Selegiline is a drug that helps reduce symptoms of early-stage Parkinson’s disease. It is also effective against depression. In addition, it increases wakefulness and motivation, may improve cognitive function, and may even increase longevity.

Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

What Is Selegiline?

Selegiline, also known as L-deprenyl, is a drug similar in structure to the brain chemical (neurotransmitter) phenylethylamine [R].

It has a wide spectrum of uses, the most popular of which involves brain health.

Mechanism of Action

Selegiline blocks the activity of MAO-B and, at higher doses, also MAO-A. These enzymes break down dopamine and other monoamine neurotransmitters (serotonin and noradrenaline) [R].

As a result, there are higher levels of dopamine, serotonin, and noradrenaline in the brain.

Selegiline: The Good

1) Selegiline Helps with Parkinson’s Disease

It increases dopamine levels in the brain. Symptoms of Parkinson’s are often caused by low levels of dopamine as cell death occurs in dopamine-related neurons [R, R].

Additionally, higher dopamine levels may improve the impaired movements characteristic of  Parkinson’s disease, especially slowness of movement (bradykinesia) [R, R].

Selegiline improved symptoms in 292 patients with early Parkinson’s (DB-RCT) [R].

In a study of 157 Parkinson’s disease patients (DB-RCT), selegiline (10 mg/day) delayed the need for levodopa therapy. It also slowed down the progression of disease symptoms when used in addition to levodopa, compared to levodopa alone [R, R, R].

Selegiline blocks the effects of MPTP, a brain toxin that causes permanent symptoms of Parkinson’s disease [R].

However, it likely does not affect lifespan in Parkinson’s disease patients [R].

2) Selegiline Combats Depression

Selegiline is an antidepressant that increases the levels of dopamine, serotonin, and norepinephrine in the brain [R].

A meta-analysis of 5 clinical studies showed that selegiline patches successfully treated symptoms of major depression like [R]:

  • Depressed mood
  • Guilt
  • Anxiety
  • Oversleeping
  • Overeating
  • Poor concentration
  • Lack of sex drive

Another meta-analysis of 5 short-term trials with 352 subjects concluded that this drug improved symptoms in major depressive disorder [R].

In 322 subjects with major depression, those who received the drug were less likely to relapse or took a longer time to relapse [R].

However, in 308 adolescents (12 to 17 years old) with major depressive disorder (DB-RCT), both selegiline and placebo decreased depression symptoms to a similar extent [R].

This drug also improved apathy in 4 patients following severe brain injury [R].

An important benefit of selegiline patches is that they produce fewer side effects than oral treatments, and they don’t require the same dietary restrictions as other drugs of the same type [R, R, R, R, R].

3) Selegiline Is an Antioxidant

Selegiline also acts as an antioxidant. It prevents the death of neurons caused by oxidative stress [R, R].

It increases the levels of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione (GSH) in mitochondria, neurons and rats [R, R, R].

4) Selegiline Assists Brain Repair

This drug increased brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) levels in a mouse model of Parkinson’s disease [R]. BDNF and GDNF are important for brain health and brain repair.

It increases BDNF, GDNF, and nerve growth factor (NGF) levels in brain cells and that helps to protect the brain from the effects of aging or disease [R, R].

5) Selegiline May Improve Memory and Learning

In a study with 32 Parkinson’s disease patients, those who received selegiline had improved memory and cognitive function [R].

This drug enhanced memory in mice with amnesia [R].

It also improved learning in old rats [R, R].

6) Selegiline May Improve Alzheimer’s Symptoms

In a review of clinical studies, 8 of 11 trials showed that selegiline improved cognitive function (word fluency and total recall), and 2 of 5 trials showed it improved behavior (anxiety and depression) associated with Alzheimer’s [R].

Selegiline improved memory in 173 subjects with mild to moderate Alzheimer’s disease [R].

It reversed cognitive impairment caused by the amyloid-beta peptide in mice [R].

However, two meta-analyses (of 17 and 13 DB-RCTs) found selegiline’s therapeutic effect in Alzheimer’s unremarkable and possibly ineffective [R, R].

7) Selegiline Increases Wakefulness and Improves Narcolepsy

This drug decreased daytime sleep episodes and their duration in two DB-RCTs with 30 and 17 narcoleptic patients [R, R].

It also increased wakefulness in rats by increasing dopamine and noradrenaline levels in the brain [R].

8) Selegiline Increases Motivation

Higher dopamine levels increase motivation by stimulating the “reward centers” of the brain [R, R].

Selegiline has been classified as a doping agent by the world anti-doping agency as a stimulant that can increase motivation in athletes [R, R].

9) Selegiline May Improve ADHD

This drug increases dopamine levels, and dopamine helps with attention and focus. Dopamine deficiency may contribute to attention deficit disorders [R].

In 11 children with ADHD (DB-RCT), selegiline improved sustained attention, learning, and peer interactions, and reduced hyperactivity [R].

In two DB-RCTs with 40 and 28 children each, this drug was as effective as methylphenidate (a central nervous system stimulant, commonly sold as Ritalin) in improving ADHD, with fewer side effects [R, R].

However, it was not more effective than placebo in 24 adults with ADHD [R].

10) Selegiline May Be Beneficial for Schizophrenia

In a pilot study with 21 patients, selegiline reduced negative and depressive symptoms of schizophrenia [R].

Furthermore, in two DB-RCTs of 67 and 40 patients with chronic schizophrenia, the combination of selegiline with antipsychotic medication showed superiority over antipsychotic medication alone in decreasing negative symptoms [R, R].

11) Selegiline May Help with Stroke Recovery

Selegiline improved recovery after stroke in 24 patients (DB-RCT) [R].

This drug seems to be beneficial after a brain infarction, by speeding up the recovery process.

It increased resistance to stroke and decreased brain damage after stroke in mice [R].

12) Selegiline May Help with Chronic Fatigue Syndrome

This drug improved anxiety, vigor, and sexual relations in 25 patients with chronic fatigue syndrome (DB-RCT) [R].

13) Selegiline May Help with Drug Withdrawal

In 12 cocaine-dependent volunteers, selegiline decreased the physical (blood pressure and heart rate) and subjective (good effects, stimulated, high, desire for cocaine) effects of cocaine [R].

However, in a double-blind trial of 300 subjects with cocaine dependence, it was no more efficient than placebo [R].

Selegiline decreased morphine-related withdrawal symptoms in rats [R].

14) Selegiline Reduces Nicotine Cravings

This drug may help people quit smoking by reducing nicotine cravings. Nicotine blocks MAOs and increases dopamine (hence the rewarding effect). Selegiline mimics the effects of nicotine on MAOs [R].

Selegiline-treated smokers with a specific nicotine-sensitive genotype (CHRNA5 rs680244 GG) experienced [R]:

  • Lower post-quit craving
  • Less post-quit depression
  • Higher rates of abstinence

Selegiline blocks the breakdown of nicotine by the CYP2A6 enzyme. This prolongs the effect of nicotine when users smoke less [R, R].

15) Selegiline May Prevent Seizures

This drug prevented seizures in mice  [R, R, R].

It also prevented seizures in a rat model of epilepsy [R].

16) Selegiline May Increase Longevity

Selegiline may prevent physical decline. Hamsters treated with selegiline show less age-related decline in both mind and body [R].

However, a later study showed that this drug lengthened the lifespan of female but not male hamsters [R].

On the other hand, selegiline prolonged lifespan in aged male rats by up to 34% [R, R, R].

However, it prolonged lifespan in female rats only when they lacked sex organs [R].

Finally, selegiline also increased the lifespan of elderly dogs [R].

Selegiline: The Bad

1) Selegiline Can Cause High Blood Pressure

High doses (>10 mg/day) of the drug stop MAO-A from breaking down tyramine. Tyramine in the bloodstream is turned into norepinephrine, which causes blood vessels to constrict, causing blood pressure to rise [R, R].

Tyramine is a naturally-occurring amino acid found in fermented meat, soy products, and aged cheese. People using selegiline may experience high blood pressure due to excess tyramine after eating >6 mg [R, R].

2) Selegiline May Cause Birth Defects

High-dose selegiline decreased fetal body weight in rats and caused postimplantation loss in rabbits [R].

However, a pregnant woman with Parkinson’s disease was treated with selegiline and levodopa and gave birth to a healthy child [R].

Selegiline Dosage

You need a prescription for both the pill/tablet form or the patch.

Selegiline pill or tablet (Eldepryl, Selegiline Hydrochloride) is normally taken twice per day, with meals. Dosages vary, the most common is two 5 mg/day pills [R].

The patch (Emsam) is available in 6, 9, or 12 mg/day doses [R].

Higher doses (6 to 20 mg/day) treat depression more effectively [R, R, R, R].

Selegiline is transformed into by-products that also increase brain dopamine [R, R]:

Side Effects

Like other MOA blockers, selegiline can have mild to severe side effects.

These include [R, R, R, R]:

  • Dizziness
  • Mouth sores (tablet only)
  • Nausea
  • Insomnia
  • Indigestion
  • Low or high blood pressure
  • Anxiety/agitation
  • Increased or abnormal sexual desire
  • Depression
  • Severe headache
  • Irregular heartbeat
  • Vomiting
  • Uncontrollable shaking
  • Hallucinations
  • REM behavior disorder, which is characterized by acting out in one’s dreams [R, R].
  • Serotonin syndrome (patch) that may lead to seizures and coma

It may worsen symptoms associated with involuntary movement (tardive dyskinesia) in Parkinson’s [R].

Selegiline withdrawal causes low blood pressure in Parkinson’s disease patients [R, R].

Limitations and Caveats

Potential benefits of this drug are based on a few clinical studies and need to be supported by larger clinical trials.

Some of the benefits have not been studied in humans.

It is always advised to be cautious when using this drug. All MAOIs should be obtained through prescription, and only after consulting a physician.


Selegiline should not be used together with these drugs because it can cause serious adverse effects:

  • Other antidepressants like fluoxetine (Prozac, Sarafem), clomipramine, and selective serotonin reuptake inhibitors (SSRIs) [R, R, R, R]
  • Painkillers like pethidine (meperidine) [R]
  • MAO blockers like linezolid or moclobemide [R]
  • Opioids or opioid-like drugs such as tramadol, dextromethorphan, methadone, or propoxyphene [R, R, R]
  • Phenethylamine [R]

Women using birth control had excess levels of selegiline (10-20x higher than normal) after treatment [R].

User Experiences

Some people have experienced brain fog and vertigo while using this drug in addition to other supplements.

For busy people or athletes, lack of restrictive diets makes the patch form more appealing than the pill or liquid drops.

Many people find the drug is effective initially but soon experience unwanted side effects.

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

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