Palmitoylethanolamide (PEA)

PEA's mechanism of action - 2015 Palmitoylethanolamide, a Natural Retinoprotectant.jpg

an endocannabinoid produced in almost every human cell

Best reviews

2021: This review looks at the power of PEA to protect the brain's astrocytes

Alternative Targets to Fight Alzheimer's Disease: Focus on Astrocytes

2021: This review looks at PEA & COVID patients

Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients

2021: A special issue of the International Journal of Molecular Sciences is dedicated to PEA

2021: This review of female pelvic medicine & reconstructive surgery suggests PEA

Cannabinoid Therapy in Female Pelvic Medicine and Reconstructive Surgery: Current Evidence and Future Directions

2021: The several mechanisms relating PEA & autism

Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence

2021: This review looks at how PEA & oleoylethanolamide binds to GPR119 & GPR55 (receptors that may one day be known as CB3 & CB4)

GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide

2021: A mini-review looks at PEA & COVID (includes one positive case study)

Micronized / ultramicronized palmitoylethanolamide (PEA) as natural neuroprotector against COVID-19 inflammation

2020: A review of PEA for pets

Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing

2020: For you basal pharma nerds out there...

The Basal Pharmacology of Palmitoylethanolamide

2020: PEA for pain (nice charts)

ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain

2020: PEA + luteolin: a review of clinical & preclinical events related to neuroinflammation

An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events

2019: Strong review of mechanisms of action

Clinical Applications of Palmitoylethanolamide in Pain Management: Protocol for a Scoping Review

2019: PEA & palliative care

The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

2019: PEA & neuroinflammation

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer's Disease

2019: Nice diagrams of PEA's synergy with other antioxidants

Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy With Different Antioxidant Molecules Present in Diets

2019: A review of PEA & asthma

Molecular Targets of Fatty Acid Ethanolamides in Asthma

2018: A review of PEA & depression

Role of Palmitoylethanolamide (PEA) in Depression: Translational Evidence: Special Section on "Translational and Neuroscience Studies in Affective Disorders"

2017: DiMarzo’s great review – history and pharmacology – charts of where it’s found (breast milk!)

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations

2017: A review of PEA & polydatin for endometriosis covers 4 studies

Micronized Palmitoylethanolamide/Trans-Polydatin Treatment of Endometriosis-Related Pain: A Meta-Analysis

2017: PEA & pain meta-analysis

Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis

2016: A review of pain covers 6 studies

Palmitoylethanolamide for the Treatment of Pain: Pharmacokinetics, Safety and Efficacy

2015: PEA & nerve compression syndromes

Palmitoylethanolamide, a Neutraceutical, in Nerve Compression Syndromes: Efficacy and Safety in Sciatic Pain and Carpal Tunnel Syndrome

2015: PEA as a homeostasis mechanism for neuroinflammation in models of stroke, spinal cord injury, traumatic brain injury, & Parkinson disease

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

2014: A review of PEA & the CNS

Palmitoylethanolamide in CNS Health and Disease

2014: PEA & antiinflammatory effects

Harnessing the Anti-Inflammatory Potential of Palmitoylethanolamide

2013: a DiMarzo review

Palmitoylethanolamide: Biochemistry, Pharmacology and Therapeutic Use of a Pleiotropic Anti-Inflammatory Lipid Mediator

2013: A great review of the history of PEA & the clinical trials for the common cold

Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe Against Influenza and Common Cold

2013: PEA & inflammation from trauma

Palmitoylethanolamide Is a New Possible Pharmacological Treatment for the Inflammation Associated With Trauma

2013: A review of PEA for cannabis dependence

Palmitoylethanolamide: From Endogenous Cannabimimetic Substance to Innovative Medicine for the Treatment of Cannabis Dependence

2013: A review of PEA in mast cells (the immune cells carrying histamine)

New Insights in Mast Cell Modulation by Palmitoylethanolamide

2012: A review of PEA’s effect on mast cells, glia cells (brain immune cells) &  neuroinflammation

Mast Cell-Glia Axis in Neuroinflammation and Therapeutic Potential of the Anandamide Congener Palmitoylethanolamide

2005: Piomelli on history of PEA's discovery

The Search for the Palmitoylethanolamide Receptor

Chart Gallery

PEA's targets
PEA's targets

2019: Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy With Different Antioxidant Molecules Present in Diets

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PEA's mechanism of action
PEA's mechanism of action

2015: Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy

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PEA's lipid changes
PEA's lipid changes

2019: Broad Lipidomic and Transcriptional Changes of Prophylactic PEA Administration in Adult Mice

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PEA's targets
PEA's targets

2019: Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy With Different Antioxidant Molecules Present in Diets

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Timeline of Research

2021: In humans with nerve pain due to rheumatic disease, a combination of PEA & acetyl-L-carnitine (a dietary supplement that is naturally produced in the human body) caused a significant decrease in pain

The synergistic effect of palmitoylethanolamide and acetyl-L-carnitine in the treatment of peripheral neuropathies secondary to rheumatic diseases

2021: In humans with Tourette’s, initial promise was seen with a combination of 10 mg of THC + 800 mg of PEA

A Phase-2 Pilot Study of a Therapeutic Combination of Δ 9-Tetrahydracannabinol and Palmitoylethanolamide for Adults With Tourette's Syndrome

2021: In rats on an obesity diet, PEA as well as oleamide (OEA – another endocannabinoid) functioned as anti-obesity nutritional interventions

Palmitoleoylethanolamide Is an Efficient Anti-Obesity Endogenous Compound: Comparison with Oleylethanolamide in Diet-Induced Obesity

2021: In the brain of a model organism, the injection of PEA or OEA mediated the brain levels of serotonin & acetylcholine

In vivo brain levels of acetylcholine and 5-hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement

2021: Case study of PEA for the neuropathic pain of shingles

Palmitoylethanolamide (PEA) in the treatment of neuropathic pain: a case study

2021: In rats with benign prostatic hyperplasia (the most common benign tumor in males), a combination of PEA & baicalein (an active ingredient in the Baikal skullcap in CV Acute) lowered inflammation, reduced oxidative stress & 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, PEA as well as the flavonoid luteolin helped to recover the sense of smell after a COVID infection

Randomized clinical trial "olfactory dysfunction after COVID-19: olfactory rehabilitation therapy vs. intervention treatment with Palmitoylethanolamide and Luteolin": preliminary results

2021: In humans with nerve pain from rheumatic diseases, PEA combined well with acetyl-l-carnitine (ALC) to lower inflammation & to increase clinical scores

Efficacy of a fixed combination of Palmitoylethanolamide and acetyl-l-carnitine (PEA + ALC FC) in the treatment of Neuropathies secondary to Rheumatic Diseases

2021: In an animal model of stroke, they already knew that PEA protects the blood-brain barrier & 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) injury through regulation of ROCK/MLC signaling

2021: In humans, this cohort analysis found that the diversity of your gut microbiome was related to your happiness & motivation via the endocannabinoid system, especially via PEA - which they call the endogenous version of CBD

Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort

2021: In mice with their left carotid artery tied off, a combination of PEA & rutin (a helpful plant pigment) reduces inflammation, oxidative stress & vascular damage

Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO-1 and NF-kB Pathways

2021: In mice with inflamed colons, a combination of polydatin (a precursor of resveratrol) & ultra-micronized PEA decreased inflammation via several pathways

PEA/Polydatin: Anti-Inflammatory and Antioxidant Approach to Counteract DNBS-Induced Colitis

2021: In microglial cells (the immune cells of the brain), PEA caused decreased inflammation & increased neuroprotection

Palmitoylethanolamide Modulation of Microglia Activation: Characterization of Mechanisms of Action and Implication for Its Neuroprotective Effects

2021: A clinical trial where PEA from Levagen+ improves many measures of sleep

Palmitoylethanolamide for Sleep Disturbance. A Double-blind, Randomised, Placebo-controlled Interventional Study

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 (nuclear receptors that control genetic transcription)

The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

2021: In mice with dermatitis, a topical containing CBD & PEA lessened inflammation

Anti-inflammatory Effect of Cannabidiol and Palmitoylethanolamide Containing Topical Formulation on Skin in a 12-O-Tetradecanoylphorbol-13-Acetate-Induced Dermatitis Model in Mice

2021: In a rat model of inflammatory pain, PEA combined well with acetyl-l-carnitine (ALC)

Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Model of Inflammatory Pain

2021: In pregnant rats, even huge doses of PEA caused no measurable harms

Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats

2021: In humans with joint pain, PEA reduced pain & improved mood

The Effect of a Dispersible Palmitoylethanolamide (Levagen+) Compared to a Placebo for Reducing Joint Pain in an Adult Population – A Randomised, Double-Blind Study

2021: In rabbits having eye surgery, PEA reduced postoperative inflammation & scarring via the nuclear PPARα receptors that control genetic transcription

Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgery in rabbits by suppressing canonical and non-canonical TGFβ signaling through PPARα

2020: PEA for neurological disorders

Food supplements based on palmitoylethanolamide plus hydroxytyrosol from olive tree or Bacopa monnieri extracts for neurological diseases

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 possible strategy to treat mast cell-induced lung inflammation in COVID-19

2020: In mice with mood disorders induced by high-fat diets, PEA limits mood disorders & cognitive dysfunction

Palmitoylethanolamide limits mood disorders and cognitive dysfunction induced by high fat diet in obese 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 Disease and Lameness Management in Four Jumping Horses: A Case Report

2020: In cells, micronized PEA combined with lipoic acid and vitamin D3 absorbed better & reduced neuroinflammation

A New Palmitoylethanolamide Form Combined with Antioxidant Molecules to Improve Its Effectivess on Neuronal Aging

2020: In a cellular model of Alzheimer’s, PEA protects the neurons & increases their survival

Astrocytic palmitoylethanolamide pre-exposure exerts neuroprotective effects in astrocyte-neuron co-cultures from a triple transgenic mouse model of Alzheimer's disease

2020: A new double-blind study finds PEA helpful for glaucoma patients

Effect of palmitoylethanolamide on inner retinal function in glaucoma: a randomized, single blind, crossover, clinical trial by pattern-electroretinogram

2020: In rats, PEA helpful for eye disorders via the PPARα nuclear receptors (which alter genetic transcription)

PPARα-Dependent Effects of Palmitoylethanolamide Against 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 Involved in Palmitoylethanolamide-Induced Vasodepressor Effects in Rats

2020: In a double-blind human study, CBD & PEA both helped reduce permeability in the colon & appear helpful for IBS

Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo-A Randomized, Placebo-controlled, Double-blind Controlled Trial

2020: For patients with coronavirus, FSD Pharma received FDA approval to submit an Investigational New Drug Application for the use of PEA to increase endogenous levels of endocannabinoids (strong history section)

2020: In patients with lower back pain, the combination of therapy & ultramicronized PEA lowered pain past clinically relevant levels as well as increasing physical & mental quality of life

Combination of Rehabilitative Therapy With Ultramicronized Palmitoylethanolamide for Chronic Low Back Pain: An Observational Study

2020: In 70 pediatric patients with migraines, ultramicronized PEA decreased the number and severity of attacks – only one patient with mild side effects (nausea and floating)

Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering From Migraine: A Pilot Study

2020: In a human study with 28 participants, Levagen helpful for exercise recovery by reducing myoglobin and lactate concentration

The Effect of Orally Dosed Levagen+™ (Palmitoylethanolamide) on Exercise Recovery in Healthy Males-A Double-Blind, Randomized, Placebo-Controlled Study

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 Local Lipid Homeostasis to Relieve Sleep Deprivation-Induced Dry Eye Syndrome

2020: Mechanistic study of how 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”

Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer's Disease

2020: In mice asphyxiated at birth, PEA attenuated the neuronal damage in corpus striatum – restored level of GFAP cells, prevented decrease of pNF-H/M and MAP-2

Partial Reversal of Striatal Damage 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”

Effects of the Glial Modulator Palmitoylethanolamide on Chronic Pain Intensity and Brain Function

2019: 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 Post Hoc Analysis of a Controlled Study in Patients With Low Back Pain – Sciatica

2019: In a human double-blind study, both CBD & PEA reduced inflammation & reducing permeability in the human colon

Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo—A Randomized, Placebo-controlled, Double-blind Controlled Trial

2019: In a human double-blind study with 111 participants, found PEA helpful for inflammation of knee osteoarthritis

A Double-Blind Randomized Placebo Controlled Study Assessing Safety, Tolerability and Efficacy of Palmitoylethanolamide for Symptoms of Knee Osteoarthritis


2019: In 23 patients with mastocytosis (accumulation of mast cells), PEA levels were increased

Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients With Mastocytosis

2019: In 30 patients with endometriosis, both ultramicronized PEA co-micronised palmitoylethanolamide/polydatin m(PEA/PLD) showed significant improvements in all measures as well as quality of life

Effect of Ultramicronized-Palmitoylethanolamide and Co-Micronized Palmitoylethanolamide/Polydatin on Chronic Pelvic Pain and Quality of Life in Endometriosis Patients: An Open-Label Pilot Study

2019: In one patient with burning mouth syndrome, after gabapentin did little, adding PEA considerably improved the pain

Add-on Administration of Ultramicronized Palmitoylethanolamide in the Treatment of New-Onset Burning Mouth Syndrome

2019: In 32 patients with bladder problems, micronized PEA combined with polydatin reduced pain & urinary frequency

Micronized Palmitoylethanolamide-Polydatin Reduces the Painful Symptomatology in Patients With Interstitial Cystitis/Bladder Pain Syndrome

2019: In mice, great study on the broad lipid changes caused by PEA

Broad Lipidomic and Transcriptional Changes of Prophylactic PEA Administration in Adult Mice

2019: In cats with hypersensitive skin, ultramicronized PEA helped increase the efficacy window of a steroid course of methylprednisolone

Effect of Dietary Supplementation With Ultramicronized Palmitoylethanolamide in Maintaining Remission in Cats With Nonflea Hypersensitivity Dermatitis: A Double-Blind, Multicentre, Randomized, Placebo-Controlled Study

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 Combination of N-Palmitoylethanolamide, Beta-Caryophyllene, Carnosic Acid, and Myrrh Extract on Chronic Neuropathic Pain: A Preclinical Study

2019: In rats with a heart attack, the combination of PEA & baicalein (from Baikal skullcap) “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”

Effects of a New Compound Containing Palmitoylethanolamide and Baicalein in Myocardial Ischaemia/Reperfusion Injury in Vivo

2019: In mice with a painful nerve injury, PEA restored cognitive behavior & neuronal functioning (long term potentiation (LTP)) via two receptors in the glutamate system

Metabotropic Glutamate Receptor 5 and 8 Modulate the Ameliorative Effect of Ultramicronized Palmitoylethanolamide on Cognitive Decline Associated With Neuropathic Pain

2019: In mice with a painful nerve injury, ultramicronized PEA was able to “reverse mechanical allodynia and thermal hyperalgesia, memory deficit and LTP” & restore “the level of glutamate and the expression of phosphorylated GluR1 subunits, postsynaptic density and neurogenesis” via PPARα

Ultra-micronized Palmitoylethanolamide Rescues the Cognitive Decline-Associated Loss of Neural Plasticity in the Neuropathic Mouse Entorhinal Cortex-Dentate Gyrus Pathway

2019: In a mouse model of PTSD, PEA was used to activate PPARα – this helped with fear extinction and 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 Behavior

2019: In rats, PEA helped greatly with depression via several different markers including stress hormones – probably via PPARα

N-Palmitoylethanolamide Exerts Antidepressant-Like Effects in Rats: Involvement of PPAR α Pathway in the Hippocampus

2019: In an animal model of dementia, PEA & oxazoline were protective

N-Palmitoylethanolamine-oxazoline (PEA-OXA): A New Therapeutic Strategy to Reduce Neuroinflammation, Oxidative Stress Associated to Vascular Dementia in an Experimental Model of Repeated Bilateral Common Carotid Arteries Occlusion

2019: In neurons, treatment with 2-AG or PEA affected microglial cells and caused protection – using them together blocked their positive effects and caused the distribution (but not the activation) of PPARα to change

Opposite Effects of Neuroprotective Cannabinoids, Palmitoylethanolamide, and 2-Arachidonoylglycerol on Function 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” – PEA increased 2-AG via stimulation of DAGL-α and -β activity – the combination of PEA & 2-AG worked at levels low enough where they didn’t work on their own

Palmitoylethanolamide Counteracts Substance P-induced Mast Cell Activation in Vitro by Stimulating Diacylglycerol Lipase Activity

2018: In 155 patients with spinal damage and pain, ultramicronized PEA helped with mild and moderate pain, but not severe – safety noted

N-Palmitoyl Ethanol Amide Pharmacological Treatment in Patients With Nonsurgical Lumbar Radiculopathy

2018: In 58 patients with depression, 600 mg of PEA twice a day + citalopram significantly improved symptoms – demonstrated a rapid-onset effect

Palmitoylethanolamide as Adjunctive Therapy in Major Depressive Disorder: A Double-Blind, Randomized and Placebo-Controlled Trial

2018: In 35 patients with burning mouth syndrome, 600 mg of ultramicronized PEA significantly reduced the pain after 60 days – no interference in the other pharmacological therapies

Efficacy of Ultramicronized Palmitoylethanolamide in Burning Mouth Syndrome-Affected Patients: A Preliminary Randomized Double-Blind Controlled Trial

2018: In 20 patients with migraines, ultramicronized PEA treatment relieved pain with no side effects

Effects of Add-On Ultramicronized N-Palmitol Ethanol Amide in Patients Suffering of Migraine With Aura: A Pilot Study

2018: In mice with pain, PEA potentiated morphine & lessened tolerance – suggested as an additive treatment

Ultramicronized N-Palmitoylethanolamine Supplementation for Long-Lasting, Low-Dosed Morphine Antinociception

2018: In mice with epilepsy, PEA injections lessens seizures, promotes neuroprotection & modulates ECS levels

Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

2018: In a mouse model of Alzheimer’s, ultramicronized PEA improved learning and memory, lessened depression & anhedonia & helped various ways on neuroinflammation

Ultramicronized Palmitoylethanolamide Rescues Learning and Memory Impairments in a Triple Transgenic Mouse Model of Alzheimer's Disease by Exerting Anti-Inflammatory and Neuroprotective Effects

2018: In aged mice, pretreatment with PEA protected the brain from Parkinson’s like damage via several mechanisms

N-palmitoylethanolamide Prevents Parkinsonian Phenotypes in Aged Mice

2018: In aged mice, PEA protected from a bacterial infection in the organs & brain

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 & caused less inflammation & tissue damage via the downregulation of several “spinal inflammatory and oxidative pathways”

Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Levels and Spinal Anti-hyperalgesic Effect

2018: In baby mice with simulated perinatal asphyxia (not able to breate), PEA treatment attenuated damage in the hippocampus & improved behavioral alterations

Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction After Perinatal Asphyxia in the Immature Rat Brain

2018: In young rats deprived of oxygen, PEA treatment reduced neuroinflammation, astrogliosis (overabundance of astrocytes) & preserved cognitive function

Palmitoylethanolamide Prevents Neuroinflammation, Reduces Astrogliosis and Preserves Recognition and Spatial Memory Following Induction of Neonatal Anoxia-Ischemia

2018: In rats with joint inflammation, micronized PEA reduced the damage, pain, upregulation of Iba1 & macrophage activation

Micronized Palmitoylethanolamide Reduces Joint Pain and Glial Cell Activation

2018: In models of Alzheimer’s, PEA dampened the reactivity of the microglia & improved viability of the neurons as well as glial neurosupport

Palmitoylethanolamide Dampens Reactive Astrogliosis and Improves Neuronal Trophic Support in a Triple Transgenic Model of Alzheimer's Disease: In Vitro and In Vivo Evidence

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 & neurons, PEA blunted the astrocyte activation caused by a challenge by Aβ42

Palmitoylethanolamide Blunts Amyloid-β42-Induced Astrocyte Activation and Improves Neuronal Survival in Primary Mouse Cortical Astrocyte-Neuron Co-Cultures

2018: PEA nanoparticles for intraocular delivery

Innovative Nanoparticles Enhance N-Palmitoylethanolamide Intraocular Delivery

2017: In a mouse with traumatic brain injury, PEA protected the brain

Palmitoylethanolamide Reduces Neuropsychiatric Behaviors by Restoring Cortical Electrophysiological Activity in a Mouse Model of Mild Traumatic Brain Injury

2017: In 100 patients with spinal damage and pain, ultramicronized PEA combined well with paracetamol & codeine to relieve pain with no side effects

Nonsurgical Lumbar Radiculopathies Treated With Ultramicronized Palmitoylethanolamide (umPEA): A Series of 100 Cases

2017: In 55 patients with lower back pain, ultramicronized PEA was an effective add-on to tapentadol for pain & improved quality of life

The Beneficial Use of Ultramicronized Palmitoylethanolamide as Add-On Therapy to Tapentadol in the Treatment of Low Back Pain: A Pilot Study Comparing Prospective and Retrospective Observational Arms

2017: In 10 patients with pain, ultramicronized PEA helped

N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients With Chronic Pain

2017: In mice with a broken tibia, a product of micronized & 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” & apoptosis

Effect of a New Formulation of Micronized and Ultramicronized N-palmitoylethanolamine in a Tibia Fracture Mouse Model of Complex Regional Pain Syndrome


2017: In mice with brain & spinal injuries, the combination of PEA and oxazoline protected the motor function & behavioral deficits & increased glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor & neurotrophin-3 as well as diminished the expression of pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, tumor necrosis factor (TNF)-α & interleukin (IL)-1β

N-Palmitoylethanolamine-Oxazoline as a New Therapeutic Strategy to Control Neuroinflammation: Neuroprotective Effects in Experimental Models of Spinal Cord and Brain Injury

2017: In microglia & macrophage cells, PEA increased CB2 expression via PPAR-α – positively increased the reactivity of the microglials

Palmitoylethanolamide Induces Microglia Changes Associated With Increased Migration and Phagocytic Activity: Involvement of the CB2 Receptor

2017: In mice with induced allergies, PEA helped to clear the bronchi & upregulated CB2 & GPR55

Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse

2017: In cells, CBD & PEA are anti-inflammatory in the inflamed human colon

Cannabidiol and Palmitoylethanolamide Are Anti-Inflammatory in the Acutely Inflamed Human Colon

2017: In intestinal cells, PEA lowered intestinal permeability via PPARα - in response to inflammatory mediators, the cells increased their PEA levels

Oleoylethanolamine and Palmitoylethanolamine Modulate Intestinal Permeability in Vitro via TRPV1 and PPARα

2017: In a canine skin model, PEA protected from the negative mast cell effects of compound 48/80

Ultramicronized Palmitoylethanolamide Counteracts the Effects of Compound 48/80 in a Canine Skin Organ Culture Model

2016: In a study of cells, animals & humans, PEA raised the level of 2-AG & potentiated it at TRPV1

The Anti-Inflammatory Mediator Palmitoylethanolamide Enhances the Levels of 2-arachidonoyl-glycerol and Potentiates Its Actions at TRPV1 Cation Channels

2016: In 27 patients with endometriosis, AEA & PEA levels increased along with condition severity

Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis

2016: This review of 12 studies of patients with pain, PEA decreased pain with no serious adverse events

Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis

2016: In humans with MS, ultramicronized PEA in addition to first-line treatment with the interferon IFN-β1a caused an improvement in pain scores, quality of life, increased levels of PEA, AEA & OEA in the serum, and a significant reduction of interferon-γ, tumor necrosis factor-α, and interleukin-17 serum profile

Oral Palmitoylethanolamide Treatment Is Associated With Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis

2016: In 72 patients with spinal cord injuries, ultramicronized PEA caused no positive effects at all for anything measured

Ultramicronized Palmitoylethanolamide in Spinal Cord Injury Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

a followup comment:

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 & a case study with a 10 year old, a combination of PEA & luteolin ameliorated symptomatology of autism

Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism

2016: In mice with heart attacks, ultramicronized PEA protected the heart via PPARα

Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO

2016: In rats with endometriosis, ultramicronized PEA – via the mast cells – lowered pain, cysts, and stones

Ultramicronized Palmitoylethanolamide Reduces Viscerovisceral Hyperalgesia in a Rat Model of Endometriosis Plus Ureteral Calculosis: Role of Mast Cells

2016: Since PEA reduced angiogenesis in several chronic inflammatory conditions, in this mouse model & patient study of Ulcerative Colitis (UC) and Crohn's Disease (CD), the researchers said PEA “inhibits colitis-associated angiogenesis, decreasing VEGF release and new vessels formation” via the PPARα and helps to regulate the angiogenic process via the mTOR/Akt axis

Palmitoylethanolamide Modulates Inflammation-Associated Vascular Endothelial Growth Factor (VEGF) Signaling via the Akt/mTOR Pathway in a Selective Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α)-Dependent Manner

2016: In colon cancer cells, PEA caused a significant reduction in proliferation, angiogenesis, and VEGF secretion & expression via PPARα’s effect on the AkT/mTOR axis

Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway

2015: in humans, this review of studies finds PEA safe & effective for glaucoma & other retinopathies (nice chart of mechanisms of action)

Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy

2015: In two patients with autism, PEA caused “rapid improvements in cognitive, behaviors, and sociability”

Beneficial Effects of Palmitoylethanolamide on Expressive Language, Cognition, and Behaviors in Autism: A Report of Two Cases

2015: In 160 dogs with red itchy skin, ultramicronized PEA was “effective and safe in reducing pruritus and skin lesions” & improving quality of life

Efficacy of Ultra-Micronized Palmitoylethanolamide in Canine Atopic Dermatitis: An Open-Label Multi-Centre Study

2015: In rats with pain, PEA delays the tolerance effects of morphine

Delay of Morphine Tolerance by Palmitoylethanolamide

2015: In rats with high blood pressure, PEA protected via several different pathways

Palmitoylethanolamide Treatment Reduces Blood Pressure 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” & inhibited NF-κB and apoptosis pathways

Effects of Palmitoylethanolamide and Silymarin Combination Treatment in an Animal Model of Kidney Ischemia and Reperfusion

2015: In rats with inflamed eyes, PEA “decreased the inflammatory cell infiltration and improved histological damage of eye tissues”, “reduced pro-inflammatory tumor necrosis factor (TNF-α) levels, protein extravasion and lipid peroxidation”, and “strongly inhibited iNOS expression and nuclear NF-κB translocation” – overall, reduced ocular inflammation

The Anti-Inflammatory Effects of Palmitoylethanolamide (PEA) on Endotoxin-Induced Uveitis in Rats

2015: In mice with induced colitis, PEA helps via CB2, GPR55, PPAR-alpha & modulation of the TRPV1 channels

Palmitoylethanolamide, a Naturally Occurring Lipid, Is an Orally Effective Intestinal Anti-Inflammatory Agent

2015: In a mouse model of MS, treatment with PEA or CBD reduced disease severity with diminished inflammation, demyelination, axonal damage & inflammatory cytokine expression – but they did not work as well together

Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice

2015: In mice with painful nerve injuries, PEA restored their glutamate functioning & the changes in amino acid release (nice graphic)

Palmitoylethanolamide Reduces Pain-Related Behaviors and Restores Glutamatergic Synapses Homeostasis in the Medial Prefrontal Cortex of Neuropathic Mice

2015: In cells challenged by the Aβ amyloids of Alzheimer’s, PEA “reduced expression of pro-inflammatory and pro-angiogenic markers” via PPARα

Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis In Vitro

2015: In neurons from mice challenged by the Aβ amyloids of Alzheimer’s, PEA rescued glutamate in non-transgenic mice but not the triple-transgenic murine model of AD

Differential Effects of Palmitoylethanolamide Against Amyloid-β Induced Toxicity in Cortical Neuronal and Astrocytic Primary Cultures From Wild-Type and 3xTg-AD Mice

2014: In 30 diabetic patients, micronized PEA effectively reduced pain – blood work & urine analysis saw no significant alterations

Micronized Palmitoylethanolamide Reduces the Symptoms of Neuropathic Pain in Diabetic Patients

2014: In 60 patients with eczema, a PEA/AEA topical improved “passive and active skin functions simultaneously”

N-palmitoylethanolamine and N-acetylethanolamine Are Effective in Asteatotic Eczema: Results of a Randomized, Double-Blind, Controlled Study in 60 Patients

2014:Iin a patient with chronic vulvar & anal pain, a topical of PEA & baclofen decreased her pain by 50% and allowed for sex again

Vulvodynia and Proctodynia Treated With Topical Baclofen 5 % and Palmitoylethanolamide

2014: In dogs with red itchy skin, PEA probably helps via the downregulation of mast cells – levels of PEA increase as the disease progresses

Increased Levels of Palmitoylethanolamide and Other Bioactive Lipid Mediators and Enhanced Local Mast Cell Proliferation in Canine Atopic Dermatitis

2014: In a rat model of Alzheimer’s, PEA was able to restore the alterations via PPARα & reverse the cognitive impairments

Palmitoylethanolamide Controls Reactive Gliosis and Exerts Neuroprotective Functions in a Rat Model of Alzheimer's Disease

2014: In mice with an inflamed colon, PEA improved transit time of GI tract & increased AEA levels, mediated by CB1 receptors (possibly via the AEA) & modulated the TRPV1 channels

Palmitoylethanolamide Normalizes Intestinal Motility in a Model of Post-Inflammatory Accelerated Transit: Involvement of CB₁ Receptors and TRPV1 Channels

2014: In the intestines of rats undergoing chemotherapy (and using mast cell knockout rats), PEA works via the mast cells for protection

Palmitoylethanolamide Regulates Development of Intestinal Radiation Injury in a Mast Cell-Dependent Manner

2014: In a rat model of inflammatory pain, micronized/ultramicronized PEA worked better orally than PEA

Micronized/ultramicronized Palmitoylethanolamide Displays Superior Oral Efficacy Compared to Nonmicronized Palmitoylethanolamide in a Rat Model of Inflammatory Pain

2014: In mice, PEA treatment increased the ability of macrophages to phagocytose (engulf & digest) E. coli

Palmitoylethanolamide Stimulates Phagocytosis of Escherichia Coli K1 by Macrophages and Increases the Resistance of Mice Against Infections

2014: In colon cells, PEA improved all macroscopic signs of ulcerative colitis & decreased all proinflammatory markers tested via PPARα

Palmitoylethanolamide Improves Colon Inflammation Through an Enteric Glia/Toll Like Receptor 4-dependent PPAR-α Activation

2013: In 24 women with endometriosis & chronic pelvic pain, micronized PEA & polydatin reduced pelvic pain, dysmenorrhea (cramps) & dyspareunia (pain during sex) but not dysuria (painful urination) & dischezia (strained stools) – overall increased 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

Chronic Idiopathic Axonal Neuropathy and Pain, Treated With the Endogenous Lipid Mediator Palmitoylethanolamide: A Case Collection

2013: In rats with a form of epilepsy, PEA reduces seizures via the PPAR-α receptors & indirectly by the CB1 receptors

Antiepileptic Action of N-palmitoylethanolamine Through CB1 and PPAR-α Receptor Activation in a Genetic Model of Absence Epilepsy

2013: In mice with spinal cord trauma, they found that PPAR-δ & PPAR-γ also contribute to PEA’s anti-inflammatory effects

Molecular Evidence for the Involvement of PPAR-δ and PPAR-γ in Anti-Inflammatory and Neuroprotective Activities of Palmitoylethanolamide After Spinal Cord Trauma

2013: In rats with high blood pressure, PEA reduced blood pressure & reduced damage to the kidneys

N-Palmitoylethanolamide Protects the Kidney From Hypertensive Injury in Spontaneously Hypertensive Rats via 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 & the reduction of microglia activation in the spinal cord

Non-neuronal Cell Modulation Relieves Neuropathic Pain: Efficacy of the Endogenous Lipid Palmitoylethanolamide

2013: PEA targets both glial & mast cells for antiinflammation & 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 & glia cells, significantly reduced mechanical allodynia & thermal hyperalgesia, and suggests use for spinal cord injuries

Palmitoylethanolamide Reduces Formalin-Induced Neuropathic-Like Behaviour Through Spinal Glial/Microglial Phenotypical Changes 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 Diseases: Therapeutic Potential of Palmitoylethanolamide in Models of Alzheimer's Disease


2013: In cells, PEA activated TRPV1, perhaps via PPARα

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 in the Treatment of Neuropathic Pain Associated With Various Pathological Conditions: A Case Series

2012: In an observational study of 600+ patients, PEA helped all of them with their treatment-resistant chronic pain & caused no adverse effects

Palmitoylethanolamide in the Treatment of Chronic Pain Caused by Different Etiopathogenesis

2012: In a patient with ALS, PEA improved clinical picture – probably via the microglia and mast cells

Amyotrophic Lateral Sclerosis Treatment With Ultramicronized Palmitoylethanolamide: A Case Report

2012: In mice, PEA helped to protect from a Parkinson’s like insult – probably via PPARα

Neuroprotective Activities of Palmitoylethanolamide in an Animal Model of Parkinson's Disease

2012: In rats, PEA protected the brain after injury by many pathways

Reduction of Ischemic Brain Injury by Administration of Palmitoylethanolamide After Transient Middle Cerebral Artery Occlusion in Rats

2012: In a mouse model of traumatic brain injury, PEA protected the brain via several pathways & improved neurobehavioral functions

Administration of Palmitoylethanolamide (PEA) Protects the Neurovascular Unit and Reduces Secondary Injury After Traumatic Brain Injury in Mice

2012: In a mouse model of Alzheimer’s, injected PEA significantly helped with learning & memory disfunction – probably via the PPARα pathway

Palmitoylethanolamide Protects Against the amyloid-β25-35-induced Learning and Memory Impairment in Mice, an Experimental Model of Alzheimer Disease

2012: In mice with intestinal injuries, pretreatment with PEA reduced inflammation & cell death – probably via the PPARα pathway

Effects of Palmitoylethanolamide on Intestinal Injury and Inflammation Caused by Ischemia-Reperfusion in Mice

2012: In mice with injured kidneys, PEA protected via several different pathways – probably via the PPARα pathway

Palmitoylethanolamide Reduces Early Renal Dysfunction and Injury Caused by Experimental Ischemia and Reperfusion in Mice

2012: In mice experiencing pain, PEA increased allopregnanolone (ALLO) levels via PPARα & it “restored the expression of two proteins involved in neurosteroidogenensis"

Implication of Allopregnanolone in the Antinociceptive Effect of N-palmitoylethanolamide in Acute or Persistent Pain

2012: In neurons challenged by the β-amyloids of Alzheimer’s (astrocytes), PEA blunted activation & improved neuronal survival

Palmitoylethanolamide Exerts Neuroprotective Effects in Mixed Neuroglial Cultures and Organotypic Hippocampal Slices via Peroxisome Proliferator-Activated Receptor-α

2012: In microglial cells, PEA caused increased phagosytosis of E. coli & 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 & showed positive effects on the myelinated fiber groups

Palmitoylethanolamide Restores Myelinated-Fibre Function in Patients With Chemotherapy-Induced Painful Neuropathy

2011: In tissue, PEA appears to regulate neurosteroidogenesis in astrocytes & increase allopregnanolone (ALLO) via PPARα

Palmitoylethanolamide Stimulation Induces Allopregnanolone Synthesis in C6 Cells and Primary Astrocytes: Involvement of Peroxisome-Proliferator Activated Receptor-α

2011: In this specialized neuron, PEA reduced the number of microglial cells & protected the neurons via PPARα

Palmitoylethanolamide Protects Dentate Gyrus Granule Cells via 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”

Effects of Palmitoylethanolamide on Release of Mast Cell Peptidases and Neurotrophic Factors After Spinal Cord Injury

2011: In astrocytes, the β-amyloids of Alzheimer’s increased PEA levels – treatment with PEA blunted its proinflammatory effects, probably via PPARα, as well as increasing 2-AG levels

Palmitoylethanolamide Counteracts Reactive Astrogliosis Induced by β-Amyloid Peptide

2010: In mice, PEA modulates the hypnotic effect of phenobarbital via PPARα’s increase of allopregnanolone (ALLO) & a positive modulation of GABA

Palmitoylethanolamide Modulates Pentobarbital-Evoked Hypnotic Effect in Mice: Involvement of Allopregnanolone Biosynthesis

2010: In canine mast cells, PEA downregulated their activity via several factors (decrease of Histamine, PGD(2) and TNFalpha)

Effects of Palmitoylethanolamide on Immunologically Induced Histamine, PGD2 and TNFalpha Release From Canine Skin Mast Cells

2009: In mice, pretreatment with PEA lowered pain via PPARα’s inhibition of NF-kappaβ nuclear signaling in dorsal root ganglia – reduced COX-2 & iNOS

Central Administration of Palmitoylethanolamide Reduces Hyperalgesia in Mice via 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 & half of them stopped using their corticosteroids

Adjuvant Treatment of Atopic Eczema: Assessment of an Emollient Containing N-palmitoylethanolamine (ATOPA Study)

2008: In mice with a model of MS, CB2 was upregulated as was 2-AG & PEA – but not AEA – PEA applied exogenously reduced disability and lowered inflammation

Study of the Regulation of the Endocannabinoid System in a Virus Model of Multiple Sclerosis Reveals a Therapeutic Effect of Palmitoylethanolamide

2008: In mice with 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” & it helped with recovery of motor function

Effects of Palmitoylethanolamide on Signaling Pathways Implicated in the Development of Spinal Cord Injury

2008: In mice, PEA helped with pain via CB1, TRPV1 & PPARγ

The Endogenous Fatty Acid Amide, Palmitoylethanolamide, Has Anti-Allodynic and Anti-Hyperalgesic Effects in a Murine Model of Neuropathic Pain: Involvement of CB(1), TRPV1 and PPARgamma Receptors and Neurotrophic Factors

2008: In rat arteries, the ability of AEA to induce relaxation was potentiated by both PEA & OEA – possibly via TRPV1

'Entourage' Effects of N-palmitoylethanolamide and N-oleoylethanolamide on Vasorelaxation to Anandamide Occur Through TRPV1 Receptors

2007: In mice with pain, preadministration of PEA reduced swelling & inflammation via PPARα

Acute Intracerebroventricular Administration of Palmitoylethanolamide, an Endogenous Peroxisome Proliferator-Activated Receptor-Alpha Agonist, Modulates Carrageenan-Induced Paw Edema in Mice

2005: Piomelli identifies PPARα as PEA’s mechanism – 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 – not mediated by CB1 or CB2

Palmitoylethanolamide increases after focal cerebral ischemia and potentiates microglial cell motility

2002: In a patient after stroke, levels of AEA, PEA & OEA all rise

Release of fatty acid amides in a patient with hemispheric stroke: a microdialysis study

2002: In cancer cells, PEA seems to potentiate the antiproliferative effects of AEA via the vanilloid system

Effect on Cancer Cell Proliferation of Palmitoylethanolamide, a Fatty Acid Amide Interacting With Both the Cannabinoid and Vanilloid Signalling Systems

2001: In breast cancer cells, PEA inhibits expression of FAAH & enhances anti-proliferative effects of AEA

Palmitoylethanolamide Inhibits the Expression of Fatty Acid Amide Hydrolase and Enhances the Anti-Proliferative Effect of Anandamide in Human Breast Cancer Cells

2001: In kidney cells, PEA enhances AEA’s stimulation of VR1

Palmitoylethanolamide Enhances Anandamide Stimulation of Human Vanilloid VR1 Receptors

1996: In neurons, PEA – but not AEA – protected against glutamate toxicity & prevented neuron loss

The ALIAmide Palmitoylethanolamide and Cannabinoids, but Not Anandamide, Are Protective in a Delayed Postglutamate Paradigm of Excitotoxic Death in Cerebellar Granule Neurons

1995: In mast cells, they found that while CB2 is present – only activation by PEA - and not AEA  - downmodulates mast cell activation – in fact, AEA antagonized the effect (“ALIAmides”)

Mast Cells Express 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 & where she coined the acronym ALIA

A Proposed Autacoid Mechanism Controlling Mastocyte Behaviour

1980: Epps finds PEA accumulating in infarcted myocardium – first to suggest that fatty molecules may play a protective role during ischemia & 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 trials shows PEA’s help for acute respiratory infections with no negative effects on antibody production

Studies on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically controlled field trials

1975: First supportive effects of PEA in cancer as a modulator of toxicity in chemotherapy found in an animal model (confirmed by Gruccu’s group in 2011)

The Effect of Long-Term Administration of N-(2-hydroxyethyl)palmitamide on the Chemotherapy of RBA Rat Leukemia

1975: First small pilot for rheumatic pain supported analgesic properties

Letter: Slow Encephalopathies, Inflammatory Responses, and Arachis Oil

1974: Two large scale double-blind trials show 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 caused 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 & muscle of rats and guinea pigs


1957: Initial discovery paper

The identification of N-(2-hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent