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

Andrew Huberman・100 minutes read

Psilocybin has therapeutic potential for mental health issues, binds to serotonin 2A receptors, induces neuroplasticity, and shows promise in treating depression and addiction, with proper setting and dosage being crucial for beneficial outcomes. Safety considerations include age, previous antidepressant use, and risk of psychotic episodes, with studies showing that psilocybin has lasting positive effects on creativity, emotional responses to music, and brain connectivity, making it a promising treatment option.

Insights

  • Psilocybin, a psychedelic, shows promise in treating depression and addiction through neuroplastic changes in brain circuits.
  • Proper therapeutic use of psilocybin involves understanding post-session effects for long-lasting improvements in mood and emotional regulation.
  • Conditions of a psilocybin journey, such as dosage and setting, significantly impact therapeutic outcomes and neuroplastic changes.
  • Safety considerations for psilocybin use include age, previous antidepressant use, and risk of psychotic episodes, especially for individuals with a family history of psychosis.
  • Psilocybin's distinct mechanism of action, binding to serotonin 2A receptors, sets it apart from other treatments like SSRIs, explaining its therapeutic potential.
  • Psilocybin induces neuroplasticity by adding new neural connections, with potential for treating conditions like depression and addiction.

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Recent questions

  • What is psilocybin and its potential therapeutic applications?

    Psilocybin is a psychedelic compound that alters consciousness and perception, showing promise in treating mental health issues like depression and addiction. It mimics serotonin, activating specific receptors to induce neuroplasticity in brain circuits related to memory and perception. Proper therapeutic use involves understanding post-session effects for long-lasting improvements in mood, insight, creativity, and emotional regulation.

  • How does psilocybin affect the brain's neural circuitry?

    Psilocybin, converted to psilocin in the brain, binds to serotonin 2A receptors, triggering visual hallucinations and changes in neural activity. It broadens sensory information flow, reduces brain modular organization, and increases communication between brain regions. This leads to expanded functional connectivity, persisting even after the drug's effects wear off, with therapeutic implications for mental health.

  • What are the safety considerations for psilocybin use?

    Safety considerations for psilocybin use include age, previous antidepressant use, and the risk of psychotic episodes, especially for individuals with a family history of psychosis. Understanding the chemistry, cell biology, and neural changes induced by psilocybin is crucial for making informed decisions about its potential therapeutic benefits.

  • How do set and setting influence a psilocybin journey?

    Set and setting, including dosage, music, eye openness, and environment, play a crucial role in determining the therapeutic outcomes and neuroplastic changes during a psilocybin journey. Proper dosage, a safe environment, and well-trained guides are essential for a successful session, with music transitioning to shape emotional and cognitive experiences.

  • What are the subjective experiences and outcomes of a psilocybin journey?

    Subjective experiences during a psilocybin journey include perceptual blending, synesthesia, ego dissolution, and feelings of connectedness. Positive therapeutic outcomes are linked to experiences like oceanic boundlessness, unity, spirituality, bliss, and insights, correlating with relief from major depression. Ego dissolution and mystical experiences are crucial components influencing therapeutic success.

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Summary

00:00

Psilocybin: Psychedelic Therapy for Mental Health

  • Psilocybin is a psychedelic that alters consciousness and perception, with potential therapeutic applications for mental health issues like depression and addiction.
  • Psilocybin mimics serotonin by activating specific serotonin receptors, leading to neuroplasticity in brain circuits related to memory and perception.
  • Psilocybin is just one of many psychedelics, including LSD, DMT, and MDMA, each with unique effects and mechanisms of action.
  • Psilocybin is converted to psilocin in the brain, which is the compound responsible for the psychedelic effects and neuroplastic changes associated with psilocybin.
  • Proper therapeutic use of psilocybin involves understanding the post-session effects, which can lead to long-lasting improvements in mood, insight, creativity, and emotional regulation.
  • The conditions of a psilocybin journey, such as dosage, setting, music, and eye openness, play a crucial role in determining the therapeutic outcomes and neuroplastic changes.
  • Psilocybin is still classified as a Schedule I drug in most areas, except for specific therapeutic settings like in Oregon for depression and addiction treatment.
  • Safety considerations for psilocybin use include age, previous antidepressant use, and risk of psychotic episodes, especially for individuals with a family history of psychosis.
  • Understanding the chemistry, cell biology, and neural changes induced by psilocybin is essential for making informed decisions about its potential therapeutic benefits.
  • Various sponsors like Eight Sleep, ROKA, and HVMN Ketone-IQ offer products related to sleep quality, eyewear, and ketone supplementation, respectively, that can enhance overall well-being.

11:49

Psilocybin: Serotonin 2A Receptor Activation Therapy

  • Psilocybin is a tryptamine, part of a group that includes DMT and 5-MeO-DMT, closely resembling serotonin structurally.
  • Serotonin is a neuromodulator, naturally produced in the brain and gut, affecting various functions like mood, pleasure, and motivation.
  • Serotonin binds to receptors, influencing neuron activity, growth factors release, gene expression changes, and more.
  • Psilocybin, resembling serotonin, mainly binds to and activates the serotonin 2A receptor, leading to specific changes in neural circuitry.
  • Psilocybin's selectivity in binding to the serotonin 2A receptor triggers visual hallucinations and other changes in neural activity.
  • Clinical trials show psilocybin's effectiveness in treating depression surpasses standard therapy and SSRIs.
  • Psilocybin's specific binding to serotonin 2A receptors leads to significant relief from depression and other disorders.
  • Understanding the serotonin 2A receptor's location in the brain, particularly in the neocortex, is crucial for comprehending psilocybin's effects.
  • Psilocybin's ability to activate serotonin 2A receptors in the prefrontal cortex and visual cortex explains its impact on mood, creativity, and visual hallucinations.
  • Psilocybin's distinct mechanism of action, selectively binding to serotonin 2A receptors, sets it apart from SSRIs and explains its therapeutic potential.

24:37

Psilocybin: Visual Hallucinations and Safety Considerations

  • Psilocybin leads to visual hallucinations due to its strong binding to serotonin 2A receptors in the visual cortex.
  • To ensure a beneficial psilocybin session, it is recommended to keep eyes closed for most of the session.
  • Open-eyed experiences during psilocybin use often focus on altered perceptions of the external environment.
  • Visual hallucinations with eyes closed can include fracturing, melting, or morphing of objects and faces.
  • Using an eye mask or ensuring closed eyes during the session can enhance introspection and emotional processing.
  • Safety precautions are crucial, especially for individuals with a history of psychotic or bipolar episodes.
  • Psilocybin use is typically focused on adults aged 25 and older due to completed brain development.
  • Psilocybin dosing in clinical studies ranges from 1 to 30 milligrams, with microdosing often repeated daily.
  • Psilocybin content in mushrooms is approximately 1%, translating to about 10 milligrams per gram of mushrooms.
  • "Heroic doses" of psilocybin, often discussed informally, refer to around 50 milligrams or 5 grams of mushrooms.

37:01

Psilocybin Trials: Safety, Setting, and Experience

  • Clinical trials have shown the effectiveness of psilocybin for treating depression and addictive disorders.
  • Set and setting are crucial factors in determining the outcome of a psilocybin journey.
  • Safety measures include ensuring individuals are 25 years or older and not on antidepressants impacting serotonin.
  • Abstaining from antidepressants before a psilocybin journey is essential.
  • The setting for a psilocybin journey should be safe and supervised by individuals not under the influence.
  • Individuals on a psilocybin journey should ideally be seated or lying down with their eyes covered.
  • Music plays a significant role in shaping the emotional and cognitive experience during a psilocybin journey.
  • The duration of a psilocybin journey typically lasts 4 to 6 hours, with a peak component of intense emotions and anxiety.
  • Music in clinical studies transitions from classical to intense percussion during the peak, then to softer melodies and nature sounds.
  • Subjective experiences on psychedelics include perceptual blending and synesthesia, where senses merge in unusual ways.

49:57

Psilocybin alters brain connectivity for therapeutic benefits.

  • Under the influence of psilocybin, individuals may experience perceptual blending, such as hearing music that seems to be controlled by their breath or visual perceptions merging with auditory experiences.
  • Some people may find that physical actions, like rubbing their fingertips on a surface, can alter their perception of music, with hand movements affecting the frequency of sound.
  • Psilocybin, when converted to psilocin, activates serotonin 2A receptors, leading to changes in perception and emotions through increased communication between neurons.
  • Pyramidal neurons, shaped like pyramids, have dendrites that extend out to communicate with other neurons, particularly in areas above them, where serotonin 2A receptors are present.
  • Psilocybin reduces the modular organization of the brain, increasing communication between different brain regions and integrating functions that are usually separate.
  • Psilocybin broadens the flow of sensory information from the periphery to higher-order brain centers, leading to a blending of senses and emotions.
  • Thalamic gating, influenced by psilocybin, allows for a broader flow of sensory information through the thalamus, resulting in less hierarchical brain activation.
  • Psilocybin increases communication across the brain, affecting the default mode network and expanding functional connectivity between brain regions.
  • The effects of psilocybin on brain networks have therapeutic implications, with expanded functional connectivity persisting even after the drug's effects wear off.
  • Research on the effects of psilocybin and MDMA on resting-state functional connectivity in healthy volunteers supports the idea of expanded brain connectivity during and after psychedelic experiences.

01:02:04

Psychedelics Enhance Brain Connectivity and Function

  • Study conducted in Robin Carhart-Harris' laboratory at UCSF focused on psychedelics and their effects on the brain and therapeutic applications.
  • Explored brain activity in healthy volunteers using brain imaging, particularly the default mode network.
  • Volunteers were given psilocybin or MDMA, leading to increased connectivity between brain areas, indicating enhanced lateral connectivity and communication.
  • Rewiring of the brain through psychedelics is aimed at adaptive changes for improved functioning, not just random rewiring.
  • Numerous studies in humans have shown that psilocybin expands brain connectivity while allowing individuals to function normally.
  • Therapeutic use of psilocybin for depression rarely leads to long-term memory issues, despite increasing brain connectivity.
  • Psilocybin enhances creativity and life experiences, as seen in studies on music perception post-psilocybin therapy for depression.
  • Psilocybin changes emotional responses to music, allowing individuals to experience joy and reducing sadness even after the drug wears off.
  • Psilocybin rewires brain connections related to emotion and auditory perception, leading to lasting positive effects on music enjoyment.
  • Psilocybin's effects on creativity and life experiences are linked to expanded brain connectivity, allowing for new learning and relationships between sensory and emotional states.

01:14:31

Psilocybin's Impact on Learning and Emotion

  • Negative outcomes often follow a pattern of cause and effect, leading to new patterns of learning.
  • Psilocybin can induce new considerations and potentially rewire emotion centers in the brain.
  • Subjective experiences with psilocybin can lead to reconsidering previous beliefs and evaluating new possibilities.
  • Psilocybin acts as a chemical activating receptors in the brain, initiating neuroplasticity processes.
  • The journey on psilocybin is compared to a boulder rolling, with the drug acting as a wedge for neuroplasticity.
  • Key experiences during a psilocybin journey include letting go, ego dissolution, and feelings of connectedness.
  • Positive therapeutic outcomes from psilocybin are linked to subjective experiences like oceanic boundlessness.
  • The intensity of oceanic boundlessness correlates with positive therapeutic outcomes, particularly relief from major depression.
  • During a psilocybin journey, the peak often involves experiences of ego dissolution and intense emotions.
  • Subjective measures like unity, spirituality, bliss, and insights during a psilocybin journey correlate with positive clinical outcomes for depression relief.

01:26:46

Navigating Anxiety in Psilocybin Therapy Journeys

  • During the peaking phase of a psilocybin journey, individuals may experience discomfort, fear, increased heart rate, and elevated blood pressure.
  • Guides should not exacerbate stress but help individuals navigate through anxiety and ego dissolution for an effective therapeutic session.
  • Anxiety levels during a psilocybin journey are inversely correlated with positive therapeutic outcomes.
  • Non-responders to psilocybin therapy tend to have higher anxiety ratings compared to responders.
  • Letting go and experiencing ego dissolution are crucial for a successful psychedelic journey, but extreme anxiety can hinder positive outcomes.
  • Proper dosage, a safe environment, and well-trained guides are essential for a successful psilocybin session.
  • Real-time tools like breathing techniques, specifically the physiological sigh, can help individuals reduce anxiety during a psychedelic session.
  • Incorporating breathing techniques in psychedelic sessions can empower individuals to self-direct their calmness and manage anxiety levels effectively.
  • Ego dissolution and mystical experiences are key components of a positive psilocybin journey, influencing therapeutic success.
  • Psilocybin shows promise in treating conditions like cancer-related depression, anxiety, treatment-resistant depression, alcohol use disorder, and tobacco addiction, with varying levels of evidence for each.

01:39:11

Psilocybin induces neuroplasticity in brain circuitry.

  • Neurogenesis, the production of new neurons in the dentate gyrus subregion of the hippocampus, occurs in humans but is not the primary way neural circuitry changes in adult humans.
  • Neurogenesis may play a role in adolescence and young childhood, as well as before birth, but the brain changes through various methods, including adding new neurons and altering connections.
  • Psilocybin and other psychedelics induce neuroplasticity mainly through adding or strengthening new neural connections or weakening existing ones.
  • Studies on psilocybin-induced neuroplasticity focus on animal models, particularly mice and rats, with some research on primates and humans.
  • Psilocybin induces neuroplasticity by adding novel connections in pyramidal neurons in the frontal cortex, other areas of the cortex, and possibly subcortical regions.
  • Psilocybin triggers the growth of dendrites and dendritic spines, resembling mushroom-shaped protrusions, which serve as sites for new excitatory connections.
  • Psilocybin induces rapid and persistent growth of dendritic spines in the frontal cortex, with these new connections persisting beyond the drug's effects.
  • Reduction in dendritic spines in the frontal cortex is observed in depressed patients, while treatments relieving depression correlate with increased spine growth.
  • Psilocybin induces both structural and functional plasticity in the human brain at therapeutic doses, with animal studies often using higher doses than humans.
  • Psilocybin induces structural and functional changes in brain circuitry, altering network connectivity and potentially explaining relief from depression through the growth of new connections.

01:51:08

Psilocybin Therapy for Depression: Recent Findings

  • Studies on using psilocybin to treat depression began around 2006 in select laboratories and increased significantly between 2018 and now.
  • Recent papers on clinical studies involving psilocybin sessions were published in prestigious journals like Phenomenal Journals, New England Journal of Medicine, and Journal of the American Medical Association Psychiatry.
  • Clinical studies typically involved one or two psilocybin sessions with dosages ranging from 0 milligrams (placebo) to 30 milligrams.
  • A study on single-dose psilocybin for treatment-resistant depression showed significant relief with the 25 milligram dose compared to lower doses.
  • Higher dosages of psilocybin led to greater relief from depressive symptoms but also increased the likelihood of adverse events, with the 25-milligram group experiencing the highest number.
  • A single dose of 25 milligrams of psilocybin provided significant and long-lasting relief from treatment-resistant depression in a majority of participants.
  • Psilocybin therapy combined with supportive psychotherapy produced rapid and sustained antidepressant effects, with effect sizes significantly greater than traditional psychotherapy or psychopharmacologic treatments.
  • Combining drug therapy with talk therapy, as seen in psilocybin therapy, was found to be more effective in treating major depressive disorder than either intervention alone.
  • Psilocybin therapy induced neuroplastic events and changes in brain connectivity, leading to relief from depression and potentially other psychiatric issues.
  • The discussion highlighted the mystical and subjective effects of psilocybin, emphasizing its potential for inducing neuroplasticity and long-lasting relief from mental health conditions.

02:04:03

"Psilocybin Journeys: Enhancing Learning and Neuroplasticity"

  • Psilocybin, when selectively activated, is linked to neocortex expansion and can enhance thinking and learning in 4-6 hour sessions known as Psilocybin Journeys.
  • The Huberman Lab podcast delved into the topic of psilocybin, exploring its mechanisms, effects on brain circuitry, safety considerations, and therapeutic potential for mental health issues.
  • Psilocybin's potential for inducing neuroplasticity excites researchers, but caution is advised for individuals with certain predispositions or conditions, emphasizing the need for safe and controlled use under trained supervision.
  • The podcast highlights the preliminary yet promising nature of psilocybin research, with plans to explore other psychedelics like LSD, ketamine, and MDMA in future episodes, while also encouraging support through subscriptions and sponsorships.
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