Consider your mind as an ocean, an ecosystem inhabited by quite a few species of fish-like neurotransmitters and their receptors, with currents of electrical energy connecting and delicately balancing all of the totally different parts. Irritation is sort of a bloom of crimson algae, harming all the things round it and upsetting the homeostasis of the setting.
Enter our hero, Palmitoylethanolamide (PEA) – a lipid messenger kindred to the endocannabinoid system and an in depth cousin of anandamide (AEA), the well-known endocannabinoid neurotransmitter. Typically known as “the endogenous model of CBD,” PEA is a powerhouse in opposition to irritation and ache. Like CBD, PEA will increase the degrees of endocannabinoids and strengthens the endocannabinoid system. And, once more like CBD, a relentless theme within the scientific literature about PEA is its extremely sturdy security profile.
In our neural ocean metaphor, PEA weighs in because the “most venerable of the leviathans,” the grinning Proper Whale, a stalwart fighter in our fixed battle in opposition to irritation and ache.
A Thriller
The PEA story begins with a thriller, which results in one other thriller – and ends with the following nice wave of the cannabinoid revolution.
We start throughout World Struggle 2 – and certainly, geopolitics performs a big function in our story. Due to the conflict effort, we discover it a affluent time for the new-ish discipline referred to as “public well being.” A wholesome inhabitants of staff was important to help the manufacturing of conflict materiel. Two NYC docs named Coburn and Moore discovered that in the event that they gave dried eggs to the poor kids of the tenements, this helped to stop rheumatic fever and different ills associated to poor vitamin. Additionally they found that egg yolks are an anti-inflammatory meals.
Often, when a plant or meals is discovered to have distinctive well being properties, scientists dig in to search out the particular molecules accountable for the helpful impact. And often these are proteins as a result of proteins are the workhorses of the cell. However on this case, because the researchers separated the assorted lessons of molecules concerned, they realized that it was the lipids – the fatty molecules – that precipitated the constructive well being results.
Proteins often is the workhorses, however they’re extra binary; often they’re both on or off. Lipids act in a extra analog method. Our cells are adept at sensing even minute modifications in lipid ranges and responding accordingly. Whereas scientists used to think about lipids as simply the foodstuff of cells, now we all know them to be a finely tuned mobile system primed to search out homeostasis and stability. However how do these fatty parts of eggs work to keep up homeostasis?
Lipid Mechanisms
The primary large breakthrough occurred within the Fifties when a group led by Dr. F.A. Kuehl recognized the energetic anti-inflammatory ingredient in egg yolks to be palmitoylethanolamide. He additionally discovered the identical molecule in soybeans and peanuts, two different anti-inflammatory meals.
However scientists struggled to grasp the mechanisms that precipitated this intriguing lipid to affect irritation. In the course of the Nineteen Sixties, some papers in animal fashions had been printed confirming the anti-inflammatory results of PEA. And in an essential flip of occasions, a group led by Dr. S. Udenfriend found that PEA naturally happens in quite a lot of mammalian organs, and at excessive ranges. So scientists realized that PEA not solely lessens irritation – our personal our bodies and brains additionally produce it as an inside regulator of irritation.
However it wasn’t till the Nineteen Seventies that the primary critical medical trials emerged, and these occurred in Czechoslovakia, a nation that now not exists. The Czech pharmaceutical firm SPOFA (United Pharmaceutical Works) developed a PEA drug known as Impulsin. To check it, they turned to the big Skoda manufacturing facility, a producer of automobiles, tanks, and industrial tools, which employed an amazing workforce. SPOFA ran a number of medical trials with the manufacturing facility staff in addition to with the navy and civilian populations. Altogether, 2,000 adults and 400 kids entered these trials.
Administered in a double-blind method (the gold-standard of recent medical trials), the entire outcomes pointed in the identical course: PEA was secure and possessed a transparent efficacy in treating respiratory infections. It diminished the incidence of fever, headache, and sore throat. And moreover, based on the Czech researchers, “No uncomfortable side effects had been registered after a number of years of medical testing of Impulsin in navy and civilian communities [emphasis added].”
The primary large breakthrough occurred when PEA was recognized because the energetic anti-inflammatory ingredient in egg yolk. And our personal brains additionally produce it.
PEA labored! This was confirmed in giant trials. However then ensued what is thought in endocannabinoid circles because the Silent Hole interval.
By way of the early Nineteen Eighties, the work of SPOFA pale away, misplaced behind the so-called Iron Curtain. Curiosity additionally waned as a result of scientists couldn’t clarify PEA’s mechanism of motion. Nobody might work out the way it really labored. PEA ended up being labeled an “unspecific immune enhancer” and the scientific neighborhood seemingly misplaced curiosity.
Rescuing PEA from Obscurity
That modified in 1993, when the human hero of our story, Dr. Rita Levi-Montalcini, entered the image.
Right here is the place geopolitics get too actual. Earlier in her life, as a Jewish scientist in Mussolini’s Italy, Dr. Levi-Montalcini misplaced her laboratory. Pressured to flee to Florence, she arrange a workstation within the basement of a home, and there she continued her work finding out the early growth of organisms – some of the difficult issues in all of science. The work she carried out in that basement led to her discovery of the mind’s nerve development components (NGFs), some of the essential neurochemical findings of the century – and resulted in her sharing the Nobel Prize in 1986.
Seven years later, whereas affiliated with the Institute of Neurobiology in Rome, Dr. Levi-Montalcini and her group printed a famed paper during which they proposed that PEA works through its management of mast cells – an essential kind of white blood cell accountable for releasing histamine. Whereas most frequently related to allergic reactions, histamine is a each a hormone and a neurotransmitter concerned within the inflammatory response. Mast cells reply to the therapeutic of wounds, the expansion of latest blood vessels, the protection in opposition to pathogens, and the rallying of the immune response.
They referred to PEA’s relationship to mast cells as “the ALIA speculation.”
A assessment of their work within the Journal of Ache and Reduction summarizes, “Autocoid or autacoid is a reasonably old school time period for a regulating molecule, domestically produced and domestically exerting its actions … PEA is shaped domestically when irritation or neurogenic ache happen, and elevated PEA concentrations are primarily based on the body-own mechanisms to deal with ache and irritation. That is known as: on-demand synthesis.”
“An ALIAmide is an autocoid synthesized in response to harm or irritation, and performing domestically to counteract such pathology. Thus, PEA is a classical instance of an ALIAmide. The mast cell quickly after the breakthrough paper of Levi-Montalcini was certainly proven to be an essential goal for the anti-inflammatory exercise of PEA, and within the interval 1993-2013 greater than 30 papers had been printed on the influence of PEA on the mast cell.”
As typically occurs with essential analysis, a partial answer to the issue of how PEA features led to a rush of scientists following up on these clues to determine precisely how PEA modulates mast cells.
PEA for Ache
A key growth in understanding PEA occurred serendipitously in 1998, when a group in Naples was finding out anandamide (AEA), the endogenous cannabinoid neurotransmitter that’s structurally much like PEA. (Each lipid compounds are “EAs” – N-acylethanolamines.) Particularly they had been researching AEA’s potential to trigger ache reduction by blocking ache transmission within the spinal wire earlier than it even reaches the mind.
For his or her experiments, they determined that they wanted a management molecule to behave as a placebo. As Dr. Daniele Piomelli relates, they needed one other endocannabinoid-like molecule that wouldn’t have the identical results. In order that they selected PEA, principally as a result of they knew that it didn’t bind to the CB1 or CB2 receptors considered inflicting the pain-relieving results. However as their paper in Nature identified, they had been fairly shocked to search out out that PEA had profound pain-relieving results as nicely.
This consequence intrigued them. If PEA doesn’t bind to the basic cannabinoid receptors CB1 and CB2, then how does it do what it does?
The researchers reasoned {that a} sister lipid molecule referred to as oleamide (OEA) labored through the PPARα (alpha) receptors. What’s particular about these PPARα receptors is that they’re nuclear receptors. They dwell not on the floor of the cell, however on the floor of its nucleus – the mobile management heart that incorporates the DNA. (In our neuronal ocean metaphor, the nucleus is Metropolis Corridor and the PPAR receptors are the bureaucrats who ship out the orders.) Activating these nuclear receptors alters the transcription of genes and therefore the manufacturing of latest proteins. Every of those new proteins would have its personal host of downstream results. Should you view the cell like a metropolis, altering genetic transcription is like hiring a complete bunch of specialised staff to repair your issues, every with their very own toolkit.
Dr. Piomelli assigned his scholar Jesse LoVerme to review PEA’s mechanism of motion. By 2005, they discovered that the PPARα receptor mediated the anti-inflammatory results of PEA, and by 2007 they decided that this relationship additionally mediated PEA’s anti-pain results. It was an enormous breakthrough.
PEA & the Entourage Impact
With the mechanism unveiled and the constructive medical results famous, PEA analysis poured forth like a spring. In 2008, UK-based scientists reported that the flexibility of anandamide to chill out the arteries was strengthened by the presence of PEA – a phenomenon described as an “entourage impact.” Revealed within the British Journal of Pharmacology, the research famous this impact occurred through the function of vanilloid receptors, that are half of a big, historic household of Transient Receptor Potential ion channels (also called TRP or “journey” receptors) that regulate core physique temperature, inflammatory ache, and different fundamental visceral sensations, such because the burning sensation of scorching meals like capsaicin.
Anandamide binds to the TRPV1 vanilloid receptor as does CBD. The endocannabinoid system and the endovanilloid system are so intertwined that anandamide is commonly described as a vanilloid compound.
Additionally in 2008, a research on PEA and neuropathic ache discovered not solely TRPV1 to be concerned, but in addition the CB1 cannabinoid receptor and one other nuclear receptor, PPARγ (gamma). And in a subsequent research of neuropathic ache, PEA helped by bettering the discharge of amino acids in addition to restoring the functioning of glutamate, the mind’s main excitatory neurotransmitter (and the topic of a earlier Challenge CBD article on this sequence).
In mouse research involving a variety of illness fashions, PEA was discovered to decrease irritation, reduce cell loss of life, and stop tissue harm – typically through a number of biochemical pathways. It even helped 4 leaping horses return to competitors after their accidents didn’t reply to some other therapy.
Scientists now consider that PEA exists – at the least at low ranges – in each single mammalian cell.
Scientific Research
Scientific experiments have additionally yielded spectacular outcomes. In sufferers with migraines, decrease again ache, burning mouth syndrome, spinal wire accidents or the neuropathy of shingles, PEA decreased ache and labored nicely as an add-on to the usual remedies. PEA additionally helped folks with bladder issues, irritable bowels, glaucoma, osteoarthritis of the knee, and train restoration. (For an intensive checklist of situations helped by PEA, see The PEA Well being Recordsdata on the finish of this text.)
In 20 sufferers present process chemo, PEA eased the ache and even confirmed “vital restoration of nerve perform.” In a affected person with ALS, PEA improved their medical image – most likely through the mast cells in addition to the microglia (the guardian immune cells of the mind). In a number of sclerosis sufferers, PEA mixed nicely with the usual therapy to enhance ache, decrease irritation, and lift high quality of life. Observational research of 600 sufferers with treatment-resistant power ache discovered PEA to be efficient and secure. In seven sufferers with power idiopathic axonal polyneuropathy (intense neuropathic ache from an unknown supply), PEA considerably diminished ache with no uncomfortable side effects, and it did the identical for 70 youngsters with migraines.
PEA is a powerhouse in opposition to irritation and ache.
In 24 girls with endometriosis and power pelvic ache, PEA mixed with polydatin (a flavonoid typically paired with PEA) helped with their cramps, their ache throughout intercourse, and with their general high quality of life; related outcomes had been later reported for 30 extra sufferers. And in 30 diabetic sufferers, PEA successfully diminished their neuropathic ache with no detrimental modifications proven of their blood work or urine evaluation. In two sufferers with autism, PEA precipitated “fast enhancements in cognitive, behaviors, and sociability.” In 58 sufferers with despair, 600 mg of PEA twice a day along with citalopram considerably and quickly improved signs. And it even works topically for people with eczema; when, utilized to the pores and skin, PEA precipitated much less itching and higher sleep with most of the sufferers stopping the usage of corticosteroids.
With respect to PEA, all through all of those research, there’s one evaluation that comes up again and again: “We additionally famous its security because of the whole absence of antagonistic results.”
PEA as a Dietary Complement
A long time of unravelling a sequence of scientific mysteries have led to thrilling discoveries that remodeled PEA from the stuff of egg yolk to the following nice dietary complement.
Within the ocean of our mind, the PEA whale emerges to work its magic by orchestrating the reducing of irritation and the discount of ache throughout all over the place it roams. ClinicalTrials.gov lists 44 medical trials for PEA which are at the moment recruiting sufferers, in course of, or accomplished. FSD Pharma has PEA in Section 2 trials to be used in opposition to an inflammatory illness of mast cell activation.
PEA is already in widespread use all over the world. In Italy and Spain, it’s an authorised nutraceutical. Lesvi, a European pharmaceutical firm, combines PEA with a number of vegetation as a nutraceutical for the mind. A Dutch agency produces a formulation known as PeaPure. And the PEA formulation referred to as Levagen+ from Gencor Pacific is touted to enhance joint well being, temper, sleep, immune system well being, train restoration, and high quality of life.
Happily it’s comparatively simple to entry food-derived PEA as a authorized well being complement within the US. Plenty of respected distributors market PEA merchandise, and one can get them organized on-line. Anecdotal accounts recommend that CBD and PEA amplify one another’s anti-inflammatory results, and mixing the 2 compounds might show to be a robust therapeutic possibility.
Lex Pelger writes articles about psychoactives and the endocannabinoid system. His first e book, SUNset, is accessible through Amazon. He publishes a weekly cannabinoid science e-newsletter Cannabinoids & the Folks and conducts 1-on-1 training periods on utilizing CBD, PEA, THC & CBDA for critical well being situations. Copyright, Challenge CBD. Will not be reprinted with out permission.
The PEA Well being Recordsdata
2013: A Kuhnian tackle evolution of PEA data
Evolution in pharmacologic pondering across the pure analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-α agonist and efficient nutraceutical
The very best PEA assessment papers:
2022: A assessment on the potential of utilizing PEA for antiseizure results
Is It Time to Take a look at the Antiseizure Potential of Palmitoylethanolamide in Human Research? A Systematic Assessment of Preclinical Proof
2021: From Gencor (producers of the PEA product Levagen+, a paper reviewing the wonders of PEA
Palmitoylethanolamide: A Potential Various to Cannabidiol
2021: This assessment of feminine pelvic drugs and reconstructive surgical procedure suggests PEA as a therapy
Cannabinoid Remedy in Feminine Pelvic Drugs and Reconstructive Surgical procedure: Present Proof and Future Instructions
2021: This assessment seems to be at PEA for autism and means that it might assist through a number of totally different mechanisms
Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Dysfunction: A Systematic Assessment of Human and Animal Proof
2021: This assessment seems to be on the energy of PEA to guard the astrocytes (important help cells of the mind) and battle Alzheimer’s illness
Various Targets to Struggle Alzheimer’s Illness: Deal with Astrocytes
2021: This assessment suggests utilizing PEA for treating COVID sufferers
Ultramicronized Palmitoylethanolamide (um-PEA): A New Doable Adjuvant Therapy in COVID-19 sufferers
2021: This assessment seems to be at how PEA and oleoylethanolamide binds to GPR119 and GPR55 (receptors which will someday be referred to as CB3 and CB4)
GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide
2021: A particular concern of the Worldwide Journal of Molecular Sciences is devoted to PEA
2021: This mini-review examines why it is smart to make use of PEA to deal with COVID (contains one constructive case research)
Micronized / ultramicronized palmitoylethanolamide (PEA) as pure neuroprotector in opposition to COVID-19 irritation
2020: A assessment of how PEA strikes via the physique
The Basal Pharmacology of Palmitoylethanolamide
2020: A assessment of PEA for pets
Palmitoylethanolamide and Associated ALIAmides: Prohomeostatic Lipid Compounds for Animal Well being and Wellbeing
2020: On utilizing PEA for ache (good charts)
ALIAmides Replace: Palmitoylethanolamide and Its Formulations on Administration of Peripheral Neuropathic Ache
2020: PEA + luteolin for neuroinflammation
An Replace of Palmitoylethanolamide and Luteolin Results in Preclinical and Scientific Research of Neuroinflammatory Occasions
2019: A very good assessment of PEA’s mechanisms of motion
Scientific Functions of Palmitoylethanolamide in Ache Administration: Protocol for a Scoping Assessment
2019: A assessment on PEA for finish of life care
The Potential Advantages of Palmitoylethanolamide in Palliation: A Qualitative Systematic Assessment
2019: A assessment on PEA for Alzheimer’s illness with a deal with neuroinflammation
Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Illness
2019: On combining PEA with different antioxidant molecules present in your weight-reduction plan (good diagrams)
Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy With Totally different Antioxidant Molecules Current in Diets
2019: A assessment of PEA for bronchial asthma
Molecular Targets of Fatty Acid Ethanolamides in Bronchial asthma
2018: A assessment of PEA for despair
Function of Palmitoylethanolamide (PEA) in Melancholy: Translational Proof: Particular Part on “Translational and Neuroscience Research in Affective Issues”
2017: DiMarzo’s nice assessment with historical past, pharmacology, and charts of the place it’s discovered (breast milk!)
The pharmacology of palmitoylethanolamide and first information on the therapeutic efficacy of a few of its new formulations
2017: A assessment of PEA and polydatin for endometriosis covers 4 research
Micronized Palmitoylethanolamide/Trans-Polydatin Therapy of Endometriosis-Associated Ache: A Meta-Evaluation
2016: A assessment of ache covers 6 research
Palmitoylethanolamide for the Therapy of Ache: Pharmacokinetics, Security and Efficacy
2016: This assessment of 12 research of sufferers with ache, PEA decreased ache with no critical antagonistic occasions
Palmitoylethanolamide, a Particular Meals for Medical Functions, within the Therapy of Persistent Ache: A Pooled Information Meta-analysis
2015: A assessment of PEA for nerve compression issues like carpal tunnel and sciatic ache
Palmitoylethanolamide, a Neutraceutical, in Nerve Compression Syndromes: Efficacy and Security in Sciatic Ache and Carpal Tunnel Syndrome
2015: PEA as a homeostasis mechanism for neuroinflammation in fashions of stroke, spinal wire harm, traumatic mind harm, and Parkinson illness
N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Technique of Decision
2015: In people, this assessment of research finds PEA secure and efficient for glaucoma and different retinopathies (good chart of mechanisms of motion)
Palmitoylethanolamide, a Pure Retinoprotectant: Its Putative Relevance for the Therapy of Glaucoma and Diabetic Retinopathy
2014: A assessment of PEA for irritation
Harnessing the Anti-Inflammatory Potential of Palmitoylethanolamide
2013: An ideal assessment of the historical past of PEA and the medical trials for the widespread chilly
Palmitoylethanolamide: A Pure Physique-Personal Anti-Inflammatory Agent, Efficient and Secure Towards Influenza and Widespread Chilly
2013: A assessment of PEA for irritation from trauma
Palmitoylethanolamide Is a New Doable Pharmacological Therapy for the Irritation Related With Trauma
2013: A assessment of PEA for hashish dependence
Palmitoylethanolamide: From Endogenous Cannabimimetic Substance to Modern Drugs for the Therapy of Hashish Dependence
2013: A assessment of PEA and the mast cells
New Insights in Mast Cell Modulation by Palmitoylethanolamide: “In view of their strategic localization at websites straight interfacing with the exterior setting, mast cells act as surveillance antennae in opposition to various kinds of harm and might bear activation, thereby regulating each innate and adaptive immune reactions via the discharge of a number of preformed and newly synthesized mediators. Mast cells at the moment are seen as key gamers in orchestrating a number of problems together with each acute and power inflammatory processes, and have a job in angiogenesis and hyperalgesia.”
2012: A assessment of PEA’s impact on mast cells, glia cells (mind help cells), and neuroinflammation
Mast Cell-Glia Axis in Neuroinflammation and Therapeutic Potential of the Anandamide Congener Palmitoylethanolamide
2012: Dr. Piomelli’s feedback on lipids and PEA
A thickening community of lipids
2007: Dr. DiMarzo on use for companion animals
Palmitoylethanolamide, Endocannabinoids and Associated Cannabimimetic Compounds in Safety Towards Tissue Irritation and Ache: Potential Use in Companion Animals
2005: Dr. Piomelli on historical past of discovery
The Seek for the Palmitoylethanolamide Receptor
A timeline of PEA analysis:
[micronized and ultra-micronized PEA means that the PEA has been put into a small particle size for better absorption]2022: Researchers look to create new molecules that assist enhance pure PEA ranges
Discovery and SAR Evolution of Pyrazole Azabicyclo[3.2.1]octane Sulfonamides as a Novel Class of Non-Covalent N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA) Inhibitors for Oral Administration
2022: A serious carotenoid from brown seaweed known as fucoxanthinol seems to assist with irritation through its modulation of the PEA pathway
Anti-Inflammatory Results of Fucoxanthinol in LPS-Induced RAW264.7 Cells via the NAAA–PEA Pathway
2022: This survey exhibits that the majority girls who used hashish or the cannabinoids THC, CBD, or PEA for gynecologic situations reported that it improved ache
Medical Hashish for Gynecologic Ache Situations: A Systematic Assessment
2022: In a mouse mannequin of weight problems, PEA restored the plasticity of their white and brown fats cells, leptin sensitivity, tissue hormone sensitivity and rewired the vitality storing white into energy-consuming brown fats cells
Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α
2022: In a research of 90 sufferers with COVID-19, PEA diminished inflammatory states, oxidative states and alterations to blood biomarkers
Results of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Levels: A Case-Management Examine
2022: In overweight mice, PEA lessened neuroinflammation in addition to anxious habits
Palmitoylethanolamide dampens neuroinflammation and anxiety-like habits in overweight mice
2021: In people with induced migraines, the PEA ranges of their spinal cords didn’t elevate for individuals who recurrently skilled episodic migraines
Spinal nociceptive sensitization and plasma palmitoylethanolamide ranges throughout experimentally-induced migraine assaults
2021: In an animal mannequin of stroke, they already knew that PEA protects the blood-brain barrier and the mind itself. This research discovered that the results weren’t solely mediated by modifications in genetic transcription (the PPARα receptor) but in addition by the regulation of the cell’s microfilaments
PEA prevented early BBB disruption after cerebral ischaemic/reperfusion (I/R) harm via regulation of ROCK/MLC signaling
2021: In people, PEA in addition to the flavonoid luteolin helped to get better the sense of odor after a COVID an infection
Randomized medical trial “olfactory dysfunction after COVID-19: olfactory rehabilitation remedy vs. intervention therapy with Palmitoylethanolamide and Luteolin”: preliminary outcomes
2021: In lung cells uncovered to the spike protein of SARS-CoV-2, ultramicronized PEA diminished all inflammatory markers
Ultramicronized Palmitoylethanolamide Inhibits NLRP3 Inflammasome Expression and Professional-Inflammatory Response Activated by SARS-CoV-2 Spike Protein in Cultured Murine Alveolar Macrophages
2021: In Greek Navy SEALS present process strenuous train, their ranges of anandamide, PEA and oleamide all elevated, suggesting an adaptive potential of the ECS in serving to with stress and heart-rate
Endocannabinoids and coronary heart price variability alterations after publicity to extended intensive bodily train of the Hellenic Navy SEALs
2021: A case research of PEA for the neuropathic ache of shingles
Palmitoylethanolamide (PEA) within the therapy of neuropathic ache: a case research
2021: In rats with spinal wire accidents, PEA alleviated the harm, inhibited irritation, mitigated oxidative stress, diminished cell loss of life and promoted motor perform restoration
PPARα agonist relieves spinal wire harm in rats by activating Nrf2/HO-1 through the Raf-1/MEK/ERK pathway
2021: In people, CBD and PEA discovered secure for the pores and skin
Tolerability Profile of Topical Cannabidiol and Palmitoylethanolamide: A Compilation of Single-Middle Randomized Evaluator-Blinded Scientific and In Vitro Research in Regular Pores and skin
2021: In rabbits having eye surgical procedure, PEA diminished postoperative irritation and scarring through the nuclear PPARα receptors
Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgical procedure in rabbits by suppressing canonical and non-canonical TGFβ signaling via PPARα
2021: In rats on an weight problems weight-reduction plan, PEA in addition to oleamide (OEA – one other endocannabinoid) functioned as anti-obesity dietary interventions
Palmitoleoylethanolamide Is an Environment friendly Anti-Weight problems Endogenous Compound: Comparability with Oleylethanolamide in Eating regimen-Induced Weight problems
2021: In mice with infected colons, a mixture of polydatin (a precursor of resveratrol) and ultra-micronized PEA decreased irritation through a number of pathways
PEA/Polydatin: Anti-Inflammatory and Antioxidant Method to Counteract DNBS-Induced Colitis
2021: In mice with their left carotid artery tied off, a mixture of PEA and rutin (a useful plant pigment) diminished irritation, oxidative stress and vascular injury
Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Harm via Modulation of the Nrf2/HO-1 and NF-kB Pathways
2021: In a human lung tissue mannequin of COVID-19 an infection, a mixture of PEA and α-lipoic acid (ALA) diminished oxidative stress and lowered the cytokine storm
A Mixture of α-Lipoic Acid (ALA) and Palmitoylethanolamide (PEA) Blocks Endotoxin-Induced Oxidative Stress and Cytokine Storm: A Doable Intervention for COVID-19
2021: In a mouse mannequin of traumatic mind harm (and a small medical research), a mixture of PEA and the flavonoid luteolin precipitated elevated neurogenesis in addition to enhancements in reminiscence recall
Co-Extremely PEALut Enhances Endogenous Restore Response Following Reasonable Traumatic Mind Harm
2021: In human cells, PEA and polydatin lowered vascular irritation
Palmitoylethanolamide related to polydatin reduces irritation in human endothelial vascular cells uncovered to doxorubicin and trastuzumab via PPAR-a and NLRP3-related pathways
2021: In people with Tourette’s, preliminary promise was seen with a mixture of 10 mg of THC + 800 mg of PEA
A Section-2 Pilot Examine of a Therapeutic Mixture of Δ 9-Tetrahydracannabinol and Palmitoylethanolamide for Adults With Tourette’s Syndrome
They discovered that “enchancment in tic signs was statistically vital inside 1 week of beginning therapy in contrast with baseline” and that “therapy led to a median enchancment in tic signs of greater than 20%.”
2021: Within the mind of a mannequin organism, the injection of PEA or OEA mediated the mind ranges of serotonin and acetylcholine
In vivo mind ranges of acetylcholine and 5-hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement
2021: In rats with benign prostatic hyperplasia (the most typical benign tumor in males), a mixture of PEA and baicalein (an energetic ingredient in Baikal skullcap) lowered irritation, diminished oxidative stress and helped to modulate apoptosis (programmed mobile suicide)
Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia
2021: In people with nerve ache from rheumatic illnesses, PEA mixed nicely with acetyl-l-carnitine (ALC) to decrease irritation and to extend medical scores
Efficacy of a set mixture of Palmitoylethanolamide and acetyl-l-carnitine (PEA + ALC FC) within the therapy of Neuropathies secondary to Rheumatic Ailments
2021: In people, this cohort evaluation discovered that the range of your intestine microbiome was associated to your happiness and motivation through the endocannabinoid system, particularly through PEA – which they name the endogenous model of CBD
Endocannabinoid system mediates the affiliation between gut-microbial variety and anhedonia/amotivation in a normal inhabitants cohort
2021: In microglial cells (the immune cells of the mind), PEA precipitated decreased irritation and elevated neuroprotection
Palmitoylethanolamide Modulation of Microglia Activation: Characterization of Mechanisms of Motion and Implication for Its Neuroprotective Results
2021: A medical trial the place PEA from Levagen+ improves many measures of sleep
Palmitoylethanolamide for Sleep Disturbance. A Double-blind, Randomised, Placebo-controlled Interventional Examine
2021: Engineering micro organism to dwell within the guts and produce PEA on demand
Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice
2021: In mice with varicocele (a dysfunction of the veins taking blood away from the testicles, a serious reason behind human infertility), PEA helped through the PPAR-α receptors
The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Results Unmasking New Therapeutic Targets in Murine Varicocele
2021: In mice with dermatitis, a topical containing CBD and PEA lessened irritation
Anti-inflammatory Impact of Cannabidiol and Palmitoylethanolamide Containing Topical Formulation on Pores and skin in a 12-O-Tetradecanoylphorbol-13-Acetate-Induced Dermatitis Mannequin in Mice
2021: In a rat mannequin of inflammatory ache, PEA mixed nicely with acetyl-l-carnitine (LAC)
Impact of Extremely-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Mannequin of Inflammatory Ache
2021: In pregnant rats, even big doses of PEA precipitated no measurable harms
Palmitoylethanolamide: Prenatal Developmental Toxicity Examine in Rats
2021: In human with joint ache, PEA diminished ache and improved temper
The Impact of a Dispersible Palmitoylethanolamide (Levagen+) In comparison with a Placebo for Lowering Joint Ache in an Grownup Inhabitants – A Randomised, Double-Blind Examine
2021: In rabbits having eye surgical procedure, PEA diminished postoperative irritation and scarring through the nuclear PPARα receptors
Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgical procedure in rabbits by suppressing canonical and non-canonical TGFβ signaling via PPARα
2020: In a mouse mannequin of Gulf Struggle sickness, publicity alters the response to PEA
Pyridostigmine bromide publicity creates power, underlying neuroimmune disruption within the gastrointestinal tract and mind that alters responses to palmitoylethanolamide in a mouse mannequin of Gulf Struggle Sickness
2020: On utilizing PEA for neurological problems
Meals dietary supplements primarily based on palmitoylethanolamide plus hydroxytyrosol from olive tree or Bacopa monnieri extracts for neurological illnesses
2020: This hypothetical paper means that the flexibility of PEA to calm mast cells within the lungs could also be a possible therapy for COVID
Sodium chromo-glycate and palmitoylethanolamide: A doable technique to deal with mast cell-induced lung irritation in COVID-19
2020: In mice with temper problems induced by high-fat diets, PEA limits temper problems and cognitive dysfunction
Palmitoylethanolamide limits temper problems and cognitive dysfunction induced by excessive fats weight-reduction plan in overweight mice
2020: In 4 leaping horses with non-responsive lameness, ultramicronized PEA for 4 months allowed them to return to competitors
Oral Supplementation with Ultramicronized Palmitoylethanolamide for Joint Illness and Lameness Administration in 4 Leaping Horses: A Case Report
2020: In cells, micronized PEA (FM-LipoMatrix®) mixed with lipoic acid and vitamin D3 absorbed higher and diminished neuroinflammation
A New Palmitoylethanolamide Type Mixed with Antioxidant Molecules to Enhance Its Effectivess on Neuronal Getting older
2020: In a mobile mannequin of Alzheimer’s, PEA protected the neurons and elevated their survival
Astrocytic palmitoylethanolamide pre-exposure exerts neuroprotective results in astrocyte-neuron co-cultures from a triple transgenic mouse mannequin of Alzheimer’s illness
2020: In people with glaucoma, PEA discovered useful
Impact of palmitoylethanolamide on internal retinal perform in glaucoma: a randomized, single blind, crossover, medical trial by pattern-electroretinogram
2020: For sufferers with COVID-19, FSD Pharma obtained FDA approval to submit an Investigational New Drug Utility for the usage of PEA to extend endogenous ranges of endocannabinoid
2020: In rats, PEA useful for eye problems through the PPARα nuclear receptors
PPARα-Dependent Results of Palmitoylethanolamide Towards Retinal Neovascularization and Fibrosis
2020: In rats, a have a look at how PEA causes vasodepression (the reducing of blood strain) through the guts’s CB1, TRPV1 and possibly GPR55 receptors, however not by CB2
Potential Mechanisms Concerned in Palmitoylethanolamide-Induced Vasodepressor Results in Rats
2020: In a double-blind human research, CBD and PEA each helped scale back permeability within the colon and seem useful for IBS
Palmitoylethanolamide and Cannabidiol Forestall Irritation-induced Hyperpermeability of the Human Intestine In Vitro and In Vivo-A Randomized, Placebo-controlled, Double-blind Managed Trial
2020: In sufferers with decrease again ache, the mixture of remedy and ultramicronized PEA lowered ache previous clinically related ranges in addition to growing bodily and psychological high quality of life
Mixture of Rehabilitative Remedy With Ultramicronized Palmitoylethanolamide for Persistent Low Again Ache: An Observational Examine
2020: In 70 pediatric sufferers with migraines, ultramicronized PEA decreased the quantity and severity of assaults with just one affected person experiencing gentle uncomfortable side effects (nausea and floating)
Tolerability of Palmitoylethanolamide in a Pediatric Inhabitants Struggling From Migraine: A Pilot Examine
2020: In a human research with 28 individuals, Levagen+ useful for train restoration by lowering myoglobin and lactate focus
The Impact of Orally Dosed Levagen+™ (Palmitoylethanolamide) on Train Restoration in Wholesome Males-A Double-Blind, Randomized, Placebo-Managed Examine
2020: In mice with dry eye induced by sleep loss, they’d decrease ranges of PEA within the lacrimal gland and its artificial enzyme (N-acylated phosphatidylethanolamine-phospholipase D) – therapy with PEA restored lipid stability and guarded the attention through PPARα
N-Palmitoylethanolamine Maintains Native Lipid Homeostasis to Relieve Sleep Deprivation-Induced Dry Eye Syndrome
2020: Mechanistic research of how the enzyme NAAA breaks down PEA
N-Acylethanolamine Acid Amidase (NAAA): Mechanism of Palmitoylethanolamide Hydrolysis Revealed by Mechanistic Simulations
2020: In a mouse mannequin of Alzheimer’s, 3 months of oral ultramicronized PEA “rescued cognitive deficit, restrained neuroinflammation and oxidative stress, and diminished the rise in hippocampal glutamate ranges”
Persistent Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Ranges in A Transgenic Murine Mannequin of Alzheimer’s Illness
2020: In mice asphyxiated at start, PEA attenuated the neuronal injury in corpus striatum, restored stage of GFAP cells in addition to stopping the lower of pNF-H/M and MAP-2
Partial Reversal of Striatal Harm by Palmitoylethanolamide Administration Following Perinatal Asphyxia
2019: In 22 sufferers with ache, PEA was efficient at lowering power neuropathic ache through “the ascending ache pathway which are doubtless pushed by rhythmic astrocytic gliotransmission”
Results of the Glial Modulator Palmitoylethanolamide on Persistent Ache Depth and Mind Operate
2019: A re-analysis of an outdated unpublished research on the efficacy of micronized PEA for decrease again ache discovered it to be extremely efficient
Micronized Palmitoylethanolamide: A Submit Hoc Evaluation of a Managed Examine in Sufferers With Low Again Ache – Sciatica
2019: in human double-blind research, each CBD and PEA diminished irritation and lowering permeability within the human colon
Palmitoylethanolamide and Cannabidiol Forestall Irritation-induced Hyperpermeability of the Human Intestine In Vitro and In Vivo—A Randomized, Placebo-controlled, Double-blind Managed Trial
2019: In a human double-blind research of 111 individuals with knee osteoarthritis, PEA discovered useful for irritation
A Double-Blind Randomized Placebo Managed Examine Assessing Security, Tolerability and Efficacy of Palmitoylethanolamide for Signs of Knee Osteoarthritis
2019: In 23 sufferers with mastocytosis (accumulation of mast cells), they’d elevated PEA ranges
Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Sufferers With Mastocytosis
2019: In 30 sufferers with endometriosis, each ultramicronized PEA and co-micronised palmitoylethanolamide/polydatin (PEA/PLD) confirmed vital enhancements in all measures in addition to high quality of life
Impact of Ultramicronized-Palmitoylethanolamide and Co-Micronized Palmitoylethanolamide/Polydatin on Persistent Pelvic Ache and High quality of Life in Endometriosis Sufferers: An Open-Label Pilot Examine
2019: In a single affected person with burning mouth syndrome, after gabapentin did little, including PEA significantly improved the ache
Add-on Administration of Ultramicronized Palmitoylethanolamide within the Therapy of New-Onset Burning Mouth Syndrome
2019: In 32 sufferers with bladder issues, micronized PEA mixed with polydatin diminished ache and urinary frequency
Micronized Palmitoylethanolamide-Polydatin Reduces the Painful Symptomatology in Sufferers With Interstitial Cystitis/Bladder Ache Syndrome
2019: In mice, nice research on the broad lipid modifications brought on by PEA
Broad Lipidomic and Transcriptional Adjustments of Prophylactic PEA Administration in Grownup Mice
2019: In cats with hypersensitive pores and skin, ultramicronized PEA helped enhance the efficacy window of a steroid course of methylprednisolone
Impact of Dietary Supplementation With Ultramicronized Palmitoylethanolamide in Sustaining Remission in Cats With Nonflea Hypersensitivity Dermatitis: A Double-Blind, Multicentre, Randomized, Placebo-Managed Examine
2019: In mice with injured spines, Noxiall (a combo of PEA, Beta-Caryophyllene, Carnosic Acid, and Myrrh) matched pregabalin and gabapentin for lessening ache and lowering mechanical and thermal sensitivities
Efficacy of a Mixture of N-Palmitoylethanolamide, Beta-Caryophyllene, Carnosic Acid, and Myrrh Extract on Persistent Neuropathic Ache: A Preclinical Examine
2019: In rats with a coronary heart assault, the mixture of PEA and baicalein from Chinese language drugs “decreases myocardial tissue harm, neutrophils infiltration, markers for mast cell activation expression as chymase and tryptase and pro-inflammatory cytokines manufacturing (TNF-α, IL-1β)” and “therapy reduces stress oxidative and modulates Nf-kB and apoptosis pathways”
Results of a New Compound Containing Palmitoylethanolamide and Baicalein in Myocardial Ischaemia/Reperfusion Harm in Vivo
2019: In mice with a painful nerve harm, PEA restored cognitive habits and neuronal functioning through two receptors within the glutamate system
Metabotropic Glutamate Receptor 5 and eight Modulate the Ameliorative Impact of Ultramicronized Palmitoylethanolamide on Cognitive Decline Related With Neuropathic Ache
2019: In mice with a painful nerve harm, ultramicronized PEA was in a position to “reverse mechanical allodynia and thermal hyperalgesia, reminiscence deficit and LTP” and restore “the extent of glutamate and the expression of phosphorylated GluR1 subunits, postsynaptic density and neurogenesis” through PPARa
Extremely-micronized Palmitoylethanolamide Rescues the Cognitive Decline-Related Lack of Neural Plasticity within the Neuropathic Mouse Entorhinal Cortex-Dentate Gyrus Pathway
2019: In a mouse with PTSD, PEA was used to activate PPARa and this helped with worry extinction, anxiousness and elevated allopregnanolone (ALLO – a gamma-aminobutyric acidergic neurosteroid implicated in temper problems)
Stimulation of Peroxisome Proliferator-Activated Receptor-α by N-Palmitoylethanolamine Engages Allopregnanolone Biosynthesis to Modulate Emotional Habits
2019: In a rat mannequin of despair, PEA helped enormously through a number of totally different markers together with stress hormones – most likely through PPARα
N-Palmitoylethanolamide Exerts Antidepressant-Like Results in Rats: Involvement of PPAR α Pathway within the Hippocampus
2019: In an animal mannequin of dementia, PEA and oxazoline had been protecting
N-Palmitoylethanolamine-oxazoline (PEA–OXA): A New Therapeutic Technique to Cut back Neuroinflammation, Oxidative Stress Related to Vascular Dementia in an Experimental Mannequin of Repeated Bilateral Widespread Carotid Arteries Occlusion
2019: In neurons, therapy with 2-AG or PEA affected microglial cells and precipitated safety however utilizing them collectively blocked their constructive results and altered the distribution (however not the activation) of PPARa
Reverse Results of Neuroprotective Cannabinoids, Palmitoylethanolamide, and 2-Arachidonoylglycerol on Operate and Morphology of Microglia
2019: In a mannequin of mast cells, they discovered “novel molecular mechanisms via which PEA controls mast cell degranulation and substance P (SP)-induced histamine launch” with PEA growing 2-AG through stimulation of DAGL-α and -β exercise and the mixture of PEA and 2-AG working collectively at low ranges once they didn’t work on their very own
Palmitoylethanolamide Counteracts Substance P-induced Mast Cell Activation in Vitro by Stimulating Diacylglycerol Lipase Exercise
2018: In 155 sufferers with spinal injury and ache, ultramicronized PEA helped with gentle and average ache, however not extreme ache, with a particular emphasis on its security
N-Palmitoyl Ethanol Amide Pharmacological Therapy in Sufferers With Nonsurgical Lumbar Radiculopathy
2018: In 58 sufferers with despair, 600 mg of PEA twice a day + citalopram considerably improved signs and demonstrated a rapid-onset impact
Palmitoylethanolamide as Adjunctive Remedy in Main Depressive Dysfunction: A Double-Blind, Randomized and Placebo-Managed Trial
2018: In 35 sufferers with burning mouth syndrome, 600 mg of ultramicronized PEA considerably diminished the ache after 60 days and precipitated no interference within the different pharmacological therapies
Efficacy of Ultramicronized Palmitoylethanolamide in Burning Mouth Syndrome-Affected Sufferers: A Preliminary Randomized Double-Blind Managed Trial
2018: In 20 sufferers with migraines, ultramicronized PEA therapy relieved ache with no uncomfortable side effects
Results of Add-On Ultramicronized N-Palmitol Ethanol Amide in Sufferers Struggling of Migraine With Aura: A Pilot Examine
2018: In mice with ache, PEA potentiated morphine and lessened tolerance, suggesting it as an additive therapy
Ultramicronized N-Palmitoylethanolamine Supplementation for Lengthy-Lasting, Low-Dosed Morphine Antinociception
2018: In mice with epilepsy, PEA injections lessened seizures, promoted neuroprotection and modulated ECS ranges
Antiepileptogenic Impact of Subchronic Palmitoylethanolamide Therapy in a Mouse Mannequin of Acute Epilepsy
2018: In a mouse mannequin of Alzheimer’s, ultramicronized PEA improved studying and reminiscence, lessened despair and anhedonia and helped with neuroinflammation through a number of strategies
Ultramicronized Palmitoylethanolamide Rescues Studying and Reminiscence Impairments in a Triple Transgenic Mouse Mannequin of Alzheimer’s Illness by Exerting Anti-Inflammatory and Neuroprotective Results
2018: In aged mice, pretreatment with PEA protected the mind from Parkinson’s disease-like injury through a number of mechanisms
N-palmitoylethanolamide Prevents Parkinsonian Phenotypes in Aged Mice
2018: In aged mice, PEA protected against a bacterial an infection within the organs and mind
Prophylactic Palmitoylethanolamide Prolongs Survival and Decreases Detrimental Irritation in Aged Mice With Bacterial Meningitis
2018: In rats with induced ache, ultramicronized PEA reached the peripheral websites extra readily and precipitated much less irritation and tissue injury through the downregulation of a number of “spinal inflammatory and oxidative pathways”
Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Ranges and Spinal Anti-hyperalgesic Impact
2018: In child mice with simulated perinatal asphyxia (not in a position to breate), PEA therapy attenuated injury within the hippocampus and improved behavioral alterations
Palmitoylethanolamide Ameliorates Hippocampal Harm and Behavioral Dysfunction After Perinatal Asphyxia within the Immature Rat Mind
2018: In younger rats disadvantaged of oxygen, PEA therapy diminished neuroinflammation, astrogliosis (overabundance of astrocytes) and preserved cognitive perform
Palmitoylethanolamide Prevents Neuroinflammation, Reduces Astrogliosis and Preserves Recognition and Spatial Reminiscence Following Induction of Neonatal Anoxia-Ischemia
2018: In rats with joint irritation, micronized PEA diminished the injury, ache and activation of macrophages
Micronized Palmitoylethanolamide Reduces Joint Ache and Glial Cell Activation
2018: In fashions of Alzheimer’s, PEA dampened the reactivity of the microglia and improved viability of the neurons in addition to glial neurosupport
Palmitoylethanolamide Dampens Reactive Astrogliosis and Improves Neuronal Trophic Help in a Triple Transgenic Mannequin of Alzheimer’s Illness: In Vitro and In Vivo Proof
2018: In rats with induced liver fibrosis, PEA protected through a number of mechanisms
Palmitoylethanolamide Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats
2018: In a combination of astrocytes and neurons, PEA blunted the astrocyte activation brought on by a problem by Aβ42 (a plaque related to Alzheimer’s illness)
Palmitoylethanolamide Blunts Amyloid-β42-Induced Astrocyte Activation and Improves Neuronal Survival in Main Mouse Cortical Astrocyte-Neuron Co-Cultures
2018: PEA nanoparticles for intraocular supply
Modern Nanoparticles Improve N-Palmitoylethanolamide Intraocular Supply
2017: In a mouse with traumatic mind harm, PEA protected the mind
Palmitoylethanolamide Reduces Neuropsychiatric Behaviors by Restoring Cortical Electrophysiological Exercise in a Mouse Mannequin of Gentle Traumatic Mind Harm
2017: In 100 sufferers with spinal injury and ache, ultramicronized PEA mixed nicely with paracetamol and codeine to alleviate ache with no uncomfortable side effects
Nonsurgical Lumbar Radiculopathies Handled With Ultramicronized Palmitoylethanolamide (umPEA): A Sequence of 100 Instances
“We additionally famous its security because of the whole absence of antagonistic results.”
2017: In 55 sufferers with decrease again ache, ultramicronized PEA was an efficient add-on to tapentadol for ache and improved high quality of life
The Useful Use of Ultramicronized Palmitoylethanolamide as Add-On Remedy to Tapentadol within the Therapy of Low Again Ache: A Pilot Examine Evaluating Potential and Retrospective Observational Arms
2017: In 10 sufferers with ache, ultramicronized PEA helped
N-of-1 Randomized Trials of Extremely-Micronized Palmitoylethanolamide in Older Sufferers With Persistent Ache
2017: In mice with a damaged tibia, a product of micronized and ultramicronized PEA precipitated “an improved therapeutic course of, fracture restoration and fibrosis rating” in addition to “decreased mast cell density, nerve development issue, matrix metalloproteinase 9 and cytokine expression” and apoptosis (mobile suicide) (correction)
Impact of a New Formulation of Micronized and Ultramicronized N-palmitoylethanolamine in a Tibia Fracture Mouse Mannequin of Advanced Regional Ache Syndrome
2017: In mice with mind and backbone accidents, the mixture of PEA and oxazoline protected the motor perform and behavioral deficits
N-Palmitoylethanolamine-Oxazoline as a New Therapeutic Technique to Management Neuroinflammation: Neuroprotective Results in Experimental Fashions of Spinal Wire and Mind Harm
2017: In microglia and macrophage cells, PEA elevated CB2 expression through PPAR-α
Palmitoylethanolamide Induces Microglia Adjustments Related With Elevated Migration and Phagocytic Exercise: Involvement of the CB2 Receptor
2017: In mice with induced allergic reactions, PEA helped to clear the bronchi and upregulated CB2 and GPR55, suggesting it use as a complement in opposition to bronchial asthma
Palmitoylethanolamide Supplementation throughout Sensitization Prevents Airway Allergic Signs within the Mouse
2017: In colon cells, CBD and PEA are anti-inflammatory
Cannabidiol and Palmitoylethanolamide Are Anti-Inflammatory within the Acutely Infected Human Colon
2017: In intestinal cells, PEA lowered intestinal permeability through PPARα and in response to inflammatory mediators, the cells elevated their PEA ranges
Oleoylethanolamine and Palmitoylethanolamine Modulate Intestinal Permeability in Vitro through TRPV1 and PPARα
2017: In a canine pores and skin mannequin, PEA protected against the detrimental results of mast cells
Ultramicronized Palmitoylethanolamide Counteracts the Results of Compound 48/80 in a Canine Pores and skin Organ Tradition Mannequin
2016: In a research of cells, animals and people, PEA raised the extent of 2-AG and potentiated its results at TRPV1
The Anti-Inflammatory Mediator Palmitoylethanolamide Enhances the Ranges of 2-arachidonoyl-glycerol and Potentiates Its Actions at TRPV1 Cation Channels
2016: In 27 sufferers with endometriosis, AEA and PEA ranges elevated together with situation severity
Elevated Systemic Ranges of Endocannabinoids and Associated Mediators Throughout the Menstrual Cycle in Girls With Endometriosis
2016: In people with a number of sclerosis, ultramicronized PEA added to the primary line therapy (interferon IFN-β1a) precipitated an enchancment in ache scores and high quality of life
Oral Palmitoylethanolamide Therapy Is Related With Decreased Cutaneous Hostile Results of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting A number of Sclerosis
2016: In 72 sufferers with spinal wire accidents, ultramicronized PEA precipitated no constructive results in any respect for something measured
Ultramicronized Palmitoylethanolamide in Spinal Wire Harm Neuropathic Ache: A Randomized, Double-Blind, Placebo-Managed Trial (followup remark: Ultramicronized Palmitoylethanolamide Therapy in Central Neuropathic Ache Following Longstanding Spinal Wire Harm: Attempt to Extinguish the Hearth After Every thing Was Burned)
2016: In a preclinical research in mice and a case research with a ten yr outdated, a mixture of PEA and luteolin ameliorated symptomatology of autism
Useful Results of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Mannequin of Autism and in a Case Report of Autism
2016: In mice with coronary heart assaults, ultramicronized PEA protected the guts through the PPARa receptors
Protecting Results of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Harm in VIVO
2016: In rats with endometriosis, ultramicronized PEA labored through the mast cells to decrease ache, in addition to the degrees of cysts and stones
Ultramicronized Palmitoylethanolamide Reduces Viscerovisceral Hyperalgesia in a Rat Mannequin of Endometriosis Plus Ureteral Calculosis: Function of Mast Cells
2016: On this mouse mannequin and affected person research of colitis and Crohn’s illness, PEA “inhibits colitis-associated angiogenesis [blood vessel formation], lowering VEGF launch and new vessels formation” through the PPARa and helped to manage the angiogenic course of through the mTOR/Akt axis
Palmitoylethanolamide Modulates Irritation-Related Vascular Endothelial Progress Issue (VEGF) Signaling through the Akt/mTOR Pathway in a Selective Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α)-Dependent Method
2016: In colon most cancers cells, PEA precipitated a big discount in proliferation, angiogenesis, and VEGF secretion and expression through PPARa’s impact on the AkT/mTOR axis
Palmitoylethanolamide Exerts Antiproliferative Impact and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line By way of a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway
2015: In two sufferers with autism, PEA precipitated “fast enhancements in cognitive, behaviors, and sociability”
Useful Results of Palmitoylethanolamide on Expressive Language, Cognition, and Behaviors in Autism: A Report of Two Instances
2015: In 160 canines with crimson itchy pores and skin, ultramicronized PEA was “efficient and secure in lowering pruritus and pores and skin lesions” and bettering high quality of life
Efficacy of Extremely-Micronized Palmitoylethanolamide in Canine Atopic Dermatitis: An Open-Label Multi-Centre Examine
2015: In rats with ache, PEA delayed the tolerance results of morphine
Delay of Morphine Tolerance by Palmitoylethanolamide
2015: In rats with hypertension, PEA protected through a number of distinction pathways
Palmitoylethanolamide Therapy Reduces Blood Strain in Spontaneously Hypertensive Rats: Involvement of Cytochrome p450-derived Eicosanoids and Renin Angiotensin System
2015: In mice with broken kidneys, PEA and silymarin mixed to scale back “kidney dysfunction, histological injury, neutrophil infiltration and oxidative stress” and inhibited NF-κB and apoptosis (mobile suicide) pathways
Results of Palmitoylethanolamide and Silymarin Mixture Therapy in an Animal Mannequin of Kidney Ischemia and Reperfusion
2015: In rats with infected eyes, PEA “decreased the inflammatory cell infiltration and improved histological injury of eye tissues” and diminished ocular irritation
The Anti-Inflammatory Results of Palmitoylethanolamide (PEA) on Endotoxin-Induced Uveitis in Rats
2015: In mice with induced colitis, PEA helps through the CB2, GPR55 and PPARa receptors in addition to the TRPV1 channels
Palmitoylethanolamide, a Naturally Occurring Lipid, Is an Orally Efficient Intestinal Anti-Inflammatory Agent
2015: In a mouse mannequin of a number of sclerosis, therapy with PEA or CBD diminished illness severity with diminished irritation, demyelination, axonal injury and inflammatory cytokine expression – however they didn’t work as nicely collectively
Interplay between the protecting results of cannabidiol and palmitoylethanolamide in experimental mannequin of a number of sclerosis in C57BL/6 mice
2015: In mice with painful nerve accidents, PEA restored their glutamate functioning and the modifications in amino acid launch (good graphic)
Palmitoylethanolamide Reduces Ache-Associated Behaviors and Restores Glutamatergic Synapses Homeostasis within the Medial Prefrontal Cortex of Neuropathic Mice
2015: In cells challenged by the Aβ amyloid plaques of Alzheimer’s illness, PEA “diminished expression of pro-inflammatory and pro-angiogenic markers” through PPARa
Palmitoylethanolamide Regulates Manufacturing of Professional-Angiogenic Mediators in a Mannequin of β Amyloid-Induced Astrogliosis In Vitro
2015: In mice neurons challenged by the Aβ amyloid plaquess of Alzheimer’s, PEA rescued glutamate in non-transgenic mice however not the triple-transgenic murine mannequin
Differential Results of Palmitoylethanolamide Towards Amyloid-β Induced Toxicity in Cortical Neuronal and Astrocytic Main Cultures From Wild-Kind and 3xTg-AD Mice
2014: In 30 diabetic sufferers, micronized PEA successfully diminished ache whereas blood work and urine evaluation noticed no vital alterations
Micronized Palmitoylethanolamide Reduces the Signs of Neuropathic Ache in Diabetic Sufferers
2014: In 60 sufferers with eczema, a PEA/AEA topical improved “passive and energetic pores and skin features concurrently”
N-palmitoylethanolamine and N-acetylethanolamine Are Efficient in Asteatotic Eczema: Outcomes of a Randomized, Double-Blind, Managed Examine in 60 Sufferers
2014: In a affected person with power vulvar and anal ache, a topical of PEA and baclofen decreased her ache by 50% and allowed for intercourse once more
Vulvodynia and Proctodynia Handled With Topical Baclofen 5 % and Palmitoylethanolamide
2014: In canines with crimson itchy pores and skin, PEA most likely helped through the downregulation of mast cells and ranges of PEA elevated because the illness progressed
Elevated Ranges of Palmitoylethanolamide and Different Bioactive Lipid Mediators and Enhanced Native Mast Cell Proliferation in Canine Atopic Dermatitis
2014: In a rat mannequin of Alzheimer’s illness, PEA was in a position to restore the alterations through PPARa and to reverse the cognitive impairments
Palmitoylethanolamide Controls Reactive Gliosis and Exerts Neuroprotective Capabilities in a Rat Mannequin of Alzheimer’s Illness
2014: In mice with an infected colon, PEA improved transit time within the GI tract and elevated AEA ranges through the CB1 receptors and TRPV1 channels
Palmitoylethanolamide Normalizes Intestinal Motility in a Mannequin of Submit-Inflammatory Accelerated Transit: Involvement of CB₁ Receptors and TRPV1 Channels
2014: Within the intestines of rats present process chemotherapy, PEA protected through the mast cells for cover
Palmitoylethanolamide Regulates Improvement of Intestinal Radiation Harm in a Mast Cell-Dependent Method
2014: In a rat mannequin of inflammatory ache, micronized/ultramicronized PEA labored higher orally than PEA
Micronized/ultramicronized Palmitoylethanolamide Shows Superior Oral Efficacy In comparison with Nonmicronized Palmitoylethanolamide in a Rat Mannequin of Inflammatory Ache
2014: In mice, PEA therapy elevated the flexibility of macrophages to phagocytose (engulf and digest) E. coli micro organism
Palmitoylethanolamide Stimulates Phagocytosis of Escherichia Coli K1 by Macrophages and Will increase the Resistance of Mice Towards Infections
2014: In colon cells, PEA improved all macroscopic indicators of ulcerative colitis and decreased all of the proinflammatory markers examined through PPARa
Palmitoylethanolamide Improves Colon Irritation By way of an Enteric Glia/Toll Like Receptor 4-dependent PPAR-α Activation
2013: In 24 girls with endometriosis and power pelvic ache, micronized PEA and polydatin diminished pelvic ache, dysmenorrhea (cramps) and dyspareunia (ache throughout intercourse) however not dysuria (painful urination) and dischezia (strained stools) in addition to bettering general high quality of life
[Administration of Micronized Palmitoylethanolamide (PEA)-transpolydatin in the Treatment of Chronic Pelvic Pain in Women Affected by Endometriosis: Preliminary Results]
2013: In 7 sufferers with power idiopathic axonal polyneuropathy (intense ache), PEA diminished ache considerably with no uncomfortable side effects
Persistent Idiopathic Axonal Neuropathy and Ache, Handled With the Endogenous Lipid Mediator Palmitoylethanolamide: A Case Assortment
2013: In a rat mannequin of epilepsy, PEA diminished seizures through the PPAR-α receptors and not directly by the CB1 receptors
Antiepileptic Motion of N-palmitoylethanolamine By way of CB1 and PPAR-α Receptor Activation in a Genetic Mannequin of Absence Epilepsy
2013: In mice with spinal wire trauma, they discovered that PPAR-δ and PPAR-γ additionally contribute to PEA’s anti-inflammatory results
Molecular Proof for the Involvement of PPAR-δ and PPAR-γ in Anti-Inflammatory and Neuroprotective Actions of Palmitoylethanolamide After Spinal Wire Trauma
2013: In rats with hypertension, PEA diminished blood strain and diminished injury to the kidneys
N-Palmitoylethanolamide Protects the Kidney From Hypertensive Harm in Spontaneously Hypertensive Rats through Inhibition of Oxidative Stress
2013: In mice with ache, PEA helped through recruitment and safety of mast cells, lower of nerve development issue, preservation of the nerves and the discount of microglia activation within the spinal wire
Non-neuronal Cell Modulation Relieves Neuropathic Ache: Efficacy of the Endogenous Lipid Palmitoylethanolamide
2013: PEA targets each glial and mast cells for anti-inflammation and neuroprotective results
Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator
2013: In mice injured by formalin, PEA activated microglia and glia cells, considerably diminished mechanical allodynia and thermal hyperalgesia, suggesting the use for spinal wire accidents
Palmitoylethanolamide Reduces Formalin-Induced Neuropathic-Like Behaviour By way of Spinal Glial/Microglial Phenotypical Adjustments in Mice
2013: In rat neuronal cells challenged with the Aβ amyloid plaques of Alzheimer’s, “PEA is ready to blunt Aβ-induced astrocyte activation and to exert a marked protecting impact on neurons”
Neuroglial Roots of Neurodegenerative Ailments: Therapeutic Potential of Palmitoylethanolamide in Fashions of Alzheimer’s Illness
2013: In cells, PEA activated TRPV1, maybe through PPARa
Activation and Desensitization of TRPV1 Channels in Sensory Neurons by the PPARα Agonist Palmitoylethanolamide
2012: In people, a case sequence on PEA for ache
Therapeutic Utility of Palmitoylethanolamide within the Therapy of Neuropathic Ache Related With Varied Pathological Situations: A Case Sequence
2012: In an observational research of 600+ sufferers, PEA helped all of them with their treatment-resistant power ache and precipitated no antagonistic results
Palmitoylethanolamide within the Therapy of Persistent Ache Attributable to Totally different Etiopathogenesis
2012: In a affected person with ALS, PEA improved the medical image, most likely through the microglia and mast cells
Amyotrophic Lateral Sclerosis Therapy With Ultramicronized Palmitoylethanolamide: A Case Report
2012: In mice, PEA helped to guard from a Parkinson’s like insult, most likely through the PPARa receptor
Neuroprotective Actions of Palmitoylethanolamide in an Animal Mannequin of Parkinson’s Illness
2012: In rats, PEA protected the mind after harm by many pathways
Discount of Ischemic Mind Harm by Administration of Palmitoylethanolamide After Transient Center Cerebral Artery Occlusion in Rats
2012: In a mouse mannequin of traumatic mind harm, PEA protected the mind through a number of pathways and improved neurobehavioral features
Administration of Palmitoylethanolamide (PEA) Protects the Neurovascular Unit and Reduces Secondary Harm After Traumatic Mind Harm in Mice
2012: In a mouse mannequin of Alzheimer’s illness, injected PEA considerably helped with studying and reminiscence disfunction, most likely through the PPARa pathway
Palmitoylethanolamide Protects Towards the amyloid-β25-35-induced Studying and Reminiscence Impairment in Mice, an Experimental Mannequin of Alzheimer Illness
2012: In mice with intestinal accidents, pretreatment with PEA diminished irritation and cell loss of life, most likely through the PPARa pathway
Results of Palmitoylethanolamide on Intestinal Harm and Irritation Attributable to Ischemia-Reperfusion in Mice
2012: In mice with injured kidneys, PEA protected through a number of totally different pathways, most likely through the PPARa pathway
Palmitoylethanolamide Reduces Early Renal Dysfunction and Harm Attributable to Experimental Ischemia and Reperfusion in Mice
2012: In mice experiencing ache, PEA elevated allopregnanolone (ALLO) ranges through the PPARa receptor
Implication of Allopregnanolone within the Antinociceptive Impact of N-palmitoylethanolamide in Acute or Persistent Ache
2012: In neurons challenged by the β-amyloids of Alzheimer’s illness, PEA blunted activation and improved neuronal survival
Palmitoylethanolamide Exerts Neuroprotective Results in Blended Neuroglial Cultures and Organotypic Hippocampal Slices through Peroxisome Proliferator-Activated Receptor-α
2012: In microglial cells, PEA precipitated elevated phagosytosis of E. coli and strep
Palmitoylethanolamide Stimulates Phagocytosis of Escherichia Coli K1 and Streptococcus Pneumoniae R6 by Microglial Cells
2011: In 20 sufferers present process chemo, PEA helped with the ache and confirmed constructive results on the myelinated fiber teams
Palmitoylethanolamide Restores Myelinated-Fibre Operate in Sufferers With Chemotherapy-Induced Painful Neuropathy
2011: In mind tissue, PEA seems to manage neurosteroidogenesis (steroid manufacturing within the mind) and enhance allopregnanolone (ALLO) through the PPARa receptor
Palmitoylethanolamide Stimulation Induces Allopregnanolone Synthesis in C6 Cells and Main Astrocytes: Involvement of Peroxisome-Proliferator Activated Receptor-α
2011: In mind cells, PEA diminished the variety of microglial cells and guarded the neurons through the PPARa receptor
Palmitoylethanolamide Protects Dentate Gyrus Granule Cells through Peroxisome Proliferator-Activated Receptor-α
2011: In mice with spinal wire accidents, PEA “diminished the diploma of the severity of spinal wire trauma via the discount of mast cell infiltration and activation [and] diminished the activation of microglia and astrocytes expressing cannabinoid CB(2) receptor”
Results of Palmitoylethanolamide on Launch of Mast Cell Peptidases and Neurotrophic Components After Spinal Wire Harm
2011: In mind cells, the β-amyloid plaques of Alzheimer’s elevated PEA ranges whereas therapy with PEA blunted their proinflammatory results, most likely through elevated 2AG ranges and the PPARa receptor
Palmitoylethanolamide Counteracts Reactive Astrogliosis Induced by β-Amyloid Peptide
2010: In mice, PEA modulated the hypnotic impact of phenobarbital through PPARa’s enhance of allopregnanolone (ALLO) in addition to a constructive modulation of GABA
Palmitoylethanolamide Modulates Pentobarbital-Evoked Hypnotic Impact in Mice: Involvement of Allopregnanolone Biosynthesis
2010: In canine mast cells, PEA downregulated their exercise through a number of components, suggesting its use for irritation and ache
Results of Palmitoylethanolamide on Immunologically Induced Histamine, PGD2 and TNFalpha Launch From Canine Pores and skin Mast Cells
2009: In mice with ache, pretreatment with PEA lowered their ache ranges through PPARa’s inhibition of signaling within the dorsal root ganglia and by the discount of COX-2 and iNOS
Central Administration of Palmitoylethanolamide Reduces Hyperalgesia in Mice through Inhibition of NF-kappaB Nuclear Signalling in Dorsal Root Ganglia
2008: On this research of 2456 sufferers with eczema, PEA topical therapy precipitated much less itching, extra sleeping and half of them stopped utilizing their corticosteroids
Adjuvant Therapy of Atopic Eczema: Evaluation of an Emollient Containing N-palmitoylethanolamine (ATOPA Examine)
2008: In a mouse mannequin of a number of sclerosis, CB2, 2AG and PEA had been upregulated and PEA utilized topically diminished incapacity and lowered irritation
Examine of the Regulation of the Endocannabinoid System in a Virus Mannequin of A number of Sclerosis Reveals a Therapeutic Impact of Palmitoylethanolamide
2008: In mice with a spinal wire harm, PEA diminished “1) the diploma of spinal wire irritation and tissue harm, 2) neutrophil infiltration, 3) nitrotyrosine formation, 4) proinflammatory cytokine expression, 5) nuclear transcription issue activation-kappaB activation, 6) inducible nitric-oxide synthase expression, and 6) apoptosis” and it helped with restoration of motor perform
Results of Palmitoylethanolamide on Signaling Pathways Implicated within the Improvement of Spinal Wire Harm
2008: In mice, PEA helped with ache through CB1, TRPV1 and PPARγ
The Endogenous Fatty Acid Amide, Palmitoylethanolamide, Has Anti-Allodynic and Anti-Hyperalgesic Results in a Murine Mannequin of Neuropathic Ache: Involvement of CB(1), TRPV1 and PPARgamma Receptors and Neurotrophic Components
2008: In rat arteries, the flexibility of AEA to induce leisure was potentiated by each PEA and OEA and the flexibility of PEA and OEA to trigger leisure could also be through TRPV1
‘Entourage’ Results of N-palmitoylethanolamide and N-oleoylethanolamide on Vasorelaxation to Anandamide Happen By way of TRPV1 Receptors
2007: In mice with ache, preadministration of PEA diminished swelling and irritation through the PPARa receptor
Acute Intracerebroventricular Administration of Palmitoylethanolamide, an Endogenous Peroxisome Proliferator-Activated Receptor-Alpha Agonist, Modulates Carrageenan-Induced Paw Edema in Mice
2005: Dr. Piomelli identifies PPARa as PEA’s mechanism and on this mouse mannequin, it diminished irritation
The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-Alpha Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide
2003: In mice, PEA potentiates the flexibility of AEA to induce microglia migration and this isn’t mediated by CB1 or CB2
Palmitoylethanolamide will increase after focal cerebral ischemia and potentiates microglial cell motility
2002: In a affected person after stroke, ranges of AEA, PEA and OEA all rise
Launch of fatty acid amides in a affected person with hemispheric stroke: a microdialysis research
2002: In most cancers cells, PEA appears to potentiate the antiproliferative results of AEA through the vanilloid system
Impact on Most cancers Cell Proliferation of Palmitoylethanolamide, a Fatty Acid Amide Interacting With Each the Cannabinoid and Vanilloid Signalling Techniques
2001: In breast most cancers cells, PEA inhibited expression of FAAH and enhanced the anti-proliferative results of AEA
Palmitoylethanolamide Inhibits the Expression of Fatty Acid Amide Hydrolase and Enhances the Anti-Proliferative Impact of Anandamide in Human Breast Most cancers Cells
2001: In kidney cells, PEA enhanced AEA’s stimulation of vanilloid receptors
Palmitoylethanolamide Enhances Anandamide Stimulation of Human Vanilloid VR1 Receptors
1996: In neurons, PEA protected in opposition to glutamate toxicity and prevented neuron loss
The ALIAmide Palmitoylethanolamide and Cannabinoids, however Not Anandamide, Are Protecting in a Delayed Postglutamate Paradigm of Excitotoxic Dying in Cerebellar Granule Neurons
1995: In mast cells, PEA downmodulated mast cell activation through the CB2 receptor
Mast Cells Categorical a Peripheral Cannabinoid Receptor With Differential Sensitivity to Anandamide and Palmitoylethanolamide
1993: Levi-Montalcini’s large paper the place she mentioned PEA labored through mast cells and the place she coined the acronym ALIA
A Proposed Autacoid Mechanism Controlling Mastocyte Behaviour
1980: Dr. Epps finds PEA accumulating in infarcted myocardium and turns into the primary to recommend that fatty molecules might play a protecting function throughout ischemia and that its presence “might signify a response of myocardial tissue to harm directed at minimizing injury and selling survival”
Accumulation of N-acylethanolamine Glycerophospholipids in Infarcted Myocardium
1979: 3 giant human trials exhibits PEA’s assist for acute respiratory infections and with no detrimental results on antibody manufacturing
Research on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically managed discipline trials
1975: The primary supportive paper on the results of PEA in most cancers as a modulator of toxicity in chemotherapy
The Impact of Lengthy-Time period Administration of N-(2-hydroxyethyl)palmitamide on the Chemotherapy of RBA Rat Leukemia
1975: The primary small pilot for rheumatic ache that supported PEA’s analgesic properties
Letter: Sluggish Encephalopathies, Inflammatory Responses, and Arachis Oil
1974: Two giant scale double-blind trials exhibits PEA serving to signs of respiratory tract infections, however not their timecourse
Prophylactic efficacy of N-2-hydroxyethyl palmitamide (impulsin) in acute respiratory tract infections
1972: In mice, PEA decreased mortality from quite a lot of immunological insults
Non-specific Resistance Induced by Palmitoylethanolamide
1965: Bachur’s work finds PEA constantly current in mind, liver and muscle of rats and guinea pigs
Fatty acid amides of ethanolamine in mammalian tissues
1957: Preliminary discovery paper
The identification of N-(2-hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent
