The most famous promoter of phenylethylamine was Dr. Alexander Shulgin and his wife Anna. Dr. Shulgin published ‘PiHKAL: A Chemical Love Story’ in 1991. PiHKAL is short for “Phenethylamines I Have Known and Loved”.
Phenylethylamines are a group of phenethylamine derivatives which contain PEA as a backbone. These derivative compounds are formed by replacing one or more hydrogen atoms in the core structure.
This class of PEA compounds include amphetamines, empathogens, stimulants, psychedelics, appetite suppressants, bronchodilators, nasal decongestants, and antidepressants.
One of the more famous PEA derivatives is Methylenedioxymethamphetamine (MDMA or Ecstasy).
Dr. Shulgin developed, tested, and published the formulas for 179 different compounds largely based around the structure of PEA in his book PiHKAL.
In this review we investigate how phenylethylamine (PEA) works in the brain.
- Anxiety & Depression. PEA activates TAAR1 and TAAR2 receptors which in turn prevents the uptake and boosts the release of the ‘feel-good’ neurotransmitters serotonin and dopamine.
- Neuroprotector. Monoamine oxidase inhibits the catecholamines like dopamine and norepinephrine. Decreases in dopamine levels are implicated in diseases like Parkinson’s. PEA helps boost dopamine and norepinephrine levels. Reducing the symptoms of neurodegenerative diseases.
- Attention Deficit Disorder (ADHD). PEA prevents the reuptake of dopamine and norepinephrine and inhibits their transport. Like the mechanism of action provided by ADHD stimulant meds. Some have found supplementing with PEA as a nootropic has decreased the symptoms of ADHD.
Table of Contents
Phenylethylamine (PEA, 2-phenylethylamine, β-phenylethylamine, phenethylamine) is a trace amine naturally synthesized from L-Phenylalanine in your brain.
Aromatic amino-acid decarboxylase converts phenylalanine to phenylethylamine. This is the same enzyme that converts phenylalanine into dopamine. And it converts it at a rate comparable to the synthesis of dopamine.
PEA can be found naturally in many cacao, algae, fungi, and bacteria as well as clover, beans, peas, and some food products such as Natto and eggs.
PEA binds to C-protein-coupled receptors TAAR1 and TAAR2, receptors reserved specifically for trace amine use.[iv] These receptors are not used by other major neurotransmitters like dopamine or norepinephrine.
How does Phenylethylamine work in the brain?
Phenylethylamine boosts brain health and function in several ways. But two in particular stand out.
- Phenylethylamine decreases depression. PEA naturally boosts the ‘feel-good’ neurotransmitters dopamine and serotonin in your brain. Studies have shown that depressed patients when tested have lower levels of PEA.[vi]
In fact, some suggest that a PEA deficit may be the cause of depression in the first place. One study had 14 patients with major depression take up to 60 mg per day of Phenylethylamine (PEA) along with 10 mg of selegiline (L-Deprenyl) for up to 50 weeks.
Researchers found that “PEA produces sustained relief of depression in a significant number of patients, including some unresponsive to the standard treatments. PEA improves mood as rapidly as amphetamine but does not produce tolerance.”[vii]
- Phenylethylamine is a mesencephalic enhancer. PEA is considered a mesencephalic enhancer which is defined as “enhancer-sensitive neurons in the brain capable of working in a split-second on a high activity level due to endogenous enhancer substances”.[viii]
This means that PEA stimulates the release of dopamine, norepinephrine, and serotonin in the brain. But unlike stimulant drugs like amphetamine, which release a flood of these neurotransmitters in an uncontrolled manner;
PEA instead only increase the amount of neurotransmitters that get released when a neuron is stimulated by receiving an impulse from a neighboring neuron.
In other words, the pattern of the neurotransmitter release in not changed. But when the neuron would normally release a neurotransmitter, a larger than normal amount is released.[ix]
The result is nearly instantaneous improvements in cognitive performance, attention, awareness, pleasure, libido, and a sense of well-being.
Phenylethylamine is an endogenous (natural or ‘built-in’) amphetamine. This mechanism of action of how prescription ADHD stimulants like Adderall work. And the basis for many Schedule 1 drugs like MDMA[x], LSD, mescaline, and (crystal) methylamphetamine.[xi]
How things go bad
Phenylethylamine (PEA) is naturally metabolized by monoamine oxidase-B (MAO-B). But as we get older, MAO-B levels rise and suppress healthy levels of PEA.
Low PEA levels have been linked to several neurological diseases. And may result in:
↓ Increased chance of ADHD
↓ Increased chance of addiction
↓ Energy levels decline
↓ Working memory and mood decline
↓ Contributing to Parkinson’s Disease
On the other hand, excess levels of PEA has been linked to migraines and paranoid schizophrenia.
Phenylethylamine (PEA) quickly crosses the blood-brain barrier once you take it. And you feel its effects right away.
Activation of TAAR1 receptors inhibit the uptake and induces the release of dopamine, norepinephrine, and serotonin. It’s like turning up the volume of neuron activity.
A higher concentration of all of these neurotransmitters increase feelings of pleasure, boosts motivation, improves memory and cognition, and reinforces impulse control.
PEA naturally maintains and regulates neuronal activity. Preventing over- or under-stimulation. When working as designed, PEA and other trace amines prevent metabolic dysfunction and neurological disorders.
As a neurotransmitter, PEA acts like, and looks similar to amphetamines. And produces effects normally associated with taking a stimulant. But unlike amphetamines, and because PEA is endogenous to the brain, side effects and tolerance are avoided.
PEA works in an area of the brain associated with emotions. Resulting in feelings of pleasure, more drive and impulse control, heightened creativity, and better sensory perception.
PEA improves libido, social behavior, a sense of wellbeing, and better overall performance.
PEA is currently being studied and used for the treatment of ADHD, depression, bipolar disorder, cognitive dysfunction like brain fog and poor concentration. And PEA looks promising for treating addiction and eating disorders.
How does Phenylethylamine feel?
PEA is rapidly broken down by monoamine oxidase-B (MAO) so unless you stack PEA with a MAO-B inhibitor, don’t expect its effects to last. Most experience a peak within 15 minutes and sustained energy for 30 min. to an hour.
If you’re ADHD or ADD, you should see an improvement in mood, attention span, focus and mental clarity. Not quite the same effect you’d get from something like Adderall but with a side benefit of more sociability.
Neurohackers report taking an MAOI (inhibitor) supplement 15 minutes before a PEA dose and the effects should last about 2 hours. And there’s no crash like you’d normally experience with a stimulant. Just a general feeling of well-being once it wears off.
As a pre-workout supplement, PEA provides a more intense and focused workout.
Older neurohackers seem to feel even more benefit when using PEA. Likely because monoamine oxidase levels over-power dopamine the older you get. And using PEA, especially with a MAOI helps restore dopamine and other neurotransmitters that are typically depressed with age.
PEA is a great nootropic for study because you should feel less anxiety, fewer panic attacks and less stress. And more motivation, a better mood, easier to maintain focus, and more energy.
Some report food cravings subside and it’s easier to lose weight.
Phenylethylamine Clinical Research
Phenylethylamine as an Antidepressant
Depression is the 2nd leading cause of disability among ages 15 – 44. By 2030, the World Health Organization predicts depression will be the leading cause of disability worldwide.[xii]
Selective serotonin reuptake inhibitors (SSRI) are the most popular antidepressant prescribed worldwide. SSRIs work by blocking the serotonin transporter and inhibiting the reuptake of serotonin. Resulting in an increase of serotonin in synapses.
But the problem is SSRIs are slow to act. And come with a host of side effects. Phenylethylamine (PEA) may be an alternative to SSRIs.
A study done in 2008 showed that PEA alters serotonin transporters by interacting with TAAR receptors. Increasing serotonin levels by preventing their reuptake just like prescription SSRIs.
The study suggested that PEA may be a safer treatment for depression than SSRIs.[xiii]
Phenylethylamine for ADHD
This discovery of a relationship between PEA levels and ADHD has excited researchers. Because it will hopefully improve levels of confidence during ADHD diagnosis. And reduce misdiagnosis and over-medication.
One study of ADHD children medicated with methylphenidate (Ritalin) had significantly higher PEA levels when using methylphenidate.[xv]
PEA binds to the TAAR1 receptor which alters monoamine transporter function. And leads to the inhibition of the reuptake of dopamine, serotonin, and norepinephrine. Which then increases the concentration of these neurotransmitters in neuron synapses.[xvi]
This increase in synaptic concentrations of dopamine can be accomplished by directly blocking the dopamine transporter. Which is how drugs like methylphenidate work to boost dopamine.
So if you are ADHD and crave chocolate, it’s likely because cocao supplies PEA.
Some naturopaths are beginning to prescribe PEA instead of stimulants like amphetamines or methylphenidate to treat ADHD.
PEA has a half-life of 5 – 10 minutes.[xvii] But the effects of PEA can be extended by using it with a MAO-B inhibitor.
If you do use a potent MAOI like selegiline (l-deprenyl) make sure you keep the dose low (i.e. 2.5 mg) or you’re in danger of inhibiting MAO-A as well. More on the “cheese effect” next.
Dosing more than recommended is NOT a good idea because you’ll likely feel jittery, irritable, get a headache, feel nausea, and very possibly force your heart rate to dangerous levels.
Phenylethylamine Side Effects
“Cheese effect”: Phenylethylamine (PEA) is metabolized by the enzyme MAO-B. And when monoamine oxidase (MAO) is inhibited by eating cheese, or any other prescription or natural MAO inhibitor (MAOI), the combination can result in a potentially dangerous increase in blood pressure.[xviii]
Studies show that selective MAO-B inhibition does NOT produce this cheese effect.[xix]
Examples of MAO-B selective inhibitors include low-dose selegiline (L-deprenyl), hordenine, Oat Straw, Glycyrrhiza uralensis (Chinese licorice root extract), Phellondendron amurense (Amur cork tree bark), Ferula assafoetida extract (resin), and Psoralea corylifolia (Bu Gu Zhi).[xx]
Do not use Phenylethylamine (PEA) if you are using a prescription MAOI like Marplan, Nardil, Azilect or Parnate, or have used one in the last 14 days.
Do not use PEA if you have phenylketonuria (PKU).
Too much PEA can cause irritability, nausea, amplified heart rate, jitteriness, and could be extremely dangerous.
Remember, Phenylethylamine (PEA) is an endogenous (natural) amphetamine. And used irresponsibly could produce the same dangerous side effects as anything else in the amphetamine-class of compounds.
Where to buy Phenylethylamine
Phenylethylamine (PEA) is available in capsules, tablets, and as a bulk powder.
DO NOT make the mistake of buying Phenylalanine instead of Phenylethylamine (PEA). Because it’s NOT the same thing. And is easily overlooked when searching for this nootropic.
You can buy Phenylethylamine in powder form from Bulk Supplements.
If you buy PEA in powder-form, you should invest in a capsule machine and make capsules. Because PEA is a particularly nasty tasting nootropic supplement.
Nootropics Expert Recommendation
I recommend using Phenylethylamine (PEA) as a nootropic supplement.
But most of us don’t get enough Phenylethylamine from our diet. So supplementation could help. Phenylethylamine is highly bioavailable, and quickly crosses the blood-brain barrier. So you should feel its effects soon after you take it.
It’s particularly helpful if you take Phenylethylamine prior to a stressful situation, workout, or physically demanding job. And it’s a great nootropic for studying.
PEA will provide the dopamine your brain needs. And doesn’t produce the stimulant crash when it wears off.
PEA is quickly degraded by monoamine oxidase-B. So to prologue its effects, stack it with a low-dose MAOI-B.
You can buy Phenylethylamine in powder form from Bulk Supplements.
[i] Janssen P.A., Leysen J.E., Megens A.A., Awouters F.H. “Does phenylethylamine act as an endogenous amphetamine in some patients?” International Journal of Neuropsychopharmacology. 1999 Sep;2(3):229-240. (source)
[ii] Miller G.M. “The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity” Journal of Neurochemistry 2011 Jan; 116(2): 164–176. (source)
[iii] Granvogl M., Bugan S., Schieberle P. “Formation of amines and aldehydes from parent amino acids during thermal processing of cocoa and model systems: new insights into pathways of the strecker reaction.” Journal of Agriculture and Food Chemistry. 2006 Mar 8; 54(5):1730-9. (source)
[iv] Khan M.Z., Nawaz W. “The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system.” Biomedicine and Pharmacotherapy. 2016 Oct;83:439-449. (source)
[v] Shannon H.E., Cone E.J., Yousefnejad D. “Physiologic effects and plasma kinetics of beta-phenylethylamine and its N-methyl homolog in the dog.” Journal of Pharmacology and Experimental Therapeutics. 1982 Oct;223(1):190-6. (source)
[viii] Shimazu S., Miklya I. “Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives.” Progress in Neuropsychopharmacological and Biological Psychiatry. 2004 May;28(3):421-7. (source)
[ix] Xie Z., Miller.GM. “Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain.” Journal of Pharmacology & Experimental Therapeutics 2008 May;325(2):617-28. doi: 10.1124/jpet.107.134247. (source)
[xi] Bunzow J.R. et. al. “Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.” Molecular Pharmacology. 2001 Dec;60(6):1181-8. (source)
[xii] World Health Association WHO. “The global burden of disease: 2004 update.” WHO Library Cataloguing-in-Publication Data; 2008. ISBN 978 92 4 156371 0.
[xiii] Xie Z., Miller G.M. “Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain” Journal of Pharmacology & Experimental Therapeutics 2008 May;325(2):617-28. (source)
[xiv] Scassellati C., Bonvicini C., Faraone S.V., Gennarelli M. “Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses.” Journal of the American Academy of Child Adolescent Psychiatry. 2012 Oct; 51(10):1003-1019. (source)
[xv] Kusaga A., Yamashita Y., Koeda T., Hiratani M., Kaneko M., Yamada S., Matsuishi T. “Increased urine phenylethylamine after methylphenidate treatment in children with ADHD.” Annals of Neurology. 2002 Sep; 52(3):372-4. (source)
[xvi] Xie Z., Miller G.M. “Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain.” Journal of Pharmacology & Experimental Therapeutics. 2008 May; 325(2):617-28. (source)
[xvii] Shannon H.E., Cone E.J., Yousefnejad D. “Physiologic effects and plasma kinetics of beta-phenylethylamine and its N-methyl homolog in the dog.” Journal of Pharmacology & Experimental Therapeutics. 1982 Oct; 223(1):190-6. (source)
[xviii] Cashin C.H. “Effect of sympathomimetic drugs in eliciting hypertensive responses to reserpine in the rat, after pretreatment with monoamineoxidase inhibitors.” British Journal of Pharmacology. 1972 Feb;44(2):203-9. (source)
As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.