How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks

00:00:00.300 | - 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.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.080 | and I'm a professor of neurobiology and ophthalmology

00:00:13.040 | at Stanford School of Medicine.

00:00:14.980 | Today, we are discussing psilocybin.

00:00:17.320 | Psilocybin is a psychedelic, meaning it modifies the psyche.

00:00:21.380 | And in doing so, it changes our level of consciousness.

00:00:25.120 | Psychedelics, such as psilocybin,

00:00:26.680 | change the way that we perceive the outside world

00:00:28.860 | and our internal world, our memories, our thoughts,

00:00:31.400 | our feelings, et cetera,

00:00:33.240 | not just while one is under the influence of psilocybin,

00:00:36.560 | but it can also fundamentally change

00:00:38.320 | all of those things afterwards

00:00:40.120 | and for a very long period of time afterwards as well,

00:00:43.200 | which is one of the reasons why there's growing excitement

00:00:45.720 | about the application of psilocybin and other psychedelics

00:00:48.900 | for the treatment of various mental health issues,

00:00:51.040 | such as depression, alcohol abuse disorder,

00:00:54.200 | and addictions of various kinds,

00:00:55.580 | as well as things like OCD and eating disorders.

00:00:58.260 | Today, we will discuss psilocybin, talking about what it is.

00:01:01.880 | In fact, you may be surprised to learn

00:01:03.400 | that psilocybin basically is serotonin.

00:01:06.760 | Now, for those of you that are familiar

00:01:08.280 | with psilocybin and serotonin,

00:01:09.520 | you might think, wait, that's not true.

00:01:10.840 | But in fact, psilocybin's main effect is to mimic serotonin,

00:01:15.440 | but it does it in a very specific way

00:01:17.720 | because it activates a subset of serotonin receptors

00:01:21.760 | in a very strong fashion,

00:01:24.320 | leading to neuroplasticity

00:01:26.920 | at the level of the neural circuits,

00:01:28.540 | that is the brain areas and connections

00:01:30.560 | that serve things like memory and perception.

00:01:33.220 | So if any of that is confusing at this point,

00:01:35.040 | I promise to make it all clear in just a few minutes.

00:01:38.280 | Psilocybin is one of many psychedelics, of course.

00:01:41.020 | There are things like LSD, DMT, 5-MeO-DMT.

00:01:44.520 | Even MDMA, while not considered a classic psychedelic,

00:01:47.660 | is considered a psychedelic in the general sense.

00:01:50.580 | Today's episode is going to focus

00:01:52.240 | on psilocybin in particular.

00:01:54.320 | I will tell you what psilocybin is,

00:01:56.840 | how it works at the molecular and cellular level.

00:02:00.140 | I'll talk about how it changes brain circuitry.

00:02:02.760 | I'll talk about the clinical effects,

00:02:04.340 | what's been demonstrated in controlled laboratory studies.

00:02:07.120 | I'll talk about dosages and translating

00:02:09.400 | from psilocybin mushrooms to actual psilocybin,

00:02:12.520 | and the compound that actually exerts

00:02:14.320 | the effects of psilocybin,

00:02:15.400 | which it turns out is not psilocybin,

00:02:16.960 | but something called psilocin.

00:02:18.880 | Psilocin is the actual compound that goes into the brain

00:02:21.880 | to create all the changes in consciousness

00:02:23.920 | and all the rewiring effects that we associate

00:02:27.580 | with psilocybin.

00:02:28.700 | So understanding how psilocybin is converted to psilocin

00:02:31.840 | has tremendous impact on the duration

00:02:35.320 | of a psilocybin journey,

00:02:36.760 | whether or not that psilocybin journey is going to lead

00:02:39.380 | to a short or longer window for neuroplasticity.

00:02:42.960 | In fact, many people don't realize this,

00:02:44.540 | but much of the positive changes that are possible

00:02:47.760 | with proper, and I do want to underscore,

00:02:50.080 | proper psilocybin therapeutic approaches

00:02:52.760 | takes place after the session in which one feels

00:02:56.640 | all the typical or typically associated effects

00:03:00.240 | of psilocybin, like hallucinations and changes

00:03:02.340 | in thought patterns, et cetera.

00:03:03.920 | So today we are going to talk a little bit about chemistry,

00:03:06.380 | but I promise to make it accessible to anyone and everyone,

00:03:08.880 | regardless of whether or not you have a background

00:03:10.440 | in chemistry or biology.

00:03:12.040 | We're going to talk about some cell biology,

00:03:13.660 | the actual neuronal changes that occur

00:03:17.300 | when one takes psilocybin.

00:03:19.120 | And we're going to talk about how neural circuits

00:03:21.500 | change over time and how all of that impacts the changes

00:03:24.800 | that most people are interested in

00:03:26.420 | when they go on a psilocybin journey.

00:03:29.120 | Things such as longstanding improvements in mood,

00:03:32.660 | things such as tremendous insight into themselves,

00:03:36.360 | into others, into their past, their present,

00:03:38.740 | and their future, and even changes in their levels

00:03:42.080 | of creativity or their ability to experience joy from music

00:03:45.740 | or their ability to dissociate in a positive way

00:03:49.280 | from things that formerly were depressing

00:03:51.840 | or triggers for depression.

00:03:53.500 | In fact, we're going to talk quite a lot

00:03:55.540 | about the conditions inside of a psilocybin journey

00:03:58.460 | that make it actually positive and therapeutic.

00:04:01.880 | This is a very important point that I'll make several times

00:04:04.420 | throughout today's episode,

00:04:06.040 | which is that just because something invokes neuroplasticity,

00:04:10.080 | changes in brain circuitry,

00:04:11.820 | does not mean that it's therapeutic,

00:04:14.380 | or I should say does not necessarily mean

00:04:16.500 | that it's therapeutic.

00:04:17.980 | For neuroplasticity to be therapeutic,

00:04:20.220 | it has to be adaptive.

00:04:21.340 | It has to allow someone to function better in life

00:04:23.900 | than they did previously.

00:04:25.620 | So today we will talk about how the conditions

00:04:28.200 | of a psilocybin journey,

00:04:29.460 | including whether or not it's done with eyes closed

00:04:31.820 | or eyes open, or whether or not people alternate

00:04:34.100 | between eyes closed and eyes open phases of that journey,

00:04:37.280 | as well as whether or not music is played

00:04:39.580 | during that journey,

00:04:40.420 | and even what types of music are played,

00:04:42.460 | will dictate whether or not somebody will feel better

00:04:46.300 | or worse in the days and weeks and years

00:04:48.460 | following that psilocybin journey,

00:04:50.620 | as well as the dosage level,

00:04:52.940 | because, as you'll soon learn as well,

00:04:55.540 | there are clinical studies showing

00:04:56.780 | that just one psilocybin journey can improve mood

00:05:00.080 | in a longstanding way,

00:05:01.100 | but most clinical trials involve two dosages,

00:05:04.840 | spaced in very precise ways from one another

00:05:08.140 | with appropriate follow-up.

00:05:09.540 | But in both of those particular journeys,

00:05:12.620 | the structure of the journey, who's present,

00:05:15.180 | who's not present, eyes open or eyes closed,

00:05:18.020 | the particular music that's played,

00:05:19.620 | all of those features make up part

00:05:21.700 | of a larger neuroplasticity trigger

00:05:24.580 | of which psilocybin is critical,

00:05:26.900 | but psilocybin is not the only variable.

00:05:29.660 | So whether or not you're interested

00:05:30.860 | in participating in a clinical study,

00:05:32.620 | or whether or not you're interested in psilocybin

00:05:34.260 | for other reasons,

00:05:35.600 | this is critical information to understand.

00:05:37.380 | So today we're going to talk about nearly every feature

00:05:39.640 | of psilocybin possible, including what psilocybin is,

00:05:43.300 | how it works at the level of chemistry, cell biology

00:05:46.900 | and neural networks and neuroplasticity.

00:05:49.460 | We will talk about the clinical studies,

00:05:51.140 | we'll talk about dosages,

00:05:52.640 | we will talk about conditions of clinical studies,

00:05:54.920 | and we will talk about the post- psilocybin journey period

00:05:58.720 | in which neuroplasticity and the various activities,

00:06:02.280 | including therapy or perhaps not therapy,

00:06:05.100 | can contribute to positive therapeutic changes

00:06:07.980 | from psilocybin.

00:06:09.020 | Now, as we go into this discussion,

00:06:10.660 | I do want to underscore the fact

00:06:12.340 | that at the time of recording this episode,

00:06:14.760 | meaning now, May, 2023,

00:06:18.500 | psilocybin is still a schedule one drug.

00:06:21.820 | It is considered illegal in the United States.

00:06:24.500 | There's perhaps just one exception to that,

00:06:26.420 | maybe a few others,

00:06:27.840 | but the main exception is in the state of Oregon.

00:06:30.400 | Psilocybin has been approved

00:06:31.960 | in particular therapeutic settings

00:06:34.420 | for use in particular conditions,

00:06:37.820 | namely depression and some forms of addiction.

00:06:40.560 | So in Oregon, it's more or less in the domain

00:06:44.020 | of decriminalized as opposed to actually legal.

00:06:47.700 | In other areas of the country,

00:06:49.180 | including Oakland, California,

00:06:50.680 | there are some areas in which it has been decriminalized,

00:06:53.840 | and perhaps there are a few others that I'm not aware of,

00:06:55.920 | but in general, psilocybin and other psychedelics

00:06:58.820 | are still considered illegal.

00:07:00.360 | And this is very important,

00:07:01.600 | I'm not just saying this to protect me,

00:07:02.760 | I'm saying this to protect you,

00:07:04.360 | possessing or certainly selling psilocybin,

00:07:07.080 | except for rare instances such as clinical studies

00:07:09.520 | in these decriminalized areas

00:07:11.600 | that I talked about a moment ago,

00:07:13.560 | is still very much not allowed under the law.

00:07:16.960 | Today, I'll also discuss safety issues.

00:07:19.140 | I'll talk about whether or not young people,

00:07:21.400 | meaning people 25 or younger,

00:07:23.720 | should consider psilocybin,

00:07:25.120 | given that their brain is still in a rampant period

00:07:28.200 | of naturally occurring neuroplasticity.

00:07:31.320 | I will also talk about dosages

00:07:33.540 | as it relates to people who have formerly been on

00:07:35.900 | or may currently be on different forms of antidepressants.

00:07:39.480 | And I will talk about people who are at risk

00:07:42.140 | for psychotic episodes,

00:07:43.640 | either because they know they themselves

00:07:46.440 | have a propensity for psychosis,

00:07:48.040 | or they have close family members who have psychosis,

00:07:51.240 | which includes things like schizophrenia,

00:07:53.040 | bipolar depression,

00:07:54.600 | as well as things like borderline personality

00:07:57.640 | and some related psychiatric conditions.

00:08:00.400 | So today's episode really will be

00:08:01.960 | a deep dive into psilocybin.

00:08:03.820 | So whether or not you think you're already familiar

00:08:05.440 | with psilocybin and its effects,

00:08:06.840 | or whether or not you're just curious about them,

00:08:09.300 | I do encourage, if you're willing,

00:08:11.320 | to try and ratchet through some of the understanding

00:08:14.260 | of how psilocybin works and what it is,

00:08:16.560 | leading up to some of the therapeutic applications

00:08:18.940 | and different patterns of dosing,

00:08:21.240 | spacing of different sessions, et cetera.

00:08:23.360 | 'Cause I do believe that with that knowledge in hand,

00:08:25.940 | you will be able to make far better,

00:08:27.920 | much more informed decisions

00:08:29.700 | about whether or not psilocybin is right for you.

00:08:33.080 | Before we begin, I'd like to emphasize that this podcast

00:08:35.660 | is separate from my teaching and research roles at Stanford.

00:08:38.200 | It is, however, part of my desire and effort

00:08:40.320 | to bring zero cost to consumer information about science

00:08:42.840 | and science-related tools to the general public.

00:08:45.380 | In keeping with that theme,

00:08:46.420 | I'd like to thank the sponsors of today's podcast.

00:08:49.260 | Our first sponsor is Eight Sleep.

00:08:51.240 | Eight Sleep makes smart mattress covers

00:08:52.840 | with cooling, heating, and sleep tracking capacity.

00:08:55.480 | Now, sleep is the foundation of mental health,

00:08:57.460 | physical health, and performance.

00:08:58.880 | Everything goes far better when we are sleeping well

00:09:01.040 | on a consistent basis.

00:09:02.200 | And one of the key things to getting a great night's sleep

00:09:05.000 | is to make sure that the temperature

00:09:06.340 | of your sleeping environment is correct.

00:09:08.120 | In fact, your body temperature has to drop

00:09:09.720 | by one to three degrees in order to fall asleep

00:09:12.640 | and stay deeply asleep.

00:09:13.900 | And waking up involves a heating up of your body

00:09:16.480 | by about one to three degrees.

00:09:18.320 | With Eight Sleep, you can program your mattress

00:09:20.560 | to be a specific temperature at the beginning, middle,

00:09:22.680 | and towards the end of your sleep night.

00:09:24.760 | Ever since I started sleeping on an Eight Sleep mattress,

00:09:27.280 | I've slept far better than I ever have.

00:09:29.520 | So it's an all around great tool

00:09:31.080 | that has tremendous functionality, not just for measuring,

00:09:33.880 | but for improving your sleep.

00:09:35.880 | If you'd like to try Eight Sleep,

00:09:37.000 | you can go to eightsleep.com/huberman

00:09:39.360 | and save $150 off their pod three cover.

00:09:41.760 | Eight Sleep currently ships in the USA, Canada, UK,

00:09:44.480 | select countries in the EU, and Australia.

00:09:46.600 | Again, that's eightsleep.com/huberman.

00:09:49.320 | Today's episode is also brought to us by Roca.

00:09:51.840 | Roca makes eyeglasses and sunglasses

00:09:53.980 | that are of the absolute highest quality.

00:09:55.920 | I've spent a lifetime working on the biology,

00:09:57.640 | the visual system, and I can tell you

00:09:59.120 | that your visual system has to contend

00:10:00.920 | with an enormous number of challenges

00:10:02.620 | in order to make sure that you can see clearly

00:10:04.480 | under any conditions.

00:10:05.800 | Roca understands all of that

00:10:07.400 | and has designed their eyeglasses and sunglasses

00:10:09.880 | so that regardless of whether or not

00:10:11.220 | you're in a very brightly lit area or a more shady area,

00:10:13.960 | or you go from brightly lit to shady areas,

00:10:16.280 | you can always see with tremendous clarity.

00:10:18.600 | Now, even though they were initially designed for sport,

00:10:20.800 | Roca eyeglasses and sunglasses

00:10:22.300 | come in a tremendous number of different aesthetics.

00:10:24.200 | So they have the kind of what I call cyborg versions

00:10:26.240 | that most people associate with triathlon glasses

00:10:29.040 | and sports related glasses,

00:10:30.520 | but they also have a tremendous number of frames

00:10:32.000 | that you feel perfectly comfortable wearing to work

00:10:34.560 | or out to dinner, et cetera.

00:10:36.200 | If you'd like to try Roca eyeglasses and sunglasses,

00:10:38.460 | you can go to Roca, that's R-O-K-A.com

00:10:41.000 | and enter the code Huberman

00:10:42.500 | to save 20% off your first order.

00:10:44.380 | Again, that's Roca, R-O-K-A.com

00:10:46.920 | and enter the code Huberman at checkout.

00:10:49.120 | Today's episode is also brought to us by HVMN Ketone IQ.

00:10:53.360 | Ketone IQ is a ketone supplement

00:10:55.240 | that increases blood ketones.

00:10:57.280 | Now, I know most people are familiar

00:10:58.800 | or at least have heard of the so-called ketogenic diet,

00:11:02.000 | which is essentially a very low carbohydrate diet.

00:11:04.380 | It's designed to get your brain

00:11:06.060 | and body functioning off ketones,

00:11:07.760 | which are a great source of fuel for the body and brain.

00:11:10.080 | However, most people, including myself, are not ketogenic.

00:11:13.560 | That is, I'm not in a ketosis state pretty much ever,

00:11:17.360 | as far as I know.

00:11:18.480 | Nonetheless, with ketone IQ,

00:11:20.380 | you can increase your blood ketones

00:11:22.000 | and thereby improve things like cognition

00:11:25.020 | and physical performance.

00:11:26.760 | I find that when taking ketone IQ,

00:11:28.600 | even if I'm eating a standard omnivore diet,

00:11:31.080 | which is the diet that I follow,

00:11:32.560 | by taking ketone IQ prior to workouts,

00:11:35.300 | sometimes on an empty stomach,

00:11:36.860 | and especially prior to doing any kind of cognitive work,

00:11:39.240 | so researching podcasts or doing work related to my lab

00:11:41.900 | or teaching, et cetera,

00:11:43.140 | that I can maintain mental clarity

00:11:45.080 | for a longer period of time.

00:11:46.560 | And it does seem to enhance my mental clarity as well.

00:11:49.320 | If you'd like to try ketone IQ,

00:11:51.240 | you can go to hvmn.com

00:11:53.140 | and use the code Huberman to get 20% off.

00:11:55.460 | Again, that's hvmn.com

00:11:57.200 | and use the code Huberman to get 20% off.

00:11:59.860 | Let's talk about psilocybin.

00:12:01.180 | And again, today we're going to focus

00:12:02.820 | specifically on psilocybin

00:12:04.300 | and we're going to set aside all the other psychedelics

00:12:06.780 | for future episodes.

00:12:08.120 | Psilocybin is what's called a tryptamine.

00:12:12.460 | That refers to its chemical composition,

00:12:15.300 | not to the so-called psychedelic trip.

00:12:17.540 | In fact, it's spelled differently.

00:12:18.660 | Tryptamine is T-R-Y-P, trip, T-R-I-P, of course.

00:12:23.660 | Tryptamines include psilocybin,

00:12:25.980 | but also things like DMT and 5-MeO-DMT.

00:12:29.340 | The tryptamine psychedelics very closely resemble

00:12:32.100 | serotonin itself.

00:12:34.300 | That's right, most of you have probably heard

00:12:36.020 | of the chemical serotonin.

00:12:37.740 | And serotonin is what's called a neuromodulator,

00:12:40.460 | which means your brain and body naturally make it

00:12:43.060 | and that it modifies or changes the activity

00:12:45.980 | of other neurons and neural circuits.

00:12:47.780 | And it does that generally by either increasing

00:12:50.780 | or decreasing the activity of those neural circuits.

00:12:54.040 | If I were to show you a picture

00:12:55.340 | of the chemical structure of psilocybin,

00:12:58.240 | or its active derivative, psilocin,

00:13:00.880 | and I were to also put right alongside it

00:13:03.860 | an image of the chemical structure of serotonin,

00:13:06.260 | provided that you weren't a chemist who really likes

00:13:09.380 | to focus on the detailed differences between things,

00:13:12.620 | you would say those look very similar.

00:13:14.380 | And indeed, psilocybin and its active form, psilocin,

00:13:18.500 | are very similar structurally and chemically

00:13:21.680 | to serotonin itself.

00:13:23.400 | Now, as I mentioned before,

00:13:24.500 | serotonin is something that you naturally make.

00:13:26.500 | And yes, it's true that about 90% of the serotonin

00:13:29.880 | in your brain and body is manufactured in your gut.

00:13:33.080 | However, contrary to popular belief,

00:13:35.320 | the serotonin in your brain is not manufactured

00:13:39.460 | from the serotonin in your gut.

00:13:40.960 | You have separate independent sources of serotonin.

00:13:44.360 | That is, you have particular neurons

00:13:45.540 | that make serotonin in your brain.

00:13:47.360 | You also have serotonin in your gut,

00:13:49.020 | and those work more or less in parallel separately.

00:13:51.980 | Now, what does serotonin do?

00:13:53.440 | This is really important to understand

00:13:55.500 | because of the similarity between psilocybin

00:13:58.400 | and its active form, psilocin, and serotonin.

00:14:01.680 | Serotonin, in that it's a neuromodulator,

00:14:05.540 | changes the activity of other neurons,

00:14:07.580 | and the net effects of those changes

00:14:10.300 | are things that you're familiar with.

00:14:11.660 | For instance, satiety,

00:14:13.620 | or the feeling that we've had enough of various things,

00:14:16.660 | such as food, or a social interaction,

00:14:19.660 | or sex, or pleasure of any kind.

00:14:23.260 | Serotonin is involved in all of that,

00:14:25.340 | and an enormous number of other things,

00:14:28.260 | such as mood regulation,

00:14:30.280 | such as our sense of pleasure itself, or lack of pleasure,

00:14:33.740 | such as whether or not we feel motivated or not motivated.

00:14:37.060 | It works in concert with other neuromodulators,

00:14:39.540 | such as dopamine, and epinephrine, and norepinephrine.

00:14:42.060 | In fact, if this were an episode about serotonin,

00:14:44.380 | which it is not,

00:14:45.980 | you would soon realize that serotonin

00:14:47.700 | is involved in so many different functions

00:14:50.960 | that impact our daily life.

00:14:53.180 | And that is one reason why

00:14:55.180 | certain antidepressant medications,

00:14:57.520 | which alter, either increase or decrease,

00:15:00.740 | the amount of serotonin transmission in the brain,

00:15:03.860 | will often have a lot of side effects

00:15:06.140 | related to things like mood, libido, appetite,

00:15:08.700 | sleep, et cetera.

00:15:10.140 | It's because serotonin is involved

00:15:11.580 | in so many different things.

00:15:13.220 | And serotonin is involved in so many different things

00:15:15.860 | because there are a lot of different

00:15:17.300 | so-called serotonin receptors.

00:15:19.000 | Serotonin is a chemical that we call a ligand,

00:15:22.140 | and the chemical ligand is simply the thing

00:15:24.460 | that plugs into the receptor for that chemical or ligand.

00:15:28.200 | The receptors, in this case, serotonin receptors,

00:15:31.060 | have the opportunity to do all sorts of different things.

00:15:33.460 | They can change the activity of neurons,

00:15:35.400 | making them more active or less active.

00:15:37.180 | They can cause growth factors to be released,

00:15:39.220 | making sure that those neurons reinforce

00:15:41.900 | or even build up stronger connections

00:15:44.040 | so that they're more likely to be active in the future.

00:15:46.500 | Serotonin binding to particular receptors

00:15:48.420 | can even change the gene expression in particular cells,

00:15:51.480 | making those cells proliferate, so make more of them,

00:15:54.180 | making those cells more robust,

00:15:56.020 | making those cells interact with new elements

00:15:59.580 | of the brain and body.

00:16:00.820 | Basically, serotonin and all these different receptors

00:16:02.980 | that it binds to has dozens, if not hundreds,

00:16:05.720 | and maybe even thousands of different functions.

00:16:08.560 | So the fact that psilocybin so closely resembles serotonin

00:16:13.480 | leads to a very important question

00:16:16.120 | that we should all be asking ourselves,

00:16:17.400 | which is why is it that psilocybin,

00:16:20.160 | which looks so much like serotonin,

00:16:21.980 | when one takes it in the form of magic mushrooms

00:16:24.680 | or some other form,

00:16:26.540 | maybe the synthetic form of psilocybin itself,

00:16:28.540 | which nowadays is manufactured in laboratories

00:16:30.940 | and placed in different psilocybin-containing foods

00:16:33.960 | and pills, et cetera,

00:16:35.280 | why that leads to complex

00:16:39.020 | yet fairly circumscribed sets of experience,

00:16:42.260 | like visual and auditory hallucinations,

00:16:44.620 | changes in particular thought patterns and neuroplasticity

00:16:48.140 | that, in many cases, in the clinical setting,

00:16:50.820 | provided things are done correctly,

00:16:52.860 | improvements in mood, relief from depression,

00:16:56.340 | relief from various compulsive disorders, et cetera, right?

00:16:59.880 | This is really what you need to understand

00:17:01.340 | if you want to understand psilocybin and how it works

00:17:04.300 | and how to make it work optimally

00:17:06.500 | for a given condition or goal.

00:17:09.700 | You have to understand what it's actually doing

00:17:11.860 | and what allows psilocybin to do fairly specific things

00:17:16.260 | in comparison to serotonin,

00:17:17.740 | even though psilocybin and serotonin are so similar,

00:17:20.700 | is that psilocybin mainly binds to

00:17:23.740 | and activates the so-called serotonin 2A receptor.

00:17:28.140 | The serotonin 2A receptor is one of, again,

00:17:31.380 | many different serotonin receptors,

00:17:33.420 | but serotonin 2A is expressed

00:17:35.980 | in particular areas of the brain

00:17:38.140 | and even on particular areas of neurons in the brain

00:17:41.860 | that allow for very specific types of changes

00:17:44.940 | in neural circuitry to take place,

00:17:46.940 | not just when one is under the influence of psilocybin,

00:17:49.740 | but afterwards as well.

00:17:51.540 | So really, in order to have a useful discussion

00:17:53.660 | about psilocybin, we need to talk a lot

00:17:56.140 | about the serotonin 2A receptor,

00:17:58.340 | but fortunately for you,

00:18:00.060 | unless you're somebody really interested

00:18:01.220 | in structural biology or cell biology,

00:18:03.340 | that discussion is not going to be about the binding pocket

00:18:06.580 | for serotonin on serotonin 2A receptor

00:18:09.220 | or a lot of the downstream signaling

00:18:10.800 | of the serotonin 2A receptor.

00:18:12.140 | We'll talk a little bit about that where it's relevant,

00:18:14.900 | but more importantly, at least for sake of today's discussion

00:18:17.680 | we're going to talk about how the serotonin 2A receptor

00:18:20.900 | is really the one responsible

00:18:22.580 | for triggering all the changes in neural circuitry

00:18:25.540 | that lead to the changes, that is the improvements in mood,

00:18:29.580 | the relief from compulsive disorders in many case,

00:18:32.780 | but really it's the serotonin 2A receptor selectivity

00:18:36.180 | of psilocybin that is leading to all the excitement

00:18:39.940 | that you hear about in terms of psilocybin

00:18:42.820 | as a therapeutic tool.

00:18:45.220 | Let me say that from a slightly different angle.

00:18:48.180 | There are data that I'll talk about today,

00:18:49.900 | which show that one, although in most cases,

00:18:53.600 | two psilocybin journeys done with particular dosages

00:18:57.140 | of psilocybin lead to maximal binding or occupancy

00:19:01.380 | of those serotonin 2A receptors in ways that lead

00:19:04.180 | to significant and unprecedented relief

00:19:06.940 | for major depression.

00:19:08.240 | In fact, you'll soon learn that the clinical trials

00:19:10.180 | for psilocybin are outperforming standard therapy

00:19:14.380 | and outperforming so-called SSRIs

00:19:17.340 | and various other antidepressants

00:19:19.200 | in terms of providing depression relief

00:19:21.340 | in ways that are frankly staggering, not just to me,

00:19:25.340 | but to the psychiatric community at large.

00:19:27.220 | And this is where so much of the excitement is coming from.

00:19:30.220 | Now that statement could be taken one way,

00:19:32.760 | which is to just say, okay, well,

00:19:34.660 | here's a compound psilocybin that outperforms SSRIs

00:19:38.060 | and therefore all the attention should be on psilocybin.

00:19:41.160 | But SSRI stands for selective serotonin reuptake inhibitor.

00:19:46.160 | In other words, the SSRIs of which there's now a lot

00:19:50.060 | of controversy, things like Prozac, Zoloft, et cetera.

00:19:53.100 | I'm sure you've heard some of this controversy.

00:19:54.580 | There are people who are very pro-SSRIs,

00:19:56.740 | although there are a growing number of people

00:19:58.620 | who really feel that the SSRIs are probably most appropriate

00:20:01.460 | for things like obsessive compulsive disorder,

00:20:03.660 | where they in fact can be very beneficial.

00:20:06.800 | But there's a lot of kind of leaning back from SSRIs

00:20:10.660 | as the be all end all for the treatment of depression

00:20:14.480 | nowadays because of the side effect profiles.

00:20:17.200 | And the fact that it's not even really clear

00:20:19.220 | that serotonin deficiencies are the major cause

00:20:21.740 | of depression in the first place.

00:20:24.020 | Now, again, we're talking about psilocybin,

00:20:25.940 | not about SSRIs, but you should be thinking,

00:20:27.960 | wait, how is it that two molecules,

00:20:31.320 | psilocybin and some particular SSRI,

00:20:34.860 | both of which look like

00:20:37.440 | and or increase serotonin transmission in the brain

00:20:40.200 | are leading to either incredibly positive

00:20:42.780 | and interesting outcomes

00:20:44.100 | or to kind of troubling side effect riddled outcomes.

00:20:47.660 | And again, it all boils back down to the selectivity

00:20:51.320 | of psilocybin to bind that serotonin 2A receptor.

00:20:54.920 | And so in order to understand how psilocybin works

00:20:57.380 | and in order to understand proper dosing profiles

00:20:59.600 | and spacing of sessions, AKA journeys,

00:21:01.880 | we really need to talk a little bit more

00:21:03.400 | about the serotonin 2A receptor,

00:21:05.760 | where it is in the brain,

00:21:07.600 | what sorts of things happen

00:21:09.280 | when psilocybin binds the serotonin 2A receptor

00:21:12.640 | and how those things set in motion the various changes,

00:21:16.300 | the neuroplasticity that allows people to feel better

00:21:19.380 | in terms of their mood.

00:21:20.460 | And as you'll soon learn, can experience more pleasure

00:21:23.040 | and joy from things like music and enhanced creativity.

00:21:26.380 | All the things that I do believe,

00:21:28.120 | whether or not people are thinking about

00:21:30.040 | or maybe even exploring psilocybin

00:21:31.960 | for recreational or therapeutic purposes,

00:21:33.900 | all the things that people want

00:21:35.720 | and are really talking about

00:21:37.400 | and perhaps even doing psilocybin in order to obtain.

00:21:40.240 | So before going any further,

00:21:41.480 | I just want to place an image in your mind.

00:21:43.880 | You can place an image in your mind

00:21:45.220 | whereby when serotonin is released in the brain naturally,

00:21:48.660 | not having taken any compound, any drug, anything,

00:21:52.720 | it's getting released at a lot of different sites,

00:21:54.120 | binding to a lot of different serotonin receptors,

00:21:56.640 | doing a lot of different things.

00:21:58.200 | When somebody takes an SSRI,

00:22:01.280 | the net effect of that selective serotonin

00:22:03.480 | reuptake inhibitor is that there's more serotonin around

00:22:06.660 | to exert its effects because it's a reuptake inhibitor

00:22:09.720 | at the synapse, the connections between neurons,

00:22:11.720 | the serotonin can do its thing more extensively

00:22:14.780 | and for longer periods of time,

00:22:16.320 | but it's doing it kind of non-specifically.

00:22:17.920 | So when you think about standard antidepressant treatments,

00:22:22.480 | at least for sake of this discussion,

00:22:24.280 | you kind of think of a sprinkling or a kind of, you know,

00:22:27.260 | spraying of serotonin at different locations in the brain

00:22:31.040 | and binding to lots of different receptors.

00:22:33.640 | Whereas when you think about psilocybin,

00:22:35.740 | even though the subjective effects are pretty diverse,

00:22:39.000 | we'll talk about those in a few moments,

00:22:41.220 | what you're really talking about is a molecule, psilocybin,

00:22:44.360 | that looks a lot like serotonin that is selectively

00:22:47.240 | and very strongly binding to and activating

00:22:50.540 | that serotonin 2A receptor.

00:22:53.120 | So that's the image I'd like you to embed in your mind.

00:22:55.520 | And then the next image I'd like you to embed in your mind

00:22:58.240 | is where these serotonin 2A receptors

00:23:01.280 | are located in the brain.

00:23:02.700 | The serotonin 2A receptors are located

00:23:06.280 | in multiple brain regions,

00:23:08.920 | but they have a tremendous amount of expression

00:23:12.080 | in the so-called neocortex,

00:23:13.600 | the outside of the brain that includes things

00:23:15.960 | like our prefrontal cortex,

00:23:17.120 | which is involved in understanding context, right?

00:23:19.880 | Which behaviors, thoughts, and speech patterns

00:23:23.040 | are appropriate for certain circumstances,

00:23:26.520 | how to switch context and category switch

00:23:29.280 | when you go from, you know, playing sports

00:23:30.640 | to hanging out with friends,

00:23:31.480 | to being in a professional setting,

00:23:32.440 | you change your behavior and the way that you speak,

00:23:34.420 | and perhaps even the way that you think.

00:23:36.000 | You might think some things that are out of context,

00:23:38.200 | but you probably keep those to yourself,

00:23:39.880 | and your ability to keep those to yourself

00:23:41.600 | are dependent on a functional prefrontal cortex.

00:23:44.160 | There are a lot of 5-HT-2A,

00:23:46.400 | and by the way, 5-HT is the abbreviation for serotonin,

00:23:49.040 | so there are a lot of serotonin 2A receptors

00:23:50.980 | in the prefrontal cortex.

00:23:52.360 | Also in other areas of the cortex

00:23:54.580 | that are associated with sensation and perception,

00:23:58.720 | that is hearing of sounds,

00:24:00.740 | that is seeing of particular things,

00:24:02.580 | and in particular, there is a very, very, very

00:24:07.460 | high expression of serotonin 2A receptors

00:24:10.100 | in the visual cortex,

00:24:12.320 | and that is one of the reasons why psilocybin

00:24:15.580 | triggers visual hallucinations,

00:24:17.940 | and provided psilocybin is present

00:24:19.980 | at sufficient enough concentration

00:24:22.160 | that is taken at a sufficient dosage,

00:24:26.060 | one will experience profound visual hallucinations

00:24:28.920 | regardless of whether or not their eyes are open

00:24:32.060 | or their eyes are closed.

00:24:34.140 | Now, that's an important fact

00:24:35.280 | because it explains one of the major effects of psilocybin

00:24:37.860 | that people experience while they are on the drug.

00:24:41.320 | Now, as I'll talk about a little bit later

00:24:42.780 | in terms of what constitutes a useful psilocybin session,

00:24:46.920 | useful meaning that it's leading

00:24:48.760 | to adaptive improvements in mood,

00:24:51.300 | adaptive improvements in creativity and cognition, et cetera,

00:24:55.080 | is that people not have their eyes open

00:24:59.120 | for at least the majority of the psilocybin session.

00:25:03.720 | This is something I've discussed with several experts

00:25:06.360 | who are running clinical studies

00:25:07.780 | on psilocybin in their laboratories,

00:25:09.480 | some of whom are going to be guests

00:25:10.640 | on the Huberman Lab podcast in upcoming episodes,

00:25:13.600 | and I can't underscore this enough.

00:25:15.780 | Because your visual cortex contains so many

00:25:18.420 | of these serotonin 2A receptors,

00:25:20.380 | and because psilocybin binds so strongly

00:25:23.800 | to that serotonin 2A receptor,

00:25:26.280 | you're going to experience a lot of visual hallucinations

00:25:29.760 | when you are under the influence of psilocybin.

00:25:31.760 | There's no surprise there.

00:25:32.720 | This has been known for hundreds, if not thousands of years.

00:25:35.660 | It's one of the main reasons why people take psilocybin.

00:25:38.760 | However, as I mentioned earlier,

00:25:41.120 | these hallucinations occur even when the eyes are closed,

00:25:44.780 | and it's now fairly well established

00:25:47.580 | that if people are to take psilocybin

00:25:50.640 | and have their eyes open,

00:25:52.640 | much of their cognition, much of their thinking,

00:25:54.880 | much of the time spent in that psilocybin journey

00:25:58.360 | is focused on the altered perceptions of things

00:26:02.040 | in the outside environment.

00:26:03.580 | Sometimes this looks like a sort of a fracturing

00:26:07.360 | of the outside world into kind of geometric shapes.

00:26:10.520 | Sometimes it appears as a kind of melting of things

00:26:14.100 | in the visual environment, including people's faces

00:26:15.880 | or a morphing of people's faces.

00:26:18.080 | All of that has a strong, let's just call it a draw

00:26:21.540 | for a lot of people who are looking

00:26:22.780 | for a highly unusual experience

00:26:24.720 | inside of the psilocybin journey.

00:26:27.760 | But I think if one's goal is to derive

00:26:31.900 | the long lasting benefit from the psilocybin experience,

00:26:36.540 | it's very clear that having an eye mask

00:26:39.680 | or some other eye covering or something that ensures

00:26:41.960 | that one's eyes are closed for the majority,

00:26:45.200 | if not the entire psilocybin session

00:26:48.080 | is going to be very useful

00:26:49.880 | because it's going to limit the extent

00:26:51.520 | to which one is focused on those outside changes

00:26:54.360 | in visual perception, AK hallucinations,

00:26:56.360 | and rather will allow the person to go inward

00:26:59.040 | to combine whatever it is that they happen to be seeing

00:27:01.920 | in their mind's eye with the different thoughts

00:27:04.740 | and memories and changes in their emotions

00:27:07.600 | that are occurring.

00:27:08.440 | And that going inward by staying in the eye mask,

00:27:12.140 | at least for the majority of the time,

00:27:13.560 | seems to be a very, if not the critical feature

00:27:17.640 | of making the psilocybin journey effective

00:27:20.200 | in the therapeutic sense.

00:27:21.680 | Now, once again, I want to cue

00:27:22.960 | to some of the safety precautions here.

00:27:25.120 | I'm going to say this at least three times

00:27:26.560 | throughout today's episode.

00:27:28.280 | As I'm talking now and various other times

00:27:30.200 | throughout today's episode,

00:27:31.040 | you may get the impression that I'm all for everybody

00:27:33.800 | doing psilocybin, and that is simply not the case.

00:27:37.040 | In order for a psilocybin journey

00:27:38.480 | to be therapeutically useful,

00:27:40.660 | it does require certain conditions and supports,

00:27:43.280 | and there are certain people for which psilocybin use

00:27:46.160 | is going to be contraindicated,

00:27:47.640 | meaning they should not do psilocybin.

00:27:49.600 | In particular, people who have existing

00:27:53.060 | or have a predisposition to psychotic episodes

00:27:57.480 | or bipolar episodes.

00:27:58.860 | Even having a first relative who has bipolar

00:28:02.880 | or schizophrenic or schizotypal issues

00:28:06.120 | can be a rule out condition.

00:28:09.400 | That is, can get someone eliminated

00:28:11.000 | from a clinical study on psilocybin

00:28:12.620 | for fear of triggering psychotic episodes,

00:28:15.040 | not just during the psilocybin journey,

00:28:16.820 | but potentially in a longstanding way.

00:28:19.260 | So again, that's really critical.

00:28:20.520 | The other thing is that everything I'm talking about today,

00:28:22.960 | unless I say otherwise, is really focused on adults,

00:28:25.360 | meaning people who are 25 years old or older,

00:28:27.960 | that is their basic wiring and rewiring of the brain

00:28:30.960 | that we call developmental neuroplasticity is completed.

00:28:34.720 | Most of the studies today that I'll talk about

00:28:36.880 | involve subjects ranging from 25 years of age

00:28:40.100 | out to about 70 years of age, but no one younger.

00:28:43.360 | So again, psilocybin and its use

00:28:46.040 | is certainly not for everybody.

00:28:47.760 | It's still illegal.

00:28:48.920 | It's being used in the clinical setting and research setting.

00:28:51.280 | There are these pockets of decriminalized areas

00:28:53.600 | and potentially soon legalization of psilocybin,

00:28:55.960 | but again, only in the proper clinical setting, okay?

00:28:58.360 | Again, I say that not just to protect myself,

00:29:01.340 | but I say that also to protect all of you.

00:29:03.440 | Psilocybin is a powerful, powerful drug,

00:29:06.160 | not just to be under the influence of,

00:29:08.060 | but also in terms of its longstanding changes

00:29:10.760 | after the effects of psilocybin have worn off.

00:29:13.960 | I'd like to take a quick break

00:29:15.480 | and acknowledge one of our sponsors, Athletic Greens.

00:29:18.380 | Athletic Greens, now called AG1,

00:29:20.840 | is a vitamin mineral probiotic drink

00:29:23.200 | that covers all of your foundational nutritional needs.

00:29:26.100 | I've been taking Athletic Greens since 2012,

00:29:28.800 | so I'm delighted that they're sponsoring the podcast.

00:29:31.000 | The reason I started taking Athletic Greens

00:29:32.600 | and the reason I still take Athletic Greens

00:29:34.680 | once or usually twice a day

00:29:36.660 | is that it gets me the probiotics that I need for gut health.

00:29:40.280 | Our gut is very important.

00:29:41.360 | It's populated by gut microbiota

00:29:43.920 | that communicate with the brain, the immune system,

00:29:45.680 | and basically all the biological systems of our body

00:29:48.080 | to strongly impact our immediate and long-term health.

00:29:51.720 | And those probiotics in Athletic Greens

00:29:53.560 | are optimal and vital for microbiota health.

00:29:57.400 | In addition, Athletic Greens contains

00:29:58.960 | a number of adaptogens, vitamins, and minerals

00:30:00.880 | that make sure that all of my foundational

00:30:02.760 | nutritional needs are met, and it tastes great.

00:30:06.220 | If you'd like to try Athletic Greens,

00:30:07.680 | you can go to athleticgreens.com/huberman,

00:30:11.080 | and they'll give you five free travel packs

00:30:13.040 | that make it really easy to mix up Athletic Greens

00:30:15.360 | while you're on the road, in the car,

00:30:16.640 | on the plane, et cetera.

00:30:17.920 | And they'll give you a year's supply of vitamin D3K2.

00:30:21.340 | Again, that's athleticgreens.com/huberman

00:30:24.020 | to get the five free travel packs

00:30:25.400 | and the year's supply of vitamin D3K2.

00:30:28.240 | Let's talk a little bit about dosing of psilocybin

00:30:30.840 | and also about microdosing of psilocybin.

00:30:33.880 | Now, this is an area that I wouldn't say is controversial,

00:30:37.100 | but that there's, how should we say this?

00:30:39.740 | There's a lot of loose thinking around this

00:30:43.620 | in the non-clinical, non-research communities.

00:30:46.740 | But within the clinical and research communities,

00:30:48.560 | there's a lot of data that's come out

00:30:50.760 | indicating what effective and safe doses,

00:30:53.980 | provided all other things are considered safe,

00:30:56.420 | safe doses of psilocybin actually are.

00:30:59.460 | And here, we really can go back to our discussion

00:31:02.680 | of psilocybin as "magic mushrooms" or mushrooms.

00:31:06.400 | And if one were to translate

00:31:08.460 | from the mushroom form of psilocybin

00:31:11.300 | to the psilocybin that's actually used in various studies,

00:31:14.900 | because frankly, in these studies,

00:31:16.820 | people aren't eating mushrooms.

00:31:18.040 | They're typically taking synthetic psilocybin,

00:31:20.040 | either intravenously, injected into a vein, or orally.

00:31:24.160 | And that's how the researchers are able

00:31:26.920 | to tightly control the amount of psilocybin.

00:31:28.940 | And the typical dosage that's used in clinical studies

00:31:33.520 | ranges from one milligram,

00:31:36.300 | often given repeatedly from day to day

00:31:40.940 | over long periods of time, so-called microdosing,

00:31:43.640 | and really that one milligram per day,

00:31:45.420 | or even up to three milligrams per day,

00:31:47.220 | repeatedly over time is what people

00:31:49.080 | generally think of as microdosing,

00:31:51.540 | as compared to, say, a 10-milligram dose given once,

00:31:56.140 | maybe twice in two separate sessions,

00:31:58.320 | or a 25 to 30-milligram dosage that's given once or twice.

00:32:03.320 | Now, those amounts of one to three milligrams,

00:32:07.640 | or 10 milligrams, or 25 to 30 milligrams

00:32:10.440 | might not mean much to those of you

00:32:12.520 | that don't think about these things in the research terms.

00:32:15.020 | Perhaps you've heard of microdosing,

00:32:17.100 | and you've also heard of macro or "heroic" dosing, okay?

00:32:21.940 | That's sort of a common,

00:32:24.000 | or I should say, popular nomenclature for psychedelics.

00:32:26.460 | And I'll circle back to that in a few minutes.

00:32:28.400 | But I think one of the questions that I hear a lot

00:32:31.220 | is how much psilocybin is present

00:32:34.440 | in a given amount of mushrooms.

00:32:36.680 | And so the way this typically works is that mushrooms

00:32:39.740 | are often discussed in terms of grams or ounces,

00:32:42.200 | so an eighth of mushrooms

00:32:43.680 | refers to an eighth of an ounce of mushrooms,

00:32:46.260 | or X number of grams of mushrooms.

00:32:49.220 | The breakdown is actually quite simple.

00:32:52.420 | 1,000 milligrams equals one gram.

00:32:55.500 | And the concentration of psilocybin

00:32:57.940 | in most so-called magic mushrooms is about 1%.

00:33:02.760 | So one gram of mushrooms being 1,000 milligrams

00:33:07.100 | means that it contains approximately,

00:33:09.440 | and again, it's approximately 10 milligrams of psilocybin.

00:33:13.980 | And in most of the clinical studies,

00:33:16.000 | it's been shown that the dosage of 25 to 30 milligrams

00:33:20.640 | given, or I should say, taken once or twice,

00:33:24.660 | we'll talk about the spacing of sessions a little bit later,

00:33:26.600 | taken once or twice is what's leading

00:33:29.640 | to the most pronounced therapeutic outcomes.

00:33:32.600 | But of course, with enhanced therapeutic outcomes,

00:33:36.600 | one also observes enhanced side effect profiles,

00:33:40.520 | or what are called adverse events.

00:33:42.640 | So there's an important nuanced conversation

00:33:44.460 | that has to take place.

00:33:45.320 | But right now we're talking about the conversion

00:33:47.380 | of grams of mushrooms to psilocybin.

00:33:49.360 | So one gram of mushrooms being 1,000 milligrams

00:33:53.360 | containing 1% psilocybin

00:33:56.440 | means that it contains 10 milligrams of psilocybin.

00:33:59.700 | Now, the so-called heroic doses that you've heard about,

00:34:02.580 | and this is something that's discussed more with the,

00:34:05.360 | let's call them traditional or classic psychonauts.

00:34:08.080 | These are people that may have an advanced degree,

00:34:10.320 | but typically are not running laboratories

00:34:12.840 | exploring the effects of psilocybin

00:34:14.560 | in controlled clinical trials.

00:34:17.260 | These are people who have been longtime explorers

00:34:20.700 | and often writers and people who have been spokespeople

00:34:23.920 | for psilocybin and other psychedelics.

00:34:26.160 | And they will often refer to the so-called heroic doses.

00:34:29.060 | It's a little bit hard to translate

00:34:30.680 | from that informal community to the scientific data,

00:34:33.980 | but in discussing that topic with various researchers

00:34:36.880 | who run laboratories at major universities

00:34:38.880 | focused on psychedelic therapies,

00:34:41.300 | what I was told is that the quote unquote heroic dose

00:34:44.500 | that's often discussed really refers to a five gram or so

00:34:49.840 | dose of mushrooms.

00:34:51.640 | So what that translates to is 50 milligrams of psilocybin.

00:34:56.640 | So when you hear someone talk about a quote unquote

00:34:58.520 | heroic dose, they're probably referring to ingestion

00:35:01.720 | of 50 milligrams or so of psilocybin,

00:35:04.860 | but in its mushroom form.

00:35:05.980 | So about five grams of mushrooms.

00:35:08.380 | And again, it's important to point out

00:35:09.880 | that the concentration of psilocybin

00:35:11.800 | in different strains of mushrooms and in different batches,

00:35:14.680 | and depending on the age of those mushrooms

00:35:16.400 | and how they've been stored, et cetera,

00:35:18.440 | can vary tremendously from batch to batch.

00:35:20.840 | In fact, there are some laboratories

00:35:22.080 | that have explored the range of psilocybin concentration

00:35:25.080 | in different mushroom strains

00:35:27.540 | and different so-called magic mushrooms.

00:35:29.580 | And that range is pretty broad.

00:35:31.200 | It's anywhere from a half percent all the way up to 2%.

00:35:36.200 | What that means is that someone might get a hold

00:35:38.420 | of one gram of mushrooms,

00:35:40.260 | thinking that they're taking 10 milligrams of psilocybin

00:35:43.040 | in those mushrooms when in fact they're actually taking 20.

00:35:45.640 | Or somebody could take three grams of mushrooms

00:35:47.420 | thinking they're taking 30 grams of psilocybin.

00:35:49.560 | And in fact, they're only taking 10

00:35:51.720 | or 15 milligrams of psilocybin.

00:35:54.300 | So the sourcing is really key.

00:35:56.340 | Obviously, as things become more legal and more regulated

00:36:00.280 | and more used in the therapeutic setting,

00:36:02.660 | or, and this is what's happening more and more,

00:36:04.840 | or as people start to rely on synthetically made psilocybin

00:36:09.340 | as opposed to using mushrooms to ingest psilocybin,

00:36:12.860 | then certainly the dosaging is going to be more consistent

00:36:16.220 | from batch to batch because we're not talking

00:36:17.740 | about batches of mushrooms.

00:36:18.660 | We're talking about batches of psilocybin itself.

00:36:21.340 | So now I'd like to take a step back

00:36:23.060 | from all this chemistry and cell biology

00:36:25.300 | and talk a little bit about the structure

00:36:27.140 | of a psilocybin journey itself

00:36:29.500 | and relate that to what we now know

00:36:32.120 | about what's happening in the brain

00:36:33.860 | during the psilocybin journey.

00:36:35.540 | And then a little bit later,

00:36:36.380 | we will return to that serotonin 2A receptor

00:36:39.180 | when we talk about some of the more lasting changes

00:36:42.340 | in brain chemistry and brain wiring

00:36:44.200 | that occur after the psilocybin journey is over.

00:36:48.060 | So let's take a couple of minutes

00:36:49.600 | and just discuss the various components

00:36:52.900 | of an effective therapeutic psilocybin journey.

00:36:55.740 | And here I'm not detailing a menu of things

00:36:58.320 | that people should do in order to pretend

00:37:00.580 | that they are a psilocybin assisted therapy coach

00:37:04.180 | or to do self-administered psilocybin therapy.

00:37:07.940 | That is not what I'm doing.

00:37:09.180 | What I am trying to do is to share with you

00:37:11.900 | the consistent components that are present

00:37:14.660 | in the clinical trials that have demonstrated

00:37:17.720 | the effectiveness of psilocybin

00:37:19.380 | for the treatment of depression

00:37:20.540 | and for other compulsive and addictive disorders.

00:37:23.180 | And those data, meaning the specific data

00:37:26.180 | related to those trials and the references themselves,

00:37:28.420 | we'll get into a little bit later.

00:37:30.020 | But we can't really have a conversation

00:37:32.340 | about psilocybin and what it does

00:37:34.200 | without talking about the so-called set and setting,

00:37:38.660 | as it's often referred to,

00:37:40.520 | that is known to at least bias the probability

00:37:44.360 | of the journey being beneficial

00:37:46.640 | and not a so-called bad trip.

00:37:48.560 | So what are the variables that make up

00:37:50.080 | an effective and safe psilocybin journey?

00:37:52.900 | And again, when we say safe,

00:37:54.920 | we're referring to people who are not prone

00:37:58.560 | to psychotic episodes.

00:38:00.000 | They don't even have a first relative

00:38:01.680 | that's prone to psychotic episodes.

00:38:04.300 | We're talking about people that are 25 years or older.

00:38:07.520 | We're talking about people that, for instance,

00:38:08.820 | are not taking antidepressants

00:38:10.940 | that impact the serotonin system.

00:38:12.400 | This is very important to understand.

00:38:13.920 | I think a lot of people don't know this,

00:38:15.900 | but as far as I know,

00:38:17.500 | all of the studies that have explored psilocybin

00:38:20.460 | for its ability to positively impact brain chemistry

00:38:24.300 | and mood and function have required

00:38:27.060 | that people either not be on or abstain

00:38:29.980 | from antidepressants in the weeks

00:38:32.500 | leading up to the psilocybin journey.

00:38:35.260 | Now, that is not to say

00:38:36.260 | that if you are currently taking SSRIs

00:38:38.060 | or something similar that you should cease taking them

00:38:39.980 | and do psilocybin.

00:38:40.820 | I'm absolutely not saying that.

00:38:42.160 | That could be very, very, very dangerous,

00:38:44.660 | if not catastrophic.

00:38:46.140 | Anytime you're going to take anything

00:38:47.500 | or stop taking anything for that matter,

00:38:49.460 | you do need to consult with your physician,

00:38:51.580 | in this case, a psychiatrist as well.

00:38:53.720 | So let's talk about psilocybin journeys

00:38:55.660 | from the subjective side and from the structural side.

00:38:58.340 | And when I say the structural side,

00:39:00.040 | what I mean is what does a psychedelic journey

00:39:02.700 | actually include?

00:39:03.880 | And here are the words set and setting

00:39:06.500 | become extremely important.

00:39:07.840 | Some of you may have heard that set and setting

00:39:10.580 | are the foundation of a well done

00:39:14.860 | or even therapeutically beneficial psychedelic journey.

00:39:18.740 | And all of that really hinges on safety and outcomes.

00:39:21.940 | So set refers to mindset,

00:39:23.600 | the mindset of the person taking the psychedelic

00:39:26.100 | and setting refers to, as the name suggests,

00:39:28.860 | the setting in which they're taking it in

00:39:30.240 | and the people that are present there.

00:39:32.220 | So let's talk about setting first.

00:39:34.100 | The setting for a psychedelic journey

00:39:36.140 | needs to be one in which the person under the influence

00:39:38.300 | of the psilocybin or other psychedelic is safe.

00:39:41.280 | That means no windows they can jump out of,

00:39:44.060 | that means no streets of moving cars they can run out into,

00:39:47.900 | that means no opportunity for getting lost,

00:39:50.600 | that means no opportunity for getting into bodies of water.

00:39:53.760 | In other words, it requires that there be at least one

00:39:57.540 | and perhaps even two or more other individuals

00:40:00.440 | who are not also taking psychedelics, right?

00:40:03.260 | Who are not also taking psychedelics,

00:40:05.520 | present in that setting to ensure

00:40:08.600 | that the person taking the psilocybin

00:40:10.720 | is not going to harm themselves or others.

00:40:13.180 | I say this not to sound like a school teacher,

00:40:15.260 | even though technically I'm a school teacher,

00:40:17.980 | but because of course I don't want anyone to get harmed.

00:40:20.860 | And I'm also aware that there's a lot of interest nowadays

00:40:24.920 | in psychedelics such as psilocybin becoming legal

00:40:28.540 | or decriminalized for their therapeutic applications.

00:40:31.900 | And if we look back to the late 1960s and early 1970s

00:40:35.500 | when the Controlled Substances Act was invoked

00:40:38.040 | to make psychedelics like psilocybin illegal,

00:40:41.000 | one of the bases for that

00:40:42.960 | was not just the geopolitical unrest at the time

00:40:46.160 | and things like the Vietnam War,

00:40:47.540 | but also some highlighted instances

00:40:50.600 | in which people did not take set

00:40:52.840 | and setting into consideration,

00:40:55.100 | took things like LSD, stared at the sun, went blind,

00:40:58.400 | or took psilocybin, went out and harmed somebody else.

00:41:02.220 | Again, these are very, very isolated instances,

00:41:05.120 | but these are the exact sort of instances

00:41:07.280 | that lead to criminalization

00:41:10.500 | or the fact that things like psilocybin and LSD

00:41:13.040 | and MDMA for that matter are considered illegal.

00:41:15.840 | Again, I completely acknowledge

00:41:17.500 | that there are a number of different factors

00:41:19.180 | making them illegal.

00:41:20.040 | We could have a whole discussion about that.

00:41:22.500 | We talked about the drug trade, the war on drugs,

00:41:24.580 | but right now is such a critical time in the history

00:41:28.660 | and the use of psychedelics

00:41:30.100 | for therapeutic and other reasons.

00:41:32.300 | And getting setting correct,

00:41:34.820 | meaning making it absolutely as safe as possible

00:41:37.440 | for the person taking the psychedelic is absolutely key.

00:41:39.900 | And one of the best ways to ensure that it's safe

00:41:42.720 | is to have responsible individuals

00:41:44.580 | who are not under the influence of psychedelics

00:41:46.500 | present in that environment.

00:41:47.980 | So that's one component of setting.

00:41:49.420 | The other component of setting that we talked about earlier,

00:41:51.820 | which turns out to be very important,

00:41:53.500 | is the opportunity and perhaps even the bias

00:41:57.020 | toward the person on the psychedelic being seated

00:42:00.220 | or ideally lying down and being in the eye mask

00:42:02.740 | or at least having their eyes covered

00:42:04.600 | so that they can combine

00:42:06.060 | any spontaneous visual hallucinations that occur

00:42:09.180 | with the various thought processes that are occurring

00:42:11.700 | while under the influence of psychedelics.

00:42:14.360 | This is far and away different than quote unquote,

00:42:17.140 | taking mushrooms and going into the woods

00:42:18.760 | or taking mushrooms and going to the beach.

00:42:21.020 | What we're talking about today

00:42:22.220 | is the use of psychedelics

00:42:23.980 | for particular brain rewiring outcomes

00:42:26.780 | that yes, can involve things

00:42:29.060 | like changing one's relationship to nature

00:42:31.260 | or changing one's relationship to somebody else

00:42:33.460 | by interacting with nature or somebody else.

00:42:35.380 | And while I'm not trying to diminish the potential value

00:42:38.300 | of those sorts of psychedelic journeys,

00:42:40.380 | if we look at the scientific data,

00:42:42.220 | the vast majority of it,

00:42:44.700 | not just in the clinical setting,

00:42:46.020 | but in terms of understanding the safety and efficacy

00:42:48.900 | and positive rewiring of brain circuitry

00:42:51.860 | that allows people to feel better,

00:42:53.360 | to understand themselves better

00:42:54.740 | and to interact with life in more adaptive ways

00:42:57.500 | going forward out of the psychedelic journey

00:42:59.740 | involve these very, let's say, you know,

00:43:04.100 | subdued settings that are typically in one room,

00:43:08.420 | a closed environment with one or two other individuals

00:43:11.140 | acting as sort of guides or helping the individual

00:43:15.280 | by talking to them from time to time

00:43:17.120 | if they feel like they have to sort through

00:43:18.580 | a particular aspect of the psychedelic journey

00:43:20.800 | that's creating anxiety.

00:43:21.920 | And we'll talk about the contour of the psychedelic journey

00:43:23.980 | that almost everyone who takes psilocybin

00:43:26.420 | at somewhere between 20 and 30 milligram dosages

00:43:29.600 | tends to experience.

00:43:30.940 | But the setting that I'm describing

00:43:33.080 | is not just a list of things to, you know,

00:43:35.260 | make sure you're safe,

00:43:36.100 | but they're really the list of things that also ensure

00:43:38.840 | that one can get the maximum benefit

00:43:41.120 | out of the psilocybin journey.

00:43:43.080 | Now, other things included in setting that are known,

00:43:45.900 | again, from scientific literature to be very influential

00:43:48.880 | in terms of the experience that one has

00:43:50.860 | and to bias things towards a positive experience

00:43:53.260 | are, again, safety, eye mask,

00:43:56.280 | but also the presence of music.

00:43:58.900 | Now, when I first heard about this

00:44:00.380 | from one of the premier researchers

00:44:02.780 | on psilocybin and other psychedelics,

00:44:04.460 | which is Robin Cardart-Harris,

00:44:05.700 | he's a professor at University of California, San Francisco,

00:44:08.780 | who's one of the major pioneers

00:44:10.580 | in the studies of psychedelics.

00:44:12.100 | And when he first started telling you

00:44:13.100 | about the critical role that music plays,

00:44:15.240 | I thought, okay, that makes sense.

00:44:16.940 | You know, music can impact our emotion,

00:44:19.880 | impact the way that we think

00:44:22.520 | and could therefore impact what one experiences

00:44:26.080 | during the psychedelic journey.

00:44:27.360 | But he really underscored for me

00:44:29.300 | the extent to which music is not just

00:44:31.820 | a sort of incidental feature of the setting

00:44:35.680 | in psychedelic set and setting,

00:44:37.420 | but that it is one of the major drivers

00:44:41.860 | of the actual cognitive and emotional experience

00:44:45.240 | that somebody has on something like psilocybin

00:44:49.080 | that allows the psilocybin journey

00:44:51.000 | to be looked at or viewed not just as beneficial,

00:44:53.760 | but, and this is quoted in the scientific literature,

00:44:56.140 | as one of the most profound and important

00:44:58.540 | positive experiences that one ever experienced

00:45:01.540 | in their life.

00:45:02.740 | So let's talk about the sorts of music

00:45:04.120 | that have been used in these clinical studies.

00:45:06.280 | Well, first of all, we need to think about

00:45:08.780 | how long the psilocybin journey itself is going to be.

00:45:12.200 | And the typical duration of the psilocybin journey

00:45:14.500 | is anywhere from four to six hours.

00:45:16.980 | It's going to depend somewhat on dose.

00:45:18.980 | It's going to depend somewhat on variability

00:45:22.380 | in people's liver metabolism.

00:45:25.340 | And it's also going to depend somewhat

00:45:27.380 | on how much food people have in their gut.

00:45:29.940 | In all the clinical studies that I read,

00:45:32.780 | it was advised that people not have any food in their gut

00:45:37.140 | at the time at which they ingest

00:45:39.060 | or injected with the psilocybin.

00:45:41.340 | It's particularly true if people

00:45:42.340 | are going to be taking psilocybin mushrooms

00:45:44.340 | in order to get their psilocybin.

00:45:45.860 | And that has been done in a few studies.

00:45:48.180 | Most studies, however, use synthetic psilocybin

00:45:50.180 | taken orally.

00:45:51.740 | Again, that's converted to psilocin in the gut

00:45:53.980 | by the acidity of the gut.

00:45:55.260 | And the acidity of the gut is going to be impacted

00:45:57.620 | by the various foods that people eat.

00:45:58.980 | And so that's one of the major reasons

00:46:00.800 | why people are advised to not eat for at least four hours

00:46:04.380 | prior to the psilocybin journey.

00:46:06.500 | So here we've got this six hour, what we're calling journey,

00:46:09.820 | 'cause that's what everyone calls it, or trip,

00:46:12.520 | that people start experiencing about 30 to 45 minutes

00:46:17.340 | after ingesting psilocybin or taking psilocybin.

00:46:21.140 | There's a peak component

00:46:22.900 | in which there's a maximal intensity of emotion

00:46:26.340 | and often that's also associated with anxiety.

00:46:29.540 | And this is very important to understand.

00:46:31.720 | The anxiety component is part of what,

00:46:34.700 | in the therapeutic setting,

00:46:35.740 | they refer to as ego dissolution.

00:46:37.980 | And that anxiety around the peak,

00:46:40.720 | and I think most people would probably hear peak experience

00:46:42.880 | and think, oh, we're talking about

00:46:44.220 | a peak positive experience.

00:46:46.580 | But no, we're referring to a peak experience and anxiety

00:46:51.580 | that people stay with and then come down from gradually

00:46:56.760 | as one goes from the second or third hour

00:46:59.780 | after taking psilocybin.

00:47:01.300 | And that tapers off slowly toward the six hour mark,

00:47:05.840 | what sometimes people refer to as parachuting back in.

00:47:09.680 | Of course, they're not, hopefully,

00:47:11.560 | I would very much hope people aren't actually

00:47:13.620 | parachuting back in while on psilocybin,

00:47:15.660 | but I think you get the idea.

00:47:17.300 | The music that's typically played in the clinical studies

00:47:22.260 | using psilocybin for the treatment of depression

00:47:24.760 | or for compulsive disorders or addiction

00:47:27.520 | tends to have a particular contour that matches with

00:47:30.960 | and can also drive that contour of the psilocybin journey

00:47:35.660 | that I just described.

00:47:37.040 | Again, we're talking about people wearing an eye mask

00:47:40.140 | with guides present.

00:47:41.600 | So people who are not taking psilocybin there as well

00:47:44.940 | to ensure that the person feels supported and is safe.

00:47:48.320 | The person is typically lying down, sometimes sitting down,

00:47:51.680 | but more often than not lying down, wearing an eye mask.

00:47:55.240 | And the music that's played at the beginning

00:47:57.520 | of the psilocybin session tends to be music

00:48:00.540 | that doesn't have a lot of vocalizations.

00:48:03.040 | It tends to be things like classical music.

00:48:04.920 | It tends to be fairly low volume,

00:48:07.020 | but that then transitions into music

00:48:10.200 | that has a lot of percussion.

00:48:13.420 | So often drums that tends to be higher volume

00:48:16.420 | that has a lot of intensity at about the time

00:48:20.460 | that one would be experiencing the peak in emotion

00:48:24.140 | and in perception, the so-called peak of the journey.

00:48:27.080 | That intense music tends to be played

00:48:30.400 | for about 45 minutes to 90 minutes,

00:48:33.780 | depending on the study one looks at.

00:48:35.940 | And then tends to transition into softer music again,

00:48:40.740 | sometimes choral type or more melodic music,

00:48:43.880 | often female voices in particular,

00:48:46.060 | and then transition into nature sounds and things

00:48:49.180 | that more or less mimic the outside natural world

00:48:51.820 | and less so synthetic things like drums or instruments

00:48:56.160 | and vocalizations and things of that sort.

00:48:58.200 | So why would it be so important that music match

00:49:01.360 | and even contribute to the subjective experience

00:49:04.180 | that people have on psychedelics?

00:49:05.620 | And here we should probably take a couple of moments

00:49:08.020 | and just talk about what those subjective experiences

00:49:10.580 | are like.

00:49:11.420 | So for people that haven't done psilocybin

00:49:12.880 | or any psychedelics, it's a little hard to describe,

00:49:16.500 | but one way to describe it is that there's a lot

00:49:19.280 | of so-called perceptual blending.

00:49:21.100 | So for instance, people in the eye mask will report seeing

00:49:24.440 | some geometric shapes and colors,

00:49:26.780 | but perhaps the music they're listening to

00:49:28.780 | will then start to change the intensity or the movement

00:49:32.800 | of whatever it is that they're seeing, hallucinating,

00:49:35.440 | inside of the eye mask in ways that are linked.

00:49:38.100 | This is referred to as synesthesia or the merging

00:49:40.940 | of different senses that are not ordinarily merged.

00:49:44.180 | In addition, people under the influence of psilocybin

00:49:46.840 | or other psychedelics for that matter,

00:49:48.900 | often will report that their pattern of breathing

00:49:51.780 | becomes linked to the perceptions of things

00:49:54.960 | that they are hearing or seeing or feeling.

00:49:57.480 | So for instance, if they take a big deep breath in

00:50:00.020 | and then a long exhale out,

00:50:01.540 | they may find that during the long exhale out,

00:50:04.240 | that the notes of music that they're hearing

00:50:06.260 | in those moments are also drawn out

00:50:09.140 | for the duration of the breath and they'll inhale

00:50:11.260 | and that they're getting at least what they perceive

00:50:13.300 | as control over the music,

00:50:15.540 | which of course they are not actually controlling

00:50:17.500 | by using their breath.

00:50:19.020 | And that perhaps their visual perceptions

00:50:21.220 | are also being merged with that.

00:50:22.820 | So those are just a couple of examples

00:50:24.580 | of how perceptual blending, AKA synesthesia,

00:50:27.840 | can occur while under the influence of psilocybin.

00:50:30.480 | And this really is highly individual

00:50:32.760 | from one person to the next.

00:50:34.180 | Some people, for instance,

00:50:35.080 | will find that if they take their fingertips

00:50:37.580 | and rub them across the couch or the chair

00:50:40.440 | that they happen to be lying down or sitting on,

00:50:42.640 | that they will experience a change in the music.

00:50:45.760 | Maybe even if they move their hand up,

00:50:47.920 | they hear an increase in frequency of sound,

00:50:49.640 | they move their hand down,

00:50:50.520 | they hear a decrease in frequency of sound,

00:50:52.080 | then all of this is linked to their emotional state

00:50:55.080 | at the same time and vice versa.

00:50:56.800 | Okay, so we're talking about a lot of perceptual

00:50:59.560 | and emotional blending and some sense of control

00:51:03.780 | over one's perceptions and emotions

00:51:06.560 | in a way that's very unordinary, even extraordinary.

00:51:11.340 | Now, we can step back from all of this

00:51:13.480 | very subjective description of the psychedelic journey

00:51:16.020 | and ask what is going on

00:51:18.300 | that would allow these sorts of things to occur?

00:51:20.860 | And there you are already equipped with an understanding

00:51:23.120 | of the cell biology and the chemistry

00:51:24.700 | that makes all of this possible.

00:51:26.420 | And that is that when psilocybin is ingested

00:51:30.060 | and then converted to psilocin,

00:51:31.620 | that's the psilocin that crosses the blood brain barrier,

00:51:34.180 | and then even though psilocin looks a lot like serotonin,

00:51:37.260 | psilocin has this incredible ability

00:51:39.060 | to predominantly activate the serotonin 2A receptor.

00:51:42.920 | Well, we can understand much of what's happening

00:51:46.600 | at a subjective level during the psychedelic journey,

00:51:49.220 | even right down to the sorts of emotions

00:51:51.120 | and perceptual blending, the synesthesia,

00:51:53.440 | we can understand a lot of that

00:51:55.020 | by understanding where the serotonin 2A receptors

00:51:58.140 | are expressed on neurons

00:52:00.140 | and what those particular neurons are doing.

00:52:02.780 | And the simplest way to describe this

00:52:04.260 | is that there's a category of neurons

00:52:06.540 | that we call pyramidal neurons.

00:52:07.900 | Pyramidal neurons are found lots of places in the brain,

00:52:10.500 | but they're called pyramidal neurons

00:52:11.700 | 'cause they're shaped like a pyramid.

00:52:13.580 | They have a cell body, which is the part of the cell

00:52:15.480 | that has the DNA in it and a lot of other important things

00:52:19.420 | like the organelles, mitochondria, et cetera.

00:52:22.280 | And then they also have what are called dendrites.

00:52:24.280 | Dendrites are the little branches or processes

00:52:27.440 | that reach out both from the bottom of these cells,

00:52:30.680 | and then these pyramidal cells are interesting

00:52:33.800 | because they also grow a branch up, up, up, up, up

00:52:37.100 | into layers of neural tissue above them,

00:52:40.440 | and they have what's called an apical branch.

00:52:42.120 | That's the part that grows up.

00:52:43.380 | And then they fan out at the top.

00:52:45.460 | And that fanning out at the top allows them to communicate

00:52:47.880 | with other neurons in their environment, okay?

00:52:49.820 | So if you're not getting a good picture of this in your mind

00:52:51.780 | from my description, I apologize,

00:52:53.540 | but simply think about putting your arms out to the side.

00:52:57.980 | And by doing that, you're able to interact with things

00:53:00.400 | that are some distance from your body.

00:53:01.900 | It's sort of an obvious thing in that case.

00:53:04.500 | These cells are effectively doing the same thing

00:53:06.640 | by extending little processes out

00:53:09.420 | into layers above them and to the sides.

00:53:12.260 | And this is really important

00:53:13.380 | because much of the serotonin 2A receptors

00:53:16.020 | that are present on neurons in the brain

00:53:17.720 | are present in those apical dendrites,

00:53:20.180 | those branches of these pyramidal neurons that are above

00:53:23.940 | and that extend out to the side of those neurons.

00:53:27.380 | And so when somebody is under the influence of psilocybin,

00:53:30.860 | that means that psilocin has bound to the receptors

00:53:35.060 | on those apical dendrites,

00:53:36.620 | and it's increasing lateral communication

00:53:39.340 | across brain areas.

00:53:40.860 | In fact, this is perhaps one of the most well-documented

00:53:44.220 | effects of psilocybin and other psychedelics,

00:53:47.200 | which is that there's a shift from the brain

00:53:50.140 | being more modular, meaning more segmented,

00:53:52.480 | like auditory neurons are communicating electrically

00:53:55.220 | and chemically, largely with other auditory neurons.

00:53:58.460 | Of course, they'll communicate

00:53:59.300 | with other types of neurons too, right?

00:54:00.700 | When I hear something off to my right,

00:54:02.220 | you know, like a snap of fingers off to the right,

00:54:04.060 | I'll turn my head, and my ability to do that

00:54:06.900 | depends on my auditory neurons being linked up

00:54:08.940 | with things like my motor system and my visual system.

00:54:11.640 | But the key thing to understand is that

00:54:14.460 | when there is psilocybin present in one system,

00:54:18.000 | that the communication of any of these pyramidal neurons,

00:54:23.140 | the ones involved in hearing,

00:54:24.300 | the ones involved in thinking,

00:54:25.940 | the ones involved in memory,

00:54:27.520 | the ones involved in visual perception

00:54:30.300 | or in the generation of visual hallucinations

00:54:32.580 | with eyes closed,

00:54:33.980 | those are all talking to many, many more other neurons,

00:54:38.860 | more extensively.

00:54:40.780 | So what happens effectively is that

00:54:42.960 | there's a reduction in the modularity,

00:54:45.180 | the separateness of function in the brain

00:54:47.540 | and an increase in what's called integration

00:54:51.100 | of communication across

00:54:53.220 | what would otherwise be disparate brain regions.

00:54:55.960 | We can say that really simply by saying

00:54:58.060 | psilocybin increases communication across the brain.

00:55:02.100 | Now, in addition to that,

00:55:03.700 | there's a reduction in what's called

00:55:05.260 | the hierarchical organization of the brain.

00:55:07.660 | Typically sensory information comes in

00:55:10.160 | from the outside environment.

00:55:11.300 | So we hear something, we see something,

00:55:12.900 | we taste something, we smell something.

00:55:15.100 | And in what's called a bottom up fashion,

00:55:18.060 | meaning bottom from the periphery,

00:55:19.840 | up, meaning it propagates up through the eyes,

00:55:24.260 | through the nose, through the ears,

00:55:25.660 | through the skin or the senses in those regions,

00:55:29.540 | I should say,

00:55:30.380 | up into areas of the brain that sit deep to the cortex,

00:55:34.880 | like the thalamus.

00:55:37.020 | And then the thalamus is sort of a way station.

00:55:39.620 | It's like a switchboard that sends visual stuff

00:55:41.620 | to the visual centers and auditory stuff

00:55:43.200 | to the auditory centers and touch stuff to the touch centers

00:55:45.600 | and things that maybe trigger a memory

00:55:48.620 | off to the memory centers of the brain, et cetera.

00:55:51.400 | That's the typical organization.

00:55:52.740 | It's hierarchical because it goes from the periphery

00:55:55.180 | up to the more complex processing regions of the brain

00:55:58.060 | that make decisions that link all of that stuff

00:56:01.100 | to prior experience, maybe plans about the future.

00:56:05.500 | When psilocybin is present in the system,

00:56:07.500 | there's a broadening of the flow of that information

00:56:11.080 | from the bottom up as well.

00:56:13.460 | Okay, and that has to do with what's called thalamic gating.

00:56:15.880 | The thalamus is a very interesting structure.

00:56:17.660 | We probably don't want to go into it

00:56:18.720 | in too much detail right now,

00:56:20.560 | but it really is like a switchboard in a way station

00:56:23.080 | saying, hey, pay attention to the visual stuff,

00:56:25.880 | pay attention to the auditory stuff,

00:56:27.180 | or just to the visual and auditory stuff,

00:56:28.780 | and ignore touch sensation for the time being

00:56:31.820 | or vice versa.

00:56:33.700 | When psilocybin is present in the system

00:56:36.180 | and when serotonin 2A receptors are activated very strongly,

00:56:40.300 | there's a tremendous broadening of the flow of information

00:56:44.120 | up and through the thalamus.

00:56:45.660 | So not only is there more communication

00:56:47.340 | of so-called higher order brain centers,

00:56:49.800 | we refer to them as higher order

00:56:51.140 | because they're involved in thinking and decision-making

00:56:53.060 | and emotion, et cetera,

00:56:54.380 | but there's also a shift in the flow of sensory information

00:56:58.380 | into the brain that can generally be described as broader

00:57:02.800 | and including more blending of the different senses.

00:57:06.360 | And when I say blending of the senses,

00:57:07.900 | I'm also referring to blending of the sense of interoception

00:57:11.540 | of our sense of our body

00:57:13.300 | and what's happening inside of our body.

00:57:15.260 | And this, without question, at least partially explains

00:57:19.660 | why when under the influence of psilocybin,

00:57:22.820 | one's breathing can be linked to a sound,

00:57:25.080 | and then suddenly the sound, one thinks,

00:57:28.260 | is being controlled by one's breathing

00:57:30.300 | or that the sound itself can be linked to something

00:57:33.200 | that we see in our mind's eye while in the eye mask.

00:57:36.600 | Essentially, what I'm describing here

00:57:37.960 | is that serotonin 2A receptor activation

00:57:41.560 | allows for more broad, less precise,

00:57:45.080 | and less hierarchical activation of brain circuitry.

00:57:48.480 | And when I say hierarchical,

00:57:50.120 | what I mean is that normally things go from periphery,

00:57:53.060 | from eyes to thalamus to visual cortex.

00:57:55.900 | However, when under the influence of psilocybin,

00:57:58.840 | as I mentioned before, even in the eye mask,

00:58:01.200 | the visual cortex is going to be very activated

00:58:03.280 | even in the absence of any visual input.

00:58:05.540 | So then if one hears a sound, perhaps from music,

00:58:10.340 | a particular motif or voice,

00:58:12.080 | and that's linked to a particular emotional state,

00:58:14.440 | that is now being blended with visual phenomenon

00:58:17.880 | occurring within the brain that have no external stimulus.

00:58:20.960 | And so while the patterns of activation in the brain

00:58:24.060 | while under the influence of psilocybin aren't random,

00:58:26.880 | they are far less channeled, far less modular,

00:58:30.080 | and far less hierarchical than would ever be the case

00:58:33.300 | when not under the influence of psilocybin.

00:58:36.420 | I'd like to just take a brief break

00:58:38.000 | and thank one of our sponsors, which is Element.

00:58:40.880 | Element is an electrolyte drink

00:58:42.280 | that has everything you need and nothing you don't.

00:58:44.520 | That means plenty of salt, sodium, magnesium, and potassium,

00:58:48.160 | the so-called electrolytes, and no sugar.

00:58:50.980 | Now, salt, magnesium, and potassium are critical

00:58:53.800 | to the function of all the cells in your body,

00:58:55.660 | in particular to the function of your nerve cells,

00:58:58.320 | also called neurons.

00:58:59.500 | And we now know that even slight reductions

00:59:02.120 | in electrolyte concentrations or dehydration of the body

00:59:05.340 | can lead to deficits in cognitive and physical performance.

00:59:08.920 | Element contains a science-backed electrolyte ratio

00:59:11.460 | of 1,000 milligrams, that's one gram of sodium,

00:59:14.560 | 200 milligrams of potassium, and 60 milligrams of magnesium.

00:59:18.080 | I typically drink Element first thing in the morning

00:59:20.120 | when I wake up in order to hydrate my body

00:59:22.260 | and make sure I have enough electrolytes.

00:59:24.040 | And while I do any kind of physical training

00:59:26.300 | and after physical training as well,

00:59:27.820 | especially if I've been sweating a lot,

00:59:29.620 | and certainly I drink Element in my water

00:59:32.440 | when I'm in the sauna and after going in the sauna

00:59:34.920 | because that causes quite a lot of sweating.

00:59:36.580 | If you'd like to try Element, you can go to Drink Element,

00:59:39.560 | that's lmnt.com/huberman,

00:59:42.140 | to claim a free Element sample pack with your purchase.

00:59:44.460 | Again, that's Drink Element, lmnt.com/huberman.

00:59:48.740 | Now, in all fairness to the scientific literature,

00:59:50.880 | there are not one, not two, not three,

00:59:53.140 | but four prominent theories of which brain networks

00:59:56.460 | are most activated during a psilocybin

00:59:59.040 | or other psychedelic journey.

01:00:00.460 | And so for those of you that are interested

01:00:01.860 | in those different models, first of all,

01:00:03.780 | please know that they are not competing models.

01:00:06.280 | While some of them disagree about some of the details,

01:00:08.720 | it's very likely that all of these models are true.

01:00:10.740 | They include things like changes

01:00:12.080 | in the so-called default mode network.

01:00:13.900 | There's a lot of interest in this.

01:00:15.260 | I've talked about it before on this podcast,

01:00:17.540 | the default mode network, 'cause the network in the brain

01:00:19.980 | that's thought to be responsible for spontaneous imagination,

01:00:23.260 | for daydreaming, and that reflects sort of

01:00:25.500 | the base activation state of the brain

01:00:29.380 | when there's no drugs in our system.

01:00:31.480 | And the default mode network is one of the systems,

01:00:34.220 | or networks rather, that is thought to be rewired

01:00:37.420 | under conditions of psilocybin or other psychedelics.

01:00:41.140 | Again, if you're interested in these models

01:00:42.700 | and comparing and contrasting them,

01:00:44.000 | there's a very nice review from Brian Roth's lab at Duke

01:00:47.700 | entitled "The Neural Basis of Psychedelic Action"

01:00:49.860 | and we'll provide a link to this in the show note captions.

01:00:52.160 | And again, I just want to emphasize that all of these models

01:00:55.860 | have been shown to be true in different studies.

01:00:58.900 | And what they all point to is more extensive communication

01:01:02.240 | between areas of the brain that normally are not as active

01:01:06.980 | at the same time while under the influence of psychedelics,

01:01:10.780 | such as psilocybin.

01:01:12.580 | The controversy in the field relates

01:01:14.160 | to which of these networks is the one that changes the most

01:01:17.260 | to explain the therapeutic outcomes

01:01:19.620 | that have been discovered in recent years.

01:01:21.060 | So again, check out that review

01:01:22.160 | if you're interested in that sort of thing.

01:01:23.980 | In the meantime, we can cut a broad swath

01:01:25.700 | through all of those models and just say that psilocybin

01:01:28.660 | expands the functional connectivity of the brain

01:01:31.980 | while one is under the influence of psilocybin.

01:01:34.420 | And it does seem that some of that expanded

01:01:36.240 | functional connectivity persists

01:01:37.780 | after the effects of psilocybin have worn off.

01:01:40.820 | And that statement about the functional connectivity

01:01:43.460 | of the brain being more expanded,

01:01:44.980 | not just during the psilocybin session, but after as well,

01:01:48.660 | has been substantiated in a number of papers.

01:01:50.520 | But one of the key papers in this area

01:01:52.400 | is one that I recommend people check out

01:01:54.380 | if they're interested in this sort of thing

01:01:55.940 | is entitled the effects of psilocybin and MDMA

01:01:58.340 | on between network resting state functional connectivity

01:02:01.340 | in healthy volunteers.

01:02:02.620 | And I like this paper for a number of reasons.

01:02:04.420 | First of all, it's a very high quality paper carried out

01:02:06.980 | in the laboratory of Robin Cardart Harris at UCSF.

01:02:10.140 | Again, one of the premier researchers

01:02:11.580 | in this area of psychedelics and their function,

01:02:14.620 | what they do in the brain

01:02:15.460 | and also their therapeutic applications,

01:02:17.120 | but also because it focused on healthy volunteers.

01:02:19.320 | They explored using brain imaging,

01:02:21.320 | what brain areas are active in a resting state.

01:02:23.780 | So things like default mode network.

01:02:25.620 | Then they had people take psilocybin or MDMA.

01:02:30.220 | And then they looked at the connectivity

01:02:32.280 | between those brain areas in those same individuals

01:02:35.880 | when they were not under the influence of these drugs

01:02:38.100 | and found more extensive connectivity.

01:02:40.180 | All of which pointed to an enhanced lateral connectivity,

01:02:44.520 | less hierarchical organization, effectively more

01:02:47.980 | interconnection and communication

01:02:49.780 | between different brain areas.

01:02:51.300 | I think not only is the fact that they looked

01:02:53.300 | at healthy volunteers very interesting and important,

01:02:55.540 | but also that they looked at this resting state

01:02:58.140 | of the brain.

01:02:58.980 | They weren't providing a particular auditory

01:03:00.740 | or visual stimulus for people to hear or look at

01:03:02.900 | while they were in the brain imaging scanner as it's called.

01:03:06.180 | Rather, they were simply looking at how the brain

01:03:08.540 | was behaving at rest.

01:03:10.280 | And so it's very clear that for people that do two

01:03:12.420 | or even just one of these psilocybin journeys

01:03:14.780 | at a particular dose,

01:03:16.400 | that the brain is actually getting rewired.

01:03:19.400 | We hear this a lot.

01:03:21.200 | Psilocybin or other psychedelics lead to plasticity.

01:03:24.000 | They rewire your brain.

01:03:25.520 | Let's go back to what we said at the beginning.

01:03:27.600 | Rewiring of the brain is not the goal.

01:03:29.680 | Adaptive rewiring of the brain is the goal.

01:03:33.860 | Rewiring that leads to new ideas that are interesting,

01:03:37.660 | that are accessible after the psychedelic journey.

01:03:41.440 | New ideas and new ways of thinking or feeling

01:03:43.680 | that allow people to function better in their lives.

01:03:46.000 | That's the goal of effective psychedelic therapies,

01:03:48.780 | not simply rewiring of the brain.

01:03:50.780 | You know, a brain injury for that matter

01:03:52.240 | will lead to rewiring of the brain,

01:03:53.760 | but that's maladaptive rewiring.

01:03:55.780 | The use of things like amphetamines or methamphetamines

01:03:58.240 | in particular will lead to rewiring of the brain,

01:04:00.840 | but that is strongly maladaptive rewiring.

01:04:04.000 | So now there are really dozens of studies conducted

01:04:07.200 | in humans using brain imaging and other techniques

01:04:10.200 | and have evaluated how things like psilocybin

01:04:13.040 | change connectivity in the brain.

01:04:14.640 | And I think the take home message is

01:04:16.720 | it expands that connectivity.

01:04:19.080 | However, it seems to do so in ways that still allow people

01:04:22.560 | to function in their daily lives.

01:04:24.360 | And one of the key things that I gleaned from the literature

01:04:26.880 | on the therapeutic use of psilocybin

01:04:29.960 | for the treatment of depression is that very seldom

01:04:34.840 | do people who take psilocybin experience

01:04:37.120 | long-term issues with memory.

01:04:39.200 | Why is that so critical?

01:04:40.180 | Well, you could imagine that increasing connectivity

01:04:42.880 | in the brain, reducing modularity,

01:04:45.240 | reducing hierarchical organization in the brain

01:04:47.600 | would lead to disruptions in memory, right?

01:04:49.320 | It's as if you're shuffling books on the bookshelf,

01:04:51.320 | so to speak, but that doesn't seem to be the case.

01:04:54.080 | Rather, it seems that the increase in connectivity

01:04:56.800 | is leading provided set and setting are correct,

01:05:00.780 | provided safety protocols are followed

01:05:03.360 | to positive rewiring or adaptive rewiring of neural tissue.

01:05:07.540 | So that's one of the things that makes psychedelics

01:05:09.860 | and psilocybin in particular very exciting

01:05:12.560 | from the therapeutic standpoint.

01:05:14.200 | And of course, we have to acknowledge

01:05:15.720 | it's also what has a lot of people excited

01:05:18.080 | about psychedelics,

01:05:19.280 | not just for the treatment of depression,

01:05:20.900 | but for expanding the brain's capabilities more generally.

01:05:23.820 | So along those lines,

01:05:25.280 | I want to touch on the issues of creativity

01:05:27.400 | and the experience of life outside of psychedelic journeys

01:05:30.760 | is impacted by psychedelic journeys.

01:05:33.000 | And here, this relates to a question that I heard a lot

01:05:35.960 | when I put the call out on social media

01:05:37.980 | that I was going to do this episode,

01:05:39.640 | and I asked people,

01:05:40.480 | what do you want to know about psilocybin?

01:05:41.300 | And one of the more common questions that I got was,

01:05:43.800 | does it increase creativity?

01:05:46.060 | Does it increase our experience of life

01:05:48.120 | in ways that are beneficial

01:05:49.320 | aside from its now documented positive effects

01:05:52.640 | in treating depression and compulsive disorders

01:05:55.140 | and addiction?

01:05:56.580 | And the short answer to this is yes,

01:06:00.460 | but that the positive effects of psychedelics,

01:06:04.400 | psilocybin in particular,

01:06:05.660 | on creativity and our experience of life

01:06:08.280 | have only been explored in a fairly narrow set of dimensions.

01:06:12.200 | However, where it's been explored,

01:06:13.640 | there's some really interesting findings.

01:06:15.000 | So one of the more interesting findings, I think,

01:06:17.140 | is a paper entitled

01:06:18.160 | Increased Low-Frequency Brain Responses to Music

01:06:20.920 | After Psilocybin Therapy for Depression.

01:06:23.260 | I think this is a really interesting paper

01:06:24.760 | because what the authors did is they took advantage

01:06:26.800 | of the fact that in these therapeutic psilocybin sessions

01:06:29.520 | that are carried out for the treatment of depression,

01:06:31.660 | music is being played.

01:06:33.800 | And there are prior studies showing that

01:06:37.320 | when music is played,

01:06:39.040 | you activate different brain areas

01:06:40.840 | depending on what sort of music is being played.

01:06:43.240 | That's somewhat obvious, perhaps,

01:06:44.920 | sad music versus intense...

01:06:48.800 | You could think about heavy metal versus choir music

01:06:52.280 | versus Gregorian chants versus punk rock music

01:06:56.140 | and on and on.

01:06:57.220 | It makes sense that different brain areas would be activated

01:07:00.340 | when different patterns of music are played.

01:07:02.280 | However, there do seem to be some universal features

01:07:04.560 | of brain activation in response to music.

01:07:06.820 | This should probably be the topic of an entire episode

01:07:08.840 | of the Huberman Lab Podcast, and indeed it will be.

01:07:11.580 | For instance, there are areas of the auditory cortex

01:07:15.020 | that are activated, no surprise there,

01:07:17.080 | and areas of the brain's reward circuitry,

01:07:19.520 | the so-called ventral striatum

01:07:21.320 | and the so-called mesolimbic reward pathway.

01:07:24.200 | Talked a lot about these in the episodes about dopamine

01:07:26.360 | that I've done previously.

01:07:27.900 | These are brain areas that lead to the release of dopamine

01:07:31.360 | in other brain areas and that reinforce certain experiences

01:07:34.280 | and that tend to give us the subjective feeling of,

01:07:36.460 | yes, I like this, I want more.

01:07:38.820 | So in this particular paper,

01:07:41.120 | what the authors did is they took advantage of the fact

01:07:43.160 | that people are in the clinic, they're on psilocybin,

01:07:47.300 | they're listening to music, and as you recall,

01:07:52.040 | the music played at different stages

01:07:54.000 | of the psilocybin journey are different.

01:07:55.520 | They have a different emotional component,

01:07:57.900 | and music is a really nice stimulus in the laboratory,

01:08:00.600 | as we say, because like with visual stimuli,

01:08:02.860 | you can break it down into high frequency, low frequency.

01:08:06.680 | Sounds like doon doon or these kinds of things.

01:08:09.640 | That was my attempt at low frequency

01:08:11.120 | versus high frequency auditory stimuli,

01:08:13.980 | or at the spatial frequency,

01:08:16.620 | or what in the auditory domain

01:08:18.000 | would be called the temporal frequency.

01:08:19.360 | Is it boom, boom, boom, or is it boom, boom, boom, boom?

01:08:23.920 | All we've changed there is the temporal frequency.

01:08:26.700 | The sound was somewhat the same,

01:08:28.060 | but the distance between those sounds was different.

01:08:31.240 | You get the idea.

01:08:33.300 | So they have access to these people

01:08:34.900 | and these different conditions,

01:08:36.200 | and they can put them in the brain scanner,

01:08:37.880 | and they can do that before and after

01:08:39.940 | having taken psilocybin.

01:08:41.560 | And the long and short of this study

01:08:43.760 | is that psilocybin changes one's experience of music,

01:08:48.380 | not just during the psilocybin journey itself,

01:08:52.540 | but thereafter.

01:08:54.500 | And in fact, it changes one's emotional response to music

01:08:58.700 | in very interesting ways.

01:09:00.380 | For instance, one of the more common features

01:09:02.160 | of major depression is that people don't derive

01:09:05.060 | as much pleasure from different types of experiences,

01:09:07.740 | whether or not it's food or sex or social experiences,

01:09:10.580 | to the point where sometimes they just stop

01:09:12.300 | trying to seek out those experiences.

01:09:14.140 | People with depression often feel as if music

01:09:18.180 | no longer has the same impact.

01:09:19.700 | It just doesn't really lift them up very much.

01:09:22.440 | This study found that people who have taken psilocybin,

01:09:26.340 | according to the parameters we talked about earlier,

01:09:29.600 | can get a return of the elevated emotionality,

01:09:32.420 | the positive emotions associated with music

01:09:35.200 | that formerly made them feel good.

01:09:37.600 | In other words, they can feel music again.

01:09:40.000 | They can feel good in response to music again.

01:09:42.520 | Now, this is interesting because in theory,

01:09:45.120 | it could be that psilocybin simply allowed them

01:09:48.660 | to access the emotions around music again more generally,

01:09:52.420 | but that's actually not what this paper

01:09:54.800 | and some other papers that have been published report.

01:09:58.640 | Rather, it seems that taking psilocybin

01:10:02.380 | can increase one's positive perception of music

01:10:05.960 | that one likes and can tone down or reduce the depressiveness

01:10:10.960 | or the sadness of music that tends to make one sad,

01:10:14.920 | even after the psilocybin has worn off

01:10:17.140 | and for a long period of time afterwards,

01:10:19.580 | maybe even forever, although no study, of course,

01:10:22.340 | can be carried out forever because forever is forever.

01:10:25.260 | What we do know, however,

01:10:26.700 | is that psilocybin can rewire the connections

01:10:29.980 | between the emotion centers in the brain

01:10:33.060 | and the networks that control auditory perception of music

01:10:36.520 | and leads to this condition in which people who felt like,

01:10:39.760 | I was depressed or I couldn't feel the music,

01:10:41.780 | I just wasn't getting the same lift and joy from it again,

01:10:44.420 | they can start to experience more joy from that music again

01:10:47.540 | and that music that made them feel sad and depressed

01:10:50.440 | has a diminished capacity

01:10:52.620 | to make them feel sad and depressed.

01:10:54.620 | And there's a lot of neuroimaging data in this paper

01:10:57.840 | that point to the specific brain areas

01:10:59.400 | that include areas like the ventral tegmental area

01:11:01.300 | that can explain why these sorts of effects will occur.

01:11:03.940 | So this isn't just subjective reports of people saying,

01:11:06.340 | oh yeah, I was depressed and music didn't feel really good,

01:11:08.980 | now it feels great, or that used to make me feel so sad

01:11:12.180 | and now I feel like I have a capacity to listen to that

01:11:14.400 | without being crushed by feelings of sadness.

01:11:18.700 | The paper included some subjective reports of that sort,

01:11:21.740 | but then was able to link those to changes

01:11:23.940 | in brain circuitry and brain activation

01:11:26.000 | in response to music using neuroimaging.

01:11:28.380 | So in that way, it really points to both the subjective

01:11:31.500 | and structural and functional changes

01:11:33.300 | that psilocybin can bring about

01:11:34.980 | through that expanded connectivity between brain areas.

01:11:38.660 | Because remember, during the psilocybin session,

01:11:41.340 | it's not as if music or the perception of music

01:11:44.500 | is specifically being looked at

01:11:46.460 | or focused on in these studies,

01:11:48.140 | rather music is playing, people are in the eye mask,

01:11:50.420 | they're feeling all sorts of things,

01:11:51.720 | they're breathing, they're hearing, they're touching,

01:11:53.380 | it's all happening all at once.

01:11:55.740 | There's a peak, it's long, there's a long taper,

01:11:58.340 | the music's changing.

01:12:00.100 | All of that took place in this study as well,

01:12:03.280 | but it is after the session

01:12:06.060 | when comparing brain activation states

01:12:08.820 | to music of a particular type, sad or happy,

01:12:11.980 | and comparing that to the patterns of brain activation

01:12:14.680 | that occurred before the psilocybin journey,

01:12:17.440 | that they discover that people's brains have rewired

01:12:20.340 | during the psilocybin session in a way

01:12:22.500 | that allows them to experience joy

01:12:24.380 | in response to music again.

01:12:26.300 | So that's one of the more rigorous studies

01:12:27.900 | I was able to find that addresses this question

01:12:31.060 | of whether or not psilocybin really does rewire the brain

01:12:34.460 | in ways that allows us to be more creative

01:12:36.900 | and experience life differently after the psilocybin session.

01:12:39.900 | Now, that paper didn't focus specifically on creativity.

01:12:42.660 | I did an entire episode on creativity

01:12:44.740 | that talked about different types of meditation,

01:12:46.920 | like open monitoring meditation.

01:12:48.460 | It talked about different patterns of thinking

01:12:50.780 | that one can actually practice to increase creativity.

01:12:53.440 | We had arguably one of the most creative people

01:12:56.340 | on the planet, Rick Rubin, came on this podcast,

01:12:59.880 | talked about the creative process

01:13:01.160 | from the perspective of music

01:13:02.720 | and his role in producing music.

01:13:04.080 | So you can check out those episodes

01:13:05.540 | if you're interested in the neural circuitry

01:13:06.960 | related to creativity.

01:13:08.540 | At least at the time of recording this episode,

01:13:11.020 | there haven't been a lot of studies looking specifically

01:13:13.320 | at the brain networks that we think are involved

01:13:15.480 | in creativity and how those change

01:13:17.860 | in response to psilocybin and other psychedelics.

01:13:20.620 | I imagine those studies are either happening now

01:13:22.540 | or will happen in the future,

01:13:24.360 | but the studies I just described,

01:13:26.440 | referring to the changes in emotionality

01:13:28.220 | and responses to music,

01:13:29.660 | I think provide a nice template for what's likely happening

01:13:33.780 | both during psilocybin journeys

01:13:35.340 | and after those psilocybin journeys

01:13:37.140 | when we talk about less hierarchical organization,

01:13:39.260 | more connectivity between brain areas.

01:13:41.900 | What it's pointing to is the fact

01:13:43.300 | that during the psilocybin journey,

01:13:45.660 | people have the opportunity to learn new relationships

01:13:49.140 | between different sensory and emotional states.

01:13:52.600 | And those new relationships seem to persist

01:13:55.980 | long after the psychedelic journey has been finished.

01:13:59.020 | And a lot of people researching psilocybin

01:14:00.900 | in the clinical setting think that that's one

01:14:02.740 | of the major reasons why psilocybin and other psychedelics

01:14:06.020 | can rewire our relationship to things more broadly.

01:14:08.620 | It allows for new learning, new contingencies.

01:14:11.300 | And when we look at depression,

01:14:13.300 | we often think, you know, diminished mood,

01:14:15.280 | people now have an appetite,

01:14:16.540 | they're not interested in social relationships

01:14:18.340 | or romantic relationships, they're really struggling.

01:14:20.620 | And all of that, of course, is true.

01:14:22.900 | But another lens to look at depression through

01:14:25.060 | is that a lot of that thinking

01:14:27.560 | and a lot of those emotional states that are negative

01:14:29.920 | are somewhat habitual.

01:14:31.020 | They relate to a sort of implicit understanding

01:14:33.860 | and living out of the idea that A leads to B leads to C.

01:14:37.360 | Okay, you seek out a relationship, it doesn't work out.

01:14:39.740 | Try a new job, you don't get the job.

01:14:41.420 | You get the job, it's no good.

01:14:42.740 | All these negative outcomes of if A, then B, then C.

01:14:45.700 | And it does seem that psilocybin can have this effect

01:14:48.720 | of invoking new patterns of learning,

01:14:50.540 | new considerations about what might be possible,

01:14:53.220 | and indeed may even lead to actual rewiring

01:14:56.280 | of the emotion centers in the brain

01:14:57.760 | with these other brain areas and vice versa

01:15:00.260 | in ways that eject people from the psilocybin session

01:15:03.540 | thinking, oh, you know, yeah,

01:15:05.420 | I used to feel this way about something,

01:15:07.460 | work, relationships, myself, et cetera,

01:15:09.820 | but I'm willing to consider this other possibility

01:15:11.860 | or this other possibility seems at least partially true

01:15:15.500 | to the extent that I'm willing to go out and evaluate that.

01:15:19.020 | Now, here I'm speaking very subjectively,

01:15:20.740 | but remember we have to tie back the subjective experiences

01:15:24.300 | and changes of things like music and emotion

01:15:26.660 | and our relationship to life and jobs and relationships

01:15:28.960 | back to the cell biology and chemistry of psilocybin

01:15:31.660 | because ultimately it really is

01:15:33.340 | just a chemical activating receptors,

01:15:35.380 | those receptors changing networks in the brain,

01:15:38.220 | and the journey itself seems to be the time

01:15:42.340 | when all of those changes are put in motion.

01:15:44.700 | It's like a boulder that gets rolling.

01:15:46.200 | In fact, I think the best way

01:15:47.980 | to think about psilocybin and other psychedelics

01:15:50.540 | is that they initiate the neuroplasticity process,

01:15:55.500 | but they are not the neuroplasticity process itself,

01:15:58.260 | and the journey itself

01:15:59.700 | is not where all the neuroplasticity occurs.

01:16:01.900 | We know that for sure.

01:16:02.980 | In fact, if you want to imagine

01:16:04.900 | how psilocybin and other psychedelics work

01:16:07.500 | to change the brain,

01:16:08.580 | think about them as a wedge that gets underneath the boulder

01:16:12.300 | that is the neuroplasticity that gets rolling forward,

01:16:15.920 | and then think about whether or not

01:16:17.700 | the plasticity is adaptive or maladaptive,

01:16:20.060 | whether or not it actually serves you in your life

01:16:21.920 | on a daily basis or not,

01:16:24.000 | depending on whether or not

01:16:25.460 | you're using your conscious brain

01:16:27.300 | to move that boulder in a particular direction, right?

01:16:29.860 | Not just bulldozing through things and destroying them,

01:16:32.180 | but clearing a path through old, ineffective,

01:16:35.660 | maybe even destructive patterns of thoughts

01:16:37.640 | or emotions, et cetera.

01:16:39.380 | I give you that analogy

01:16:40.300 | because I think it more accurately captures

01:16:42.280 | what psychedelics like psilocybin are doing,

01:16:45.160 | rather than the typical discussion around psychedelics

01:16:48.560 | that we tend to hear,

01:16:49.400 | which is that, oh, it creates plasticity,

01:16:51.180 | and plasticity is what you want.

01:16:52.940 | For the next couple of minutes,

01:16:53.940 | I'd like to focus on some of the key and stereotype

01:16:57.380 | that is characteristic experiences

01:16:59.140 | that people tend to have during a psilocybin journey,

01:17:02.000 | because there's some really interesting research on this.

01:17:04.040 | These are phrases that perhaps you've heard before,

01:17:06.540 | things like letting go, ego dissolution,

01:17:09.840 | feelings of connectedness.

01:17:11.740 | While all of that is very subjective on the one hand,

01:17:14.700 | those words are heard often enough and repeatedly enough

01:17:19.640 | in psilocybin sessions and after psilocybin sessions,

01:17:23.100 | along with this description of the psilocybin experience

01:17:26.120 | as one of the most profound of one's life,

01:17:29.200 | or one of the most positive, in the ideal case,

01:17:31.880 | of one's life, that they are worth exploring.

01:17:34.540 | We should also, of course, explore the so-called bad trip,

01:17:37.740 | the possibility that someone will have a not good time

01:17:41.020 | or even very frightening time

01:17:42.860 | while under the influence of psilocybin.

01:17:45.360 | So there have been some scientific studies

01:17:47.320 | that have explored what sorts of subjective experiences,

01:17:50.300 | that is thoughts and feelings,

01:17:52.500 | insights that people have,

01:17:55.560 | that relate to positive therapeutic outcomes,

01:17:58.300 | and more generally with the sense

01:17:59.580 | that the psilocybin journey was positive

01:18:01.580 | or maybe even tremendously positive in one's life.

01:18:04.580 | So while there's a century or more

01:18:06.260 | of writings about psychedelics that describe things

01:18:09.060 | like enhanced feelings of connectedness

01:18:10.800 | or dissolution of the ego, the loss of one's sense of self,

01:18:14.380 | and then the regaining of one's sense of self and so on,

01:18:17.340 | there's a particular paper that describes

01:18:19.020 | some of those things in terms of rating scales,

01:18:21.540 | that is the sorts of tests that people can take

01:18:23.980 | in which they answer particular questions

01:18:26.280 | and that link back to things like feelings of connectedness

01:18:28.980 | and ego dissolution that allows us to put some numbers

01:18:31.700 | to those experiences and to look at some of the statistics

01:18:34.860 | associated with those experiences.

01:18:36.220 | And this is really what's important

01:18:37.200 | about scientific studies,

01:18:38.580 | whether or not a measure is subjective,

01:18:40.160 | so if someone's self-reporting how they felt or feel,

01:18:42.740 | or whether or not it's measure of blood pressure

01:18:44.740 | or of a chemical in the bloodstream, et cetera,

01:18:47.540 | it's the use of numbers and statistics

01:18:49.180 | that allows comparison between different groups

01:18:51.540 | and that can be compared between studies

01:18:54.340 | that allows us to make some firm conclusions

01:18:56.740 | about what sorts of things psilocybin may

01:18:59.300 | or may not be doing when it's effective or not.

01:19:01.860 | So the paper I'd like to highlight is entitled

01:19:03.820 | "Quality of Acute Psychedelic Experience

01:19:06.340 | Predicts Therapeutic Efficacy of Psilocybin

01:19:08.640 | for Treatment-Resisted Depression."

01:19:10.980 | I'll put a link to this paper in the show note captions.

01:19:13.940 | But the basic contour of this paper is that

01:19:16.100 | they looked at subjects that underwent

01:19:18.280 | two different psilocybin sessions,

01:19:20.660 | one at a relatively low-ish dose

01:19:23.460 | of 10 milligrams of psilocybin.

01:19:25.300 | Again, that would be equivalent to about one gram

01:19:27.200 | of psychedelic mushrooms, more or less.

01:19:29.860 | And a second session involving subjects

01:19:32.620 | taking 25 milligrams of psilocybin,

01:19:35.660 | or what's roughly equivalent to somebody taking

01:19:37.660 | two and a half grams of psilocybin mushrooms.

01:19:40.620 | Those people then answered what's called

01:19:44.220 | the altered states of consciousness questionnaire,

01:19:47.140 | which allowed them to address, and here I'm paraphrasing,

01:19:48.960 | the quality of experiences

01:19:50.560 | in the 25 milligrams psilocybin session.

01:19:53.440 | So without going into too much detail,

01:19:55.160 | it's often the case in these sorts of two-session studies

01:19:57.860 | that subjects will take a slightly lower dose of psilocybin

01:20:00.760 | to familiarize themselves with the experience,

01:20:03.080 | and then the higher dose that leads

01:20:04.560 | to the more intense experience,

01:20:06.180 | intense meaning a bigger, more intense peak,

01:20:08.860 | a longer session overall,

01:20:10.900 | greater distortions in emotionality

01:20:12.940 | and perceptual experience,

01:20:13.920 | all the stuff we talked about before.

01:20:16.000 | So what this study found is that one of the key features,

01:20:18.380 | if not the key feature of a positive, quote unquote,

01:20:23.380 | psychedelic experience is this sense

01:20:26.520 | of oceanic boundlessness occurring at some point

01:20:29.840 | during the psychedelic journey.

01:20:31.200 | Now, oceanic boundlessness doesn't necessarily mean anything

01:20:34.360 | to any of us.

01:20:35.920 | It probably means different things to different people.

01:20:38.320 | It's this idea that one is experiencing

01:20:41.760 | something extremely unusual, even mystical,

01:20:45.360 | kind of beyond this world and one's normal experience,

01:20:49.280 | but that it's not aligned

01:20:50.540 | with any specific outcome in the moment.

01:20:52.840 | It's not directly attached to any one feeling

01:20:55.900 | or memory or thought process.

01:20:57.240 | It's this, I think it's a little bit tough to describe

01:20:59.600 | because I can guarantee you,

01:21:00.560 | I'm not on psilocybin or any psychedelics right now,

01:21:03.840 | and I can only imagine that you're not,

01:21:06.260 | although some of you might be.

01:21:07.640 | I can't even imagine what this podcast would be like

01:21:11.240 | for somebody on psilocybin at this moment.

01:21:12.920 | But in any case, oceanic boundlessness,

01:21:15.800 | a feeling of the experience being mystical

01:21:19.200 | and not really heading in any one particular direction,

01:21:21.780 | just a feeling of massive connectedness

01:21:24.480 | with one's environment, both in the room and session,

01:21:27.960 | perhaps with the guides, with oneself, with one's past,

01:21:30.820 | with one's present, people outside the room,

01:21:33.840 | with the entire world, maybe even the universe,

01:21:36.040 | that sort of thing.

01:21:37.460 | The intensity of that experience of oceanic boundlessness,

01:21:43.040 | the mystical experience,

01:21:44.320 | seems to be positively correlated

01:21:47.720 | with positive therapeutic outcomes,

01:21:50.600 | that is relief from major depression.

01:21:53.520 | Now, during the psychedelic journey,

01:21:55.440 | as we talked about before,

01:21:56.480 | there are a number of steps that one typically goes through.

01:21:59.220 | So there's the buildup to first experiencing the effects

01:22:02.100 | of the drug about maybe 20 to 45 minutes

01:22:04.880 | into the journey or trip, then the peak.

01:22:08.120 | And it is during that peak that people often feel

01:22:11.200 | the sense of oceanic boundlessness.

01:22:13.440 | However, it's also often the case

01:22:17.480 | that it is during the peak

01:22:19.560 | where the maximum intensity of emotion,

01:22:22.840 | and we know based on direct measurements,

01:22:25.960 | also increases in blood pressure and heart rate,

01:22:28.980 | often very significant increases in anxiety and fear as well,

01:22:33.680 | that people will experience things like ego dissolution.

01:22:37.120 | And the guide's role at that point is, of course,

01:22:39.960 | to keep the person safe,

01:22:41.040 | make sure they don't run out of the room,

01:22:42.320 | jump out of a window, run into traffic.

01:22:44.380 | Sadly, these are things that have happened

01:22:46.200 | outside of a strong, healthy, safe set and setting.

01:22:51.200 | But the guide's role is to keep the person safe,

01:22:53.900 | but also to encourage them to let go

01:22:56.620 | and move through that experience,

01:22:58.380 | to experience the anxiety, allow it to peak,

01:23:01.380 | allow them to see that they're not going to die

01:23:03.340 | from that anxiety, they're not going to dissolve,

01:23:05.220 | they won't lose their sense of self completely,

01:23:07.840 | or they may temporarily feel

01:23:09.240 | as if they lose their sense of self,

01:23:10.900 | but then they feel it restored

01:23:13.280 | at various intervals during the peak

01:23:14.980 | or as they exit that peak and move toward the, say,

01:23:18.800 | second, third, fourth, fifth hour of the session.

01:23:22.640 | So when exactly these feelings of oceanic boundlessness

01:23:26.080 | and ego dissolution occur varies from person to person,

01:23:29.620 | but typically it's during the peak that the ego dissolution,

01:23:32.440 | the fear and the need to quote unquote let go

01:23:35.800 | is most typical.

01:23:37.500 | I think perhaps the best way to describe the data

01:23:39.880 | in this paper in a way that's meaningful to everybody

01:23:42.680 | is to refer you to figure two,

01:23:44.760 | which if you're not looking at the paper,

01:23:46.480 | won't mean anything to you, but I'll describe it.

01:23:48.200 | And if you do want to take a look at figure two,

01:23:50.200 | again, you can access the paper in the show note captions.

01:23:52.840 | What they did is they looked

01:23:53.920 | at a number of different subjective measures,

01:23:56.360 | things like experience of unity,

01:23:59.240 | the feeling that one is connected to others and to the world,

01:24:03.460 | things like spirituality,

01:24:05.200 | whether or not the whole thing felt

01:24:06.320 | like a spiritual experience,

01:24:07.720 | whether or not it was a blissful state,

01:24:09.180 | whether or not there were insights,

01:24:10.340 | whether or not somebody felt disembodied, out of body,

01:24:13.600 | whether or not somebody had a lot of anxiety,

01:24:16.520 | whether or not they had these synesthesia,

01:24:18.040 | these blending of visual auditory touch and breathing

01:24:20.740 | and things of that sort.

01:24:22.000 | And they addressed which of those measures

01:24:24.320 | related to the positive clinical outcomes

01:24:27.000 | that were observed later after the psilocybin wore off.

01:24:30.280 | And while I'm not going to go point by point

01:24:32.540 | through each one of these measures,

01:24:34.160 | there's a general feature to emerge from the study,

01:24:36.160 | which is that the experience of unity,

01:24:40.300 | the sense that the psilocybin journey was spiritual,

01:24:44.000 | an experience of bliss at some point

01:24:46.740 | inside of the psilocybin journey,

01:24:48.440 | the sense that there were insights,

01:24:50.680 | that there were learnings about one's life and oneself.

01:24:54.400 | When those things were experienced very strongly,

01:24:57.240 | that correlated with the person being what was called

01:24:59.760 | a responder to the psilocybin treatment,

01:25:01.680 | meaning they got relief from their depression.

01:25:03.840 | Whereas people who felt less of that, okay,

01:25:06.200 | so the non-responders, as they're called,

01:25:09.860 | the people who do not benefit so much in the long run

01:25:12.300 | from the psilocybin treatment,

01:25:14.200 | tended to report less of an experience of unity,

01:25:16.840 | less of a spiritual experience,

01:25:18.380 | less of a blissful state, less insightfulness, and so on.

01:25:23.380 | Whereas there were very few differences

01:25:24.800 | between the people that derived benefit

01:25:26.320 | from the psilocybin treatment and those did not,

01:25:28.860 | along the dimensions of synesthesia,

01:25:31.360 | this blending of different perceptions

01:25:32.980 | that ordinarily doesn't occur for most people.

01:25:35.540 | Or complex imagery, right?

01:25:38.380 | Put simply, everyone who took psilocybin in this study

01:25:42.220 | at 25 milligrams saw complex imagery.

01:25:44.980 | They saw a lot of hallucinations,

01:25:47.420 | but just seeing hallucinations did not lead

01:25:49.380 | to the positive clinical outcomes in terms of mood.

01:25:51.980 | Anxiety was a very interesting measure here

01:25:55.960 | because ordinarily we think of the ego dissolution,

01:25:58.620 | the letting go is such a key component

01:26:00.360 | of the psychedelic journey

01:26:01.640 | in terms of the positive therapeutic outcomes.

01:26:03.540 | This has been discussed quite a lot.

01:26:05.260 | And in full disclosure, Robin Carter-Harris

01:26:07.640 | has already come on to record an episode

01:26:09.420 | of the Huberman Lab podcast.

01:26:10.500 | That episode hasn't been released yet,

01:26:11.920 | but it will be released soon.

01:26:13.100 | And he talks about the importance of this letting go

01:26:16.060 | in terms of the positive clinical outcomes

01:26:18.460 | of the psilocybin journey.

01:26:19.520 | And indeed that is true.

01:26:21.280 | And I should also mention that Dr. Matthew Johnson

01:26:23.220 | from Johns Hopkins, who also runs a laboratory

01:26:25.740 | exploring psychedelics and their role in treating things

01:26:28.740 | like eating disorders and depression, et cetera,

01:26:31.020 | also doing incredible work,

01:26:32.420 | also talked about the importance of letting go

01:26:34.680 | during the psilocybin journey, this ego dissolution,

01:26:36.720 | this ability to move through the anxiety.

01:26:39.460 | And again, I can't underscore this enough

01:26:41.540 | because it's been told to me over and over again

01:26:43.820 | by the top researchers in this area

01:26:46.060 | that people will head into that peaking phase

01:26:48.820 | of the psilocybin journey.

01:26:49.980 | And oftentimes it is not pleasant for them.

01:26:52.220 | They're feeling like it's uncomfortable, it's scary,

01:26:54.200 | and their heart rate is up and their blood pressure is up

01:26:56.260 | and they're having a hard time calming down

01:26:58.220 | than they want to calm down.

01:26:59.340 | But it does seem that while the guides

01:27:02.080 | should not ramp them up and get them more stressed,

01:27:05.160 | that the ability to move through that stressful period,

01:27:07.360 | to somewhat guide oneself or to be encouraged

01:27:10.460 | to guide oneself through that peak

01:27:12.420 | and that anxiety and the fear of losing oneself

01:27:15.800 | and the so-called ego dissolution that occurs

01:27:18.180 | is an important feature

01:27:19.260 | for an effective therapeutic session.

01:27:21.240 | In this study, anxiety itself was inversely correlated

01:27:27.340 | with a positive therapeutic outcome.

01:27:30.900 | Okay, so this is important and somewhat nuanced.

01:27:33.180 | On the one hand, I'm telling you that the letting go,

01:27:35.900 | the ego dissolution does seem to be important

01:27:38.460 | in terms of reporting a psychedelic experience

01:27:41.540 | as effective as having accomplished something

01:27:43.860 | and perhaps even explaining some of the long-term

01:27:46.500 | positive effects to emerge from that psychedelic journey,

01:27:48.780 | in this case, psilocybin journey.

01:27:50.920 | However, non-responders, that is people who did psilocybin

01:27:55.920 | but did not have a positive therapeutic outcome

01:28:01.080 | in comparison to the responders,

01:28:03.360 | those non-responders tended to have higher

01:28:07.420 | subjective ratings of anxiety than did the responders.

01:28:11.900 | So this is important and what it speaks to is the fact that,

01:28:15.100 | well, yes, letting go during the session,

01:28:17.140 | experiencing some anxiety,

01:28:18.700 | perhaps even ego dissolution and the dissolving of self

01:28:22.000 | and then the return of self is important.

01:28:24.860 | It is also important, it seems,

01:28:26.740 | that anxiety not be so, so high

01:28:30.140 | or subjectively experienced as so high

01:28:33.180 | that one does not experience the positive neuronal rewiring

01:28:36.480 | that leads to a more pervasive elevated mood, okay?

01:28:39.580 | So I'm definitely saying two things at once

01:28:42.100 | because I'm trying to capture the data accurately.

01:28:44.000 | It would not be fair for me to say,

01:28:45.860 | just let go, experience as much anxiety as is possible

01:28:49.740 | and that's part of the process.

01:28:51.720 | Yes, letting go, again, in air quotes,

01:28:53.680 | seems to be important for one's experience

01:28:57.020 | of the psychedelic journey in particular around the peak

01:28:59.340 | that occurs about two hours in or so.

01:29:01.960 | However, extreme levels of anxiety

01:29:05.140 | seem inversely correlated or negatively correlated,

01:29:07.920 | would be the better way to put it,

01:29:09.220 | with the positive therapeutic outcome

01:29:11.360 | or relief from depression.

01:29:13.140 | So this takes us back to all of the things

01:29:15.160 | we've been talking about thus far,

01:29:17.020 | not just the chemistry and biological action of psilocybin,

01:29:19.520 | but the key importance of getting dosage right,

01:29:21.880 | the key importance of making sure

01:29:24.340 | that you're in a safe environment,

01:29:25.700 | but also one in which the guides

01:29:27.100 | really know what they're doing.

01:29:28.540 | I think this is one of the biggest

01:29:31.300 | and most important reasons for having well-trained guides,

01:29:35.140 | who really understand the contour of the psychedelic journey

01:29:38.780 | but are also trained in how to help somebody

01:29:41.720 | with their anxiety in real time

01:29:43.220 | while they're under the effects of psilocybin.

01:29:46.380 | And of course, to help people integrate

01:29:47.780 | those feelings of high anxiety

01:29:49.060 | and maybe guide them back down to a calmer state

01:29:52.060 | during the psychedelic session itself.

01:29:54.420 | Here I can just mention some unpublished data and studies,

01:29:57.680 | and again, this are very preliminary,

01:29:59.420 | but through discussions with Dr. Matthew Johnson,

01:30:02.380 | who's running these psilocybin

01:30:03.620 | and other sorts of psychedelic trials at Johns Hopkins,

01:30:06.740 | he and I discussed the importance

01:30:09.100 | of having a real-time tool to adjust anxiety

01:30:11.940 | while under the influence of psychedelics like psilocybin.

01:30:15.460 | And there he asked,

01:30:17.580 | and they've started to incorporate, is my understanding,

01:30:20.140 | some of the real-time respiration tools,

01:30:22.620 | that is, breathing tools that we know,

01:30:25.100 | based on work in my laboratory,

01:30:26.340 | Dr. David Spiegel's laboratory,

01:30:28.220 | can reduce anxiety very quickly in real time,

01:30:30.900 | and that involves the use of the so-called physiological psi.

01:30:33.480 | I've talked a lot about this before on previous podcasts,

01:30:35.980 | so rather than explain it to you again here now,

01:30:38.340 | we'll put a link to the physiological psi.

01:30:40.180 | I do a demonstration of it in the show note captions.

01:30:42.780 | I'll also link to a recent paper

01:30:44.260 | that we published in Cell Reports Medicine.

01:30:45.920 | This was a collaborative work that my laboratory did

01:30:48.160 | with Dr. David Spiegel's laboratory

01:30:50.520 | at Stanford School of Medicine,

01:30:52.140 | showing that the physiological psi

01:30:53.580 | is among the different deliberate respiration techniques,

01:30:57.240 | one of the fastest and most effective ways

01:30:59.200 | to reduce levels of autonomic arousal,

01:31:01.560 | AKA anxiety or stress.

01:31:03.520 | And Dr. Matthew Johnson's laboratory

01:31:05.540 | has started to incorporate physiological psi

01:31:08.280 | within these psychedelic sessions

01:31:10.260 | as a tool that the guides can refer people to

01:31:13.580 | before the session begins, teaching it to them,

01:31:16.620 | so they realize they can calm themselves down,

01:31:18.620 | if necessary, in real time.

01:31:19.940 | It works the first time, it works every time.

01:31:22.160 | This is not because it's some magic breathing technique

01:31:24.460 | that I created, it certainly is not.

01:31:25.980 | This is a naturally occurring pattern of breathing

01:31:28.260 | that occurs in sleep and in waking,

01:31:29.540 | but that when done deliberately leads to very rapid

01:31:33.040 | and quite significant decreases in stress and anxiety.

01:31:36.720 | And then when people are inside of the psychedelic session,

01:31:38.980 | if they feel their anxiety levels are going too high,

01:31:41.260 | they're heading toward what might be called

01:31:43.160 | a quote unquote bad trip, they're starting to panic

01:31:46.200 | or really think they're going to have a panic attack or die.

01:31:49.080 | Again, the subjective experience is going to be layered

01:31:51.060 | on top of the physiological experience

01:31:52.760 | of one's heart rate being really elevated,

01:31:54.600 | so stress and agitation.

01:31:56.660 | By using the physiological psi

01:31:58.200 | inside of the psychedelic session, Dr. Johnson's laboratory,

01:32:02.080 | and I believe at least one other laboratory

01:32:04.420 | are starting to use breathing techniques,

01:32:06.860 | such as the physiological psi, as a way for these people

01:32:10.500 | who are under the influence of psilocybin

01:32:11.900 | to self-direct their own calm

01:32:14.480 | and to bring that level of anxiety down

01:32:16.980 | so that they can continue to move through the peak

01:32:19.300 | and move through the other phases of the psychedelic journey

01:32:21.460 | in ways that could be most beneficial for them.

01:32:23.980 | So to close out the description

01:32:25.280 | of this really wonderful study,

01:32:27.860 | and by the way, it's another one

01:32:28.880 | from the Carthart-Harris Laboratory,

01:32:30.380 | about the subjective experience of ego dissolution

01:32:34.420 | or oceanic boundlessness, this mystical state,

01:32:36.940 | as so key as a component of a positive psilocybin journey.

01:32:41.340 | I'll just read for you the final sentence of this paper

01:32:43.340 | because it captures it so well.

01:32:45.660 | Quote, "It seems vital that appropriate consideration

01:32:48.620 | is paid to the importance of promoting

01:32:50.080 | a certain kind of experience,

01:32:52.100 | as the quality of that experience

01:32:53.600 | may be the critical determinant of therapeutic success."

01:32:57.440 | Now, before we move into what will be

01:32:59.120 | a very brief description of some of the other

01:33:01.340 | rewiring phenomena that psilocybin can induce,

01:33:04.080 | and then into some of the therapeutic applications

01:33:07.960 | of psilocybin as they relate to these recent,

01:33:09.940 | really exciting clinical trials for depression

01:33:12.120 | and addictive disorders and things of that sort,

01:33:14.620 | I just want to cue everybody to a paper

01:33:16.280 | that I think many people will want to take a look at

01:33:18.760 | in thinking about psilocybin,

01:33:20.940 | and I'll provide a link to this paper as well

01:33:22.620 | in the show note captions.

01:33:24.100 | This paper is entitled "Therapeutic Use of Psilocybin,

01:33:26.800 | Practical Considerations for Dosing and Administration."

01:33:30.220 | And this is a wonderful paper

01:33:32.000 | because it really goes step-by-step

01:33:34.680 | through the pharmacology of psilocybin,

01:33:37.620 | of which you now understand a bit,

01:33:39.000 | but it goes into a bit more detail.

01:33:41.100 | But then it also really nicely describes

01:33:43.220 | the contour of a psilocybin session

01:33:44.840 | and what's happening at the level of chemistry,

01:33:47.260 | early, middle, peak,

01:33:49.100 | and toward the end of the psilocybin session.

01:33:50.820 | And then also importantly,

01:33:52.400 | it gets into issues of dosage and translating

01:33:54.700 | from mushrooms to psilocybin itself, to psilocin,

01:33:57.520 | things I talked about earlier, but in a bit more detail,

01:33:59.700 | if you'd like to see that detail.

01:34:01.100 | And then perhaps most importantly,

01:34:02.840 | there's a section on contraindications

01:34:05.560 | where it points out that, of course,

01:34:07.860 | women who are pregnant or breastfeeding,

01:34:11.340 | people who have a predisposition to psychosis,

01:34:14.040 | those people should really avoid the use of psilocybin

01:34:17.580 | and other psychedelics entirely.

01:34:19.880 | It also talks about where the evidence

01:34:22.540 | is strong, moderate, and weak

01:34:26.340 | for the use of psilocybin for treatment of various disorders.

01:34:29.040 | And I can just summarize that very quickly

01:34:31.040 | because it's where we're going ahead in a few minutes,

01:34:32.620 | which is that the most evidence

01:34:34.100 | for positive therapeutic outcomes response to psilocybin

01:34:38.000 | taken and conducted in the manner

01:34:40.620 | that we've been describing today

01:34:41.720 | in terms of dosage and journey set and setting

01:34:44.180 | is for cancer-related depression,

01:34:46.580 | cancer-related anxiety,

01:34:49.700 | and treatment-resistant depression.

01:34:51.840 | That's where most of the evidence resides.

01:34:54.100 | There's also some evidence

01:34:55.840 | for the use of psilocybin journeys.

01:34:58.460 | And again, this is typically one or two psilocybin journeys

01:35:01.280 | spaced, in the cases of two journeys,

01:35:04.060 | anywhere from one to two weeks apart.

01:35:06.540 | And again, with all of the same contour of supports

01:35:09.580 | and setting that we've been talking about today.

01:35:12.300 | And there, there's some evidence for improvement

01:35:15.420 | in terms of outcomes in alcohol use disorder independence

01:35:18.420 | and tobacco addiction.

01:35:19.900 | And then finally, there's the least amount of evidence,

01:35:21.700 | although there is clinical trial support

01:35:24.740 | for relief or partial relief,

01:35:27.180 | for obsessive compulsive disorder,

01:35:30.080 | cluster headaches and migraines,

01:35:32.040 | and demoralization due to AIDS diagnosis, okay?

01:35:35.600 | So this paper has a lot of really interesting information

01:35:38.840 | in terms of different conditions, in terms of dosage,

01:35:41.860 | and again, contraindications

01:35:44.060 | and what's called adverse events.

01:35:46.080 | What sorts of bad things can and do happen

01:35:49.740 | as a consequence of psilocybin and other types

01:35:52.140 | of psychedelic journeys,

01:35:52.980 | both during and after those psilocybin

01:35:55.740 | or psychedelic sessions.

01:35:56.780 | And we'll talk a bit more about this

01:35:58.300 | when we go into some of those clinical studies,

01:36:00.060 | because adverse reactions is always a key measure

01:36:02.660 | in any clinical study.

01:36:03.980 | So very soon we'll get into the more recent clinical studies

01:36:06.500 | related to psilocybin for the use of treating depression

01:36:10.140 | and some other conditions.

01:36:11.640 | But before we do that, I'd be remiss if I didn't talk about

01:36:15.380 | how psilocybin does and does not change the brain,

01:36:18.220 | what is and what is not known about that.

01:36:20.300 | In fact, when I put out the call

01:36:21.660 | for questions about psilocybin,

01:36:23.900 | many of the questions related to these issues.

01:36:27.060 | The first thing to understand is that a psilocybin journey

01:36:29.860 | is really a way to try and put that wedge under the boulder,

01:36:34.020 | as I described it, to try and invoke neuroplasticity

01:36:36.940 | of a particular kind.

01:36:38.540 | And in that way, it's kind of remarkable,

01:36:40.060 | if you think about it, that everyone has different lives,

01:36:42.820 | different experiences, psychedelics, in this case, psilocybin,

01:36:46.060 | are activating these brain networks that each of us has

01:36:48.980 | more broadly than they would normally be activated.

01:36:51.380 | These are very abnormal patterns of thinking and perceiving

01:36:55.140 | and experiencing our emotional and physical life, et cetera.

01:36:59.420 | And yet so often the outcomes are positive, not always,

01:37:03.340 | but the outcomes are positive, the experience is positive,

01:37:05.620 | even though it might have these anxiety moments

01:37:07.760 | or components within them.

01:37:09.420 | It's very important to understand that psilocybin

01:37:13.060 | and the journey, while important,

01:37:15.800 | are not really what all of this is about.

01:37:17.720 | It's really about neuroplasticity.

01:37:19.960 | So researchers, in particular neuroscientists,

01:37:22.260 | are very intensely interested in understanding

01:37:24.880 | what sorts of neuroplasticity psilocybin creates,

01:37:28.040 | because it turns out there are lots of different types

01:37:31.700 | or processes involved with neuroplasticity.

01:37:34.260 | For instance, brain networks, behavior, thinking, emotion,

01:37:38.700 | et cetera, can change because of the addition of new neurons.

01:37:41.740 | That's one form of neuroplasticity

01:37:43.380 | that's referred to as neurogenesis,

01:37:44.980 | the production of new neurons,

01:37:46.540 | most typically in the so-called dentate gyrus

01:37:49.300 | or other subregions of the hippocampus,

01:37:51.200 | a brain area involved in learning and memory.

01:37:53.980 | Neurogenesis in other regions of the adult human brain

01:37:59.060 | are exceedingly rare, and to be honest,

01:38:01.460 | may not occur at all.

01:38:02.560 | This is a debated area.

01:38:04.040 | We could do an entire episode about this,

01:38:06.720 | but for the most part,

01:38:08.180 | neuroscientists don't really believe that your neocortex,

01:38:10.920 | your striatum, your cerebellum,

01:38:13.880 | has that much neurogenesis that's related

01:38:16.560 | to learning and memory of new things or new experiences,

01:38:19.760 | and we don't actually think that occurs

01:38:22.680 | as a consequence of taking psilocybin either.

01:38:25.580 | Now, some of you who are familiar with, for instance,

01:38:28.780 | the cerebellum might be saying,

01:38:29.960 | wait, what about granular cell proliferation

01:38:32.180 | in the cerebellum?

01:38:33.180 | Or what about the rostral migratory stream

01:38:35.700 | from the subventricular zone where there are neuroblasts

01:38:39.540 | spitting out little new neurons that migrate into the nose

01:38:42.020 | to replenish the olfactory neuron population?

01:38:44.420 | Yes, that's all true.

01:38:45.780 | That does occur.

01:38:46.740 | It's been observed in mice, it's been observed in monkeys,

01:38:48.920 | and to some extent, it's been observed in humans,

01:38:51.840 | but it's not, again, I repeat,

01:38:54.120 | it is not a prominent feature of learning

01:38:58.060 | and acquisition of new skills,

01:38:59.740 | new ideas, or new emotional states.

01:39:01.680 | Perhaps the best supported evidence for neurogenesis

01:39:05.900 | underlying new thoughts, experiences, abilities,

01:39:09.420 | emotions, et cetera, is the production of new neurons

01:39:12.080 | in that dentate gyrus subregion of the hippocampus,

01:39:14.580 | and that probably does occur in humans,

01:39:16.580 | but neurogenesis is not really the dominant mode

01:39:20.700 | of changing neural circuitry in adult humans.

01:39:23.360 | It might be a player in adolescence, in young childhood.

01:39:28.360 | It is certainly a player before we are born

01:39:31.120 | when we are still in utero,

01:39:32.140 | but then the brain is being wired up in many different ways,

01:39:35.620 | including the addition of new neurons

01:39:36.980 | and changing of connections.

01:39:38.900 | All of this is to say that while neurogenesis

01:39:41.900 | is a really sticky idea and it makes great headlines,

01:39:45.420 | the addition of new neurons is not really the way

01:39:47.440 | that the brain changes under psilocybin,

01:39:51.460 | other psychedelics, or just generally.

01:39:53.780 | It's perhaps responsible for maybe 1% to 2%,

01:39:57.660 | and I'm being generous there, of the rewiring events

01:40:00.540 | that are going to be most important for all of us.

01:40:03.180 | So we need to set that down and cement that there

01:40:06.420 | until further evidence comes out to the contrary.

01:40:08.780 | That's certainly where I,

01:40:09.860 | and here I feel comfortable speaking

01:40:11.740 | for the majority of neuroscientists out there,

01:40:13.380 | professional neuroscientists, that is.

01:40:15.720 | The papers showing adult neurogenesis are interesting,

01:40:19.020 | but they don't really explain most of the plasticity

01:40:20.940 | that occurs in the adult human brain.

01:40:23.740 | So if neurogenesis ain't it, what is?

01:40:27.200 | Well, it's very clear that psilocybin, other psychedelics,

01:40:31.380 | and any sort of behavioral or drug intervention

01:40:34.160 | that can induce neuroplasticity does so largely

01:40:37.780 | through the addition or strengthening

01:40:39.980 | of new neural connections or through the elimination

01:40:42.220 | or weakening of other neural connections.

01:40:45.200 | And if you look at the data exploring the mechanistic basis

01:40:49.220 | for psilocybin-induced neuroplasticity,

01:40:52.800 | it's mostly focused on animal brains, animal models,

01:40:56.860 | mice and rats in particular, a little bit on primates,

01:40:59.460 | but mostly mice and rats because that's where

01:41:01.020 | the interventions can be done of knockout animals,

01:41:03.780 | of imaging the brain in real time.

01:41:06.300 | Of course, there are the beautiful studies

01:41:08.340 | of Robin Cardart-Harris and others exploring neuroplasticity

01:41:12.080 | at the level of brain imaging,

01:41:13.540 | at the level of ultrasound measurements,

01:41:15.420 | of how active are certain brain areas in humans,

01:41:17.820 | how extensive is the modularity

01:41:20.180 | or not extensive is the modularity, et cetera,

01:41:21.780 | the stuff we talked about earlier.

01:41:23.020 | So in other words, there are neuroplasticity studies

01:41:25.260 | with the effects of psilocybin in humans.

01:41:28.020 | But in terms of underlying mechanisms of neuroplasticity,

01:41:31.420 | I think the predominant theory is that psilocybin

01:41:34.700 | induces neuroplasticity through the addition

01:41:37.260 | of novel connections in those pyramidal neurons

01:41:40.340 | of the frontal cortex, elsewhere in the cortex,

01:41:42.400 | and certainly also in the visual cortex,

01:41:44.540 | probably also subcortically as well,

01:41:46.260 | below the cerebral cortex in areas like the thalamus,

01:41:49.500 | maybe even in the brainstem as well.

01:41:52.100 | And that those neuroplasticity events

01:41:54.220 | are structural and functional.

01:41:56.220 | And they involve a couple of basic events,

01:41:58.220 | the most prominent of which is the growth of dendrites.

01:42:01.020 | Dendrites are those little branches or processes

01:42:03.260 | that come out of the neurons,

01:42:05.180 | not just the pyramidal neurons, but other neurons as well.

01:42:07.520 | But since we're talking mainly

01:42:08.460 | about pyramidal neurons today,

01:42:10.000 | both the apical, those ones that top,

01:42:11.820 | they're called the apical tufts,

01:42:12.660 | they're the ones that reach laterally

01:42:14.800 | to connect with other neurons,

01:42:16.260 | communicate with other neurons that we talked about before,

01:42:17.940 | as well as the dendrites that come out of the base

01:42:20.060 | of those pyramidal neurons.

01:42:21.640 | Those processes grow in response to psilocybin,

01:42:24.540 | as well as the addition of what are called dendritic spines.

01:42:27.940 | So the dendrites are the branches,

01:42:30.020 | the spines are these little protrusions that grow out.

01:42:32.380 | They actually, and here,

01:42:33.740 | I don't know if this is coincidence or not.

01:42:35.860 | Again, I always say, I wasn't consulted at the design phase,

01:42:38.300 | but these little protrusions

01:42:39.280 | actually look like little mushrooms.

01:42:41.060 | They have a little stalk and they have a little head,

01:42:43.220 | a little spine head, and those little spines.

01:42:46.780 | So think of these as like little tiny mushroom appearing.

01:42:50.360 | Okay, they aren't actual mushrooms.

01:42:51.900 | Okay, the first person that puts in the comments,

01:42:54.200 | oh my goodness, I learned today

01:42:55.500 | that mushrooms grow out of our neurons

01:42:57.400 | when we take magic mushrooms.

01:42:58.540 | That is not what I'm saying.

01:43:00.180 | What I'm saying is that these little mushroom-shaped

01:43:02.520 | protrusions that we're calling dendritic spines

01:43:05.060 | do in fact grow out of dendritic branches of neurons

01:43:09.360 | when animals ingest psilocybin

01:43:13.180 | or are injected with psilocybin,

01:43:15.140 | and that those little mushroom-shaped protrusions

01:43:18.060 | are the sites of new excitatory connections,

01:43:21.140 | new locations for input from other neurons

01:43:25.220 | to activate those neurons

01:43:27.260 | that have those little mushroom-shaped protrusions.

01:43:29.620 | If you'd like to see examples of this,

01:43:31.260 | both movies and still shots, it's pretty remarkable.

01:43:33.940 | There's a paper that I'll provide a link to

01:43:35.420 | in the show note captions.

01:43:36.340 | This was published in the journal Neuron,

01:43:38.180 | Cell Press Journal, excellent journal,

01:43:39.860 | entitled "Psilocybin induces rapid and persistent growth

01:43:42.540 | "of dendritic spines in the frontal cortex in vivo."

01:43:45.720 | So these measurements were done in the mouse equivalent,

01:43:48.140 | more or less, of the prefrontal cortex.

01:43:50.380 | There's some interesting details in this paper,

01:43:52.300 | for instance, that those new connections persist,

01:43:55.060 | so they don't just grow out during the psilocybin

01:43:58.420 | being active in the bloodstream and brain of the animal,

01:44:01.220 | they persist, okay?

01:44:02.360 | So this may, again, may explain

01:44:05.020 | some of the persistent changes that occur in people

01:44:07.740 | after psilocybin journeys.

01:44:09.460 | They may too grow new spines.

01:44:11.580 | I should also mention that a reduction

01:44:13.420 | in the number of dendritic spines,

01:44:14.820 | these little mushroom-shaped protrusions,

01:44:16.400 | in the frontal cortex neurons of humans

01:44:19.540 | occurs in depressed patients,

01:44:21.180 | we know that from post-mortem tissue,

01:44:23.260 | and that drugs that relieve depression or that treatments,

01:44:26.380 | including behavioral treatments,

01:44:28.620 | that provide some relief from depression

01:44:31.260 | do seem to be correlated with increases in spine growth

01:44:34.580 | in frontal cortex neurons as well.

01:44:36.400 | So this raises a very interesting idea,

01:44:38.100 | which is perhaps it's the growth of new connections,

01:44:42.340 | these new dendritic spines, in particular neurons,

01:44:44.740 | that's created by administration of psilocybin

01:44:47.940 | that explains the relief from depression

01:44:49.840 | that people experience.

01:44:50.980 | So this is just one paper,

01:44:52.260 | but it's one paper of a growing body of work

01:44:55.640 | showing that yes, indeed, psilocybin induces

01:44:58.560 | both structural and functional plasticity

01:45:00.640 | in the human and animal brain.

01:45:03.180 | It does that in the human brain at therapeutic doses

01:45:06.380 | of anywhere from 10 to 25,

01:45:08.280 | perhaps even 30 milligrams per session,

01:45:10.020 | one or two sessions.

01:45:11.540 | I should mention that the mouse studies

01:45:13.800 | tended to use quite high doses of psilocybin.

01:45:17.120 | I was actually, I wasn't shocked,

01:45:19.080 | but I was somewhat wide-eyed for a moment

01:45:21.240 | to realize that most of the studies

01:45:22.660 | looking at changes in plasticity in the mouse brain

01:45:26.860 | in response to psilocybin use the equivalent

01:45:29.140 | of one milligram per kilogram of body weight,

01:45:32.240 | which is if you do the math and you translate

01:45:34.640 | what we were talking about before in terms of dosages,

01:45:36.420 | I'll just spare you all the time,

01:45:38.540 | it's about double the sorts of dosages

01:45:41.260 | that are typically used in humans,

01:45:42.980 | maybe even triple in some cases.

01:45:44.980 | Now it's often the case in animal studies

01:45:47.060 | because of the metabolism of animals being different,

01:45:49.320 | but also because seeing effects of drugs

01:45:52.920 | in animal studies can be difficult.

01:45:55.880 | They did use a dose response anywhere from zero

01:45:57.960 | to 0.25 to half to one to two milligrams

01:46:01.460 | per kilogram of psilocybin in the study.

01:46:02.900 | So they had a dose response curve,

01:46:04.560 | but focused mainly on this one milligram

01:46:06.220 | per kilogram dosage.

01:46:08.160 | In any event, the point is that many of the studies

01:46:10.160 | that describe these pretty dramatic structural changes

01:46:13.260 | in the animal brain, most typically the mouse brain

01:46:16.240 | in response to psilocybin,

01:46:17.560 | used dosages of psilocybin that if translated to humans

01:46:20.400 | would be about double the human therapeutic dose.

01:46:23.400 | So that is something that we need to take

01:46:24.700 | into consideration.

01:46:25.880 | Nonetheless, it's very clear that in both animal studies

01:46:28.220 | and humans, psilocybin is inducing both structural

01:46:31.380 | and functional changes in brain circuitry.

01:46:33.600 | And that in humans, the network connectivity

01:46:36.640 | is being changed dramatically.

01:46:37.840 | We talked about those data earlier

01:46:39.680 | and that the underlying basis for that might be,

01:46:42.480 | again, might be, we don't know for sure,

01:46:44.820 | the addition of new dendritic spines on these pyramidal

01:46:47.620 | neurons that we've been talking about repeatedly

01:46:49.600 | throughout today's episode.

01:46:50.660 | Although neurogenesis, perhaps,

01:46:53.340 | and other modes of neuroplasticity,

01:46:54.880 | such as the elimination of certain connections,

01:46:56.760 | perhaps related to unhealthy maladaptive thoughts

01:46:59.980 | or our feeling that a particular sad song

01:47:02.420 | is overwhelmingly sad.

01:47:04.100 | It could be the case that those sorts of things

01:47:06.360 | change subjectively because of the removal

01:47:08.340 | of neural connections.

01:47:09.180 | If you're going to think like a neurobiologist

01:47:11.060 | or scientist for that matter,

01:47:13.360 | you don't ever want to think that one mechanism

01:47:15.480 | can explain all the effects of a given drug

01:47:17.280 | or a given experiences.

01:47:18.560 | Almost certainly likely to be the consequence

01:47:21.240 | of multiple mechanisms acting in parallel.

01:47:24.280 | And because I know there are people out there

01:47:25.800 | who would like to know even more about the neuroplasticity

01:47:28.880 | induced by psychedelics, including psilocybin,

01:47:32.060 | there's a wonderful review that I provide a link to

01:47:34.160 | in the show note captions entitled,

01:47:36.000 | Psychedelics and Neuroplasticity,

01:47:37.600 | a Systematic Review Unraveling the Biological

01:47:39.920 | Underpinnings of Psychedelics.

01:47:42.240 | This review is great because it goes a step beyond

01:47:44.940 | just psilocybin, psilocin binding

01:47:47.240 | to the serotonin 2A receptor

01:47:49.260 | and things like brain-derived neurotrophic factor.

01:47:51.360 | It actually talks a lot about the intracellular signaling

01:47:54.400 | and exactly how neurons change their excitability patterns

01:47:57.480 | based on this activation of the serotonin 2A receptor.

01:48:00.400 | It's probably more detailed than most of you out there

01:48:02.400 | are interested in, but if you are interested

01:48:04.640 | in that level of detail,

01:48:05.780 | this is a wonderful open access review.

01:48:08.140 | So a few minutes ago,

01:48:08.980 | I talked about where there is strong, modest,

01:48:12.200 | and somewhat weak, or rather I should say minimal evidence

01:48:16.300 | for the therapeutic use of psilocybin

01:48:18.700 | to treat various disorders.

01:48:19.900 | And across the board, it really appears

01:48:22.220 | that major depression and so-called intractable depression

01:48:27.220 | in some cases is where we're seeing

01:48:29.460 | the most exciting research to date.

01:48:32.220 | Now keep in mind that because of the Controlled Substances

01:48:34.620 | Act being invoked in 1970 in the United States,

01:48:37.700 | and because it was only just a few years ago, really,

01:48:40.420 | only about five years ago,

01:48:42.300 | that psychedelics, including psilocybin,

01:48:45.520 | received what's called breakthrough status at the FDA,

01:48:49.340 | that there are now a lot of clinical trials

01:48:51.220 | exploring how psilocybin can impact various things

01:48:54.300 | like mood disorders, addictive disorders, and so on.

01:48:57.260 | Prior to 2018, when that therapeutic breakthrough potential

01:49:00.980 | was established in the United States,

01:49:03.060 | I think a lot of people

01:49:04.060 | in the so-called psychedelics community had the sense

01:49:06.580 | and really the belief that these drugs

01:49:09.020 | had enormous potential,

01:49:10.700 | but they just weren't being explored that extensively.

01:49:12.660 | So I do want to give a nod to the incredible researchers,

01:49:17.100 | such as Robin Cardart-Harris, but also Matthew Johnson,

01:49:20.140 | Roland Griffiths, Nolan Williams, and many others.

01:49:23.760 | Okay, I'm certainly not listing off everybody.

01:49:26.260 | That would take hours.

01:49:27.500 | But those researchers have really pioneered

01:49:31.060 | both the legal efforts and the funding efforts,

01:49:33.240 | and most importantly, the research efforts

01:49:35.060 | defining the clinical data that I'm about to describe.

01:49:38.140 | And here, I'm going to summarize the clinical data

01:49:40.740 | in a bit of a top contour fashion,

01:49:42.740 | just giving you the kind of highlights.

01:49:44.940 | We will, of course, provide links to the papers

01:49:46.900 | if you'd like to look into it further.

01:49:48.540 | But I'm only giving you the top contour

01:49:50.540 | because I've had the great fortune

01:49:52.140 | of having Matthew Johnson on this podcast before.

01:49:54.300 | You can find that episode at HubermanLab.com.

01:49:57.420 | Just simply put Matt's name or psychedelics

01:49:59.740 | into the search function.

01:50:00.740 | It'll take you to that episode in all formats,

01:50:03.380 | or links to all formats, rather.

01:50:05.480 | I've also had the great fortune of sitting down recently

01:50:07.500 | with Dr. Robin Cardart-Harris to talk about his work

01:50:10.740 | at University of California, San Francisco

01:50:12.860 | on psilocybin, LSD, ayahuasca, and DMT

01:50:17.260 | as it relates to depression and other disorders.

01:50:19.940 | And that episode, which also will be released

01:50:22.380 | at HubermanLab.com and on all platforms,

01:50:24.680 | YouTube, Apple, Spotify,

01:50:25.700 | really goes in depth into these clinical studies

01:50:28.420 | and what those studies really look like.

01:50:30.460 | Who's in the room?

01:50:31.980 | Whether or not people just get one dose or two doses,

01:50:34.820 | how far apart those are separated,

01:50:37.320 | all of that is covered in extensive detail

01:50:39.660 | in that what I found to be wonderful discussion

01:50:42.440 | with Dr. Robin Cardart-Harris.

01:50:44.060 | So if you're interested in all of the details

01:50:47.020 | as it relates to clinical application of psychedelics,

01:50:49.960 | stay tuned for that episode soon.

01:50:52.020 | Again, you can find that at HubermanLab.com

01:50:54.260 | and on all platforms.

01:50:56.140 | In the meantime, I would be remiss

01:50:58.100 | if I didn't include a bit of discussion

01:51:00.740 | about what has been observed

01:51:02.780 | in terms of using psilocybin journeys

01:51:05.360 | as a way to treat depression,

01:51:07.260 | because the data are just oh so exciting.

01:51:09.700 | Again, these data really started to surface

01:51:12.460 | as the consequence of studies that were initiated

01:51:14.360 | around 2006 in just a few select laboratories,

01:51:19.240 | and then really picked up

01:51:21.140 | in terms of the number of laboratories

01:51:22.880 | and number of studies between 2018 and now.

01:51:26.600 | So what you'll notice is that most of the papers

01:51:28.460 | I'm about to describe were published in,

01:51:30.260 | for instance, phenomenal journals,

01:51:32.300 | New England Journal of Medicine in 2021,

01:51:36.260 | New England Journal of Medicine, November, 2022,

01:51:39.960 | Journal of the American Medical Association Psychiatry

01:51:44.180 | just very recently, 2021.

01:51:45.740 | So these are very recent papers.

01:51:47.340 | Essentially, all of these clinical studies

01:51:50.460 | involve either one or two psilocybin sessions.

01:51:55.460 | The dosages that were explored range from zero milligrams,

01:51:58.980 | so placebo, if you will, 10 milligrams,

01:52:02.420 | some cases 25 milligrams, in some cases 30 milligrams.

01:52:06.580 | And most typically, people received the same dosage

01:52:10.360 | for both sessions if indeed they did both sessions.

01:52:12.880 | However, there's at least one study

01:52:15.020 | looking at just one single episode

01:52:18.280 | of psilocybin administration.

01:52:19.780 | So this is the paper entitled, no surprise,

01:52:21.780 | single dose psilocybin for treatment resistant episode

01:52:24.340 | of major depression.

01:52:25.500 | This was published in the New England Journal of Medicine

01:52:27.540 | November of 2022.

01:52:29.060 | I'll just summarize the results

01:52:31.780 | of this single application study.

01:52:34.900 | They randomly assigned subjects

01:52:36.180 | who had treatment resistant depression,

01:52:37.660 | so they'd resisted treatment to other things,

01:52:40.200 | to receive a single dose

01:52:41.440 | of a synthetic formulation of psilocybin.

01:52:43.660 | So they're not eating mushrooms,

01:52:44.860 | they're getting a synthetic dose of psilocybin,

01:52:47.900 | but the dose is known of either 25 milligrams,

01:52:51.620 | 10 milligrams, or one milligram, which was the control.

01:52:55.460 | And they received psychological support.

01:52:57.540 | There were a number of different tests,

01:52:58.740 | subjective tests of depression,

01:53:00.340 | taken before and after the psilocybin journey.

01:53:05.560 | They had about 75 to 79 participants in each group,

01:53:10.400 | again, at the three different doses,

01:53:11.500 | 25, 10 or one milligram.

01:53:13.480 | And they looked at the changes in these scores,

01:53:16.980 | these depression related scores on these tests.

01:53:19.480 | There are many results from this paper one could summarize,

01:53:21.640 | but among the most important results

01:53:22.860 | I can summarize from the discussion,

01:53:24.140 | and here I'm paraphrasing that the change in baseline

01:53:26.580 | levels of depression that is,

01:53:28.580 | at week three, following the psilocybin session,

01:53:32.940 | was significantly better,

01:53:34.240 | that is people experienced more relief,

01:53:36.440 | or more people experienced more relief,

01:53:39.260 | from the 25 milligram dose than from the one milligram dose.

01:53:43.380 | And this is important,

01:53:44.620 | there was no significant difference

01:53:46.420 | between the 10 milligram dose and the one milligram dose.

01:53:49.420 | This really points to the fact

01:53:51.640 | that the 25 to 30 milligram dose that's used

01:53:54.520 | in the largest numbers of studies

01:53:56.280 | exploring treatment resistant depression,

01:53:58.560 | really seems to be, I don't want to say the best dose,

01:54:01.240 | but the most effective dose,

01:54:02.840 | at least in this clinical context,

01:54:05.400 | in this set and setting,

01:54:06.940 | and with this particular patient population.

01:54:08.880 | So we want to be careful to say that,

01:54:10.800 | so that one doesn't just translate the 25 milligrams

01:54:13.280 | is better than 10 milligrams,

01:54:14.760 | although in this study,

01:54:15.600 | it was for sake of treatment resistant depression relief.

01:54:20.200 | There were a number of other key aspects of this paper,

01:54:23.340 | in particular, the exploration of so-called adverse events.

01:54:26.300 | So things like headaches, propensity for self-harm,

01:54:29.320 | actual self-harm, anxiety, and so on.

01:54:33.440 | It's worth mentioning that there were adverse events

01:54:36.880 | in essentially every group.

01:54:38.740 | The number of adverse events was highest

01:54:42.180 | in the 25 milligram dose group.

01:54:44.220 | This is observed in other studies as well.

01:54:46.400 | With higher dosages, there tends to be greater relief

01:54:49.840 | from depressive symptoms,

01:54:51.080 | but also a greater chance for adverse events.

01:54:55.620 | Some of those adverse events can be quite severe,

01:54:58.080 | so feelings of suicidal ideation, et cetera.

01:55:00.720 | Some of them, one could consider a little less severe,

01:55:03.440 | mild headache, or severe headache that was transient,

01:55:07.520 | or anxiety that was transient.

01:55:08.940 | Again, highly individual responses.

01:55:10.840 | We could go line by line and table by table

01:55:14.280 | through this paper, which we won't,

01:55:15.980 | because there's a lot of data.

01:55:17.500 | Again, we'll provide a link to this paper

01:55:18.940 | if you'd like to peruse it yourself.

01:55:20.740 | It's fairly straightforward to read.

01:55:22.320 | That's one thing that's nice about these clinical trials

01:55:24.720 | is they tend to be written in fairly non-technical language,

01:55:27.400 | although there's a little bit of technical language.

01:55:29.660 | The important point is that a single dose

01:55:31.240 | of 25 milligrams of psilocybin provided significant relief

01:55:35.440 | from treatment of resistant depression

01:55:37.280 | in this particular patient population.

01:55:39.080 | But it is not the case that 100% of the people

01:55:41.620 | who took 25 milligrams of psilocybin

01:55:43.840 | experienced that relief.

01:55:44.680 | However, the majority of them did.

01:55:47.200 | Now, when you say majority in science,

01:55:48.720 | you really need to look to numbers.

01:55:50.440 | And the reason I'm not telling you,

01:55:52.260 | oh, it was 75% or 60% or 50%

01:55:55.420 | is because it depends on which time point

01:55:57.720 | people were analyzed.

01:55:59.360 | People were asked about their level of depression relief

01:56:02.700 | immediately after, one week after, two weeks after,

01:56:05.580 | three weeks after.

01:56:07.320 | And the degree of relief tended to change over time.

01:56:10.300 | In fact, it tended to diminish over time,

01:56:12.080 | but it was also stable, or remarkably stable, I should say,

01:56:15.860 | at least by my read,

01:56:17.420 | in the 25 milligram dose group.

01:56:20.200 | And that is summarized nicely in figure two of the paper,

01:56:23.460 | because they explored these people's levels of depression

01:56:26.080 | out to week 12,

01:56:28.140 | and they still saw a significant degree of depression relief

01:56:32.280 | 12 weeks after the single 25 milligram

01:56:35.700 | psilocybin dose session.

01:56:37.680 | So as I mentioned earlier,

01:56:38.980 | there are now about a dozen or so excellent studies,

01:56:42.020 | clinical trials exploring the use of single

01:56:44.760 | or two-session psilocybin treatment

01:56:47.260 | in that 25 to 30 milligram range,

01:56:50.140 | which seems to be the most effective dose

01:56:52.380 | for long-lasting relief from depression.

01:56:54.740 | Each one of those studies explored something different,

01:56:59.080 | as is important.

01:57:00.180 | Replication is also important, of course,

01:57:01.980 | in order to validate previous studies.

01:57:04.200 | But for instance, there have been comparisons of psilocybin

01:57:08.060 | versus SSRIs or other antidepressants.

01:57:11.140 | There have been comparisons of psilocybin

01:57:13.280 | plus psychoanalysis or cognitive behavioral therapy

01:57:17.240 | versus cognitive behavioral therapy alone

01:57:19.340 | or psychoanalysis alone.

01:57:20.980 | And so there's a lot of evaluation now

01:57:23.240 | of the clinical outcomes and the statistical outcomes

01:57:27.040 | of these subjective measures

01:57:28.940 | and even some objective measures of neurochemistry

01:57:31.740 | where that's possible in terms of trying to understand

01:57:35.100 | if and how psilocybin is effective

01:57:37.440 | for the treatment of depression.

01:57:38.880 | And the major takeaway is that,

01:57:40.460 | indeed, it does seem to be the case.

01:57:42.080 | And the numbers that I feel comfortable

01:57:44.420 | not throwing out there but putting out to you

01:57:46.540 | reflect my conversation with Robin Cardhart-Harris.

01:57:49.220 | Again, that will be released soon at hubermanlab.com,

01:57:52.800 | as well as takeaways from what I would say

01:57:56.060 | are the six broadest studies,

01:57:59.480 | meaning they have the widest range of age groups,

01:58:02.460 | the broadest demographic in terms of the subjects,

01:58:05.720 | their backgrounds, their levels of education,

01:58:08.300 | men, women, ethnicity, et cetera.

01:58:10.940 | And a lot of that can be summarized

01:58:13.380 | in the paper entitled "Effects of Psilocybin-Assisted Therapy

01:58:15.900 | "on Major Depressive Disorder."

01:58:17.360 | This was a particular randomized clinical trial.

01:58:20.480 | But in the discussion, I think they summarize it quite well,

01:58:23.620 | which is that if you look at the number of people

01:58:27.560 | who take this 25 milligram dose twice

01:58:31.820 | in sessions spaced about a week apart,

01:58:34.760 | what you will find is that anywhere from 60 to 75%

01:58:39.580 | of the people who have major depressive disorder

01:58:42.420 | who do these psilocybin sessions in the proper setting,

01:58:44.820 | report a good experience with it,

01:58:46.880 | have minimal adverse events coming out of those sessions,

01:58:50.540 | and in the weeks following,

01:58:51.900 | those people experience substantial positive relief

01:58:57.780 | from major depression in ways that other treatments

01:59:00.740 | that they've explored, including antidepressant drugs,

01:59:04.900 | cognitive behavioral therapy, and other types of therapy

01:59:07.620 | alone could not provide.

01:59:09.540 | Now, it's a general feature of these clinical trials

01:59:12.580 | focusing on psilocybin that people are asked

01:59:14.540 | to stop taking their antidepressants

01:59:16.300 | prior to participating in the trial.

01:59:18.300 | It's also a general feature of these trials

01:59:21.100 | that people are encouraged to not suddenly start

01:59:24.300 | their antidepressant treatment immediately afterwards,

01:59:27.220 | because of course that could confound the results

01:59:29.020 | of the psilocybin treatment.

01:59:30.420 | However, and this is a very important thing to note,

01:59:33.120 | all subjects were encouraged not to avoid

01:59:36.260 | taking those antidepressant medications

01:59:38.900 | if in fact their clinician felt that it was important

01:59:42.020 | for their immediate and long-term survival.

01:59:44.460 | So no one should be reckless in thinking about

01:59:47.060 | what to add or delete from their drug protocol

01:59:51.020 | when dealing with depression, right?

01:59:52.480 | The outcomes could be very severe in that case.

01:59:55.460 | Nonetheless, we can paraphrase from the discussion

01:59:58.820 | of the paper I just mentioned,

02:00:01.000 | because it really highlights the incredible results

02:00:03.060 | that psilocybin applied in these particular

02:00:05.700 | therapeutic settings are providing.

02:00:07.800 | And here again, I'm paraphrasing.

02:00:09.860 | The present trial showed that psilocybin administered

02:00:12.300 | in the context of supportive psychotherapy,

02:00:14.520 | consisting of approximately 11 hours of psychotherapy,

02:00:18.920 | so this is going to be two sessions of the psilocybin

02:00:22.940 | with proper therapeutic support,

02:00:25.460 | produced large rapid and sustained antidepressant effects.

02:00:28.580 | The effect sizes reported in the study

02:00:30.260 | were approximately 2.5 times greater

02:00:33.060 | than the effects sizes found in psychotherapy.

02:00:37.060 | And more than four times greater than the effect sizes

02:00:39.520 | found in psychopharmacologic depression treatment studies.

02:00:42.940 | In other words, four times the positive effect

02:00:45.200 | observed with typical SSRIs

02:00:47.980 | or other pharmacology of that sort.

02:00:50.540 | These findings are consistent with the literature

02:00:53.360 | that showed that combined pharmacotherapy and psychotherapy

02:00:56.300 | were more efficacious in the treatment

02:00:57.760 | of major depressive disorder than either intervention alone.

02:01:01.300 | So again, this points to the fact that combining

02:01:04.020 | drug therapy with talk therapy, as it's often called,

02:01:07.880 | is going to be more effective than either treatment alone.

02:01:10.340 | Here are the drug therapy, psilocybin therapy.

02:01:12.940 | And again, please don't take the fact that in these studies,

02:01:15.440 | they tended to ask people to not take

02:01:17.140 | their antidepressant medication heading into the study

02:01:19.580 | as a sign that one should stop taking

02:01:21.000 | their antidepressant medication.

02:01:22.180 | Rather, I think this study and other studies like it,

02:01:24.820 | again, which we'll provide links to in the show note

02:01:27.520 | captions that are discussed extensively in the episode

02:01:30.020 | with Dr. Cardart-Harris soon to come,

02:01:32.460 | really point to the incredible role that psilocybin can have

02:01:36.860 | in creating an experience inside of the session,

02:01:40.460 | the journey or the trip, as it's called,

02:01:43.060 | as well as initiating neuroplastic events,

02:01:45.860 | perhaps the addition of dendritic spines,

02:01:47.300 | maybe even some new neurons, maybe,

02:01:49.620 | although I don't think that's the predominant mode,

02:01:52.120 | but that leads to these more extensive connectivities

02:01:54.660 | in the brain, the so-called reduction in modular networks,

02:01:58.900 | enhanced activity in brain areas that normally

02:02:02.460 | wouldn't be talking to one another,

02:02:03.620 | but not doing that in any kind of haphazard way.

02:02:06.360 | It really does seem that the one or two sessions

02:02:08.780 | of psilocybin that induce these feelings of ego dissolution,

02:02:13.140 | that induce these feelings of oceanic boundlessness, right?

02:02:15.780 | So mystical, right?

02:02:17.300 | And in many ways, it's what I find so incredible

02:02:19.540 | about psilocybin and other psychedelics

02:02:22.100 | is that despite the highly mystical, highly subjective,

02:02:26.660 | and still at this time, somewhat top contour understanding

02:02:31.220 | of how they might exert their effects,

02:02:34.120 | you can highlight boldface and underline might there, right?

02:02:36.660 | Because it hasn't really been firmly established

02:02:38.920 | what the exact cell biological rewiring events are,

02:02:42.480 | but there is now what I would refer to

02:02:43.760 | as a center of mass of data that point to the fact

02:02:47.140 | that psilocybin, when taken in the appropriate set

02:02:49.900 | and setting, the appropriate dosages,

02:02:52.740 | can invoke the sorts of neuroplasticity

02:02:55.220 | and changes in emotionality, in perceptual experience,

02:02:59.320 | not just during the psychedelic session,

02:03:01.220 | but for long periods of time after the psychedelic session

02:03:04.260 | that can provide really remarkable relief

02:03:06.660 | from things like major depression

02:03:08.220 | and perhaps other psychiatric issues as well.

02:03:11.140 | And of course, I realize that many of you are listening to

02:03:13.260 | and are watching this episode

02:03:14.620 | and you're not necessarily depressed

02:03:16.220 | or thinking about psychedelics like psilocybin

02:03:18.700 | in the context of depression.

02:03:20.380 | I hope today's discussion allowed you to better understand

02:03:22.860 | how psychedelics and psilocybin in particular,

02:03:26.300 | because that's what we've been talking about,

02:03:28.420 | are able to exert these incredible effects

02:03:30.240 | that they seem to exert.

02:03:31.500 | This is not a call for everyone to run out

02:03:34.840 | and do psilocybin, it is absolutely not that.

02:03:37.800 | It is, however, my attempt to really put a magnifying lens

02:03:41.100 | on this incredible area of research that's happening,

02:03:43.180 | not just in the context of clinical trials,

02:03:45.300 | but in the context of trying to understand how serotonin

02:03:49.120 | and how drugs like psilocybin,

02:03:50.860 | which in many ways mimics serotonin,

02:03:52.680 | and more particularly the activation of particular receptors

02:03:55.440 | in the brain, like the serotonin 2A receptor.

02:03:57.320 | I mean, just sit back and think about that.

02:03:58.980 | The selective activation of this receptor,

02:04:01.420 | which is, by the way, associated with the expansion

02:04:04.780 | of the neocortex across evolution,

02:04:07.140 | didn't mention that before, but indeed it is,

02:04:09.820 | how that can lead to enhanced ways of thinking,

02:04:12.780 | changed ways of thinking,

02:04:14.180 | actual learning inside of this short four-hour

02:04:17.820 | or six-hour session that we call the psilocybin journey.

02:04:21.160 | So as is often the case, perhaps as is always the case

02:04:24.460 | here on the Huberman Lab Podcast,

02:04:26.060 | we did a deep dive into a topic today,

02:04:28.120 | into the topic of psilocybin, what it is, how it works,

02:04:32.560 | the different ways in which it changes brain circuitry,

02:04:35.260 | how it creates the experiences that we think of

02:04:38.060 | as the psilocybin journey, what the safety issues are,

02:04:41.760 | what the so-called set and setting are

02:04:43.900 | that can lend themselves to positive therapeutic outcomes.

02:04:47.100 | And in doing so,

02:04:47.940 | my goal was really to highlight several things.

02:04:49.560 | First of all, I am very excited

02:04:51.980 | about the potential for psychedelics such as psilocybin

02:04:55.940 | to provide relief for mental health issues

02:04:58.140 | that to date have been very hard for people to access.

02:05:01.660 | In addition to that,

02:05:02.700 | I'm just fundamentally interested in the brain

02:05:05.020 | and how it works and how it can change

02:05:06.780 | this thing we call neuroplasticity.

02:05:08.540 | To me, neuroplasticity is the holy grail

02:05:11.380 | of the human nervous system.

02:05:13.240 | As far as we know, we are the animal

02:05:15.500 | that can have long-lasting neuroplasticity

02:05:17.980 | throughout the lifespan.

02:05:19.540 | And if it requires the use of compounds

02:05:22.380 | in a safe and controlled way, such as psilocybin,

02:05:24.960 | in order to achieve maximal plasticity

02:05:27.240 | in a short amount of time, that's exciting.

02:05:29.380 | But of course, that also needs to be considered

02:05:31.420 | with all of the safety precautions in mind

02:05:33.540 | that we talked about earlier,

02:05:34.420 | including the fact that people who have a predisposition

02:05:38.340 | or who have psychosis or bipolar disorder

02:05:40.500 | or a relative that has psychosis or bipolar disorder,

02:05:44.980 | younger people, meaning people 25 years of age and younger,

02:05:48.180 | and really anyone who's not working with a dedicated

02:05:50.780 | and highly trained physician

02:05:52.420 | needs to be very cautious about these compounds as well.

02:05:54.540 | They're very exciting.

02:05:55.840 | I think psilocybin is an exciting

02:05:57.300 | and super interesting compound

02:05:59.140 | for basic and clinical reasons

02:06:00.620 | and for other reasons as well.

02:06:02.120 | But they are sharp blades, as we say.

02:06:05.180 | And with sharp blades, you can do incredible things,

02:06:07.420 | but you can also cut yourself very badly.

02:06:09.820 | So all those considerations need to be taken to mind.

02:06:12.440 | So I consider the science and use of psilocybin

02:06:15.220 | to be an exciting but still preliminary area

02:06:18.820 | that I certainly am paying a lot of attention to

02:06:21.900 | and I know there's a lot of excitement about.

02:06:23.860 | So stay tuned for the episode

02:06:25.180 | with Dr. Robin Cardart-Harris,

02:06:26.940 | and we will probably revisit psilocybin,

02:06:28.880 | and we will certainly revisit the other psychedelics

02:06:31.580 | and non-classical psychedelics,

02:06:33.140 | including LSD, DMT, 5-MeO-DMT, ketamine, MDMA, mescaline,

02:06:38.140 | and all the rest in future episodes as well.

02:06:42.420 | If you're learning from and/or enjoying this podcast,

02:06:44.620 | please subscribe to our YouTube channel.

02:06:46.380 | That's the best zero-cost way to support us.

02:06:48.700 | In addition, please subscribe to the podcast

02:06:50.900 | on both Apple and Spotify.

02:06:52.500 | And on both Apple and Spotify,

02:06:53.720 | you can also leave us up to a five-star review.

02:06:56.280 | If you have questions for me or comments about this

02:06:58.520 | or any other podcasts or topics that you'd like me to cover

02:07:01.420 | or guess you would like me to interview

02:07:02.780 | on the Huberman Lab Podcast,

02:07:04.300 | please put those in the comment section on YouTube.

02:07:06.760 | I do read all the comments.

02:07:08.580 | In addition, please check out the sponsors mentioned

02:07:10.500 | at the beginning and throughout today's episode.

02:07:12.180 | That's the best way to support this podcast.

02:07:14.520 | Not so much during today's episode,

02:07:15.900 | but on many previous episodes of the Huberman Lab Podcast,

02:07:18.280 | we talk about supplements.

02:07:19.380 | While supplements aren't necessary for everybody,

02:07:21.540 | many people do derive tremendous benefit from them

02:07:23.600 | for things like enhancing the quality

02:07:25.360 | and duration of their sleep,

02:07:26.740 | for things like improving focus,

02:07:27.960 | and for hormone augmentation, and much more.

02:07:30.680 | The Huberman Lab Podcast is proud to have partnered

02:07:32.560 | with Momentous Supplements.

02:07:33.780 | If you'd like to learn more about the supplements discussed

02:07:35.580 | on the Huberman Lab Podcast,

02:07:37.060 | you can go to Live Momentous, spelled O-U-S,

02:07:39.480 | so livemomentous.com/huberman.

02:07:42.220 | If you haven't already subscribed to our Huberman Lab Podcast

02:07:44.780 | neural network newsletter,

02:07:46.400 | the neural network newsletter

02:07:47.560 | is a completely zero-cost newsletter

02:07:49.960 | that includes summaries of podcast episodes

02:07:51.900 | and summaries of protocols,

02:07:53.220 | things like a toolkit for improving your sleep,

02:07:56.480 | a toolkit for improving focus,

02:07:58.100 | toolkit for neuroplasticity,

02:07:59.900 | toolkit related to deliberate cold

02:08:01.500 | or deliberate heat exposure,

02:08:02.540 | to fitness, to flexibility, and much more.

02:08:04.240 | Again, all zero cost.

02:08:05.820 | Simply go to HubermanLab.com, go to the menu,

02:08:08.700 | scroll down to newsletter, and provide your email.

02:08:11.400 | We do not share your email with anybody,

02:08:13.260 | and again, the newsletter is completely zero cost,

02:08:15.240 | and to see previous newsletters,

02:08:17.000 | you can simply scroll down a bit further

02:08:19.340 | on that neural network newsletter page at HubermanLab.com,

02:08:22.180 | and you'll find downloadable PDFs,

02:08:23.780 | and you can just click on any of those PDFs,

02:08:26.100 | no signup required.

02:08:27.420 | And if you're not already following me on social media,

02:08:29.620 | it's Huberman Lab on Instagram, Twitter,

02:08:31.820 | Facebook, and LinkedIn.

02:08:33.700 | And on all those places,

02:08:34.960 | I discuss science and science-related tools,

02:08:37.260 | some of which overlaps with the content

02:08:38.800 | of the Huberman Lab Podcast,

02:08:40.380 | but much of which is distinct from the content

02:08:42.240 | covered here on the Huberman Lab Podcast.

02:08:44.000 | So again, it's Huberman Lab on Instagram,

02:08:46.820 | Facebook, Twitter, and LinkedIn.

02:08:48.740 | Thank you once again for joining me for today's discussion,

02:08:51.080 | all about psilocybin.

02:08:52.760 | And last, but certainly not least,

02:08:55.020 | thank you for your interest in science.

02:08:56.900 | [upbeat music]

02:08:59.480 | (upbeat music)

How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks | Huberman Lab Podcast

Chapters