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

**Andrew D. Huberman** (0:00)
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, we are discussing psilocybin. Psilocybin is a psychedelic, meaning it modifies the psyche. And in doing so, it changes our level of consciousness. Psychedelics such as psilocybin change the way that we perceive the outside world and our internal world, our memories, our thoughts, our feelings, et cetera, not just while one is under the influence of psilocybin, but it 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's growing excitement about the application of psilocybin and other psychedelics 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 psilocybin, talking about what it is. In fact, you may be surprised to learn that psilocybin basically is serotonin. Now, for those of you that are familiar with psilocybin and serotonin, you might think, wait, that's not true. But in fact, psilocybin'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. Psilocybin is one of many psychedelics, of course. There are things like LSD, DMT, 5-MeO, DMT. Even MDMA, while not considered a classic psychedelic, is considered a psychedelic in the general sense. Today's episode is going to focus on psilocybin in particular. I will tell you what psilocybin 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 psilocybin mushrooms to actual psilocybin and the compound that actually exerts the effects of psilocybin, which it turns out is not psilocybin, but something called psilocin. Psilocin is the actual compound that goes into the brain to create all the changes in consciousness and all the rewiring effects that we associate with psilocybin. So understanding how psilocybin is converted to psilocin has tremendous impact on the duration of a psilocybin journey, whether or not that psilocybin journey is going to lead to a short or longer window for neuroplasticity. 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 psilocybin therapeutic approaches takes place after the session in which one feels all the typical or typically associated effects of psilocybin like hallucinations and changes in thought patterns, et cetera. 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 or not you have a background in chemistry or biology. We're going to talk about some cell biology, the actual neuronal changes that occur when one takes psilocybin. 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 psilocybin journey. Things such as longstanding improvements in mood, things such as tremendous insight into themselves and to others, into their past, their present and their future. And even changes in their levels of creativity or their ability to experience joy from music or their ability to dissociate in a positive way from things that formerly were depressing or triggers for depression. In fact, we're going to talk quite a lot about the conditions inside of a psilocybin journey that make it actually positive and therapeutic. This is a very important point that I'll make several times throughout today's episode, which is that just because something invokes neuroplasticity, changes in brain circuitry, does not mean that it's therapeutic. Or I should say, it does not necessarily mean that it's therapeutic. 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 psilocybin 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 or 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 psilocybin journey, as well as the dosage level. Because as you'll soon learn as well, there are clinical studies showing that just one psilocybin journey can improve mood in a longstanding way, but most clinical trials involve two dosages, spaced in very precise ways from one another with appropriate follow-up. But in both of those particular journeys, the structure of the journey, who's present, who's not present, eyes open or eyes closed, the particular music that's played, all of those features make up part of a larger neuroplasticity trigger of which psilocybin is critical, but psilocybin is not the only variable. So whether or not you're interested in participating in a clinical study or whether or not you're interested in psilocybin for other reasons, this is critical information to understand. So today we're going to talk about nearly every feature of psilocybin possible, including what psilocybin is, how it works at the level of chemistry, cell biology and neural networks and neuroplasticity. We will talk about the clinical studies, we'll talk about dosages, we will talk about conditions of clinical studies, and we will talk about the post psilocybin journey period in which neuroplasticity and the various activities, including therapy or perhaps not therapy, can contribute to positive therapeutic changes from psilocybin. 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 2023, psilocybin is still a schedule one drug. It is considered illegal in the United States. There's perhaps just one exception to that, maybe a few others, but the main exception is in the state of Oregon, psilocybin has been approved in particular therapeutic settings for use in particular conditions, namely depression and some forms of addiction. So in Oregon, it's more or less in the domain of a decriminalized as opposed to actually legal. In other areas of the country, including Oakland, California, there's some areas in which it has been decriminalized and perhaps there are a few others that I'm not aware of, but in general, psilocybin and other psychedelics are still considered illegal. And this is very important, not just saying this to protect me, I'm saying this to protect you. Possessing or certainly selling psilocybin, except for rare instances such as clinical studies and these decriminalized areas that I 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 or not young people, meaning people 25 or younger, should consider psilocybin, 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 formerly been on or may currently be on different forms of antidepressants. And I will talk about people who are at risk for psychotic 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, as well as things like borderline personality and some related psychiatric conditions. So today's episode really will be a deep dive into psilocybin. So whether or not you think you're already familiar with psilocybin and its effects or whether or not you're just curious about them, I do encourage if you're willing to try and ratchet through some of the understanding of how psilocybin works and what it is, leading up to some of the therapeutic applications and different patterns of dosing, spacing of different sessions, et cetera, because I do believe that with that knowledge in hand, you will be able to make far better, much more informed decisions about whether or not psilocybin is right for you. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and 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 8Sleep. 8Sleep makes smart mattress covers with cooling, heating and sleep tracking capacity. Now, sleep is the foundation of mental health, physical health and performance. Everything goes far better when we are sleeping well on a consistent basis. And one of the key things to getting a great night's sleep is to make sure that the temperature of your sleeping environment is correct. In fact, your body temperature has to drop by one to three degrees in order to fall asleep and stay deeply asleep. And waking up involves a heating up of your body by about one to three degrees. 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