Published May 2023 on YouTube

How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks | Huberman Lab Podcast

1. Psilocybin, Legal Considerations

Psilocybin and Serotonin:Andrew explains how psilocybin, a psychedelic, mimics serotonin and can lead to neuroplasticity in the brain. He discusses the growing excitement around the use of psilocybin and other psychedelics for the treatment of mental health issues such as depression, alcohol abuse, and eating disorders.+
Psilocybin Chemistry:Andrew explains the molecular and cellular effects of psilocybin and how it changes brain circuitry. He discusses the clinical effects, dosages, and how silosin is the actual compound that exerts the effects of psilocybin. Andrew emphasizes the importance of proper psilocybin therapeutic approaches and how neuroplasticity must be adaptive to be therapeutic.+
Psilocybin Deep Dive:Andrew discusses the various features of psilocybin, including what it is, how it works, clinical studies, dosages, and conditions. He also talks about the post-psilocybin journey period and the role of neuroplasticity in contributing to positive therapeutic changes. Additionally, he emphasizes the importance of understanding the legal status of psilocybin and safety concerns, including dosages for people on antidepressants and those at risk for psychotic episodes.+

2. Sponsors: Eight Sleep, ROKA, HVMN

Andrew discusses the importance of sleep for mental and physical health and introduces Eight Sleep, a mattress cover that helps regulate temperature for optimal sleep. He also shares his experience with Ketone IQ, a supplement that can improve cognitive and physical performance.+

3. Psilocybin's Chemistry

Psilocybin's Chemical Composition:Andrew explains that psilocybin is a tryptamine, which closely resembles serotonin in its chemical composition. Contrary to popular belief, the serotonin in your brain is not manufactured from the serotonin in your gut.+
Psilocybin and Serotonin:Andrew explains the relationship between serotonin and psilocybin, and how the similarity between the two leads to a range of effects on the brain and body. He discusses the many functions of serotonin and its receptors, and why psilocybin can cause hallucinations, changes in thought patterns, and improvements in mood and mental health.+

4. Psilocybin's Selectivity

Psilocybin's Selectivity:Andrew explains how psilocybin's selectivity towards the serotonin two A receptor is responsible for triggering changes in neural circuitry that lead to improvements in mood and relief from compulsive disorders. He also discusses how two psilocybin journeys can lead to significant relief for major depression.+
Psilocybin vs. SSRIs:Andrew discusses how psilocybin outperforms SSRIs in treating depression and how the selectivity of psilocybin to bind to the serotonin two A receptor is key to understanding its therapeutic effects.+

5. Psilocybin and Serotonin

Psilocybin and Serotonin Receptors:Andrew explains how psilocybin selectively binds to serotonin two A receptors in the brain, particularly in the neocortex, including the prefrontal cortex and visual cortex. This triggers visual hallucinations and affects behavior, thoughts, and speech patterns depending on the context.+
Psilocybin and Visual Perception:Andrew explains how psilocybin affects the visual cortex and why it's important to keep eyes closed during a psilocybin session to focus on inner experiences rather than external visual hallucinations. He emphasizes that having an eye mask or other covering is critical to making the psilocybin journey effective in a therapeutic sense.+

6. Psilocybin Safety

Andrew emphasizes the importance of safety when it comes to psilocybin use. He warns that it is not for everyone and can be contraindicated for those with certain predispositions or conditions. He stresses that psilocybin is a powerful drug that should only be used in a proper clinical setting.+

7. Sponsor: AG1 (Athletic Greens)

Andrew talks about the importance of gut health and how Athletic Greens helps him meet his nutritional needs, including probiotics. He also shares a special offer for listeners to try Athletic Greens.+

8. Psilocybin Dosages

Psilocybin Dosing:Andrew Huberman discusses the effective and safe dosages of psilocybin, including microdosing with 1-3 milligrams and larger doses of 10-30 milligrams. He also explains the concentration of psilocybin in magic mushrooms and the use of synthetic psilocybin in clinical studies.+
Psilocybin Dosage:Andrew explains the conversion of grams of mushrooms to psilocybin and discusses the so-called "heroic doses" of psilocybin. He emphasizes the importance of sourcing and dosaging consistency as different strains of mushrooms and batches can vary tremendously in psilocybin concentration.+

9. Psilocybin Journey Components

Psilocybin Journey Components:Andrew Huberman discusses the consistent components present in clinical trials that have demonstrated the effectiveness of psilocybin for the treatment of depression and other compulsive and addictive disorders. He emphasizes the importance of set and setting, referring to mindset and the setting in which the journey takes place, in ensuring a safe and effective psilocybin journey.+
Safe Psychedelic Journeys:Andrew Huberman emphasizes the importance of set and setting for safe and beneficial psychedelic journeys. A safe environment with responsible individuals present is crucial to prevent harm and maximize the benefits of the journey. He also discusses the importance of a subdued setting, such as a closed room with guides, for maximum benefit.+

10. The Power of Music

The Power of Music:Andrew speaks with Robin Cardart Harris, a professor at University of California, San Francisco, about the critical role that music plays during a psilocybin journey. Music is not just an incidental feature of the setting in psychedelic set and setting, but one of the major drivers of the actual cognitive and emotional experience. The episode also discusses the duration of a psilocybin journey and the importance of not having any food in the gut prior to ingesting psilocybin.+
Psilocybin Music:Andrew explains how music is used during psilocybin sessions to help guide the emotional journey. The music starts with classical music and transitions to intense percussion during the peak of the experience, before transitioning back to softer music and nature sounds.+

11. Psychedelic Perception

Psychedelic Perception:Andrew explains the subjective experiences people have on psychedelics, including perceptual blending and synesthesia. He also discusses how psilocybin activates the serotonin two A receptor, allowing for these experiences to occur.+
Serotonin and Neurons:Andrew explains how serotonin two A receptors are expressed on neurons and what those particular neurons are doing. He talks about parameter neurons and how they are shaped like a pyramid. He also explains how these cells are effectively doing the same thing by extending little processes out into layers above them and to the sides.+
Psilocybin and Brain Integration:Andrew explains how psilocybin increases communication across the brain, reducing the modularity and hierarchical organization of the brain. This leads to integration of communication across what would otherwise be disparate brain regions.+
Psilocybin and Brain Circuitry:Andrew explains how psilocybin affects brain circuitry by broadening the flow of information and activating serotonin two A receptors. This results in less precise and less hierarchical activation of brain circuitry, allowing for more blending of different senses and emotional states.+

12. Sponsor: LMNT

Andrew discusses the importance of electrolytes in the body, particularly for nerve cells and cognitive and physical performance. He recommends Element, an electrolyte drink with a science-backed ratio of sodium, potassium, and magnesium, for hydration and replenishing electrolytes during physical activity or after sweating.+

13. Psychedelic Brain Networks

Psychedelic Brain Networks:Andrew discusses the different brain networks that are activated during a psychedelic journey and the changes that occur in the Default Mode Network. He also highlights the enhanced lateral connectivity and interconnection between different brain areas as a result of psilocybin.+
Psilocybin and Brain Connectivity:Andrew discusses the use of psilocybin in rewiring the brain and expanding connectivity. He emphasizes that the goal is adaptive rewiring that leads to new ideas and ways of thinking that allow people to function better in their lives. Psilocybin seems to increase connectivity in the brain in ways that still allow people to function in their daily lives, without experiencing long-term issues with memory.+

14. Psilocybin and Music

Psychedelics and Creativity:Andrew discusses how psilocybin impacts creativity and our experience of life. He mentions a study that shows increased low-frequency brain responses to music after psilocybin therapy for depression. Different brain areas are activated depending on what sort of music is being played, and there are universal features of brain activation in response to music.+
Psilocybin and Music:Andrew discusses a study that shows how psilocybin changes one's emotional response to music, even after the psilocybin journey. This is particularly interesting for people with major depression who often feel as if music no longer has the same impact.+
Psilocybin and Music:Andrew discusses a study that found psilocybin can increase positive perception of music and reduce the sadness of music that tends to make one sad. Psilocybin can rewire the connections between the emotion centers in the brain and the networks that control auditory perception of music, leading to an increased capacity to experience joy in response to music again.+

15. Psilocybin and Creativity

Psilocybin and Creativity:Andrew discusses the potential connection between psilocybin and creativity, highlighting the lack of studies on the brain networks involved in creativity during psilocybin journeys. He also explains how psilocybin can rewire our relationship to things more broadly by allowing for new learning and new contingencies.+
Psilocybin and Neuroplasticity:Andrew explains how psilocybin initiates the neuroplasticity process, leading to new patterns of learning and rewiring of emotion centers in the brain. He uses the analogy of a wedge getting underneath a boulder to describe how psilocybin clears a path through old, ineffective patterns of thoughts or emotions.+

16. Psilocybin Insights

Psilocybin Experiences:Andrew discusses some of the key and stereotype experiences that people tend to have during a psilocybin journey, including letting go, ego dissolution, and feelings of connectedness. He also explores the possibility of a bad trip and highlights a scientific study that puts numbers to subjective experiences related to positive therapeutic outcomes.+
Oceanic Boundlessness:Andrew discusses a study on psilocybin and the key feature of a positive psychedelic experience: oceanic boundlessness. This mystical feeling of connectedness with one's environment is positively correlated with relief from major depression. The experience occurs during the peak of the journey and is not aligned with any specific outcome.+
Psilocybin Experience:Andrew discusses the experience of ego dissolution during the peak of a psilocybin journey and the role of a guide in keeping the person safe. He also talks about the correlation between positive clinical outcomes and the experience of unity, spirituality, bliss, and insights during the psilocybin journey.+

17. Psychedelic Anxiety Insights

Psilocybin Therapy Insights:Andrew Huberman shares insights from a study on psilocybin therapy, highlighting the importance of anxiety management during the psychedelic journey. While ego dissolution is a key component, non-responders tended to have higher anxiety ratings, indicating a balance is necessary for positive outcomes.+
Psychedelic Anxiety Relief:Andrew Huberman discusses the importance of well-trained guides to help individuals manage anxiety during psychedelic experiences. He also mentions preliminary studies on the use of real-time respiration tools to reduce anxiety during the effects of psilocybin.+
Psychedelic Breathing:Andrew discusses the benefits of using the physiological PSI breathing technique to reduce anxiety during psychedelic sessions. This technique can be taught to individuals before the session begins, allowing them to self-direct their own calm and improve the quality of their experience.+

18. Therapeutic Use of Psilocybin

Andrew discusses the therapeutic applications of psilocybin as it relates to recent clinical trials for depression and addictive disorders. He highlights the most evidence-based outcomes for psilocybin therapy and shares a paper that provides practical considerations for dosing and administration, including contraindications and adverse events.+

19. Psilocybin and Neuroplasticity

Psilocybin Neuroplasticity:Andrew explains that psilocybin journeys are a way to invoke neuroplasticity of a particular kind. Researchers are interested in understanding what sorts of neuroplasticity psilocybin creates because it turns out there are lots of different types or processes involved with neuroplasticity.+
Neurogenesis and Neuroplasticity:Andrew Huberman explains that while neurogenesis is not the dominant mode of changing neural circuitry in adult humans, psilocybin and other psychedelics induce neuroplasticity largely through the addition or strengthening of new neural connections or through the elimination or weakening of other neural connections. The mechanistic basis for psilocybin-induced neuroplasticity is mostly focused on animal models, particularly mice and rats.+
Psilocybin and Neuroplasticity:Andrew explains that psilocybin induces neuroplasticity through the addition of novel connections in the neurons of the frontal cortex and elsewhere. This neuroplasticity involves the growth of dendrites and dendritic spines, which are the sites of new excitatory connections. The dendritic spines look like little mushrooms and are the result of animals ingesting psilocybin.+
Psilocybin and Neuroplasticity:Andrew discusses how psilocybin induces both structural and functional plasticity in the human and animal brain, potentially explaining the relief from depression that people experience. He also mentions a review that goes into detail about how neurons change their excitability patterns based on the activation of the serotonin two A receptor.+

20. Psilocybin's Therapeutic Potential

Psilocybin's Therapeutic Potential:Andrew discusses the exciting research on psilocybin's potential to treat major depression and intractable depression. He acknowledges the researchers who have pioneered the legal and funding efforts to explore this potential and provides a top contour summary of the clinical data.+
Psilocybin for Depression:Andrew discusses recent clinical studies that explore the use of psilocybin to treat depression. These studies involve one or two psilocybin sessions with dosages ranging from zero to 30 milligrams. Results show that a single dose of psilocybin can significantly improve baseline levels of depression, with the 25 milligram dose being the most effective.+
Psilocybin for Depression:Andrew discusses the effectiveness of psilocybin at treating treatment-resistant depression, with a focus on the optimal dosage and potential adverse effects. He also highlights the stability of the effects over time, with significant relief still present 12 weeks after a single dose of 25 milligrams of psilocybin.+

21. Psilocybin for Depression

Psilocybin for Depression:Andrew discusses the effectiveness of psilocybin as a treatment for depression, citing various clinical trials and studies that have shown promising results with a 25 to 30 milligram dose. He highlights that 60% to 75% of people with major depressive disorder who undergo psilocybin sessions report positive experiences with minimal adverse events.+
Psilocybin for Depression:Andrew discusses the results of clinical trials that show psilocybin administered in the context of supportive psychotherapy produces large, rapid, and sustained antidepressant effects. The effect sizes reported in this study were approximately 2.5 times greater than the effect sizes found in psychotherapy and more than four times greater than the effect sizes found in psychopharmacologic depression treatment studies.+

22. Psychedelics and Neuroplasticity

Andrew discusses the potential of psychedelics, particularly psilocybin, in enhancing neuroplasticity and providing relief for mental health issues. He highlights the importance of safety precautions and working with a trained physician when considering these compounds. The episode provides insights into the science and use of psilocybin and previews future episodes on other psychedelics.+

23. Supporting the Huberman Lab

Andrew shares ways to support the Huberman Lab podcast, including subscribing to their YouTube channel and podcast on Apple and Spotify, leaving a review, and checking out their supplement partner Momentous. He also mentions their free Neural Network Newsletter and social media accounts.+