Rankings / Mood, Anxiety & Stress

Psilocybin

Mood, Anxiety & Stress · Classic psychedelic / 5-HT2A agonist

Tier B

Reviewed by Read Off Label · Last reviewed · How we grade

psychedelicbdnfcontrolled-substance
6.6 / 10
Tier B
Ev 8 Bn 6.5 Sf 5

Bottom line

Read Off Label grades Psilocybin as B (6.6/10) based on strong evidence, med-high benefit magnitude, and a med-risk safety profile.

Compass COMP360 Ph3 COMP005 (June 2025) met primary endpoint (-3.

Studied, labeled, or reported-use context: 1-5 g dried mushrooms (recreational); 25 mg synthetic psilocybin (clinical); 50-500 mg 'microdose' — Schedule I US (DEA); legal in regulated contexts: Oregon (Measure 109), Colorado (Prop 122), decriminalized in some cities; legal for therapy in Australia; not individualized guidance.

What the evidence says

Compass COMP360 Ph3 COMP005 (June 2025) met primary endpoint (-3.6 MADRS diff, p<0.001); COMP006 (Feb 2026) confirmed durability at 26 weeks; NDA rolling submission targeted Q4 2026 with possible approval late 2026/early 2027. Microdosing trials consistently fail to beat placebo despite anecdotes. Griffiths/Carhart-Harris foundational work.

Mechanism

Prodrug to psilocin; 5-HT2A receptor agonist (primary); promotes neuroplasticity via BDNF, dendritic spine formation; acute ego dissolution; default mode network modulation

Studied, labeled, or reported dose & route

1-5 g dried mushrooms (recreational); 25 mg synthetic psilocybin (clinical); 50-500 mg 'microdose'

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

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Common questions

What does the evidence show about Psilocybin's effects?
Read Off Label rates the evidence for Psilocybin as Strong and the benefit magnitude as med-high, producing an overall grade of B (6.6/10). Compass COMP360 Ph3 COMP005 (June 2025) met primary endpoint (-3.
What safety findings are reported for Psilocybin?
Psilocybin has a med risk profile in the database. Med (HPPD rare, 'bad trips', cardiovascular caution; contraindicated with psychosis risk) Legal status: Schedule I US (DEA); legal in regulated contexts: Oregon (Measure 109), Colorado (Prop 122), decriminalized in some cities; legal for therapy in Australia.
What doses or routes are reported for Psilocybin?
1-5 g dried mushrooms (recreational); 25 mg synthetic psilocybin (clinical); 50-500 mg 'microdose' This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
How does Psilocybin work?
Prodrug to psilocin; 5-HT2A receptor agonist (primary); promotes neuroplasticity via BDNF, dendritic spine formation; acute ego dissolution; default mode network modulation

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.