Psilocybin, Legal Considerations

Sponsors: Eight Sleep, ROKA, HVMN

Psilocybin Becomes Psilocin in the Gut, Serotonin

The Serotonin 2A Receptor, Therapeutic Outcomes SSRIs vs. Psilocybin

Serotonin Receptor Expression; Visual Hallucinations & Eyes Closed

Safety & Cautions for Specific Patient Populations

Sponsor: AG1 (Athletic Greens)

Psilocybin, “Magic Mushrooms” Dosing, Micro-Dosing, “Heroic Doses”

Psychedelic Journey: Set, Setting & Support

Music & the Psilocybin Journey; Duration of Effects

Psilocybin & the Brain: Subjective Experiences, Perception

Sponsor: LMNT

Brain Networks & Therapeutic Outcomes

Creativity; Music, Emotionality & Psychedelic Journeys

Depression & Psychedelics as Neuroplasticity “Wedge”

Positive Psychedelic Journeys, Unity, “Oceanic Boundlessness”

“Bad Trips”, Anxiety & Physiological Sighs

Therapeutic Use of Psilocybin

Neuroplasticity, Structural Brain Changes & Psilocybin

Psychedelics: Therapeutic Breakthroughs & Depression

Combining Psilocybin Therapy & Talk Therapy, Antidepressant Effects

Psilocybin Experience & Mental Health

Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Neural Network Newsletter, Social Media

The Huberman Lab Podcast discusses science and science-based tools for everyday life. In this episode, psilocybin, a psychedelic with potential therapeutic applications for mental health issues, is discussed. The episode covers what psilocybin is, how it works at the molecular and cellular level, clinical effects, dosages, and conditions of a psilocybin journey. Safety issues are discussed, including for young people and those at risk for psychotic episodes. The podcast aims to provide free information about science and science-related tools to the general public. The episode is sponsored by various companies, and the speaker discusses the benefits of their products. Psilocybin has positive effects on creativity and experience of life. The quality of the experience may be the critical determinant of therapeutic success. Psilocybin induces neuroplasticity in the brain, which involves the addition or strengthening of new neural connections or the elimination or weakening of other neural connections. Psilocybin is being researched for therapeutic use in various disorders, with major depression and treatment-resistant depression showing the most promising results. Combining drug therapy with talk therapy is more effective than either treatment alone. The science and use of psilocybin will be revisited in future episodes.

- The Huberman Lab Podcast discusses science and science-based tools for everyday life.
- The episode focuses on psilocybin, a psychedelic that modifies the psyche and changes levels of consciousness.
- Psilocybin has potential therapeutic applications for mental health issues such as depression, alcohol abuse disorder, and addictions.
- The episode covers what psilocybin is, how it works at the molecular and cellular level, clinical effects, dosages, and conditions of a psilocybin journey.
- Psilocybin is still a Schedule I drug and illegal in most areas, and safety issues are discussed, including for young people and those at risk for psychotic episodes.

- The podcast is separate from the speaker's teaching and research roles at Stanford.
- The podcast aims to provide free information about science and science-related tools to the general public.
- The episode is sponsored by Eight Sleep, Roka, and HVMN Ketone IQ, with discount codes provided for each sponsor.
- The speaker discusses the benefits of Eight Sleep's smart mattress covers, Roka's high-quality eyeglasses and sunglasses, and HVMN Ketone IQ's ketone supplement.

- Psilocybin causes perceptual blending and synesthesia, where different senses merge and influence each other.
- Psilocybin activates serotonin 2A receptors, which increases communication across the brain and reduces the modularity of brain function.
- Psilocybin broadens the flow of sensory information into the brain, allowing for more blending of different senses and interoception.
- Serotonin 2A receptor activation allows for less precise and less hierarchical activation of brain circuitry.
- Under the influence of psilocybin, patterns of activation in the brain are less channeled and less hierarchical.

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- There are four prominent theories about which brain networks are most activated during a psilocybin or other psychedelic journey.
- Psilocybin expands the functional connectivity of the brain while one is under the influence of psilocybin, and some of that expanded functional connectivity persists after the effects of psilocybin have worn off.
- Psilocybin leads to adaptive rewiring of the brain, which allows people to function better in their lives.
- Psilocybin increases connectivity in the brain, but it does not seem to disrupt memory.
- Psychedelics and psilocybin are exciting from a therapeutic standpoint because they can lead to positive rewiring or adaptive rewiring of neural tissue.

- Psilocybin has positive effects on creativity and experience of life
- A study found that psilocybin changes one's emotional response to music, even after the session
- 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
- The study included subjective reports and neuroimaging data to support the findings.

1. The podcast has covered different types of meditation and patterns of thinking to increase creativity.
2. Studies on the neural circuitry related to creativity and psychedelics are limited, but studies on changes in emotionality and responses to music provide a template for what may be happening during and after psilocybin journeys.
3. Psilocybin can rewire our relationship to things more broadly by invoking new patterns of learning and considerations about what might be possible.
4. Psilocybin initiates the neuroplasticity process, but it is not the neuroplasticity process itself. It is like a wedge that gets underneath the boulder that is the neuroplasticity that gets rolling forward.

- Psilocybin journeys are characterized by phrases like letting go, ego dissolution, and feelings of connectedness.
- A positive psychedelic experience is correlated with a sense of oceanic boundlessness, which is a feeling of mystical connectedness with one's environment.
- The intensity of the oceanic boundlessness experience is positively correlated with positive therapeutic outcomes, such as relief from major depression.
- During the peak of the psilocybin journey, people may experience ego dissolution, anxiety, and fear, but guides can help them move through these experiences.
- The experience of unity, spirituality, bliss, and insights during the psilocybin journey is positively correlated with positive therapeutic outcomes.

- Psilocybin treatment led to complex imagery and hallucinations in all participants in the study.
- Letting go and experiencing some anxiety during the psilocybin journey seems to be important for positive therapeutic outcomes, but extreme levels of anxiety are negatively correlated with relief from depression.
- Well-trained guides who understand the contour of the psychedelic journey and are trained in how to help somebody with their anxiety in real-time are important.
- Real-time respiration tools, such as the physiological sigh, can be used to reduce anxiety during the psychedelic session and promote positive therapeutic outcomes.
- The quality of the experience may be the critical determinant of therapeutic success.

- The text discusses a paper titled "Therapeutic Use of Psilocybin, Practical Considerations for Dosing and Administration" that provides information on the pharmacology of psilocybin, the contour of a psilocybin session, dosage, contraindications, and adverse events.
- The paper highlights that psilocybin is not recommended for pregnant or breastfeeding women and people with a predisposition to psychosis.
- The most evidence for positive therapeutic outcomes with psilocybin is for cancer-related depression, cancer-related anxiety, and treatment-resistant depression.
- There is also some evidence for improvement in alcohol use disorder independence and tobacco addiction.
- The least amount of evidence is for obsessive-compulsive disorder, cluster headaches and migraines, and demoralization due to AIDS diagnosis.

- Psilocybin induces neuroplasticity in the brain, which involves the addition or strengthening of new neural connections or the elimination or weakening of other neural connections.
- Neurogenesis, the production of new neurons, is not the dominant mode of changing neural circuitry in adult humans, and psilocybin does not significantly increase neurogenesis.
- Psilocybin induces the growth of dendrites and dendritic spines, which are the sites of new excitatory connections in neurons, and this may explain the relief from depression that people experience.
- Psilocybin induces both structural and functional changes in brain circuitry in both animal studies and humans, and the underlying basis for this may be the addition of new dendritic spines on pyramidal neurons.
- Multiple mechanisms are likely to be involved in the neuroplasticity induced by psychedelics, including psilocybin.

- Psilocybin is being researched for therapeutic use in various disorders.
- Major depression and treatment-resistant depression show the most promising results.
- Clinical studies involve one or two psilocybin sessions with dosages ranging from 10 to 30 milligrams.
- A single dose of 25 milligrams of psilocybin provided significant relief from treatment-resistant depression in a particular patient population.
- Adverse events were observed in every group, with higher dosages having a greater chance for adverse events.

- Psilocybin is a tryptamine, similar in structure to serotonin
- Serotonin is a neuromodulator that affects various functions in the brain and body
- Serotonin binds to different receptors, causing various effects
- Psilocybin, when taken, leads to specific experiences and improvements in mood and disorders, despite its similarity to serotonin

- Psilocybin treatment in the 25-30 milligram range has been found to be effective for long-lasting relief from depression in clinical trials.
- Studies have compared psilocybin to other antidepressants and therapies, and the results show that psilocybin is more effective.
- Psilocybin administered in the context of supportive psychotherapy produced large, rapid, and sustained antidepressant effects, with effect sizes four times greater than typical SSRIs or other pharmacology.
- Combining drug therapy with talk therapy is more effective than either treatment alone.
- Psilocybin can induce neuroplasticity and changes in emotionality and perceptual experience, providing remarkable relief from major depression and other psychiatric issues.

- The episode discussed the effects of psilocybin on depression and brain circuitry.
- The potential for psilocybin to provide relief for mental health issues is exciting, but safety precautions must be taken.
- Psilocybin is an exciting and interesting compound for basic and clinical reasons, but it is still a preliminary area of research.
- The science and use of psilocybin will be revisited in future episodes.

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- Psilocybin mainly binds to and activates the serotonin 2A receptor in the brain, which allows for specific changes in neural circuitry.
- Clinical trials show that psilocybin outperforms standard therapy and SSRIs in providing relief for major depression.
- The selectivity of psilocybin to bind to the serotonin 2A receptor is what leads to its therapeutic effects.
- Understanding the serotonin 2A receptor and how psilocybin binds to it is important for understanding how psilocybin works and proper dosing profiles.
- Psilocybin can lead to improvements in mood, relief from compulsive disorders, and enhanced creativity.

- Serotonin is released naturally in the brain and binds to different receptors, while SSRIs increase the amount of serotonin available to exert its effects.
- Psilocybin selectively and strongly binds to the serotonin 2A receptor, which is highly expressed in the neocortex, including the prefrontal cortex and visual cortex.
- Psilocybin triggers visual hallucinations due to its high expression in the visual cortex, and it is recommended to have eyes closed during a psilocybin session to limit focus on external changes in visual perception and allow for inward reflection.
- Psilocybin has potential therapeutic benefits for improving mood, creativity, and cognition.

- Psilocybin use requires certain conditions and supports for therapeutic usefulness
- Psilocybin use is contraindicated for people with existing or predisposition to psychotic or bipolar episodes
- Information provided is focused on adults aged 25 years or older
- Psilocybin use is still illegal and only used in proper clinical and research settings
- Psilocybin is a powerful drug with longstanding changes after its effects wear off

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- Psilocybin dosing and microdosing is a topic with a lot of loose thinking in non-clinical and non-research communities.
- In clinical studies, safe and effective doses of psilocybin range from 1-3 milligrams per day for microdosing, to 10 milligrams or 25-30 milligrams for macro or heroic dosing.
- The concentration of psilocybin in most magic mushrooms is about 1%, meaning one gram of mushrooms contains approximately 10 milligrams of psilocybin.
- The so-called heroic dose refers to a five gram dose of mushrooms, which translates to 50 milligrams of psilocybin.
- The concentration of psilocybin in different strains of mushrooms and batches can vary greatly, making sourcing important.

- The author discusses the structure of a psilocybin journey and its relationship to brain chemistry.
- The set and setting of a psilocybin journey are important for safety and positive outcomes.
- The setting should be safe and include responsible individuals who are not under the influence of psychedelics.
- The person taking psilocybin should ideally be seated or lying down with their eyes covered to combine visual hallucinations with thought processes.
- The scientific data suggests that subdued settings with one or two guides are most effective for positive rewiring of brain circuitry.

- Safety, eye mask, and music are important factors in creating a positive experience during a psilocybin journey.
- Music is a major driver of the cognitive and emotional experience during the journey.
- The duration of the journey is typically 4-6 hours and anxiety is a component of the peak experience.
- The music played during the journey transitions from classical to intense percussion to softer music and nature sounds. 
- The person taking psilocybin is typically lying down with an eye mask and guides present for support and safety.

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