Selegiline (also called deprenyl) is a selective MAO-B inhibitor, originally approved for Parkinson's disease, that's been used off-label for decades as a low-dose tool for cognitive resilience, mood, libido, and brain aging. It works by slowing the enzyme that breaks down dopamine in the brain, so the dopamine you produce sticks around longer and signals more. The practical effect at low doses is steadier focus, motivation, and drive, with a slow build rather than a stimulant kick.

Most people taking it outside a Parkinson's context use it at 1-5 mg a few times a week, aiming for the brain-aging and cognitive end of the dose-response curve rather than the antidepressant end. At those low doses it's selective for MAO-B, doesn't interact with tyramine in food, and has a clean tolerability profile. The catch is that it's a real MAO inhibitor with real drug interactions, so it sits in a different category from a typical nootropic and needs to be respected as such.

Deep-dive

Dosage:

• Cognitive and longevity use: 1-5 mg orally, 2-5 days per week. Most people land at 1-2.5 mg taken in the morning. This stays clearly within the MAO-B selective range, avoids tyramine restrictions, and matches the dosing range Knoll worked in for his anti-aging research
• Start low and titrate slow: Begin at 1 mg every other day for 2 weeks. Selegiline is irreversible, so steady-state effects build over time. Increases of more than 1-2 mg every 2-3 weeks are not recommended. The metabolites include amphetamine and methamphetamine derivatives that can disturb sleep and cause overstimulation if you escalate too fast
• Timing: Take in the morning. The active metabolites have stimulant properties and can interfere with sleep if taken later. Empty stomach or with a light meal is fine. Avoid tyramine-heavy meals (aged cheeses, cured meats, fermented foods, draft beer) close to dosing if you're on the higher end of the range or if you're a woman on oral contraceptives, where effective exposure can be 10-20x higher
• Forms: Oral tablets and capsules (5 mg) are the standard prescription form sold as Eldepryl and generics. Orally disintegrating tablets (Zelapar, 1.25 mg) bypass first-pass metabolism and produce higher CNS levels at lower doses. The transdermal patch (Emsam, 6/9/12 mg per 24h) is for depression and bypasses gut MAO-A. For low-dose nootropic use, standard oral 5 mg tablets quartered or a liquid dilution work fine
• Women on hormonal contraceptives or oral HRT: Halve or quarter the dose. The CYP3A4 inhibition from ethinylestradiol can raise selegiline exposure 10-20 fold. A 1 mg dose for an OC user behaves more like a 10-20 mg dose, which puts you past MAO-B selectivity and into territory requiring tyramine restrictions
• Older adults: Start at 1 mg twice weekly, monitor standing blood pressure for orthostatic drops. The cognitive and neuroprotective rationale is strongest in this population but so is sensitivity to side effects
• Cycling: Because selegiline is an irreversible inhibitor, MAO-B enzyme function only returns as new enzyme is synthesised, which takes around 2 weeks after stopping. Continuous low-dose use is the standard approach. Some users cycle 5 days on, 2 days off, but there's no specific evidence this is better
• Antidepressant dosing is different. If you're using selegiline for depression rather than cognitive support, the relevant doses are 6-12 mg/24h transdermal or 20-30 mg oral, both of which lose MAO-B selectivity and require classical MAOI precautions including tyramine restrictions and a strict drug interaction list. This is not a self-managed dose range

Here's what you can expect:

At 1-2.5 mg taken consistently for 2-4 weeks, most people notice steadier motivation, easier task initiation, slightly better mood floor, and sometimes a mild libido lift. It's not a stimulant, the effect builds rather than hits. Compared to caffeine or modafinil, the texture is closer to feeling like you have more drive than usual rather than feeling pushed.

Some people get nothing at sub-2 mg doses and need 5 mg to feel any subjective effect. Others are sensitive to the amphetamine metabolites and find 1 mg keeps them up at night. There's significant individual variability, much of it driven by baseline dopamine tone and CYP3A4 activity.

For cognitive performance specifically, expect modest gains in tasks involving sustained attention, working memory, and motivation, rather than a jump in raw processing speed. The neuroprotective and longevity benefits, if they exist in humans, are slow and not subjectively felt.

If you're using it for libido, the literature on the original deprenyl rat studies and clinical reports in older men suggests this is one of the more reliable subjective effects. Knoll's rats had striking restoration of sexual activity at the same dose used for lifespan extension.