Psilocybin
Psilocin
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a naturally occurring prodrug found in over 200 species of mushrooms, most notably Psilocybe cubensis. Upon ingestion, it is rapidly dephosphorylated to psilocin, which acts as a partial agonist at serotonin 5-HT2A receptors. Psilocybin has been used ceremonially for thousands of years and is currently undergoing a renaissance in clinical research for treatment-resistant depression, PTSD, end-of-life anxiety, and addiction.
Starting dose. 100-200mcg — (microdose) or 50-100mg dried mushroom equivalent
Morning, on an empty stomach. Do not dose in the evening (may disrupt sleep).
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
Psilocybin is a prodrug rapidly converted to psilocin by alkaline phosphatase in the gut and liver. Psilocin acts primarily as a partial agonist at serotonin 5-HT2A receptors, with additional affinity for 5-HT2C, 5-HT1A, and other serotonin receptor subtypes. 5-HT2A activation on cortical pyramidal neurons increases glutamate release and promotes neuroplasticity.
At macro doses, psilocin disrupts the default mode network (DMN) - the brain network associated with self-referential thinking and ego - leading to increased connectivity between brain regions that do not normally communicate. This is thought to underlie both the psychedelic experience and the therapeutic 'reset' effect observed in depression.
At microdoses, the mechanism is less clear but is hypothesized to involve sub-threshold 5-HT2A stimulation that promotes BDNF expression, dendritic spine growth, and enhanced neural plasticity without perceptual distortion. The Stamets Stack adds lion's mane (nerve growth factor promotion) and niacin (vasodilation for CNS delivery).
What to expect
Microdose Day 1-7: Subtle mood and perceptual changes on dose days. Establishing baseline response and optimal dose.
Evidence
References for this compound are being re-checked against their source records. We are not showing them until each one is confirmed to support the claim it sits under.
Interactions & stacking
Two different questions: what is documented about running these together, and what is documented about drawing them into the same syringe. A good pharmacological partner can still have to be pinned separately.
Documented together
Keep separate
Check any specific pair in the Stack & Interaction Checker, which answers both questions separately. Absence of a documented conflict is not evidence of safety.
Pharmacokinetics
Psilocin, active metabolite
Oral (psilocin plasma peak)
Complete clearance of psilocin
Oral (first-pass conversion of psilocybin to psilocin)
(macro-dose perceptual effects). Microdose effects are sub-perceptual and difficult to time precisely.
Hepatic (UGT1A10 glucuronidation of psilocin, MAO-A oxidative deamination). Renal excretion of metabolites. CYP2D6 polymorphisms affect metabolism rate.
Storage. Store dried mushroom material in airtight containers with desiccant at room temperature, away from light and moisture. Synthetic psilocybin is stored at -20C for long-term stability. Capsules should be kept cool and dry.
Regulatory status
Schedule I controlled substance in the United States (DEA). FDA Breakthrough Therapy designation for treatment-resistant depression (2018, COMPASS Pathways) and major depressive disorder (2019, Usona Institute). Decriminalized in several US cities (Denver, Oakland, Seattle, etc.) and Oregon (Measure 109 - regulated therapeutic use since 2023). Illegal in most countries worldwide.
Put it to work
Calculate, log & track
Open Psilocybin straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
Open Psilocybin in the app →Go deeper
The guide & community
The complete Psilocybin walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
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