The Science of PEA
BY DR RICHARD KAUFMAN
NEURVANA amplifies the activity of key natural neurotransmitters in your brain for increased longevity, slower aging, higher performance, a sense of wellbeing and a renewed youthful functioning body. It has unique rapid uplifting effects on mood, mental activity, attention, motivation, alertness, creativity, awareness, energy, stamina, physical activity, pleasurable feelings, sexuality, and sensory perceptions.
NEURVANA contains beta-phenylethylamine (PEA), 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 actions 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.
Amplies Neurotransmitter Signals for Peak Mental and Physical Performance at Any Age NEURVANA is literraly a ‘neuroamplier’ for a higher perforamce in life. PEA enhances the electronic coupling in the synaptic gap between nerve cells. It boosts the signal strenght of neurotranmitters 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 activty for higher performance throughout your body. And it does not matter how old you are to experience a noticable performance improvement in daily activites.
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 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 re h ab ilit at in g ou r b rain s’ cat echo lamin e syst em wit h mesencephalic enhancer substances (including
PE A an d it s d erivat ives) it ’s possib le t o t ran sf orm 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
NEURVANA 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
NEURVANA 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” neurohormone/neurotransmitter–it activates a feeling of pleasure and euphoric sense of wellbeing.
Increased Energy, Alertness and Sensory Perception
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
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 NDRI and SSRI
PEA 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.
Clinically Proven
Researchers have found that PEA controlled chronically low moods in 60% of persons–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 boosts of both acute and chronic low moods 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 Neurochemical of Love and Libido
PEA has aphrodisiacal qualities and produces feelings of romance and love. 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 suggests that high PEA levels lead to increased sex drive and activity, while low levels reflect the loss of libido in depression.
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
NEURVANA® 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,”
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 Neutransmitter 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 Neural Biology and Homeostasis
PEA is neural guardian of homeostasis (maintaining healthy metabolic equilibrium). The binding of PEA with TAAR1 protects delicate neural circuitry offset disrupting, harmful changes. PEA limits overstimulation of nerve cells by excessive neurotransmitter signaling, to prevent nerve cell damage and abnormal functioning.
Endogenous Amphetamine-Like Stimulating Neurotransmitters
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.
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.
Protected Patent-pending Nanosphere Delivery
NEURVANA is formulated with a patent-pending “Self-emulsifying Nanosphere Delivery System.” It uses
natural phospholipids and medium-chain triglycerides to form a nanoemulsion (covering) in the intestinal tract, enhancing bioavailability (delivery) of PEA. NEURVANA is 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
NEURVANA should not be used by individuals under the age of 18 years. Do not use NEURVANA if you are pregnant or nursing.
Do not take Phenylethylamine 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 Phenylethylamine if have phenylketonuria (PKU).
If you are on medication or have a health condition, consult a physician before use.
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This product is not intended to diagnose, treat, cure, or prevent any disease.
As a Mesencephalic Enhancer & Neuroamplifier
PEA – An Endogenous Mesencephalic Enhancer and Neuroamplifier
by DR RICHARD CLARK KAUFMAN
Joseph Knoll, M.D. is a Hungarian neurochemist, pharmacologist and Nazi concentration camp survivor. Dr. Knoll is best known for developing the drug l-deprenyl (Selegiline), the first selective monoamine oxidase-B (MAO-B) inhibitor. L-deprenyl is derived from the endogenous trace amine beta-Phenylethylamine (PEA). Both of them are powerful mesencephalic enhancers, neuromodulators and neuroprotectors.
For more than half a century Dr. Knoll has conducted research and published numerous articles about his research with PEA as an endogenous mesencephalic activity enhancer key role in the operation of innate and acquired drives and its synthetic derivatives. They modulate, amplify and protect our brain’s circuitry. According to Knoll, enhancer regulation can be defined as the existence of enhancer-sensitive neurons in the brain capable of working in a split-second on a significantly higher activity level due to endogenous enhancer substances from his testing of beta-Phenylethylamine (PEA).
The endogenous enhancer substance PEA enhances the impulse-propagation mediated release of catecholamines and serotonin. Enhancer substances may have their own receptors on specific enhancer- sensitive neurons that facilitate the release of neurotransmitters depending on neuronal firing activity.
Neuroamplifer of neurotransmitter signal strength activity
Knoll and colleagues discovered through experiments is PEA and its cousin deprenyl and PEA are “Neuroampliers”. They enhance the electronic coupling in the synaptic gap junction of linked regions of cells for greater signal strenght in the pulses of neurotranmsitter release by increasing the signal-to-noise ratio for stronger signal firing. In other word, PEA more efficiently couples the release of neurotransmitters to the electrical impulse that triggers their release. In so doing, this turns up the volume level of catecholamime nerve activityfor enhancing their overall effects.
This can be of great importance for cognitive enhancment, of clnical importance in Parkinson’s disease and Alzheimer’s disease, where the nigrostriatal tract and mesolimbic-cortical circuits under-function and for effectively treating depression due to an under-activity of both dopamine and noradrenalin neurons. This is an important mechanism reposnsible for the the stimulting effects of Modafinil and other stimulant drugs.
Catecholamines keep the higher brain centers active
After 45 years of research, Knoll has concluded that the regulation of lifespan must be located in the brain. His research convinced him that the role of the catecholaminergic neurons is to keep the higher brain centers in a continually active state. Their intensity dynamically changes within broad limits according to physiological requrements. Knoll’s research shows that catecholaminergic nerve activity peaks at sexual maturity, and then begins a long, gradual decline thereafter.
Knoll’s animal research has shown catecholaminergic activity, learning ability, sexual activity and longevity to be inextricably interlinked. According to Dr. Knoll continuous decline of the mesencephalic enhancer regulation during the post-developmental phase of life is in causal relationship with the age-related decline performance and contributes to the manifestation of age-related diseases.
Catecholamines are the inter-related neurotransmitters dopamine, noradrenalin, and adrenalin. Catecholamines are neuromodulators and the transmitters for activating the the mesolimbic-cortical brain circuit and the locus coeruleus. Catecholamines maintain wakefulness, cognition, concentration, alertness areness and attention. Dopamine, the neurotranmitter for feeling pleasure, is the transmitter for a brainstem circuit – the nigrostriatal tract. This connects the substantia nigra and the striatum, a nerve tract s controling bodily movement that deteriorates with age and malfunctions in Parkinson’s disease
Improve performance at any age, delay decline and extend health lifespan
Knoll argues that the quality and duration of life is a function of the inborn efficiency of the catecholaminergic brain machinery, “A high performing longer living individual has a more active, more slowly deteriorating catecholaminergic system than low performing, shorter living peers .” He states that is that the activity of our catecholaminergic system can be improved at any time during life. Therefore its feasible to transform a lower performing, shorter living individual to a better performing, longer living one. It does matter how old you are., for performance improvement.
To postpone age related decline, extend lifespn and improve performance, Dr. Knoll recommends enhancing the activity of the catecholaminergic engine of the brain from sexual maturity until death via the administration of a daily dose of a mesencephalic enhancer substance. And PEA is the brains endogenous mesencephalic enhancer substance.
References
1. Garcia-Rill E, Heister D, et al.. “Electrotonic coupling: novel mechanism for sleep-wake control”. Sleep 30 (2007) 11: 1405–14.
2. Knoll, J. The Brain and Its Self: A Neurochemical Concept of Innate and Acquired Drives. (2005) Springer Verlag
3. Knoll, J. Enhancer regulation/Endogenous and Synthetic Enhancer Compounds: A Neurochemical Concept of the Innate and
Acquired Drives. Neurochem Res (2003) 28:1187-1209.
4. Knoll, J. Analysis of the effect of (-)-BPAP, a selective enhancer of the impulse propagation mediated release of catecholamines
and serotonin in the brain. Life Sci (2003) 72:2915-2921.
5. Knoll, J. The mechanism of the anti-aging effect of Deprenyl Anti-aging Bulletin Winter (2003) International Antiaging Systems
Ltd
6. Knoll, J. (-)Deprenyl (selegiline), a catecholaminergic activity enhancer (CAE) substance acting in the brain. Pharmacol Toxicol
(1998) 82:57-66.
7. Knoll, J. “Sexual performance and longevity” Exp Gerontal (1997) 32, 539-52.
8. Knoll, J. et al “Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain” Life Sci (1996) 58, 2101-
14.
9. Knoll, J. et al. “Deprenyl and (-) -1-phenyl-2-propylaminopentane [(-)PPAP], act primarily as potent stimulants of action- potential-transmitter release coupling in the catecholaminergic neurons” Life Sci (1996) 58, S17-27.
10. Knoll, J. et al “Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain” Life Sci (1996) 58, 2101-
14.
11. Knoll, J., Miklya, I., Knoll, B., Markó, R., Kelemen, K. (-)Deprenyl and
(-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons. Life Sci (1996) 58:817-827.
12. Knoll, J., Knoll, B., Miklya, I. High performing rats are more sensitive toward catecholaminergic activity enhancer (CAE)
compounds than their low performing peers. Life Sci (1996) 58:945-952.
13. Knoll, J. “Memories of my 45 years in research” Pharmacol Toxicol (1994) 75, 65-72.
14. Knoll, J., Yen, T.T., Miklya, I. Sexually low performing male rats die earlier than their high performing peers and (-) deprenyl treatment eliminates this difference. Life Sci (1994) 54:1047-1057.
15. Knoll, J. “Deprenyl (selegeline): the history of its development and pharmacological action” Acta Neurol Scand (Suppl) (1983) 95,
57-80
16. Knoll, J. The theory of active reflexes. An analysis of some fundamental mechanisms of higher nervous activity. Pages 1 -131, (1969) Publishing House of the Hungarian Academy of Sciences, Budapest, Hafner Publishing Company, New York.
17. Shimazu S, Miklya I. Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives. Prog Neuropsychopharmacol Biol Psychiatry. 2004 May;28(3):421-7.
18. Urbano F, Leznik E, Llinas R “Modafinil enhances thalamocortical activity by increasing neuronal electrotonic coupling”. June
2007. (30): 12554–9
This product is not intended to diagnose, treat, cure, or prevent any disease
pea_an_endogenous_mesencephalic_enhancer_and_neuroamplifier.pdf
For Depression & Neurobehavioral Disorders
The Role and Use of PEA in Depression & Neurobehavioral Disorders
by DR RICHARD CLARK KAUFMAN
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.
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) includes:
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)
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.
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. (1996). Sustained antidepressant effect of PEA replacement. Journal 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
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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.
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This product is not intended to diagnose, treat, cure, or prevent any disease
use_of_pea_in_depression_and_neurobehavioral_disorders.pdf