A mushroom-derived compound studied as an occasional supervised session, not a daily medicine. Human evidence is strongest for rapid, sometimes lasting relief of depression, with less certain signals for anxiety in serious illness, problem drinking or smoking, and overall well-being. Aging effects rest only on cells and mice. Risks are generally manageable when screened and supervised. (Full Review)

Protocol

Dose

25 mg

Single moderate-to-high oral dose (~25–30 mg per 70 kg)

Setting

Supervised

One or two trained monitors present for the full 4–6 hour session

Structure

3-phase

Preparation sessions before, integration sessions after dosing

Time to effect

Depression relief

Days

Often apparent within days, building over the following weeks

Distress in serious illness

>6 months

Reduced anxiety and depression persisting after a single session

Well-being gains

6–14 months

Sustained life-satisfaction increases in healthy volunteers

Benefits

High: Rapid, durable relief of depression

Medium: Reduced anxiety and existential distress in serious illness; substance use disorder remission; durable gains in well-being and psychological flexibility

Low: Increased trait openness, mindfulness, and emotional processing

Speculative: Cellular and organismal geroprotection; anti-inflammatory and neuroprotective potential

Contraindications

Personal or first-degree family history of schizophrenia, schizotypal, or bipolar I disorder

Uncontrolled hypertension (>160/100 mmHg)

Recent myocardial infarction (<6 months)

Unstable coronary disease

Significant heart-valve disease

Pregnancy or breastfeeding

Lithium

Key Interactions

SSRIs and SNRIs (e.g., sertraline, escitalopram, fluoxetine, venlafaxine, duloxetine)

MAOIs (e.g., phenelzine, tranylcypromine)

Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, clomipramine) and tramadol

Antipsychotics and other 5-HT2A antagonists (e.g., risperidone, quetiapine)

Serotonergic over-the-counter agents (e.g., dextromethorphan)

Serotonergic or MAO-inhibiting supplements (St. John's Wort, 5-HTP, L-Tryptophan, syrian rue)

Blood-pressure-raising supplements or stimulants (e.g., high-dose caffeine, yohimbine, synephrine)

Risk & Side Effects

High: Acute anxiety, fear, and challenging experiences; transient nausea, headache, and elevated blood pressure

Medium: Precipitation of psychosis or mania in predisposed individuals; worsening mood or suicidality after the session

Low: Hallucinogen persisting perception disorder

Speculative: Cardiac valve effects from chronic repeated dosing

Monitoring

Marker	Target	Why
Blood pressure	<120/80 mmHg at rest	Session transiently raises it
Heart rate / ECG (QTc)	Resting HR 50–70 bpm; QTc <450 ms (men), <460 ms (women)	Screens for arrhythmia risk before a sympathetically stimulating session
Liver enzymes (ALT / AST)	ALT <25 U/L (men), <20 U/L (women); AST similar	Psilocin is cleared largely by liver conjugation
Columbia Suicide Severity (C-SSRS)	No active suicidal ideation	Establishes psychiatric safety and a comparison point

Cadence: Vital signs during and immediately after the session; mood and suicide-risk at 1 day, 1 week, and 4 weeks post-session; longer-term follow-up every 3–6 months if repeat sessions are considered

Qualitative Assessment

Sustained improvement in mood, outlook, and sense of meaning beyond the acute session
Better sleep quality and daytime energy
Greater psychological flexibility — less rigid rumination, more openness
Improved engagement with relationships, work, and valued activities
Reduction in cravings or compulsive behaviors where substance use was the target

Psilocybin for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment