Psilocybin for Health & Longevity - Quick Reference Sheet
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Psilocybin for Health & Longevity

Created on 08/22/2026 – Quick Reference based on Evidence Review created using AI4L / Grok 4 – Audit

Psilocybin is used as one or two supported sessions, not a daily longevity supplement. In screened adults it can lastingly improve depression, cancer-related distress, drinking, and smoking. No human aging trial exists. Harms are nausea, headache, a temporary blood-pressure rise, and overwhelming sessions. Psychotic illness and lithium use are outside the safety data. Evidence does not support routine longevity use. (Full Review)

Protocol

Johns Hopkins high-dose model
about 20 then 30 mg/70 kg
Two oral sessions several weeks apart, with ~11 hours of preparatory and integrative psychotherapy
Compass/Usona single-capsule model
25 mg
One synthetic oral dose plus psychological support
Time of day
Morning or early afternoon
The 4–6 hour acute course plus afterglow would otherwise collide with sleep
Time to effect
Depressive symptom reduction
Next day
When it occurs, often measurable the next day and may persist weeks to months
Cancer-related anxiety and existential distress
Rapid
Many still improved at 6–6.5 months
Fewer heavy drinking days in alcohol use disorder
Over 32 weeks
Two high-dose sessions embedded in 12 weeks of psychotherapy

Benefits

Contraindications
  • Personal history of schizophrenia, schizoaffective disorder (psychosis with mood episodes), or other primary psychotic disorder
  • Bipolar I disorder, or a first-degree relative with bipolar I or schizophrenia
  • Current manic episode or mixed state (mania and depression at once)
  • Uncontrolled hypertension, recent myocardial infarction (<90 days), decompensated heart failure (heart failure with fluid backup and poor organ perfusion), or known aneurysm
  • Pregnancy or breastfeeding
  • Active lithium therapy
  • Age under 18 in medical protocols
  • Acute suicidality with plan or intent outside a high-monitoring research ward
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Key Interactions
  • MAO inhibitors (phenelzine, tranylcypromine, moclobemide, some Banisteriopsis preparations)
  • Daily SSRIs/SNRIs (sertraline, escitalopram, venlafaxine; SNRIs are serotonin-norepinephrine reuptake inhibitors)
  • 5-HT2A antagonists (ketanserin, risperidone, olanzapine)
  • Tramadol, bupropion, theophylline, and other seizure-threshold drugs
  • Stimulants (amphetamine, high-dose caffeine, cocaine)
  • Cannabis and alcohol
  • St John's wort, 5-HTP (5-hydroxytryptophan, a serotonin precursor), SAMe (S-adenosylmethionine)
  • Other psychedelics (LSD [lysergic acid diethylamide], DMT [N,N-dimethyltryptamine], mescaline, MDMA [3,4-methylenedioxymethamphetamine])
  • Antihypertensives (lisinopril, amlodipine, hydrochlorothiazide)
    •

Risk & Side Effects

  • High: Acute nausea, headache, and dizziness; transient blood-pressure and heart-rate rise; challenging psychological experience
    •
  • Medium: Suicidal ideation or self-injury in depressed samples; mania or psychosis in vulnerable people
    •
  • Low: Hallucinogen persisting perception disorder (HPPD)
    •
  • Speculative: Heart-valve disease with frequent 5-HT2B stimulation
    •

Monitoring

Marker Target Why
Resting blood pressure <120/80 mmHg Acute pressor effect
Resting heart rate 60–80 bpm Acute tachycardia
Urine or serum hCG Negative Pregnancy exclusion
hs-CRP No psilocybin-specific target; track change from personal baseline (functional goals often <0.7 mg/L) Speculative inflammation/longevity pathway
PHQ-9 <5 (minimal symptoms) Primary psychiatric endpoint in non-trial use

Cadence: Before a first high-dose session: psychiatric history, pregnancy test when applicable, resting blood pressure and heart rate, and current serotonergic or lithium use. During the session, blood pressure and mental state repeatedly through the peak (about 1.5–3 hours) until the person is clear to leave. Afterward, mood, sleep, substance use, and suicidality at about 1 day, 1 week, 4 weeks, and 3 months.

Qualitative Assessment

  • Sleep continuity and next-day grogginess
  • Alcohol or cigarette use (timeline follow-back)
  • Cognitive flexibility and rumination, not just mood
  • Meaning-making versus lingering fear after the session
  • Emergence of mania, unusual beliefs, or suicidal thinking
Not medical advice. Educational distillation of a single evidence review. Confirm any decision with a qualified clinician, especially in the presence of prescription drugs or chronic conditions.