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 pieces round it and upsetting the homeostasis of the surroundings.
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 Right Whale, a stalwart fighter in our fixed battle in opposition to irritation and ache.
A Thriller
The PEA story begins with a thriller, which ends up in one other thriller — and ends with the following nice wave of the cannabinoid revolution.
We start throughout World Battle 2 – and certainly, geopolitics performs a major function in our story. Due to the battle effort, we discover it a affluent time for the new-ish subject often known as “public well being.” A wholesome inhabitants of staff was important to help the manufacturing of battle materiel. Two NYC medical doctors named Coburn and Moore discovered that in the event that they gave dried eggs to the poor youngsters of the tenements, this helped to stop rheumatic fever and different ills associated to poor vitamin. In addition they found that egg yolks are an anti-inflammatory meals.
Normally, when a plant or meals is discovered to have distinctive well being properties, scientists dig in to search out the particular molecules chargeable for the useful 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 varied lessons of molecules concerned, they realized that it was the lipids – the fatty molecules — that brought on the optimistic well being results.
Proteins would be 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 adjustments 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 huge breakthrough occurred within the Nineteen Fifties when a group led by Dr. F.A. Kuehl recognized the lively 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 know the mechanisms that brought on this intriguing lipid to affect irritation. Through the Nineteen Sixties, some papers in animal fashions had been revealed confirming the anti-inflammatory results of PEA. And in an necessary flip of occasions, a group led by Dr. S. Udenfriend found that PEA naturally happens in a number 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 severe 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 referred to as Impulsin. To check it, they turned to the big Skoda manufacturing facility, a producer of vehicles, tanks, and industrial tools, which employed an incredible 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 youngsters entered these trials.
Administered in a double-blind method (the gold-standard of recent medical trials), all the outcomes pointed in the identical path: PEA was protected and possessed a transparent efficacy in treating respiratory infections. It reduced the incidence of fever, headache, and sore throat. And moreover, in response to 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].”
PEA labored! This was confirmed in massive trials. However then ensued what is understood in endocannabinoid circles because the Silent Hole interval.
By the early Nineteen Eighties, the work of SPOFA light 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 may work out the way it really labored. PEA ended up being labeled an “unspecific immune enhancer” and the scientific group 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 improvement of organisms — probably the most difficult issues in all of science. The work she carried out in that basement led to her discovery of the mind’s nerve progress components (NGFs), probably the most necessary 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 revealed a famed paper during which they proposed that PEA works by way of its management of mast cells – an necessary kind of white blood cell chargeable for releasing histamine. Histamine, whereas most frequently related to allergy symptoms, 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 review of their work within the Journal of Ache and Aid summarizes, “Autocoid or autacoid is a quite 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 referred to as: on-demand synthesis.”
“An ALIAmide is an autocoid synthesized in response to damage 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 necessary goal for the anti-inflammatory exercise of PEA, and within the interval 1993-2013 greater than 30 papers had been revealed on the impression of PEA on the mast cell.”
PEA for Ache
As typically occurs with necessary 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. A key improvement 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 capability to trigger ache aid 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 wished one other endocannabinoid-like molecule that wouldn’t have the identical results. So that they selected PEA, principally as a result of they knew that it didn’t bind to the CB1 or CB2 receptors regarded as inflicting the pain-relieving results. However as their paper in Nature identified, they had been fairly stunned to search out out that PEA had profound pain-relieving results as properly.
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 often known as oleamide (OEA) labored by way of the PPARα (alpha) receptors. What’s particular about these PPARα receptors is that they’re nuclear receptors. They reside, not on the floor of the cell, however on the floor of its nucleus – the mobile management middle that comprises 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. When you view the cell like a metropolis, altering genetic transcription is like hiring an entire 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 effects of PEA, and by 2007 they decided that this relationship additionally mediated PEA’s anti-pain effects. It was an enormous breakthrough.
PEA & the Entourage Impact
With the mechanism unveiled and the optimistic medical results famous, PEA analysis poured forth like a spring. In 2008, UK-based scientists reported that the power of anandamide to chill out the arteries was strengthened by the presence of PEA — a phenomenon described as an “entourage impact.” Printed within the British Journal of Pharmacology, the study famous this impact occurred by way of the function of vanilloid receptors, that are half of a big, historic household of Transient Receptor Potential ion channels (often known as TRP or “journey” receptors) that regulate core physique temperature, inflammatory ache, and different primary 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 usually described as a vanilloid compound.
Additionally in 2008, a study 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 study of neuropathic ache, PEA helped by enhancing 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 Venture 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 forestall tissue damage – typically by way of a number of biochemical pathways. It even helped 4 leaping horses return to competition after their accidents didn’t reply to another therapy.
Scientists now consider that PEA exists — a minimum of at low ranges — in each single mammalian cell.
Medical Research
Medical experiments have additionally yielded spectacular outcomes. In sufferers with migraines, lower back pain, burning mouth syndrome, spinal cord injuries, or the neuropathy of shingles, PEA decreased ache and labored properly as an add-on to the usual therapies. PEA additionally helped folks with bladder problems, irritable bowels, glaucoma, osteoarthritis of the knee, and exercise recovery. (For an in depth record of situations helped by PEA, see The PEA Well being Information on the finish of this text.)
In 20 patients 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 by way of the mast cells in addition to the microglia (the guardian immune cells of the mind). In multiple sclerosis sufferers, PEA mixed properly with the usual therapy to enhance ache, decrease irritation, and lift the standard of life. Observational research of 600 sufferers with treatment-resistant chronic pain discovered PEA to be efficient and protected. In seven sufferers with chronic idiopathic axonal polyneuropathy (intense neuropathic ache from an unknown supply), PEA considerably lowered ache with no uncomfortable side effects, and it did the identical for 70 children with migraines.
In 24 ladies with endometriosis and chronic pelvic pain, 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; comparable outcomes had been later reported for 30 more patients. And in 30 diabetic patients, PEA successfully lowered their neuropathic ache with no unfavourable adjustments proven of their blood work or urine evaluation. In two sufferers with autism, PEA brought on “fast enhancements in cognitive, behaviors, and sociability.” In 58 sufferers with depression, 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 brought on much less itching and higher sleep with lots 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 time and again: “We additionally famous its safety because of the complete absence of opposed 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 decreasing of irritation and the discount of ache throughout in all places 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 around the globe. In Italy and Spain, it’s an accepted nutraceutical. Lesvi, a European pharmaceutical firm, combines PEA with a number of crops as a nutraceutical for the mind. A Dutch agency produces a formulation referred to as PeaPure. And the PEA formulation often known 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 straightforward to entry food-derived PEA as a authorized well being complement within the US. Quite a lot of respected distributors market PEA merchandise, and one can get them organized on-line. Anecdotal accounts counsel that CBD and PEA amplify one another’s anti-inflammatory results, and mixing the 2 compounds may show to be a strong therapeutic possibility.
See different articles within the Get to Know a Neurotransmitter sequence.
Lex Pelger writes articles about psychoactives and the endocannabinoid system. He publishes a weekly cannabinoid science publication Cannabinoids & the People and conducts 1-on-1 education sessions on utilizing CBD, PEA, THC & CBDA for severe well being situations. © Copyright, Venture CBD. Will not be reprinted with out permission.
The PEA Well being Information & Overview Papers
- 2013: A Kuhnian take on evolution of PEA knowledge
Evolution in pharmacologic considering across the pure analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-α agonist and efficient nutraceutical - 2022: A review on the potential of using PEA for antiseizure effects
Is It Time to Take a look at the Antiseizure Potential of Palmitoylethanolamide in Human Research? A Systematic Overview 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 review of female pelvic medicine and reconstructive surgery suggests PEA as a treatment
Cannabinoid Remedy in Feminine Pelvic Drugs and Reconstructive Surgical procedure: Present Proof and Future Instructions - 2021: This review looks at PEA for autism and suggests that it may help via several different mechanisms
Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Dysfunction: A Systematic Overview of Human and Animal Proof - 2021: This review looks at the power of PEA to protect the astrocytes (essential support cells of the brain) and fight Alzheimer’s disease
Various Targets to Battle Alzheimer’s Illness: Concentrate on Astrocytes - 2021: This review suggests using PEA for treating COVID patients
Ultramicronized Palmitoylethanolamide (um-PEA): A New Attainable Adjuvant Remedy in COVID-19 sufferers - 2021: This review looks at how PEA and oleoylethanolamide binds to GPR119 and GPR55 (receptors that may one day be known as CB3 and CB4)
GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide - 2021: A special issue of the International Journal of Molecular Sciences is dedicated to PEA
- 2021: This mini-review examines why it makes sense to use PEA to treat COVID (includes one positive case study)
Micronized / ultramicronized palmitoylethanolamide (PEA) as pure neuroprotector in opposition to COVID-19 irritation - 2020: A review of how PEA moves through the body
The Basal Pharmacology of Palmitoylethanolamide - 2020: A review of PEA for pets
Palmitoylethanolamide and Associated ALIAmides: Prohomeostatic Lipid Compounds for Animal Well being and Wellbeing - 2020: On using PEA for pain (nice 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 Medical Research of Neuroinflammatory Occasions - 2019: A good review of PEA’s mechanisms of action
Medical Functions of Palmitoylethanolamide in Ache Administration: Protocol for a Scoping Overview - 2019: A review on PEA for end of life care
The Potential Advantages of Palmitoylethanolamide in Palliation: A Qualitative Systematic Overview - 2019: A review on PEA for Alzheimer’s disease with a focus on neuroinflammation
Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Illness - 2019: On combining PEA with other antioxidant molecules found in your diet (nice diagrams)
Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy With Totally different Antioxidant Molecules Current in Diets - 2019: A review of PEA for asthma
Molecular Targets of Fatty Acid Ethanolamides in Bronchial asthma - 2018: A review of PEA for depression
Function of Palmitoylethanolamide (PEA) in Melancholy: Translational Proof: Particular Part on “Translational and Neuroscience Research in Affective Issues” - 2017: DiMarzo’s great review with history, pharmacology, and charts of where it’s found (breast milk!)
The pharmacology of palmitoylethanolamide and first knowledge on the therapeutic efficacy of a few of its new formulations - 2017: A review of PEA and polydatin for endometriosis covers 4 studies
Micronized Palmitoylethanolamide/Trans-Polydatin Remedy of Endometriosis-Associated Ache: A Meta-Evaluation - 2016: A review of pain covers 6 studies
Palmitoylethanolamide for the Remedy of Ache: Pharmacokinetics, Security and Efficacy - 2016: This review of 12 studies of patients with pain, PEA decreased pain with no serious adverse events
Palmitoylethanolamide, a Particular Meals for Medical Functions, within the Remedy of Continual Ache: A Pooled Information Meta-analysis - 2015: A review of PEA for nerve compression problems like carpal tunnel and sciatic pain
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 models of stroke, spinal cord injury, traumatic brain injury, and Parkinson disease
N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Technique of Decision - 2015: In humans, this review of studies finds PEA safe and effective for glaucoma and other retinopathies (nice chart of mechanisms of action)
Palmitoylethanolamide, a Pure Retinoprotectant: Its Putative Relevance for the Remedy of Glaucoma and Diabetic Retinopathy - 2014: A review of PEA for inflammation
Harnessing the Anti-Inflammatory Potential of Palmitoylethanolamide - 2013: A great review of the history of PEA and the clinical trials for the common cold
Palmitoylethanolamide: A Pure Physique-Personal Anti-Inflammatory Agent, Efficient and Secure Towards Influenza and Widespread Chilly - 2013: A review of PEA for inflammation from trauma
Palmitoylethanolamide Is a New Attainable Pharmacological Remedy for the Irritation Related With Trauma - 2013: A review of PEA for cannabis dependence
Palmitoylethanolamide: From Endogenous Cannabimimetic Substance to Progressive Drugs for the Remedy of Hashish Dependence - 2013: A review of PEA and the mast cells
New Insights in Mast Cell Modulation by Palmitoylethanolamide: “In view of their strategic localization at websites immediately interfacing with the exterior surroundings, mast cells act as surveillance antennae in opposition to several types of damage and might endure activation, thereby regulating each innate and adaptive immune reactions by way of the discharge of a number of preformed and newly synthesized mediators. Mast cells at the moment are considered as key gamers in orchestrating a number of issues together with each acute and persistent inflammatory processes, and have a task in angiogenesis and hyperalgesia.” - 2012: A review of PEA’s effect on mast cells, glia cells (brain support cells), and neuroinflammation
Mast Cell-Glia Axis in Neuroinflammation and Therapeutic Potential of the Anandamide Congener Palmitoylethanolamide - 2012: Dr. Piomelli’s comments 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 history of discovery
The Seek for the Palmitoylethanolamide Receptor
A Timeline of PEA Analysis
- 2022: Researchers look to create new molecules that help increase natural PEA levels
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 major carotenoid from brown seaweed called fucoxanthinol appears to help with inflammation via its modulation of the PEA pathway
Anti-Inflammatory Results of Fucoxanthinol in LPS-Induced RAW264.7 Cells by way of the NAAA-PEA Pathway - 2022: This survey shows that most women who used cannabis or the cannabinoids THC, CBD, or PEA for gynecologic conditions reported that it improved pain
Medical Hashish for Gynecologic Ache Situations: A Systematic Overview - 2022: In a mouse model of obesity, PEA restored the plasticity of their white and brown fat cells, leptin sensitivity, tissue hormone sensitivity and rewired the energy storing white into energy-consuming brown fat cells
Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α - 2022: In a study of 90 patients with COVID-19, PEA reduced inflammatory states, oxidative states and alterations to blood biomarkers
Results of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Levels: A Case-Management Research - 2022: In obese mice, PEA lessened neuroinflammation as well as anxious behavior
Palmitoylethanolamide dampens neuroinflammation and anxiety-like conduct in overweight mice - 2021: In humans with induced migraines, the PEA levels in their spinal cords didn’t raise for those who regularly experienced episodic migraines
Spinal nociceptive sensitization and plasma palmitoylethanolamide ranges throughout experimentally-induced migraine assaults - 2021: In an animal model of stroke, they already knew that PEA protects the blood-brain barrier and the brain itself. This study found that the effects weren’t only mediated by changes in genetic transcription (the PPARα receptor) but also by the regulation of the cell’s microfilaments
PEA prevented early BBB disruption after cerebral ischaemic/reperfusion (I/R) damage by way of regulation of ROCK/MLC signaling - 2021: In humans, PEA as well as the flavonoid luteolin helped to recover the sense of smell after a COVID 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 exposed to the spike protein of SARS-CoV-2, ultramicronized PEA reduced 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 undergoing strenuous exercise, their levels of anandamide, PEA and oleamide all increased, suggesting an adaptive ability of the ECS in helping with stress and heart-rate
Endocannabinoids and coronary heart fee variability alterations after publicity to extended intensive bodily train of the Hellenic Navy SEALs - 2021: A case study of PEA for the neuropathic pain of shingles
Palmitoylethanolamide (PEA) within the therapy of neuropathic ache: a case research - 2021: In rats with spinal cord injuries, PEA alleviated the injury, inhibited inflammation, mitigated oxidative stress, reduced cell death and promoted motor function recovery
PPARα agonist relieves spinal wire damage in rats by activating Nrf2/HO-1 by way of the Raf-1/MEK/ERK pathway - 2021: In humans, CBD and PEA found safe for the skin
Tolerability Profile of Topical Cannabidiol and Palmitoylethanolamide: A Compilation of Single-Heart Randomized Evaluator-Blinded Medical and In Vitro Research in Regular Pores and skin - 2021: In rabbits having eye surgery, PEA reduced postoperative inflammation and scarring via the nuclear PPARα receptors
Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgical procedure in rabbits by suppressing canonical and non-canonical TGFβ signaling by way of PPARα - 2021: In rats on an obesity diet, PEA as well as oleamide (OEA – another endocannabinoid) functioned as anti-obesity nutritional interventions
Palmitoleoylethanolamide Is an Environment friendly Anti-Weight problems Endogenous Compound: Comparability with Oleylethanolamide in Weight loss program-Induced Weight problems - 2021: In mice with inflamed colons, a combination of polydatin (a precursor of resveratrol) and ultra-micronized PEA decreased inflammation via several pathways
PEA/Polydatin: Anti-Inflammatory and Antioxidant Method to Counteract DNBS-Induced Colitis - 2021: In mice with their left carotid artery tied off, a combination of PEA and rutin (a helpful plant pigment) reduced inflammation, oxidative stress and vascular damage
Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Damage by way of Modulation of the Nrf2/HO-1 and NF-kB Pathways - 2021: In a human lung tissue model of COVID-19 infection, a combination of PEA and α-lipoic acid (ALA) reduced 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 Attainable Intervention for COVID-19 - 2021: In a mouse model of traumatic brain injury (and a small clinical study), a combination of PEA and the flavonoid luteolin caused increased neurogenesis as well as improvements in memory recall
Co-Extremely PEALut Enhances Endogenous Restore Response Following Reasonable Traumatic Mind Damage - 2021: In human cells, PEA and polydatin lowered vascular inflammation
Palmitoylethanolamide related to polydatin reduces irritation in human endothelial vascular cells uncovered to doxorubicin and trastuzumab by way of PPAR-a and NLRP3-related pathways - 2021: In humans with Tourette’s, initial promise was seen with a combination of 10 mg of THC + 800 mg of PEA
A Section-2 Pilot Research 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 mean enchancment in tic signs of greater than 20%.” - 2021: In the brain of a model organism, the injection of PEA or OEA mediated the brain levels 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 common benign tumor in males), a combination of PEA and baicalein (an active ingredient in Baikal skullcap) lowered inflammation, reduced oxidative stress and helped to modulate apoptosis (programmed cellular suicide)
Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia - 2021: In humans with nerve pain from rheumatic diseases, PEA combined well with acetyl-l-carnitine (ALC) to lower inflammation and to increase clinical scores
Efficacy of a hard and fast mixture of Palmitoylethanolamide and acetyl-l-carnitine (PEA + ALC FC) within the therapy of Neuropathies secondary to Rheumatic Illnesses - 2021: In humans, this cohort analysis found that the diversity of your gut microbiome was related to your happiness and motivation via the endocannabinoid system, especially via PEA – which they call the endogenous version of CBD
Endocannabinoid system mediates the affiliation between gut-microbial variety and anhedonia/amotivation in a basic inhabitants cohort - 2021: In microglial cells (the immune cells of the brain), PEA caused decreased inflammation and increased neuroprotection
Palmitoylethanolamide Modulation of Microglia Activation: Characterization of Mechanisms of Motion and Implication for Its Neuroprotective Results - 2021: A clinical trial where PEA from Levagen+ improves many measures of sleep
Palmitoylethanolamide for Sleep Disturbance. A Double-blind, Randomised, Placebo-controlled Interventional Research - 2021: Engineering bacteria to live in the guts and produce PEA on demand
Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice - 2021: In mice with varicocele (a disorder of the veins taking blood away from the testicles, a major cause of human infertility), PEA helped via 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 inflammation
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 model of inflammatory pain, PEA combined well 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 huge doses of PEA caused no measurable harms
Palmitoylethanolamide: Prenatal Developmental Toxicity Research in Rats - 2021: In human with joint pain, PEA reduced pain and improved mood
The Impact of a Dispersible Palmitoylethanolamide (Levagen+) In comparison with a Placebo for Decreasing Joint Ache in an Grownup Inhabitants – A Randomised, Double-Blind Research - 2021: In rabbits having eye surgery, PEA reduced postoperative inflammation and scarring via the nuclear PPARα receptors
Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgical procedure in rabbits by suppressing canonical and non-canonical TGFβ signaling by way of PPARα - 2020: In a mouse model of Gulf War illness, exposure alters the response to PEA
Pyridostigmine bromide publicity creates persistent, underlying neuroimmune disruption within the gastrointestinal tract and mind that alters responses to palmitoylethanolamide in a mouse mannequin of Gulf Battle Sickness - 2020: On using PEA for neurological disorders
Meals dietary supplements primarily based on palmitoylethanolamide plus hydroxytyrosol from olive tree or Bacopa monnieri extracts for neurological ailments - 2020: This hypothetical paper suggests that the ability of PEA to calm mast cells in the lungs may be a potential treatment for COVID
Sodium chromo-glycate and palmitoylethanolamide: A potential technique to deal with mast cell-induced lung irritation in COVID-19 - 2020: In mice with mood disorders induced by high-fat diets, PEA limits mood disorders and cognitive dysfunction
Palmitoylethanolamide limits temper issues and cognitive dysfunction induced by excessive fats weight-reduction plan in overweight mice - 2020: In 4 jumping horses with non-responsive lameness, ultramicronized PEA for four months allowed them to return to competition
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®) combined with lipoic acid and vitamin D3 absorbed better and reduced neuroinflammation
A New Palmitoylethanolamide Kind Mixed with Antioxidant Molecules to Enhance Its Effectivess on Neuronal Growing old - 2020: In a cellular model of Alzheimer’s, PEA protected the neurons and increased 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 humans with glaucoma, PEA found helpful
Impact of palmitoylethanolamide on inside retinal perform in glaucoma: a randomized, single blind, crossover, medical trial by pattern-electroretinogram - 2020: For patients with COVID-19, FSD Pharma received FDA approval to submit an Investigational New Drug Application for the use of PEA to increase endogenous levels of endocannabinoid
- 2020: In rats, PEA helpful for eye disorders via the PPARα nuclear receptors
PPARα-Dependent Results of Palmitoylethanolamide Towards Retinal Neovascularization and Fibrosis - 2020: In rats, a look at how PEA causes vasodepression (the lowering of blood pressure) via the heart’s CB1, TRPV1 and probably GPR55 receptors, but not by CB2
Potential Mechanisms Concerned in Palmitoylethanolamide-Induced Vasodepressor Results in Rats - 2020: In a double-blind human study, CBD and PEA both helped reduce permeability in the colon and appear helpful for IBS
Palmitoylethanolamide and Cannabidiol Stop Irritation-induced Hyperpermeability of the Human Intestine In Vitro and In Vivo-A Randomized, Placebo-controlled, Double-blind Managed Trial - 2020: In patients with lower back pain, the combination of therapy and ultramicronized PEA lowered pain past clinically relevant levels as well as increasing physical and mental quality of life
Mixture of Rehabilitative Remedy With Ultramicronized Palmitoylethanolamide for Continual Low Again Ache: An Observational Research - 2020: In 70 pediatric patients with migraines, ultramicronized PEA decreased the number and severity of attacks with only one patient experiencing mild side effects (nausea and floating)
Tolerability of Palmitoylethanolamide in a Pediatric Inhabitants Struggling From Migraine: A Pilot Research - 2020: In a human study with 28 participants, Levagen+ helpful for exercise recovery by reducing myoglobin and lactate concentration
The Impact of Orally Dosed Levagen+™ (Palmitoylethanolamide) on Train Restoration in Wholesome Males-A Double-Blind, Randomized, Placebo-Managed Research - 2020: In mice with dry eye induced by sleep loss, they had lower levels of PEA in the lacrimal gland and its synthetic enzyme (N-acylated phosphatidylethanolamine-phospholipase D) – treatment with PEA restored lipid balance and protected the eye via PPARα
N-Palmitoylethanolamine Maintains Native Lipid Homeostasis to Relieve Sleep Deprivation-Induced Dry Eye Syndrome - 2020: Mechanistic study 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 model of Alzheimer’s, 3 months of oral ultramicronized PEA “rescued cognitive deficit, restrained neuroinflammation and oxidative stress, and reduced the increase in hippocampal glutamate levels”
Continual 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 birth, PEA attenuated the neuronal damage in corpus striatum, restored level of GFAP cells as well as preventing the decrease of pNF-H/M and MAP-2
Partial Reversal of Striatal Harm by Palmitoylethanolamide Administration Following Perinatal Asphyxia - 2019: In 22 patients with pain, PEA was effective at reducing chronic neuropathic pain via “the ascending pain pathway that are likely driven by rhythmic astrocytic gliotransmission”
Results of the Glial Modulator Palmitoylethanolamide on Continual Ache Depth and Mind Perform - 2019: A re-analysis of an old unpublished study on the efficacy of micronized PEA for lower back pain found it to be highly effective
Micronized Palmitoylethanolamide: A Publish Hoc Evaluation of a Managed Research in Sufferers With Low Again Ache – Sciatica - 2019: in human double-blind study, both CBD and PEA reduced inflammation and reducing permeability in the human colon
Palmitoylethanolamide and Cannabidiol Stop 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 study of 111 participants with knee osteoarthritis, PEA found helpful for inflammation
A Double-Blind Randomized Placebo Managed Research Assessing Security, Tolerability and Efficacy of Palmitoylethanolamide for Signs of Knee Osteoarthritis - 2019: In 23 patients with mastocytosis (accumulation of mast cells), they had increased PEA levels
Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Sufferers With Mastocytosis - 2019: In 30 patients with endometriosis, both ultramicronized PEA and co-micronised palmitoylethanolamide/polydatin (PEA/PLD) showed significant improvements in all measures as well as quality of life
Impact of Ultramicronized-Palmitoylethanolamide and Co-Micronized Palmitoylethanolamide/Polydatin on Continual Pelvic Ache and High quality of Life in Endometriosis Sufferers: An Open-Label Pilot Research - 2019: In one patient with burning mouth syndrome, after gabapentin did little, adding PEA considerably improved the pain
Add-on Administration of Ultramicronized Palmitoylethanolamide within the Remedy of New-Onset Burning Mouth Syndrome - 2019: In 32 patients with bladder problems, micronized PEA combined with polydatin reduced pain and urinary frequency
Micronized Palmitoylethanolamide-Polydatin Reduces the Painful Symptomatology in Sufferers With Interstitial Cystitis/Bladder Ache Syndrome - 2019: In mice, great study on the broad lipid changes caused by PEA
Broad Lipidomic and Transcriptional Modifications of Prophylactic PEA Administration in Grownup Mice - 2019: In cats with hypersensitive skin, ultramicronized PEA helped increase 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 Research - 2019: In mice with injured spines, Noxiall (a combo of PEA, Beta-Caryophyllene, Carnosic Acid, and Myrrh) matched pregabalin and gabapentin for lessening pain and reducing mechanical and thermal sensitivities
Efficacy of a Mixture of N-Palmitoylethanolamide, Beta-Caryophyllene, Carnosic Acid, and Myrrh Extract on Continual Neuropathic Ache: A Preclinical Research - 2019: In rats with a heart attack, the combination of PEA and baicalein from Chinese medicine “decreases myocardial tissue injury, neutrophils infiltration, markers for mast cell activation expression as chymase and tryptase and pro-inflammatory cytokines production (TNF-α, IL-1β)” and “treatment reduces stress oxidative and modulates Nf-kB and apoptosis pathways”
Results of a New Compound Containing Palmitoylethanolamide and Baicalein in Myocardial Ischaemia/Reperfusion Damage in Vivo - 2019: In mice with a painful nerve injury, PEA restored cognitive behavior and neuronal functioning via two receptors in 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 injury, ultramicronized PEA was able to “reverse mechanical allodynia and thermal hyperalgesia, memory deficit and LTP” and restore “the level of glutamate and the expression of phosphorylated GluR1 subunits, postsynaptic density and neurogenesis” via 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 fear extinction, anxiety and increased allopregnanolone (ALLO – a gamma-aminobutyric acidergic neurosteroid implicated in mood disorders)
Stimulation of Peroxisome Proliferator-Activated Receptor-α by N-Palmitoylethanolamine Engages Allopregnanolone Biosynthesis to Modulate Emotional Habits - 2019: In a rat model of depression, PEA helped greatly via several different markers including stress hormones – probably via PPARα
N-Palmitoylethanolamide Exerts Antidepressant-Like Results in Rats: Involvement of PPAR α Pathway within the Hippocampus - 2019: In an animal model of dementia, PEA and oxazoline were protective
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, treatment with 2-AG or PEA affected microglial cells and caused protection but using them together blocked their positive effects and altered the distribution (but not the activation) of PPARa
Reverse Results of Neuroprotective Cannabinoids, Palmitoylethanolamide, and 2-Arachidonoylglycerol on Perform and Morphology of Microglia - 2019: In a model of mast cells, they found “novel molecular mechanisms through which PEA controls mast cell degranulation and substance P (SP)-induced histamine release” with PEA increasing 2-AG via stimulation of DAGL-α and -β activity and the combination of PEA and 2-AG working together at low levels when they didn’t work on their own
Palmitoylethanolamide Counteracts Substance P-induced Mast Cell Activation in Vitro by Stimulating Diacylglycerol Lipase Exercise - 2018: In 155 patients with spinal damage and pain, ultramicronized PEA helped with mild and moderate pain, but not severe pain, with a special emphasis on its safety
N-Palmitoyl Ethanol Amide Pharmacological Remedy in Sufferers With Nonsurgical Lumbar Radiculopathy - 2018: In 58 patients with depression, 600 mg of PEA twice a day + citalopram significantly improved symptoms and demonstrated a rapid-onset effect
Palmitoylethanolamide as Adjunctive Remedy in Main Depressive Dysfunction: A Double-Blind, Randomized and Placebo-Managed Trial - 2018: In 35 patients with burning mouth syndrome, 600 mg of ultramicronized PEA significantly reduced the pain after 60 days and caused no interference in the other pharmacological therapies
Efficacy of Ultramicronized Palmitoylethanolamide in Burning Mouth Syndrome-Affected Sufferers: A Preliminary Randomized Double-Blind Managed Trial - 2018: In 20 patients with migraines, ultramicronized PEA treatment relieved pain with no side effects
Results of Add-On Ultramicronized N-Palmitol Ethanol Amide in Sufferers Struggling of Migraine With Aura: A Pilot Research - 2018: In mice with pain, PEA potentiated morphine and lessened tolerance, suggesting it as an additive treatment
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 levels
Antiepileptogenic Impact of Subchronic Palmitoylethanolamide Remedy in a Mouse Mannequin of Acute Epilepsy - 2018: In a mouse model of Alzheimer’s, ultramicronized PEA improved learning and memory, lessened depression and anhedonia and helped with neuroinflammation via several methods
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 brain from Parkinson’s disease-like damage via several mechanisms
N-palmitoylethanolamide Prevents Parkinsonian Phenotypes in Aged Mice - 2018: In aged mice, PEA shielded from a bacterial an infection within the organs and mind
Prophylactic Palmitoylethanolamide Prolongs Survival and Decreases Detrimental Inflammation in Aged Mice With Bacterial Meningitis - 2018: In rats with induced pain, ultramicronized PEA reached the peripheral sites more readily and caused less inflammation and tissue damage via the downregulation of several “spinal inflammatory and oxidative pathways”
Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Ranges and Spinal Anti-hyperalgesic Impact - 2018: In baby mice with simulated perinatal asphyxia (not able to breate), PEA treatment attenuated damage in the hippocampus and improved behavioral alterations
Palmitoylethanolamide Ameliorates Hippocampal Harm and Behavioral Dysfunction After Perinatal Asphyxia within the Immature Rat Mind - 2018: In young rats deprived of oxygen, PEA treatment reduced neuroinflammation, astrogliosis (overabundance of astrocytes) and preserved cognitive function
Palmitoylethanolamide Prevents Neuroinflammation, Reduces Astrogliosis and Preserves Recognition and Spatial Reminiscence Following Induction of Neonatal Anoxia-Ischemia - 2018: In rats with joint inflammation, micronized PEA reduced the damage, pain and activation of macrophages
Micronized Palmitoylethanolamide Reduces Joint Ache and Glial Cell Activation - 2018: In models of Alzheimer’s, PEA dampened the reactivity of the microglia and improved viability of the neurons as well as 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 via several mechanisms
Palmitoylethanolamide Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats - 2018: In a mixture of astrocytes and neurons, PEA blunted the astrocyte activation caused by a challenge by Aβ42 (a plaque associated with Alzheimer’s disease)
Palmitoylethanolamide Blunts Amyloid-β42-Induced Astrocyte Activation and Improves Neuronal Survival in Main Mouse Cortical Astrocyte-Neuron Co-Cultures - 2018: PEA nanoparticles for intraocular delivery
Progressive Nanoparticles Improve N-Palmitoylethanolamide Intraocular Supply - 2017: In a mouse with traumatic brain injury, PEA protected the brain
Palmitoylethanolamide Reduces Neuropsychiatric Behaviors by Restoring Cortical Electrophysiological Exercise in a Mouse Mannequin of Delicate Traumatic Mind Damage - 2017: In 100 patients with spinal damage and pain, ultramicronized PEA combined well with paracetamol and codeine to relieve pain with no side effects
Nonsurgical Lumbar Radiculopathies Handled With Ultramicronized Palmitoylethanolamide (umPEA): A Sequence of 100 Circumstances
“We additionally famous its security because of the complete absence of opposed results.” - 2017: In 55 patients with lower back pain, ultramicronized PEA was an effective add-on to tapentadol for pain and improved quality of life
The Helpful Use of Ultramicronized Palmitoylethanolamide as Add-On Remedy to Tapentadol within the Remedy of Low Again Ache: A Pilot Research Evaluating Potential and Retrospective Observational Arms - 2017: In 10 patients with pain, ultramicronized PEA helped
N-of-1 Randomized Trials of Extremely-Micronized Palmitoylethanolamide in Older Sufferers With Continual Ache - 2017: In mice with a broken tibia, a product of micronized and ultramicronized PEA caused “an improved healing process, fracture recovery and fibrosis score” as well as “decreased mast cell density, nerve growth factor, matrix metalloproteinase 9 and cytokine expression” and apoptosis (cellular 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 brain and spine injuries, the combination of PEA and oxazoline protected the motor function and behavioral deficits
N-Palmitoylethanolamine-Oxazoline as a New Therapeutic Technique to Management Neuroinflammation: Neuroprotective Results in Experimental Fashions of Spinal Twine and Mind Damage - 2017: In microglia and macrophage cells, PEA increased CB2 expression via PPAR-α
Palmitoylethanolamide Induces Microglia Modifications Related With Elevated Migration and Phagocytic Exercise: Involvement of the CB2 Receptor - 2017: In mice with induced allergies, PEA helped to clear the bronchi and upregulated CB2 and GPR55, suggesting it use as a supplement against 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 via PPARα and in response to inflammatory mediators, the cells increased their PEA levels
Oleoylethanolamine and Palmitoylethanolamine Modulate Intestinal Permeability in Vitro by way of TRPV1 and PPARα - 2017: In a canine skin model, PEA protected from the negative effects of mast cells
Ultramicronized Palmitoylethanolamide Counteracts the Results of Compound 48/80 in a Canine Pores and skin Organ Tradition Mannequin - 2016: In a study of cells, animals and humans, PEA raised the level of 2-AG and potentiated its effects 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 patients with endometriosis, AEA and PEA levels increased along with condition severity
Elevated Systemic Ranges of Endocannabinoids and Associated Mediators Throughout the Menstrual Cycle in Girls With Endometriosis - 2016: In humans with multiple sclerosis, ultramicronized PEA added to the first line treatment (interferon IFN-β1a) caused an improvement in pain scores and quality of life
Oral Palmitoylethanolamide Remedy Is Related With Decreased Cutaneous Antagonistic Results of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting A number of Sclerosis - 2016: In 72 patients with spinal cord injuries, ultramicronized PEA caused no positive effects at all for anything measured
Ultramicronized Palmitoylethanolamide in Spinal Twine Damage Neuropathic Ache: A Randomized, Double-Blind, Placebo-Managed Trial (followup remark: Ultramicronized Palmitoylethanolamide Treatment in Central Neuropathic Pain Following Longstanding Spinal Cord Injury: Try to Extinguish the Fire After Everything Was Burned) - 2016: In a preclinical study in mice and a case study with a 10 year old, a combination of PEA and luteolin ameliorated symptomatology of autism
Helpful Results of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Mannequin of Autism and in a Case Report of Autism - 2016: In mice with heart attacks, ultramicronized PEA protected the heart via the PPARa receptors
Protecting Results of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Damage in VIVO - 2016: In rats with endometriosis, ultramicronized PEA worked via the mast cells to lower pain, as well as the levels of cysts and stones
Ultramicronized Palmitoylethanolamide Reduces Viscerovisceral Hyperalgesia in a Rat Mannequin of Endometriosis Plus Ureteral Calculosis: Function of Mast Cells - 2016: In this mouse model and patient study of colitis and Crohn’s disease, PEA “inhibits colitis-associated angiogenesis [blood vessel formation], decreasing VEGF release and new vessels formation” via the PPARa and helped to regulate the angiogenic process via the mTOR/Akt axis
Palmitoylethanolamide Modulates Irritation-Related Vascular Endothelial Progress Issue (VEGF) Signaling by way of the Akt/mTOR Pathway in a Selective Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α)-Dependent Method - 2016: In colon cancer cells, PEA caused a significant reduction in proliferation, angiogenesis, and VEGF secretion and expression via PPARa’s effect on the AkT/mTOR axis
Palmitoylethanolamide Exerts Antiproliferative Impact and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line By a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway - 2015: In two patients with autism, PEA caused “rapid improvements in cognitive, behaviors, and sociability”
Helpful Results of Palmitoylethanolamide on Expressive Language, Cognition, and Behaviors in Autism: A Report of Two Circumstances - 2015: In 160 dogs with red itchy skin, ultramicronized PEA was “effective and safe in reducing pruritus and skin lesions” and improving quality of life
Efficacy of Extremely-Micronized Palmitoylethanolamide in Canine Atopic Dermatitis: An Open-Label Multi-Centre Research - 2015: In rats with pain, PEA delayed the tolerance effects of morphine
Delay of Morphine Tolerance by Palmitoylethanolamide - 2015: In rats with high blood pressure, PEA protected via several difference pathways
Palmitoylethanolamide Remedy Reduces Blood Strain in Spontaneously Hypertensive Rats: Involvement of Cytochrome p450-derived Eicosanoids and Renin Angiotensin System - 2015: In mice with damaged kidneys, PEA and silymarin combined to reduce “kidney dysfunction, histological damage, neutrophil infiltration and oxidative stress” and inhibited NF-κB and apoptosis (cellular suicide) pathways
Results of Palmitoylethanolamide and Silymarin Mixture Remedy in an Animal Mannequin of Kidney Ischemia and Reperfusion - 2015: In rats with inflamed eyes, PEA “decreased the inflammatory cell infiltration and improved histological damage of eye tissues” and reduced ocular inflammation
The Anti-Inflammatory Results of Palmitoylethanolamide (PEA) on Endotoxin-Induced Uveitis in Rats - 2015: In mice with induced colitis, PEA helps via the CB2, GPR55 and PPARa receptors as well as the TRPV1 channels
Palmitoylethanolamide, a Naturally Occurring Lipid, Is an Orally Efficient Intestinal Anti-Inflammatory Agent - 2015: In a mouse model of multiple sclerosis, treatment with PEA or CBD reduced disease severity with diminished inflammation, demyelination, axonal damage and inflammatory cytokine expression – but they did not work as well together
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 injuries, PEA restored their glutamate functioning and the changes in amino acid release (nice 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 disease, PEA “reduced expression of pro-inflammatory and pro-angiogenic markers” via 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 but not the triple-transgenic murine model
Differential Results of Palmitoylethanolamide Towards Amyloid-β Induced Toxicity in Cortical Neuronal and Astrocytic Main Cultures From Wild-Sort and 3xTg-AD Mice - 2014: In 30 diabetic patients, micronized PEA effectively reduced pain while blood work and urine analysis saw no significant alterations
Micronized Palmitoylethanolamide Reduces the Signs of Neuropathic Ache in Diabetic Sufferers - 2014: In 60 patients with eczema, a PEA/AEA topical improved “passive and active skin functions simultaneously”
N-palmitoylethanolamine and N-acetylethanolamine Are Efficient in Asteatotic Eczema: Outcomes of a Randomized, Double-Blind, Managed Research in 60 Sufferers - 2014: In a patient with chronic vulvar and anal pain, a topical of PEA and baclofen decreased her pain by 50% and allowed for sex again
Vulvodynia and Proctodynia Handled With Topical Baclofen 5 % and Palmitoylethanolamide - 2014: In dogs with red itchy skin, PEA probably helped via the downregulation of mast cells and levels of PEA increased as the disease progressed
Elevated Ranges of Palmitoylethanolamide and Different Bioactive Lipid Mediators and Enhanced Native Mast Cell Proliferation in Canine Atopic Dermatitis - 2014: In a rat model of Alzheimer’s disease, PEA was able to restore the alterations via PPARa and to reverse the cognitive impairments
Palmitoylethanolamide Controls Reactive Gliosis and Exerts Neuroprotective Features in a Rat Mannequin of Alzheimer’s Illness - 2014: In mice with an inflamed colon, PEA improved transit time in the GI tract and increased AEA levels via the CB1 receptors and TRPV1 channels
Palmitoylethanolamide Normalizes Intestinal Motility in a Mannequin of Publish-Inflammatory Accelerated Transit: Involvement of CB₁ Receptors and TRPV1 Channels - 2014: In the intestines of rats undergoing chemotherapy, PEA protected via the mast cells for protection
Palmitoylethanolamide Regulates Improvement of Intestinal Radiation Damage in a Mast Cell-Dependent Method - 2014: In a rat model of inflammatory pain, micronized/ultramicronized PEA worked better 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 treatment increased the ability of macrophages to phagocytose (engulf and digest) E. coli bacteria
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 signs of ulcerative colitis and decreased all the proinflammatory markers tested via PPARa
Palmitoylethanolamide Improves Colon Irritation By an Enteric Glia/Toll Like Receptor 4-dependent PPAR-α Activation - 2013: In 24 women with endometriosis and chronic pelvic pain, micronized PEA and polydatin reduced pelvic pain, dysmenorrhea (cramps) and dyspareunia (pain during sex) but not dysuria (painful urination) and dischezia (strained stools) as well as improving overall 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 patients with chronic idiopathic axonal polyneuropathy (intense pain), PEA reduced pain significantly with no side effects
Continual Idiopathic Axonal Neuropathy and Ache, Handled With the Endogenous Lipid Mediator Palmitoylethanolamide: A Case Assortment - 2013: In a rat model of epilepsy, PEA reduced seizures via the PPAR-α receptors and indirectly by the CB1 receptors
Antiepileptic Motion of N-palmitoylethanolamine By CB1 and PPAR-α Receptor Activation in a Genetic Mannequin of Absence Epilepsy - 2013: In mice with spinal cord trauma, they found that PPAR-δ and PPAR-γ also contribute to PEA’s anti-inflammatory effects
Molecular Proof for the Involvement of PPAR-δ and PPAR-γ in Anti-Inflammatory and Neuroprotective Actions of Palmitoylethanolamide After Spinal Twine Trauma - 2013: In rats with high blood pressure, PEA reduced blood pressure and reduced damage to the kidneys
N-Palmitoylethanolamide Protects the Kidney From Hypertensive Damage in Spontaneously Hypertensive Rats by way of Inhibition of Oxidative Stress - 2013: In mice with pain, PEA helped via recruitment and protection of mast cells, decrease of nerve growth factor, preservation of the nerves and the reduction of microglia activation in the spinal cord
Non-neuronal Cell Modulation Relieves Neuropathic Ache: Efficacy of the Endogenous Lipid Palmitoylethanolamide - 2013: PEA targets both glial and mast cells for anti-inflammation and neuroprotective effects
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, significantly reduced mechanical allodynia and thermal hyperalgesia, suggesting the use for spinal cord injuries
Palmitoylethanolamide Reduces Formalin-Induced Neuropathic-Like Behaviour By Spinal Glial/Microglial Phenotypical Modifications in Mice - 2013: In rat neuronal cells challenged with the Aβ amyloid plaques of Alzheimer’s, “PEA is able to blunt Aβ-induced astrocyte activation and to exert a marked protective effect on neurons”
Neuroglial Roots of Neurodegenerative Illnesses: Therapeutic Potential of Palmitoylethanolamide in Fashions of Alzheimer’s Illness - 2013: In cells, PEA activated TRPV1, perhaps via PPARa
Activation and Desensitization of TRPV1 Channels in Sensory Neurons by the PPARα Agonist Palmitoylethanolamide - 2012: In humans, a case series on PEA for pain
Therapeutic Utility of Palmitoylethanolamide within the Remedy of Neuropathic Ache Related With Varied Pathological Situations: A Case Sequence - 2012: In an observational study of 600+ patients, PEA helped all of them with their treatment-resistant chronic pain and caused no adverse effects
Palmitoylethanolamide within the Remedy of Continual Ache Attributable to Totally different Etiopathogenesis - 2012: In a patient with ALS, PEA improved the clinical picture, probably via the microglia and mast cells
Amyotrophic Lateral Sclerosis Remedy With Ultramicronized Palmitoylethanolamide: A Case Report - 2012: In mice, PEA helped to protect from a Parkinson’s like insult, probably via the PPARa receptor
Neuroprotective Actions of Palmitoylethanolamide in an Animal Mannequin of Parkinson’s Illness - 2012: In rats, PEA protected the brain after injury by many pathways
Discount of Ischemic Mind Damage by Administration of Palmitoylethanolamide After Transient Center Cerebral Artery Occlusion in Rats - 2012: In a mouse model of traumatic brain injury, PEA protected the brain via several pathways and improved neurobehavioral functions
Administration of Palmitoylethanolamide (PEA) Protects the Neurovascular Unit and Reduces Secondary Damage After Traumatic Mind Damage in Mice - 2012: In a mouse model of Alzheimer’s disease, injected PEA significantly helped with learning and memory disfunction, probably via 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 injuries, pretreatment with PEA reduced inflammation and cell death, probably via the PPARa pathway
Results of Palmitoylethanolamide on Intestinal Damage and Irritation Attributable to Ischemia-Reperfusion in Mice - 2012: In mice with injured kidneys, PEA protected via several different pathways, probably via the PPARa pathway
Palmitoylethanolamide Reduces Early Renal Dysfunction and Damage Attributable to Experimental Ischemia and Reperfusion in Mice - 2012: In mice experiencing pain, PEA increased allopregnanolone (ALLO) levels via 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 disease, PEA blunted activation and improved neuronal survival
Palmitoylethanolamide Exerts Neuroprotective Results in Blended Neuroglial Cultures and Organotypic Hippocampal Slices by way of Peroxisome Proliferator-Activated Receptor-α - 2012: In microglial cells, PEA caused increased phagosytosis of E. coli and strep
Palmitoylethanolamide Stimulates Phagocytosis of Escherichia Coli K1 and Streptococcus Pneumoniae R6 by Microglial Cells - 2011: In 20 patients undergoing chemo, PEA helped with the pain and showed positive effects on the myelinated fiber groups
Palmitoylethanolamide Restores Myelinated-Fibre Perform in Sufferers With Chemotherapy-Induced Painful Neuropathy - 2011: In brain tissue, PEA appears to regulate neurosteroidogenesis (steroid production in the brain) and increase allopregnanolone (ALLO) via the PPARa receptor
Palmitoylethanolamide Stimulation Induces Allopregnanolone Synthesis in C6 Cells and Main Astrocytes: Involvement of Peroxisome-Proliferator Activated Receptor-α - 2011: In brain cells, PEA reduced the number of microglial cells and protected the neurons via the PPARa receptor
Palmitoylethanolamide Protects Dentate Gyrus Granule Cells by way of Peroxisome Proliferator-Activated Receptor-α - 2011: In mice with spinal cord injuries, PEA “reduced the degree of the severity of spinal cord trauma through the reduction of mast cell infiltration and activation [and] reduced the activation of microglia and astrocytes expressing cannabinoid CB(2) receptor”
Results of Palmitoylethanolamide on Launch of Mast Cell Peptidases and Neurotrophic Elements After Spinal Twine Damage - 2011: In brain cells, the β-amyloid plaques of Alzheimer’s increased PEA levels while treatment with PEA blunted their proinflammatory effects, probably via increased 2AG levels and the PPARa receptor
Palmitoylethanolamide Counteracts Reactive Astrogliosis Induced by β-Amyloid Peptide - 2010: In mice, PEA modulated the hypnotic effect of phenobarbital via PPARa’s increase of allopregnanolone (ALLO) as well as a positive modulation of GABA
Palmitoylethanolamide Modulates Pentobarbital-Evoked Hypnotic Impact in Mice: Involvement of Allopregnanolone Biosynthesis - 2010: In canine mast cells, PEA downregulated their activity via several factors, suggesting its use for inflammation and pain
Results of Palmitoylethanolamide on Immunologically Induced Histamine, PGD2 and TNFalpha Launch From Canine Pores and skin Mast Cells - 2009: In mice with pain, pretreatment with PEA lowered their pain levels via PPARa’s inhibition of signaling in the dorsal root ganglia and by the reduction of COX-2 and iNOS
Central Administration of Palmitoylethanolamide Reduces Hyperalgesia in Mice by way of Inhibition of NF-kappaB Nuclear Signalling in Dorsal Root Ganglia - 2008: In this study of 2456 patients with eczema, PEA topical treatment caused less itching, more sleeping and half of them stopped using their corticosteroids
Adjuvant Remedy of Atopic Eczema: Evaluation of an Emollient Containing N-palmitoylethanolamine (ATOPA Research) - 2008: In a mouse model of multiple sclerosis, CB2, 2AG and PEA were upregulated and PEA applied topically reduced disability and lowered inflammation
Research 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 cord injury, PEA reduced “1) the degree of spinal cord inflammation and tissue injury, 2) neutrophil infiltration, 3) nitrotyrosine formation, 4) proinflammatory cytokine expression, 5) nuclear transcription factor activation-kappaB activation, 6) inducible nitric-oxide synthase expression, and 6) apoptosis” and it helped with recovery of motor function
Results of Palmitoylethanolamide on Signaling Pathways Implicated within the Improvement of Spinal Twine Damage - 2008: In mice, PEA helped with pain via 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 Elements - 2008: In rat arteries, the ability of AEA to induce relaxation was potentiated by both PEA and OEA and the ability of PEA and OEA to cause relaxation may be via TRPV1
‘Entourage’ Results of N-palmitoylethanolamide and N-oleoylethanolamide on Vasorelaxation to Anandamide Happen By TRPV1 Receptors - 2007: In mice with pain, preadministration of PEA reduced swelling and inflammation via 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 in this mouse model, it reduced inflammation
The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-Alpha Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide - 2003: In mice, PEA potentiates the ability of AEA to induce microglia migration and this is not mediated by CB1 or CB2
Palmitoylethanolamide will increase after focal cerebral ischemia and potentiates microglial cell motility - 2002: In a patient after stroke, levels of AEA, PEA and OEA all rise
Launch of fatty acid amides in a affected person with hemispheric stroke: a microdialysis research - 2002: In cancer cells, PEA seems to potentiate the antiproliferative effects of AEA via the vanilloid system
Impact on Most cancers Cell Proliferation of Palmitoylethanolamide, a Fatty Acid Amide Interacting With Each the Cannabinoid and Vanilloid Signalling Methods - 2001: In breast cancer cells, PEA inhibited expression of FAAH and enhanced the anti-proliferative effects 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 against glutamate toxicity and prevented neuron loss
The ALIAmide Palmitoylethanolamide and Cannabinoids, however Not Anandamide, Are Protecting in a Delayed Postglutamate Paradigm of Excitotoxic Demise in Cerebellar Granule Neurons - 1995: In mast cells, PEA downmodulated mast cell activation via the CB2 receptor
Mast Cells Specific a Peripheral Cannabinoid Receptor With Differential Sensitivity to Anandamide and Palmitoylethanolamide - 1993: Levi-Montalcini’s big paper where she said PEA worked via mast cells and where she coined the acronym ALIA
A Proposed Autacoid Mechanism Controlling Mastocyte Behaviour - 1980: Dr. Epps finds PEA accumulating in infarcted myocardium and becomes the first to suggest that fatty molecules may play a protective role during ischemia and that its presence “may signify a response of myocardial tissue to injury directed at minimizing damage and promoting survival”
Accumulation of N-acylethanolamine Glycerophospholipids in Infarcted Myocardium - 1979: 3 large human trials shows PEA’s help for acute respiratory infections and with no negative effects on antibody production
Research on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically managed subject trials - 1975: The first supportive paper on the effects of PEA in cancer 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 first small pilot for rheumatic pain that supported PEA’s analgesic properties
Letter: Sluggish Encephalopathies, Inflammatory Responses, and Arachis Oil - 1974: Two large scale double-blind trials shows PEA helping symptoms of respiratory tract infections, but not their timecourse
Prophylactic efficacy of N-2-hydroxyethyl palmitamide (impulsin) in acute respiratory tract infections - 1972: In mice, PEA decreased mortality from a variety of immunological insults
Non-specific Resistance Induced by Palmitoylethanolamide - 1965: Bachur’s work finds PEA consistently present in brain, liver and muscle of rats and guinea pigs
Fatty acid amides of ethanolamine in mammalian tissues - 1957: Initial discovery paper
The identification of N-(2-hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent
