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

Created on 08/03/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 4.8 – Audit

Selegiline is a decades-old prescription drug that blocks a brain enzyme controlling dopamine, with well-supported value in protecting the brain's dopamine system in Parkinson's disease and, as a skin patch, easing depression. Its longevity reputation rests on mixed animal studies and antioxidant lab findings; a lifespan benefit in people remains unproven rather than disproven. (Full Review)

Protocol

Longevity Dose
1-5 mg/day
Or 5 mg two-to-three times per week; below symptomatic doses
Timing
Morning only
Avoid afternoon or evening dosing to limit insomnia
Route
Oral or patch
Patch reduces amphetamine metabolites; keep oral at or below 10 mg/day for MAO-B selectivity
Time to effect
Mood & Alertness
Days to 2 weeks
Earliest perceptible change
Neuroprotection
Months to years
Not directly perceptible
Lifespan Effects
Months to years, if real
Not directly perceptible

Benefits

Contraindications
  • Serotonergic antidepressants (SSRIs, SNRIs, TCAs)
  • Other MAO inhibitors (phenelzine, tranylcypromine, rasagiline, linezolid, methylene blue)
  • Certain opioids (meperidine, tramadol, methadone, dextromethorphan)
  • Pheochromocytoma
  • Uncontrolled hypertension or recent cardiovascular events
  • Pregnancy or breastfeeding
  • Bipolar disorder at risk of manic activation
    •
Key Interactions
  • Sympathomimetics and stimulants (OTC decongestants, amphetamine stimulants, cough-cold products)
  • Serotonergic or catecholaminergic supplements (St. John's Wort, 5-HTP, L-tryptophan, tyrosine, high-dose caffeine)
  • Additive blood-pressure-lowering agents (antihypertensives)
    •

Risk & Side Effects

  • High: Insomnia and overstimulation; serotonin syndrome with serotonergic drugs
    •
  • Medium: Orthostatic hypotension and dizziness; nausea and gastrointestinal upset; hypertensive reaction at high doses
    •
  • Low: Headache; transdermal application-site reactions
    •
  • Speculative: Long-term amphetamine-metabolite exposure
    •

Monitoring

Marker Target Why
Blood pressure (supine & standing) ~110-125 / 70-80 mmHg, <20 mmHg systolic drop on standing Detects orthostatic hypotension and any pressor response
Resting heart rate ~55-70 bpm Screens for stimulant-type cardiovascular effect from amphetamine metabolites
ALT and AST ALT <25 U/L (men) / <20 U/L (women); AST ~15-25 U/L Confirms healthy hepatic function for a liver-metabolized drug
Vitamin B6 (pyridoxal-5-phosphate) ~30-80 nmol/L MAO-inhibitor use can affect B6-dependent pathways; relevant with long-term use

Cadence: Blood pressure and heart rate at 1-2 weeks after starting or dose change, again at 4-6 weeks, then every 6-12 months once stable; liver enzymes and B6 reviewed annually for long-term users

Qualitative Assessment

  • Sleep quality and time to fall asleep (worsening flags mistimed or excessive dosing)
  • Energy, motivation, and mood through the day
  • Cognitive clarity, focus, and processing speed
  • Absence of jitteriness, palpitations, or lightheadedness on standing
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.