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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.
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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.