The Role and Use of PEA in Depression & Neurobehavioral Disorders

The Phenylethylamine Hypothesis of Depression
According to the "Phenylethylamine Hypothesis of Depression" proposed in 1974, the endogenous trace
amine Beta- Phenylethylamine (PEA) sustains psychological energy just as thyroid hormone sustains
physical energy And a deficit of PEA produces depressions. The Phenylethylamine hypothesis goes on to
state that PEA is a neuromodulator of mood, attention, pleasure-seeking behavior, and libido.
The phenylethylamine hypothesis led to simple safe and effective way of treating depression and other
affective disorders by based on years of research conducted by Dr. Hector Sabelli and colleagues. Take
an oral replacement of PEA as replacement to correct an underlying deficiency or defect in neural
transmitter functioning. The majorities of depressed individuals show a significant reduction in their
symptoms or have complete recovery without any adverse reactions. Plus, there're is significant
increases in cognitive performance functions, attention, awareness, and feelings of pleasure, libido,
normal social behavior and sense of wellbeing.

PEA. More than Endogenous Amphetamine in our Brain

The Phenylethylamine Hypothesis of Depression stems from the observation that amphetamines
increased energy and relieved depressive symptoms of depressive patients. Amphetamine is essentially
phenylethylamine with an added methyl group. Studies show that PEA 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.
The stimulant effects of amphetamines and PEA are attributed to the release of catecholamines
(noradrenalin, dopamine). This is the basis for the catecholamine hypothesis of depression. However
current research shows that PEA is significantly more effective than amphetamine in relieving
depression and has therapeutic value in a wide range of neurological and behavioral disorders,
Endogenous Mesencephalic Enhancer and Transmitter Signal Amplifier
Starting around 1995, Dr Joesph Knoll and his colleagues began presenting their evidence of PEA as an
endogenous "mesencephalic enhancer". There are enhancer-sensitive neurons in the brain work in a
split-second on a high activity level due to endogenous enhancer substances. The mesencephalic
enhancer PEA enhancers of the impulse propagation mediated release of catecholamines (dopamine,
epinephrine) and serotonin in the brain.
PEA is a "Neuroamplier" of transmitter signals. PEA enhances the electronic coupling in the synaptic gap junction of linked regions of cells for greater signal strenght in the pulses of neurotranmsitter release. PEA increases sing the signal-to-noise ratio for stronger signal firing. This means that PEA more efficiently couples the release of neurotransmitters to the electrical impulse that triggers their release. This turns up the volume level of catecholamime nerve activity for enhancing their overall effects causing a larger release of neurotransmitters in response to a given nerve signal. It's like amplying the volume level of of neurotranmitter activity. NEURVANA® Edge 2010

PEA induces higher concentration, continuous strong release, and greater activity of dopamine (for
motivational drive, feelings of pleasure and sense of wellbeing), norepinephrine (the brain's stimulant
for wakefulness, alertness, energy and attention) acetylcholine (for memory, learning, smartness and
cognitive functions), and serotonin (for good moods and feelings, and impulse control).
It's well known that catecholamines and serotonin in the brain play a crucial role in the control of mood.
Major depression is associated with a deficiency in the activity of these systems, providing the rational
for antidepressant effect of enhancer substances like PEA

Neuromodulator that alters Transporter Functions by binding TAAR1
Studies conducted in the last five years, have focused on how PEA and other trace amines function as a
neuromodulator and alter monoamine transporter function by binding with paired Trace Amine-
Associated Receptors (TAAR). TAAR1 is a G protein coupled receptor that's activated by PEA and certain
monoamines and amphetamine-related psychostimulants.
The activation of TAAR1 by PEA significantly inhibits the uptake and induces efflux of its partner
neurotransmitters- dopamine, norepinephrine, and serotonin. These actions by PEA increase the
extracellular levels of these neurotransmitters by inhibiting their reuptake into the presynaptic cell. And
this increases their available level to bind to the postsynaptic receptor.
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. This makes PEA
and other trace amines perfect candidates for the development of novel therapeutics for a wide range
of human disorders. Their therapeutic potential is supported by numerous pharmaceutical companies
conducting active trace amine research projects.
The Therapeutic Use of PEA in Neurobehavioral Disorders

According to this model, 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. A current list with extensive references (under PEA Therapeutics
in the Reference Section)
AFFECTIVE DISORDERS ( depression, bipolar disorder) ATTENTION DEFICIT / HYPERACTIVITY DISORDER (very short attention span, impulsiveness, hyperactivity, distractibility) 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) NEURVANA® Edge 2010

PEA's Antidepressant, Anti-Anxiety & Attention-Focusing Potential
There is clear, distinct difference in PEA's effectiveness on catecholminergic and serotonergic neurons.
PEA is more potent in enhancing the stimulation-evoked release and reuptake of catecholamines
especially dopamine when compared with serotonin. This indicates that PEAs neurmodulation in
catecholaminergic and serotonergic neurons is not identical on the molecular level.
There is substantial evidence that PEA produces stronger actions as a NDRI (Norepinephrine-Dopamine
Reuptake Inhibitor) than as an SSRI (Selective Serotonin Reuptake Inhibitors) Their combined actions
indicate how PEA works as an antidepressant, anti-anxiety, anti-addiction and attention-focusing
complement or alternative to standard treatments.
PEA has actions of an NDRI such as Ritalin Wellbutrin, Zyban, etc. PEA has actions of an SSRI like Celexa, Orizac and Paxil, etc. In terms of safety, PEA does produce the adverse reactions and side effects of the popular pharmaceutical NDRIs and SSRIs. It's due to PEA's self-regulating mechanisms of synaptic transport and receptor functioning, homeostatic control of neurotransmissions and intrinsic neuroprotective properties. Treating Depression with PEA. An Early Case Study
It was discovered that the amount of PEA in the brains of depressed patients was less than that of
normal individuals, and giving PEA orally to individuals suffering from depression reversed the
depressive condition. In fact, most antidepressant drug treatments act by increasing the level of PEA in
the brain.
In one study, PEA was shown to decrease the symptoms of depression in 60% the patients tested, the same outcome expected from taking an SSRI. The patients did not develop tolerance, and PEA remained effective over time. None of the side effects associated with conventional antidepressant drugs was experienced. About 60% showed immediate recovery in as little as a half an hour. Most patients did not gain weight. In fact many actually lost the weight they had gained on the conventional antidepressant therapy. NEURVANA® Edge 2010

General References
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. Sabelli, H. (2000). Aminoacid precusors for depression. Psychiatric Times, 17. 42-49 PEA control of depression in 60% of depressed patients; the same percentage as major antidepressants like
Prozac--but without adverse effects.

Sabelli, H. (1998). Phenylethylamine replacement as a rapid and physiological treatment for depression. Psycheline, 2,(3), 32-39. Sabelli, H., Fink, P., Fawcett, J. and Tom, C. (1996ournal of Neuropsychiatry and Clinical Neurosciences, 8, 168-171. 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. Sabelli, H.C., Fahrer, R, Doria Medina R, and Ortiz Frágola E. (1994). Phenylethylamine replacement rapidly relieves depression. Journal of Neuropsychiatry, 6, 203. Reduction in PEA metabolism with depression in psychiatric patients
Gonzalez-Sastre in Spain, 1988, Acta Psychiatrica Scandinavica, 78,208-210. Sabelli, H., Carlson-Sabelli, L., Levy, A. and Patel, M. (1995). Anger, fear, depression and crime: Physiological and psychological studies using the process method. In Robertson and Combs (Eds.), Chaos Theory in the Life Sciences. (pp 65-88), Mahwah, New Jersey: Erlbaum. Sandler, et al, in the UK, 1979, (Clin Chim Acta, 93,169-171. Sabelli, H., Javaid, J., Fawcett, J. and Kravitz, H. (1990). Urinary phenylacetic acid in panic disorder with and without depression, Acta Psychiatrica Scandinavica, 82, 14-16. Sabelli, H.C, Fawcett, J, Gusovsky, F, et al. (1983). Urinary phenylacetate: a diagnostic test for depression? Science, 220, 1187-1188. Sabelli, H.C., Fawcett, J, Gusovsky, F. et al (1986). Clinical studies on the phenylethylamine hypothesis of affective disorder, Journal of Clinical Psychiatry, 47, 66-70. Tsugi, et al, in Japan, 1986, Anal Biochem, 153,116-120. PEA as a Mesencephalic Enhancer and Neurotransmitter Signal Amplifier
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PEA and Catecholamines
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PEA, Trace Amines and TARR1

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PEA Therapeutics

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