Selegiline – An Overview
Selegiline (AKA Deprenyl) is a medication that is officially used to treat Parkinson’s Disease.
However, many users also take off-label it for its nootropic effects.
The main nootropic uses of selegiline are for:
- Alertness and Attention
Selegiline seems to increase the availability of dopamine and serotonin by preventing its breakdown.
It also has some antioxidant and neurogenerative properties that may help it protect the brain, especially as you age.
In most Western countries, including the US, selegiline is a prescription-only medication. It usually goes under the brand names Deprenyl or Emsam.
What Does Selegiline Do?
Selegiline and Parkinsons
There is evidence that selegiline is effective at slowing the progression of Parkinson’s Disease.1Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease N Engl J Med. 1989
Most researchers have believed for a while that Parkinson’s is related to low dopamine levels.
This may be caused by the neurons that produce dopamine dying off due to toxicity.
Selegiline blocks the action of MAO-B enzymes that destroy dopamine molecules.2Spencer JP, et al. Evaluation of the pro-oxidant and antioxidant actions of L-DOPA and dopamine in vitro: implications for Parkinson’s disease Free Radic Res. 1996 3Jenner P. Oxidative stress in Parkinson’s disease Ann Neurol. 2003 4Heikkila RE, et al. Monoamine oxidase and the bioactivation of MPTP and related neurotoxins: relevance to DATATOP J Neural Transm Suppl. 1990
One major 800 patient study found that selegiline significantly improved the treatment of Parkinson’s over a number of years.
This seems to be pretty robust evidence that selegiline has some positive effects on this condition.5DATATOP: a multicenter controlled clinical trial in early Parkinson’s disease. Parkinson Study Group Arch Neurol. 1989
Other follow-up studies conclude that selegiline can greatly improve the mental and physical symptoms of this disease.
Researchers believe that it can significantly slow the neurological degradation, and delay the need for additional treatment.
These are all positives for anyone dealing with this condition.6Giladi N, et al. Freezing of gait in PD: prospective assessment in the DATATOP cohort Neurology. 2001 7Pålhagen S, et al. Selegiline delays the onset of disability in de novo parkinsonian patients. Swedish Parkinson Study Group Neurology. 1998 8Larsen JP, Boas J, Erdal JE. Does selegiline modify the progression of early Parkinson’s disease? Results from a five-year study. The Norwegian-Danish Study Group Eur J Neurol. 1999 9Chava Peretz, et al. Comparison of Selegiline and Rasagiline Therapies in Parkinson Disease: A Real-life Study Clin Neuropharmacol. 2016
Selegiline For Depression
Selegiline’s action on serotonin and norepinephrine may make it useful as an antidepressant.
In large enough quantities, selegiline switches from blocking MAO-B to blocking MAO-A.
MAO-A breaks down serotonin and norepinephrine. So, selegiline could boost these neurotransmitters by preventing their breakdown.
This could treat some types of depression that are caused by low levels of these chemicals.10Finberg JP. Update on the pharmacology of selective inhibitors of MAO-A and MAO-B: focus on modulation of CNS monoamine neurotransmitter release Pharmacol Ther. 2014
Some studies show that MAO-A levels in some depression sufferers may be elevated by as high as 35%.11Meyer JH, et al. Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression Arch Gen Psychiatry. 200612Lipper S, Murphy DL, Slater S, Buchsbaum MS.. Comparative behavioral effects of clorgyline and pargyline in man: a preliminary evaluation Psychopharmacology (Berl). 1979
There is also evidence that selegiline can lower MAO-A by up to 30%.
There are several studies that point to selegiline as an effective treatment for depression in some people.
In fact, Selegiline may offer similar relief as other MAOI antidepressants but without nearly as many side-effects.
Most of these studies were done using a deprenyl transdermal patch.13Mann JJ, et al. A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor Arch Gen Psychiatry. 1989 14Joanna S Fowler, et al. Evidence that Formulations of the Selective MAO-B Inhibitor, Selegiline, which Bypass First-Pass Metabolism, also Inhibit MAO-A in the Human Brain Neuropsychopharmacology. 2015 15Amsterdam JD. A double-blind, placebo-controlled trial of the safety and efficacy of selegiline transdermal system without dietary restrictions in patients with major depressive disorder J Clin Psychiatry. 2003
MAOI inhibitors like selegiline be a potentially useful treatment for a very vulnerable yet substantial sub-population of mood disorder patients.
Some people who do not respond to SSRIs or other types of antidepressants may find relief with this family of medication.16Shulman KI, Herrmann N, Walker SE. Current place of monoamine oxidase inhibitors in the treatment of depression CNS Drugs. 2013
Selegiline For ADHD
Most models implicate dopamine deficiency in ADHD. Selegiline can prevent the breakdown of dopamine and may help with symptoms of this disorder.
A few studies show that selegiline may help with ADHD symptoms in children. It may even help as well or better than traditional medication like Ritalin.17Akhondzadeh S, et al. Selegiline in the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial Prog Neuropsychopharmacol Biol Psychiatry. 2003 18Mohammadi MR, et al. Selegiline in comparison with methylphenidate in attention deficit hyperactivity disorder children and adolescents in a double-blind, randomized clinical trial J Child Adolesc Psychopharmacol. 2004 19Rubinstein S, Malone MA, Roberts W, Logan WJ. Placebo-controlled study examining effects of selegiline in children with attention-deficit/hyperactivity disorder J Child Adolesc Psychopharmacol. 2006
That said, there have not been any large scale studies showing that it is effective for ADHD in adults. However, some users claim that it has helped them with focus.
Does Selegiline Help With Anxiety?
There have not been many human studies focusing on selegiline and anxiety.
However, there is some evidence from animal trials that this MAOI may also have some use in treating this condition, which often occurs alongside depression.20L De Angelis, et al. The anxiolytic-like properties of two selective MAOIs, moclobemide and selegiline, in a standard and an enhanced light/dark aversion test Pharmacol Biochem Behav. 2000
How Selegiline Works In The Brain
Selegiline works as a monoamine oxidase inhibitor (MAOI). In lower doses it inhibits MAO-B, and it can also inhibit MAO-A in higher doses.
MAOs are enzymes that are responsible for breaking down serotonin, dopamine, and norepinephrine.
All of these neurotransmitters play an important role in mood and mental function.
So, by preventing their breakdown, there are more of these neurotransmitters available for the brain to use. This may positively affect cognition in a variety of ways.21Knoll J. Deprenyl (selegiline): the history of its development and pharmacological action Acta Neurol Scand Suppl. 1983 22Doller HJ, Connor JD. Changes in neostriatal dopamine concentrations in response to levodopa infusions J Neurochem. 1980
Selegiline also acts as an antioxidant. It can clear out potentially damaging free-radicals before they damage the brain cells. This is a particular issue for people who are under a lot of stress.
Selegiline does this by encouraging the production of anti-inflammatory agents such as glutathione and superoxide dismutase. This can preserve the overall health of your brain as you age.23Thiffault C, Quirion R, Poirier J.. The effect of L-deprenyl, D-deprenyl and MDL72974 on mitochondrial respiration: a possible mechanism leading to an adaptive increase in superoxide dismutase activity Brain Res Mol Brain Res. 1997 24Ebadi M, Sharma S, Shavali S, El Refaey H. Neuroprotective actions of selegiline J Neurosci Res. 2002 25Thomas CE, Huber EW, Ohlweiler DF.. NHydroxyl and peroxyl radical trapping by the monoamine oxidase-B inhibitors deprenyl and MDL 72,974A: implications for protection of biological substrates Free Radic Biol Med. 1997
It can also increase brain-derived neurotrophic factor (BDNF). This is your brain’s ability to grow new neurons. This is critical for your ability to create new neural connections and heal itself when it gets injured.
This could be part of why it is effective at treating Parkinson’s Disease.26Mizuta I, et al. Selegiline and desmethylselegiline stimulate NGF, BDNF, and GDNF synthesis in cultured mouse astrocytes Biochem Biophys Res Commun. 2000
How Much Selegiline Should I Take?
For Parkinson’s Disease and depression, the standard selegiline dose is 5mg twice per day.
Selegiline Potential Side Effects
It is important to know that this drug may cause an attack of high blood pressure (hypertensive crisis), which may be fatal.
This is because selegiline is an MAOI, and may result in a dangerous buildup of certain neurotransmitters.
You may want to avoid foods that contain the compound tyramine. This includes aged cheese and some fermented foods.
Tyramine may cause a hypertensive crisis if consumed with MAOIs.
Other side effects include:
- Abdominal pain
- Dry mouth
- Stomach upset
Selegiline Reddit Reviews
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