The Science of PEA

by

DR. RICHARD CLARK KAUFMAN

Neuroamplifier for Peak Performance

PEA amplifies the activity of the major neurotransmitters in your brain for increased longevity, peak mental-and-physical performance, slower aging, a sense of wellbeing and a renewed youthful functioning body. PEA has unique rapid-uplifting effects on mood, energy, mental abilities, attention, focus, motivation, alertness, awareness, pleasurable, physical performance, creativity, sexuality, and sensory perceptions.

PEA (beta-phenylethylamine) is a naturally occurring trace amine neurotransmitter (chemical signal messenger between nerves) and neuroregulator that’s normally synthesized in the brain from the amino acid phenylalanine. PEA amplifies the signal strength and effectiveness of the major neurotransmitters in the human brain to improve your life.

PEA increases the effects of dopamine (for wellbeing and feeling pleasure), norepinephrine (the brain’s stimulant for wakefulness and higher performance), acetylcholine (for improving memory and mental activity), and serotonin (for better mood emotion and impulse control). PEA is a highly-concentrated neurotransmitter in the limbic system (the brain’s emotional center) that increases motivation, physical drive, feelings and social activity.

PEA... the Brains Endogenous Mesencephalic Enhancer

According to researchers PEA is an endogenous “mesencephalic enhancer”. It plays a key role in the functioning of our innate and acquired drives. There are enhancer-sensitive neurons in the brain that work in a split-second on a high activity level due to PEA. In mere microseconds, PEA causes an impulse-mediated release of catecholamines (dopamine, epinephrine) and serotonin in the brain. There’re rapid occurring improvements in cognitive performance, attention, awareness, pleasure, libido, and sense of wellbeing.

Due to the progressive decay of the mesencephalic enhancer regulation with the passing of time, the daily use of an enhancer substance like PEA during post-developmental life could significantly slow the age-related decay of behavioral performances, prolong life, and prevent the precipitation or delay the onset of Parkinson's disease and Alzheimer's disease.

PEA... Amplifies Neurotransmitter Signals for Peak Mental and Physical Performance at Any Age

PEA is literally a ‘neuroamplier’ for a higher performance in life. PEA enhances the electronic coupling in the synaptic gap between nerve cells. It boosts the signal strength of neurotransmitters by increasing their signal-to-noise ratio. This means that PEA more efficiently couples the release of neurotransmitters to the electrical impulse that triggers their release. The end result… PEA cranks up the volume of neurotransmitter activity for higher performance throughout your body. And it does not matter how old you are to experience a noticeable performance improvement in daily activities.

Protects Sensitive Brain Circuitry

PEA protects our delicate neural circuits by preventing over-excitation or under-stimulation of neural transmissions. PEA keeps the entire system in balance and neural activity operating more efficiently and safely within dynamic limits for peak performance.

Longevity, Slower Aging, Youthful Functions

PEA is a powerful weapon for fighting aging. It has a unique ability to help delay aging, extend healthy life span, and restore more youthful mental and physical functions. PEA is a “catecholamine activity enhancer” that according to researchers improves the activity of dopamine/noradrenalin neurons, which have a pivotal role in regulating aging. According to the pioneering research of Dr. Joseph Knoll, a respected neurochemist, pharmacologist and emeritus professor, catecholamine (neurotransmitters such as dopamine and norepinephrine) levels reach a maximum at sexual maturity, and then begin a long, gradual downhill slide. The rate of decline decides how fast a person ages. According to Dr. Knoll, catecholamine levels, learning ability, sexual activity and longevity are all interlinked. The efficiency of your catecholamine brain machinery plays a major role in determining the quality and duration of your life. Higher-performing, longer-living individuals have a more active, more slowly deteriorating catecholamine system than their lower-performing, shorter-living peers.

By rehabilitating our brains’ catecholamine system with enhancer substances (including PEA and its derivatives) it’s possible to transform a lower-performing, shorter-living individual into a better-performing, longer-living one with more youthful mental and physical functions.

Starting around age 25, there’s a lifelong decline in catecholamine neurotransmitters (epinephrine, norepinephrine, and dopamine), a slower decline in the indoleamine neurotransmitter (serotonin), and a shifting imbalance of the catecholamine/serotonin ratio. Catecholamine deficiencies and neurotransmitter imbalances are a principal cause of loss of “hypothalamic sensitivity” for the progressive metabolic shifts that produce aging and the diseases of aging, according to Dr. Vladimir Dilman’s Neuroendocrine Theory of Aging.

According to Dr. Dilman, a renowned Russian biogerontologist, aging is caused by a progressive loss of sensitivity by the hypothalamus (and related structures in the brain) to feedback inhibition from hormones and neurotransmitters. Throughout your lifespan, this loss of sensitivity produces a progressive shifting away from internal balance and altered levels of hormones, neurotransmitters and cell signalers. These are the cause of many post-maturational diseases, accelerated aging, and earlier death. The Neuroendocrine Theory of Aging explains in detail how this causes the major diseases of aging, which contribute to over 85% of early deaths of middle-aged and elderly individuals.

To correct catecholamine deficiencies to help delay aging, prolong life span, prevent aging disorders, and restore youthful biological functions, Dr. Dilman and other aging researchers have suggested: (1) Increase neurotransmitter production and activity; (2) Decrease catecholamine breakdown from MAO-B enzymes; (3) Correct neurotransmitter deficiency and imbalance of the catecholamine/serotonin ratio; (4) Inhibit neurotransmitter re-uptake, to increase intersynaptic neurotransmitter levels; and (5) Correct the decrease in receptor sensitivity and responsiveness of target cells and tissues to neurotransmissions.

Rehabilitates Neurotransmitter Systems that Fight Aging

PEA increases neurotransmitter production and activity, helps correct the neurotransmitter deficiency and imbalance of the catecholamine/serotonin ratio, inhibits neurotransmitter re-uptake, and regulates the responses of cells to neurotransmissions for a stable internal equilibrium. .

PEA is the parent compound of l-deprenyl, a catecholamine-enhancing, dopamine-increasing, and neuroprotective compound with proven life-extension actions in animal research. L-deprenyl produces a huge spike in brain PEA that contributes to its anti-aging actions.

The Brain’s Natural and Safe Stimulant

PEA has invigorating, stimulating, energizing effects. PEA acts on the central nervous system to produce alertness, wakefulness, attention, energy and endurance. Unlike drug stimulants that are highly addictive and harmful to your health, PEA is free of harmful side-effects, and is non-toxic and non-addictive. PEA does not overexcite the nervous system and damage cells, but protects neurons. PEA doesn’t deplete neurotransmitter levels, PEA regulates them. This avoids the “crashing upon cessation of use” common with stimulant drugs.

Feelings of Happiness, Pleasure and Emotional Wellbeing

PEA is an immediate shot of “happiness, pleasure, and emotional well being,” even during those stressful times. PEA increases the release and activity of dopamine, which is associated with the pleasure system of the brain and considered a "feel good" neuromodulator/neurotransmitter--it activates a feeling of pleasure and euphoric sense of wellbeing.

Increased Energy, Alertness and Sensory Perceptions

The boost of energy-generating catecholamines (dopamine and noradrenalin) produces amphetamine-like stimulation and performance enhancement. PEA induces behavioral and physiological effects similar to those of amphetamine. Unlike amphetamine and other stimulant drugs, PEA is endogenous to the brain. PEA does not develop tolerance or dependency, or produce any side effects. PEA has been referred to by researchers as an "endogenous amphetamine” because it’s produced by your brain. After ingesting PEA, people commonly report a surge of energy, wakefulness, alertness, and heightened senses.

Increased Cognitive Power and Smartness

PEA helps upgrade your mind with faster thinking, increased attention, quicker decision making, greater sensory awareness, less brain-fog and immediate, easy memory access. PEA releases acetylcholine, a neurotransmitter that plays an integral role in learning and memory. Brain receptors respond to acetylcholine by facilitating memory and higher cognitive functions. In addition, PEA increase noradrenalin, the brain's version of adrenaline, which is required for alertness, concentration, and “get up and go.” An increase in glutamate from PEA can throw switches to the “on” position in memory-forming circuits, making it easier to form memories.

Help for Attention Disorders, Addictions and Substance Abuse

Current research on PEA’s trace amine receptor neuromodulator and neurotransmitter actions are reaping rewards. PEA is proving beneficial for attenuating attention-related problems, controlling addictions, overcoming substance abuse and correcting neurobehavioral problems. This is an exciting area of research for PEA with many practical uses and clinical implications.

Proven Mood-Brightener for Relief of Depression

The “Phenylethylamine Hypothesis of Depression” states that PEA sustains psychological energy just as thyroid hormone sustains physical energy And a deficit of PEA produces depression The Phenylethylamine hypothesis goes on to state that PEA is a neuromodulator of mood, attention, pleasure-seeking behavior and libido.

Scientist tell us that a deficit in PEA s brain content and/or a decrease in the turnover of endogenous PEA is causal factor in subclinical and clinical depressive conditions. And taking PEA orally to replace and increase PEA brain levels may dispatch the symptoms. It gives individuals an elevation of mood and increased quality of life.

A Natural Internal NDRI and SSRI

In terms of safety, PEA does produce the adverse effects of pharmaceutical NDRIs and SSRIs. It’s due to PEA’s self-regulating control of neurotransmissions and its intrinsic neuroprotective propertiesPEA is a research-proven to quickly boost a depressive mood of sadness, hopelessness, discouragement, and being “down in the dumps.” PEA is potent in enhancing the release of catecholamines and blocking their reuptake, especially of dopamine. PEA has similar actions with serotonin, but just not as powerful. That means that PEA is a strong NDRI (Norepinephrine-Dopamine Reuptake Inhibitor) and weaker acting SSRI (Selective Serotonin Reuptake Inhibitor). Their synergistic actions make PEA an ideal nutraceutical complement or alternative to standard protocols

In terms of safety, PEA does produce the adverse effects of pharmaceutical NDRIs and SSRIs. It’s due to PEA’s self-regulating control of neurotransmissions and its intrinsic neuroprotective properties.

Rapid Sustained Depression Relief in 60% of Patients

In multiple clinical trials, PEA produced a rapid and sustained relif of depression in 60% of the patients after two weeks. In one trial the patients were prevosly resistant to a wide range of treatments including SSRIs and MAOIs . They begain showing mood elevation within a day or two of taking PEA. Other reported effects included restoration of energy, concentration, motivation and sex drive. PEA treatment improved their sleep and thrre were no side effects.

The success rate for treating depression with PEA is is the same percentage as the major Serotonin-Selective Re-uptake Inhibitors (SSRIs)--but without their serious side effects and toxicity. In fact, PEA has produced sustained relief of both acute and chronic depression in a significant number of people, including some unresponsive to standard protocols, according to research psychopharmacologist and psychiatrist Dr. Hector Sabelli.

Runner’s Euphoric High

Moderate exercise normally increases PEA levels, so researchers now believe that this increase causes the euphoric mood often called "runners' high." What about the natural substances called endorphins, previously linked to runners' high? Endorphins don't penetrate the brain and when chemicals were administered to block the binding of endorphins to their neuron receptors, the runners still experienced euphoric high. Also, depressed people tend to have low PEA levels, so the researchers say there now is an explanation of why exercise is a natural antidepressant.

The Mediator of Psychological Energy, Love, Self-Love and Libido

Freud developed the concept of a single psychobiological energy as the source of our mental, emotional and sexual energy. This single energy is the driving force for sexual libido, pleasure-seeking behavior, interpersonal energy, love, warmth, affection and other personal attributes. Modern research with PEA provides a neurophysiogical basis for Freud’s model of the 19th century.

PEA actions on neurotransmissions have produced sexual arousal and erections in research studies. PEA is shown to create feeling of love, self-love, emotional warmth and sexual pleasure. According to Dr. Hector Sabelli, who has extensively studied PEA, “I believe that PEA may be the hormone of libido,” not just testosterone. Sabelli's research found that high PEA levels lead to increased sex drive, pleasure-seeking activity and courage while low levels reflect the loss of libido, physical drive and emotions in depression. In short, PEA is a natural aphrodisiac.

Fat Burning and Weight loss

PEA’s ability to elevate blood catecholamine levels may be useful in the thermogenic (heat-caused) burning of stored body fat for losing weight. Increased levels of epinephrine and norepinephrine can stimulate beta-adrenergic receptors located on adipose (fat) tissue to release fatty acids into circulation as a fuel source. In other words, PEA turns up your cellular thermostat to burn fat for energy. Plus, catecholamines act on hormone-sensitive lipase, the enzyme for removing fat from storage sites. In addition, PEA has demonstrated appetite-reducing activity, reducing food intake in animal research.

Supercharged Physical and Athletic Performance

PEA can increase physical energy, stamina, concentration, coordination, reaction and thinking time, spatial recognition, motivation, and confidence in most adults. PEA is a natural biochemical stimulant that increases actions of dopamine, norepinephrine and serotonin neurotransmitters for greater physical and mental performance.

PEA helps prevent the age-related gradual decline in physical activity and performance after reaching maturity. By raising catecholamine activity to youthful levels, PEA helps elevate the ceiling for “maximum physical performance,” especially in individuals past their prime.

How PEA Works

When taken orally, PEA easily crosses the blood-brain barrier. It is rapidly available in the brain as an neuroamplifier of neurotransmitter signal strength, neuroregulator of transmitter transport, and excitatatory (stimulating) neurotransmitter in different region of the brain.

Amplifies Neurotransmitter Activity

PEA is released from nerve vesicles in the brain, causing a larger release of neurotransmitters in response to a given nerve signal. It’s like “cranking up the volume” of nerve-cell activity. PEA induces higher concentration, continuous strong release, and greater activity of dopamine (for feeling pleasure and wellbeing), norepinephrine (the brain’s stimulant for get-up-and-go), acetylcholine (for memory and cognitive functions), and serotonin (for good moods and feelings, and impulse control).

Modulates Neurotransmitter Functions by binding TAAR1

PEA modulates neurotransporter functions by binding with its paired Trace Amine-Associated Receptor 1(TAAR1). TAAR1 is a G-protein coupled receptor that’s activated by PEA and certain monoamines. Activation of TAAR1 by PEA significantly inhibits the uptake and induces efflux of the neurotransmitters dopamine, norepinephrine, and serotonin. PEA increases the extracellular levels of these neurotransmitters by inhibiting their reuptake into the presynaptic cell. And this increases their beneficial activity throughout your body.

Guardian of Neurobiology and Homeostastic Regulator Against Metablic Dysfunctions

PEA is neural guardian of homeostasis (maintaining healthy metabolic equilibrium). The binding of PEA with TAAR1 protects delicate neural circuitry against harmful changes. PEA self-regulates transmitter activity to prevent over-excitation of under-stimulation transmitter signal strength and activity. PEA acts as an homeostatic controller to maintain the neuronal activity within defined physiological limits to prevent metabolic dysfuctions and neurological disorders. This makes PEA and other trace amines perfect candidates for the development of novel therapeutics for a wide range of human disorders

Endogenous Amphetamine-Like Stimulating Neurotransmitter

PEA is an excitatory neurotransmitter with its own receptor and a chemical structure similar to amphetamines that induces behavioral and electrophysiological effects similar to those of amphetamine, Unlike amphetamine, PEA is endogenous to the brain and does not develop tolerance or dependency, or produce any side effects. of amphetamines sold under tradename Aderall® and the adverse effects of the popular drug stimulant Ritalin® that is prescribed for treating Attention Deficit Disorders.

Concentrated Limbic System Neurotransmitter

PEA is highly concentrated in the limbic system of the brain, the center of emotions. The interaction of PEA with its chemical receptor sends signals to the brain that can improve emotions, pleasurable feelings, motivation, physical drives, impulse control, social behavior, sexuality, creativity, and sensory perceptions, the sense of wellbeing and overall performance.

Trigger of Brain Plasticity and Neurogenesis

PEA may trigger neurotransmitters for “Brain Plasticity” and “Neurogenesis” (the forming of new brain cells, information processing connections and functions) that increase cognition, learning, memory, skills, smartness and performance. The mechanism is thought to involve PEAs action of increasing dopamine neurotransmitter from synapses and acting as a dopamine reuptake inhibitor in certain brain regions.

Actions of PEA on Neurotransmitters

• Stimulates dopamine’s nerve terminals and activity for feeling pleasure, libido and emotional wellbeing;
• Increases epinephrine and norepinephrine catecholamine activity, for energy production and inhibition of their reuptake;
• Increases the action of acetylcholine for cognitive functions by stimulating the AMPA glutamatergic receptors;
• Elevates mental alertness and mood by suppressing the inhibitory effects of GABA-B receptors;
• Enhances serotonin release and its uplifting activity on mood, emotions and control.

Furthermore, PEA self-regulates transmitter activity to prevent over-excitation of under-stimulation transmitter signal strength and activity. Thus PEA acts as an homeostatic controller to maintain the neuronal activity of monoamine neurotransmitters within defined physiological limits.

Present and Future Therapeutic Use

PEA may be therapeutically useful in any disorder associated with an alteration in the functioning of its partner neurotransmitters. In the case of PEA, it’s primarily the transmitter’s dopamine, norepinephrine, serotonin and acetylcholine. This gives PEA the ability to alleviate the symptoms of vast number neurological dysfunctions and behavioral disorders without addressing the underlying pathology of the disease. Convincing evidence has been presented for using PEA in the treatment for a wide range of neurological dysfunctions and behavioral disorders.

• AFFECTIVE DISORDERS ( depression, bipolar disorder)
• ATTENTION DEFICIT / HYPERACTIVITY DISORDER
• COGNTIVE DYSFUNCTON ( brain fog, confusion, forgetfulness, poor concentration, sluggish cognitive tempo slowed reaction times, diminished awareness)
• DRUG ABUSE & SUBSTANCE DEPENDENCE (alcoholism, nicotine dependence, addictions to methamphetamines, cocaine opiods & pyschostimulants)
• ADDICTED BEHAVIOR (gambling, sexual addiction )
• EATING DISORDERS (obesity. anorexia)

More Uplifting and Effective than Phenylalanine

The human brain forms PEA from the essential amino acid l-phenylalanine by an enzyme-driven cellular process. Phenylalanine is the precursor to the amino acid tyrosine, which produces the neurotransmitters dopamine, norepinephrine and adrenalin in a sequential process, but phenylalanine supplements don’t significantly boost PEA concentrations. And phenylalanine supplements can boost catecholamine neurotransmitter levels excessively, producing anxiety, headaches and hypertension. What’s worse, some people’s biochemistry transforms phenylalanine into the nasty, neurotoxic (brain-damaging) metabolites. By contrast, PEA safely increases amplies the activity of dopamine, norepinephrine and other brain transmitters to produce desirable and remarkable effects.

Fast-acting but Short-lived.

The human body can synthesize significant quantities of PEA, but functional levels of a PEA remain fairly low because it’s usually broken down by the enzyme MAO-B within several hours. As result, PEA effects are relatively short acting. So the fast-acting PEA compound is best taken by most people every 3-4 several hours for an immediate boost and for maintaining activity throughout the day.

Bioperine®, a Natural Bioavailability Enhancer of PEA

Bioperine® is a patented standardized extract that contains 95 percent piperine, a phytochemical that enhances the bioavailability of PEA. Piperine increases absorption from the gut and inhibits MAO-B from breaking down dopamine, with mood-brightening effects. The synergy between Bioperine® and PEA can increase and extend the effects of PEA.

Protective Patent-pending Nanoemulsion Delivery

PEA is best formulated with a patent-pending “Self-emulsifying Nanosphere Delivery System.” Natural phospholipids and medium-chain triglycerides form a nanosphere protective covering in the intestinal tract, enhancing bioavailability (delivery) of PEA., PEA should be manufactured in protective coated tablets that safe-guard PEA from degradation in the harsh acidic environment of the stomach and carry PEA to the intestinal tract. PEA is rapidly released for PEA intestinal absorption, enhanced delivery to the bloodstream and transport to the brain.

Warnings

Do not use PEA if you are pregnant or nursing.

Do not take PEA if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), or tranylcypromine (Parnate) within the past 14 days. MAO inhibitors prolong and increase the actions of phenylethylamine. Do not take PEA if have PKU phenylketonuria If you are on medication or have a health condition, consult a physician before using PEA.

References

1. Bailey BA, Phillips SR, Boulton AA, In vivo release of endogenous dopamine, 5-hydroxytryptamine and some of their metabolites from rat caudate nucleus by phenylethylamine. Neurochem Res. 1987, 12: 173-178.
2. Baker GB, Bornstein RA, Rouget AC, et al. Phenylethylaminergic mechanisms in attention-deficit disorder. Biol Psychiatry 1991; 29:15-22.
3. Bakhle YS, and Youdim MB. Metabolism of phenylethylamine in rat isolated perfused lung: evidence for monoamine oxidase 'type B' in lung. Br J Pharmacol. 1976, 56(1): 125-127.
4. Birkmayer W, Riederer P, Linauer W, Knoll J. L-deprenyl plus Lphenylalanine in the treatment of depression. J Neural Transm 1984; 59: 81-7.
5. Blenau W, Balfanz S, Baumann A. Amtyr1: characterization of a gene from honeybee (Apis mellifera) brain encoding a functional tyramine receptor. J Neurochem 2000; 74: 900-8.
6. Borison RL, Mosnaim AD, Sabelli HC. Brain 2-phenylethylamine as a major mediator for the central actions of amphetamine and methylphenidate. Life Sci 1975; 17: 1331-43
7. Borison RL, Mosnaim AD, Sabelli HC. Brain 2-phenylethylamine as a major mediator for the central actions of amphetamine and methylphenidate. Life Sci 1975; 17: 1331-4
8. Branchek TA, Blackburn TP. Trace amine receptors as targets for novel therapeutics: legend, myth and fact. Curr Opin Pharmacol 2003; 3: 90-97.
9. Camp BJ. Action of N-methyltyramine and N-methyl beta-phenylethylamine on certain biological systems. Am J Vet Res. 1970, 31(4): 755-762.
10. Comings DE, Ferry L, Bradshaw-Robinson S, et al. The dopamine D2 receptor (DRD2) gene: a genetic risk factor in smoking.Pharmacogenetics 1996; 6: 73-9.
11. Comings DE, Muhleman D, Ahn C, Gysin R, Flanagan SD. The dopamine D2 receptor gene: a genetic risk factor in substance abuse. Drug Alcohol Depend 1994; 34: 175-80
. 12. Comings DE, Rosenthal RJ, Lesieur HR, et al. A study of the dopamine D2 receptor gene in pathological gambling. Pharmacogenetics 1996; 6: 223-3
13. Cooper SJ, Dourish CT. Hypodipsia, stereotypy and hyperactivity induced by beta-phenylethylamine in the water-deprived rat. Pharmacol Biochem Behav. 1984, 20(1): 1-7.
14. Dilman V, Dean W. The Neuroendocrine Theory of Aging, The Center for Bio-Gerontology, Pensacola, 1992.
15. Dilman V. The Law of Deviation of Homeostasis and Diseases of Aging, John Wright.PSG, 1981.
16. Dilman, V.M., and Young, J.K. Development, Aging and Disease--A New Rationale for an Intervention Strategy. Harwood Academic Publishers, Chur, Switzerland, 1994.
17. Dourish CT, Boulton AA. The effects of acute and chronic administration of beta-phenylethylamine on food intake and body weight in rats. Prog Neuropsychopharmacol. 1981, 5(4): 411-414.
18. Dourish CT, et al. Deutrium substitution enhances the effects of b-phenylethylamine on spontaneous motor activity in the rat. Pharmacol. Biochem. Behav. 1983, 19: 471-475.
19. Dyck LE, Durden DA, Boulton AA. Formation of β - phenylethylamine from the antidepressant, β-phenylethylhydrazine. Biochem Pharmacol 1985; 34: 1925-9.
20. Fischer E, Spatz H, Heller B, Reggiani H. Phenethylamine content of human urine and rat brain, its alterations in pathological conditions and after drug administration. Experientia 1972; 28: 307-8.
21. Fuxe K, Grobecker H, Jonsson J. The effect of β-phenylethylamine on central and peripheral monoamine-containing neurons. Eur J Pharmacol 1967; 2: 202-7.
22. Greenshaw AJ, Juorio AV, Boulton AA. Behavioral and neurochemical effects of deprenyl and β-phenylethylamine in 23. Greenshaw AJ, Sanger DJ, Blackman DE. Effects of damphetamineand of β-phenylethylamine on fixed interval
24. Greenshaw AJ. Functional interactions of 2-phenylethylamine and of tryptamine with brain catecholamines: implications for psychotherapeutic drug action. Prog Neuropsychopharmacol Biol Psychiatry 1989; 13: 431-43. 25. Greenshaw AJ. β-Phenylethylamine and reinforcement. Prog Neuropsychopharmacol Biol Psychiatry 1984; 8: 615-20.
26. Grimsby J, et al. Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet. 1997, 17(2): 206-210
27. Grimsby J, Toth M, Chen K, et al. Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet 1997;17: 206-10
28. Janssen PA, Leysen JE, Megens AA, Awouters FH. Does phenylethylamine act as an endogenous amphetamine in some patients? Int J Neuropsychopharmcol 1999; 2: 229-240.
29. Kato M. et al β-Phenylethylamine modulates acetylcholine release in the rat striatum: involvement of a dopamine D2 receptor mechanism European Journal of Pharmacology 2001 418(1-2): 65-71
30. Kim K-A, von Zastrow M. Old drugs learn new tricks: insights from mammalian trace amine receptors. Mol Pharmacol 2001; 60: 1165-7.
31. Knoll, J. Enhancer regulation/Endogenous and Synthetic Enhancer Compounds: A Neurochemical Concept of the Innate and Acquired Drives. Neurochem Res (2003) 28:1187-1209.
32. Knoll, J. et al (1996) (-)-Deprenyl and (-) -1-phenyl-2-propylaminopentane [(-)PPAP], act primarily as potent stimulants of action-potential-transmitter release coupling in the catecholaminergic neurons Life Sci 58, S17-27.
33. Knoll, J. et al Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain Life Sci 1996 58, 2101-14
34. Knoll, J. Memories of my 45 years in research Pharmacol Toxicol 1994 75, 65-72.
35. Knoll, J. The Brain and Its Self: A Neurochemical Concept of Innate and Acquired Drives. (2005) Springer Verlag
36. Knoll, J., 1998. (_)Deprenyl (selegiline), a catecholaminergic activity enhancer (CAE) substance acting in the brain. Pharmacol. Toxicol.82, 57– 66.
37. Koch, R., Moats, R., Guttler, F., Guldberg, P. and Nelson, M. Blood-brain phenylalanine relationships in persons with phenylketonuria. Pediatrics 2000, 106:1093 – 1096.
38. Kusaga A, Yamashita Y, Koeda T, et al. Increased urine phenylethylamine after methylphenidate treatment in children with ADHD. Ann Neurol 2002; 52: 372-4
39. Lawford BR, Young RM, Noble EP, et al. The D(2) dopamine receptor A(1) allele and opioid dependence: association with heroin use and response to methadone treatment. Am J Med Genet 2000; 96: 592-8.
40. Nakamura M, Ishii A, Nakahara D. Characterization of b-phenylethylamine-induced monoamine release in rat nucleus accumbens: a microdialysis study. Eur. J. Pharmacol. 1998, 349: 163-169.
41. Neuropsychiatr Genet 2003; 116: 103-25
42. Noble EP. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am J Med Genet B
43. O'Hara BF, Smith SS, Bird G, et al. Dopamine D2 receptor RFLPs, haplotypes and their association with substance use in black and Caucasian research volunteers. Hum Hered 1993; 43: 209-18.
44. O'Reilly R, Davis BA, Durden DA, Thorpe L, Machnee H, Boulton AA. Plasma phenylethylamine in schizophrenic patients. Biol Psychiatry. 1991, 30(2): 145-150.
45. Paetsch PR, Baker GB, Greenshaw AJ. Induction of functional down-regulation of β-adrenoceptors in rats by 2-phenylethylamine. J Pharm Sci 1993; 82: 22-4.
46. Parker EM, Cubeddu LX. Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding. J Pharmacol Exp Ther 1988; 245: 199-210.
47. Paterson IA, Juorio AV, Boulton AA. 2-Phenylethylamine: a modulator of catecholamine transmission in the mammalian central nervous system? J. Neurochem. 1990, 55: 1827-1837.
48. Paul SM, Hulihan-Giblin B, Skolnick P. (+)-Amphetamine binding to rat hypothalamus: relation to anorexic potency for phenylethylamines. Science 1982; 218: 487-90.
49. Popplewell DA, Coffey PJ, Montgomery AM, Burton MJ. A behavioural and pharmacological examination of phenylethylamine-induced anorexia and hyperactivity--comparisons with amphetamine. Pharmacol Biochem Behav. 1986, 25(4): 711-716
50. Raiteri M, Del Carmine R, Bertollini A, Levi G. Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine, and 5-hydroxytryptamine. Eur J Pharmacol 1977, 41: 133-143.
51. Risner ME, Jones BE. Characteristics of beta-phenethylamine selfadministration by dog. Pharmacol Biochem Behav 1977; 6: 689-96.
52. Sabelli HC, Javaid JI. Phenylethylamine modulation of affect: therapeutic and diagnostic implications. J Neuropsychiatry Clin Neurosci. 1995, 7(1): 6-14.
53. Sabelli, H. (1998). Phenylethylamine replacement as a rapid and physiological treatment for depression. Psycheline, 2,(3), 32-39.
54. Sabelli, H. (2000). Aminoacid precusors for depression. Psychiatric Times, 17. 42-49
55. Sabelli, H. (2002). Phenylethylamine deficit and replacement in depressive Illness. In D. Mishooulon and J.F. Rosenbaum. (Eds.), Natural medications for psychiatric disorders. (pp 83-110), Baltimore: Lippencott Williams and Wilkins.
56. Sabelli, H., Fink, P., Fawcett, J. and Tom, C. (1996). Sustained antidepressant effect of PEA replacement. Journal of Neuropsychiatry and Clinical Neurosciences, 8, 168-171.
57. Sabelli, H.C and Javaid J.I. (1995). Phenylethylamine modulation of affect: Therapeutic and diagnostic implications. Journal of Neuropsychiatry and Clinical Neurosciences, 7, 6-14.
58. Sabelli, H.C., Fahrer, R, Doria Medina R, and Ortiz Frágola E. (1994). Phenylethylamine replacement rapidly relieves depression. Journal of Neuropsychiatry, 6, 203.
59. Scriver, C.R. and Kaufman, S. Hyperphenylalaninemia: Phenylalanine Hydroxylase Deficiency. In, The Metabolic and Molecular Basis of Inherited Disease. 8th Edition, 2001. Scriver, Beaudet, et al. McGraw-Hill. Chapter 77, pg. 1667 - 1724.

60. Shannon HE, Thompson WA. Behavior maintained under fixedinterval and second-order schedules by intravenous injections of endogenous noncatecholic phenylethylamines in dogs. J Pharmacol Exp Ther 1984; 228: 691-5. 61. Smith TA. Phenylethylamine and related compounds in plants. Phytochemistry 1977, 16: 9-18.
62. Szabo A, Billett E, Turner J. Phenylethylamine, a possible link to the antidepressant effects of exercise? Br J Sports Med 2001; 35: 342-3.
63. Takahashi N. Dopaminergic genes and substance abuse. Adv Pharmacol 998; 42: 1024-32.
64. Wolf ME, Mosnaim AD. Phenylethylamine in neuropsychiatric disorders. Gen Pharmacol 1983; 14: 385-90.
65. 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. Pharmacology and Experimental Therapeutics 2008 May: 325(2):617-28.
66. Xie, Z., Miller, G.M., Trace Amine-Associated Receptor 1 Is a Modulator of the Dopamine Transporter. April 2007 vol. 321 no. 1 128-136 Reynolds GP. Phenylethylamine - a role in mental illness. Trends Neurosci 1979; 2: 265.
67. Yu PH. Pharmacological and clinical implications of MAO-B inhibitors. Gen Pharmacol. 1994, 25(8): 1527-1539.Berry, M.D., The Potential of Trace Amines and Their Receptors for Treating Neurological and Psychiatric Diseases. Reviews on Recent Clinical Trials, 2007, 2, 3-19 3
68. Zametkin AJ, Karoum F, Rapoport JL, Brown GL, Wyatt RJ. Phenylethylamine excretion in attention deficit disorder. J Am Acad Child Psychiatry 1984; 23: 310-4.

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