Psilocybin for Health & Longevity - Quick Reference Sheet

Psilocybin for Health & Longevity

Created on 08/21/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 – Audit

One supervised dose of this mushroom compound shifts mood and behavior for weeks to months. Evidence is strongest for depression symptoms; thinner for heavy drinking, tobacco, cocaine, and serious-illness distress. Common harms fade within a day or two. Participants can tell what they took, and funders often have a stake. The slowed-aging claim rests on cells and mice. (Full Review)

Protocol

Standard supported-session model
25 mg oral, one session
Synthetic psilocybin; living-room setting, eyeshades and music; two monitors for six to eight hours.
Two-dose model
Two sessions, 3–5 weeks apart
25 mg then 25–40 mg per 70 kg, embedded in twelve weeks of psychotherapy.
Time of day
9:00 to 10:00 in the morning
Standard timing; acute effects resolve by early evening rather than into the night.
Time to effect
Depressive symptoms
Day 2
Largest separation from control at weeks two to three; durability in weeks to months.
Heavy drinking
Over eight months
Two supervised doses alongside twelve weeks of manualized psychotherapy.
Well-being and trait openness
Beyond one year
Openness gains persisted only after a complete mystical-type experience.

Benefits

Contraindications
  • Monoamine oxidase inhibitors (phenelzine, tranylcypromine, moclobemide)
  • Personal or first-degree family history of schizophrenia, schizoaffective, or bipolar I disorder
  • Uncontrolled hypertension (at or above 140/90 mmHg despite treatment)
  • Unstable cardiovascular disease (infarction within 6 months, unstable angina, NYHA III–IV heart failure, moderate-or-greater valve regurgitation)
  • Corrected QT above 450 ms (men) or 470 ms (women)
  • Seizure disorder, or current lithium therapy
  • Child-Pugh Class B or C liver impairment
  • Pregnancy and breastfeeding
  • Active suicidal ideation with intent or plan
Key Interactions
  • Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (escitalopram, sertraline, venlafaxine)
  • Tricyclic antidepressants (amitriptyline, imipramine)
  • Antipsychotics (risperidone, olanzapine, quetiapine)
  • Over-the-counter serotonergic medicines (dextromethorphan, high-dose diphenhydramine)
  • Serotonergic supplements (St John's wort, 5-hydroxytryptophan, L-tryptophan, S-adenosylmethionine)
  • Monoamine-oxidase-inhibiting botanicals (Syrian rue, harmala alkaloids)
  • Stimulants (amphetamine, methylphenidate, high-dose caffeine)
  • Other interventions (cannabis, alcohol, other psychedelics)

Risk & Side Effects

  • High: Nausea and vomiting; headache and dizziness; acute anxiety and challenging experience; transient rise in blood pressure and heart rate
  • Medium: Symptom worsening and suicidal ideation; precipitation of mania, hypomania, or psychosis
  • Low: Hallucinogen persisting perception disorder; transient cognitive and functional impairment
  • Speculative: Cardiac valvulopathy with repeated low-dose exposure; adverse effects in the postpartum period; tumor-promoting potential of delayed senescence

Monitoring

Marker Target Why
Resting blood pressure Below 120/80 mmHg Psilocybin transiently raises it; a high baseline matters
Corrected QT interval (QTc) Below 440 ms (men), below 460 ms (women) Arrhythmia vulnerability during the sympathetic surge
hs-CRP Below 1.0 mg/L Systemic inflammation psilocybin is proposed but not shown to lower
ALT Below 25 U/L (men), below 20 U/L (women) Hepatic clearance of psilocin; impairment raises exposure
eGFR Above 90 mL/min/1.73 m² Metabolites renally excreted; reduced clearance prolongs exposure
PHQ-9 score 4 or below Primary success criterion where depression was the reason for dosing
GAD-7 score 4 or below Anxiety component, which often moves independently of mood
Trait openness No established target; track change from own pre-session score Most reproducible personality change after high-dose exposure
Epigenetic age No established target; track change from own baseline, one provider Only human-measurable proxy for the geroprotection hypothesis

Cadence: Baseline 2–4 weeks before a session; blood pressure and pulse before dosing and at 30, 60, 90, 120 minutes; symptom scales at day 2, day 8, week 3, week 6, then quarterly through year 1; blood pressure, liver enzymes, and inflammatory markers annually with repeated exposure; echocardiogram only after frequent sustained low-dose exposure.

Qualitative Assessment

  • Sleep quality and how rested mornings feel, week by week
  • Energy and drive through the afternoon, distinct from mood
  • Emotional reactivity — how quickly small setbacks escalate
  • Cognitive clarity and the ease of switching between tasks
  • Sense of meaning, connection, and engagement with people and work
  • Cravings for alcohol or nicotine, where those were the target
  • Any lingering visual disturbances, however mild