled

01:58:41.460 | that that's kind of on the list of interest.

01:58:44.900 | And there's even some incentives in the FDA pathways

01:58:49.900 | for incentivizing folks to explore that use in young people.

01:58:55.840 | I know in some of the work that I helped with

01:58:57.840 | in pushing psilocybin into phase 2B clinical research,

01:59:02.840 | the FDA said, "Well, why can't you give this to kids?"

01:59:09.580 | It's like, are you aware that depression is a problem

01:59:13.400 | with adolescents?

01:59:15.400 | And it's really interesting

01:59:18.340 | because this FDA is very concerned about pseudospecificity.

01:59:23.100 | - Where do you define pseudospecificity?

01:59:24.860 | - You put out a drug and say,

01:59:25.980 | "Oh, this is good for men, but not women.

01:59:28.860 | This is good for black folks, but not white folks."

01:59:31.620 | And now sometimes there's a very good rationale for that.

01:59:34.680 | Like when we're talking about hormones

01:59:36.740 | and for a specific, for men versus women,

01:59:40.500 | and there's certain issues,

01:59:43.700 | certain disease states like maybe sickle cell anemia

01:59:47.800 | that's more relevant.

01:59:48.640 | - Taste hacks, things like that.

01:59:49.480 | - Yeah, exactly.

01:59:51.000 | But absent of something that they're very concerned

01:59:53.940 | about saying, "Oh, this is for this type of person,

01:59:56.740 | but not that type of person."

01:59:57.980 | So age is one of those things.

01:59:59.580 | And also this recognition,

02:00:01.880 | much like the emphasis at NIH with rodent studies

02:00:06.380 | and human studies that like,

02:00:07.300 | you can't just say you're studying men

02:00:08.800 | or just you need a rationale if you're only-

02:00:11.720 | - Yeah, to be clear to people, it's a recent switch,

02:00:15.340 | but there's a stipulation in every federally funded grant

02:00:19.820 | that both sexes, we don't refer to gender

02:00:22.820 | in scientific studies, unless it's a study of gender per se,

02:00:26.460 | we refer to sex, meaning biological sex.

02:00:28.880 | So that there's a stipulation that in order to receive

02:00:32.180 | and continue to receive funding,

02:00:33.460 | you have to do studies on both males and females

02:00:37.680 | of that species, including humans.

02:00:39.860 | - And at least even if you're not powered for it,

02:00:42.020 | at least looking at that in exploratory analysis,

02:00:44.660 | like as a grant reviewer, I'm charged with looking at,

02:00:48.260 | did they address like sex

02:00:49.720 | as a biologically relevant variable?

02:00:51.780 | - Right, does the same drug have different effects

02:00:55.420 | in males versus females?

02:00:56.740 | - Right, and you can at least look at the trends,

02:00:58.700 | even again, if you're under power

02:01:00.100 | to look at those between subject type effects.

02:01:02.940 | - Which is a great shift that didn't exist in 10 years ago.

02:01:07.120 | Sounds like we're both on grants panels.

02:01:10.500 | As study section members, you didn't have to do that.

02:01:12.500 | Now it's an important biological variable.

02:01:14.580 | If you don't look at that,

02:01:16.180 | you essentially won't get your funding.

02:01:18.600 | - And age is a similar thing.

02:01:19.960 | So it's the whole idea like,

02:01:21.180 | man, if something could help kids, like what's the rationale?

02:01:23.960 | So I think there's going to be,

02:01:24.960 | now obviously you're going to have in those studies,

02:01:28.420 | at least just as much, probably more,

02:01:31.020 | it should be more of a cautionary approach.

02:01:34.740 | It's probably going to be,

02:01:36.040 | would certainly whatever disease states are looked at

02:01:39.260 | are going to have to be probably treatment resistant,

02:01:41.340 | at least as a first step.

02:01:42.620 | - Suicidal depression.

02:01:44.080 | - Yeah, yeah, and so all of that in the mix,

02:01:46.660 | but hey, if this stuff really helps people,

02:01:51.500 | that are 25 or 30,

02:01:54.500 | what's the rationale that it won't help a younger person?

02:01:57.980 | And there's these generic kind of concerns

02:02:00.100 | about the developing nervous system

02:02:02.720 | is more susceptible to problem.

02:02:05.300 | I mean, it cuts both ways,

02:02:06.460 | 'cause it's also more plastic generally and adaptable,

02:02:10.060 | maybe resilient to injury in certain ways.

02:02:12.700 | But you hear the rhetoric about kids, their brains and drugs

02:02:16.280 | and it's like the developing brain is a special concern.

02:02:20.460 | So yeah, but I think we're going to be

02:02:22.140 | seeing research eventually.

02:02:23.800 | - That's interesting.

02:02:24.720 | I went to the high school that is infamous,

02:02:29.320 | sadly, Gunn High School, for having the highest degree,

02:02:33.340 | at least at one point, of suicide rate.

02:02:36.080 | - Wow.

02:02:36.920 | - And a very large number of suicides.

02:02:39.020 | This was written up in the Times and elsewhere.

02:02:41.440 | - Is it a very academically successful school?

02:02:44.020 | - It's a very academically- - So there's a lot

02:02:44.860 | of high pressure, kinda, yeah. - Yeah, very academically

02:02:46.960 | demanding school to the point where they've restricted,

02:02:50.220 | the kids will meet often at 6.30 a.m.

02:02:53.040 | or 6 a.m. before school for study groups

02:02:55.200 | and things of that sort.

02:02:56.400 | So some of it may relate to that.

02:02:58.640 | But I have to say that even prior

02:03:00.160 | to all that academic pressure,

02:03:03.240 | when I went there, the pressure wasn't like that.

02:03:06.680 | You know, we had an unusual number of suicides

02:03:10.660 | for whatever reason.

02:03:11.800 | And so the idea of kids being prescribed

02:03:17.180 | and I want to emphasize prescribed, not just using,

02:03:19.340 | but prescribed psychedelics for therapeutic purposes,

02:03:22.120 | I think might make some people bulk,

02:03:24.580 | but the idea of kids killing themselves

02:03:29.460 | should also make people bulk.

02:03:30.780 | And so I'm relieved to hear that there's going to be

02:03:34.180 | a rational, scientific, safe,

02:03:37.380 | clinical trial-based exploration of this.

02:03:40.020 | I want to ask you about the current status

02:03:45.380 | of these drugs and compounds.

02:03:47.000 | I'm pretty active on social media,

02:03:51.280 | more so on Instagram than on Twitter.

02:03:53.280 | But as I have been on Twitter a little bit more recently,

02:03:57.280 | I've noticed that there's a lot of dialogue

02:04:00.700 | around your account and other people's accounts

02:04:02.560 | around a couple of themes related to psychedelics.

02:04:04.760 | First of all, what is the status of the transition

02:04:08.440 | to legality for prescription purposes?

02:04:11.960 | So medical doctors, MDs prescribing it legally

02:04:15.940 | for therapeutic purposes.

02:04:17.960 | That's the first question.

02:04:19.040 | The second question is what is the status

02:04:22.080 | as it relates to possession and criminal charges?

02:04:25.560 | So for a long time, I lived in Oakland

02:04:28.720 | where we were one day told not too long ago,

02:04:32.060 | it is now quote unquote decriminalized is what I was told.

02:04:35.200 | I double checked people, but what does that mean?

02:04:38.840 | And then the other issue and the third question,

02:04:41.760 | and we can parse these one by one,

02:04:43.480 | is this issue of let's just say I'm aware

02:04:46.980 | of a lot of investor dollars going into companies

02:04:50.360 | that are essentially companies focused on psychedelics

02:04:55.360 | as therapeutics or psychedelics generally.

02:04:58.800 | I have to assume that they are investing

02:05:01.040 | in anticipation of a shift in the legal status.

02:05:04.100 | And there's a lot of interest now,

02:05:07.640 | like will psilocybin become a taxable thing

02:05:11.480 | just like marijuana?

02:05:12.400 | So let's start with the question of like,

02:05:14.360 | what is going on in the US legally?

02:05:18.080 | Is it illegal to possess and sell and use these compounds?

02:05:23.080 | My understanding is you can still go to jail

02:05:26.520 | for having these compounds in your possession

02:05:30.280 | or for selling.

02:05:31.120 | - Right, so even though the legal landscape

02:05:35.580 | is very different than with cannabis,

02:05:38.280 | there are some similarities.

02:05:39.700 | So one of the similarities is that regardless

02:05:42.080 | of what local municipal, whether city or state

02:05:45.800 | has decriminalized, and that word itself

02:05:49.420 | can mean many things.

02:05:50.580 | So some forms of decriminalization is close

02:05:54.240 | to what folks would call legalization

02:05:56.820 | and others are like pretty weak, just saying,

02:05:59.720 | we suggest that the police make

02:06:02.040 | it their lowest law enforcement priority,

02:06:03.860 | that type of thing.

02:06:04.700 | - Turn the other cheek kind of thing.

02:06:06.400 | - Right, but even the cops can still choose to.

02:06:09.200 | - But someone could get pulled over for one thing,

02:06:11.740 | searched and then by definition,

02:06:13.720 | if it's illegal and they find it,

02:06:15.320 | then they have to do something about it.

02:06:17.960 | - And that'll probably be determined

02:06:19.560 | by both judicial precedent, is it going to be thrown out

02:06:23.600 | and just the local prosecutor, even before,

02:06:26.440 | like are they going to choose even at post arrest

02:06:28.560 | are going to pursue to really go after those charges,

02:06:31.940 | make those charges stick.

02:06:33.700 | So I think that's still in play

02:06:34.920 | and it's going to depend on the municipality,

02:06:36.420 | but like cannabis, federally,

02:06:38.960 | these are all schedule one compounds.

02:06:40.640 | - Which means they're illegal.

02:06:41.840 | - Which means they're illegal.

02:06:43.880 | The caveat to that, just as has always been the case

02:06:46.140 | since Prop 215 in California with cannabis in '96,

02:06:49.360 | is that, hey, 99% of drug enforcement

02:06:54.160 | is done at the local and state level.

02:06:55.720 | The DEA, which is the federal level of law enforcement

02:06:59.600 | is a tiny fraction of the arrests.

02:07:02.480 | They got, I mean, most people that arrested for any drug

02:07:04.860 | are done by local or state level authorities,

02:07:09.860 | but it's still technically illegal.

02:07:13.180 | And so you can, and they could potentially,

02:07:15.980 | and depending on the ambiguity of the local law,

02:07:18.420 | even those local officials could charge you

02:07:20.140 | with a federal crime.

02:07:21.800 | And theoretically, the feds could always come in.

02:07:27.100 | Now, although you'll, again, a similar case

02:07:30.980 | with the whole cannabis history,

02:07:33.380 | it was the, the feds came in in the early days,

02:07:36.960 | but the folks that were basically highly visible,

02:07:39.840 | they went after Tommy Chong for selling bongs.

02:07:42.620 | But I remember him being on "The Tonight Show" one time,

02:07:45.400 | and I think it was back in the Jay Leno days,

02:07:47.320 | he says, "But oh, along the Santa Monica boardwalk,

02:07:50.220 | like every shop sells bongs.

02:07:51.580 | How did you go to prison for a half year for bongs?"

02:07:53.720 | It's 'cause he was, and there-

02:07:55.220 | - 'Cause he was famous.

02:07:56.060 | - 'Cause he was, you know, Tommy Chong.

02:07:57.820 | And there were some high profile cannabis groups

02:08:02.340 | that were distributing it and they were very vocal.

02:08:04.500 | Those were the ones raided by the DEA in the early days,

02:08:06.900 | not the ones kind of keeping to themselves,

02:08:08.920 | keeping it quiet and just doing their thing.

02:08:10.540 | So there's always the potential for selective enforcement.

02:08:14.600 | And so, you know, in like this initiative in Oregon,

02:08:17.260 | which is a state level legalization of psilocybin therapy,

02:08:22.260 | which is really interesting, you know,

02:08:24.140 | part of their plan for two years is to figure out

02:08:26.620 | how to integrate with the federal level.

02:08:30.300 | And I don't know how that's gonna go

02:08:32.100 | because like, unless you rewrite

02:08:34.420 | the Controlled Substances Act,

02:08:36.020 | it seems like the best you're gonna get

02:08:37.460 | is a tolerance from the federal government.

02:08:40.900 | And you know, and that could be very, you know,

02:08:45.580 | hey, you change administrations.

02:08:48.020 | - And this is psilocybin by a prescription

02:08:51.020 | from a medical doctor, or you're talking about therapists

02:08:54.460 | who have master's degrees or PhDs

02:08:58.780 | or self-appointed coaches or something like that.

02:09:01.980 | Administering psilocybin, but without any oversight.

02:09:06.740 | - So this is all getting figured out in the Oregon case.

02:09:09.500 | And again, there's that two year period of like,

02:09:11.480 | basically we're gonna figure this out.

02:09:13.100 | And so-- - What is it with Oregon?

02:09:14.780 | - They're ahead with a lot of, you know, euthanasia.

02:09:18.220 | - I love the state of Oregon.

02:09:19.580 | But it's interesting how you have these pockets.

02:09:22.520 | Oregon, Vermont seems to be one.

02:09:24.720 | You know, you've got these kind of pockets

02:09:26.560 | where people are experimental with plant compounds.

02:09:30.720 | They seem to be green, woodsy areas, at least in my mind.

02:09:34.320 | But there's sort of a culture around plants

02:09:37.120 | and the use of plants as therapeutics.

02:09:39.240 | - And combine that with the West,

02:09:41.040 | just more geographically of more of the anti-federalism,

02:09:46.040 | the anti, I mean, the Oregon ranchers from several years ago

02:09:49.580 | that held up the, you know, the whatever wildlife place,

02:09:53.820 | you know, and that was a big showdown with the feds,

02:09:55.780 | you know, and the, you know, just kind of the West

02:09:59.040 | is kind of known for, you know, more of those issues.

02:10:02.280 | So you combine the two,

02:10:03.500 | the hippie-dippie California-Oregon vibe

02:10:05.720 | with the kind of anti-- - Yeah, although I wouldn't

02:10:06.560 | think it's becoming less hippie-dippie than,

02:10:09.920 | although it was, there's always been a tradition,

02:10:13.160 | not just in the culture around drugs,

02:10:15.440 | but certainly in academia and in tech, et cetera,

02:10:18.400 | that the West has been a place where people have tried

02:10:22.720 | to throw off traditionalism and kind of lineage

02:10:27.280 | and like who your parents are, what school you went to,

02:10:30.240 | and the past as a determinant of what's next

02:10:35.000 | and exciting about the future.

02:10:36.720 | Whereas, and here we are an East Coast institution guy

02:10:39.680 | and a West Coast institution guy,

02:10:41.320 | I think that it's this idea of kind of innovation

02:10:46.120 | and the future versus do we stay grounded

02:10:49.120 | in history and tradition? - Right.

02:10:51.600 | - And of course there are great institutions on both sides.

02:10:53.860 | What's interesting is that Hopkins, Johns Hopkins Medical

02:10:57.620 | School, I think of as a real East Coast academic institution,

02:11:02.020 | it is on the East Coast, but here you are doing these very

02:11:07.020 | pioneering and important and exploratory studies

02:11:12.300 | in a, certainly not a hippie-dippie environment.

02:11:14.960 | - Right, oh yeah, very conservative psychiatry department,

02:11:18.000 | even amongst psychiatry departments.

02:11:19.580 | And as a psychologist in the psychiatry department,

02:11:21.940 | psychiatry is certainly more conservative than psychology,

02:11:25.160 | even within academics, but even amongst psychiatry

02:11:27.640 | departments, it's a very conservative department.

02:11:30.700 | - So we've got the law at the federal level,

02:11:32.960 | we've got the law at the state and local level,

02:11:35.800 | and then we've got this question of whether or not

02:11:38.240 | it's going to be physicians, so MDs, people with PhDs

02:11:43.240 | or master's degrees, or whether or not it will be

02:11:45.140 | kind of a free-for-all for consumption.

02:11:48.760 | - The life coaches. - The life coaches

02:11:50.560 | and the general public, I mean, cannabis,

02:11:53.600 | I'm not a pot smoker, it's never appealed to me,

02:11:57.640 | that's just me and my pharmacology, but you can buy cannabis

02:12:02.640 | most places in the US without a ton of risk, it seems, right?

02:12:08.840 | Are we going to see a time in which you can essentially

02:12:13.980 | go into a shop on Abbot Kinney Boulevard in Venice,

02:12:18.400 | California, and right now you can go buy marijuana

02:12:21.580 | if you have a marijuana carta, that's my understanding.

02:12:24.200 | I see a lot of people going in and out of these stores.

02:12:27.100 | The police certainly have no problem with it.

02:12:28.840 | Is there going to come a time where people

02:12:30.360 | can just go buy psilocybin?

02:12:32.680 | Do you think- - Like they do in Amsterdam

02:12:34.280 | and have for a long time. - Do you think

02:12:35.120 | that time is coming?

02:12:36.260 | - I think so, at a certain point,

02:12:42.920 | and I don't know how long.

02:12:46.500 | It's hard to imagine our current level

02:12:51.500 | of drug criminalization holding up for,

02:12:57.080 | and I'm thinking like large spans of time,

02:12:58.940 | like really in a hundred years,

02:13:00.360 | are we going to be doing this 500 years?

02:13:02.200 | Like how could that, it's not going to be sustainable.

02:13:04.580 | - But in five years, for instance.

02:13:06.140 | - So I don't think so in the United States.

02:13:09.720 | I do think eventually you're going to see something

02:13:13.280 | like that 'cause there's going to be no way,

02:13:15.080 | and I think we're going to,

02:13:16.640 | I hope that we're going to eventually come so strongly,

02:13:21.420 | we're going to move on from this model of criminalizing drugs

02:13:25.500 | that we're really going to focus on regulating drugs

02:13:28.140 | at the right level for that drug.

02:13:29.580 | And I like the word regulation better than legalization.

02:13:33.260 | So, I mean, I could imagine what one day regulation,

02:13:36.660 | smart regulation might mean for psychedelics.

02:13:38.960 | Maybe it could mean that there will be,

02:13:41.620 | whether or not you have a diagnosis of a problem,

02:13:44.760 | it may be that even for personal exploration,

02:13:46.980 | you can do this legally,

02:13:48.560 | but you first have to maybe take a court, get a drive,

02:13:51.380 | and this has been, I'm not the first to say this,

02:13:52.940 | but get equivalent of a driver's license.

02:13:55.160 | You have to go to get some sort of training.

02:13:58.000 | Maybe your first number of experiences

02:14:00.660 | need to be with trained guides who can facilitate it.

02:14:05.020 | And then the public health information for anyone using this

02:14:08.060 | that this is what riskier use is.

02:14:10.720 | All use is going to have risk.

02:14:12.000 | This is what riskier use is.

02:14:13.240 | This is less risky use.

02:14:14.660 | These are the factors.

02:14:16.160 | So I think eventually we're going to be getting for any,

02:14:18.060 | but I would say the same thing

02:14:19.240 | for like methamphetamine and heroin and cocaine,

02:14:23.920 | like all of these drugs,

02:14:24.760 | it's hard to imagine the current approach

02:14:27.080 | of just feeding a black market

02:14:29.520 | and really exacerbating a lot of the harms from drugs.

02:14:32.840 | You know, that happens under the current model.

02:14:36.400 | It's hard to imagine that maintaining.

02:14:38.080 | That isn't to say, I think it should be

02:14:40.720 | in all of the 7-Elevens, you know,

02:14:42.520 | sold to kids at the other extreme,

02:14:45.700 | but I do think it's probably not going to be soon

02:14:48.180 | in the United States.

02:14:50.060 | I do want to make the major point

02:14:51.660 | that even if psychedelics had never been made illegal,

02:14:55.300 | I think the trajectory of the medical research right now

02:14:59.000 | would still need to happen.

02:15:00.700 | If it's effective as an antidepressant,

02:15:03.860 | like we need it to be, you know,

02:15:06.860 | there's all the evidence suggesting

02:15:08.780 | that whatever disorder we're talking about,

02:15:10.500 | the efficacy is going to be increased

02:15:12.180 | and the risks are going to be mitigated drastically

02:15:15.980 | in the types of models we're talking about

02:15:18.080 | with the screening, with the preparation,

02:15:20.460 | with the integration of cognitive behavioral therapy

02:15:22.700 | or what have you,

02:15:23.540 | depending on the disorder you're treating,

02:15:25.420 | with the integration afterwards with the professionals.

02:15:28.500 | So we would be doing it anyway.

02:15:32.580 | So it's not like this versus that.

02:15:34.360 | So I don't see it as a race between the decriminalization

02:15:37.060 | or legalization of these compounds

02:15:38.840 | versus their medical development.

02:15:40.360 | Some people who are psychedelic fans

02:15:42.120 | get all into a bunch about the medical development.

02:15:47.400 | They say, you guys want to like,

02:15:49.200 | you want to keep it only for, you know,

02:15:51.960 | for your medical research and I retire

02:15:54.040 | and you want to be in control of it as academics.

02:15:57.400 | And my take is I didn't make it illegal for anyone.

02:16:00.840 | We're only moving the needle in one direction.

02:16:03.380 | And again, even if it was already illegal,

02:16:05.680 | and I've done plenty of survey research of people reporting,

02:16:09.200 | they took mushrooms for fun or for personal exploration.

02:16:12.240 | And they said, my God, why am I smoking?

02:16:14.840 | And they quit smoking 20 years because of it,

02:16:16.760 | or it's helped with their depression

02:16:18.300 | or it's helped with them overcoming alcoholism

02:16:20.340 | or these different, sometimes that happens out of the blue

02:16:22.960 | when people use psychedelics.

02:16:24.640 | Nonetheless, obviously the efficacy rates

02:16:27.720 | are going to be higher when you bring it

02:16:29.260 | into these medical models and it's going to be safer.

02:16:31.860 | So we're going to, you know, so we need to be pushing that.

02:16:34.880 | And my best guess is that MDMA is going to be approved

02:16:38.300 | within the next three years.

02:16:39.820 | - And for prescription by a physician.

02:16:42.040 | - Yes, in, and not just, you know,

02:16:44.480 | take two and call me in the morning,

02:16:46.160 | but in the clinics,

02:16:47.200 | the way that those PTSD trials are being run.

02:16:50.080 | So the MDMA would be approved for PTSD

02:16:52.800 | and every disorder needs to be looked at separately.

02:16:55.100 | And it's going to only be approved for those things.

02:16:56.900 | Now there's going to be questions about-

02:16:58.740 | - Right, because approved and legalized and regulated,

02:17:00.340 | or, you know, now we're getting into the nuance.

02:17:02.600 | I think when people hear it's going to be approved

02:17:04.400 | in two years, they think that they'll be able to buy

02:17:07.540 | and sell and use MDMA without legal consequences.

02:17:10.000 | And I do not think that's going to be the situation.

02:17:12.480 | It's not the way it is.

02:17:13.480 | And I will say that I think the quote unquote

02:17:18.300 | psychedelic community, I mean,

02:17:20.120 | they've been doing what they want to

02:17:21.840 | and will carry on doing what they want to anyway, right?

02:17:25.840 | It's not like the legal status has prevented them

02:17:29.160 | from doing what they're doing.

02:17:30.800 | In fact, unlike Leary and Timothy Leary and Huxley

02:17:35.840 | and some of the others that were very vocal

02:17:38.720 | and lost their jobs and some who even went to jail, et cetera.

02:17:41.900 | I mean, you've got a lot of public figures now

02:17:43.980 | like McKenna and others who are just basically

02:17:45.740 | out there talking about psychedelics.

02:17:47.980 | Michael Pollan, who is more of a writer,

02:17:50.140 | foodie guy gone psychedelic dabbler, writer guy.

02:17:53.460 | I know he's kind of a polymath, but you know,

02:17:57.820 | the legal status didn't seem to hinder their,

02:18:01.840 | at least online career.

02:18:02.900 | So I don't know, I haven't looked at their bank accounts,

02:18:05.260 | but I'm imagining they're doing just fine, right?

02:18:08.060 | So the fact that the work is happening

02:18:10.220 | inside of big institutions,

02:18:12.760 | I think it's important that you point out,

02:18:14.820 | and I'm just trying to underscore that that's in no way

02:18:19.020 | antagonistic to what people are doing.

02:18:20.880 | It's in support of a different sort of mission,

02:18:23.800 | which is to explore the validity in different contexts

02:18:26.780 | in a really controlled way, which I really, you know,

02:18:31.060 | I think it's a really important mission.

02:18:34.900 | I want to make sure that I ask you about

02:18:36.660 | the other really important mission that you're involved in

02:18:39.340 | with respect to psychedelics,

02:18:40.540 | which is not about depression per se,

02:18:43.680 | but is about a neurologic injury or head injury.

02:18:47.740 | I realize it's early days for this,

02:18:49.460 | but I think there's a lot of concussion out there, sadly.

02:18:54.220 | There's a lot of TBI, traumatic brain injury,

02:18:57.020 | not just from sports.

02:18:58.060 | I think people sometimes forget that it's not,

02:19:00.380 | the major source of traumatic head injury is not football.

02:19:04.260 | It's not hockey.

02:19:05.300 | It's not boxing.

02:19:06.980 | It's not any of that stuff.

02:19:08.520 | It's construction workers and it's people.

02:19:10.900 | I mean, if you've ever seen the helmets

02:19:12.180 | that construction workers wear, I mean-

02:19:14.060 | - The jackhammer, oh my God.

02:19:15.620 | - The jackhammer.

02:19:16.460 | - How could that not be just like-

02:19:17.660 | - I have a colleague that works on this in bioengineering.

02:19:19.820 | And when you look at the, you know, we always think sports,

02:19:22.660 | but there are many people who make a living

02:19:25.860 | in a way that is over time is detrimental to their brain.

02:19:30.100 | And they don't have the option of just not being

02:19:32.320 | a professional athlete or something of that sort.

02:19:34.920 | - And if they're not doing the construction,

02:19:36.760 | someone else needs to do it.

02:19:37.600 | - Someone else has to do it, right.

02:19:39.000 | And we forget, for some reason,

02:19:41.120 | and I too, it didn't occur to me until I heard it,

02:19:43.300 | like the people who were doing construction

02:19:45.500 | and then of course with bike accidents and falls

02:19:48.340 | and things like that as well.

02:19:49.720 | - Military.

02:19:50.560 | - Military, absolutely.

02:19:52.320 | So what do you think is the potential for these compounds,

02:19:57.320 | particularly psilocybin, but other compounds as well

02:20:01.040 | for the treatment and possible even reversal

02:20:04.940 | of neurological injuries and what sorts of things

02:20:08.540 | are you excited to do in that realm?

02:20:10.260 | - Yeah, so this is definitely on the more exploratory end.

02:20:13.140 | So it's based upon, so, you know, this is sort of

02:20:17.020 | beyond the improvement of psychiatric disorders

02:20:21.220 | like depression or depression and anxiety

02:20:25.740 | associated with a terminal illness

02:20:28.860 | or a substance use disorder, the addiction.

02:20:31.280 | So those are sort of psychiatric disorders.

02:20:34.900 | So this is, you know, there are anecdotes of people saying

02:20:39.900 | that psychedelics have helped heal their brain.

02:20:47.240 | You know, they've been in one of these situations,

02:20:49.480 | like in sports, a sport where there's repetitive head impact

02:20:53.560 | and they're claiming that using psychedelics

02:20:56.940 | has actually improved their cognitive function,

02:20:59.740 | for example, improved their memory,

02:21:02.200 | including improved their mood,

02:21:05.340 | but it's kind of more of the, you know,

02:21:08.260 | the cognitive function, things like memory are...

02:21:11.880 | Now, the caveat is if you've successfully

02:21:14.720 | improved someone's depression,

02:21:15.920 | you can get some cognitive improvement too,

02:21:18.200 | but that's a more of a weaker, more indirect effect.

02:21:21.660 | But if you take these anecdotes and you combine it

02:21:24.720 | way across orders of analysis to the rodent research

02:21:28.480 | from several labs like David Olson, Brian Roth,

02:21:32.800 | these folks that have shown different forms

02:21:35.220 | of neuroplasticity unfolding after,

02:21:38.160 | like sort of post-acutely.

02:21:41.960 | So after, in the days following the administration

02:21:44.440 | of psychedelic compounds,

02:21:46.680 | a variety of psychedelic compounds,

02:21:48.640 | and even some non-psychedelic structural analogs

02:21:52.860 | that you see these different forms of neuroplasticity.

02:21:56.760 | So the growth of dendrites and new connections

02:22:00.380 | being formed with different neurons.

02:22:02.960 | So those effects may be at play

02:22:07.960 | and they improve in the psychiatric treatments

02:22:11.580 | that we're dealing with.

02:22:13.320 | We don't know that, it seems like a decent guess,

02:22:15.660 | and we're going to be figuring out whether that's the case.

02:22:18.340 | But another potential that that sets up

02:22:20.660 | is that maybe that's what's going on with these claims

02:22:24.540 | of improvements from neurological issues,

02:22:31.120 | that there's actually a repair of the brain

02:22:36.120 | from injuries underlying things that,

02:22:41.920 | situations where there's repetitive head impact,

02:22:44.220 | perhaps there's a potential for helping folks recover

02:22:47.280 | from stroke and disorders like that.

02:22:50.700 | There's a wide variety of disorders.

02:22:53.660 | Now, it's a bit of magic and a bit of like,

02:22:56.700 | it's something that the enthusiasts kind of

02:22:59.100 | can do some hand-waving and claim that this is already known.

02:23:02.140 | It is more exploratory.

02:23:04.120 | But what I'm hoping to do is some work with retired athletes

02:23:07.620 | who have been exposed, but by the nature of their sport,

02:23:12.640 | for example, NNA athletes in the UFC,

02:23:15.680 | who have been exposed to repetitive head impacts

02:23:18.920 | like a lot of sports, a lot of sports expose people to,

02:23:23.920 | and who are retired from the sport

02:23:26.100 | and are suffering from say depression,

02:23:28.920 | which can impart result from those types

02:23:32.880 | of that history of head impact.

02:23:36.060 | See if we can fix the depression,

02:23:39.460 | but then also as a cherry on top

02:23:41.740 | and a more exploratory aim,

02:23:44.060 | see if we can have evidence of improvement

02:23:47.580 | in cognitive function and associate like using MRI,

02:23:50.780 | see if it affects gray matter over time,

02:23:53.120 | these types of things to see if there are actually

02:23:54.980 | some evidence of this improved,

02:23:56.840 | like this more direct repair of the brain.

02:24:01.440 | But again, it is very sort of like,

02:24:04.060 | we've got some rodent data,

02:24:05.340 | we've got some human anecdotes.

02:24:07.140 | - We will acknowledge its early days

02:24:11.020 | and we look forward to seeing the data.

02:24:14.100 | I appreciate how cautious you are and tentative you are,

02:24:17.220 | you're not drawing any conclusions.

02:24:19.020 | I think from a purely logical

02:24:23.420 | and somewhat mechanistic perspective,

02:24:26.220 | I mean, if we assume that lack of ability to focus

02:24:29.740 | or degradation and mood is the reflection

02:24:34.260 | of neurons in the brain, I think we can agree on that.

02:24:36.900 | Some dialogue between neurons in the brain

02:24:39.580 | and that what needs to be changed

02:24:41.060 | is the nature of that dialogue, aka neuroplasticity.

02:24:44.940 | We know that reordering of neural circuitry

02:24:47.820 | in the adult requires these things like intense focus

02:24:51.740 | followed by rest, et cetera.

02:24:52.980 | But the basis for that, like beneath focus is the mechanism,

02:24:56.820 | is a mechanism rather,

02:24:58.700 | beneath the bin that we call deep rest is a mechanism

02:25:01.820 | and those mechanisms are neuromodulator driven.

02:25:05.660 | So to me, I'm not reviewing your grant,

02:25:09.840 | but from a rational perspective,

02:25:13.380 | it seems that drugs that increase certain neuromodulators

02:25:17.620 | like serotonin or dopamine in a controlled way,

02:25:21.720 | and then coupling that with learning of some sort,

02:25:25.500 | sensory input of some sort,

02:25:27.120 | it makes sense that that would lead to,

02:25:31.020 | could, I should say, lead to reordering of circuitry

02:25:33.660 | that would allow for better thinking, better mood,

02:25:37.300 | many of the same things that you've observed

02:25:40.000 | in the clinical trials for depression.

02:25:42.500 | So the rationale is really strong.

02:25:44.780 | I think that's a very exciting area.

02:25:47.180 | I get asked all the time about TBI

02:25:48.900 | and traumatic brain injury.

02:25:50.020 | And right now, it's kind of,

02:25:52.940 | there isn't a whole lot that people can do

02:25:56.180 | and people are dabbling in the space of hyperbaric chambers

02:25:59.820 | and people will do sauna and breath work

02:26:02.380 | and people are kind of clipping at the margins

02:26:05.180 | of what really is a problem that resides deep to the skull.

02:26:08.220 | So I think, I just want to applaud the exploration.

02:26:11.960 | I think it's great provided that exploration

02:26:13.940 | is being done in a controlled way.

02:26:15.260 | It sounds like that's what you're doing with the UFC.

02:26:18.980 | - Yeah, so that, they were really gracious

02:26:22.540 | and had myself and a few of my colleagues

02:26:25.140 | out to their headquarters in Vegas.

02:26:26.860 | - Impressive place, right?

02:26:28.020 | - It's in process.

02:26:29.660 | There's a dialogue going on there.

02:26:31.100 | I'm hopeful that there's going to be some work with them,

02:26:34.700 | but it's in process now in terms of exploring it.

02:26:37.540 | There's a real interest and I'm just really impressed

02:26:40.740 | by the organization and their commitment

02:26:42.620 | to athlete health and we'll see.

02:26:46.420 | - Yeah, I am too.

02:26:47.260 | We have a colleague out there,

02:26:51.220 | we're doing a little bit of work with them, Duncan French,

02:26:53.100 | who's a serious academic in his own right.

02:26:55.020 | And I think when people hear UFC,

02:26:56.500 | they just think about the octagon and fighting

02:26:58.920 | and pay-per-view fights and things.

02:27:00.580 | But in talking with them,

02:27:02.080 | and I'm sure you've had these discussions as well,

02:27:04.780 | they are very much interested in the health

02:27:06.700 | and longevity of their fighters.

02:27:08.900 | They are also interested in the health and longevity

02:27:11.800 | of their fighters being a template

02:27:13.260 | for how to treat traumatic brain injury

02:27:15.420 | and improve human performance in other sports

02:27:18.020 | and in the general public.

02:27:19.660 | And I think it's not an image of the UFC

02:27:22.300 | that is commonly comes to mind

02:27:23.900 | 'cause they haven't been particularly verbal

02:27:27.620 | about it in the press, but I think it's great

02:27:29.140 | they're bringing in academics, I mean, geeks like us

02:27:31.620 | going out to the UFC Performance Center.

02:27:33.920 | I mean, you do MMA, but I'm basically just a geek

02:27:36.240 | walking through the place.

02:27:37.380 | But the fact that they're interested in talking

02:27:38.920 | to scientists is really, I'm biased here,

02:27:42.180 | but a point in their favor.

02:27:43.720 | Along the lines of other groups and individuals

02:27:47.860 | that have impacted the space that you're working in

02:27:50.220 | in this pioneering of the psychedelic space,

02:27:53.040 | a few years ago, I think if someone submitted a grant

02:27:57.540 | saying I want to study how psilocybin

02:28:01.440 | impacts human depression, I'm guessing,

02:28:04.660 | having worked on these panels before,

02:28:06.480 | that the response might've been closer to,

02:28:09.900 | well, we need to do a lot of studies in rodents

02:28:12.020 | and a lot of studies in primates,

02:28:13.320 | and then maybe, just maybe, we could explore these drugs

02:28:16.820 | because the National Institutes of Health

02:28:18.580 | actually has a whole institute devoted to addiction, right,

02:28:22.780 | of exploring compounds only in terms

02:28:24.840 | of their negative effects, right,

02:28:26.700 | which is where I've gotten all of my NIH funding

02:28:29.980 | over my career. - Which is so interesting,

02:28:31.140 | right, and it's a super important institute,

02:28:33.300 | I want to be clear, there are amazing people there.

02:28:35.580 | But philanthropy and foundations have been very important

02:28:40.580 | in supporting pioneering research.

02:28:43.140 | And so maybe we just talk a little bit about that.

02:28:46.820 | So your lab receives funding from taxpayer dollars

02:28:51.100 | through the National Institutes of Health.

02:28:53.300 | Is that mainly where your funding comes from?

02:28:56.140 | - So our group has gotten some funding from,

02:29:00.900 | like, say, the National Institute on Drug Abuse, NIDA,

02:29:03.540 | for some, a small subset of the psychedelic work,

02:29:06.860 | but only for some work geared towards understanding

02:29:11.700 | these things as drugs of abuse.

02:29:13.240 | Of course, when you do a study, though, you can--

02:29:14.700 | - Show us how they're, explore how they're bad.

02:29:17.020 | - Right, but when you're doing that,

02:29:18.460 | you can explore the good stuff, too.

02:29:23.980 | But the large majority of the work,

02:29:27.280 | and the most interesting work,

02:29:28.320 | has been funded by philanthropy.

02:29:30.180 | - Private philanthropy. - Now, I still have

02:29:32.060 | some grant support from NIDA outside of psychedelics.

02:29:36.280 | I'm shifting more and more of my time

02:29:41.180 | towards focusing only on psychedelics,

02:29:43.880 | and in fact, us getting the center-level funding

02:29:47.900 | from some really big-picture philanthropists

02:29:51.900 | helped me to start to make that transition.

02:29:54.820 | But groups like the Hefta Research Organization,

02:29:57.440 | Dennis McKenna, which is one of the founding members,

02:29:59.840 | the brother of Terrence McKenna,

02:30:01.260 | who is, by the way, an ethnobotanist,

02:30:02.900 | that's what his PhD is in. - What does that mean,

02:30:04.180 | ethnobotanist?

02:30:05.260 | - Studying the, essentially, the anthropology

02:30:08.380 | of psychoactive plant use, so--

02:30:12.500 | - You can get a degree in that?

02:30:13.740 | - Yeah, yeah, yeah, you know, hanging out with cultures

02:30:17.180 | and studying their use of these compounds

02:30:19.220 | in the traditional ways. - Wow, at Hopkins?

02:30:22.340 | That degree exists at Johns Hopkins?

02:30:24.140 | - I don't think that degree exists at Hopkins,

02:30:26.420 | but I mean, the kind of the most,

02:30:28.680 | and as you know from academia, I'm not,

02:30:32.620 | sometimes folks, I'm not sure how many people's PhD

02:30:35.740 | is actually in ethnobotany,

02:30:38.620 | or is actually in something else,

02:30:40.580 | but the real focus is, like,

02:30:42.180 | my degree is general experimental psychology,

02:30:45.120 | but I say human. - 10,000 kids out there

02:30:46.340 | just decided they're going to major in ethnobotany,

02:30:48.820 | but, you know, the--

02:30:49.660 | - I mean, one of the pioneers of the psychedelic area

02:30:52.340 | before Leary and before, and actually,

02:30:54.340 | he was late even for the human researchers,

02:30:56.440 | like folks like Humphrey Osmond and Abraham Hoffer

02:30:59.100 | and Sidney Cohen were earlier,

02:31:00.580 | but even before those folks, Richard Schultes at Harvard,

02:31:04.180 | he was, I mentioned him earlier in the conversation,

02:31:06.640 | discovered all of this, these various tribes

02:31:10.060 | using ayahuasca or yage, a different name

02:31:12.980 | for the same thing, throughout South America,

02:31:16.060 | and these DMT-containing snuffs and all of this.

02:31:19.100 | So, you know, that was, you know, ethnobotany,

02:31:22.180 | this kind of intersection of anthropology

02:31:25.500 | and these psychoactive plant compounds.

02:31:29.300 | So, the Hefta Research Institute,

02:31:31.900 | which Dennis is a founding and active member of,

02:31:36.820 | a board member, they have funded a lot of our early work.

02:31:41.160 | There's also an organization called the Beckley Institute,

02:31:46.520 | based in England, that Lady Amanda Fielding

02:31:50.100 | has been the head of, that has,

02:31:52.320 | they provided the first funding

02:31:54.060 | for our psilocybin smoking cessation research,

02:31:57.940 | and the Hefta came in and provided subsequent funding,

02:32:00.920 | but it's, and then there are other groups,

02:32:03.100 | a Council on Spiritual Practices,

02:32:04.960 | a great guy named Bob Jesse,

02:32:07.740 | funded some of the original work at Hopkins,

02:32:09.580 | looking at the nature of mystical experience,

02:32:11.300 | outside of treating disease states or disorders,

02:32:14.780 | but just understanding these, like,

02:32:17.960 | people take these compounds and astonishingly, you know,

02:32:22.000 | frequently we'll say that was the most important

02:32:24.160 | everything I've ever experienced.

02:32:25.460 | It's like, what the hell is that?

02:32:27.020 | - Yeah, I had someone mention recently,

02:32:28.900 | I think this might surprise people a little bit,

02:32:30.680 | certainly surprise me, I had a friend

02:32:31.960 | who adores his children.

02:32:35.280 | He's got three children, he adores his children,

02:32:38.440 | happy marriage and great, great father,

02:32:40.960 | they're both great parents, and he told me that,

02:32:43.840 | as part of a clinical trial, he had a DMT experience,

02:32:48.620 | that he claims, he said, I'd love to tell you

02:32:51.140 | that the birth of my children was as profound,

02:32:53.860 | but that was a more profound experience

02:32:55.860 | than the birth of my children,

02:32:57.620 | any one of them and all of them combined.

02:32:59.940 | And I was like, wow, now I've never done DMT,

02:33:01.520 | but I was like, wow, that's a pretty strong statement.

02:33:03.320 | Now, he did it in the context of one of these,

02:33:05.280 | you know, clinical explorations.

02:33:07.020 | I assume that was part of a legal clinical trial,

02:33:10.220 | but the, I mean, that's saying something,

02:33:13.240 | it's saying something, I mean, he's a very rational,

02:33:15.300 | very grounded guy, otherwise, but,

02:33:20.300 | so philanthropy, foundations, and then in-

02:33:23.980 | - Most recently, and so I just, I can't,

02:33:25.840 | 'cause I can't skip it, our center-

02:33:27.400 | - Oh yeah, you can't skip it, you can't skip magic.

02:33:29.500 | I see.

02:33:30.340 | - That's like, we, I mean, the Heffter group,

02:33:33.220 | the Beckley group, I mean, these are wonderful,

02:33:35.640 | I mean, these are people that have been holding

02:33:37.000 | the flame alive during the darkest hours,

02:33:38.980 | like the, same thing with the MAPS organization,

02:33:42.140 | more on the MDMA side, like holding that candle

02:33:44.760 | during the darkest years, that, you know, so we've,

02:33:47.540 | but, you know, smaller organizations connected to smaller,

02:33:51.540 | but growing over time, you know, pockets of wealth,

02:33:54.560 | but, you know, we basically limped on,

02:33:57.380 | limped along on a wing and a prayer until recently,

02:34:00.620 | when we got the $17 million gift,

02:34:03.140 | so that we could create a nominal center.

02:34:04.780 | And as you know, basically to the university,

02:34:06.680 | that means you get a certain number of dollars,

02:34:08.580 | and a lot of them, you can call yourself a center.

02:34:10.860 | You know, it's a capital investment, you know,

02:34:13.980 | staff, you know, equipment, salary support,

02:34:17.800 | which has always been the huge thing for us.

02:34:20.660 | But the $17 million gift,

02:34:22.660 | which was split between the Cohen Foundation,

02:34:26.460 | so Steven and Alexandra Cohen, and they covered half of it,

02:34:30.340 | and the other half, the Tim Ferriss collaborative,

02:34:32.940 | basically Tim and a few friends,

02:34:35.860 | ponied up that the, you know,

02:34:37.940 | divided the rest of that half of that $17 million gift,

02:34:41.820 | and came together to just, I mean,

02:34:44.340 | it just, it's completely transformed our,

02:34:46.900 | the work that we've done, and our ability to,

02:34:49.540 | like, to fully delve into this area,

02:34:53.500 | and not worry that like, oh, if I focus on this,

02:34:56.500 | rather than putting another three NIDA grants

02:34:59.060 | on some other topic that may or may not get funded,

02:35:02.100 | like if I focus too much on the psychedelics,

02:35:04.380 | am I putting my career at jeopardy?

02:35:06.060 | But like, so-

02:35:06.900 | - So you're now not only a tenured professor,

02:35:08.560 | you're also a full endowed-

02:35:11.100 | - Right, so that came a few months ago-

02:35:11.940 | - By the way, when you say somebody

02:35:13.200 | is a fully endowed professor,

02:35:15.100 | I want to be very clear what that means.

02:35:16.340 | That means that there's funding-

02:35:17.180 | - Well, it might mean all of the above, but no, I'm joking.

02:35:20.340 | - I have no knowledge of your particular situation,

02:35:23.300 | but you probably do.

02:35:26.020 | - Just kidding.

02:35:26.860 | - But sure, the,

02:35:28.140 | what we're essentially saying is that funding,

02:35:32.520 | which does not change somebody's salary level,

02:35:35.580 | I just want to be clear,

02:35:36.420 | 'cause I think the general public isn't,

02:35:38.420 | there's no reason why they would understand

02:35:40.420 | all the nuts and bolts of how this works.

02:35:42.180 | - Academia is weird.

02:35:43.020 | - Yeah, academia is weird

02:35:43.980 | because we're not talking about increasing,

02:35:46.540 | we're not talking about an endowment that,

02:35:48.340 | or philanthropy that went to increase Matt's salary.

02:35:52.180 | That's something that's set at the university level.

02:35:55.660 | It's always been said, and it is,

02:35:58.500 | at least it's still true now, which is that, you know,

02:36:00.420 | nobody goes into science for the money,

02:36:02.060 | at least not at the academic level.

02:36:05.900 | Not in academia, but allows people to devote

02:36:10.900 | more of their time and energy to these exploratory realms,

02:36:15.860 | like psychedelic research, or in the case of my lab,

02:36:18.940 | the work that we're doing with David Spiegel's lab

02:36:20.860 | on respiration, breath work, and hypnosis

02:36:23.220 | for modulating brain states.

02:36:24.900 | These are not typically areas

02:36:26.600 | that the National Institutes of Health

02:36:28.020 | and other major organizations

02:36:29.260 | have institutions set up to support.

02:36:33.140 | Now, there is an exciting initiative

02:36:35.820 | which is the NCCIH, which is Complementary Health.

02:36:38.780 | - Right, used to be NCAM.

02:36:40.740 | - Yeah, at NIH. - Yeah, they changed their name.

02:36:42.580 | - And now we're not just throwing out acronyms

02:36:44.400 | just to bat back and forth acronyms,

02:36:46.660 | but I think what we're looking, what we're seeing now

02:36:49.940 | is a movement toward science and scientists and clinicians

02:36:54.940 | and the general public and philanthropy

02:36:58.660 | being engaged in this dialogue, which says,

02:37:01.900 | okay, there are problems in the world,

02:37:04.380 | depression, head trauma, psychological trauma, PTSD, ADHD.

02:37:09.380 | These problems clearly exist.

02:37:12.920 | The solutions are going to involve behaviors

02:37:15.580 | that are going to involve nutrition, supplementation,

02:37:18.420 | social connection.

02:37:19.300 | However, there are drugs.

02:37:21.460 | There are compounds that can change the brain

02:37:23.660 | and allow the brain to change its circuitry

02:37:26.380 | through experience.

02:37:27.220 | And psychedelics are one of several others,

02:37:31.140 | but one of the powerful levers, it sounds like.

02:37:34.660 | And I just want to say that I think the reason

02:37:38.460 | I reached out to you and I'm so excited to sit down

02:37:41.140 | and chat with you is because I see very few people

02:37:46.140 | inside the halls of academia who have thrown their arms

02:37:51.160 | around this issue of psychedelics in a way

02:37:54.440 | and gone through the trouble of trying to find the funding

02:37:56.820 | to get it done, gone through the trouble

02:37:59.700 | of trying to set up clinical trials.

02:38:01.300 | I know what's involved in doing this.

02:38:02.700 | It's so complicated.

02:38:03.980 | It's so time-consuming and painstaking,

02:38:06.880 | and you've made real progress.

02:38:08.580 | I mean, you guys are publishing papers.

02:38:10.580 | There's a new dialogue emerging that isn't just books

02:38:13.620 | on bookshelves and psychonaut gurus on the internet

02:38:18.620 | who also play an important role,

02:38:21.140 | but you're really moving this field forward.

02:38:24.380 | And I know there are others as well.

02:38:25.880 | There are colleagues in England and others as well.

02:38:28.300 | We acknowledge them.

02:38:29.620 | But I just want to say personally that I'm like inspired

02:38:34.340 | and impressed by the way that you've gone about this

02:38:37.480 | and the level of rigor.

02:38:38.980 | I mean, when I ask you a question about serotonin,

02:38:41.640 | most people will just kind of kick back to me.

02:38:43.380 | Well, yeah, you got receptors and you got a ligand,

02:38:45.260 | but I mean, it's clear to me that you care about the details

02:38:49.880 | and that you care about the future of this area.

02:38:52.980 | And you also really care about these patients

02:38:55.480 | and these individuals.

02:38:56.460 | So I know I'm speaking on behalf of a ton of people now

02:39:00.280 | and in the future that don't even know

02:39:02.820 | what they're going to receive as a consequence of this.

02:39:05.240 | I just want to voice a real sincere thank you

02:39:10.240 | for that effort.

02:39:11.400 | It's like your lab and your work matters.

02:39:13.960 | And that's a really special and unique thing.

02:39:17.940 | - I appreciate that.

02:39:19.140 | I had a good colleague, in fact, shared some grant support

02:39:22.700 | under the multi-PI system years ago.

02:39:24.880 | And she actually took a job at NIH as a review officer.

02:39:29.880 | And I remember her telling me,

02:39:32.780 | and she actually left when she had multiple RO1s.

02:39:34.900 | So it's like, she didn't move to it.

02:39:35.740 | - The RO1s are kind of the bread and butter, big grants

02:39:39.500 | that every card carrying,

02:39:43.420 | it's a mark of respect in our community

02:39:45.140 | to have one or several of these, yeah.

02:39:47.340 | - Yeah, yeah.

02:39:48.180 | And it's like, you eat what you kill in academia.

02:39:50.980 | It gets to what we're talking about later.

02:39:52.220 | It's like, you don't make more money

02:39:53.860 | by pulling more grants, but you're able to pay the salary

02:39:56.900 | that like the university doesn't pay you your salary.

02:40:01.100 | It goes through them.

02:40:02.800 | - You're just able to do more work.

02:40:04.280 | - Yeah, and you're able to,

02:40:06.240 | and if you don't pull in the grants to cover your salary,

02:40:08.620 | your job can come to an end.

02:40:09.820 | Even if you're tenured at a place like Hopkins,

02:40:12.820 | they can do tricks like slowly lower your salary over these.

02:40:15.940 | - Or they just take away your space.

02:40:19.360 | - Yeah, they put you in a closet

02:40:20.940 | and give you no support for trainees

02:40:23.260 | and basically make life hell for you.

02:40:25.140 | So you can drive a cab in Baltimore

02:40:27.300 | and call yourself a full professor at Hopkins,

02:40:29.540 | truthfully, but you may have no ability

02:40:32.140 | to get anything done. - I'm sure they're out there.

02:40:33.980 | - But yeah, I remember one of the things

02:40:35.900 | this colleague said, who is successful,

02:40:38.260 | but left on top said, "I really don't know

02:40:40.660 | that I'm making a difference in the world."

02:40:42.180 | And she did some great memory research

02:40:44.900 | and connected to drugs, also connected to aging.

02:40:48.480 | But she said, "I don't feel the impact

02:40:52.700 | of what I'm doing in the real world."

02:40:54.420 | And it's unfortunately there for a lot of academe.

02:40:57.020 | What we do, it stays in the Iver Tower.

02:40:59.340 | The world is a beautiful but messed up place.

02:41:03.480 | And a lot of this doesn't disseminate

02:41:05.360 | and because of the various structures,

02:41:08.520 | the way the world is set up.

02:41:09.760 | And thankfully, because the work that our group,

02:41:14.760 | as well as a few others around the world

02:41:18.640 | over the last 20 years, it's like you do have

02:41:21.100 | an emerging psychedelic startup industry now

02:41:23.700 | with billions of dollars of investment.

02:41:25.100 | And yeah, that's gonna turn into both good and bad,

02:41:28.680 | like it's upping the ante.

02:41:30.300 | Like there's gonna be a lot of good and bad

02:41:32.100 | that comes from that, but any new technology

02:41:34.860 | is gonna result in that.

02:41:35.780 | But we've got psilocybin designated

02:41:38.420 | for two separate entities as a breakthrough therapy

02:41:41.540 | by the FDA and people may not realize.

02:41:43.720 | And MDMA is designated as a breakthrough therapy for PTSD.

02:41:48.560 | This is a really big deal.

02:41:50.000 | That's a very high, I mean, pharma companies

02:41:53.560 | would pay millions of dollars to get their new drug

02:41:57.940 | a designation like that.

02:41:59.540 | And what it means is early research is showing,

02:42:02.160 | saying it shows a high potential for treating disorders

02:42:05.080 | that don't have very good treatments.

02:42:07.240 | So we're in, we're probably, again,

02:42:10.640 | a few years away from both MDMA

02:42:12.240 | and probably a year or two after that psilocybin

02:42:14.080 | being treated for PTSD and depression respectively.

02:42:18.420 | This is, we have to wait for the phase three studies,

02:42:20.820 | but if the results hold up, even if the effect size

02:42:24.420 | is like halved of what we're seeing now,

02:42:26.900 | it's still gonna be a lot larger than what you're seeing

02:42:29.600 | with the traditional medications.

02:42:31.180 | And so it's gonna be approved if the data hold up

02:42:33.740 | and it probably will for my judgment.

02:42:36.140 | So I feel like what I'm doing is actually having

02:42:40.200 | a positive impact in the world in a way that,

02:42:43.120 | and I feel lucky that I got interested in an area

02:42:46.000 | that happens to plug into a place in the world

02:42:48.760 | where there is that opportunity,

02:42:51.460 | where some great colleagues and friends

02:42:53.800 | are focused on areas where I wish they had the opportunity

02:42:58.200 | for their work to be disseminated.

02:42:59.700 | I wish that, I mean, I was lucky to be interviewed

02:43:02.080 | on 60 Minutes because of this work.

02:43:04.400 | And I was like, oh my God, I know so many,

02:43:05.960 | there's a bit of imposter syndrome.

02:43:09.040 | Like, oh my God, I know so many scientists

02:43:11.520 | that deserve more so than me to have that level of exposure.

02:43:16.520 | But if you happen to be in that place

02:43:20.000 | where you gotta do your best to make it work,

02:43:24.920 | to take advantage of that luck

02:43:26.520 | and that intersection of the world and to push it.

02:43:29.400 | And I've been lucky, but also did take a bit of a leap

02:43:32.160 | of faith early on.

02:43:33.920 | I did have some advisors that told me like,

02:43:37.360 | you've got a really promising pedigree early on.

02:43:39.740 | Like, are you sure you want to focus much time

02:43:42.220 | on this psychedelic stuff?

02:43:43.360 | - You've embraced risk.

02:43:44.900 | I mean, I think that, I mean,

02:43:46.440 | the world's changed since in 2020, certainly,

02:43:50.080 | but channels like social media, podcasts

02:43:53.800 | and things of that sort,

02:43:55.200 | your exposure is because people are interested

02:43:58.080 | in these topics and that's why people like myself

02:44:00.760 | are interested in talking to you.

02:44:03.160 | I mean, at Stanford, there are now a few labs

02:44:06.900 | starting to explore psychedelics more at the mechanistic

02:44:09.880 | level, but so in animal models, excellent labs,

02:44:13.480 | but also I can imagine because of the pioneering work

02:44:17.620 | that you've done at Hopkins,

02:44:18.560 | it'll start to become more common.

02:44:20.880 | I'm certain that people are going to have questions

02:44:22.840 | about how to get in contact with you and learn more.

02:44:26.000 | If people have trauma, PTSD, depression,

02:44:30.900 | it's likely that they're going to start seeking ways

02:44:35.160 | in which they can potentially participate

02:44:37.300 | in clinical trials.

02:44:39.180 | You're very active on Twitter, active, I should say,

02:44:42.220 | you've got other obligations,

02:44:43.340 | but where you are active on social media,

02:44:45.100 | you're active on Twitter.

02:44:46.000 | It's drug, it's @drug_researcher, correct?

02:44:50.360 | - Right, right, right.

02:44:51.580 | - Okay.

02:44:52.420 | - Drug_researcher, that's how to find me.

02:44:55.940 | - Great account, by the way.

02:44:57.340 | Matthew and I recently got into a dialogue there

02:45:01.040 | about some of the deeper effects of psychedelics

02:45:03.380 | in the literature versus how they're being discussed

02:45:05.780 | in the general public.

02:45:06.740 | And I follow his account and it's a really wonderful account

02:45:09.820 | for whether or not you have a science background or not.

02:45:13.740 | If people are, and I'm going to try and persuade you

02:45:16.420 | to be more active on Instagram,

02:45:17.940 | but I don't know if I'll succeed in that.

02:45:19.340 | - I'll try to get my Instagram game going on.

02:45:20.180 | - You're a busy guy and I get it.

02:45:22.060 | I'm running a lab too, I get it, you're busy,

02:45:23.740 | but drug_researcher there as well.

02:45:27.740 | - Same handle.

02:45:29.060 | - The same handle.

02:45:30.660 | Your lab at Hopkins is pretty straightforward

02:45:33.180 | to find through a Google search of your name,

02:45:35.260 | Matthew Johnson, Johns Hopkins University.

02:45:37.740 | Are there portals for people to explore clinical trials,

02:45:42.740 | participation in clinical trials of various kinds?

02:45:45.060 | - Yeah, and so in our group,

02:45:46.820 | so you go to hopkinspsychedelic.org, that's the website.

02:45:51.500 | And if you can't remember that,

02:45:52.740 | just Johns Hopkins Psychedelic.

02:45:54.700 | - Yeah, we will provide a link.

02:45:55.540 | - And you're going to find us.

02:45:57.380 | It'll be the first thing that pops up.

02:45:59.300 | And we have, trust me, if we have a study on something,

02:46:03.140 | it's going to be on that website.

02:46:04.780 | - That means they're being very polite.

02:46:07.220 | So I will be a little bit more aggressive and say,

02:46:09.420 | don't email him directly.

02:46:10.980 | He won't see that email.

02:46:12.460 | Wait until there's a posting for a study

02:46:14.540 | and then sign up through the correct portal.

02:46:16.380 | - And I try to get back to those emails,

02:46:18.220 | but frankly, and it's 'cause, you know,

02:46:21.620 | I'm lucky the area has taken off so much,

02:46:23.620 | but there are many days where I simply get so many requests

02:46:27.060 | that I can't get through my day.

02:46:28.900 | Yeah, if I answer all the, so yeah, trust me.

02:46:32.380 | And something that a lot of folks don't get

02:46:34.260 | in being in academia like we are,

02:46:35.900 | it's easy to forget how people don't,

02:46:38.020 | understandably don't realize this.

02:46:40.220 | This is experimental research.

02:46:42.400 | It's FDA approved as an experiment.

02:46:45.300 | You know, so we're working towards formal FDA approval

02:46:47.900 | for straight up clinical use.

02:46:49.060 | But right now someone can't bring me a case

02:46:51.480 | of some idiosyncratic thing and say,

02:46:56.140 | I'm suffering from this complex constellation

02:46:58.220 | of depression. - You're not a clinician.

02:46:59.060 | - Yeah, I'm not a clinician, and even if I was,

02:47:02.100 | I wouldn't be able to treat them with psilocybin

02:47:05.180 | or to send them anywhere that was legal to take it.

02:47:10.180 | You know, so if we're gonna be treating you,

02:47:14.500 | it has to be, or anyone else in the United States

02:47:17.140 | or most other countries for that matter,

02:47:19.280 | it's gonna have to be under the guise

02:47:20.720 | of a very specific protocol.

02:47:22.680 | This number of milligrams to treat PTSD,

02:47:26.260 | to treat major depressive disorder,

02:47:28.080 | to treat treatment resistant tobacco use disorder,

02:47:32.940 | so nicotine addiction, very specific studies.

02:47:36.460 | This is not one-off treatment.

02:47:38.540 | And folks say like, oh, I can pay to go out to Baltimore.

02:47:41.760 | If you see, oh, my son has this complex,

02:47:45.040 | like in their tragic cases.

02:47:47.880 | So if you're interested in a study, go to our website.

02:47:50.660 | If it's not on their website, we don't have a study on it.

02:47:54.480 | There are gonna be forthcoming studies.

02:47:56.020 | So I'm gonna be starting studies on opioid addiction

02:47:58.860 | and PTSD and an LSD study for chronic pain.

02:48:02.120 | The day that those are open for recruitment,

02:48:05.600 | they're gonna be up on our website.

02:48:06.960 | So that's where you look to see everything.

02:48:09.240 | And in fact, I would just recently, a couple of days ago,

02:48:11.260 | put up a couple of survey studies,

02:48:12.560 | also where we post links to our survey studies.

02:48:15.400 | So if you've had psychedelics and you've taken them

02:48:18.200 | for therapeutic intent for PTSD or for depression

02:48:21.720 | or anxiety, you can find a link.

02:48:23.600 | And also if you've done breath work for those reasons,

02:48:25.760 | we have a link for a study of that type up there now,

02:48:28.580 | which is a holotropic style breath,

02:48:30.500 | very psychedelic type of breathing technique

02:48:33.900 | that can lead to some of these similar experiences.

02:48:37.180 | So it's up there.

02:48:38.040 | More broadly outside of our group,

02:48:40.500 | 'cause there's a growing number of groups

02:48:42.400 | in the US and in Europe doing this research,

02:48:45.580 | but you can go to clinicaltrials.gov.

02:48:49.320 | And if you look in for the main search term of psilocybin

02:48:54.480 | or MDMA or psychedelic plugin, those terms,

02:48:58.080 | you can get a list of the growing number.

02:49:00.160 | I mean, I think there's over 40, maybe it's been a while.

02:49:04.600 | There might be over 50 now, I don't know,

02:49:06.120 | but studies with just psilocybin going on right now

02:49:09.400 | on clinicaltrials.gov.

02:49:10.920 | So check out clinicaltrials.gov to see what's going on,

02:49:13.840 | but it's going to be, if you're going to do anything legal,

02:49:17.480 | it's going to be in the context of a very specific study.

02:49:20.320 | It's not going to be one-off treatment.

02:49:22.600 | - Right, and I should say, and not just legal,

02:49:25.180 | but also supported in the right framework

02:49:28.960 | that you described of having a team, et cetera.

02:49:32.100 | Obviously people will do what they will do.

02:49:34.640 | Oh yeah, go ahead.

02:49:38.480 | - I will say, I never encourage people to take drugs of any,

02:49:41.640 | I don't encourage caffeine use.

02:49:42.960 | Every drug has its risk.

02:49:44.520 | - I encourage my own caffeine use, but nobody else's.

02:49:47.800 | - I'm drinking up right now, this is great.

02:49:49.640 | - Yeah, this is a very strong mate is what we're drinking.

02:49:52.160 | It does not lead to a alteration in my perception of self

02:49:56.560 | to the extent that we talked about earlier.

02:49:58.360 | However, this conversation wasn't a good example

02:50:02.000 | of how we can enter a perceptual bubble.

02:50:03.960 | I learned so much about psychedelics

02:50:07.160 | and the future of this for sake of mental health

02:50:10.340 | and other aspects of health.

02:50:12.060 | Matt, thank you so much for your time, for your knowledge.

02:50:16.660 | And I think you put it best earlier for holding the candle

02:50:20.960 | in a very dark time and then now there's light.

02:50:24.720 | - Thank you.

02:50:25.680 | Well, thanks for helping to spread that light.

02:50:27.240 | And I really appreciate what you've been doing.

02:50:30.280 | This is a great, great medium that you have going on.

02:50:33.280 | So thank you for doing it.

02:50:35.240 | - Well, it's my pleasure, thank you.

02:50:37.520 | Thank you for joining me for my conversation

02:50:39.500 | with Dr. Matthew Johnson.

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02:52:00.200 | [upbeat music]

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

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