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A Deep Dive into Psilocybin: Chemistry, Neuroplasticity, and Therapeutic Applications

• Psilocybin is a psychedelic compound that modifies consciousness and changes the way we perceive the world, our memories, thoughts, and feelings.

• Psilocybin mimics serotonin by activating a subset of serotonin receptors, leading to neuroplasticity of neural circuits associated with memory and perception.

• Psilocybin is one of many psychedelics, including LSD, DMT, and MDMA, but this episode will focus on psilocybin in particular.

• Silosin is the actual compound that goes into the brain to create all the changes in consciousness and rewiring effects associated with psilocybin.

• The structure of a psilocybin journey, including eye movements, music, and dosage, impacts the therapeutic effects of neuroplasticity.

• Proper psilocybin therapeutic approaches take place after the session, leading to long-standing improvements in mood, insight, creativity, and dissociation.

• Psilocybin is still a Schedule I drug in the United States, except for rare instances such as clinical studies and decriminalized areas like Oregon and Oakland.

• Safety issues include whether young people should consider psilocybin, dosage for those on antidepressants, and those at risk for psychotic episodes.

• Tryptamines, including psilocybin, closely resemble serotonin, a neuromodulator that changes the activity of other neurons and is involved in many daily functions.

• Serotonin is naturally made in the gut and brain, with separate independent sources, and impacts mood, pleasure, motivation, and appetite.

• Antidepressant medications that alter serotonin transmission in the brain often have side effects related to mood, libido, appetite, sleep, etc.

• Sponsors of the podcast include 8 Sleep, Roca, and HVMN Ketone IQ, providing tools for improving sleep, eyewear, and cognitive and physical performance.Understanding Psilocybin: The Science Behind its Therapeutic Potential

• Serotonin is involved in many different functions in the brain due to the presence of different serotonin receptors.

• Psilocybin closely resembles serotonin and binds selectively to the serotonin 2A receptor.

• The serotonin 2A receptor is responsible for triggering changes in neural circuitry that lead to therapeutic benefits of psilocybin.

• Psilocybin has specific effects compared to serotonin due to its selectivity for the serotonin 2A receptor.

• Clinical trials have shown that psilocybin outperforms standard therapy and antidepressants in providing relief from depression and other compulsive disorders.

• SSRIs and psilocybin both increase serotonin transmission in the brain, but psilocybin's therapeutic effects are due to its selective binding to the serotonin 2A receptor.

• Serotonin 2A receptors are located in the neocortex, including the prefrontal cortex and visual cortex, which explains the visual hallucinations triggered by psilocybin.

• Psilocybin sessions are more effective when the eyes are closed to limit focus on external visual perception and allow for inward reflection.

• Psilocybin use is contraindicated for people with existing or predisposition to psychotic or bipolar episodes.

• Psilocybin is a powerful drug that should only be used in proper clinical or research settings.

• Effective and safe doses of psilocybin have been established through clinical and research studies.

• Microdosing of psilocybin is a popular topic in non-clinical settings, but its effectiveness and safety have not been established through rigorous research.Understanding Psilocybin Dosages and the Components of a Therapeutic Journey

• Psilocybin used in clinical studies is synthetic and administered intravenously or orally in controlled doses ranging from 1 to 30 milligrams.

• Microdosing typically refers to daily doses of 1-3 milligrams, while macro or "heroic" dosing refers to 10-50 milligrams.

• One gram of magic mushrooms contains approximately 10 milligrams of psilocybin, with concentrations varying from 0.5% to 2% depending on strain and storage.

• The structure of a psilocybin journey involves "set and setting" - mindset and environment - to ensure safety and maximize therapeutic benefits.

• The setting should be safe and include at least one sober individual to prevent harm and guide the journey.

• Eye masks and lying down are recommended to enhance the internal experience, and music is a critical driver of the cognitive and emotional experience.

• The duration of a psilocybin journey is typically 4-6 hours, depending on dose, liver metabolism, and food intake.

• The journey includes a peak experience of maximal intensity, often associated with anxiety, which is part of the therapeutic process of ego dissolution.

• The therapeutic outcomes of psilocybin include positive rewiring of brain circuitry, improved mood, and adaptive behavior.

• Clinical studies have shown efficacy in treating depression, addiction, and compulsive disorders, but participants must abstain from antidepressants in the weeks leading up to the journey.

• The use of synthetic psilocybin and regulated dosages will become more common as psilocybin moves towards legalization and therapeutic use.

• Understanding the dosages and components of a psilocybin journey is crucial for safe and effective therapeutic outcomes.The Science of Psychedelic Journeys

• Psilocybin is a psychedelic compound found in certain mushrooms that can produce profound changes in perception and emotion.

• The experience of a psilocybin journey typically lasts several hours, with effects gradually tapering off after the peak experience.

• Clinical studies using psilocybin for the treatment of depression, addiction, and compulsive disorders use specific types of music to match and drive the journey's emotional and perceptual contours.

• The music played at the beginning of the session is typically classical and low volume, transitioning into percussion-heavy music during the peak experience, and then into softer music and nature sounds towards the end.

• The subjective experience of a psilocybin journey involves perceptual blending, or synesthesia, where different senses are merged and linked.

• Psilocybin activates the serotonin 2A receptor, which allows for more extensive communication between brain regions and reduces the modularity and hierarchical organization of brain function.

• Psilocybin also broadens the flow of sensory information into the brain, creating more blending of different senses and linking of emotional and perceptual experiences.

• The activation of serotonin 2A receptors is particularly strong in apical dendrites, the branches of pyramidal neurons that extend upwards and outwards, allowing for lateral communication across brain regions.

• There are four prominent theories of which brain networks are most activated during a psychedelic journey, but they all point to expanded functional connectivity of the brain.

• The controversy in the field relates to which network changes the most to explain the therapeutic outcomes of psychedelics.

• Psilocybin expands the functional connectivity of the brain both during and after the effects of the drug have worn off.

• A key paper in this area is "The effects of psilocybin and MDMA on between-network resting-state functional connectivity in healthy volunteers," which explores the brain areas active in a resting state and the effects of psilocybin and MDMA on functional connectivity.