How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks
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Welcome to the huberman lab podcast, where we discuss science and science space tools for everyday life. I made her huberman, and i'm a professor of neutral logy and opposite gy at stanford school of medicine. Today we are discussing, solicit an silicic.

Ben is a psychiatric meaning. IT modifies the psyche. And in doing so, IT changes our level of consciousness. Psychodeviant s such a solicitation and changed the way that we perceive the outside world and our internal world, our memories, our thoughts, our feelings at sea, not just, well, one is under the influence of slyvia. But I can also fundamentally change all of those things afterwards.

And for a very long period of time afterwards as well, which is one of the reasons why there is growing excitement about the application of sillas, ivan and other psychodeviant s for the treatment of various mental health issues such as depression, alcohol abuse disorder and addictions of various kinds, as well as things like ocd and eating disorders. Today, we will discuss slice, yvan, talking about what IT is. In fact, you may be surprised to learn that solicited, and basically is serotonin.

Now, for those of you there are familiar, are silicon and serotonin. You might think, wait, that's not true. But in fact, solicitor's main effect is to mimic serotonin.

But IT does IT in a very specific way, because IT activates a subset of serotonin receptors in a very strong fashion, leading to neuroplasticity at the level of the neural circuits, that is, the brain areas and connections that serve things like memory and perception. So if any of that is confusing at this point, I promise to make IT all clear in just a few minutes. Sullivan is one of many psychiatrically.

Of course, there are things like L D D, mt, five, M O D, mt, even md ma will not considered a classic psychiatric. C is considered a psychiatric in the general sense. Today's episode is going to focus on silicon, yvan.

In particular, I will tell you what soliciting on is how IT works at the molecular and cellular level. I'll talk about how IT changes brain circuitry. I'll talk about the clinical effects, what's been demonstrated in controlled laboratory studies. I'll talk about dosages and translating from slice ban mushrooms to actually solicit an and the compound that actually exerts the effects of silicates, on which IT turns out is not solicited on, but something silicon. Silicon is the actual compound that goes into the brain to create all the changes and consciousness and all the rewiring effects that we associate with sillas yvon.

So understanding how silicon band is converted to silicon has tremendous impact on the duration of a solicit an journey, whether or not that solicit an journey is going to lead to a short or longer window for neural plasticity. In fact, many people don't realize this, but much of the positive changes that are possible with proper, and I do want to underscore proper suicide and therapeutics approaches, takes place after the session, in which one feels all the know typical or typically associated effects of suicide, and like hallucinations and changes and thought patterns at sea. So today we are going to talk a little bit about chemistry, but I promise to make IT accessible to anyone and everyone, regardless of whether not you have a background in chemistry.

biology. We're going to talk about some cell biology, the actual neuronal changes that occur when one takes sicyon. And we're going to talk about how neural circuits change over time and how all of that impacts the changes that most people are interested in when they go on a sulfide and journey.

Things such as lone standing, improvements in mood, things such as tremendous insight into themselves, into others, into their past, their present, in their future, and even changes in their levels of creativity or their ability to experience joy from music, or their ability to associate in a positive way from things that formally were depressing or trigger for depression. In fact, we're going to talk quite a lot about the conditions inside of a silicide, an journey that make IT actually positive. And therapy iud.

This is a very important point that i'll make several times throughout today's episode, which is that just because something evokes neural plasticity changes in brain circuitry does not mean that it's their aioc or I should say, does not necessarily mean that it's therapeutic. C for neuroplasticity to be therapeutic, IT has to be adaptive. IT has to allow someone to function Better in life than they did previously.

So today we will talk about how the conditions of a salient journey, including whether or not it's done with eyes closed or eyes open, or whether or not people alternate between eyes closed and eyes open phases of that journey, as well as whether not music is played during that journey. And even what types of music are played will dictate whether or not somebody will feel Better or worse in the days and weeks and years following that suicide journey, as well as the dosage level. Because as you'll soon learn as well, there are clinical study showing that just one solicitation and journey can improve mood in a long standing way.

But most clinical trials involve two dosages space in very precise ways from one another with appropriate follow up. But in both of those particular journey, the structure of the journey, whose present, who's not present, eyes open, your eyes closed, the particular music that's played, all of those features make up part of a larger neuroplasticity trigger, of which sillas yvon is critical. But slice bon is not the only variable.

So whether or not you're interested in participating in a critical study or whether not you're interested in cilli, ivan, for other reasons, this is critical information to understand. So today, we're going to talk about nearly every feature of silicide impossible, including what Sullivan is, how IT works at the level of chemistry, cl, biology and neural networks and neuroplasticity. We will talk about the clinical studies, will talk about dosages.

We will talk about conditions of clinical studies, and we will talk about the post, solve and journey period in which ticket and the various activities, including therapy, or perhaps not therapy, can contribute to positive therapeutic changes from soli ban. Now as we go into this discussion, I do want to underscore the fact that at the time of recording this episode, meaning now may twenty twenty three, Sullivan is still a schedule one drug, IT is considered illegal in the united states is perhaps just one exception to that, maybe a few others. But the main exception is in the state of oregon, suicide ban has been approved in particular therapeutic settings for use in particular conditions, namely depression in some forms of addiction.

So in organ, it's more less in the domain of decriminalized as opposed to actually legal in other areas of the country, including oakland, california, there are some areas in which IT has been decriminalized and props. There are a few others that i'm not aware of, but in general, Sullivan and other psychic lcs are still considered illegal. This is very important, not just saying this to protect me, i'm saying this to protect you.

Possessing or certainly selling slice ibn, except for rare ants, insist, such as clinical studies and these decriminalized areas that have talked about a moment ago is still very much not allowed under the law. today. I'll also discuss safety issues. I'll talk about whether not Young people, meaning people twenty five or Younger, should consider seller. And given that their brain is still in a rampant period of naturally occurring neuroplasticity, I will also talk about dosages as IT relates to people who have formally been on or may currently beyond different forms of anti depression.

And I will talk about people who are at risk for psychotic c episodes, either because they know they themselves have a propensity for psychosis, or they have close family members who have psychosis, which includes things like schizophrenia, bipolar, depression and as well as things like borderline personality and some related psychiatric conditions. So today is the episode really will be a deep dive into slice bon. So whether not you think you're already familiar with sliced on in its effects or whether or not you're just curious about them.

I do encourage if you're willing to try and catch IT through some of the understanding of how suasive and works and what IT is leading up to some of the therapeutic applications and different patterns of dosing spacing of different sessions. That said, a because I do believe that with that knowledge in hand, you will be able to make far Better, much more informed decisions about whether not suicide ban is right for you. Before we begin, i'd like emphasize that this podcast is separate from my teaching researchers at stanford.

IT is, however, part of my desired effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, i'd like to thank the sponsors of today's podcast. Our first sponsor is element.

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Today's episode is also brought to us by waking up, waking up as a meditation APP that includes hundreds of meditation programs, mindfulness trainings, yoga eja, recessions and nsd r non sleep depressed protocols. I started using the waking up up a few years ago because even though i've been doing regular meditation since my teens and I started doing yoga eja about a decade ago, my dad mentioned to me that he had found an APP, turned out to be the waking up APP, which could teach you meditations of different durations, and that had a lot of different types of meditations to place the bringing body into different states, and that he liked IT very much. So I gave the waking up up a try, and I too found IT to be extremely useful, because sometimes I only have few minutes to meditate, other times have longer to meditate.

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Yoga edra is a process of linger still, but keeping an active mind. It's very different than most meditations. And there is excEllent scientific data to show that yoga eja and something similar to IT called non sleep deep breast or nsd r, can greatly restore levels of cognitive and physical energy even, which is to a short ten minute session.

If you'd like to try the waking up up, you can go to waking up dot com slash huberman and access a free thirty day trial. Again, that's waking up dot com slash huberman to access a free thirty day trial. Let's talk about sicyon on.

And again, today, we're going to focus specifically on soliciting, and we're going to set aside all the other psychiatric for future episodes. Suicide on is what's called a trip to me that refers to its chemical composition, not to the so called psychiatric trip. In fact, that smell differently.

Trip to me in as T R Y P trip. T R I P, of course, trip to means include silica ban, but also things like D M T and five M D mt. The trip to mean psychiatrically are very closely resemble serotonin itself.

That's right. Most of you have probably heard of the chemical serotonin. And serotonin is what's called a neuromodulator, which means your brain and body naturally make IT, and that IT modifies or changes the activity of other neurons and neural circuits. And IT does that generally by either increasing or decreasing the activity of those neural circuits.

If I were to show you a picture of the chemical structure of Sullivan or its active derivative silicon, and I were to also put right along side IT in the image of the chemical structure of serotonin, provided that you weren't a chemist who really likes to focus on the detailed differences between things, you would say those look very similar. And indeed, slice van and its active form silicon are very similar structurally and chemically to serotonin itself. Now, as I mentioned before, serotonin is something that you naturally make.

And yes, it's true that about ninety percent of the serotonin in your brain and body is manufactured in your gut. However, contrary to popular belief, the service tony in your brain is not manufactured from the cereal tony in your gut. You have separate independent sources of serotonin, that is, you are particular neons that make serotonin in your brain.

You also have serotonin in your gut. And those work more less than parallel separately. Now what is service? Tony, do this is really important. Understand, because of the similarity between silica ban and its act, inform, silent and serotonin. Serotonin, and that is a newer modulator changes, the activity of other neurons.

And the net effects of those changes are things that you're familiar with, for instance, satie or the feeling that we've had enough of various things such as food or a social interaction or sex or pleasure of any kind. Sir tony is involved in all of that. And an enormous number of other things such as mood regulation, such as our sense of pleasure itself or lack of pleasure, such as whether or not we feel motivated or not motivated.

IT works in concert with other neuromodulators, such as doping and epomeo, nor epinephrine. Fact, if this were an episode about car ot onan, which IT is not, you would soon realize that serotonin is involved in so many different functions that impact our daily life. And that is one reason why certain anti depression medications, which alter, either increase or decrease the amount of serotonin transmission in the brain, will often have a lot of side effects related to things like mood, libido, appetite, sleep at sea.

It's because ceretani is involved in so many different things, and serotonin is involved in so many different things, because there are a lot of different so called serotonin receptors. Serotonin is a chemical that we call a ligand, and the chemical ligand is simply the thing that plugged into the reception for that chemical, or ligand, the receptions. In this case, a OTA.

A receptors have the opportunity to do all sorts of different things. They can change the activity of neurons, making them more active, less active. They can cause growth factors to be released, making sure that those neurons reinforce or even build up stronger connections so that they're more likely to be active in the future. Serotonin in buy into particular receptor ors can even change the gene expression in particular cells, making those cells proliferation, make more of them, making those cells more robust, making those cells and interact with new elements of the brain and body, basically serotonin, and all these different recipes that depends to as dozens, if not hundreds, and maybe even thousands of different functions.

So the fact that slyvia so closely resemble serotonin leads to a very important question that we should all be asking ourselves, which is, why is IT that cilli ivan, which looks so much like serotonin when one takes IT in the form of magic mushrooms, or some other form may be the synthetic form of silicon band itself, which nowadays is manufactured in laboratories and placed in different silica and containing food and pills at seta. why? That leads to complex, yet fairly circumscribe sets of experience like visual and auditory hallucinations, ges, in particular, thought patterns and neural plasticity that, in many cases, in the clinical settle, provided things are done correctly, improvements in mood relief from depression, relief from various compulsive disorders at sea, right? This is really what you need to understand.

If you won't understand Sullivan and how IT works and how to make IT work optimates for a given condition or goal, you have to understand what it's actually doing and what allows solarian to do fairly specific things in comparison to serotonin, even though so lybian and serotonin are so similar, is that solicit ve been mainly binds to and activates the so called serotonin two a receptor, the serotonin a recept tor is one of, again, many different serotonin recept tors. But cereal, tony to a is expressed in particular areas of the brain, and even on particular areas of neurons in the brain that allow for very specific types of changes in neural circuit tree to take place, not just when one is under the influence of silica ban, but afterwards as well. So really, in order to have a useful discussion about solicitation, we need to talk a lot about the serotonin in two a receptor.

But unfortunately for you, unless you're somebody really interested in structural biology or self biology, that discussion is not going to be about the binding pocket for serotonin on serotonin into a recept tor or a lot of the downstream signaling in the ertong into a recept. Will talk a little bit about that where it's relevant. But more importantly, at least for sake of today's discussion, we're going to talk about how the serotonin a receptor is really the one responsible for trigger ing, all the changes in neural circuitry that lead to the changes, that is, the improvements in mood, the relief from compulsive disorders in many case.

But really it's the serotonin two a receptor selectivity of that is leading to all the excitement that you hear about. In terms of slicer ban as a therapeutic tool, I need to say that from a slightly different angle, there are data that i'll talk about today, which show that one, although in most cases, to solve ban journeys done with particular dosages of solicited on lead to maximum binding or occupying y of those serotonin a receptors in ways that lead to significant and unprecedented relief for major depression. In fact, you'll soon learn that the clinical trials for soliciting on are outperforming standard therapy and outperforming so called essa is and various other anti depression in terms of providing depression relief in ways that are Frankly staggering IT not just to me, but to the psychiatric community at large.

And this is what you're so much the excitement is coming from. Now that statement could be taken one way, which is to just say, okay, well, here's a compound so ivon that outperforms as sr. s.

And therefore all the attention should be on Sullivan. But S, S, R, I stands for selective serotonin reuptake inhibitor. In other words, the sis of which there is now a lot of controversy, things like projects at sea. I'm sure you ve heard some of this controversy. There are people who are very pro S S, as though there are growing number of people who really feel that the ssr eyes are probably most appropriate for things like obsessive compulsion disorder, where they in fact can be very beneficial.

But there is a lot of kind of leaning back from accessorize as the ball indal for the treatment of depression nowaday because of the side effect profiles and the fact that not even really clear that serotonin deficiencies are the major cause of depression in the first place. Now, again, we're talking about suicide and not about us. Sr, ize, but you should be thinking, weight, how is IT that two molecules, Sullivan and some particular ssi, both of which look like and or increase their own and transmission in the brain, are leading to either incredibly positive and interesting outcomes, or two kind of troubling side effect riddled outcomes.

And again, IT all boils back down to the selectivity of solicited to bind that seron into a receptor. And so in order to understand how suicide an works, and in order to understand proper dozing profiles and spacing of sessions A K journeys, we really need to talk a little bit more about the serotonin, a receptor where IT is in the brain. What sorts of things happen when soli ban bines the serotonin a receptor, and how those things set in motion, the various changes, the neuroplasticity that allows people to feel Better in terms of their mood, and, as you'll soon learn, can experience more pleasure, joy from things like music and enhance creativity.

All the things that I do believe, whether not people are thinking about or maybe even an expLoring suicide and for recreation or therapy purposes, all the things that people want and are really talking about and perhaps even doing solicit van in order to obtain. So before going any further, I just want to place an image in your mind. You can place an image your mind wear by when serotonin is released in the brain, naturally, not having taken any compound, any drug, anything.

It's going released a lot of different sites, binding to a lot of different are toning recept tors doing a lot of different things. When somebody takes an sri, the net effect of that selective serotonin reuptake ken hibor is that there's more serotonin around to exert its effects because it's a reuptake ken hibor at the synapse, the connections between neurons, the seton's, can do its thing more extensively and for longer periods of time. But is doing IT kind of non specifically so when you think about standard entity depressed and treatments, at least for sake of this disgusting, you kind of think of a springing or kind of um you know spring of serotonin, different locations in the brain and binding to lots of different receptors.

Whereas when you think about suicide, and even though the subjective effects are pretty diverse, we'll talk about those in a few moments where you're really talking about is. A molecule suicide band that looks a lot like serotonin, that is selectively and very strongly binding to an activating that serotonin to a receptor, so that the im like you to embedding your mind, and then the next im like you to embed in your mind, is where these certa into a recept tors are located in the brain. Now, these certa into a recept tors are located in multiple brain regions, but they have a tremens amount of expression in the so called neocortex, the outside of the brain.

That includes things like our preferences cortex, which is involved in understanding context, which behaviors, thoughts and speech patterns are appropriate for certain circumstances. Um how to switch context and category switch. When you go from you know playing sports to hang out with friends to being in a professional setting, you change your behavior in the way that you speak, and perhaps even the way that you think you might think.

Some things that are out of context, we probably keep those to yourself. And you're ability to keep those to yourself are dependent on a functional preferences. cortex. There are a lot of five ht to a, and by the way, five ht is the revision for serotonin.

So there are a lot of serotonin, a recept tors, in the prefrontal to cortex, also in other areas of the cortex that are associated with sensation and perception, that is, hearing of sounds that is seen or particular things. And in particular, there is a very, very, very high expression of satan in two a receptors in the visual cortex. And that is one of the reasons why suicide triggers visual fluctuations.

And provided Sullivan is present at sufficient enough concentration, that is taken at a sufficient dosage, one will experience profound visual whose and regardless of whether or not their eyes are open or their eyes are closed. Now that's an important fact, because IT explains one of the major effects of suicide and that people experience while they are on the drug. Now i'll talk about a little bit later in terms of what constitutes a useful sulfide and session, useful, meaning that is leading to adaptive improvements in mood, adaptive of improvements in creativity and cognition.

Eta is that people not have their eyes open for at least the majority of the slice ban session. This is something I i've discussed with several experts who are running clinical studies on solicited on in their laboratories, some of whom are going to be guessed on the hulk cast and upcoming episodes. And I can't underscore this enough because your visual cortex contains so many of these serotonin two a receptors and because sicilian bds so strongly to that serita into a receptor, you're going to experience a lot visual fluctuations when you are under the influence of Sullivan.

No surprise there. This has been known for hundreds, if not thousands of years. It's one of the main reasons why people take a however, as I mentioned earlier, these fluctuates, occur even when the eyes are closed. And it's now fairly well established that if people are to take Sullivan and have their eyes open, much of their cognition, much of their thinking, much of the time spent in that sulfide and journey is focused on the altered perceptions of things in the outside environment.

Sometimes this looks like a um sort of a fracturing of the outside world into kind of geometric shapes, sometimes appearance as a kind of melting of things in the visual environment, including people's faces or a morphing of people's faces. All of that has a strong and it's just call IT a draw for a lot of people who are looking for a highly unusual experience inside of the suicide an journey. But think if one's goal is to derive the long lasting benefit from the suicide ban experience is very clear that having an eyes mask or some other eye covering or something that ensures that one's eyes are closed for the majority of not the entire sulfide and session is going to be very useful because it's going to limit the extent to which one is focused on those outside changes in visual perception, A K hallucinations.

And rather will allow the person to go inward, to combine whatever is that they happen to be seeing in their mind's eye with the different thoughts and memories and changes in their emotions that are occurring. And that going inward by staying in the I mask, at least for the majority of the time, that seems to be a very, if not the critical feature of making the suicide band journey effective in the therapeutic sense. Now once again, I want to cute to some of the safety precautions here, going to say this at least three times throughout today's episode.

I'm talking now in very other times throughout today's episode, you may get the impression that i'm all for everybody doing solicit van, and that is simply not the case in order for a silicas ve an journey to be therapeutic ticals useful IT does require certain conditions and supports. And there are certain people for which solicitous news is going to be contractor ated, meaning they should not do solicit an in particular people who have existing or have a previous position to psychotic episodes or bipolar episodes. Even having a first relative who has bipolar or schizophrenic or schizophrenia issues can be a rule out condition, that is, can get someone eliminated from a clinical study on Sullivan for fear of trigger ing psychotic episodes, not just during the solicited and journey, but potentially in a long standing way.

So again, that's really critical. The other thing is that everything i'm talking about today, unless I say otherwise, is really focused on adult, meaning people who are twenty five years old or older, that is, they are basic wiring. And rewiring of the brain that we call developmental neuroplasticity is completed, right?

Most of the studies today that i'll talk about involve subjects ranging from twenty five years of age out to about seventy years of age, but no one Younger. So again, Sullivan and its use is certainly not for everybody, is still illegal. It's being used in the clinical setting and research setting, though these pockets of decriminalized areas and potentially suing legalization of silvan.

But again, only in the proper clinical setting. Again, again, I say that not just to protect myself, but I say that also to protect all of you. So as an is a powerful, powerful drug, not just to be under the influence of, but also in terms of its long standing changes after the effects of suicide and have worn out, i'd like to take a quick break and acknowledge one of our sponsors, athletic Greens.

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Health, our god is very important, is populated by got microbiome that communicate with the brain, the immune system and basically all the biological systems of our body to strongly impact our immediate and long term health. And those probiotics and athletic Greens are optimal and vital for microbiology alth. In addition, athletic Greens contains a number of adaptations in vitamins and minerals that make sure that all of my foundational nutritional needs are met and IT tastes great.

If you'd like to try athletic Greens, you can go to athletic Greens dot com slash huberman and theyll give you five free travel packs that make IT really easy to mix up athletic Greens while you're on the road, in the car, on the plane, at sea and they'll you a year supply of vitamin d 3k two again， that's a letter Greenstock comes slash huberman to get the five free travel packs and the year supply of vitamin d 3k two。 Talk a little bit about dosing of Sullivan and also about microdot ing of Sullivan. Now this is an area that I won't say is controversial, but that there's how do should we say this? There's a lot of loose thinking around this in the non clinical, non research communities.

But within the clinical research communities, there is a lot of data that's come out indicating what effective and safe doses provided. All other things are considered safe. Safe doses of Sullivan actually are.

And here we really can go back to our discussion of Sullivan as coton quote, magic mushrooms or mushrooms. And if one we're to translate from the mushroom form of slice ivan to the solver ban, that's actually used in various studies because Frankly, in these studies, people aren't eating mushrooms. They're typically taking synthetic, solicited an either introduce eos ly injected into a vain or orally.

And that's how the researchers are able to tightly control the amount of suicide. And and the typical dosage that used in clinical studies ranges from one milligram, often given IT repeatedly from day today over long periods of time, so called microdot. And really that one milligrams per day or even up to three milligrams per day repeatedly over time, is what people generally think of as microdot as compared to, say, a ten milligram dose given once, maybe twice in two separate sessions, or a twenty five to thirty milligram dosage that's given once or twice.

Now, those amounts of one to three milligrams or ten milligrams or twenty five to thirty milligrams might not mean much to those of you that don't think about these things in the research terms. Perhaps you've heard of micro dosing and you ve also heard of macro or heroic doing. Okay, that sort of common or or I was just a popular Normal creature for psychology, and i'll circle back to that in a few minutes.

But I think one of the questions that I hear a lot is how much Sullivan is present in a given amount of mushrooms. And so the way this typically works is that mushrooms are often discussed in terms of grams or answers. So in eighth of mushrooms, in first to an eighth of an ounce of mushrooms, or X, A number of grams of mushrooms, the breakdown is actually quite simple.

One thousand milligrams equals one gram and the concentration of suicide an in most so called magic mushrooms is about one percent. So one gram of mushrooms being one thousand milligrams means that IT contains approximate. And again, it's approximately ten milligrams of Sullivan.

And in most of the clinical studies, it's been shown that the dosage of twenty five to thirty milgram given, or I should like taken once or twice. We'll talk about the spacing of session a little bit later. Taken once or twice is what's leading to the most pronounced diabetic outcomes.

But of course, with enhanced their reputed outcomes, one also observes enhanced side effect profiles where what are called adverse events. So there's an important nuances conversation that has to take place. But right now we're talking about the conversion of grams of mushrooms to solve bit.

So one gram of mushrooms being one thousand milgram containing one percent slice van means that IT contains ten milligrams of solicited and now the so called heroic doses that you've heard about. And this is something that discussed. More with that, let's call the traditional or classic psychology. These are people that may have an advance degree but typically are not running laboratories expLoring the effects of slyvia and controlled clinical trials. These are people who um have been long time explores and often writers and people who have been spokespeople for slicer ban and other psychic delicate s and they will often refer to the so called heroic doses.

It's a little bit hard to translate from that informal community to the scientific data, but in discussing that topic with various researchers who run laboratories at major universities focused on psychiatric therapies, what I was told is that the coding heroic dose that often discuss really refers to a five gram or so dose of mushrooms. So what that translates to is fifty milligrams of solicited on. So when you hear someone talk about a and heroic dose, they're probably referring to injustice of fifty milligrams or so of slyvia, but in its mushroom forms, so about five grams of mushrooms.

And again, it's important to point out that the concentration of slicer ban in different strains of mushrooms and in different batches, depending on the age of those mushrooms and how they've been stored at at a, can vary tremendous ly from batch to batch. In fact, there are some laboratories that have explored the range of Sullivan concentration in different mushrooms strains and different so called magic mushrooms. And that range is pretty broad.

It's anywhere from a half percent all the way up to two percent. What that means is that someone might get a hold of one gram of mushrooms, thinking that they're taking ten milligrams of Sullivan in those mushrooms when in fact they're actually taking or somebody could take three grams of mushrooms thinking they're taking thirty grams of Sullivan and in fact, they're only taking ten or fifteen militants of suicide. So the sourcing is really key, obviously, as things become more legal and more regulated and more used in the thai uc setting or and this is what's happening more and more or as people start to rely on synthetically made slyvia as opposed to using mushrooms to enjoy solicitation, then certainly, the doc ging is going to be more consistent from batch to batch because we're talking about beaches of mushrooms.

Were talking about batches of Sullivan itself. So now i'd like to take a step back from all this chemistry and cell biology and talk a little bit about the structure of a silicide journey itself and relate that to what we now know about what's happening in the brain during the solver de in journey. And then a little bit later, we will return to that salata in two a receptor when we talk about some of the more lasting changes in brain chemistry, in brain wiring that occur after the Sullivan journey is over.

So let's take a couple of minutes and just discuss the various components of an effective therapeutic sol siven journey. And here i'm not detAiling a menu of things that people should do in order to pretend that they are a slice bean assisted therapy coach or uh to do self administered solicit an therapy that is not what i'm doing. What I trying to do is to share with you the consistent components that are present in the clinical trials that i've demonstrated, the effectiveness of Sullivan for the treatment of depression and for other compulsive and addictive disorders and those data, meaning the specific data related to those trials and the references themselves, will get into a little bit later.

But we can't really have a conversation about Sullivan and what IT does without talking about the so called set and setting, as is often referred to, that is known to at least biased the probability of the journey being beneficial and not a so called bad trip. So what are the variables that make up an effective and safe Sullivan journey? And again, when we say safe, we are referring to people who are not point to psychotic episodes.

They don't even have a first relative that's prone to psychotic episodes talking about people that are twenty five years or older. We're talking about people that, for instance, are not taking inside the presence that impact the serotonin system. This is very important. understand?

I think a lot of people don't know this, but as far as I know, all of the studies that have explored solver ban for its ability to positively impact brain chemistry and mood and function have required that people either not beyond or abstain from entire depressions in the weeks leading up to the solicitation. An journey. Now that is not to say that if you are currently taking us S R ize or something similar, that you should cease ze taking them and do solde.

And I am absolutely not saying that they be very, very, very dangerous, if not catastrophic, anytime we're gonna take anything or stop taking anything for that matter. You do need to consult with your physician as guess the syria rist as well. So let's talk about suicide and journeys from the subjective side and from the structural side.

And when I say the structural side, what I mean is, what is a psychiatric journey actually include? And here the words set and setting become extremely important. Some of you may have heard that set and setting are the foundation of a well done or even theraputics beneficial psychedelic journey.

And all of that really hinges on safety and outcomes. So set refers to mindset, the mindset of the person taking the psychiatric. And setting refers to as the names, just the setting in which they're taking IT in and the people that are present there.

So let's talk about setting first. The setting for psychiatric journey needs to be one in which the person under the influence of the suicide and other psychiatric is safe. That means no windows they can jump out of.

That means no streets of moving cars they can run out into. That means no opportunity ity for getting lost. That means no opportunity for getting into bodies of water.

In other words, this requires that there will be at least one, and perhaps even two or more other individuals who are not also taking psychic delicate s right, who are not also taking psychic delicate present in that setting to ensure that the person taking the solicited and is not going to harm themselves or others. I say this not this sounds like a school teacher, even though technically i'm a school teacher, but because of course, I don't want anyone to get harmed. And i'm also aware that there's a lot of interest nowaday in psychodeviant s such a Sullivan becoming legal or decriminalized for their therapeutic applications.

And if we look back to the late one thousand nine hundred and sixties and early one thousand nine hundred and seventies, when the control substances is act was invoked to make psychedelic like suicide an illegal, one of the basis for that was not just the geopolitical unrest at the time and things like the viet now more, but also some highlighted instances in which people did not take set and setting into consideration. Took things like eladio, stared at the sun, went blind, or took slicer ben, went out and harmed somebody else. Again, these are very, very isolated instances, but these are the exact sort of instances that lead to criminalization, or the fact that things like L I an, L D and M D M A, for that matter, are considered illegal.

Again, I completely acknowledge that there are a number of different factors making them me illegal. We can have a whole discussion about that, and we talk about the drug trade, the war on drugs, but right now is such a critical time in the history and the use psychiatrically for therapeutic and other reasons, and getting setting correct meaning, making IT absolutely as safe as possible for the person taking the psychology is absolutely key. And one of the best ways to ensure that is safe is to have responsible individuals who are not under the influence of psychiatrically present in that environment.

So that's one component of setting. The other component of setting that we talk about earlier, which turns out to be very important, is the opportunity and perhaps even the bias toward the person on the psychiatric being seated or ideally lying down and being in the eyes mask, or at least having their eyes covered, so that they can combine any spontaneous visual illustrations that occur with the vary thought processes that are occurring well under the influence of psychiatric. This is far and away different.

Then, quote, quote, taking mushrooms and going into the woods are taking mushrooms and going to the beach. What we're talking about today is the use of psychedelics for particular brain rewiring outcomes that, yes, can involve things like changing one's relationship to nature. We're changing one's relationship to somebody else by interacting with nature or somebody else.

And while i'm not trying to diminish the potential value of those sorts of psychiatric journeys, if we look at the scientific data, the vast majority of IT, not just in the clinical setting, but in terms of understanding the safety and efficacy and positive rewiring of brain circuitry that allows people to feel Better, to understand themselves Better and to interact with life in more adaptive ways going forward. Out of the psychology, turney involve these very, what's say, you know, subdued settings that are typically in one room, a closed environment, with one or two other individuals acting a sort of guides or helping the individual by talking to them from time to time. If they feel like they have to sort through a particular aspect of the psychology journey that's creating anxiety.

We will talk about the control of the psychiatric journey that almost everyone who take Sullivan at somewhere between twenty and thirty gram dosages tends to experience. But the setting that i'm describing is not just a list of things to, you know, make sure you're safe, but they're really the list of things that also ensure that one can get the maximum benefit out of the silicide and journey. Now, other things included in setting that are known, again, from scientific literature, to be very influential in terms of the experience that one has and to buy things towards positive are against safety.

I mask, but also the presence of music. Now, when I first heard about this from one of the premier researchers on slice ban and other psychic oxes, which is Robin cdr Harris, a professor at university of california center from cisco, who's one of the major pioneers in the studies of psychiatric. And when he first start telling me about the critical role that music plays, I thought, okay, that makes sense.

You know music can impact our emotion, impact um the way that we think and could therefore impact of what one experiences during the psychiatric journey. But he really underscored for me the extent to which music is not just a um sort of incidental feature of the setting in psychiatric set in setting, but that IT is one of the but that IT is one of the major drivers of the actual cognitive and emotional experience that somebody has on something like suicide. And that allows the Sullivan journey to be looked at or viewed, not just as beneficial, al, but and this is quoted in the scientific literature as one of the most profound and important positive experiences that one ever experienced in their life.

So let's talk about the sorts of music that have been used in these clinical studies. First of all, we need to think about how long the suicide an journey itself is going to be. And the typical duration of the Sullivan journey is anywhere from four to six hours.

It's going to to depend somewhat on dose. It's going to to depend somewhat on variability in people's liver metabolism, and it's also going to depend somewhat on how much food people have in their gut. In all the clinical studies that I read, IT was advised that people not have any food in their gut at the time at which they ingest or injected with a solicited on.

It's particularly true if people are going to be taking suicide in mushrooms in order to get their slice van. And that has been done in a few studies. Most studies, however, used synthetic, solicited and taken orally.

Again, that's converted to silicon in the gut by the city of the gut. And the a city of the gut is going to be impacted by the various foods that people eat. And so that's one of the major reasons why people are advised do not eat for at least four hours prior to the suicide, an journey.

So here we've got this six hour, what we're calling journey, because that's what everyone calls IT or trip, that people start experiencing about thirty to forty five minutes after ingesting Sullivan or taking sales von. There's a peak component in which there's a maximum intensity of emotion and often it's also associated with anxiety. And this is very important.

Understand the anxiety component is part of what in the theraputics citing they refer to as ego dissolution and that anxiety around the peak. And I think most people would probably hear peak experience and think, oh, we're talking about a peak positive experience. But no, we are referring to a peak experience in anxiety that people stay with and then come down from gradually, as one goes from the second or third hour after taking suicide.

And and that tapers off slowly toward the six hour mark. What sometimes people referred to as para shooting back in, of course um they're not hopefully I would very much hope people aren't actually para shooting back in well on sillas open. But I think you you get the idea the music that typically played in the clinical studies using solymi for the treatment of depression or for compulsive disorders or addiction, tens of a particular on tour that matches with and can also drive that can tour of the silica journey that I just described.

Again, we're talking about people wearing, and I mask with, guides present, so people who are not taking so on there as well to ensure that the person feels supported and is safe. The person is typically lying down, sometimes sitting down, but more often not lying down, wearing and I am ask and the music that's played at the beginning of the suicide de and session tends to be music that doesn't have a lot of vocalizations. IT tends to be things like classical music.

IT tends to be fairly low volume, but that then transitions into music that has a lot of percussion, so often drums, that tends to be higher volume. That has a lot of intensity at about the time that one would be experiencing the peak in emotion and in perception. This is called peak of the journey.

That intense music tends to be played for about forty five minutes to ninety minutes, depending on the study one looks at, and then tends to transition into softer music again, sometimes coral type Melody music, often female voices in particular, and then transition into nature sounds and things, the more less mimic the outside natural world and less so um synthetic things like drums or instruments and vocalizations and things of that sort. So why would I be so important that music match and even contribute to the subjective experience that people have on psychiatry? Xs, here we should probably take a couple of moments and just talk about what those subjective experiences are like.

So for people that haven't done, solicited in or any psychodeviant s, it's a little hard to describe. But one way to describe IT is that there's a lot of so called perceptual blending. So for instance, people in the I mask will report seeing some geometric shapes and colors, but perhaps the music their listening to will then start to change the intensity or the movement of whatever is that they're seeing, fluctuating inside of the I mask in ways that are linked. This is referred to a sydney sia, or the merging of different senses that are not ordinarily merged. In addition, people under the influence of Sullivan or other psychic licence for that matter, often will report that their pattern of breathing becomes linked to the perceptions of things that they are hearing or seeing or feeling.

So for instance, if they take a big, deep breath in and then a long x hail out, they may find that during the long x hell out, that the notes of music that they're hearing in those moments are also drawn out for the duration of the breath they'll in hill, and that they're getting at least what they perceive as control over the music, which of course, they are not actually controlling by using their breath, and that perhaps their visual perceptions are also being merged with that. So those are just a couple of examples of how perceptual blending a synthesia can occur while under the influence of Sullivan. And this really is highly individual from one person to the next.

Some people, for instance, will find that if they take their fingertips and rub them across the couch or the chair that they happen to be lying down or sitting on, that they will experience a change in the music um maybe even if they you know they move their hand up, they hear an increase in frequency of sound. They move their hand down the here decrease and frequency of sound and that all of this is linked to their emotional state at the same time and vice versa. We're talking about a lot of perceptual and emotional blending and some sense of control over one's perceptions and emotions in a way that's very an ordinary, even extraordinary.

We can step back from all of this very subjective description of psychiatric journey and ask what is going on that would allow these sorts of things to occur. And there you are already equipped with an understanding of the cell biology in the chemistry that makes all of this possible. And that is that when slice van is ingest ted and then converted to silicon, that the silicon that crosses the blood brain barrier.

And even though silicon looks a lot like serotonin, silicon has this incredible ability to predominantly activate the serotonin to a receptor. Well, we can understand much of what's happening at a subjective level during the psychiatric journey, even right down to the sort of emotions and perceptual blending this synthesia. We can understand a lot of that by understanding where the serotonin a receptors are expressed on neons and what those particular neurons are doing.

And the simplest way describe this is that there's a category of neurons that we call param minal neurons. Criminal neurons are found lots of places in the brain, but they called criminal neons, because are shape like a pym's. They have a cell body, which is the part of the cell that has the DNA in IT.

A lot of other important, the things like the organisms might a country at eta, and then they also have what are called dendrites dendrites. So the little branches or processes that reach out both from the bottom of these cells and then these criminal cells are interesting, because they also grow a branch up, up, up, up into layers of neural tissue above them, and they have to call an appeal branch. That's the part that grows up.

And then they fan out at the top, and that handing out at the top of allows them to communicate with other neurons in their environment. okay. So if you're not getting a good picture of this in your mind, for my description, I apologize, but simply think about putting your arms out to the side.

And by doing that, you are able to interact with things that are some distance from your body of an obvious thing. In that case, these cells are effectively doing the same thing by extending little processes out into layers above them, into the sides. And this is really important, because much of the seaton into a receptors that are present on neurons in the brain are present in those epical dendrites, those branches of these criminal neurons that are above and that extend out to the side of those neurons.

And so when somebody is under the influence of Sullivan, that means that cycle in has bound to the receptors on those epical dendrites and its increasing lateral communication across brain areas. In fact, this is perhaps one of the most well documented effects of slice ban and other psychodeviant s, which is that there is a shift from the brain being more modular, meaning more segmented. Like auditory neurons are communicating electrically in chemically, largely with other auditory neurons.

Of course, we'll communicate with other types of neurons too, right? When I hear something off to my right, like a snap of fingers off right, i'll turn my head. And my ability to do that depends on my auditory neurons being linked up with things like my motor's system in my visual system.

But the key thing understand is that when they're a slicin present in one system, that the communication of any of these parameter neurons, the ones involved in hearing, the ones involved in thinking, the ones involved in memory, the ones involved in visual perception, or in the generation of visual fluctuation with eyes closed, those are all talking to many, many more other neurons more extensively. So what happens effectively is that there is a reduction in the modulator, the separate ness of function in the brain, and an increase in what's called integration of communication across what would otherwise be desperate brain regions. We can say that really simply by saying suicide, and increases communication across the brain.

Now, in addition to that, there's a reduction in what's called the hierarchical organization of the brain. Typically, sensor information comes in from the outside environment. So we hear something, we see something, we takes something, we smell something.

And in what's called the bottom up fashion, mean bottom from the periphery up, meaning IT propagate up through the eyes, through the nose, through the ears, through the skin, where the senses in those regions, I should say, up into areas of the brain that sit deep to the cortex, like the film is, and then the film as is, sort of a way station, like a switchboard that sends visual stuff to the visual centers, in auditory stuff to the auditory centers, in touch stuff to the touch centers, and things that I may be triggered memory after the memory centers of the brain seta. That's the typical organization. It's high article, because IT goes from the periphery up to the more complex processing regions of the brain that make decisions, that linker of that stuff to prior experience, maybe plans about the future.

When saliva is present in the system, there is a broader of the flow of that information from the bottom up as well. OK, that has to do with what's called flaming gating. The salome's is a very interesting structure. We probably don't want to go to IT too much detail right now.

But IT really is like a switchboard in a way station saying, hey, pay tension to the visual stuff, pay tension to the auditory stuff, or just to the visual and tory stuff, and ignore, you know, touch sensation for the time being. We revise versa until the ion is present in the system and when settle into a receptors are activated very strongly. There is a tremendous broader of the flow of information up and through the Thomas.

So not only is there more communication of so called higher order brain centers, we refer to them as higher because they involved in thinking and decision making an emotion at sea. But there's also a shift in the flow of sensory information into the brain that can generally be described as a broader and including more blending of the different senses. And when I say blending of the senses, i'm also referring to blending of the sense of interaction, tion of our sense of our body and what's happening inside of our body.

And this, without question, at least partially explains why went under the influence of Sullivan, one's breathing can be linked to a sound, and then suddenly the sound, one thinks is being controlled by one's breathing, or that the sound itself can be linked to something that we see in our minds eye. Well, in the I ask, essentially what i'm describing here is that serotonin, a receptor activation, allows for more road, less precise and less hierarchical activation of brain circuitry. And when I say hierarchical, what I mean is that Normally things go from per iffy, from ice to famous, to visual cortex.

However, when under the influence of Sullivan I mentioned before, even in the eye ask, the visual cortex is going to be very activated, even in the absence of any visual input. So then if one hears a sound perhaps from music, a particular motive for voice, and that's linked to a particular emotional state that is now being blended with visual phenomenon occurring within the brain that have no external stimulus. And so while the patterns of activation in the brain well under the influence of Sullivan aren't random, they are far less channel, far less modular and far less hierarchical than would ever be the case when not under the influence of suicide.

Now, in all fairness to the scientific literature, there are not one, not two, not three, but four prominent theories of which brain networks are most activated during a silicide in a other psychiatric journey. And so for those of you, they are interested in those different models. First of all, please know that they are not competing models.

While some of them disagree about some of the details, is very likely that all of these models are true. They include things like changes in the so called default mode network. There's a lot of interest in this.

I've talked about that before on this podcast, the default de network, because the network in the brain that thought to be responsible for spontaneous imagination, for daydreaming, and that reflects all of the base activation state of the brain when there is no drugs in our system. And the default mode network is one of the systems or networks, rather, that is thought to be required under conditions of Sullivan or other psychodeviant s. Again, if you're interested in these models and comparing and contrasting them, there's a very nice review from brian ross.

Slab at duke entitled the neural basis of the delic action will provide a link to this in the shown out captions. And again, I just won emphasize that all of these models have been shown to be true in different studies, and what they all point to is more extensive communication between areas of the brain that Normally are not as active at the same time. While under the influence of psychedelics, such a silicic van, the controversy the field relates to which of these networks is the one that changes the most to explain the therapeutic outcomes that have been discovered in recent years.

So again, check out the review. You're interested in that sort of thing. In the meantime, we can cut a broad swap through all of those models and just say that silicon on expands the functional connectivity of the brain, while one is under the influence of sicilian on. And IT does seem that some of that expanded functional connectivity persists after the effects of silicon ibn have worn off.

And that statement about the functional connectivity of the brain being more expanded and not just during the Sullivan session but after as well, has been substantiated a number of papers, but one of the key papers in this area as one that I recommend people check out if they're interested in the sort of thing, is entitled the effects of Sullivan and md ma on between network resting state, functional connectivity and healthy volunteers. And I like this paper for a number of reasons. First of all, a very high quality paper Carried out in the laboratory of Robin carara Harris, ucsf, again, one of the premier researchers in this area of psychoanalytic s and their function, what they do in the brain, and also their therapeutic applications.

But also because IT focus on healthy volunteers, they explored, using brain imaging, what brain areas are active in arresting state. So things like default mode network, then they had people take sillas, IBM or M D M A. And then they looked at the connectivity between those brain areas in those same individuals when they were not under the influence of these drugs, and found more extensive connectivity, all of which pointed to an enhanced lateral connectivity, less hierarchical organization, effectively more interconnection and communication between different brain areas.

I think not only is the fact that they looked at healthy volunteers very interesting and important, but also that they looked at this resting state of the brain. They weren't providing a particular auditory visual stimulus for people to hear or look at while they were in the brain imaging scanner. It's rather they were simply looking at how the brain was behaving at rest.

And so it's very clear that for people that do two or even just one of the solstice and journeys, and in particular dose, that the brain is actually getting required. Now we hear this a lot solicited, and other psychiatrically leads to plastics. They require your brain.

Let's go back to what we said. The beginning. Rewiring ing of the brain is not the goal. Adaptive rewiring of the brain is the goal, right rewiring, that leads to new ideas that are interesting that are accessible after the psychology, new ideas and new ways of thinking or feeling that allow people to function Better in their lives. That's the goal of effective psychology therapies, not simply rewiring of the brain.

You a brain injury for that matter will lead to rewrite or the brain, but that's more adaptive rewiring. The use of things like ephedrine es or method fedex es to particular, it'll lead to rewiring of the brain. But that is strongly more adaptive rewiring.

So now there are really dozens of studies conducted in humans using brain imaging and other techniques have evaluated how things like suicide ve and change connectivity in the brain. And I think the takeoff messages IT expands that connectivity. However, IT seems to do so in ways that still allow people to function in their daily lives.

And one of the key things that I gleaned from the literature on the thai decus of Sullivan for the treatment of depression is that very seldom do people who take solicited and experience long term issues with memory. Why is that so critical? Well, you could imagine that increasing connectivity in the brain, reducing modularity, reducing high arracan organization in the brain, would lead to disruptions in memory, right? IT says if you're shufu books on the bookshelf, so to speak.

But that doesn't seem to be the case. Rather, IT seems that the increase in connectivity is leading, provided and setting are correct. Provided safety protocols are followed to positive rewiring or adapt tive remarry of neural tissue.

So that's one of the things that makes psychedelics and suicide and in particular, very exciting from the therapeutic standpoint. And of course, we have to acknowledge it's also what has a lot of people excited about psychedelics, not just for the treatment of depression, but for expanding the brain capabilities more generally. So long those lines I want to touch on, the issues of creativity and the experience of life outside of psychiatry.

Journey is impacted by psychiatric journeys. And here this relates to a question that I heard a lot when I put the call out on social media, that I was going to do this episode. And I ask people, what do you want know about social? And one of the more common questions that I got was, does IT increase creativity? Does IT increase our experience of life in ways that are beneficial, aside from it's now documented positive effects in treating depression and compulsive disorders in addiction.

And the short answer to this is yes, but that the positive effects of psychiatric, so i've been in particular on creativity and our experience of life have only been explored in a fairly narrow set of dimensions. However, where it's been explorer, there's some really interesting findings. So one of the more interesting findings, I think, is the paper entitled increased low frequency brain responses to music after suicide and therapy for depression. I think this is a really interesting paper, because what the authors did is they took advantage of the fact that in these theraputics licious sessions, they were Carried out for the treatment of depression.

Music is being played and there are prior studies showing that when music is played you activate different brain area depending on what sort of music is being played that somewhat obvious perhaps you know sad music versus intense um you can think about heavy metal versus um quire music versus regression and chance versus punk rock music and on and on IT makes sense that different brain areas would be activated when different patterns of music are played however, they do seem to be some universal features of brain activation in response to music this should probably be the topic of an entire episode of the human man out podcast. And I need IT will be, for instance, there are areas of the auditory cortex that are activated, no surprise there. And areas of the brain's reward circuitry, the so called ventures striatum and the so called me olympic reward pathway, talked a lot about these in the episodes about dopamine that i've done previously.

These are brain areas that lead to the release of dopamine in other brain areas and that reinforce certain experiences and that tend to give us the subjective feeling of, yes, I like this. I want more so in this particular paper. What the authors did is they took a advances of the fact that people learn the clinic.

They are on solygia. They're listening to music. And as you recall, the music played at different stages of the suicide journey are different. They have a different emotional component.

And music is a really nice stimulus in the laboratories, we say, because like with visual stimulus, you can break them down into high frequency, low frequency, right? Sounds like doing or these kinds of things. That was my attempt at low frequency versus high frequency.

Auditory stimulate or at the space al frequency, or what in the auditory domain would be called the temporal frequency. Is that or is that all will change their is the temporal frequency. The sound was somewhat the same, but the distance between those sounds was different.

You get the idea, so they have access to these people and these different conditions, and they can put them in the brain scanner, and they can do that before and after having taken. And the long short of this study is that suicide ban changes one's experience of music, not just during the sicilian journey itself, but thereafter. And in fact, IT changes ones emotional response to music in very interesting ways.

For instance, one of the more common features of major depression is that people don't derive as much pleasure from different types of experiences, whether not its food or sex or social experiences, to the point where sometimes they just stop trying to seek out those experiences. People with depression often feels if music no longer has the same impact, IT just doesn't really lift them up very much. This study found that people who have taken silica van cording to the prams we talked about earlier can get a return of the elevated emotionality, the positive emotions associated with music that formally, they them feel good.

In other words, they can feel music again. They can feel good in response to music again. Now this is interesting because in theory, IT could be that sliced and simply allowed them to access the emotions around music, again, more generally, but that's actually not what this paper and some other papers that have been published report. Rather, IT seems that taking suicide ban can increase one's positive perception of music that won likes, and can tone down or reduce the depression veness or the sadness of music that tends to make one sad even after the cell sivan has worn off and for a long period of time afterwards, maybe even forever, although no study, of course, can be Carried out forever, because forever is forever.

What we do know, however, is that slyvia can rewire the connections between the emotion centers in the brain and the networks that control auditory perception of music, and leads to this condition in which people who felt like I was depressed so I couldn't feel the music, I just wasn't game, the same lift and joy from IT again, they can start to experience more joy from that music again. And the music that made them feel sad and depressed has a diminished capacity to make them feel sad and depressed. And there's a lot of neural imaging data in this paper that point to the specific brain areas that include areas like the venture al tegmental area that can explain why these sorts of effects will occur.

So this isn't just objective reports of people saying, oh yeah, you know, I was depressed, him and music didn't feel really good, now feels great, or that used to make me feel so sad. And now I feel like I have a capacity to listen to that without being crushed by feelings of sadness. The paper included some subjective reports of that sort, but then was able to link those to changes in brain circuitry and brain activation in response to music using newer imaging.

So in that way, IT really points to both the subjective and structural and functional changes that slicer ving can bring about through that expanded connectivity between brain years. Because remember, during the Sullivan session, it's not as if music or the perception of music is specifically being looked dead or focused on in these studies. Rather, music is playing.

People are in the air mass. They're feeling all sorts of things. They are breathing, they're hearing, they're touches, all happening all at once. There's a peak, it's long, there's a long taper, the music changing. Okay, all of that took place in this study as well.

But IT is after the session, when comparing brain activation states to music of a particular types, sad or happy, and comparing that to the patterns of brain activation, that I could be the solicited and journey that they discovered that people's brains have required during the suicide and session in a way that allows them to experience joy in response to music again. So that's one of the more rigorous studies I was able to find that addresses this question of whether or not silicide and really does rewire the brain in ways that allows us to be more creative and experiences life differently after the Sullivan session. Now that paper didn't specifically on creativity.

I didn't entire episode on creativity to talk about different types of meditation, like open monitoring meditation, to talk about different patterns of thinking that one can actually practice to increase creativity. We had arguably one of the most creative people on the planet, rick rubin, came on this podcast talk about the creative process from the perspective of music and his role in producing music. So you can check out those episodes if you're interested in the neural circuitry related to creativity, at least at the time of recording this episode.

There haven't been a lot of studies looking specifically at the brain networks that we think are involved in creativity and how those change in response to silicic van and other psychiatrically. Imagine those studies are either happening now or will happen in the future. But the states I just described referred to the changes and emotionality and responses to music, I think, provide a nice template for what's likely happening both during silicide ban journey, after those solicited and journeys.

When we talk about less hierarchical organization, more connectivity between brain, really what is pointing to is the fact that during the solicited and journey, people have the opportunity to learn new relationships between different sensory and emotional states, and those new relationships seem to persist long after the psychiatric journey has been finished. And a lot of people researching silicic ban in the clinical setting think that that's one of the major reasons why silicon on and other psychiatrically can require our relationship to things more broadly. IT allows for new learning, new contingencies.

And when we look at depression, we often think, you know, diminish mood. People have an appetite. They are interested in social relationships, are romantic. Relationships are really struggling. And all of that, of course, is true.

But another lens to look at depression through is that a lot of that thinking, and a lot of those emotional states that are negative are somewhat habitual. They relate to a sort of implicit understanding and living out of the idea that a leads to b leads to see, okay, you seek out a relationship. IT doesn't work out.

Try a new job. You don't get the job. You get the job. It's no good. All these negative outcomes of, if a, then b, then c and IT does seem that Sullivan can have this effect of invoking new patterns of learning, new considerations about what might be possible, and indeed may lead to actual rewiring of the emotion centers in the brain with these other brain areas.

And vice vera in ways that eject people from the Sullivan session thinking, oh, you know, yeah, used to feel this way about something, work relationships myself, at such a but i'm willing to consider this other possibility, or this other possibility seems at least partially true to the extent that i'm willing to go out and evaluate that. Now here I am speaking very subjectively. But remember, we have to tie back the subjective experiences and changes of things like music and emotion in our relationship to life and jobs and relationships back to the cl biology and chemistry of suicide.

And because ultimately, IT really is just a chemical activating receptors. Those receptors ors changing networks in the brain. And the journey itself seems to be the time when all of those changes are put in motion.

It's like a bolder that gets rolling. In fact, I think the best way to think about suicide and other psychic alics is that they initiate the neuroplasticity process, but they are not the neuroplasticity process itself. And the journey itself is not where all the neuroplasticity occurs. We know that for sure. In fact, if you want to imagine how solicited an and other psychiatric s work to change the brain, think about them as a wedge that gets underneath the border, that is, the neuroplasticity that gets rolling forward.

And then think about whether not the plasticity is adapt of a man adaptive, whether not IT actually serves you in your life on a daily basis or not, depending on whether not you're using your conscious brain to move that bolder in a particular direction, right? Not just bulldoze through things and destroying them, but clearing a path through old and effective, maybe even destructive, patterns of thoughts or emotions. That said, I give you that analogy.

Gy, because I get more accurately captures what psych licks like suicide van are doing, rather than the typical discussion around psychology that we tend to hear, which is that, oh, IT creates plasticity and plastics. Ity is what you want. For the next couple of minutes, i'd like to focus on some of the key and stereotypes, that is, characteristic experiences that people tend to have during a suicide and journey, because there are some really interesting research on this.

These are phrases that perhaps you've heard before, things like letting go, ego dissolution, feelings of connectiveness. Well, all of that is very subjective. On the one hand, those words are heard often enough and repeatedly enough in suicide sessions and after suicide and sessions, along with this description of the solicit, an experience as one of the most profound of one's life, or one of the most positive in the ideal case of one's life, that they are worth expLoring.

We should also, of course, explore the so called a bad trip, the possibility that someone will have a not good time, or even very frightening time, while under the influence of Sullivan. So there have been some scientific studies that have explored what sorts of subjective experiences, that is, thoughts and feelings, insights that people have, that relate to positive theraputics comes, and more generally, with the sense that the silicide and journey was positive, or maybe even tremendously positive in one's life. So while there's a century more of writing about psychedelics, s that described things like enhancement, illness of connectivity or dissolution of the ego, the loss of one sense of self and then the regaining of one sense of self and so on.

There is a particular paper that describes some of those things in terms of rating scales, that is, the sort of tests that people can take in which they answer particular questions, and that link back to things like feelings of connectiveness and ego dissolution. That allows us to put some numbers to those experiences and to look at some of the statistics associated with those experiences. And this is really what's important about scientific studies, whether not a measure of subjective of someone self reporting how they felt or feel, or whether not at measure of blood pressure or of a chemical in the bloodstream, and said a is the use of numbers and statistics that allows comparison between different groups and that can be compared between studies that allows us to make some firm conclusions about what sorts of things slicer and may or may not be doing when it's effective or not.

So the paper i'd like the highlight is entitled quality of acute psychiatric experience predicts theraputics 自 acy of solicited on for treatment resistant depression。 I'll put a link to this paper in the showed captions, but the basic counter this paper is that they looked at subjects that underwent two different Sullivan sessions, one at a relatively low ish dose of ten milligrams of saliva, and that would be equivalent to about one gram of psychiatric mushrooms, more or less, and a second session involving subjects taking twenty five milligrams of soliciting, or what's roughly equivalent to somebody taking two and a half grams of suicide and mushrooms. Those people then answered what's called the altered states of consciousness questionnaire, which allow them to address in here and paraphrase in the quality of experiences in the twenty five milligram Sullivan session.

So without going to too much detail is often the case in these sorts of two session studies that subjects will take a slightly lower dose of Sullivan to familiarize ze themselves with the experience, and then the higher dose that leads to the more intensive experience, intense, meaning a bigger, more intense peak, a longer session, overall, greater distortions in emotionality and perceptual experience, all the stuff we talked about before. So what the study found is that one of the key features, if not the key feature of a positive, quote, quote, psychedelic experience, is the sense of oceanic boundlessness occurring at some point during the psychiatric journey. Now, oceanic boundlessness doesn't necessarily mean anything to any of us IT.

Probably many different things to different people. What's this idea that one is experiencing something extremely unusual, even mystical, and a beyond this world and one's Normal experience, but that is not aligned with any specific outcome in the moment. It's not directly attached to anyone feeling or memory of thought processes. This IT means a little bit tough to describe because I can guarantee i'm not unsolved in any psychiatric right now and I can only imagine um that you're not a little some of you might be I can even imagine what this podcast would um be like for somebody on soul seven at this moment but in any case, oceanic barley ness, a feeling of the experience being mystical and not really heading in any one particular direction.

Just a feeling of massive connectiveness with one's environment, both in the room and session, perhaps with the guides with oneself, with one's s past, with ones present, people outside the room, with the entire world, maybe in the universe, that sort of thing, the intensity of that experience of oceanic boundlessness, the mystic experience, seems to be positively correlated with positive therapeutic outcomes, that is, relief from major depression. Now during the psychedelic c journey, as we talked about before, there are number of steps that one typically goes through. So there's the build up to first experiencing the effects of the drug about maybe twenty to forty five minutes into the journey or trip.

Then the peak and IT is during that peak that people often feel the sense of oceanic boundlessness. However, it's also often in the case that IT is during the peak with a maximum intensity of emotion, and we know based on direct measurements, also increases in blood pressure and heart rate, often very significant increases in the xiety and fear as well, that people will experience things like ego dissolution. And the guidance role at that point is, of course, to keep the person safe, make sure they don't run out the room, jump out of the window, run into traffic sadd.

These are things that have happened outside of a strong, healthy, safe set and setting. But the guidman's role is to keep the person safe, but also to encourage them to let go and move through that experience, to experience things. I allow IT to peak, allow them to see that they're not going to die from that anxiety.

They're not going to dissolve. They won't lose their sense of self completely, or they make temporarily feels if they lose their sense of self, but then they feel IT restored at various intervals during the peak, or as they exit that peak and move toward the, say, second, third, fourth, five hour of the session. So when exactly these feelings of oceanic boundlessness and ego dissolution occur varies from person to person, but typically it's during the peak that the ego dissolution, the fear and the need to let go is most typical.

I think perhaps the best way to describe the data in this paper in way that's meaningful to everybody is to refer you to figure to which, if you're not looking at the paper won't mean anything to you. But i'll describe IT. And if you do want to take a look at figure to you again, you can access the paper in the shoote captions. What they did is they looked at a number of different subjective measures, things like experience of unity, the feeling that one is connected to others into the world.

Things like spirituality, whether not the whole thing felt like a spiritual experience, whether not he was a blissful state, where are not there were insights, whether not somebody felt diamonded out of body, whether not somebody had a lot of anxiety, whether or not they had these sydney sisia, these blending of visual, auditory, touch and breathing and things of that sort, and they dress which of those measures related to the positive clinical outcomes that were observe later after the Sullivan war off? And well, i'm not going to go point by point to reach one of these measures. There's a general feature to emerge from the study, which is that the experience of unity, the sense that the suicide, an journey was spiritual in experience of bliss at some point inside of the soldier, an journey, the sense that they were insights that they were learnings about one's life and oneself when those things were experienced very strongly, that correlated with the person being what was called a responder to the solver de intriguing, meaning they got relief from their depression.

Where as people who felt less of that, okay, so the non responders, as they're called, the people who do not benefit so much in the long run from the silicide and treatment, tended to report less of an experience of unity, less of a spiritual experience, less of a blissful state, less insightfulness and so on, whether there were very few differences between the people that derive benefit from the suicide van treatment and those did not alone. The dimension of synthetic sia, this blending of different perceptions that ordinarily doesn't occur for most people, or complex imagery, right? Put simply, everyone who took solace, ivan, in the study at twenty five milligrams, saw a complex imagery.

They saw lot of fluctuations. But just seeing hallucinations did not lead to the positive clinical outcomes. In terms of mood, anxiety was a very interesting measure here, because ordinarily we think of the ego dissolution, the letting go is such a key component of the psychiatric journey in terms of the positive therapeutic outcomes. This has been discussed quite a lot.

And in full disclosure, Robin cartel Harris has already come on to record an episode of the huberman lab podcast that episode sn been released yet, but I will be released soon and he talks about the importance of this letting go in terms of the positive clinical outcomes of the Sullivan journey and indeed that is true ah and I should also mention the doctor Matthew Johnson from john hopkins ins, who also runs a laboratory expLoring psychology s and their role in treating things like eating disorders and depression. IT set, also doing incredible work, also talked about the importance of letting go during the cell eventually, this ego dissolution, this ability to move through the anxiety. And again, I can't underscore this enough because it's been told to me over and over again by the top researchers in the areas that people head into that peaking phase of the Sullivan journey.

And often times, IT is not pleasant for them. They're feeling like it's uncomfortable at scary and their heart rate is up and their blood pressure is up and they're having a hard time calm down and they want to calm down. But IT does seem that while the guides should not ramp them up and get them more stressed, but the ability to move through that stressful period somewhat guide oneself, or to be encouraged to guide oneself through that peak, and that anxiety and the fear of losing oneself and the so called ego dissolution that occurs, is an important feature for an effective therapeutic session.

In this study, anxiety itself was inversely correlated with a positive therapeutic outcome. yes. So this is important and somewhat knew us. On the one hand, i'm telling you that the letting go, the ego dissolution does seem to be important in terms of reporting a psychiatric experience as effective as having accomplish something and perhaps even explaining some of the long term possible effects to emerge from that psychiatric journey, in this case, solicitous and journey.

However, non responders, that is, people who did solve ban but did not have a positive therapeutic outcome in comparison to the responders. Those non responders tended to have higher subjective ratings of anxious. When did the responders? So this is important.

And what IT speaks to is the fact that, well, yes, letting go during the session, experiencing some of his ID, perhaps even ego dissolution, and of dissolving yourself, and then the return of self is important. IT is also important. IT seems that anxiety not be so so high or subject vely experienced as so high that one does not experience the positive neuronal rewiring that leads to a more pervasive elevated mood.

So i'm definitely saying two things at once because i'm trying to capture the data accurately. I would not be fair for me to say just let go experiences as much in his as as possible, and that's part of the process. Yes, letting go again in air quote seems to be a important for one's experience of the psychiatry journey, in particular, around the peak that occurs about two hours in or so.

However, extreme levels anx ID seem inversely correlated or negatively correlated would be the Better way to put IT with the positive theraputics outcome and relief from depression. So this takes us back to all of the things we've been talking about this far, not just the chemistry, biological action of Sullivan, but the key importance of getting dosage right, the key importance of making sure that you're in a safe environment, but also one in which the guides really know what they're doing. I think this is one of the biggest and most important reasons for having well trained guides who really understand the contour of the psychedelic journey, but are also trained in how to help somebody with their anxious in real time while they are under the effects of Sullivan.

And of course, to help people integrate those feelings of hands, maybe guide them back down to a common state during the syriac section itself. Here I can just mention some unpublish data and studies. And again, this are very preliminary, but through discussions with doctor Matthew Johnson, who is running the solicited and other sorts of psychiatric trials at john's hopkins, and I discuss the importance of having a real time tool to adJusting xiety, while under the influencing of psychiatric s like silicide.

And and there he asked, and they've started to incorporate, is my understanding, some of the real time recipe tion tools, that is, breathing tools. That we know based on work in my laboratory, doctor with speakers laboratory can reduce anxiety very quickly in real time. And that involves the use of the so called physiological sigh.

I i've talked a lot about this before in previous podcast, rather than explain IT, you again here now will put a link to the physical ological side. I do a demonstration of IT in the showroom. Te captions will also linked to a recent paper that we published and sell reports.

medicine. This was a collaborative work that my laboratory did with doctor David beagle's laboratory at stamford school of medicine, showing that the physiological size among the different deliberate aspiration techniques, one of the fastest and most effective ways to reduce levels of autonomic rows or AK, anxiety or stress. And doctor Matthew john's laboratory started to incorporate physiological size within these psychiatric sessions as a tool that the guides can refer people to before the session begins, teaching IT to them so they realized they can calm themselves down if necessary, in real time.

IT works the first time. IT works every time. This is not because it's some magic breathing technique that I created. IT certainly is not. This is a naturally occurring pattern of breathing that curves in sleep and and waking, but that, when done deliberately, leads to very rapid and quite significant decreases in stress and anxiety. And then when people are inside of the psychedelic session, if they feel their anxiety levels are going to hi, they're heading, told what might be called a one quote, bad trip, they're starting to panic, or really think they are going to have a panic attack or die again. The subjective experiences can be layer on top of the physiological experience of one's heart rate being really elevated, so stress and agitation by using the physiological side inside of a psychiatric session.

Doctor john's laboratory, and I believe at least one other laboratory are starting to use breathing techniques such as the physio gc side as a way for these people who are under the influence of suicide and to self direct their own calm and to bring that level anxious down, so that they can continue to move through the peak and move through the other phases of the psychology journey, ways that could be most beneficial for them. So to close out the description of this really wonderful study, and by the way, it's another one from the hard heart hairs laboratory about the subjective experience of ego dissolution or oceanic baldassare, this mystic state as so key as a component of a positive Sullivan journey, i'll just read, view the final sentence of this paper because IT captures IT so well. Quote, IT seems vital that appropriate consideration is paid to the importance of promoting a certain kind of experience, as the quality of that experience may be the critical determinant of their appetite success.

Now before we move into what will be a very brief description of some of the other rewiring phenomenon that solicit an can induce, and then into some of the therapeutic applications of Sullivan as they relate to these recent really exciting clinical trials for depression and addictive disorders and things of that sort, I just wanted cue everybody to a paper that I think many people will want to take a look at in thinking about slyvia. And i'll provide a link to this paper as well in the shower note captions. This paper is entitled therapist accuse of solicited and practical considerations for dosing and administration.

And this is a wonderful paper, because IT really goes step by step through the pharma logy of suivant, of which you now understand a bit, but IT goes into a bit more detail. But then they also really nicely describes the content or of a Sullivan session and what's happening at the level of chemistry, early middle peak, and told the end of the suicide and session. And then also importantly, gets into issues of dosage and translating from mushrooms to solve van itself to silicon.

I talked about earlier, but in a bit more detail, if you like to see that detail. And then perhaps most importantly, there's a section on country indications where he points out that, of course, women who are pregnant or breast feeding, people who have a pretty position to psychosis, those people should really avoid the use of Sullivan and other psychotic alics entirely. IT also talks about where the evidence is strong, moderate and weak for the use of Sullivan for treatment of various disorders.

And I can summarize that very quickly because it's where we're going ahead in a few minutes, which is that the most evidence of positive therapeutic outcomes response to slow Simon, taken and conducted in the manner that we ve been describing today in terms of dosage and journey said and setting is for cancer related depression, cancer related anxiety and treatment resistance depression. That's where most of the evidence resides. There's also some evidence for the use of sillas ivan journeys.

And again, this is typically one or two solicitation journeys space in the cases of two journeys anywhere from one to two weeks apart. And again, with all of the same control of supports and set in setting that we've been talking about today. And there, there are some evidence for improvement in terms of outcomes in alcohol use, disorder independence and tobacco addiction.

And then finally, there's the least amount of evidence, although there is class child support for relief or partial relief for obsessive compulsive disorder, cluster headaches and migrants and demoralization due to aided diagnosis. And so this paper has a lot of really interesting information in terms of different conditions, terms of dosage and again, country intimations and what's called adverse events. What sorts of bad things can and do happen as a consequence of silicon band and other types of psychology journeys, both during and after those solicited on or psychology sessions?

We'll talk a bit more about this when we go into some of those clinical studies because adversity reactions is always a key measure in any clinical study. So very soon we'll get into the more recent clinical studies related to so savan for the use of treating depression and some other conditions. But we before we do that, i'd be remiss if I didn't talk about how solicited an does and does not change the brain.

What isn't what is not known about that? In fact, when I put out the for questions about Sullivan, many of the questions related to these issues, the first thing understand is that a Sullivan journey, it's really a way to try and put that wedge under the bolder, as I described IT, to try invoke era plasticity of our particular kind. In that way, it's kind of remarkable.

If you think about that, everyone has different lives, different experiences. Psychodeviant s in this case, Sullivan are activating these brain networks that each of us has more broadly than they would Normally be activated. These are very abNormal patterns of thinking and perceiving, experiencing our emotional and physical life seta.

And yet, so often the outcomes are positive, not always, but the outcomes are positive. The experience is positive. Even though I might have this, anxiety moments are components within them. It's very important to understand that suicide van and the journey, while important, are not really what all of this is about. It's really about neural plasticity.

So researchers, in particular neuroscientists, are very intensely interested in understanding what sorts of neural plasticity so alive and create because IT turns out there are a lots of different types where processes involved with neuroplasticity, for instance, brain network's behavior, thinking, emotion, that seta, can change because of the decision of new neurons. That's one form of neuroplasticity that's referred to as neurogenesis, the production of new neurons, most typically in the so called the dentist gift s or other sub regions of the hip campus. A brain area involved in learning and memory neurogenesis in other regions of the adult human brain are exceedingly rare and, to be honest, may not occur at all.

This is a debated area. We could do an entire episode about this, but for the most part, neuroscientists don't really believe that your neocortex, your stride m, your cerebel has that much neurogenesis that's related to learning in memory of new things or new experiences. And we don't actually think that occurs as a consequence of taking Sullivan either.

Now some of you who are familiar with, for instance, the cereBellar might be saying, wait, what about granular cell proliferation in the cerebel m, or what about the ostroe migratory stream from the submarine truculent zone, where their narrow blast spitting out little new that migrate into the nose to replenish h the old factory or on population? Yes, that's all true. That does occur.

It's been observed in mice. It's been observed in monkeys. And to some extent, it's been observed in humans. But it's not again, I repeat, IT is not a prominent feature of learning and acquisition of new skills, new ideas or new emotional states.

Perhaps the best supported evidence for neurosis underlying new thoughts, experiences, abilities, emotions at sea is the production of new neurons. In that. Then take our suburb of the hip campus, and that probably does occur in humans.

But neurogenesis is not really the dominant mode of changing neural circuitry in adult humans. IT might be a player in adolescence, in Young childhood. IT is certainly a player before we are born, when we are still in utero.

But then the brain has been wired up in many different ways, including the addition of neurons and changing of connections. All this is to say that while neurogenesis is a really sticky idea and he makes great headlines, the addition of new neurons is not really the way that the brain changes under suicide. And other psychic, delicate or just generally, it's perhaps responsible for maybe one to two percent.

And i'm being generous there of the rewiring events that are going to be most important for all of us. So we need to set that down and and to cement that there until further evidence comes out to the contrary. That certainly were I. And here I feel comfortable speaking for the majority of neuroscientists out their professional neuroscientists. That is, the paper showing adult or genesis are interesting, but they don't really explain most of the plastics vickers in the adult human brain.

So if neo genesis ain't IT, what is? Well, it's very clear that Sullivan, other psychic, delicate and any sort of behavioral a drug intervention that can induce neal plasticity does so largely through the edition or strengthening of new neal tions or through the elimination or weakening of other neural connections. And if you look at the data expLoring the mechanistic basis for sicilian induce neuroplasticity, it's mostly focused on animal brain, animal models, mice and rats in particular, a little bit on primates, but mostly myse and rats, because that's where the interventions can be done of knockout animals, of imaging the brain in real time course.

There are the beautiful studies of Robin karar terrace and others expLoring neuroplasticity at the level of brain imaging, at the level of ultrasound measurements, of how active are certain brain areas in humans, how extensive us. Know the modularity or not extensive, as the modular IT IT said, are the stuff we talked about earlier. So in other words, there are newer plastic to these studies with the effects of suicide an in humans.

But in terms of underlying mechanisms of neuroplasticity, think the predominant theory is that. Sillas ici been induced neuroplasticity through the addition of novel connections in those parameters, neurons of the front cortex, elsewhere in the cortex, and certainly also in the visual cortex, probably also sub cortical, as well below the arrival cortex in areas like the followers, maybe even in the brain stem as well. And that those neuroplasticity events are structural and functional, and they involve a couple of basic events, the most prominent of which is the growth of dendrites dendrites, are those low branches or processes that come out of the the neurons, not just the criminal neurons, but other neurons as well.

But since we're talking mainly about criminal neurons today, but the epical, those ones that top, the're called the epical, tough to the ones that reach laterally to connect with other neurons, communicate with other neurons. So we talked about before as well as the dendrites to come out of the base of those parameters, neurons, those processes grow in response to solicit ban, as well as the addition of water called dendritic spine. So the dendrites, the branches, the spines, are these little protrusions that grow out, actually.

And here I don't know this this coincidence or not. I would say I wasn't consult the design phase. But these little peach sions actually look like little mushrooms.

They have a little stock, and they're a little head, a little spine head and those little spine. So think this is like little tiny mushrooms appearing. okay? They aren't actual mushrooms.

okay. The first person puts in the comments, oh my god. Ss, I learned today that mushrooms grow out of our neurons when we take magic mushrooms. That is not what i'm saying. What i'm saying is that these little mushroom shaped petruchio that we're calling danger red expand do, in fact, you grow out of danger tic branches of neurons when animals in just suicide or are injected with solymi.

And that those little mushroom shaped petula ons are the sites of new, exciting tory connections, new locations for input from other neurons to activate those neurons that have those little mushroom shape productions. If you'd like to see examples of this, both movies and still shots, is pretty remarkable. There is a paper that will provide a link to in the shown note captions.

This was publishing the journal neuron Price journal excEllent general entitled Sullivan induced rapid and persistent growth of deterred expands in the frontal cortex in vivo. So these measurements were done in the mouse equivalent, more less of the prefrontal cortex. There are some interesting details in this paper, for instance, that those new connections persist, so they don't just grow out during the sliced and being active in the bloodstream and rain of the animal, they persist.

And so this may again, may explain some of the persistent changes that occur in people after suicide in journeys, they may to grow new spins. I should also mention that a reduction in the number of generic expands his low mushroom shape. Productions in the frontal cortex neurons of humans occurs in depressed patients.

We know that from post morum tissue and that drugs that relieve depression, or that treatments, including behavioral treatments that provide some relief from depression, do seem to be correlated with increases in spine growth in frontal cortex irons as well. So this raises a very interesting idea, which is perhaps it's the growth of new connections. These new gender expands, in particular, neurons, that's created by administration of sicyon, in that explains the relief from depression that people experience.

So this is just one paper, but it's one paper of a growing body of work showing that, yes, indeed, silly. Ivan induces both structural and functional plasticity in the human and animal brain. IT does that in the human brain at therapeutic c doses of anywhere from ten to twenty five, perhaps you, in thirty milligrams procession, one or two sessions. I should mention that the mouths studies tended to use quite high doses of suicide.

And I was actually, I wasn't shocked, but I was somewhat, why died for a moment to realize that most of the studies, looking at changes in plasticity, in the mouse sprain and responsible Simon, use the equivalent of one milligram per kilogram of body weight, which is, if you do the math and you translate what we are talking about before foreign ms. Of dosages also just spare you all the time. It's about double the sorts of dosages that are typically used in humans, maybe even triple in some cases.

Now it's often in the case in animal studies because of the metabolic of animals being different, but also because seeing effects of drugs in animal studies can be difficult. Um they did use a dose response anywhere from zero zero point two five to half to one to two milgram per kilogram of Sullivan in the study. So they had a dose response curve but focus mainly on this one milligram per kilogram dosage.

In any event, the point is that many of the studies that describe these pretty dramatic structural changes in the animal brain, most typically the mouse, spring in response to solicit an use dosages of cells IBM that, if translate to humans, would be about double the human therapeutics. So that is something that we need to take into consideration none's. It's very clear that in both animal studies and humans, so sivan is inducing both structural and functional changes, brain circuitry, and that in humans, the network connectivity is being changed dramatically.

We talk about those data earlier and that the underlying basis for that might be, again, might be we don't know for sure. The addition of new generation expands on these parameters. Neurons that we've been talking about repeatedly throughout to this episode, although no genocide, perhaps in other modes of neural plasticity, such as the elimination of certain connections, perhaps related to unhealthy maladaptive thoughts, or our feeling that a particular sad song is overwhelmingly sad, IT could be the case that those sorts of things change objectively because of the removal of neural connections.

If you're going to think like a neurobiologist or scientist for that matter, you don't everyone to think that one mechanism can explain all the effects of a given dragger or given experiences, almost certainly likely to be the consequence of multiple mechanisms acting in parallel. And because I know there are people out there who would like to know even more about the neuroplasticity induced by psychedelics, including soli, don, there's a wonderful review that I provide a link to in the showed te captions entitled psychodeviant s and neuroplasticity a systematic review unraveling the biological underpinning of codex s. This review is great because IT goes a step beyond just slice band silicon binding to the third one into a receptor, and things like brain derived in a trophy factor.

IT actually talks a lot about the interest seller signaling and exactly how neurons change their excitability patterns based on this activation of the settle into a receptor. Probably more detail than most of you out there are interested in. But if you are interested in that left of detail, this is a wonderful open access review. So a few minutes ago, I talked about where there is strong, modest and somewhat weak, or rather, I should say, minimal evidence for the theraputics of Sullivan to treat various disorders. And across the board, IT really appears that major depression and so called intractable depression in some cases, is where we're seeing the most exciting research to date.

Now keep in mind that because of the controlled substance to act being invoked in one thousand nine hundred and seventy in the united states, and because IT was only just a few years ago, really only about five years ago, that psychodeviant s including suicide ban received what's called the breakthrough status at the fda, that there are now a lot of clinical trials expLoring how Sullivan can impact various things like mood disorders, addictive disorders and so on, prior to twenty eighteen, when that the era pute breakthrough potential was established in united states. Think a lot of people in the so called syc doc community had the sense in the really the belief that these drugs had enormous potential, but I just weren't being explored that extensively. So I do want to give a nod to the incredible researchers such as Robin card Harris, but also Matthew Johnson, rolin griffis, knowler Williams and many others.

Okay, i'm certainly listening off everybody that would take hours, but those researchers are really pioneers, both the legal efforts and the funding efforts and most importantly, the research efforts defining the clinical data that i'm about to describe. And here, i'm going onto summarized the clinical data in a bit of a top con to our fashion, just giving you the kind of highlights. We will, of course, provide links to the papers if you'd like to look into IT further.

But i'm only giving you the top on tour because i've had the great fortune of having Matthew Johnson on this podcast before you can find that episode burn in lab 点 com。 Just simply put math name or psychiatrically into the search functions. I'll take you to that episode in all formats or links to all formats.

Rather, i've also had the great fortune of sitting down recently with doctor Robert cardi Harris to talk about his work at university of california, cecco on suicide, an elastic IOS sa and d mt. As IT relates to depression and other disorders. And that epsom, which also will be released at human man lab at a command on all platforms.

Youtube, spotify really goes in depth into these clinics, studies and what those studies really look like, who's in the room, whether not people just get one dose or two doses, how far apart ths are separated, all of that is covered in extensive detail in that. What I found to be wonderful discussion with doctor Robin and carta here. So if you're interested in all of the details as IT relates to clinical application of psychological um stay tuned for that episode soon.

Again, you can find that at huberman lapdog com and on all platforms. In the meantime, I would be remiss if I didn't include a bit of discussion about what has been observed in terms of using Sullivan journeys as a way to treat depression, because the data are just all so exciting. Again, these data really started to surface as the consequences studies that were initiated around two thousand six in just a few select laboratories, and then really picked up in terms of the number of laboratories and number of studies between twenty eighteen and now.

So what your nose is that most of the papers are about to describe. We were publish in, for instance, phenomenal journals new england journal medicine in twenty twenty one, new england journal medicine november twenty twenty two um journal of the american medical association psychiatry just very recently twenty twenty ones. These are very recent papers.

Essentially all of these clinical studies involve either one or two suicide and sessions. The dosages that were explored range from zero milligrams of placebo, if you will, ten milligrams, some cases twenty five milligrams, in some cases thirty milligrams. And most typically, people receive the same dosage for both sessions, if indeed they did both sessions.

However, there's at least one study looking at just one single episode of Sullivan administration. So this is the paper entitled no surprise single do solvin for treatment resistant episode of major depression. This published in the new england journal medicine in november of twenty twenty two.

I'll just summarized the results of this. Single application study, they randomly ly assigned subjects who had treatment resistance depression. So they'd resisted treatment to other things to receive a single dose of a synthetic formulation of silicon band.

So they're not eating mushrooms. They're getting a synthetic dose of silicon band, but the dose is known of either twenty five milligrams, ten milligrams or one milligram, which was the control. And they receive psychological support.

There were a number of different tests, objective tests of depression taken before and after the cell. Simon journey. They had about seventy five to seventy nine participants in each group, again, at the three different doses, twenty five, ten or one milligram. And they looked at the changes in these scores, these depression related scores on these tests.

There are many results from newspaper one could summarized, but among the most important results I can summary from the discussion in here and periphery that the change in baseline levels of depression, that is, at week three following the suicide and session, was significantly Better. That is, people experienced more relief, or more people experienced more relief from the twenty five milligram dose, then from the one milligram dose. And this is important.

There was no significant difference between the ten milligram dose and the one milligram dose. This really points to the fact that the twenty five to thirty milligram dose that's used in the largest numbers of studies expLoring treatment resistant depression really seems to be, I know I say, the best dose, but the most effective dose, at least in this clinical context, in this set, in setting and with this particular patient population. So we want to be careful to say that.

So that one doesn't just translate the twenty five milligrams is Better than ten million ms. Although in this study IT was for the sake of treatment resistant depression relief, there are number of other key aspects of this paper, in particular the exploration of so called adverse events. So things like headaches, propensity for self harm, actual self harm, anxiety and so on, it's worth mentioning that there were adverse events in essentially every group.

The number of adverse events was highest in the twenty five milligram dose group. This is observed in other studies as well. With higher dosages, there tends to be greater relief from depressive symptoms, but also a greater chance for adverse events.

Some of those adverse events can be quite severe, so feelings of suicide, ation IT said a, some of them, one could consider a little less severe, mild headache or severe headache that was transient or anxiety that was transit. And again, highly individual responses. We could go lined by line and by table through this paper, which we won't because there's a lot of data.

Again, we will provide a link to this paper if you would like to prove IT yourself. It's fairly straight forward to read. That's one thing that's nice about these clinical trials as they intend to be written in fairly non technical language, although there's a little bit of technical language.

The important point is that a single dose of twenty five milligrams of silicon provided significant relief from treatment resistance depression in this particular patient population. But IT is not the case that one hundred percent of the people who took twenty five milligrams of solicited and experiences that relief, however, the majority of them did when you say majority and science really need to look to numbers. And the reason i'm not telling you, oh, IT was seventy five percent or sixty percent, fifty percent is because IT depends on which timeout people were analyzed.

People were asked about their level of depression relief immediately after, one week after, two weeks after, three weeks after. And the degree of relief tended to change over time. In fact, he tended to diminish over time. But IT was also stable, or remarkably stabilized, say, at least by my read in the twenty five milligram dose group.

And that is summarized nicely and figure two of the paper, because they explored these people's levels of depression out to weak twelve, and they still saw a significant degree of depression relief twelve weeks after the single twenty five milligram Sullivan dose session. So as I mentioned earlier, there are now about a dozen or so excEllent studies, clinical trials, expLoring the use of single or two session solicited and treatment in that twenty five to thirty milligram range, which seems to be the most effective dose for a long lasting relief from depression. Each one of those studies explored something different, as this important replication is also important, of course, in order to validate previous studies.

But for instinct, there have been comparisons of suicide an versus assi ze or other antidepressants. There been comparisons of Sullivan plus psychoanalysis or carbon behavioral therapy versus cogent behavioral therapy alone or psychoanalysis alone. And so there is a lot of evaluation now of the clinical outcomes and the statistical outcomes of these subjective measures and even some objective measures of neurochemistry where that's possible in terms of trying to understand if and how Sullivan is effective for the treatment depression.

And the major take away is that IT does seem to be the case and the numbers that I feel comfortable not throwing out there but putting out to you reflect my conversation with Robin card card Harris again, that will be released soon and he woman love out com, as well as take away from what I would say are that six brothers studies, meaning they have the widest range of age groups that brought a demographic in terms of the subjects, their backgrounds, their levels of education, men, women, ethnicity, etta. And a lot of that can be summarized in the paper entitled effects of silica bean assist therapy on major depressive disorder. This was a particular randomized clinical trial.

But in the discussion, I think they summarize IT quite well, which is that if you look at the number of people who take this twenty five milligram dose twice in session space, about a week apart, what you will find is that anywhere from sixty to seventy five percent of the people who have major depressive disorder, who do these solicited and sessions in the proper setting, report a good experience with IT, have minimal adverse events coming out of those sessions. And in the week's following, those people experience substantial positive relief for major depression in ways that other treatments that they explored, including the percent drugs, coding, behavioral therapy and other types of therapy alone, could not provide. Now it's a general feature of these clinical trials focusing on syl IBM that people are asked to stop taking their antidepressants or to participating in the trial.

It's also a general feature of these trials that people are encouraged to not suddenly start their into a depressive treatment immediately afterwards because, of course, that could confirm the results of the sulfide and treatment. However, and this is a very important thing to note, all subjects were encouraged not to avoid taking those into the present medications if, in fact, their clinical felt that IT was important for their immediate and long term survival. So, you know, no one should be reckless and thinking about what to add or delete from their drug protocol when dealing with depressions, or the outcomes could be very severe.

In that case, we can paraphrase from the discussion of the paper I just mention, because IT really highlights the incredible results that slicer de and applied in these particular therapeutic executors are providing. And here again, i'm parities sing. The present trial showed that suicide ban, administered in the context of supportive psychotherapy, consisting of approximately eleven hours of psychotherapy, so this is going to be two sessions of the illicit, and with proper diapered tic support, produced large, rapid and sustained entire depressing effects.

The effect sizes reported in the study where approximately two point five times greater than the effect sizes found in psychotherapy and more than four times greater than the effect sizes found in psycho pharmacologic depression treatment studies, in other words, four times the positive effect observed with typical accessorize or other pharmacology of that sort. These findings are consistent with the literature that shows that combine pharma therapy and psychotherapy were more efficient in the treatment of major depressive disorder than either intervention alone. Again, this pots of the fact that combining drug therapy with talk therapy, as is often called, is going to be more effective than the either treatment alone.

Here are the drug therapy, suicide and therapy. And again, please don't take the fact that in these studies they attended to ask people to not take their into depression medication heading into the study as a sign that one should stop taking their enter depression medication. Rather, I think this study and other studies like IT again, which will provide links to in the shown of captions that are discussed extensively in the episode with docker art Harris soon to come really point to the incredible role that suicide ban can have in creating an experience inside of the session.

The ney or the trip as it's called, as well as initiating neuroplasticity vents, perhaps the addition of general expense, maybe even some new neons, maybe, although I don't think that's the predominant mode, but that leads to these more extensive connectivity in the brain, is so called reduction in modular networks, enhanced activity in brain areas that Normally wouldn't be talking to one another, but not doing that in any kind of hap hazards. Weight IT really does seem that the one or two sessions of suicide, and that induce these feelings of ego dissolution, that induce these feelings of oceanic bonnetless, right? So mystical in many ways, it's what I find so incredible about Sullivan and other psychic licks, is that despite the highly mystical, highly subjective and still, at this time, somewhat top on to our understanding of how they might exert their effects, you can highlight bold face and underline might there, right? Because hasn't really been firmly established what the exact sell biological rewiring events are.

But there is now what I would refer to as the center of mass of data that point, the fact that solicit an, when taken in the appropriate set and setting, and the appropriate dosages can invoke the sort of neural plastic is the and changes in emotionality in perceptual experience, not just during the psychedelic session, but for a long periods of time after the psychedelic session, that can provide really remarkable relief from things like major depression and perhaps other psychiatric issues as well. And of course, I realized that many of you are listening to and you're watching this episode and you're not necessarily depressed or are thinking about psychedelics like saliva in the context of depression. I hope today's discussion allowed you to Better understand how psychodeviant ics and suicide, and in particular, because that's what we have been talking about, are able to exert these incredible effects that they seem to exert.

This is not a call for everyone to run out and do so lyda IT is absolutely not that IT is. However, my attempt to really put a magnifying lens on this incredible area of research that's happening not just in the context of clinical trials, but in the context of trying understand how serotonin and how drugs like seller van, which many ways mimic serotonin, and more particularly, the activation of particular receptions in the brain, like the service tone and two a receptor. And just sit, I can think about that, the selective activation of this receptor, which is, by the way, associated with the expansion of the neo cortex across evolution.

Didn't mention that before, but indeed, IT is how that can lead to enhances ways of thinking, changed ways of thinking, actual learning inside of this short four hour, six hour session that we call the suicide an journey. So as is often in the case, perhaps as is always the case, you're on the huberman and broadcast. We did a deep dive into a topic today, into the topic of silica yan, what IT is, how IT works, the different ways in which changes brain circuitry, how IT creates the experiences that we think of as the solicited and journey, what the safety issues are, what the so called set and setting are that can lend themselves to positive theraputics comes.

And in doing so, my goal was really to highlight several things. First of all, I am very excited about the potential for psychedelic such a Sullivan to provide a relief for mental health issues that to date have been very hard for people to access. In addition to that, i'm just fundamentally interested in the brain and how IT works and how I can change this thing we call on the neuroplasticity. To me, new plastic is the holy grail of the human nervous system, as well as we know we are the animal that can have long lasting neural plastic throughout the lifespan. And if IT requires the use of compounds in a safe, controlled way, such a sillas in order to achieve maximum plastics in a short amount of time, that's exciting.

But of course, that also needs to be considered with all of the safety precautions in mind that we talk about early, including the fact that people who have a predisposition or who have the psychosis or by polar disorder relative that has psychosis or bipolar disorder, Younger people, many people twenty five years of age and Younger, and really anyone who is not working with a dedicated and highly trained physician needs to be very cautious about these compounds as well. They're very exciting. I think sales i've isn't exciting and super interesting compound for basic and clinical reasons and for other reasons as well.

But they are sharp blades, as we say. And with sharp blades, you can do incredible things, but you can also cut yourself very badly. So all those considerations need to be taken to mind. So I consider the science and use of Sullivan to be an exciting but still preliminary area that I certainly paying a lot of attention to. And I know there's a lot of excitement about.

So stay tuned for the episode with doctor Robin hardart Harris, and we will probably revisit Sullivan, and we will certainly revisit the other psychic licks and non classical psychodeviant s including lsd, D M T five, M O D M T kadee, M D M A meslin and all the rest in future episodes as well. If you're learning from and enjoying this podcast, please submit our youtube channel. That's the best zero cost way to support us.

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