Palmitoylethanolamide (PEA)
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an endocannabinoid produced in almost every human cell
Best reviews
2023: A review of PEA for facial pain
Orofacial Pain Management: An Overview of the Potential Benefits of Palmitoylethanolamide and Other Natural Agents
https://pubmed.ncbi.nlm.nih.gov/37111679/
2023: A review of 11 studies on using PEA for chronic pain
Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials
https://pubmed.ncbi.nlm.nih.gov/36986081/
2022: In a rat model of sciatic nerve damage, PEA decreased the intensity & duration of the pain, stabilized the microglia & astroglia (brain immune cells) & lowered neuroinflammation by several mechanisms
Analgesic Activity of Palmitoylethanolamide on Neuropathic Pain in Rats
https://link.springer.com/article/10.1134/S1819712422030047
2022: In a review of 933 patients using PEA for neuropathic pain, it helped with pain reduction & quality of life
Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence
https://pubmed.ncbi.nlm.nih.gov/36015298
2022: In a strong review of 33 studies on PEA for cognitive decline, it found that PEA improved neurobehavioral functions like memory & learning, reduced oxidative stress & inflammation, rebalanced glutamate (the brains most excitatory neurotransmitter), increased neuron survival & promoted neurogenesis (the creation of new brain cells) + so much more
Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
https://pubmed.ncbi.nlm.nih.gov/36387000/
2022: A review of PEA for neurodegenerative disorders & defects of the brain’s white matter (connective sheaths around nerve fibers)
Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications
https://www.mdpi.com/2218-273X/12/9/1191
2022: A review on what does PEA does at our synapses for neurodegeneration & neuroinflammation
Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders
https://pubmed.ncbi.nlm.nih.gov/36009055
2022: This review looks at the ability of PEA to help with neuromuscular diseases, especially those involving acetylcholine
Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function
https://pubmed.ncbi.nlm.nih.gov/35740883
2022: A review of PEA for neurodegenerative disorders
Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans
https://www.mdpi.com/2218-273X/12/5/667
2022: A book chapter on using PEA & polydatin for bladder pain & cystitis
Treatment of Interstitial Cystitis/Bladder Pain Syndrome with Palmitoylethanolamide/Polydatin
https://link.springer.com/chapter/10.1007/978-3-030-94174-1_23
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
https://pubmed.ncbi.nlm.nih.gov/33921556/
2021: This review looks at PEA & COVID patients
Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients
https://www.mdpi.com/1424-8247/14/4/336
2021: A special issue of the International Journal of Molecular Sciences is dedicated to PEA
https://www.mdpi.com/journal/ijms/special_issues/Palmitoylethanolamide_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
https://link.springer.com/article/10.1007/s11884-021-00632-5
2021: The several mechanisms relating PEA & autism
Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
https://www.mdpi.com/2072-6643/13/4/1346/htm
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
https://pubmed.ncbi.nlm.nih.gov/33494185/
2021: A mini-review looks at PEA & COVID (includes one positive case study)
Micronized / ultramicronized palmitoylethanolamide (PEA) as natural neuroprotector against COVID-19 inflammation
https://pubmed.ncbi.nlm.nih.gov/33636368/
2020: A review of PEA for pets
Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing
https://www.mdpi.com/2306-7381/7/2/78
2020: For you basal pharma nerds out there...
The Basal Pharmacology of Palmitoylethanolamide
https://pubmed.ncbi.nlm.nih.gov/33114698/
2020: PEA for pain (nice charts)
ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain
https://pubmed.ncbi.nlm.nih.gov/32727084/
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
https://pubmed.ncbi.nlm.nih.gov/32150935/
2019: Strong review of mechanisms of action
Clinical Applications of Palmitoylethanolamide in Pain Management: Protocol for a Scoping Review
https://pubmed.ncbi.nlm.nih.gov/30621775/
2019: PEA & palliative care
The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review
https://pubmed.ncbi.nlm.nih.gov/31113223/
2019: PEA & neuroinflammation
Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer's Disease
https://pubmed.ncbi.nlm.nih.gov/31396087/
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
https://pubmed.ncbi.nlm.nih.gov/31514292/
2019: A review of PEA & asthma
Molecular Targets of Fatty Acid Ethanolamides in Asthma
https://pubmed.ncbi.nlm.nih.gov/30939862/
2018: A review of PEA & depression
Role of Palmitoylethanolamide (PEA) in Depression: Translational Evidence: Special Section on "Translational and Neuroscience Studies in Affective Disorders"
https://pubmed.ncbi.nlm.nih.gov/30391203/
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
https://pubmed.ncbi.nlm.nih.gov/27539936/
2017: A review of PEA & polydatin for endometriosis covers 4 studies
Micronized Palmitoylethanolamide/Trans-Polydatin Treatment of Endometriosis-Related Pain: A Meta-Analysis
https://pubmed.ncbi.nlm.nih.gov/28617258/
2017: PEA & pain meta-analysis
Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis
https://pubmed.ncbi.nlm.nih.gov/28727699/
2016: A review of pain covers 6 studies
Palmitoylethanolamide for the Treatment of Pain: Pharmacokinetics, Safety and Efficacy
https://pubmed.ncbi.nlm.nih.gov/27220803/
2015: PEA & nerve compression syndromes
Palmitoylethanolamide, a Neutraceutical, in Nerve Compression Syndromes: Efficacy and Safety in Sciatic Pain and Carpal Tunnel Syndrome
https://pubmed.ncbi.nlm.nih.gov/26604814/
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
https://www.ncbi.nlm.nih.gov/pubmed/26055231
2014: A review of PEA & the CNS
Palmitoylethanolamide in CNS Health and Disease
https://pubmed.ncbi.nlm.nih.gov/24844438/
2014: PEA & antiinflammatory effects
Harnessing the Anti-Inflammatory Potential of Palmitoylethanolamide
https://pubmed.ncbi.nlm.nih.gov/24952959/
2013: a DiMarzo review
Palmitoylethanolamide: Biochemistry, Pharmacology and Therapeutic Use of a Pleiotropic Anti-Inflammatory Lipid Mediator
https://pubmed.ncbi.nlm.nih.gov/23394521/
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
https://pubmed.ncbi.nlm.nih.gov/24066256/
2013: PEA & inflammation from trauma
Palmitoylethanolamide Is a New Possible Pharmacological Treatment for the Inflammation Associated With Trauma
https://pubmed.ncbi.nlm.nih.gov/22697514/
2013: A review of PEA for cannabis dependence
Palmitoylethanolamide: From Endogenous Cannabimimetic Substance to Innovative Medicine for the Treatment of Cannabis Dependence
https://pubmed.ncbi.nlm.nih.gov/23896215/
2013: A review of PEA in mast cells (the immune cells carrying histamine)
New Insights in Mast Cell Modulation by Palmitoylethanolamide
https://pubmed.ncbi.nlm.nih.gov/23394523/
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
https://pubmed.ncbi.nlm.nih.gov/23108549/
2005: Piomelli on history of PEA's discovery
The Search for the Palmitoylethanolamide Receptor
https://pubmed.ncbi.nlm.nih.gov/15963531/
Chart Gallery
2022: Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications
2019: Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy With Different Antioxidant Molecules Present in Diets
2019: Broad Lipidomic and Transcriptional Changes of Prophylactic PEA Administration in Adult Mice
2022: Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications
Timeline of Research
2023: In a mouse model of cognitive decline & Alzheimer’s disease, PEA protected memory & lessened shrinking of the hippocampus (memory center of the brain)
Chronic administration of palmitoylethanolamide counteracts cognitive decline in Tg2576 Mice
https://iris.uniroma1.it/handle/11573/1669443
2023:In a tissue study of pelvic pain of the bladder, a mixture of PEA, hempseed oil & maritime pine bark extract reduced inflammatory cytokines
Micronized Palmitoylethanolamide, Hempseed Oil, and Maritime Pine Bark Dry Extract (Pelvipea®) for Pelvic Pain: An In Vitro Study for Urothelial Inflammation Treatment
https://pubmed.ncbi.nlm.nih.gov/36831284/
2023: In retinal cells of the eyes, PEA protected them from reactive oxygen species & cell death
Effect of palmitoylethanolamide on degeneration of a human-derived retinal pigment epithelial cell induced by all-trans retinal
https://pubmed.ncbi.nlm.nih.gov/36816211/
2023: In a study of mast cells & astrocytes (2 key support cells of the brain), PEA delayed their tolerance to morphine
Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
https://www.mdpi.com/2218-273X/13/2/233
2022: A PEA nanoparticles to treat sarcopenia (a loss of muscle mass)
Design, Characterization, and In Vitro Assays on Muscle Cells of Endocannabinoid-like Molecule Loaded Lipid Nanoparticles for a Therapeutic Anti-Inflammatory Approach to Sarcopenia
https://pubmed.ncbi.nlm.nih.gov/35336022/
2022: In heart cells exposed to typical chemotherapy drugs, PEA protected them from cell death & inflammation via the PPAR-α pathway (nuclear receptors that on & off genetic transcription) & the NLRP3-related pathways (related to inflammation)
The analgesic compound palmitoylethanolamide reduces inflammation in human cardiomyocytes and vascular endothelial cells exposed to doxorubicin and anti-HER2 monoclonal antibody through PPAR-α and NLRP3-related pathways
https://www.annalsofoncology.org/article/S0923-7534(22)01894-4/fulltext
2022: On using PEA for chronic pelvic pain syndrome
Chronic Pelvic Pain Syndrome, General Conservative and Medical Management and Palmitoylethanolamide (PEA) Efficacy
https://web.archive.org/web/20221119222632id_/https://www.onlinescientificresearch.com/articles/chronic-pelvic-pain-syndrome-general-conservative-and-medical-management-and-palmitoylethanolamide-pea-efficacy.pdf
2022: In a mouse model of hemophilia, PEA helped with pain & the symptoms of arthritis such as joint inflammation
Palmitoylethanolamide Attenuates Pain-like Behavior in Factor VIII Deficient Mice
https://ashpublications.org/blood/article/140/Supplement%201/5578/492940
2022: In mice with lupus, PEA helped with inflammation in a variety of situations via Toll receptors
Comprehensive lipidomics of lupus-prone mice using LC-MS/MS identifies the reduction of palmitoylethanolamide that suppresses TLR9-mediated inflammation
https://pubmed.ncbi.nlm.nih.gov/35485445/
2022: In humans with acute mania being treated with lithium & risperidone, 600 mg of PEA caused a significantly lower score on the Young Mania Rating Scale
Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania: a randomized, double-blind and placebo-controlled trial
https://pubmed.ncbi.nlm.nih.gov/35737597
2022: In humans with schizophrenia, PEA combined with risperidone (a common treatment) helped with their negative symptoms (functional, verbal, and social performance loss) but little change in their positive symptoms (hallucinations, delusions, confused thoughts, disorganized speech)
Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial
https://pubmed.ncbi.nlm.nih.gov/35917650
2022: In brain cells, the toxicity of the chemotherapy treatment paclitaxel is lessened by PEA
Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons
https://pubmed.ncbi.nlm.nih.gov/36551301
2022: In a model of intracerebral hemorrhage (bleeding in the brain – the second most common cause of stroke), PEA lowered neuroinflammation & improved motor function via the PPAR-α receptors (nuclear receptors that control genetic transcription) in microglial cells (the immune cells of the brain)
Palmitoylethanolamide ameliorates neuroinflammation via modulating PPAR-α to promote the functional outcome after intracerebral hemorrhage
https://www.sciencedirect.com/science/article/pii/S0304394022002051
2022: In a rat model of temporal lobe epilepsy, PEA reduced the amount of neurodestruction & helped to retain healthy behaviors
Neuroprotective Effect of Palmitoylethanolamide in the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy
https://link.springer.com/article/10.1134/S0022093022020132
2022: In a tissue model of Alzheimer’s disease, PEA & luteolin (a flavonoid commonly paired with PEA) reduces neuronal inflammation & astrocyte reactivity while restoring homeostasis of the oligodendrocytes via the PPAR nuclear receptors (controllers of genetic transcription)
Co-Ultramicronized Palmitoylethanolamide/Luteolin Restores Oligodendrocyte Homeostasis via Peroxisome Proliferator-Activated Receptor-α in an In Vitro Model of Alzheimer’s Disease
https://www.mdpi.com/2227-9059/10/6/1236
2022: In a tissue study, PEA protects heart cells from the toxicity & inflammation of anti-cancer treatments
The analgesic compound palmitoylethanolamide reduces inflammation in human cardiomyocytes and vascular endothelial cells exposed to doxorubicin and anti-HER2 monoclonal antibody through PPAR-α and NLRP3-related pathways
https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e24054
2022: On using PEA to reduce the tolerance to opiates & enhance their painkilling abilities
Role of PEA in Reduction of Opiate Tolerance
https://www.jbclinpharm.org/articles/role-of-pea-in-reduction-of-opiate-tolerance.pdf
2022: In patients with diabetes experiencing neuropathic body pain, 600 mg of PEA lowered their pain & inflammation scores significantly as well as improving their sleep & mood
A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain
https://pubmed.ncbi.nlm.nih.gov/36057884
2022: In a mouse model of pain from chemotherapy, PEA helped with the pain as well as the mood disorders
The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice
https://pubmed.ncbi.nlm.nih.gov/36009049
2022: In humans with tension headaches, PEA worked almost as well as ibuprofen for moderate headaches & for severe headaches, PEA worked faster
Efficacy of Palmitoylethanolamide (Levagen+TM) Compared to Ibuprofen for Reducing Headache Pain Severity and Duration in Healthy Adults: A Double-Blind, Parallel, Randomized Clinical Trial
https://www.scirp.org/journal/paperinformation.aspx?paperid=118715
2022: In humans with pelvic pain, a combination of PEA & magnesium reduced pain & increased quality of life
A Palmitoylethanolamide (PEA) and Magnesium Based Product (PEAMag) Reduces the Pain and Improves Quality of Life in Patients Affected by Acute and Chronic Pelvic Pain
http://www.clinicalcasereportsint.com/open-access/a-palmitoylethanolamide-pea-and-magnesium-based-product-peamag-reduces-the-8862.pdf
2022: In patients with episodic migraines, a small pilot study finds that PEA helps decrease the frequency of migraines & the amount of medication needed for pain
Palmitoylethanolamide-based nutraceutical Calmux® in preventive treatment of migraine
https://pubmed.ncbi.nlm.nih.gov/35598579
2022: In a tissue model of Alzheimer’s disease, PEA & luteolin (a flavonoid commonly paired with PEA) reduces neuronal inflammation & astrocyte reactivity while restoring homeostasis of the oligodendrocytes via the PPAR nuclear receptors (controllers of genetic transcription)
Co-Ultramicronized Palmitoylethanolamide/Luteolin Restores Oligodendrocyte Homeostasis via Peroxisome Proliferator-Activated Receptor-α in an In Vitro Model of Alzheimer’s Disease
https://www.mdpi.com/2227-9059/10/6/1236
2022: This survey shows that most women who used cannabis or cannabinoids (THC, CBD, PEA) for gynecologic conditions found that it improved pain
Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review
2022: In a mouse model of obesity, PEA restored the plasticity of their white & brown fat cells, leptin sensitivity, tissue hormone sensitivity & 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
https://www.mdpi.com/1999-4923/14/2/338
2022: In a study of 90 patients with COVID-19, PEA reduced inflammatory states, oxidative states & alterations to blood biomarkers
Effects of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Stages: A Case-Control Study
https://pubmed.ncbi.nlm.nih.gov/35215365/
2022: In obese mice, PEA lessened neuroinflammation as well as anxious behavior
Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice
https://pubmed.ncbi.nlm.nih.gov/35176443/
2021: In a mouse model of seizures, while PEA did not reduce the seizures, it did increase the effectiveness of the drug ganaxolone & reduced mortality
Investigating the synergistic effect of palmitoylethanolamide and ganaxolone in PTZ-induced tonic-clonic seizures
http://sjku.muk.ac.ir/browse.php?a_id=6998&sid=1&slc_lang=en
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 levels during experimentally-induced migraine attacks
https://pubmed.ncbi.nlm.nih.gov/33587406/
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
https://pubmed.ncbi.nlm.nih.gov/34340527/
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
https://www.sciencedirect.com/science/article/abs/pii/S0006291X21009335
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
https://pubmed.ncbi.nlm.nih.gov/34002020/
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
https://pubmed.ncbi.nlm.nih.gov/34156697/
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 Pro-Inflammatory Response Activated by SARS-CoV-2 Spike Protein in Cultured Murine Alveolar Macrophages
https://www.mdpi.com/2218-1989/11/9/592/htm
2021: In Greek Navy SEALS undergoing (mindbendingly) strenuous exercise, their levels of anandamide, PEA & oleamide all increased, suggesting an adaptive ability of the ECS in helping with stress & heart-rate
Endocannabinoids and heart rate variability alterations after exposure to prolonged intensive physical exercise of the Hellenic Navy SEALs
https://academic.oup.com/eurheartj/article/42/Supplement_1/ehab724.2751/6394752
2021: Case study of PEA for the neuropathic pain of shingles
Palmitoylethanolamide (PEA) in the treatment of neuropathic pain: a case study
https://pubmed.ncbi.nlm.nih.gov/34289728/
2021: From Gencor, a paper reviewing the wonders of PEA
Palmitoylethanolamide: A Potential Alternative to Cannabidiol
https://pubmed.ncbi.nlm.nih.gov/34842030/
2021: Natural Product Insider’s Kristin McPhee on endocannabinoids & fatty acids to help our endocannabinoid system – with a nice focus on PEA
https://www.naturalproductsinsider.com/herbs-botanicals/endocannabinoids-beyond-hemp-and-cbd
2021: In rats with spinal cord injuries, PEA alleviated the injury, inhibited inflammation, mitigated oxidative stress, reduced cell death & promoted motor function recovery
PPARα agonist relieves spinal cord injury in rats by activating Nrf2/HO-1 via the Raf-1/MEK/ERK pathway
https://pubmed.ncbi.nlm.nih.gov/34799468/
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
https://pubmed.ncbi.nlm.nih.gov/33654018/
2021: In humans, CBD & PEA found safe for the skin
Tolerability Profile of Topical Cannabidiol and Palmitoylethanolamide: A Compilation of Single-Center Randomized Evaluator-Blinded Clinical and In Vitro Studies in Normal Skin
https://pubmed.ncbi.nlm.nih.gov/34022073/
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
https://www.sciencedirect.com/science/article/abs/pii/S0006295220306341
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
https://www.mdpi.com/2072-6643/13/8/2589
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
https://www.mdpi.com/2076-3921/10/3/464
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
https://pubmed.ncbi.nlm.nih.gov/33781184/
2021: In a human lung tissue model of COVID-19 infection, a combination of PEA & α-lipoic acid (ALA) reduced oxidative stress & lowered the cytokine storm
A Combination of α-Lipoic Acid (ALA) and Palmitoylethanolamide (PEA) Blocks Endotoxin-Induced Oxidative Stress and Cytokine Storm: A Possible Intervention for COVID-19
https://pubmed.ncbi.nlm.nih.gov/34405764/
2021: In a mouse model of traumatic brain injury (and a small clinical study), a combination of PEA & the flavonoid luteolin caused increased neurogenesis as well as improvements in memory recall
Co-Ultra PEALut Enhances Endogenous Repair Response Following Moderate Traumatic Brain Injury
https://pubmed.ncbi.nlm.nih.gov/34445417/
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
https://www.minervamedica.it/en/journals/minerva-orthopedics/article.php?cod=R14Y2021N03A0336
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
https://pubmed.ncbi.nlm.nih.gov/34340527/
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
https://www.mdpi.com/2072-6643/13/8/2589
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
https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.15409
2021: Case study of PEA for the neuropathic pain of shingles
Palmitoylethanolamide (PEA) in the treatment of neuropathic pain: a case study
https://pubmed.ncbi.nlm.nih.gov/34289728/
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
https://pubmed.ncbi.nlm.nih.gov/34202665/
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
https://pubmed.ncbi.nlm.nih.gov/34156697/
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
https://pubmed.ncbi.nlm.nih.gov/34056884/
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
https://www.sciencedirect.com/science/article/abs/pii/S0006291X21009335
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
https://pubmed.ncbi.nlm.nih.gov/34002020/
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
https://pubmed.ncbi.nlm.nih.gov/33781184/
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
https://www.mdpi.com/2076-3921/10/3/464
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
https://www.mdpi.com/1422-0067/22/6/3054/htm
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
https://europepmc.org/article/ppr/ppr309634
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
https://www.mdpi.com/2072-6643/13/3/734/htm
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
https://pubmed.ncbi.nlm.nih.gov/33654018/
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
https://www.mdpi.com/1422-0067/22/4/1967/htm
2021: In pregnant rats, even huge doses of PEA caused no measurable harms
Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats
https://pubmed.ncbi.nlm.nih.gov/33576293/
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
https://www.sciencedirect.com/science/article/abs/pii/S0006295220306341
2020: PEA for neurological disorders
Food supplements based on palmitoylethanolamide plus hydroxytyrosol from olive tree or Bacopa monnieri extracts for neurological diseases
https://pubmed.ncbi.nlm.nih.gov/33170159/
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
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236677/
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
http://www.sins.it/medias/860-congress-book.pdf#page=38
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
https://pubmed.ncbi.nlm.nih.gov/32825646/
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
https://www.mdpi.com/2076-3425/10/7/457
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
https://www.sciencedirect.com/science/article/abs/pii/S0024320520307876
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
https://www.nature.com/articles/s41598-020-67527-z
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
https://iovs.arvojournals.org/article.aspx?articleid=2764802
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
https://www.ncbi.nlm.nih.gov/pubmed/32248195
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
https://www.ncbi.nlm.nih.gov/pubmed/31054246
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)
https://www.ganjapreneur.com/drug-trial-planned-for-synthetic-cannabinoid-covid-19-treatment/
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
https://pubmed.ncbi.nlm.nih.gov/31863365/
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
https://pubmed.ncbi.nlm.nih.gov/32377286/
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
https://pubmed.ncbi.nlm.nih.gov/32106527/
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
https://pubmed.ncbi.nlm.nih.gov/32047441/
2020: Mechanistic study of how NAAA breaks down PEA
N-Acylethanolamine Acid Amidase (NAAA): Mechanism of Palmitoylethanolamide Hydrolysis Revealed by Mechanistic Simulations
https://pubs.acs.org/doi/abs/10.1021/acscatal.0c02903
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
https://pubmed.ncbi.nlm.nih.gov/32033363/
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
2015: In a rat model of cystitis, PEA protected the bladder, lessened pain & lowered urination
Protective effect of palmitoylethanolamide in a rat model of cystitis
https://pubmed.ncbi.nlm.nih.gov/25463999/
2015: In mice with damaged kidneys, PEA & silymarin combined to reduce “kidney dysfunction, histological damage, neutrophil infiltration and oxidative stress” and inhibited NF-κB and apoptosis pathways
Effects of Palmitoylethanolamide and Silymarin Combination Treatment in an Animal Model of Kidney Ischemia and Reperfusion
https://pubmed.ncbi.nlm.nih.gov/25981305/
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
https://pubmed.ncbi.nlm.nih.gov/26664738/
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
https://pubmed.ncbi.nlm.nih.gov/26491593/
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
https://pubmed.ncbi.nlm.nih.gov/26283633/
2015: In rats with pain, PEA delays the tolerance effects of morphine
Delay of Morphine Tolerance by Palmitoylethanolamide
https://pubmed.ncbi.nlm.nih.gov/25874232/
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
https://pubmed.ncbi.nlm.nih.gov/25951330/
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
https://pubmed.ncbi.nlm.nih.gov/25981305/
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
https://pubmed.ncbi.nlm.nih.gov/25934566/
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
https://pubmed.ncbi.nlm.nih.gov/25205418/
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
https://www.ncbi.nlm.nih.gov/pubmed/25637488
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
https://pubmed.ncbi.nlm.nih.gov/26260027/
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
https://pubmed.ncbi.nlm.nih.gov/25801844/
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
https://pubmed.ncbi.nlm.nih.gov/25765918/
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
https://pubmed.ncbi.nlm.nih.gov/24804094/
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
https://pubmed.ncbi.nlm.nih.gov/25071367/
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
https://pubmed.ncbi.nlm.nih.gov/24691823/
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
https://pubmed.ncbi.nlm.nih.gov/24423192/
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
https://pubmed.ncbi.nlm.nih.gov/25210802/
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
https://pubmed.ncbi.nlm.nih.gov/24818658/
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
https://pubmed.ncbi.nlm.nih.gov/24848354/
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
https://pubmed.ncbi.nlm.nih.gov/25164769/
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
https://pubmed.ncbi.nlm.nih.gov/24927796/
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
https://pubmed.ncbi.nlm.nih.gov/24082036/
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]
https://pubmed.ncbi.nlm.nih.gov/24051945/
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
https://pubmed.ncbi.nlm.nih.gov/24049461/
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
https://pubmed.ncbi.nlm.nih.gov/23206503/
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
https://pubmed.ncbi.nlm.nih.gov/23374874/
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
https://pubmed.ncbi.nlm.nih.gov/23917217/
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
https://pubmed.ncbi.nlm.nih.gov/23394519/
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
https://www.ncbi.nlm.nih.gov/pubmed/23813098
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
https://pubmed.ncbi.nlm.nih.gov/23394524/
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
https://pubmed.ncbi.nlm.nih.gov/23394526/
2013: In cells, PEA activated TRPV1, perhaps via PPARα
Activation and Desensitization of TRPV1 Channels in Sensory Neurons by the PPARα Agonist Palmitoylethanolamide
https://pubmed.ncbi.nlm.nih.gov/23083124/
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
https://pubmed.ncbi.nlm.nih.gov/23166447/
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
https://pubmed.ncbi.nlm.nih.gov/22845893/
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
https://pubmed.ncbi.nlm.nih.gov/22998138/
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
https://pubmed.ncbi.nlm.nih.gov/22912680/
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
https://pubmed.ncbi.nlm.nih.gov/23046519/
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
https://pubmed.ncbi.nlm.nih.gov/22884901/
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
https://pubmed.ncbi.nlm.nih.gov/22414817/
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
https://pubmed.ncbi.nlm.nih.gov/22469754/
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
https://pubmed.ncbi.nlm.nih.gov/22772472/
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
https://pubmed.ncbi.nlm.nih.gov/21890273/
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
https://pubmed.ncbi.nlm.nih.gov/22405189/
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
https://pubmed.ncbi.nlm.nih.gov/22244572/
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
https://pubmed.ncbi.nlm.nih.gov/22229320/
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
https://pubmed.ncbi.nlm.nih.gov/21554431/
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
https://pubmed.ncbi.nlm.nih.gov/20221904/
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
https://pubmed.ncbi.nlm.nih.gov/21354467/
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
https://pubmed.ncbi.nlm.nih.gov/21255263/
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
https://pubmed.ncbi.nlm.nih.gov/19864116/
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
https://pubmed.ncbi.nlm.nih.gov/19625089/
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
https://pubmed.ncbi.nlm.nih.gov/19386271/
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)
https://pubmed.ncbi.nlm.nih.gov/18181976/
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
https://pubmed.ncbi.nlm.nih.gov/18657182/
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
https://pubmed.ncbi.nlm.nih.gov/18367664/
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
https://pubmed.ncbi.nlm.nih.gov/18602217/
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
https://pubmed.ncbi.nlm.nih.gov/18695637/
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
https://pubmed.ncbi.nlm.nih.gov/17565008/
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
https://pubmed.ncbi.nlm.nih.gov/15465922/
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
https://www.ncbi.nlm.nih.gov/pubmed/12944505
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
https://www.ncbi.nlm.nih.gov/pubmed/12154273
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
https://pubmed.ncbi.nlm.nih.gov/12570018/
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
https://pubmed.ncbi.nlm.nih.gov/11485574/
2001: In kidney cells, PEA enhances AEA’s stimulation of VR1
Palmitoylethanolamide Enhances Anandamide Stimulation of Human Vanilloid VR1 Receptors
https://pubmed.ncbi.nlm.nih.gov/11602256/
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
https://pubmed.ncbi.nlm.nih.gov/8633002/
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
https://pubmed.ncbi.nlm.nih.gov/7724569/
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
https://pubmed.ncbi.nlm.nih.gov/7505999/
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
https://pubmed.ncbi.nlm.nih.gov/7397206/
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
https://pubmed.ncbi.nlm.nih.gov/392005/
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
https://pubmed.ncbi.nlm.nih.gov/1214924/
1975: First small pilot for rheumatic pain supported analgesic properties
Letter: Slow Encephalopathies, Inflammatory Responses, and Arachis Oil
https://pubmed.ncbi.nlm.nih.gov/51386/
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
https://pubmed.ncbi.nlm.nih.gov/4439865/
1972: In mice, PEA caused decreased mortality from a variety of immunological insults
Non-specific Resistance Induced by Palmitoylethanolamide
https://pubmed.ncbi.nlm.nih.gov/4561079/
1965: Bachur’s work finds PEA consistently present in brain, liver & muscle of rats and guinea pigs
FATTY ACID AMIDES OF ETHANOLAMINE IN MAMMALIAN TISSUES
https://pubmed.ncbi.nlm.nih.gov/14284696/
1957: Initial discovery paper
The identification of N-(2-hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent
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
https://pubmed.ncbi.nlm.nih.gov/31447580/
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
https://pubmed.ncbi.nlm.nih.gov/31269891/
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
https://www.ncbi.nlm.nih.gov/pubmed/31054246
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
https://pubmed.ncbi.nlm.nih.gov/30927159/
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
https://pubmed.ncbi.nlm.nih.gov/31355297/
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
https://pubmed.ncbi.nlm.nih.gov/31496832/
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
https://pubmed.ncbi.nlm.nih.gov/30858732/
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
https://pubmed.ncbi.nlm.nih.gov/31828153/
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
https://pubmed.ncbi.nlm.nih.gov/31244590/
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
https://pubmed.ncbi.nlm.nih.gov/31237065/
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
https://pubmed.ncbi.nlm.nih.gov/31316381/
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
https://pubmed.ncbi.nlm.nih.gov/30668378/
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
https://pubmed.ncbi.nlm.nih.gov/30970677/
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
https://pubmed.ncbi.nlm.nih.gov/30266286/
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
https://pubmed.ncbi.nlm.nih.gov/30955840/
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
https://pubmed.ncbi.nlm.nih.gov/30635472/
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
https://pubmed.ncbi.nlm.nih.gov/30660740/
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
https://pubmed.ncbi.nlm.nih.gov/31787870/
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
https://pubmed.ncbi.nlm.nih.gov/31878942/
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
https://pubmed.ncbi.nlm.nih.gov/29364513/
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
https://pubmed.ncbi.nlm.nih.gov/29486338/
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
https://pubmed.ncbi.nlm.nih.gov/30361792/
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
https://pubmed.ncbi.nlm.nih.gov/30177906/
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
https://pubmed.ncbi.nlm.nih.gov/29910726/
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
https://pubmed.ncbi.nlm.nih.gov/29593494/
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
https://pubmed.ncbi.nlm.nih.gov/29382825/
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
https://pubmed.ncbi.nlm.nih.gov/29552727/
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
https://pubmed.ncbi.nlm.nih.gov/30505308/
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
https://pubmed.ncbi.nlm.nih.gov/29615912/
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
https://pubmed.ncbi.nlm.nih.gov/29662433/
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
https://pubmed.ncbi.nlm.nih.gov/30058012/
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
https://pubmed.ncbi.nlm.nih.gov/30121836/
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
https://pubmed.ncbi.nlm.nih.gov/29576849/
2018: In rats with induced liver fibrosis, PEA protected via several mechanisms
Palmitoylethanolamide Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats
https://pubmed.ncbi.nlm.nih.gov/30057547/
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
https://pubmed.ncbi.nlm.nih.gov/29154284/
2018: PEA nanoparticles for intraocular delivery
Innovative Nanoparticles Enhance N-Palmitoylethanolamide Intraocular Delivery
https://pubmed.ncbi.nlm.nih.gov/29643808/
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
https://pubmed.ncbi.nlm.nih.gov/28321191/
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
https://pubmed.ncbi.nlm.nih.gov/29157725/
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
https://pubmed.ncbi.nlm.nih.gov/29258432/
2017: In 10 patients with pain, ultramicronized PEA helped
N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients With Chronic Pain
https://pubmed.ncbi.nlm.nih.gov/29210011/
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
https://pubmed.ncbi.nlm.nih.gov/28594885/
correction: https://pubmed.ncbi.nlm.nih.gov/30044864/
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
https://pubmed.ncbi.nlm.nih.gov/28095731/
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
https://pubmed.ncbi.nlm.nih.gov/28336953/
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
https://www.ncbi.nlm.nih.gov/pubmed/29311913/
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
https://pubmed.ncbi.nlm.nih.gov/28954820/
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
https://pubmed.ncbi.nlm.nih.gov/27623929/
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
https://pubmed.ncbi.nlm.nih.gov/28585337/
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
https://pubmed.ncbi.nlm.nih.gov/25598150/
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
https://pubmed.ncbi.nlm.nih.gov/26887427/
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
https://pubmed.ncbi.nlm.nih.gov/26815246/
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
https://pubmed.ncbi.nlm.nih.gov/26857391/
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
https://pubmed.ncbi.nlm.nih.gov/27227691/
a followup comment:
Ultramicronized Palmitoylethanolamide Treatment in Central Neuropathic Pain Following Longstanding Spinal Cord Injury: Try to Extinguish the Fire After Everything Was Burned
https://pubmed.ncbi.nlm.nih.gov/28301405/
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
https://pubmed.ncbi.nlm.nih.gov/27701827/
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
https://pubmed.ncbi.nlm.nih.gov/26844976/
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
https://pubmed.ncbi.nlm.nih.gov/25974242/
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
https://pubmed.ncbi.nlm.nih.gov/27219328/
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