Selegiline: Benefits, Dosing, Where To Buy, And More!

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Key Information

Selegiline treats Parkinson’s Disease:

Selegiline blocks the enzyme that breaks down dopamine, improving the symptoms and progression of Parkinson’s.

Selegiline may help with depression:

Selegiline also inhibits the enzyme that degrades serotonin and norepinephrine, boosting the mood and energy of some depressed patients.

Selegiline has nootropic effects:

Selegiline increases the availability of neurotransmitters that enhance cognition, such as memory, focus, and motivation.

Selegiline acts as an antioxidant:

Selegiline protects the brain from oxidative stress and inflammation, and stimulates the growth of new neurons.

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In the vast landscape of nootropics and cognitive enhancers, selegiline stands out as a unique and multifaceted compound. Originally developed as a treatment for Parkinson’s disease, this monoamine oxidase B (MAO-B) inhibitor has garnered attention for its potential benefits in depression, neuroprotection, and even longevity. As a holistic health enthusiast and founder of, I believe in exploring promising substances like selegiline from a comprehensive, evidence-based perspective. In this article, we’ll dive deep into the mechanisms, benefits, risks, and practical considerations surrounding selegiline use.

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What is Selegiline?

Selegiline, also known as L-deprenyl, is a medication primarily prescribed for the treatment of Parkinson’s disease and major depressive disorder. As an irreversible selective inhibitor of MAO-B, selegiline works by preventing the breakdown of dopamine in the brain, leading to increased dopaminergic activity. This mechanism underlies its therapeutic effects in Parkinson’s, as well as its potential cognitive and mood-enhancing properties.

Beyond its medical indications, selegiline has captured the interest of the nootropic community for several reasons:

  • Cognitive enhancement: Studies suggest selegiline may improve memory, learning, attention, and overall brain function, particularly in aging populations.
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  • Neuroprotection: Selegiline has demonstrated antioxidant and neuroprotective effects, potentially slowing the progression of neurodegenerative diseases.
  • Anti-aging: Animal studies have shown remarkable lifespan extension of up to 40% with selegiline treatment, sparking interest in its potential longevity benefits for humans.

How Selegiline Works in the Brain

Selegiline’s primary mechanism of action is the selective inhibition of MAO-B, one of two isoforms of the monoamine oxidase enzyme responsible for breaking down neurotransmitters like dopamine. By blocking MAO-B, selegiline allows dopamine to accumulate in the brain, enhancing its effects on movement, motivation, reward, and cognitive function.

Interestingly, at higher doses (>20mg/day), selegiline loses its selectivity and begins to inhibit MAO-A as well. MAO-A is responsible for metabolizing serotonin, so its inhibition can lead to increased serotonergic activity, which may underlie selegiline’s antidepressant effects at these doses.

In addition to its MAO-B inhibition, selegiline has demonstrated neuroprotective and antioxidant properties:

  • Increases production of neurotrophic factors like brain-derived neurotrophic factor (BDNF), which support the growth, survival, and plasticity of neurons.
    Learn More: BDNF (Brain Derived Neurotrophic Factor)
  • Enhances the activity of antioxidant enzymes like superoxide dismutase, helping to scavenge harmful free radicals and prevent oxidative damage to brain cells.
  • May protect against neurotoxins and slow the progression of neurodegeneration, as seen in Parkinson’s disease.

Selegiline Benefits

Parkinson’s Disease Treatment

Selegiline is FDA-approved for the treatment of Parkinson’s disease, both as monotherapy in early stages and as an adjunct to levodopa/carbidopa in more advanced cases. By enhancing dopaminergic activity, selegiline can help alleviate motor symptoms, slow disease progression, and allow for lower doses of levodopa, thus reducing side effects.

Antidepressant Effects

At higher doses that inhibit MAO-A, selegiline acts as an antidepressant, likely through increasing serotonin and norepinephrine levels. The transdermal patch formulation (Emsam) is FDA-approved for the treatment of major depressive disorder, offering a unique option for those who haven’t responded to traditional antidepressants. Selegiline may be particularly useful for atypical and treatment-resistant depression.

Cognitive Enhancement and Anti-Aging

While more human research is needed, selegiline shows promise as a cognitive enhancer and anti-aging intervention. Animal studies have demonstrated improvements in memory, learning, attention, and problem-solving, as well as lifespan extensions of up to 40%. These effects are thought to be mediated by selegiline’s dopaminergic, neuroprotective, and antioxidant properties.

Selegiline Dosage and Administration

Selegiline dosage varies depending on the condition being treated and the route of administration:

  • Parkinson’s disease: 5-10mg/day orally, typically divided into two doses
  • Depression: 6-12mg/24hr via transdermal patch (Emsam)
  • Cognitive enhancement and longevity: 1-5mg/day orally or sublingually

For nootropic purposes, it’s best to start with the lowest effective dose and titrate up based on individual response. Sublingual or buccal administration (holding the tablet under the tongue or against the cheek) can help bypass first-pass metabolism and reduce exposure to amphetamine metabolites compared to oral ingestion.

Side Effects and Safety Considerations

While generally well-tolerated, selegiline does come with potential side effects and safety concerns:

  • Common side effects: nausea, dry mouth, dizziness, insomnia, orthostatic hypotension
  • Tyramine interaction: At higher doses that inhibit MAO-A, consuming tyramine-rich foods (aged cheeses, cured meats, soy sauce, etc.) can lead to dangerous hypertensive crisis. Lower selective doses avoid this risk.
  • Serotonin syndrome: Combining selegiline with other serotonergic drugs like SSRIs, SNRIs, or tramadol can cause life-threatening serotonin toxicity.
  • Psychosis and mania: Rarely, selegiline may induce psychotic symptoms or manic episodes in susceptible individuals.

To minimize risks, it’s crucial to work with a knowledgeable healthcare provider, avoid contraindicated drug and food combinations, and monitor for any adverse effects. Gradual tapering is recommended when discontinuing selegiline to prevent withdrawal symptoms.

Selegiline vs. Other Medications

Selegiline is often compared to other medications used for Parkinson’s disease, depression, or cognitive enhancement. Here’s a quick overview:

RasagilineSelective MAO-B inhibitorMore potent and selective than selegiline, once-daily dosingLess research on cognitive and anti-aging effects
PhenelzineNon-selective MAO inhibitorEffective for treatment-resistant depression and anxietyMore drug and food interactions, sedation, weight gain
AmantadineNMDA antagonist and dopamine agonistImproves Parkinson’s symptoms, also used for ADHD and fatiguePsychosis, livedo reticularis, edema

Where to Buy Selegiline

Selegiline is a prescription medication in most countries, meaning you’ll need to consult with a licensed healthcare provider to obtain it legally. It’s available in various forms:

  • Oral tablets and capsules, prescribed for Parkinson’s disease and off-label for depression and cognitive enhancement
  • Transdermal patches (Emsam), FDA-approved for major depressive disorder
  • Sublingual tablets, sometimes obtainable through online pharmacies or research chemical vendors, but beware of quality control issues and legal risks

For optimal safety and efficacy, it’s best to work with a knowledgeable physician or integrative health practitioner who can help you weigh the risks and benefits, determine appropriate dosing, and monitor your response.

Selegiline Discussions on Reddit

Reddit communities like r/Nootropics offer a wealth of anecdotal reports and discussions on selegiline use for cognitive enhancement and mental health. Here are some notable threads:

Selegiline as a Nootropic and Antidepressant

“Selegiline has been life changing for me, but I was taking it for the purposes of depression. Anhedonia is no joke when your depression makes you jaded. Within a day I could feel it working and this was just with one single 5mg sublingual dose.”

u/SamuelKonkinIII in discussion ‘Selegiline is too good. Where’s the catch?’

Many users report significant improvements in depression, anhedonia, motivation, and overall quality of life with selegiline, often noticing benefits within days of starting treatment.

Dosage and Cycling Recommendations

“It builds up in the body and gains momentum and you must discontinue and clear your system from it regularly. I could definitely see it having antiaging properties.”

u/ej00807 in discussion ‘Why is noone into anti aging talking about selegiline? Increases maximum lifespan by 40 % ????’

Because selegiline irreversibly inhibits MAO-B, effects can persist for weeks after discontinuation until the body synthesizes new enzyme. Many users recommend cycling selegiline, taking breaks every few months to allow MAO-B levels to normalize and prevent tolerance.

Side Effects and Interactions

“The main side effects of the patch form for depression include application- site reactions , insomnia , diarrhea , and sore throat . A lot of the side effects are because of extra dopamine, which your doctor can remedy by scaling back on L-DOPA and other dopamine precursors that doctors prescribe alongside selegiline.”

u/PragmaticPulp in discussion ‘Selegiline is too good. Where’s the catch?’

While selegiline is generally well-tolerated, side effects can occur, particularly at higher doses. The transdermal patch seems to have a lower risk of adverse reactions compared to oral administration. Most side effects relate to excess dopamine and can be managed by adjusting the dose of selegiline or other dopaminergic medications.

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