Phenethylamine

Phenylethylamine or Phenethylamine (PEA) is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the mammalian central nervous system. It is biosynthesized from the amino acid phenylalanine by enzymatic decarboxylation. Besides mammals, phenethylamine is found in many other organisms and foods such as chocolate, especially after microbial fermentation. It is sold as a dietary supplement for purported mood and weight loss-related therapeutic benefits; however, orally ingested phenethylamine is usually inactive on account of extensive first-pass metabolism by monoamine oxidase (MAO) into phenylacetic acid, preventing significant concentrations from reaching the brain.

The group of phenethylamine derivatives is referred to as the phenethylamines. Substituted phenethylamines, substituted amphetamines, and substituted methylenedioxyphenethylamines (MDxx) are a series of broad and diverse classes of compounds derived from phenethylamine that include stimulants, psychedelics, and entactogens, as well as anorectics, bronchodilators, decongestants, and antidepressants, among others.

Chemistry
Phenethylamine is an amine, consisting of a benzene ring and an aminoethyl group. It is a colorless liquid at room temperature. Phenethylamine is soluble in water, ethanol, and ether. Similar to other low-molecular-weight amines, it has a fishy odor. Upon exposure to air, it forms a solid carbonate salt with carbon dioxide. Phenethylamine is strongly basic and forms a stable crystalline hydrochloride salt with a melting point of 217 °C. Phenethylamine is also a skin irritant and possible sensitizer.

Phenethylamine has an inactive constitutional isomer 1-phenylethylamine, which itself has two stereoisomers: (R)-(+)-1-phenylethylamine and (S)-(-)-1-phenylethylamine.

Pharmacology
Phenethylamine, similarly to amphetamine, acts as a releasing agent of norepinephrine and dopamine. However when taken orally it is rapidly metabolized.

Abnormally low concentrations of endogenous phenethylamine are found in those suffering from attention-deficit hyperactivity disorder (ADHD) and often in clinical depression, whereas abnormally high concentrations have been discovered to have a strong, positive correlation with the incidence of schizophrenia.

Pharmacokinetics
Phenylethylamine's half-life is 5–10 minutes. Phenylethylamine is metabolized by MAO-A, MAO-B, aldehyde dehydrogenase, and dopamine-beta-hydroxylase. If initial phenylethylamine brain concentration was low, phenylethylamine brain levels can be increased by a 1000-fold when taking a MAO Inhibitor, and by 3-4 times if the initial concentration was high. Alcohol and THC increase phenylethylamine levels by a 4-fold.

Chocolate theory of love
In the early 1980s, researcher Michael Liebowitz, author of the popular 1983 book The Chemistry of Love, remarked to reporters that "chocolate is loaded with PEA." This became the focus for an article in The New York Times, which was then taken up by the wire services and then by magazine free-lancers, evolving into the now-eponymous "chocolate theory of love." However, as noted earlier, phenethylamine is rapidly metabolized by the enzyme MAO-B, preventing significant concentrations from reaching the brain, thus contributing no perceptible psychoactive effect without the use of a monoamine oxidase inhibitor (MAOI).