What is PEA ?

(PEA), also known as beta- phenyl-ethyl-amine or 2-phenyl-ethyl-amine, is a central nervous system stimulant. Normal amounts of PEA produced in the body support healthy energy levels, attention and focus, well-being, happiness, and cognitive function.

PEA is a bio-genic mono-amine or a substance with one amino acid group connected to an aromatic ring that acts as a neurotransmitter and/or hormone in the body. However, PEA is found at very low levels in the central nervous system and is therefore called a trace amine. PEA does not act like a classic neurotransmitter, and its molecular mechanism of action differs from other bio-genic amines, such as serotonin or dopamine.

PEA, as a trace amine, is an endogenous amphetamine and is present in only small amounts in the brain compared to classic neurotransmitter amines such as norepinephrine, dopamine, and serotonin.1 PEA is a neuromodulator, influencing the effects of central monoamine neurotransmitters (dopamine, norepinephrine, and serotonin). Trace amines like PEA are synthesized in monoaminergic nerve terminals and have their own set of receptors called trace amine-associated receptors (TAARs). These receptors are widely expressed in the brain and are involved in:

· Attention

· Cravings

· Focus

· Mood & Emotion

· Motor Control

· Nerve health

· Reward & Motivation

· Sleep-Wake Cycle

· Stress Response

PEA is made in monoaminergic neurons located in the central nervous system from the amino acid L- phenylalanine. This is accomplished through the enzyme amino acid decarboxylase (AADC), which converts L- phenylalanine to PEA at a rate similar to the central synthesis of dopamine. Unlike classical neurotransmitters, PEA is not stored in neurons but instead is broken down primarily through monoamine oxidase (MAO-B), which catabolizes PEA at a very rapid rate to phenylacetic acid (PAA), which will be discussed further. Because it is broken down so rapidly, its ability to act as a stimulant is weak and short-acting. PEA, dopamine, norepinephrine, epinephrine synthesis and metabolism pathway Phenyl-ethyl-amine Synthesis. PEA is produced from phenylalanine and requires vitamin B6. It is rapidly degraded to phenylacetic acid (PAA) and N- Methylphenethylamine (NMPEA). Vitamin B2 is a cofactor in the breakdown of PEA to phenylacetic acid (PAA). Enzymes and Cofactors found in Multiple Monoamine Pathways 1) Aromatic L-amino acid decarboxylase (AADC) + Vitamin B6 2) Monoamine oxidase (MAO) + Vitamin B2 3) Catechol-O-Methyltransferase (COMT) + Magnesium + S-adenosylmethionine (SAMe) Neurotransmitters and Metabolites DHPG: 3,4- dihydroxyphenylglycol, DHMA: 3,4-dihydroxymandelic acid, DOPAC: 3,4-dihydroxyphenylacetic acid, DOPAL: 3,4-dihydroxyphenylacetaldehyde, DOPEGAL: 3,4- dihydroxyphenylglycolaldehyde, HMA: 4-hydroxy-3-methoxyphenylacetaldehyde / homovanillin, HVA: homovanillic acid, MHPG: 3-methoxy-4-hydroxyphenylglycol (aka MOPEG), MOPEGAL: 3-methoxy-4-hydroxyphenylglycolaldehyde, NMPEA: N-Methylphenethylamine, VMA: vanillylmandelic acid, 3-MT: 3- methoxytyramine, Enzymes AD: aldehyde dehydrogenase, ADH: alcohol dehydrogenase, AR: aldehyde reductase, DBH: Dopamine Beta-Hydroxylase, LAAO: L- amino-acid oxidase, PH: alanine Hydroxylase, PNMT: phenylethanolamine N-methyltransferase, TAT: Tyrosine aminotransferase, TH: Tyrosine hydroxylase, Cofactors BH4: Tetrahydrobiopterin, Fe: Iron, SAMe: S-adenosylmethionine, Vit: Vitamin

PEA is considered an endogenous amphetamine, but its stimulatory abilities are weak and short. PEA levels produced by the body under normal physiological conditions support healthy energy levels, which is why they are often of interest to athletes.

PEA is a nootropic substance that supports mental performance. Through its ability to amplify the effects of other neurotransmitters and brain chemicals, including acety-L-choline, PEA increases motivation for finishing tasks and enhances cognitive function and problem-solving abilities. Acety-L-choline acts as a neurotransmitter and neuromodulator that plays a role in many bodily functions, particularly learning and memory. By enhancing acety-L-choline actions, PEA can support cognitive function and improve focus and attention span.

Enhances Mood Balanced levels of PEA contribute to happiness, pleasure, emotional well-being, and having an upbeat attitude. Levels of the PEA metabolite, PAA, are low in unhappy people. Conversely, employing strategies to improve mood in this group of people raises PEA concentrations in the brain. PAA itself acts like a natural endorphin, producing what’s known as a “runner’s high.”

Low PEA is linked to:

• Brain fog
• Cravings
• Low energy levels
• Inability to concentrate
• Not feeling motivated
• Social introversion
• Unhappiness

High PEA may be associated with:

• Jitteriness
• Increased heart rate
• Muscle stiffness
• Nervousness
• Shakiness
• Rising blood pressure

Alterations in PEA levels may occur due to changes in Aromatic L-amino acid decarboxylase (AADC, a rare genetic disorder that affects the nervous system) or Monoamine Oxidase B (MAO-B), the enzymes involved in PEA synthesis and breakdown. Low dietary protein, maldigestion, or malabsorption can impact PEA levels, as protein is a source of L-phenylalanine. Lack of exercise is another contributor to low PEA levels (more on this later). Certain medications that interfere with PEA production, such as Monoamine Oxidase Inhibitors (MAOIs), are antidepressants that block the activity of monoamine oxidase, the enzyme responsible for breaking down neurotransmitters, including PEA. This inhibition leads to increased levels of PEA and other neurotransmitters in the brain.

PEA boosts the effectiveness and actions of catecholamine neurotransmitters. Most evidence indicates that it both amplifies the release of and competitively blocks the reuptake of all the monoamines: dopamine, norepinephrine, and serotonin. PEA is localized around dopaminergic neurons and regulates dopaminergic neurotransmission. It plays a role in dopamine’s pleasure-producing effects. High doses of PEA significantly increase serotonin levels, but serotonin can inhibit PEA.

Urinary neurotransmitter testing for PEA has been used as a screening tool for monitoring PEA levels in various populations, including individuals seeking to support attention and focus, learning and memory, and mood. Major universities and research facilities throughout the world continue to use this technology for measuring neurotransmitter levels in patients with a variety of mental health conditions.

Several strategies can be used to support healthy levels of PEA.

PEA as a Nootropic Supplement Phenyl-ethyl-amine can be consumed as a dietary supplement. The typical Phenyl-ethyl-amine dose is 100 to 500 mg daily. Clinicians often start their patients on a lower dose and gradually increase the amount. PEA should also not be taken together with medications that increase serotonin levels, as this can cause an excess of serotonin. Testing PEA and serotonin levels before beginning supplementation is recommended.

PEA is found in several food sources. 1 It’s produced through bacterial fermentation, especially Bacillus subtilis, so some fermented foods can be an excellent source of PEA.13

• Almonds
• Blue-green algae
• Chickpeas
• Chocolate
• Eggs
• Flaxseeds
• Green peas
• Lentils
• Natto and some cheeses
• Soybeans
• Walnuts

PEA is also made through the conversion of L-phenylalanine from food. Consequently, eating high-protein foods rich in L-phenylalanine (This amino acid helps produce three key brain neurotransmitters: dopamine, norepinephrine, and epinephrine. DL-phenylalanine helps promote alertness, mood, and appetite control.), such as eggs, chicken, turkey, beef, and dairy, can also raise PEA levels. Supplementation of L-phenylalanine, vitamin B6, vitamin B2, and riboflavin can improve PEA synthesis and clearance. 

Exercise and PEA: Exercise is known to elevate levels of PEA and/or its metabolites. For example, in one study, the PEA metabolite PAA increased 77% after exercise, according to 24-hour urine samples from healthy men. The researchers concluded that exercise likely increases PEA, which could explain the known mood-boosting effect of physical activity.

PEA is the only neurotransmitter that crosses the blood-brain barrier freely and bidirectionally. Low PEA in urine serves as a recognized biomarker in ADHD. ADHD patients who respond well to treatment typically show marked increases in urinary PEA levels. On the flip side, high PEA (it can be very high) is associated with anxiety. High PEA can be addressed by supplementing with SAMe, vitamin B2, a combination of zinc and copper, or nutritional lithium.

Takase K, Oda S, Kuroda M, Funato H (2013) Monoaminergic and Neuropeptidergic Neurons Have Distinct Expression Profiles of Histone Deacetylases. PLoS ONE

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