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Monday, February 9, 2015

The Birth and Ascendence of N-PEA; A non-addictive Endocannibinoid and Ultimate Nemesis of THC (From a Rhetorical Competition standpoint)

This article has been exclusively written for TrueLIFE Research - TeamTLR.com and to foster further progress within research with the valuable endocannabinoid substrate N-PEA
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While THC certainly is the "cannabinoid" most are more familiar with - another cannabinoid has been sparking much more scientific appeal and attention - this cannabinoid is not "traditional" by any means, but certainly has demonstrated itself worthy in pain and inflammation, among other disorders.

The name of it is Palmitoylethanolamide (also known as N-PEA, and referred to as simply "PEA" within medical study). This chemical is NOT the same as PHENYL-ETHYLAMINE; another unrelated chemical (a stimulant) with the same "PEA" as it's acronym.




The chemical was discovered in the late 1950's...


Significant studies on this chemical began before the 1980's; and the heat of it's research was published in "The Lancet" - an older but respectable, and somewhat notorious worldwide medical journal(1) (2)

Notably, when 1.8 grams of N-PEA was compared to 3 grams of aspirin - it was seen to have similar analgesic efficacy, and very potent influence on mast cell overexcitation.
In the 1990s, the relation between anandamide and PEA was described, and the expression of receptors sensitive for those two molecules on mast cells was first demonstrated by the group of Nobel prize winner Rita Levi-Montalcini.(3)

Specifically, one group of researchers; published promising (and additive) evidence -  demonstrating that PEA could alleviate, in a dose-dependent manner, pain behaviors elicited in mice-pain models and could downregulate hyperactive mast cells.(4)(5) PEA and related compounds such as anandamide also seem to have synergistic effects in models of pain and analgesia.(6)

The effects on mast cells are remarkable, because there aren't many remedies at all with as good as scientific background and follow-up studies as Palmitoylethanolamide (N-PEA).



In a variety of animal models PEA seems promising, and researchers could demonstrate relevant clinical activity in a variety of disorders, from multiple sclerosis to neuropathic pain.(7)(8).

It also was seen as an effective natural anti-convulsant(!).


2011; another highlight for N-PEA - demonstrates it having potent anti-depressant effects comparable to the popular anti-depressant Fluoxetine AKA Prozac(9).

Even more significantly, attentiveness to it's neuroprotective abilities became even more powerful when it was demonstrated to directly counter reactive astrogliosis induced by beta-amyloid peptides(SEE HERE).
Now, astrogliosis is an abnormal increase in the number of astrocytes (specific glial cells in the brain and spinal cord) due to the destruction of nearby neurons from CNS trauma, infection, ischemia, stroke, autoimmune responses, and neurodegenerative disease. Astrocyte excess can cause nerve/tissue damage and impair axon regeneration(!).

More research on it's anti-inflammatory, neuroprotective, and pain - relieving effects were confirmed in the following year; 2012(10)(11).

                                    2012 STUDIES on N-PEA

Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-α

Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series


Research on N- PEA , again, has taken quite the spotlight research years , a 2013 article with a bold title - (Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide)  confirms N-PEA's mechanism of action as a PPAR agonist. It's described as a unique and very effective nutraceutical - something memorable as nutraceuticals have gained notoriety in many places in the scientific community.

An excerpt from the same article was also INCREDIBLY significant in the identification and worth of N-PEA.


The history of the development of insights into the biological role of PEA after its identification in 1957 is worth telling because it demonstrates the close interrelationship between the scientific context and the development of scientific facts.

Thus the discovery of and testing of N-PEA was not only a checkpoint for science, but also an important vehicle for later defined guidelines and a coming scientific revolution , of sorts.



Messina , Italy - an area known for it's A+ medical schooling and criteria standards( University of Messina), also became a part of N-PEA's growing interest, which is quickly turning into a phenomenon of sorts , in the scientific community. Emanuela Esposito and Salvatore Cuzzocrea published a review to CNS & Neurological Disorders - Drug Targets, 2013, 12, 55-61 - the study was principally overseen in Department of Biological and Environmental Sciences, University of Messina(!).




The conclusions came up to confirm and reiterate it's neuroprotective potential.


Here's a quote.




"PEA appears to exert its protective effect by decreasing the development of cerebral edema, down-regulating the inflammatory cascade, and limiting cellular necrosis and apoptosis. All these are plausible mechanisms of neuroprotection."



If this wasn't enough, an article/study in Med Hypothesis; (a well-respected medical journal noted for it's deposits/studies of information that would later be utilized in a significant manner or that remain a poster child for studies to come) - soon was the site of the resonating ability of N-PEA to yet again emerge as a fundamental and yet rare breakthrough in science .

It was demonstrated to prove useful in treating cannabis dependence (12) (go figure, an endocannibinoid like chemical could drift people away from the gaping hole of cannabis dependence).

Another study (13) goes on to prove N-PEA as an antioxidant that has prevented kidneys from succumbing to hypertensive damage, and direct protective effects against hypertension related disorders.

JUNE 2013, a year where influenza is certainly more talked about, what with the swine flu warning flag being aired in past years and up to, certainly was the right timing for N-PEA to come up YET AGAIN; this time as the new hero in fighting influenza and the common cold(14)

Amazing..., and then a NOVEMBER 2013 study shows that N-PEA is able to correct or modulate gut homeostasis, helping to ALLEVIATE gut disorders such as IRRITABLE BOWEL SYNDROME(I.B.S) and INFLAMMATORY BOWEL DISEASES (I.B.D).

Finally , in 2014 - the wand of science yielded yet another justification for N-PEA, again proving it's neuroprotective effects - this time in a more suitable model ; ALZHEIMER'S DISEASE(14). This study was published in the prestigious  "Cell Death and Disease" publications. 

Many other studies, including with major research companies like Pfizer have published serene and worthwhile data on N-PEA - which has further skyrocketed it's overall interest, appeal and it's magnitude on those awaiting more plausible, and safer treatments for the following disorders.



  • Pain and inflammation.
  • Neurodegenerative disorders; including Alzheimer's,
  • Gut disorders (I.B.S / I.B.D)
  • Depression
  • Metabolic Disorders / Leptin sensitivity (!)
  • Cold / Flue and infection treatment/recovery.
AND ADDITIONALLY, SUCH INTEREST HAS BEEN SHOWN IT TO BE EFFECTIVE....
  • As an anti-convulsant.
  • As a cellular activity modulator ; and to demonstrate the significance of the PPAR-A ; peroxisome proliferator-activated receptor alpha - in multiple disorders.
  • As an add-on or augmentor  of traditional analgesics.
  • As an investigate or comparative tool in finding cures for neurodegenerative diseases - even though it is quite efficient and powerful by itself - this speaks for it's significance even more as it becomes the new "gold-standard" in scientific / medical advancement, one likely to stay with the pace as we accelerate to the next phase in scientific enlightenment and advancement.

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