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.

Typical use: 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.

What this is

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

Dose & route

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

Citations

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Common questions

Does Psilocybin work?
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.
Is Psilocybin safe?
Psilocybin has a med risk profile in published human data. 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. This is not medical advice — see the disclaimer.
What is the typical dose for Psilocybin?
1-5 g dried mushrooms (recreational); 25 mg synthetic psilocybin (clinical); 50-500 mg 'microdose'
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.