Research database
Every study on this site, in one list. Type any word: a species, a symptom, a compound, a method. The search looks through the whole entry, not only the title.
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595 studies
- Effectiveness of an Oral Supplementation of Phycocyanin and Palmitoylethanolamide for a Short-Term Prophylaxis of Menstrual Migraine: A Retrospective Observational Study
This retrospective observational study found:
Observational studyHumansWith phycocyanin - Levagen+ (palmitoylethanolamide) alleviates joint pain and reduces the impact of joint pain in canines and felines: a double-blind, placebo-controlled, randomized clinical trial
The trial found:
Randomised controlled trialDogsCats - Palmitoylethanolamide (PEA) regulates cell cycle progression and promotes an anti-inflammatory transcriptomic signature in C2C12 skeletal muscle cells
The study found:
Laboratory studyOther animals - The Effects of Palmitoylethanolamide or Ibuprofen on the Abundance Profile and Synthesis Rate of Proteins in C2C12 Skeletal Myotubes
PEA increased synthesis of 101 proteins and reduced synthesis of 2, mostly ribosomal proteins; ibuprofen increased synthesis of 165 proteins and reduced 7, with broader changes across muscle contraction, extracellular matrix, carbohydrate and lipid metabolism proteins.
Laboratory studyOther animals - Expression of concern: "Adelmidrol, a Palmitoylethanolamide Analogue, as a New PharmacologicalTreatment for the Management of Inflammatory Bowel Disease" [Mol. Pharmacol. 2016; 90: 549-561] by Cordaro M, Impellizzeri D, Gugliandolo E, et al
The journal published an expression of concern for the 2016 paper "Adelmidrol, a Palmitoylethanolamide Analogue, as a New Pharmacological Treatment for the Management of Inflammatory Bowel Disease" by Cordaro M, Impellizzeri D, Gugliandolo E et al (PMID 27625036).
ReviewOther animals - Expression of concern: "Acute Intracerebroventricular Administration of Palmitoylethanolamide, an Endogenous Peroxisome Proliferator-α Activated Receptor-Agonist, Modulates Carrageenan-Induced Paw Edema in Mice" [J Pharmacol. Exp. Ther. 2007; 322: 1137-1143] by D'Agostino G, La Rana G, Russo R, et al
The journal published an expression of concern for the 2007 paper "Acute Intracerebroventricular Administration of Palmitoylethanolamide, an Endogenous Peroxisome Proliferator-Activated Receptor-Alpha Agonist, Modulates Carrageenan-Induced Paw Edema in Mice" by D'Agostino G, La Rana G, Russo R et al (PMID 17565008).
ReviewOther animals - Ultramicronized palmitoylethanolamide restores astrocyte-neuron metabolic coupling and Klotho/FGF21 signaling in a triple-transgenic mouse model of Alzheimer's disease
3xTg-AD mice showed lactate build-up, glutamine/glutamate imbalance, taurine depletion and reduced FGF21, Klotho and insulin receptor expression.
Laboratory studyOther animals - Low-dose combination of ultramicronized palmitoylethanolamide and docosahexaenoic acid on neurosteroid and neuroinflammatory dysregulation in autism spectrum disorders
This laboratory study found:
Laboratory studyOther animalsWith docosahexaenoic acid (DHA) - Expression of concern: "Effects of Palmitoylethanolamide on Signaling Pathways Implicated in the Development of Spinal Cord Injury" [J Pharmacol. Exp. Ther. 2008; 326: 12-23] by Genovese T, Esposito E, Mazzon E, et al
The journal published an expression of concern for the 2008 paper "Effects of Palmitoylethanolamide on Signaling Pathways Implicated in the Development of Spinal Cord Injury" by Genovese T, Esposito E, Mazzon E et al (PMID 18367664).
ReviewOther animals - Phospholipid-Based Delivery System Optimizes the Solubility and Systemic Exposure of Palmitoylethanolamide and Supports Clinical Benefits in Chronic Neuropathic Low Back Pain
The trial found:
Randomised controlled trialHumans - Comparison of effectiveness of a food supplement product versus Fosfomycin in the treatment of female recurrent urinary tract infections: Preliminary results of a multicenter comparative observational study
This multicenter observational study found:
Observational studyHumansWith D-mannose, N-acetylcysteine, Lactobacillus rhamnosus, hibiscus extract - Palmitoylethanolamide in Human and Animal Obesity
Given the inflammation-obesity link, the authors argue palmitoylethanolamide could be a strategy in human obesity, noting it is already sold as a veterinary food supplement.
ReviewHumansDogsCats - Palmitoylethanolamide for Nickel Allergy: Plausible, Untested, and Worth Considering
The authors propose that PEA, through PPAR-alpha signalling, mast cell stabilisation, reduced VEGF expression and improved gut barrier integrity, could address nickel allergic contact dermatitis and systemic nickel allergy syndrome.
ReviewHumans - Sustained Palmitoylethanolamide Infusion Restores Incentive Motivation and Synaptic Plasticity in the Tg2576 Mouse Model of Alzheimer's Disease
PEA rescued conditioned place preference performance in Tg2576 mice, increased dendritic spines in wild-type and Tg2576 mice in the entorhinal cortex and dentate gyrus, and increased PPAR-alpha and BDNF expression in the prefrontal cortex, including in mice without baseline deficits.
Laboratory studyOther animals - RETRACTED: Peritore et al. Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat. Int. J. Mol. Sci. 2020, 21, 3509
The journal retracted the article "Ultramicronised Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat" by Peritore AF et al (PMID 32429243).
ReviewOther animalsWith paracetamol - Efficacy, safety, and tolerability of palmitoylethanolamide in the management of diabetic neuropathic pain: a systematic review and meta-analysis
This meta-analysis found:
Meta-analysisHumans - Water-Dispersible Palmitoylethanolamide (PEA) Supplementation for Functional Improvement in Adults With Chronic Sciatica-Related Back Pain: A Pilot Clinical Trial
This pilot clinical trial found:
Open-label, no control groupHumansWith Acmella oleracea extract - Palmitoylethanolamide supplementation partly modulates eccentric exercise-induced changes in the bioactive lipid profile of skeletal muscle tissue
Many lipid mediators derived from arachidonic, docosahexaenoic, linoleic and alpha-linolenic acids fell 48 hours after exercise on placebo but stayed level or rose on PEA.
Randomised controlled trialHumans - Palmitoylethanolamide/Baicalin Supplementation and Changes in Pain and Sudomotor Function in Type 2 Diabetes: A Retrospective Matched Real-World Cohort Study
The median pain score fell from 5.5 to 3.0 in the supplement group (p < 0.0001) and did not change in the comparison group, which started at 2.0.
Observational studyHumansWith baicalin - Synergistic modulation of nociceptive and inflammatory pain by palmitoylethanolamide and Cucumis sativus extract in a monosodium-iodoacetate induced osteoarthritic rat model
The PEA plus Cucumis sativus combination improved pain thresholds and limb function more than either alone (p<0.0001) and cut serum IL-1beta and MMP-13 by about 50%.
Laboratory studyOther animalsWith Cucumis sativus extract (branded Ostizeel) - Temporal effects of Palmitoylethanolamide (PEA) in modulating knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled trial
This trial found:
Randomised controlled trialHumans - Targeting PTSD with ultramicronized palmitoylethanolamide: Results from a randomized trial integrating pharmacotherapy and cognitive behavioral therapy
The largest improvement was in the group given palmitoylethanolamide with therapy, where the PTSD score fell from 67.3 to 20.0.
Randomised controlled trialHumans - Probiotics and palmitoylethanolamide (PEA) for osteoarthritic pain: individual effects in a multiple baseline design study
This case series found:
Case seriesHumansWith probiotics (Bifidobacterium animalis BB12, Lactobacillus rhamnosus LGG, Saccharomyces boulardii) - Investigating Properties of Palmitoylethanolamide in Physiology and Disease: Far Beyond an Anti-Inflammatory Shield
The authors describe wide-ranging protective effects in laboratory work and report a good tolerability record in people, with minimal risk of drug interactions.
ReviewHumansOther animals - Serenoa Repens-Lycopene-Selenium and Epilobium-Palmitoylethanolamide-Calendula after transperineal prostate biopsy: a tertiary single center experience
The study found:
Observational studyHumansWith Epilobium and Calendula (with or without a saw palmetto, lycopene and selenium product) - Palmitoylethanolamide ameliorates postoperative cognitive dysfunction via microglial PPARα-mediated anti-inflammatory and neuroprotective mechanisms
PEA improved short- and long-term memory in aged mice with postoperative cognitive dysfunction.
Laboratory studyOther animals - N-Palmitoylethanolamide enhances antinociceptive effect of tramadol in neuropathic rats
PEA alone was about five times more potent than tramadol against hyperalgesia and about eight times more potent against allodynia.
Laboratory studyOther animalsWith tramadol - Phase 2 study of palmitoylethanolamide combined with luteoline in frontotemporal dementia patients
This phase 2 trial found:
Randomised controlled trialHumansWith luteolin - Retrospective Evaluation of L-Acetyl Carnitine and Palmitoylethanolamide as Add-On Therapy in Patients with Fibromyalgia and Small Fiber Neuropathy
A median fall of 19 points on the questionnaire in the add-on group (p < 0.001), versus 1 point in the standard care group (p = 0.12).
Observational studyHumansWith acetyl-L-carnitine, Boswellia serrata and vitamins B6 and E - Palmitoylethanolamide (PEA) Induces an Increase in Spleen Regulatory T Cells, Reduces CD8 + Cells and TNF-α Levels in Target Organs, and Protects Mice From Graft-Versus-Host Disease-Related Mortality Through PPAR Activation Without Compromising the Graft-Versus-Tumour Response
This lab study found:
Laboratory studyOther animals - Effective Management of Chronic Low Back Pain in the Elderly: A One-Year Cohort Study of Oxygen-Ozone Therapy Under CT Guidance Combined with Alpha Lipoic Acid, Palmitoylethanolamide, and Myrrh
At one month, 32.94% of patients reported excellent improvement, with mean VAS falling from 8.17 to 2.81.
Observational studyHumansWith alpha-lipoic acid and myrrh, alongside CT-guided oxygen-ozone paravertebral injections - Effects of palmitoylethanolamide in clinical high-risk for psychosis: A nonrandomized open-label trial
This open-label trial found:
Open-label, no control groupHumans - Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations
Most included trials rated good quality on the Joanna Briggs Institute tool, two rated fair.
ReviewHumans - Enhancement of peripheral fatty acyl ethanolamide signaling prevents stress-induced social avoidance and anxiety-like behaviors in male rats
URB937 prevented social avoidance after social defeat and anxiety-like behaviour after predator odour.
Laboratory studyOther animals - Unlocking Relief: Investigating the Impact of a Fixed Combination of Acetyl-L-Carnitine and Palmitoylethanolamide on Traumatic Acute Low Back Pain
The study found:
Observational studyHumansWith acetyl-L-carnitine, alpha-lipoic acid, Boswellia serrata, vitamins E and B6 - The Effects of a Food Supplement, Based on Co-Micronized Palmitoylethanolamide (PEA)–Rutin and Hydroxytyrosol, in Metabolic Syndrome Patients: Preliminary Results
The trial found:
Randomised controlled trialHumansWith rutin and hydroxytyrosol - Evaluation of the nutraceutical Palmitoylethanolamide in reducing intraocular pressure (IOP) in patients with glaucoma or ocular hypertension: a systematic review and meta-analysis
A significant reduction in intraocular pressure with palmitoylethanolamide across the pooled studies.
Meta-analysisHumans - Mechanisms and clinical applications of palmitoylethanolamide (PEA) in the treatment of neuropathic pain
Experimental evidence, the authors say, shows palmitoylethanolamide reduces pain and inflammation and lowers the need for other drugs.
ReviewHumans - The effects of formulated palmitoylethanolamide supplementation on indicators of stress and heart rate variability in female university students: a randomised cross-over trial
The trial found:
Randomised controlled trialHumans - Palmitoylethanolamide: A Multifunctional Molecule for Neuroprotection, Chronic Pain, and Immune Modulation
The review describes PEA acting mainly through PPAR-alpha, with additional effects via CB1/CB2, GPR55 and TRPV1.
ReviewHumansOther animals - Evaluation of N-palmitoylethanolamine (PEA) binding to nuclear receptors through docking and molecular dynamics studies
The simulations ranked hepatocyte nuclear factor 4 (gamma and alpha) and retinoic acid receptor gamma as the strongest predicted binders.
Laboratory studyOther animals - In Vitro Neuroprotective Effects of a Mixed Extract of Bilberry, Centella asiatica, Hericium erinaceus, and Palmitoylethanolamide
The combination preserved intestinal barrier integrity.
Laboratory studyOther animalsWith Hericium erinaceus, bilberry extract and Centella asiatica - Time-controlled online SPE: strategic approach for N-acylethanolamines quantification in complex matrices
The method measured PEA in horse plasma down to 0.27 ng/mL and reported what the authors describe as the first data on endogenous PEA and oleoylethanolamide levels in horses.
Laboratory studyHorses - Discovery of a long-acting nanocrystal formulation of INND-2201, a new co-drug of pregabalin and palmitoylethanolamide with synergistic analgesic effects
INND-2201 was slowly metabolised into pregabalin and PEA and produced synergistic antinociceptive effects orally, with ED50 values of 4.43 mg/kg (inflammatory pain) and 5.54 mg/kg (neuropathic pain).
Laboratory studyOther animalsWith INND-2201 (a co-drug combining pregabalin and PEA, tested as a single conjugate molecule) - Evaluation of the Clinical Efficacy of a Novel Palmitoylethanolamide–Equisetum arvense Supplement for the Management of Chronic Pain: Findings from a Prospective Clinical Trial
This trial found:
Open-label, no control groupHumansWith Equisetum arvense (horsetail) - Investigating Hybrid PLGA-Lipid Nanoparticles as an Innovative Delivery Tool for Palmitoylethanolamide to Muscle Cells
The hybrid nanoparticles had a mean size of about 150 nm, 79% encapsulation efficiency and drug loading of 44.2 mg/g, with enhanced drug release from amorphised PEA.
Laboratory studyOther animals - Pharmacokinetics of micronized and water dispersible palmitoylethanolamide in comparison with standard palmitoylethanolamide following single oral administration in male Sprague-Dawley rats
All PEA formulations raised total AUC and Cmax compared with non-micronised PEA.
Laboratory studyOther animals - Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial
This randomized trial found:
Randomised controlled trialHumansWith melatonin - Palmitoylethanolamide (Levagen+) for acute menstrual pain: a randomized, crossover, double-blind, placebo-controlled trial
Pain scores were lower on PEA than placebo at 1, 1.5, 2 and 2.5 hours (p = 0.045, 0.009, 0.015, 0.039), about 25 percent lower at 2.5 hours.
Randomised controlled trialHumans - Lipid mediator palmitoylethanolamide (PEA) inhibits pathogenic T cell differentiation in vitro and in vivo
PEA suppressed differentiation of Th1, Th17 and Th2 cells by inhibiting their master transcription factors, without affecting regulatory T cell differentiation.
Laboratory studyOther animals - Chronic palmitoylethanolamide administration via slow-release subcutaneous pellets promotes neuroprotection and mitigates neuroinflammation in the Tg2576 mouse model of Alzheimer's disease
An 8-fold fall in astrocyte activation and a 6-fold fall in oxidative protein damage in the hippocampus, less activation of microglia, restoration of nerve cell spine density to normal levels, and better recognition memory (novelty preference 57.5% against 44.5%).
Laboratory studyOther animals - A Decades-Long Journey of Palmitoylethanolamide (PEA) for Chronic Neuropathic Pain Management: A Comprehensive Narrative Review
The authors describe anti-inflammatory and pain-related effects through PPAR-alpha and the endocannabinoid system, and describe the safety and tolerability record as favourable.
ReviewHumans - Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding
The meta-analysis found:
Meta-analysisHumans - Palmitoylethanolamide in the Treatment of Pain and Its Clinical Application Prospects
Palmitoylethanolamide acts through PPAR-alpha and the endocannabinoid system across multiple targets, with a low rate of adverse reactions, mainly mild gastrointestinal discomfort and dizziness.
ReviewHumans - Lactiplantibacillus sp. LP03 alleviates pulmonary fibrosis by modulating gut microbiota and elevating host palmitoylethanolamide to suppress TGF-β1/Smad2/3-mediated EMT
The probiotic strain LP03 reduced mortality, inflammation, lung thickening, collagen deposition and EMT in bleomycin-treated mice, restored gut microbial balance and raised serum PEA.
Laboratory studyOther animals - A Sensitive Ultrahigh-Performance Liquid Chromatography/Tandem Mass Spectrometry Method for the Simultaneous Analysis of Phytocannabinoids and Endocannabinoids in Plasma and Brain
Calibration was linear (R2 > 0.99) from 0.02 to 500 ng/mL.
Laboratory studyOther animals - Therapeutic potential of clinically proven natural products in the management of dementia
Yokukansan, Souvenaid, BDW, Hupergene, Bacopa monnieri, omega-3, tramiprosate and palmitoylethanolamide are named as natural products with reported efficacy against dementia, with proposed mechanisms described.
ReviewHumans - Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study
This observational study found:
Observational studyHumans - Palmitoylethanolamide causes dose-dependent changes in brain function and the lipidome
An inverse dose response appeared in one imaging measure, with the lowest dose producing the largest effect, alongside a dose-dependent rise in functional connectivity.
Laboratory studyOther animals - Palmitoylethanolamide, an endogenous fatty acid amide, and its pleiotropic health benefits: A narrative review
Palmitoylethanolamide is described as having anti-inflammatory, antimicrobial, immunostimulatory, neuroprotective and pain-reducing actions, with high tolerability and safety reported in the animal and human studies cited.
ReviewHumansOther animals - Effect of Palmitoylethanolamide Compared to a Placebo on the Gut Microbiome and Biochemistry in an Overweight Adult Population: A Randomised, Placebo Controlled, Double-Blind Study
This randomised, placebo-controlled, double-blind study found:
Randomised controlled trialHumans - EXPRESSION OF CONCERN: Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism
The journal published an expression of concern for the 2017 paper "Beneficial Effects of Co-Ultramicronised Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism" by Bertolino B et al (PMID 27701827).
ReviewOther animalsHumansWith luteolin - Endocannabinoids, endocannabinoid-like compounds and cortisone in head hair of health care workers as markers of stress and resilience during the early COVID-19 pandemic
This observational study found:
Observational studyHumans - PEALut in the Dietary Management of Patients with Acute Ischemic Stroke: A Prospective Randomized Controlled Clinical Trial
This prospective randomized controlled trial found:
Controlled trialHumansWith luteolin (co-ultramicronised palmitoylethanolamide and luteolin, PEALut) - Assessing the biobehavioral effects of ultramicronized-palmitoylethanolamide monotherapy in autistic adults with different severity levels: a report of two cases
This case series found:
Case seriesHumans - The Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY) Study: An Open-Label Feasibility Trial of Ultramicronized-Palmitoylethanolamide Oral Supplementation in Clinical High-Risk State for Psychosis
This is a study protocol: it describes a planned single-arm, open-label, proof-of-concept trial and states its aims, but reports no outcome results in the abstract.
Open-label, no control groupHumans - Therapeutic Potential of Palmitoylethanolamide in Gastrointestinal Disorders
Benefit reported in irritable bowel and inflammatory bowel disease studies, with a lack of toxicity at high doses; the authors call for more human studies.
ReviewHumans - Effectiveness of Palmitoylethanolamide (Levagen+) Compared to a Placebo for Reducing Pain, Duration, and Medication Use during Migraines in Otherwise Healthy Participants—A Double-Blind Randomised Controlled Study
More migraine events resolved at 2 hours and at 8 hours in the Levagen+ group than in the placebo group, pain scores were lower at 1.5 and 4 hours, and rescue medication was used less often.
Randomised controlled trialHumans - Oleoylethanolamide and Palmitoylethanolamide Enhance IFNβ-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells
The study found:
Laboratory studyHumansWith interferon beta (co-exposure); oleoylethanolamide tested in parallel - Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics
The trial found:
Randomised controlled trialHumansWith luteolin; alpha-lipoic acid in two arms - Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain Related to Chronic Inflammatory Demyelinating Polyneuropathy: A Proof-of-Concept Study
Pain intensity (p = 0.0015), neuropathic pain symptoms (p = 0.0007) and quality of life (p = 0.0036) improved during treatment.
Open-label, no control groupHumans - Dysfunction in endocannabinoids, palmitoylethanolamide, and degradation of tryptophan into kynurenine in individuals with depressive symptoms
Kynurenine and the kynurenine to tryptophan ratio were associated with 2-AG, AEA and PEA, and these markers separated people with depressive symptoms from those without.
Observational studyHumans - Efficacy of mast cell directed therapies in irritable bowel syndrome: a systematic review
The review found:
ReviewHumansWith polydatin (palmitoylethanolamide-polydatin was one of the therapies reviewed) - Cannabinoids and Sleep: Exploring Biological Mechanisms and Therapeutic Potentials
This review reported:
ReviewHumans - Treatment of Established Chemotherapy-Induced Neuropathy with N-Palmitoylethanolamide: A Randomized, Double-Blind Phase II Pilot Study
The trial found:
Randomised controlled trialHumans - Palmitoylethanolamide and polydatin in pediatric irritable bowel syndrome: A multicentric randomized controlled trial
The trial found:
Randomised controlled trialHumansWith polydatin - Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy
The trial found:
Randomised controlled trialHumansWith superoxide dismutase, alpha lipoic acid, B vitamins, vitamin E, magnesium and zinc - Palmitoylethanolamide and Luteolin for Postinfectious Olfactory Disorders: How Clinically Meaningful Is Its Effect?
The supplement group improved in odour discrimination and overall smell scores, and the training-only group did not, the authors reported.
Randomised controlled trialHumansWith luteolin - PEA-OXA restores cognitive impairments associated with vitamin D deficiency-dependent alterations of the gut microbiota
PEA-OXA countered the cognitive impairment and the biochemical and electrophysiological changes seen in vitamin D deficient mice, which otherwise showed poorer cognition, impaired long-term potentiation and hippocampal neuroinflammation.
Laboratory studyOther animalsWith PEA-OXA (2-pentadecyl-2-oxazoline, a PEA analogue, tested alone) - The Effect of Palmitoylethanolamide (PEA) on Skeletal Muscle Hypertrophy, Strength, and Power in Response to Resistance Training in Healthy Active Adults: A Double-Blind Randomized Control Trial
This trial found:
Randomised controlled trialHumans - Formulated Palmitoylethanolamide Supplementation Improves Parameters of Cognitive Function and BDNF Levels in Young, Healthy Adults: A Randomised Cross-Over Trial
Serum BDNF rose more on palmitoylethanolamide than placebo (p = 0.0057), with better scores on two measures of one memory task.
Randomised controlled trialHumans - Revitalizing the skin: Exploring the role of barrier repair moisturizers
Moisturisers containing physiological lipids and functional ingredients such as palmitoylethanolamide, built on biomimic technology, are reported to benefit barrier-disrupted skin and to be generally well tolerated.
ReviewHumans - Nutraceutical formulation based on a synergic combination of melatonin and palmitoylethanolamide for the management of allergic events
The formulation reduced COX-2 mRNA transcription by 30% versus stimulated controls (p<0.0001) and inhibited COX-2 enzyme activity directly (IC50 152 micrograms/mL).
Laboratory studyHumansWith melatonin - Inflammatory-Targeted Lipid Carrier as a New Nanomaterial to Formulate an Inhaled Drug Delivery System
The study found:
Laboratory studyOther animals - Endocannabinoid-related molecules predict the metabolic efficacy of GLP-1 receptor agonism in humans with obesity
The study found:
Observational studyHumans - Palmitoylethanolamide in Postmenopausal Metabolic Syndrome: Current Evidence and Clinical Perspectives
Laboratory and preliminary clinical data suggest palmitoylethanolamide affects blood lipids, insulin sensitivity and inflammation through PPAR-alpha, the authors say.
ReviewHumansOther animals - Micronized/ultramicronized palmitoylethanolamide improves depression and fatigue in coronavirus disease 2019 (COVID-19) survivors
The study found:
Observational studyHumans - New insights in the mechanisms of opioid analgesia and tolerance: Ultramicronized palmitoylethanolamide down-modulates vascular endothelial growth factor-A in the nervous system
The study found:
Laboratory studyOther animalsWith morphine - Ultramicronized N-palmitoylethanolamine Contributes to Morphine Efficacy Against Neuropathic Pain: Implication of Mast Cells and Glia
The study found:
Laboratory studyOther animalsWith morphine - Efficacy of Palmitoylethanolamide, Epilobium and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III
After one month all measures improved from baseline, including the symptom index (median 18.6 at baseline), urinary white cells, PSA and pain VAS.
Open-label, no control groupHumansWith Epilobium and Calendula extract - Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain
Micron-size forms have higher oral efficacy than plain powder, cross the gut wall and blood-brain barrier, and can be used as an add-on to analgesics, with animal data showing they limit opioid tolerance.
ReviewHumansOther animals - Associations between Social Adversity and Biomarkers of Inflammation, Stress, and Aging in Children
Cumulative social adversity was associated with higher levels of all inflammatory markers and with cortisol in a U-shaped pattern, but there were no significant relationships between cumulative adversity and cortisone, the neuromodulation biomarkers (including PEA) or epigenetic ageing.
Observational studyHumans - Infectious disease for the rhinologist
COVID-19 olfactory dysfunction is reported to vary by variant, with olfactory training remaining the main treatment; platelet-rich plasma injections and oral ultramicronised palmitoylethanolamide plus luteolin are noted to have shown early results.
ReviewHumansWith luteolin (ultramicronised palmitoylethanolamide with luteolin, as discussed in the review) - Efficacy of Topical Palmitoylethanolamide (Levagen+) for the Management of Eczema Symptoms: A Double-Blind, Comparator-Controlled, Randomized Clinical Trial
This double-blind, comparator-controlled, randomized trial found:
Randomised controlled trialHumansTopical - Palmitoylethanolamide-Incorporated Elastic Nano-Liposomes for Enhanced Transdermal Delivery and Anti-Inflammation
PEA-ENL showed efficient transdermal delivery and skin retention with negligible toxicity toward HaCaT cells and no allergic reaction in the human skin patch test.
Laboratory studyHumansOther animalsTopical - Absorption, anti-inflammatory, antioxidant, and cardioprotective impacts of a novel fasting mimetic containing spermidine, nicotinamide, palmitoylethanolamide, and oleoylethanolamide: A pilot dose-escalation study in healthy young adult men
Plasma PEA, oleoylethanolamide and 1-methylnicotinamide rose after the supplement in a dose-dependent way.
Randomised controlled trialHumansWith spermidine, nicotinamide, oleoylethanolamide - Prevention of Protease-Induced Degradation of Desmoplakin via Small Molecule Binding
Several molecules, including sodium dodecyl sulfate, palmitoylethanolamide, GW0742, salirasib, eprosartan mesylate and GSK1838705A, prevented degradation of wild-type and disease-variant desmoplakin by trypsin and calpain without changing protease activity.
Laboratory studyOther animals - Ultramicronized Palmitoylethanolamide and Luteolin: Drug Candidates in Post-COVID-19 Critical Illness Neuropathy and Positioning-Related Peripheral Nerve Injury of the Upper Extremity
This is presented as the first reported successful treatment of post-COVID-19 critical illness neuropathy with positioning-related nerve injury using ultramicronised palmitoylethanolamide and luteolin, described as a pilot case.
Case seriesHumansWith luteolin - Neuropathic pain in cats: Mechanisms and multimodal management
This presents a structured approach to recognising and managing neuropathic pain in cats, drawing on the literature and the author's own experience.
ReviewCats - Palmitoylethanolamide Does Not Affect Recovery from Exercise-Induced Muscle Damage in Healthy Males
Palmitoylethanolamide did not improve soreness, strength or jump performance, and had no effect on molecular markers of muscle damage or repair.
Randomised controlled trialHumans - Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis
This meta-analysis found:
Meta-analysisHumans - Emerging drugs for the treatment of irritability associated with autism spectrum disorder
This review found:
ReviewHumans - The Comparative Efficacy of Palmitoylethanolamide (PEA) With the Combination of Pregabalin and Nortriptyline on Post-extraction Trigeminal Neuropathy by Using Magnetic Resonance (MR) Neurography: A Randomized Clinical Trial
All three groups had a significant decrease in mean pain scores after treatment, with the combination group showing the greatest reduction.
Randomised controlled trialHumansWith pregabalin and nortriptyline (a separate comparator arm, and also combined with palmitoylethanolamide in a third arm) - Palmitoylethanolamide (PEA) for Prevention of Gastroesophageal Inflammation: Insights from In Vitro Models
PEA reduced the inflammatory response caused by HCl exposure, and this effect was greater when combined with the plant extracts.
Laboratory studyHumansWith Zingiber officinale, Musa × paradisiaca, Opuntia ficus-indica and Olea europaea plant extracts - A Fixed Combination of Palmitoylethanolamide and Melatonin (PEATONIDE) for the Management of Pain, Sleep, and Disability in Patients with Fibromyalgia: A Pilot Study
This pilot study found:
Open-label, no control groupHumansWith melatonin - Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice through Oral Administration of Palmitoylethanolamide
Palmitoylethanolamide reduced clinical signs of colitis, reduced gross mucosal injury and suppressed leukocyte recruitment at inflamed venules in DSS-induced experimental colitis.
Laboratory studyOther animals - N-palmitoylethanolamide attenuates negative emotions induced by morphine withdrawal in mice
Palmitoylethanolamide reduced anxiety- and depression-like behaviours linked to morphine withdrawal and reduced serotonin, noradrenaline and dopamine levels in the hippocampus and prefrontal cortex.
Laboratory studyOther animals - Adelmidrol ameliorates liver ischemia-reperfusion injury through activating Nrf2 signaling pathway
Adelmidrol reduced liver ischaemia-reperfusion injury in mice.
Laboratory studyOther animalsWith adelmidrol (a PEA analogue, tested alone) - Lysosome targeting fluorescent probe for NAAA imaging and its applications in the drug development for anti-inflammatory
The study found:
Laboratory studyOther animals - A Brief Review on the Novel Therapies for Painful Diabetic Neuropathy
First-line drugs, capsaicin and spinal cord stimulation are covered alongside newer targets such as NMDA receptors and the endocannabinoid system.
ReviewHumans - Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence
This systematic review found:
ReviewHumans - The Effect of Levagen+ (Palmitoylethanolamide) Supplementation on Symptoms of Allergic Rhinitis—A Double-Blind Placebo-Controlled Trial
This double-blind placebo-controlled trial found:
Randomised controlled trialHumans - Efficacy of Palmitoylethanolamide and Luteolin Association on Post-Covid Olfactory Dysfunction: A Systematic Review and Meta-Analysis of Clinical Studies
The meta-analysis found:
Meta-analysisHumansWith luteolin - Genetic Knockout of Fatty Acid Amide Hydrolase Ameliorates Cisplatin-Induced Nephropathy in Mice
Faah knockout mice had less cisplatin kidney injury than wild-type mice, with higher PEA and OEA, lower NF-kappa-B activity, DNA damage markers and IL-1 beta, and less macrophage and leukocyte infiltration.
Laboratory studyOther animalsHumans - Palmitoylethanolamide: A Potential Alternative to Cannabidiol
CBD's evidence base is insufficient and its regulatory status unclear, the authors say.
ReviewHumans - To Go Where Nature Leads: Focus on Palmitoylethanolamide and Related ALIAmides as Innovative Approach to Neuroinflammatory and Pain-Related Disease States in Honor of Doctor Francesco Della Valle
The PubMed abstract is truncated to a single word, so no findings can be reported here.
ReviewHumans - N-palmitoylethanolamide synergizes the antinociception of morphine and gabapentin in the formalin test in mice
This laboratory study found:
Laboratory studyOther animalsWith morphine and gabapentin (each tested separately in combination with palmitoylethanolamide) - Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial
The trial found:
Randomised controlled trialHumansWith luteolin - Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?
This study found:
Observational studyHumansWith luteolin (co-ultramicronised PEA-LUT), with olfactory training - Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial
PEA-LUT with olfactory training improved quantitative smell loss compared with training alone, but the effect on parosmia was limited.
Randomised controlled trialHumansWith luteolin (co-ultramicronised PEA-LUT), with olfactory training - Effect of palmitoylethanolamide on degeneration of a human-derived retinal pigment epithelial cell induced by all-trans retinal
Palmitoylethanolamide reduced ARPE-19 cell death and reactive oxygen species (including mitochondrial ROS) triggered by all-trans retinal, improved retinal function, protected retinal pigment epithelial and photoreceptor cells from death, and lessened light-induced fundus damage in the mouse model.
Laboratory studyHumansOther animals - Antidepressant Medication Does Not Contribute to the Elevated Circulating Concentrations of Acylethanolamides Found in Substance Use Disorder Patients
This observational study found:
Observational studyHumans - Longitudinal course of endocannabinoids and N-acylethanolamines in hair of mothers and their children in the first year postpartum: investigating the relevance of maternal childhood maltreatment experiences
This observational study found:
Observational studyHumans - A randomised controlled trial assessing the potential of palmitoylethanolamide (PEA) to act as an adjuvant to resistance training in healthy adults: a study protocol
This is a protocol only; no results are reported.
Randomised controlled trialHumans - Dietary oleic acid contributes to the regulation of food intake through the synthesis of intestinal oleoylethanolamide
This laboratory study found:
Laboratory studyOther animals - G protein-coupled receptor 55 activated by palmitoylethanolamide is associated with the development of nocturia associated with circadian rhythm disorders
GPR55 was mainly in the urothelial layer.
Laboratory studyOther animals - Ramulus Cinnamomi essential oil exerts an anti-inflammatory effect on RAW264.7 cells through N-acylethanolamine acid amidase inhibition
This laboratory study found:
Laboratory studyHumansOther animals - Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density
The study found:
Observational studyHumans - Optimization of Fermentation Conditions and Metabolite Profiling of Grape Juice Fermented with Lactic Acid Bacteria for Improved Flavor and Bioactivity
The study found:
Laboratory studyOther animals - Inhibiting immunoregulatory amidase NAAA blocks ZIKV maturation in Human Neural Stem Cells
Inhibiting NAAA reduced Zika replication by about one log10 in human neural stem cells and led to release of immature, non-infectious virions, linked to impaired furin cleavage of prM that blocked viral maturation.
Laboratory studyHumans - Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials
Pain scores improved with a pooled standardised mean difference of 1.68 in favour of palmitoylethanolamide (95% CI 1.05 to 2.31), though heterogeneity was high (I² = 93%).
Meta-analysisHumans - Alpha-Lipoic Acid, Palmitoylethanolamide, Myrrh, and Oxygen-Ozone Therapy Improve Pharmacological Therapy in Acute Painful Lumbosacral Radiculopathy due to Herniated Disc
The trial found:
Controlled trialHumansWith alpha-lipoic acid and myrrh - Changes in plasma endocannabinoids concentrations correlate with 18F-FDG PET/MR uptake in brown adipocytes in humans
AEA, EPEA and OEA fell during cooling in both groups, more steeply in those with active brown fat.
Observational studyHumans - Sex differences in endocannabinoid tone in a pilot study of cannabis use disorder and acute cannabis abstinence
The study found:
Observational studyHumans - Effect of an Enteroprotective Complementary Feed on Faecal Markers of Inflammation and Intestinal Microbiota Composition in Weaning Puppies
The trial found:
Controlled trialDogsWith bovine colostrum and Bacillus subtilis (Normalia Extra, Innovet) - Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosis in vivo
PEA alone did not significantly prolong survival or reduce fungal burden.
Laboratory studyOther animalsWith amphotericin B (in one arm; palmitoylethanolamide also tested alone) - A randomized interventional clinical trial assessing the safety and effectiveness of PeaNoc XL tablets in managing joint pain and inflammation in arthritis patients
All four inflammatory markers fell from baseline in the add-on group (TNF-alpha p < 0.01, IL-1 beta p < 0.001, IL-6 p < 0.01, CRP p < 0.01), and WOMAC pain, stiffness and function also improved from baseline; the standard-therapy group showed no significant change.
Open-label, no control groupHumansWith astaxanthin - Hair endocannabinoids predict physiological fear conditioning and salivary endocannabinoids predict subjective stress reactivity in humans
Salivary endocannabinoids predicted subjective stress responses but not cortisol reactivity.
Observational studyHumans - Activation of cannabinoid type 1 receptor (CB1) modulates oligodendroglial process branching complexity in rat hippocampal cultures stimulated by olfactory ensheathing glia-conditioned medium
Olfactory ensheathing glia expressed CB1, FAAH and MAGL, and released anandamide, 2-AG, PEA and OEA.
Laboratory studyOther animals - Intrarectal Administration of Adelmidrol plus Hyaluronic Acid Gel Ameliorates Experimental Colitis in Mice and Inhibits Pro-Inflammatory Response in Ex Vivo Cultured Biopsies Derived from Ulcerative Colitis-Affected Patients
The gel reduced the histological damage score and increased ZO-1 and occludin expression in both the mouse model and the human specimens.
Laboratory studyHumansOther animalsWith adelmidrol (a PEA analogue) with hyaluronic acid, as a gel - Role of PPAR-Allopregnanolone Signaling in Behavioral and Inflammatory Gut-Brain Axis Communications
Stress and obesogenic diets are proposed to suppress PPAR-alpha in brain, gut, fat and immune cells, favouring inflammation and mood instability, while PPAR-alpha modulators, including palmitoylethanolamide, are said to improve microbiome composition, inflammation and anxiety or depression in rodent models.
ReviewHumansOther animals - Palmitoylethanolamide counteracts high-fat diet-induced gut dysfunction by reprogramming microbiota composition and affecting tryptophan metabolism
Inflammatory markers in the colon were lower, serotonin was higher and kynurenine lower, with a shift in gut bacteria towards butyrate-producing types.
Laboratory studyOther animals - What Is the Role of Palmitoylethanolamide Co-Ultramicronized with Luteolin on the Symptomatology Reported by Patients Suffering from Long COVID? A Retrospective Analysis Performed by a Group of General Practitioners in a Real-Life Setting
All patient-reported symptoms improved with supplementation, especially pain, mood, fatigue, brain fog and smell and taste.
Observational studyHumansWith luteolin - Exploring the Protective Effect against 7,12-Dimethylbenz[a]anthracene-Induced Breast Tumors of Palmitoylethanolamide
Palmitoylethanolamide reduced tumour area and volume, increased average oxygen saturation and decreased total haemoglobin (indicating reduced hypoxia-driven blood vessel growth), and reduced DMBA-driven liver and kidney toxicity on histopathology.
Laboratory studyOther animals - Isolation and characterization of N-(2-Hydroxyethyl)hexadecanamide from Colletotrichum gloeosporioides with apoptosis-inducing potential in breast cancer cells
Palmitoylethanolamide was isolated from Colletotrichum gloeosporioides.
Laboratory studyHumans - The Efficacy of Palmitoylethanolamide (Levagen+) on the Incidence and Symptoms of Upper Respiratory Tract Infection—A Double Blind, Randomised, Placebo-Controlled Trial
This double-blind, randomised, placebo-controlled trial found:
Randomised controlled trialHumans - Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study
A 36-hour fast changed the plasma metabolome and had immunomodulatory effects on macrophages.
Open-label, no control groupHumansOther animals - Novel Approach to the Treatment of Neuropathic Pain Using a Combination with Palmitoylethanolamide and Equisetum arvense L. in an In Vitro Study
The combination crossed the intestinal barrier model without cytotoxicity, reached the nerve model, and modulated nerve recovery after Schwann cell injury.
Laboratory studyOther animalsWith Equisetum arvense L. (horsetail) extract - Palmitoylethanolamide and acetyl-L-carnitine act synergistically with duloxetine and pregabalin in fibromyalgia: results of a randomised controlled study
The add-on group showed further improvement on all three measures: the pain index (p = 0.048), the impact questionnaire (p = 0.033) and the status questionnaire (p = 0.017).
Randomised controlled trialHumansWith acetyl-L-carnitine - Orofacial Pain Management: An Overview of the Potential Benefits of Palmitoylethanolamide and Other Natural Agents
Clinical data on palmitoylethanolamide in orofacial pain are still lacking, the authors say, and they set out the mechanism case for testing it.
ReviewHumans - Exploring Outcome Priorities and Real-Life Management of Chemotherapy-Induced Peripheral Neurotoxicity: A Survey of the Italian Association for the Study of Pain members
This survey found:
Observational studyHumans - In Vitro and In Vivo Safety of Hyaluronic Acid-Decorated Microparticles for Intravitreal Injection of Palmitoylethanolamide, Citicoline, or Glial-Cell-Derived Neurotrophic Factor
This safety study found:
Laboratory studyHumansOther animals - Sphingosine Kinases at the Intersection of Pro-Inflammatory LPS and Anti-Inflammatory Endocannabinoid Signaling in BV2 Mouse Microglia Cells
This laboratory study found:
Laboratory studyOther animals - Distribution of an analgesic palmitoylethanolamide and other N-acylethanolamines in human placental membranes
This laboratory study found:
Laboratory studyHumans - Micronized Palmitoylethanolamide, Hempseed Oil, and Maritime Pine Bark Dry Extract (Pelvipea®) for Pelvic Pain: An In Vitro Study for Urothelial Inflammation Treatment
This in vitro study found:
Laboratory studyHumansWith hempseed oil and maritime pine bark dry extract (combined as Pelvipea) - Labour and premature delivery differentially affect the expression of the endocannabinoid system in the human placenta
This laboratory study found:
Laboratory studyHumans - Could serum endocannabinoid and N-acylethanolamine levels be important in bipolar disorder?
PEA levels were higher, and OEA and 2-AG lower, in patients with at least one lifetime depressive episode than in those with none; anandamide did not differ.
Observational studyHumans - Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
Morphine increased mast cell degranulation, which PEA pretreatment prevented.
Laboratory studyOther animals - Assay of NAAA Activity
NAAA prefers palmitoylethanolamide as a substrate at acidic pH, and NAAA inhibitors show anti-inflammatory and analgesic actions in animal models, the chapter reports.
Laboratory studyOther animals - Neuro-Gastro-Cannabinology: A Novel Paradigm for Regulating Mood and Digestive Health
The authors describe the endocannabinoid system's role in gut motility, permeability, secretion, immunity and visceral pain, and its two-way relationship with the microbiota and mood.
ReviewHumans - A Combination of α-Lipoic Acid (ALA) and Palmitoylethanolamide (PEA) Blocks Endotoxin-Induced Oxidative Stress and Cytokine Storm: A Possible Intervention for COVID-19
The combination reduced reactive oxygen species and nitric oxide and modulated the main cytokines, whether given before or after LPS.
Laboratory studyHumansWith alpha-lipoic acid - Endocannabinoid and perceived stress: Association analysis of endocannabinoid levels in hair versus levels in plasma and urine
No association was found between hair levels and plasma or urine levels of endocannabinoids or N-acylethanolamines.
Observational studyHumans - Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome
The trial found:
Randomised controlled trialHumansWith luteolin - Quantification of Analgesic and Anti-Inflammatory Lipid Mediators in Long-Term Cryopreserved and Freeze-Dried Preserved Human Amniotic Membrane
The study found:
Laboratory studyHumans - Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies
Corticosteroid nasal sprays shortened smell loss compared with several alternatives, and were more effective than palmitoylethanolamide plus luteolin, omega-3 supplementation and olfactory training.
ReviewHumansWith luteolin (palmitoylethanolamide and luteolin was one of the comparators reviewed) - Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages
The study found:
Laboratory studyOther animals - N-palmitoylethanolamine modulates hippocampal neuroplasticity in rats with stress-induced depressive behavior phenotype
PEA improved the depression-like phenotype, prevented the stress-induced fall in BrdU-positive cells, increased BrdU/NeuN co-localisation and raised synaptic protein levels in the hippocampus.
Laboratory studyOther animals - Proteomics and metabolomics profiling reveal panels of circulating diagnostic biomarkers and molecular subtypes in stable COPD
The study found:
Observational studyHumans - Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania: A randomized, double-blind, placebo-controlled trial
This randomized, double-blind, placebo-controlled trial found:
Randomised controlled trialHumans - Herbal Cannabis Use Is Not Associated with Changes in Levels of Endocannabinoids and Metabolic Profile Alterations among Older Adults
This open-label study found:
Open-label, no control groupHumans - Review of Alzheimer's disease drugs and their relationship with neuron-glia interaction
The abstract gives no specific findings on palmitoylethanolamide.
ReviewHumansOther animals - Melatonin synergizes with the antinociceptive effect of N-palmitoylethanolamide and paracetamol
All three compounds produced a concentration-dependent antinociceptive effect, with palmitoylethanolamide more potent (EC30 7.4±0.2 mg/paw) than melatonin (EC30 20.5±3.1 mg/paw) or paracetamol (EC30 41.8±2.6 mg/paw).
Laboratory studyOther animalsWith melatonin and paracetamol - Effects of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Stages: A Case–Control Study
CRP, IL-6 and neutrophil-to-lymphocyte ratio were lower in the treated group at 28 days, with lower D-dimer and higher antibody levels.
Controlled trialHumans - Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α
This lab study found:
Laboratory studyHumansOther animals - Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders
Actions through PPAR-alpha, GPR55 and TRPV1 are described, alongside early clinical signs of effect on cortical plasticity in frontotemporal dementia.
ReviewHumansOther animalsWith luteolin - Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease
Chronic treatment eased the decrease in complex-I respiration rate and complex V (FoF1-ATPase) activity and the drop in ATP content in cortical mitochondria, but did not improve impaired mitochondrial bioenergetics or depolarisation-induced glutamate release in the hippocampus.
Laboratory studyOther animals - Inhibition of triple negative breast cancer-associated inflammation and progression by N- acylethanolamine acid amide hydrolase (NAAA)
This lab study found:
Laboratory studyHumansOther animals - Antioxidant and Anti-Inflammatory Activity of Combined Phycocyanin and Palmitoylethanolamide in Human Lung and Prostate Epithelial Cells
The phycocyanin and palmitoylethanolamide combination protected against cytotoxicity and reduced both reactive oxygen species production and inflammatory cytokine transcription.
Laboratory studyHumansWith phycocyanin - Oxygen-Ozone Therapy Associated with Alpha Lipoic Acid Plus Palmitoylethanolamide and Myrrh versus Ozone Therapy in the Combined Treatment of Sciatic Pain Due to Herniated Discs: Observational Study on 318 Patients
Complete remission in 76.4 percent with ozone alone and 77.8 percent with ozone plus the supplement.
Observational studyHumansWith alpha-lipoic acid and myrrh - New Approach to Chronic Back Pain Treatment: A Case Control Study
In Group A, complete remission of pain was recorded in 206 patients (83.7%) at one week, 191 (77.6%) at three months and 178 (72.3%) at six months.
Controlled trialHumansWith alpha-lipoic acid and myrrh, with CT-guided periradicular oxygen-ozone injections - Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence
In animal models, supplementation reduced seizure frequency and severity, in some cases comparably to antiseizure drugs, with pretreatment more effective.
ReviewOther animals - Lipidomics of Cell Secretome Combined with the Study of Selected Bioactive Lipids in an In Vitro Model of Osteoarthritis
TNF-alpha raised PGE2 release, and 2-AG raised it further.
Laboratory studyHumans - Distribution of Cannabinoid Receptors in Keratinocytes of Healthy Dogs and Dogs With Atopic Dermatitis
Keratinocytes of both healthy and atopic dogs showed all seven receptors.
Laboratory studyDogs - Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long-term cannabis users: A secondary analysis of a case-control study
The study found:
Observational studyHumans - Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
In animal models the compound improved memory and learning and reduced oxidative, inflammatory and astrocyte markers, with the authors noting the protective effect may matter less once disease is established.
Meta-analysisHumansOther animals - The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice
Ultramicronised palmitoylethanolamide reduced the development of hypersensitivity, which went with reduced spinal and hippocampal pro-inflammatory cytokines and reduced depressive- and anxiety-like behaviours.
Laboratory studyOther animals - Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study
Odour identification improved by an average of 10.7 points at 3 months (p < 0.0001), with improvements in parosmia and in mental clouding.
Open-label, no control groupHumansWith luteolin - Oral Adelmidrol Administration Up-Regulates Palmitoylethanolamide Production in Mice Colon and Duodenum through a PPAR-γ Independent Action
Adelmidrol increased palmitoylethanolamide levels in the duodenum and colon in a dose- and time-dependent manner and increased expression of the enzymatic machinery for palmitoylethanolamide metabolism.
Laboratory studyOther animalsWith adelmidrol (a PEA analogue, tested alone) - Palmitoylethanolamide and Related ALIAmides for Small Animal Health: State of the Art
Studies in dogs and cats covered here include an open multi-centre trial of 160 dogs given 10 mg/kg a day for 56 days and the cat trial by Noli and colleagues.
ReviewDogsCats - Why Use Nutraceutical Strategies for the Irritable Bowel Syndrome?
These compounds act through several mechanisms, including restoring the microbiota, strengthening the gut barrier, and immunomodulatory, anti-inflammatory and antinociceptive actions.
ReviewHumans - Intestinal Disorder in Zebrafish Larvae (Danio rerio): The Protective Action of N-Palmitoylethanolamide-oxazoline
Repeated DSS exposure caused gut alteration with increased mucus production and increased inflammatory and endoplasmic-reticulum stress gene expression.
Laboratory studyOther animalsWith N-palmitoylethanolamide-oxazoline (PEA-OXA, a PEA analogue, tested alone) - Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo-Controlled Clinical Trial
The trial found:
Randomised controlled trialHumansWith luteolin - Investigational drugs for the treatment of olfactory dysfunction
Comparing topical and systemic treatment results can suggest whether an olfactory disorder has a peripheral or central origin, the authors argue, and treatments tested in COVID-19 smell loss might also be options for neurodegenerative olfactory disease.
ReviewHumans - Central GPR55 may prevent nicotine reinforcing actions: a preliminary study
Injections of LPI, PEA, the GPR55 agonist ML184 and the GPR55 antagonist ML193 each interfered with nicotine-induced place preference.
Laboratory studyOther animals - Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons
This laboratory study found:
Laboratory studyOther animals - Co-Ultramicronized Palmitoylethanolamide/Luteolin Restores Oligodendrocyte Homeostasis via Peroxisome Proliferator-Activated Receptor-α in an In Vitro Model of Alzheimer's Disease
Beta-amyloid 1-42 triggered astrocyte reactivity and inflammation, reduced growth factors needed for oligodendrocyte precursor cell maturation, and left oligodendrocytes with low surface area and few arborisations.
Laboratory studyOther animalsWith luteolin (co-ultramicronised with palmitoylethanolamide, PEALut) - Palmitoylethanolamide Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial
Soluble P-selectin fell in the palmitoylethanolamide group compared with placebo (P = 0.0078), as did IL-1 beta and IL-2.
Randomised controlled trialHumans - Palmitoylethanolamide (PEA) Inhibits SARS-CoV-2 Entry by Interacting with S Protein and ACE-2 Receptor
This laboratory study found:
Laboratory studyHumans - α-Acylamino-β-lactone N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors Encapsulated in PLGA Nanoparticles: Improvement of the Physical Stability and Protection of Human Cells from Hydrogen Peroxide-Induced Oxidative Stress
The nanoparticles had a single-size population, were stable over time and temperature, retained the compound well and improved its photostability compared with the free molecule.
Laboratory studyHumansWith URB866 (a NAAA inhibitor that raises the body's own palmitoylethanolamide), loaded in PLGA nanoparticles; PEA itself was not given - Palmitoylethanolamide-based nutraceutical Calmux in preventive treatment of migraine
Headache days fell from 10 to 6.6 a month, painkiller days from 9.2 to 4.1, and pain intensity from 8.1 to 5 out of 10 (all p < 0.005).
Open-label, no control groupHumans - The endocannabinoid system and related lipids as potential targets for the treatment of migraine-related pain
Endocannabinoids and PEA appear to reduce trigeminal pain signalling through several migraine-related pathways in animal models, and inhibiting endocannabinoid-degrading enzymes has been a research focus, the authors report.
ReviewHumansOther animals - Targeting Neuroinflammation in Osteoarthritis with Intra-Articular Adelmidrol
This review states:
ReviewHumansOther animalsWith adelmidrol (a PEA analogue) with high molecular weight hyaluronic acid, by intra-articular injection - Circulating Endocannabinoids in Canine Multicentric Lymphoma Patients
PEA, oleoylethanolamide and anandamide were higher in dogs with lymphoma than in healthy dogs.
Observational studyDogs - Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management
This observational study found:
Observational studyHumans - Palmitoylethanolamide attenuates neurodevelopmental delay and early hippocampal damage following perinatal asphyxia in rats
This laboratory study found:
Laboratory studyOther animals - Effects of fatty acid metabolites on nocturia
This laboratory study found:
Laboratory studyOther animals - Looking for Responders among Women with Chronic Pelvic Pain Treated with a Comicronized Formulation of Micronized Palmitoylethanolamide and Polydatin
More than half of women were good responders.
Meta-analysisHumansWith polydatin - MED1/BDNF/TrkB pathway is involved in thalamic hemorrhage-induced pain and depression by regulating microglia
This laboratory study found:
Laboratory studyOther animalsHumansWith luteolin (co-ultramicronised PEA plus luteolin, PEALut) - Aerosol-Administered Adelmidrol Attenuates Lung Inflammation in a Murine Model of Acute Lung Injury
Aerosol adelmidrol reduced LPS-induced lung damage and airway infiltration, reduced mast cell numbers and chymase and tryptase expression, raised antioxidant enzymes, and reduced NF-kB activation and pro-inflammatory cytokines.
Laboratory studyOther animalsWith adelmidrol (a PEA analogue, tested alone) - Palmitoylethanolamide (PEA) in the treatment of neuropathic pain: a case study
Pain relief was effective within 48 hours of starting palmitoylethanolamide at 900 mg per day, the author reports.
Case seriesHumans - Dietary supplements for intestinal inflammation
Remission in IBD is achieved in under 50% of cases, the authors say, and they propose adding supplements such as probiotics, butyrate, phosphatidylcholine, lactoferrin, palmitoylethanolamide, silymarin and omega-3 to the diet.
ReviewHumans - Endocannabinoid System in Polycystic Kidney Disease
Patients had higher IL-6 and IL-1b and lower plasma AEA, 2-AG and related lipids than healthy people.
Observational studyHumans - Effects of omega-3 supplementation on components of the endocannabinoid system and metabolic and inflammatory responses in adipose and liver of peripartum dairy cows
The trial found:
Controlled trialOther animals - Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis
The meta-analysis found:
Meta-analysisHumans - Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice
Treated obese mice explored the open centre of the arena more (6.94 against 4.07 m), had lower TNF-alpha and IL-1 beta in blood, restored GABA levels in the amygdala, and showed less activation of brain immune cells.
Laboratory studyOther animals - Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans
Laboratory evidence points to protective and anti-inflammatory effects in models of the major neurodegenerative diseases, the authors report.
ReviewHumansOther animals - The Effect of Palmitoylethanolamide on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers—A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial
Repeated heat pain fell, cold and heat pain tolerance rose, pressure tolerance and conditioned pain modulation increased, and wind-up and allodynia decreased after palmitoylethanolamide.
Randomised controlled trialHumans - N-Acylethanolamine acid amidase (NAAA) exacerbates psoriasis inflammation by enhancing dendritic cell (DCs) maturation
The study found:
Laboratory studyHumansOther animals - Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review
The review found:
ReviewHumansWith Reviewed studies included PEA-combination medicines (partners not named in the abstract) alongside cannabis products - Metabolomics of bronchoalveolar lavage in children with persistent wheezing
Children with persistent wheezing had a distinct lung metabolome, with higher choline, oleamide, butyrylcarnitine, palmitoylethanolamide and several phosphatidylcholines.
Observational studyHumans - Levels of bioactive endogenous lipids and health-related quality of life in Chronic Idiopathic Axonal Polyneuropathy
Patients with neuropathic pain had lower 2-AG (P = 0.03) but no difference in PEA (P = 0.95), OEA or SEA.
Observational studyHumans - The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?
Enteric glia are immune-competent cells supporting gut barrier integrity, neuroprotection, motility and sensation, and the authors summarise how endocannabinoid receptors, enzymes and ligands including palmitoylethanolamide might modulate them.
ReviewHumansOther animals - The multitarget FAAH inhibitor/D3 partial agonist ARN15381 decreases nicotine self-administration in male rats
ARN15381 dose-dependently reduced self-administration of a high nicotine dose but not a lower dose.
Laboratory studyOther animalsWith ARN15381 (a FAAH inhibitor and D3 partial agonist), URB597 and CJB090; palmitoylethanolamide itself was not given - Synergistic antinociceptive effects of concomitant NAAA and peripheral FAAH inhibition
Each inhibitor on its own reduced pain behaviour and paw inflammation.
Laboratory studyOther animalsWith URB937 (a peripheral FAAH inhibitor) and ARN19702 (a NAAA inhibitor), enzyme inhibitors that raise the body's own palmitoylethanolamide and anandamide; PEA itself was not given - Non-drug pain relievers active on non-opioid pain mechanisms
Preclinical and clinical findings together suggest these compounds deserve closer attention, and combinations of a few act on many pain pathways, the authors say.
ReviewHumansOther animals - Design, Characterization, and In Vitro Assays on Muscle Cells of Endocannabinoid-like Molecule Loaded Lipid Nanoparticles for a Therapeutic Anti-Inflammatory Approach to Sarcopenia
The study found:
Laboratory studyOther animals - Profound Modification of Fatty Acid Profile and Endocannabinoid-Related Mediators in PPARα Agonist Fenofibrate-Treated Mice
Fenofibrate reduced weight gain, food intake, feed efficiency and liver lipids, sharply reduced essential fatty acids such as 18:3n3, and increased 16:1n7 and 18:1n9.
Laboratory studyOther animals - Experience with nutraceutical supplements in the treatment of pelvic pain in gynaecology: case reports
Pelvic pain and dyspareunia were largely resolved with the multimodal approach, which included the alpha-lipoic acid, palmitoylethanolamide and myrrh supplement, and other analgesic, anti-inflammatory and antineuropathic medicines could be reduced or withdrawn, the author reports for each case.
Case seriesHumansWith alpha-lipoic acid and myrrh (a nutraceutical supplement), within a multimodal programme that also included hormone therapy, antineuropathic drugs, injections, behavioural and physical interventions - Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction
For PEA plus luteolin versus no intervention, only a single 12-person RCT was found, and the authors rate the certainty of evidence as very low across all outcomes, saying they cannot draw meaningful conclusions from the numerical results.
ReviewHumansWith luteolin (in the included trial) - Comprehensive lipidomics of lupus-prone mice using LC-MS/MS identifies the reduction of palmitoylethanolamide that suppresses TLR9-mediated inflammation
This laboratory study found:
Laboratory studyOther animals - Targeting NAAA counters dopamine neuron loss and symptom progression in mouse models of parkinsonism
The toxins raised NAAA and lowered PEA in cells and mouse dopamine neurons.
Laboratory studyHumansOther animalsWith NAAA gene deletion or NAAA inhibitors, which raise the body's own palmitoylethanolamide; PEA itself was not given - The Expanded Endocannabinoid System Contributes to Metabolic and Body Mass Shifts in First-Episode Schizophrenia: A 5-Year Follow-Up Study
First-episode psychosis was marked by higher N-acylethanolamine concentrations, including palmitoylethanolamide, and lower 2-AG.
Observational studyHumans - Therapeutic Potential of Diacerein in Management of Pain
Diacerein and rhein appear to affect several pain mediators, including palmitoylethanolamide, though the authors say clinical trials and mechanism studies are still needed.
ReviewHumansOther animals - A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain
Total pain, pain interference and NPSI scores were lower than placebo from week 2 onward (P ≤ 0.001), with better sleep and mood scores and lower IL-6 and CRP.
Randomised controlled trialHumans - The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study
This retrospective cohort study found:
Observational studyHumans - Could Palmitoylethanolamide Be an Effective Treatment for Long-COVID-19? Hypothesis and Insights in Potential Mechanisms of Action and Clinical Applications
Palmitoylethanolamide is put forward as a possible treatment for long-COVID, particularly fatigue and myalgia, reasoning from its proposed anti-inflammatory and cytokine-modulating properties and a hypothesised role for mitochondrial dysfunction in long-COVID.
ReviewHumans - Endocannabinoid and steroid analysis in infant and adult nails by LC-MS/MS
This observational study found:
Observational studyHumans - Anti-inflammatory Effect of Cannabidiol and Palmitoylethanolamide Containing Topical Formulation on Skin in a 12-O-Tetradecanoylphorbol-13-Acetate-Induced Dermatitis Model in Mice
This laboratory study found:
Laboratory studyOther animalsTopicalWith cannabidiol - Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial
This randomized, double-blinded, placebo-controlled trial found:
Randomised controlled trialHumans - Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate
This study of MS patients found:
Observational studyHumans - First Evidence of the Protective Effects of 2-Pentadecyl-2-Oxazoline (PEA-OXA) in In Vitro Models of Acute Lung Injury
This in vitro study found:
Laboratory studyHumansWith PEA-OXA (2-pentadecyl-2-oxazoline, a PEA analogue, tested alongside ultramicronised PEA) - Mutual Links between the Endocannabinoidome and the Gut Microbiome, with Special Reference to Companion Animals: A Nutritional Viewpoint
Gut dysbiosis and altered endocannabinoidome tone interact, the authors say, and this may relate to gastrointestinal and metabolic disease and neuroinflammatory disorders.
ReviewDogsCatsHumans - Palmitoylethanolamide gels edible oils
This study found:
Laboratory studyOther animals - Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence
This meta-analysis found:
Meta-analysisHumans - Cannabinoids for the Treatment of Dermatologic Conditions
Selective CB2 agonists were reported effective in diffuse cutaneous systemic sclerosis and dermatomyositis; dronabinol for trichotillomania; sublingual CBD and THC for pain in epidermolysis bullosa.
ReviewHumans - Sex differences in endocannabinoids during 3 years of Mediterranean diet intervention: Association with insulin resistance and weight loss in a population with metabolic syndrome
This study found:
Observational studyHumans - Investigating the Long-Term Effect of an Interdisciplinary Multimodal Rehabilitation Program on Levels of Bioactive Lipids and Telomerase Activity in Blood from Patients with Chronic Pain
This open-label study found:
Open-label, no control groupHumans - Effects of Gabexate Mesylate on the Gut Microbiota and Metabolomics in Rats with Sepsis
This study found:
Laboratory studyOther animals - Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications
The authors summarise PEA's analgesic, neuroprotective, immune-modulating and anti-inflammatory actions and recent findings that PEA-containing formulations promote oligodendrocyte differentiation, the first step in myelin formation.
ReviewHumansOther animals - Interventions for Improving Long COVID-19 Symptomatology: A Systematic Review
Only two intervention studies met the criteria.
ReviewHumansWith luteolin, with olfactory rehabilitation (in the included trial) - Alterations of Stress-Related Glucocorticoids and Endocannabinoids in Hair of Chronic Cocaine Users
The study found:
Observational studyHumans - Novel Drug Candidate Prediction for Intrahepatic Cholangiocarcinoma via Hub Gene Network Analysis and Connectivity Mapping
151 key genes and 10 hub genes were identified.
Laboratory studyHumans - Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses
The study found:
Laboratory studyOther animalsWith NAAA gene deletion (CRISPR-Cas9) or the NAAA inhibitor F96, which raise the body's own palmitoylethanolamide; PEA itself was not given - Modulation of type 1 cannabinoid receptor activity by cannabinoid by-products from Cannabis sativa and non-cannabis phytomolecules
The cannabinoids tested showed partial agonist activity at CB1R, and the phytomolecules modulated delta-9-THC-dependent binding and signalling in vitro and in vivo.
Laboratory studyOther animals - Intrapersonal Stability of Plasma Metabolomic Profiles over 10 Years among Women
The study found:
Observational studyHumans - Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies
The review found:
Meta-analysisHumans - Palmitoylethanolamide ameliorates neuroinflammation via modulating PPAR-α to promote the functional outcome after intracerebral hemorrhage
Palmitoylethanolamide reduced neuroinflammation by inhibiting upregulation of NF-kB, IL-1beta and TNF-alpha, both in cells and in mice, improved motor function and promoted hematoma clearance after intracerebral haemorrhage.
Laboratory studyOther animals - Vitamin D Deficiency Induces Chronic Pain and Microglial Phenotypic Changes in Mice
This lab study found:
Laboratory studyOther animals - Bioactive lipids in inflammatory bowel diseases - From pathophysiological alterations to therapeutic opportunities
The abstract does not single out palmitoylethanolamide findings or give numbers.
ReviewHumansOther animals - The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele
PPAR-alpha and TLR4 both play a part in how varicocele affects the testis, based on changes in these receptors and downstream markers across wild-type and knockout mice given PEA-um.
Laboratory studyOther animals - Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Model of Inflammatory Pain
The combined product at 5 mg/kg reduced swelling, heat sensitivity, mast cell infiltration and inflammatory markers, more than either compound alone at higher doses, and more than a 200 mg/kg plain mixture.
Laboratory studyOther animalsWith acetyl-L-carnitine - Altered endocannabinoid-dynamics in craniopharyngioma patients and their association with HPA-axis disturbances
This observational study found:
Observational studyHumans - Hair-based biomarkers in women with major depressive disorder: Glucocorticoids, endocannabinoids, N-acylethanolamines, and testosterone
Women with depression had lower hair cortisol and cortisone than controls.
Observational studyHumans - A Phase-2 Pilot Study of a Therapeutic Combination of Delta-9-Tetrahydracannabinol and Palmitoylethanolamide for Adults With Tourette's Syndrome
This phase-2 pilot study found:
Open-label, no control groupHumansWith delta-9-tetrahydrocannabinol (THC) - Palmitoylethanolamide/Luteolin as Adjuvant Therapy to Improve an Unusual Case of Camptocormia in a Patient with Parkinson's Disease: A Case Report
Adding um-PEALut to carbidopa/levodopa improved dyskinesia and reduced camptocormia.
Case seriesHumansWith luteolin (co-ultramicronised with palmitoylethanolamide, um-PEALut) - Effectiveness of Nonpharmacologic Treatments of Burning Mouth Syndrome: A Systematic Review
This review of burning mouth syndrome treatments found:
ReviewHumans - PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis
Both compounds reduced the hypersensitivity that oxaliplatin produced, and PEA-OXA did so more than ultramicronised PEA.
Laboratory studyOther animalsWith PEA-OXA (2-pentadecyl-2-oxazoline, a PEA analogue, tested alongside ultramicronised PEA) - Co-Ultra PEALut Enhances Endogenous Repair Response Following Moderate Traumatic Brain Injury
The study found:
Laboratory studyHumansOther animalsWith luteolin (co-ultramicronised PEA plus luteolin, Glialia) - Palmitoylethanolamide: A Natural Compound for Health Management
PEA is well tolerated and without side effects in animals and humans, say the authors, who list applications in immunity, brain health, allergy, pain, joint health, sleep and recovery.
ReviewHumansOther animals - Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
Altered PEA and endocannabinoid levels and receptor expression are reported in autism.
ReviewHumansOther animals - N-Acylethanolamine Acid Amidase Inhibition Potentiates Morphine Analgesia and Delays the Development of Tolerance
The study found:
Laboratory studyOther animalsWith AM11095 (a brain-permeable NAAA inhibitor that raises the body's own palmitoylethanolamide) given with morphine; PEA itself was not given - Palmitoylethanolamide Modulation of Microglia Activation: Characterization of Mechanisms of Action and Implication for Its Neuroprotective Effects
Palmitoylethanolamide lowered the inflammatory signals produced after the toxin, kept microglia in their branched resting shape, cut calcium responses by about 45 to 49%, and abolished seizure-like over-activity in nerve cell networks.
Laboratory studyOther animals - Ultramicronized Palmitoylethanolamide in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation
Ultramicronised palmitoylethanolamide reduced alteration of coagulation markers and pro-inflammatory cytokine release in plasma and lung caused by LPS infusion, prevented fibrin deposition and lung damage, and reduced mast cell numbers and their serine protease release.
Laboratory studyOther animals - Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia
Testosterone caused BPH-like changes with raised DHT, androgen receptor and 5-alpha-reductase, plus more inflammation, apoptosis and oxidative stress.
Laboratory studyOther animalsWith baicalein - Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer's Disease
Treated mice had stronger colon contractions (19.46 against 8.98 g per g of tissue), less amyloid in the colon, lower IL-1 beta, and less bacterial toxin in the blood (25.85 against 67.8 ng/mL).
Laboratory studyOther animals - Randomized clinical trial "olfactory dysfunction after COVID-19: olfactory rehabilitation therapy vs. intervention treatment with Palmitoylethanolamide and Luteolin": preliminary results
The trial found:
Randomised controlled trialHumansWith luteolin - Spinal nociceptive sensitization and plasma palmitoylethanolamide levels during experimentally induced migraine attacks
Plasma PEA rose at 120 minutes in the migraine group but not in controls.
Controlled trialHumans - Endocannabinoid markers in autism spectrum disorder: A scoping review of human studies
This review found:
ReviewHumans - Ultramicronized Palmitoylethanolamide Inhibits NLRP3 Inflammasome Expression and Pro-Inflammatory Response Activated by SARS-CoV-2 Spike Protein in Cultured Murine Alveolar Macrophages
Spike protein exposure increased all measured inflammatory markers and ACE-2 expression in a concentration-dependent way.
Laboratory studyOther animals - Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?
The authors say the evidence supports micronised palmitoylethanolamide as a dietary add-on for chronic pain in dogs and cats, alongside standard treatment rather than in place of it.
ReviewDogsCats - Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?
The evidence supports a place for micronised palmitoylethanolamide in the dietary management of chronic pain in dogs and cats, the authors say.
ReviewDogsCats - Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats
No treatment-related effect on any maternal, reproductive or fetal measure at any dose.
Laboratory studyOther animals - Discovery and SAR Evolution of Pyrazole Azabicyclo[3.2.1]octane Sulfonamides as a Novel Class of Non-Covalent N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA) Inhibitors for Oral Administration
The authors identified compound 50 (ARN19689), which inhibited human NAAA at low nanomolar concentration (IC50 0.042 micromolar) by a non-covalent mechanism and was systemically available.
Laboratory studyHumansOther animals - A Palmitoylethanolamide Producing Lactobacillus paracasei Improves Clostridium difficile Toxin A-Induced Colitis
This laboratory study found:
Laboratory studyOther animals - Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice
Co-administration of the engineered bacteria and palmitate released PEA over time and reduced clinical and histological damage, neutrophil infiltration, pro-inflammatory cytokines and oxidative stress markers, with improved epithelial barrier integrity.
Laboratory studyOther animals - Co-Ultramicronized Palmitoylethanolamide/Luteolin-Induced Oligodendrocyte Precursor Cell Differentiation is Associated With Tyro3 Receptor Upregulation
Tyro3 mRNA rose during OPC differentiation and PEALut increased this rise further, while reducing Axl and Mertk expression.
Laboratory studyOther animalsWith luteolin (co-ultramicronised PEA/luteolin, PEALut) - N-acylethanolamine regulation of TLR3-induced hyperthermia and neuroinflammatory gene expression: A role for PPARα
This laboratory study found:
Laboratory studyOther animals - NAAA-regulated lipid signaling governs the transition from acute to chronic pain
Disabling NAAA in the spinal cord within 72 hours of injury halted the development of chronic pain in male and female mice.
Laboratory studyOther animalsWith Small-molecule NAAA inhibitors, which raise the body's own palmitoylethanolamide; PEA itself was not given - Antinociceptive Profile of ARN19702, (2-Ethylsulfonylphenyl)-[(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone, a Novel Orally Active N-Acylethanolamine Acid Amidase Inhibitor, in Animal Models
This laboratory study found:
Laboratory studyOther animals - N-acylethanolamine acid amidase (NAAA) inhibition decreases the motivation for alcohol in Marchigian Sardinian alcohol-preferring rats
This laboratory study found:
Laboratory studyOther animalsWith ARN19702, ARN077 and ARN726 (NAAA inhibitors that raise endogenous PEA and OEA, tested alone) - Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO-1 and NF-kB Pathways
PEA/rutin treatment reduced the vascular morphology change caused by carotid ligation, along with MCP-1, ICAM-1, the cytokines IL-1beta, IL-6 and TNF-alpha, and markers of oxidative and nitrosative stress.
Laboratory studyOther animalsWith rutin - Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats
This laboratory study found:
Laboratory studyOther animals - Different roles for the acyl chain and the amine leaving group in the substrate selectivity of N-Acylethanolamine acid amidase
Catalytic efficiency depended strictly on fatty acyl chain length in both saturated and monounsaturated substrates, while the enzyme tolerated a wider range of polar head changes.
Laboratory studyOther animals - The Role of PPAR Alpha in the Modulation of Innate Immunity
PPAR-alpha suppresses inflammatory reactions and modulates innate immune cells, with examples from parasitic, bacterial and viral infections, the authors summarise.
ReviewHumansOther animals - Characterization of the peripheral FAAH inhibitor, URB937, in animal models of acute and chronic migraine
This laboratory study found:
Laboratory studyOther animalsWith URB937 (a FAAH inhibitor that raises endogenous PEA and anandamide, tested alone) - Involvement of the γ Isoform of cPLA2 in the Biosynthesis of Bioactive N- Acylethanolamines
This laboratory study found:
Laboratory studyOther animals - The immune system and autism spectrum disorder: association and therapeutic challenges
Immune involvement in autism spectrum disorder shows up as microbiome and gut-brain axis changes, higher pro-inflammatory cytokines in patients, and more autoimmune disorders in first-degree relatives.
ReviewHumans - Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy
Palmitoylethanolamide improved liver function and reduced hepatic pathological changes, lipid accumulation and fibrosis in MCD-diet mice.
Laboratory studyOther animals - GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide
Oleoylethanolamide and palmitoylethanolamide are reported to affect glucose balance, inflammation, anaphylaxis, pain and appetite, acting through nuclear receptors, ion channels and membrane receptors including PPAR-alpha, TRPV1, GPR119 and GPR55.
ReviewHumansOther animals - Effectiveness of a nutraceutical agent in the non-surgical periodontal therapy: a randomized, controlled clinical trial
Pocket depth (p = 0.003) and bleeding (p < 0.001) improved more at 6 months in the supplement group, with better attachment gains at 30 and 60 days, lower inflammatory markers, and lower pain scores in the two days after treatment.
Randomised controlled trialHumansWith baicalin - Anti-inflammatory activity of palmitoylethanolamide ameliorates osteoarthritis induced by monosodium iodoacetate in Sprague-Dawley rats
The laboratory study found:
Laboratory studyOther animals - PEA prevented early BBB disruption after cerebral ischaemic/reperfusion (I/R) injury through regulation of ROCK/MLC signaling
PEA inhibited the enzyme ROCK2 and reduced early barrier disruption after oxygen-glucose deprivation.
Laboratory studyOther animals - Palmitoylethanolamide counteracts brain fog improving depressive-like behaviour in obese mice: Possible role of synaptic plasticity and neurogenesis
The study found:
Laboratory studyOther animals - NAAA inhibitor F96 attenuates BBB disruption and secondary injury after traumatic brain injury (TBI)
The study found:
Laboratory studyOther animalsWith F96 (a NAAA inhibitor that raises the body's own palmitoylethanolamide); PEA itself was not given - Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgery in rabbits by suppressing canonical and non-canonical TGFβ signaling through PPARα
PEA reduced postoperative inflammation and fibroproliferation and prevented scar formation through PPAR-alpha; blocking PEA breakdown with F96 gave the same result.
Laboratory studyOther animals - Implications of dysregulated endogenous cannabinoid family members in the pathophysiology of endometriosis
Plasma endocannabinoids did not differ between patients and controls, but palmitoylethanolamide was significantly higher in endometriosis lesions than in patients' own endometrium, while CB2 receptor expression was lower in lesions.
Observational studyHumansOther animals - Palmitoylethanolamide and hemp oil extract exert synergistic anti-nociceptive effects in mouse models of acute and chronic pain
The study found:
Laboratory studyOther animalsWith hemp oil extract - Tolerability profile of topical cannabidiol and palmitoylethanolamide: a compilation of single-centre randomized evaluator-blinded clinical and in vitro studies in normal skin
The study found:
Controlled trialHumansTopicalWith cannabidiol - Design and Structure-Activity Relationships of Isothiocyanates as Potent and Selective N-Acylethanolamine-Hydrolyzing Acid Amidase Inhibitors
The compounds produced were low nanomolar inhibitors of human NAAA with more than 100-fold selectivity over other enzymes, plasma half-life above 2 hours and microsomal half-life of about 15 to 30 minutes.
Laboratory studyHumansOther animals - A Glucuronic Acid-Palmitoylethanolamide Conjugate (GLUPEA) Is an Innovative Drug Delivery System and a Potential Bioregulator
GLUPEA raised cellular PEA and 2-AG more than the same concentration of PEA and increased 2-AG-induced TRPV1 desensitisation.
Laboratory studyOther animalsWith GLUPEA (a glucuronic acid-PEA conjugate prodrug, tested against ultramicronised PEA) - Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort
Alpha diversity was directly associated with anhedonia/amotivation (beta -0.37; 95% CI -0.71 to -0.03; P=0.03).
Observational studyHumans - Endocannabinoids and Heart Rate Variability Alterations after Exposure to Prolonged Intensive Physical Exercise of the Hellenic Navy SEALs
After intense physical exercise, hair AEA, PEA and OEA were notably increased, while 2-AG did not change.
Observational studyHumans - In vivo brain levels of acetylcholine and 5-hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement
Both OEA and PEA significantly increased acetylcholine and 5-hydroxytryptamine levels in the basal forebrain.
Laboratory studyOther animals - Conjugated Linoleic Acid and Brain Metabolism: A Possible Anti-Neuroinflammatory Role Mediated by PPARα Activation
CLA is taken up and metabolised in brain tissue, where it induces synthesis of the endogenous PPAR-alpha ligands palmitoylethanolamide and oleoylethanolamide, possibly through a positive feedback loop, the authors say.
ReviewHumansOther animals - Different Dietary N-3 Polyunsaturated Fatty Acid Formulations Distinctively Modify Tissue Fatty Acid and N-Acylethanolamine Profiles
Different n-3 sources changed tissue fatty acids and N-acylethanolamine levels in distinct ways.
Laboratory studyOther animals - Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients
Drawing on earlier laboratory and clinical work, the authors propose that palmitoylethanolamide's effects on immune response and inflammation could limit organ damage in COVID-19, while noting pharmacokinetic data are limited.
ReviewHumansOther animals - Burning mouth syndrome: a review of therapeutic approach
The author lists pharmacological treatments used for burning mouth syndrome, including capsaicin, clonazepam, low-dose aripiprazole, alpha-lipoic acid, duloxetine, amitriptyline, gabapentin, pregabalin and ultramicronised palmitoylethanolamide, plus non-pharmacological options such as cognitive therapy, laser therapy, acupuncture and rTMS.
ReviewHumans - Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects
um-PEA inhibited cancer cell proliferation via PPAR-alpha and GPR55, caused G2/M cell cycle arrest (linked to cyclin B1/CDK1 upregulation) and DNA fragmentation, and reduced cell migration by lowering MMP2 and raising TIMP1.
Laboratory studyHumansOther animals - Impact of Circulating N-Acylethanolamine Levels with Clinical and Laboratory End Points in Hemodialysis Patients
This observational study found:
Observational studyHumans - NAPE-specific phospholipase D regulates LRRK2 association with neuronal membranes
Loss of NAPE-PLD, the enzyme that makes N-acylethanolamines such as palmitoylethanolamide from NAPEs, caused NAPEs to accumulate, shifted LRRK2 from membranes to cytosol and reduced total LRRK2.
Laboratory studyHumansOther animals - Efficacy of a fixed combination of palmitoylethanolamide and acetyl-l-carnitine (PEA+ALC FC) in the treatment of neuropathies secondary to rheumatic diseases
Pain VAS improved more in the combination group across all three conditions (sciatica p = 0.032, carpal tunnel p = 0.025, lower-limb neuropathy p = 0.041), and the condition-specific scores also favoured the combination.
Controlled trialHumansWith 82 patients with rheumatoid arthritis or spondyloarthritis and a neuropathy under 12 months old confirmed by electromyography: 42 given the combination on top of standard therapy (18 sciatica, 16 carpal tunnel, 8 lower-limb neuropathy) and 40 matched patients on standard therapy alone (20, 15 and 5) - Management of Acute Lung Injury: Palmitoylethanolamide as a New Approach
um-PEA reduced lung tissue damage, the wet/dry weight ratio, myeloperoxidase activity, immune cell infiltration and mast cell degranulation after LPS challenge, and lowered IL-6, IL-1beta, TNF-alpha and IL-18 release while reducing NF-kappa-B and MAPK (ERK1/2, JNK, p38) activation.
Laboratory studyOther animals - PEA/Polydatin: Anti-Inflammatory and Antioxidant Approach to Counteract DNBS-Induced Colitis
Oral PEA/polydatin reduced macroscopic and histological colon damage, neutrophil infiltration, cytokine release, malondialdehyde, nitrotyrosine, PARP, ICAM-1 and P-selectin, while inhibiting NF-kappa-B and increasing SIRT-1 and Nrf2 expression.
Laboratory studyOther animalsWith polydatin (comicronised with ultramicronised PEA) - Phytotherapics in COVID19: Why palmitoylethanolamide?
No PEA-specific data on COVID-19 are reported.
ReviewHumans - Roles of Endocannabinoids and Endocannabinoid-Like Molecules in Energy Homeostasis and Metabolic Regulation: A Nutritional Perspective
Endocannabinoids are described as stimulating feeding and lipid and glucose anabolism, while oleoylethanolamide suppresses appetite.
ReviewHumansOther animals - Palmitoylethanolamide for sleep disturbance. A double-blind, randomised, placebo-controlled interventional study
This randomised, double-blind, placebo-controlled study found:
Randomised controlled trialHumans - Micronized / ultramicronized palmitoylethanolamide (PEA) as natural neuroprotector against COVID-19 inflammation
One 45-year-old woman with COVID-19 was, in the authors' words, treated with success using micronised and ultramicronised PEA.
ReviewHumans - Impaired Duodenal Palmitoylethanolamide Release Underlies Acid-Induced Mast Cell Activation in Functional Dyspepsia
This laboratory study found:
Laboratory studyHumansOther animals - The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: a double-blind, randomized, placebo-controlled proof-of-concept study
This trial found:
Randomised controlled trialHumansWith JNJ-42165279 (a FAAH inhibitor that raises endogenous PEA, anandamide and OEA, tested alone) - Successful and Unsuccessful Brain Aging in Pets: Pathophysiological Mechanisms behind Clinical Signs and Potential Benefits from Palmitoylethanolamide Nutritional Intervention
Ultramicronised palmitoylethanolamide has been tested repeatedly in animal models of age-related neurodegeneration with encouraging results, the authors say, and they suggest it may support brain ageing in pets.
ReviewDogsCats - Advances in Alternative and Integrative Medicine in the Treatment of Depression: A Review of the Evidence
Evidence favoured an antidepressant effect for several supplements, though the authors say efficacy and tolerability need confirming in further high-quality studies.
ReviewHumans - Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain
This systematic review found:
Meta-analysisOther animals - Mediterranean diet consumption affects the endocannabinoid system in overweight and obese subjects: possible links with gut microbiome, insulin resistance and inflammation
The Mediterranean diet lowered plasma anandamide (p=0.02), raised the oleoylethanolamide to palmitoylethanolamide ratio (p=0.009) and the oleoylethanolamide to anandamide ratio (p=0.006), and increased faecal Akkermansia muciniphila (p=0.026), independent of weight change.
Randomised controlled trialHumans - Hair endocannabinoid concentrations in individuals with acute and weight-recovered anorexia nervosa
Anandamide and all endocannabinoid-related compounds, including palmitoylethanolamide, were elevated in acute anorexia and fell with short-term weight restoration.
Observational studyHumans - Sepsis-associated encephalopathy and septic encephalitis: an update
The authors describe delirium as the main sign, inflammation and blood-brain barrier changes as causes, and antibiotics as the backbone of treatment.
ReviewHumans - Genetically-targeted photorelease of endocannabinoids enables optical control of GPR55 in pancreatic β-cells
The OCT-ligand method allowed PEA to be released at defined cell membranes.
Laboratory studyOther animals - N-acylethanolamine-hydrolysing acid amidase: A new potential target to treat paclitaxel-induced neuropathy
This laboratory study found:
Laboratory studyOther animals - Involvement of acid ceramidase in the degradation of bioactive N-acylethanolamines
This laboratory study found:
Laboratory studyHumansOther animals - Alternative Targets to Fight Alzheimer's Disease: Focus on Astrocytes
Palmitoylethanolamide can modulate astrocytes according to their morphological and functional state, the authors say, and they suggest this as a possible disease-modifying approach worth exploring.
ReviewHumansOther animals - Simultaneous quantification of steroid hormones and endocannabinoids (ECs) in human hair using an automated supported liquid extraction (SLE) and LC-MS/MS - Insights into EC baseline values and correlation to steroid concentrations
A validated method was produced, using surrogate-analyte calibration for steroids and background correction for endocannabinoids.
Observational studyHumans - Improving Chemotherapy-Induced Peripheral Neuropathy in Patients with Breast or Colon Cancer after End of (Neo)adjuvant Therapy: Results from the Observational Study STEFANO
Sensory neuropathy improved in 31 percent of breast cancer patients and 17 percent of colon cancer patients; motor neuropathy in 38 and 20 percent.
Observational studyHumansWith a patented fatty acid mixture (OnLife) - PPARα agonist relieves spinal cord injury in rats by activating Nrf2/HO-1 via the Raf-1/MEK/ERK pathway
PEA reduced spinal cord injury in rats, inhibited inflammatory responses, reduced oxidative stress and apoptosis, and improved motor function recovery.
Laboratory studyOther animals - Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma
The abstract reports no palmitoylethanolamide-specific findings or numbers.
ReviewHumansOther animals - Palmitoylethanolamide counteracts hepatic metabolic inflexibility modulating mitochondrial function and efficiency in diet-induced obese mice
This lab study found:
Laboratory studyHumansOther animals - Childhood trauma and being at-risk for psychosis are associated with higher peripheral endocannabinoids
People with both high-risk status and childhood trauma had higher palmitoylethanolamide (p<0.001) and anandamide (p<0.001) than controls and than those without trauma.
Observational studyHumans - Effects of Palmitoylethanolamide Combined with Luteoline on Frontal Lobe Functions, High Frequency Oscillations, and GABAergic Transmission in Patients with Frontotemporal Dementia
This open-label study found:
Open-label, no control groupHumansWith luteolin (PEA-LUT) - Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent
Peripheral CB1 blockade reversed liver steatosis and improved liver injury in wild-type but not PPAR-alpha knockout mice.
Laboratory studyOther animalsWith AM6545 (a peripheral CB1 receptor blocker, tested alone) - Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer's Disease
Chronic oral um-PEA was absorbed and reached the mice's brains.
Laboratory studyOther animals - Astrocytic palmitoylethanolamide pre-exposure exerts neuroprotective effects in astrocyte-neuron co-cultures from a triple transgenic mouse model of Alzheimer's disease
This lab study found:
Laboratory studyOther animals - Associating Emergency Medical Services personnel's workload, trauma exposure, and health with the cortisol, endocannabinoid, and N-acylethanolamine concentrations in their hair
This observational study found:
Observational studyHumans - Chronic Psychosocial Stress Causes Increased Anxiety-Like Behavior and Alters Endocannabinoid Levels in the Brain of C57Bl/6J Mice
This lab study found:
Laboratory studyOther animals - Increased Absorption of Palmitoylethanolamide Using a Novel Dispersion Technology System (LipiSperse)
The dispersion form gave an area under the curve 1.75 times that of the standard form (p < 0.05), with a higher peak rise (11.12 against 7.96 pmol/mL) and an earlier peak (105 against 125 minutes).
Randomised controlled trialHumans - Beyond the Canonical Endocannabinoid System. A Screening of PPAR Ligands as FAAH Inhibitors
The authors screened their PPAR agonist library for FAAH-inhibiting activity to find a lead compound with a dual PPAR/FAAH profile, and propose a binding mode from docking.
Laboratory studyOther animals - Essential fatty acids deficient diet modulates N-Acylethanolamide profile in rat's tissues
The study found:
Laboratory studyOther animals - Synergic Therapeutic Potential of PEA-Um Treatment and NAAA Enzyme Silencing In the Management of Neuroinflammation
Ultramicronised PEA at 3 and 10 micromolar protected viability in all cell lines after inflammatory stimulation.
Laboratory studyHumansOther animals - Fatty acid amide hydrolase inhibition normalises bladder function and reduces pain through normalising the anandamide/palmitoylethanolamine ratio in the inflamed bladder of rats
URB937 did not change normal bladders.
Laboratory studyOther animals - N-Palmitoylethanolamine Maintains Local Lipid Homeostasis to Relieve Sleep Deprivation-Induced Dry Eye Syndrome
Sleep deprivation lowered palmitoylethanolamide in the lacrimal gland, mainly through reduced expression of its synthetic enzyme NAPE-PLD.
Laboratory studyOther animals - An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events
Palmitoylethanolamide is protective and anti-inflammatory in laboratory models but has no antioxidant activity of its own, which the authors give as the reason for pairing it with the flavonoid luteolin.
ReviewHumansOther animalsWith luteolin - Effect of N-palmitoylethanolamine-oxazoline on comorbid neuropsychiatric disturbance associated with inflammatory bowel disease
Daily oral PEA-OXA reduced weight loss, macroscopic damage, colon shortening, histological change and inflammation after DSS.
Laboratory studyOther animalsWith PEA-OXA (a PEA analogue, tested alone) - A new role for anandamide: defective link between the systemic and skin endocannabinoid systems in hypertrophic human wound healing
The study found:
Observational studyHumans - Endocannabinoid concentrations in hair and mental health of unaccompanied refugee minors
Associations between hair lipids and psychological symptoms were weak and inconsistent; only 2-AG correlated positively with depression.
Observational studyHumans - Management of Traumatic Brain Injury: From Present to Future
Secondary injury after traumatic brain injury is described as an inflammatory cascade with blood-brain barrier breakdown, oedema, immune cell infiltration and cytokine release, and the authors review neuroprotective strategies against it.
ReviewHumansOther animals - Synthesis, Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide
The study found:
Laboratory studyHumansOther animalsWith RePEA (a PEA analogue, tested alone and against PEA) - ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain
Clinical trials of several formulations are described in diabetic neuropathy, chemotherapy-related neuropathy, carpal tunnel syndrome, sciatica-type pain and jaw joint pain, with safety and tolerability rated high.
ReviewHumansOther animals - Protective effects of Colomast®, A New Formulation of Adelmidrol and Sodium Hyaluronate, in A Mouse Model of Acute Restraint Stress
This laboratory study found:
Laboratory studyOther animalsWith adelmidrol (a PEA analogue) with sodium hyaluronate (Colomast) - N-Acylphosphatidylethanolamines and N-acylethanolamines increase in saliva upon food mastication: the influence of the individual nutritional status and fat type in food
The study found:
Controlled trialHumans - Fatty Acid Amides Synthesized from Andiroba Oil (Carapa guianensis Aublet.) Exhibit Anticonvulsant Action with Modulation on GABA-A Receptor in Mice: A Putative Therapeutic Option
This laboratory study found:
Laboratory studyOther animalsWith fatty acid amides FAA1 and FAA2 synthesised from andiroba oil (tested alone; not palmitoylethanolamide itself) - Looking for a Treatment for the Early Stage of Alzheimer's Disease: Preclinical Evidence with Co-Ultramicronized Palmitoylethanolamide and Luteolin
This laboratory study found:
Laboratory studyOther animalsWith luteolin (co-ultramicronised PEA/luteolin, PEALut) - Measuring the placebo effect in carpal tunnel syndrome
Both groups improved, and the study reported:
Randomised controlled trialHumans - Disease-Specific Derangement of Circulating Endocannabinoids and N-Acylethanolamines in Myeloproliferative Neoplasms
The study found:
Observational studyHumans - Inhibition of fatty acid amide hydrolase in the CNS prevents and reverses morphine tolerance in male and female mice
This laboratory study found:
Laboratory studyOther animalsWith URB597 and URB937 (FAAH inhibitors, tested alone), with morphine - Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis
This laboratory study found that adelmidrol-treated mice showed:
Laboratory studyOther animalsWith adelmidrol (a PEA analogue, tested alone) - ENDOCANNABINOIDS RECEPTORS MEDIATED CENTRAL AND PERIPHERAL EFFECTS (REVIEW)
Anandamide, 2-AG and palmitoylethanolamide are described as endocannabinoids, with PEA proposed to bind a 'CB2-like' receptor; the authors summarise CB1 and CB2 distribution and signalling, analgesic actions involving PPAR-alpha, TRPV receptors and COX-2, and possible roles in memory, Alzheimer's disease, schizophrenia and depression.
ReviewHumansOther animals - Sodium chromo-glycate and palmitoylethanolamide: A possible strategy to treat mast cell-induced lung inflammation in COVID-19
Sodium cromoglycate and/or PEA are proposed to suppress mast cell activation and release of pro-inflammatory mediators in the lungs of COVID-19 patients.
ReviewHumansWith sodium cromoglycate (proposed partner) - Effects of Tacrolimus and Other Immune Targeting Compounds on Binge-Like Ethanol Drinking in High Drinking in the Dark Mice
Tacrolimus reduced ethanol intake and blood alcohol levels, and reduced saccharin but not water intake.
Laboratory studyOther animals - Oral Supplementation with Ultramicronized Palmitoylethanolamide for Joint Disease and Lameness Management in Four Jumping Horses: A Case Report
Lameness resolved in all four horses, the authors reported, and the horses returned to showjumping competition without recurrence during the report period.
Case seriesHorses - Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing
PEA is described as a nutritional factor known since the 1950s with pro-resolving functions, acting through many overlapping targets rather than one, the authors say, summarising experimental and clinical studies of ALIAmides in animal health.
ReviewDogsCatsOther animals - Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain
This laboratory study found:
Laboratory studyOther animals - Night Migratory Songbirds Exhibit Metabolic Ability to Support High Aerobic Capacity during Migration
This laboratory study found:
Laboratory studyOther animals - Impact of circadian rhythmicity and sleep restriction on circulating endocannabinoid (eCB) N-arachidonoylethanolamine (anandamide)
This trial found:
Randomised controlled trialHumans - Pyridostigmine bromide exposure creates chronic, underlying neuroimmune disruption in the gastrointestinal tract and brain that alters responses to palmitoylethanolamide in a mouse model of Gulf War Illness
PB alone caused little change in neuromuscular transmission, but altered how PEA affected the gut and brain.
Laboratory studyOther animals - Analogous modulation of inflammatory responses by the endocannabinoid system in periodontal ligament cells and microglia
Anandamide countered the morphological changes caused by inflammation and cut inflammatory gene expression more than 100-fold.
Laboratory studyHumansOther animals - Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris
This laboratory study found:
Laboratory studyHumansWith cannabidiol (tested alone; PEA was a measured lipid) - Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway
This laboratory study found:
Laboratory studyOther animalsWith fucoxanthinol (a seaweed carotenoid that inhibits NAAA and raises cellular PEA, tested alone) - Naturally Occurring Cannabinoids and their Role in Modulation of Cardiovascular Health
The endocannabinoid system has a limited role under normal conditions, the authors say, but its over-activation is linked to cardiovascular conditions, and activation may also be a protective compensation.
ReviewHumansOther animals - Food supplements based on palmitoylethanolamide plus hydroxytyrosol from olive tree or Bacopa monnieri extracts for neurological diseases
The three compounds share reported neuroprotective actions against shared features of neurodegenerative disease, the authors say, including protein aggregation, oxidative stress, apoptosis, excitotoxicity, calcium imbalance and inflammation.
ReviewHumansOther animalsWith hydroxytyrosol (olive extract) and Bacopa monnieri extract, discussed as supplement partners - Effect of Hataedock Treatment on Epidermal Structure Maintenance through Intervention in the Endocannabinoid System
Hataedock treatment reduced clinical scores (p<0.01) and histological signs, raised cannabinoid receptor and barrier protein expression, raised E-cadherin and GPx4, lowered CD1A, and reduced p-ERK, p-JNK, p-mTOR and epidermal thickness.
Laboratory studyOther animalsWith Douchi (fermented soybean) extract used as Hataedock; genistein and PEA compared in a separate involucrin assay - ASP8477, a fatty acid amide hydrolase inhibitor, exerts analgesic effects in rat models of neuropathic and dysfunctional pain
The study found:
Laboratory studyOther animalsWith ASP8477 (a FAAH inhibitor that raises brain PEA and OEA, tested alone) - Effect of intravenous, perioperative-administered lidocaine on serum levels of endocannabinoids and related N-acylethanolamines in children
Levels were similar in controls and patients before surgery.
Controlled trialHumans - The anti-inflammatory and immune-modulatory effects of OEA limit DSS-induced colitis in mice
The study found:
Laboratory studyOther animalsWith oleoylethanolamide (OEA, a related lipid, tested alone; PEA was not given) - An Observational Study of the Application of a Topical Cannabinoid Gel on Sensitive Dry Skin
The observational study found:
Observational studyHumansTopical - Design and synthesis of cyanamides as potent and selective N-acylethanolamine acid amidase inhibitors
The study found:
Laboratory studyHumansOther animals - The Effect of Orally Dosed Levagen+™ (palmitoylethanolamide) on Exercise Recovery in Healthy Males—A Double-Blind, Randomized, Placebo-Controlled Study
The trial found:
Randomised controlled trialHumans - Potential Mechanisms Involved in Palmitoylethanolamide-Induced Vasodepressor Effects in Rats
PEA dose-dependently inhibited vasopressor responses to sympathetic stimulation and noradrenaline, and lowered resting blood pressure.
Laboratory studyOther animals - A New Palmitoylethanolamide Form Combined with Antioxidant Molecules to Improve Its Effectivess on Neuronal Aging
The FM-LipoMatrix PEA formulation with lipoic acid and vitamin D3 showed better absorption than the other formulations, predicting higher plasma levels.
Laboratory studyOther animalsWith lipoic acid and vitamin D3 (tested with a proprietary PEA formulation, FM-LipoMatrix) - Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering from Migraine: A Pilot Study
Monthly attacks fell from 13.9 to 6.5 (p < 0.001), and 63.9 percent of children had at least a halving of attack frequency.
Open-label, no control groupHumans - Dietary interventions for multiple sclerosis-related outcomes
This meta-analysis found:
Meta-analysisHumans - Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries. A Systematic Review
The authors argue that neuroinflammation is normally kept in check by locally made palmitoylethanolamide, and that oral micronised forms restore that control; the trials are reviewed on that basis.
ReviewHumans - N-Acylethanolamine Acid Amidase (NAAA): Structure, Function, and Inhibition
NAAA is described as a lysosomal cysteine hydrolase in immune cells that deactivates PEA, with NAAA-regulated PEA signalling at PPAR-alpha presented as a control point for starting and resolving inflammation.
ReviewHumansOther animals - N-Acylethanolamine Acid Amidase contributes to disease progression in a mouse model of multiple sclerosis
This laboratory study found:
Laboratory studyOther animals - Ocular Formulation Based on Palmitoylethanolamide-Loaded Nanostructured Lipid Carriers: Technological and Pharmacological Profile
The nanostructured lipid carrier formulation delivered substantial PEA levels to the retina after a single instillation, and significantly reduced retinal TNF-alpha in streptozotocin-induced diabetic rats.
Laboratory studyOther animalsTopical - The Basal Pharmacology of Palmitoylethanolamide
This review found:
ReviewHumansOther animals - Relative Deficiency of Anti-Inflammatory N-Acylethanolamines Compared to Prostaglandins in Oral Lichen Planus
PTGS2 was about 4-fold higher in oral lichen planus than in controls, and the PTGS2 to NAPEPLD ratio was significantly raised.
Observational studyHumans - Effect of palmitoylethanolamide on inner retinal function in glaucoma: a randomized, single blind, crossover, clinical trial by pattern-electroretinogram
Retinal response amplitude was higher during the palmitoylethanolamide period (0.56 microvolts, p < 0.001), eye pressure was lower by 1.58 mmHg (p < 0.001), and quality of life scores improved.
Randomised controlled trialHumans - The Protective Effects of Pre- and Post-Administration of Micronized Palmitoylethanolamide Formulation on Postoperative Pain in Rats
Pre- and post-treatment with PEA-m reduced mast cell activation and nerve growth factor at the incision site, and reduced spinal phospho-ERK, Iba1, GFAP and NF-kappa-B activity while affecting BDNF expression.
Laboratory studyOther animals - Increased Anandamide and Decreased Pain and Depression after Exercise in Fibromyalgia
This controlled trial found:
Controlled trialHumans - Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP3652, a Reversible Fatty Acid Amide Hydrolase Inhibitor, in Healthy, Nonelderly, Japanese Men and Elderly, Japanese Men and Women: A Randomized, Double-blind, Placebo-controlled, Single and Multiple Oral Dose, Phase I Study
This phase I study found:
Randomised controlled trialHumansWith ASP3652 (a FAAH inhibitor that raises endogenous PEA, tested alone) - Peripheral deficiency and antiallodynic effects of 2-arachidonoyl glycerol in a mouse model of paclitaxel-induced neuropathic pain
Paclitaxel lowered 2-AG in paw skin only; anandamide, PEA and OEA were not significantly changed, and MAGL expression was unchanged.
Laboratory studyOther animalsWith 2-arachidonoyl glycerol and JZL184 (a MAGL inhibitor), tested alone; PEA was a measured lipid - Effects of a High-Protein Diet on Cardiometabolic Health, Vascular Function, and Endocannabinoids-A PREVIEW Study
This controlled trial found:
Controlled trialHumans - Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia
Perinatal asphyxia reduced pNF-H/M and MAP-2 reactive areas and protein expression, and reduced GFAP-positive cell numbers, without changing total GFAP protein.
Laboratory studyOther animals - Natural Potent NAAA Inhibitor Atractylodin Counteracts LPS-Induced Microglial Activation
Atractylodin inhibited NAAA with an IC50 of 2.81 micromolar by reversible competitive inhibition, docking to the catalytic cavity near Trp181 and Leu152.
Laboratory studyOther animalsWith atractylodin (a NAAA inhibitor that raises cellular PEA, tested alone) - PPARα-Dependent Effects of Palmitoylethanolamide Against Retinal Neovascularization and Fibrosis
Profibrotic changes were present in OIR and VLDLR-knockout retinas.
Laboratory studyOther animals - Perceptions and recommendation behaviors of dermatologists for medical cannabis: A pilot survey
The survey found:
Observational studyHumans - Joint Synovial Fluid Metabolomics Method to Decipher the Metabolic Mechanisms of Adjuvant Arthritis and Geniposide Intervention
Twenty metabolites differed between arthritic and normal rats.
Laboratory studyOther animalsWith geniposide (tested alone; PEA was a measured metabolite) - Role of pannexin-1 in the cellular uptake, release and hydrolysis of anandamide by T84 colon cancer cells
This lab study found:
Laboratory studyHumans - Role of cannabinoid receptor 1 and the peroxisome proliferator-activated receptor α in mediating anti-nociceptive effects of synthetic cannabinoids and a cannabinoid-like compound
All three compounds restored paw withdrawal threshold and weight-bearing in a dose-dependent way and restored locomotor activity.
Laboratory studyOther animals - Effects of the glial modulator palmitoylethanolamide on chronic pain intensity and brain function
This open-label study found:
Open-label, no control groupHumans - Sinerga may prevent recurrent respiratory infections in allergic children
Sinerga significantly reduced the number of respiratory infections and the size of both inferior and middle turbinates compared with standard therapy alone, though no figures are given in the abstract.
Controlled trialHumansWith Kluyveromyces marxianus B0399, bovine colostrum and phenylalanine (the Sinerga supplement) - Prediction of preterm labour from a single blood test: The role of the endocannabinoid system in predicting preterm birth in high-risk women
This observational study found:
Observational studyHumans - Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer's Disease
Preclinical models show neuroprotective effects of palmitoylethanolamide, particularly micronised and ultramicronised forms.
ReviewHumansOther animalsWith luteolin (in the single case study cited) - Ultra-micronized palmitoylethanolamide rescues the cognitive decline-associated loss of neural plasticity in the neuropathic mouse entorhinal cortex-dentate gyrus pathway
Nerve injury reduced pain thresholds, spatial memory and LTP, altered dentate gyrus synapse structure and glutamate receptor expression, and raised glutamate and 2-AG levels.
Laboratory studyOther animals - Metabotropic Glutamate Receptor 5 and 8 Modulate the Ameliorative Effect of Ultramicronized Palmitoylethanolamide on Cognitive Decline Associated with Neuropathic Pain
Nerve injury reduced memory and LTP.
Laboratory studyOther animals - Cocaine-Induced Reinstatement of Cocaine Seeking Provokes Changes in the Endocannabinoid and N-Acylethanolamine Levels in Rat Brain Structures
The study found:
Laboratory studyOther animals - Micronized Palmitoylethanolamide-Polydatin Reduces the Painful Symptomatology in Patients with Interstitial Cystitis/Bladder Pain Syndrome
Pain fell progressively over 6 months (p < 0.0001), with lower symptom and problem scores and lower urinary frequency.
Open-label, no control groupHumansWith polydatin - Add-on administration of ultramicronized palmitoylethanolamide in the treatment of new-onset burning mouth syndrome
Gabapentin alone gave poor symptom control, with a VAS score of 8-9.
Case seriesHumans - Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer
The review covers Serenoa repens, Pygeum, Urtica, lycopene, selenium, pollen extract, beta-sitosterol and polyphenols.
ReviewHumans - Impaired brain endocannabinoid tone in the activity-based model of anorexia nervosa
The study found:
Laboratory studyOther animals - A co-ultramicronized palmitoylethanolamide/luteolin composite mitigates clinical score and disease-relevant molecular markers in a mouse model of experimental autoimmune encephalomyelitis
The study found:
Laboratory studyOther animalsWith luteolin (co-ultramicronised PEA/luteolin, PEALut) - Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain
The study found:
Laboratory studyOther animalsWith N-palmitoyl-D-glucosamine (a related ALIAmide, not PEA, tested alone in plain and micronised forms) - Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo: A Randomized, Placebo-controlled, Double-blind Controlled Trial
The trial found:
Randomised controlled trialHumans - Micronized Palmitoylethanolamide: A Post Hoc Analysis of a Controlled Study in Patients with Low Back Pain – Sciatica
Number needed to treat was 1.7 for pain (95% CI 1.4 to 2) and 1.5 for function (95% CI 1.4 to 1.7) at 600 mg a day.
Randomised controlled trialHumans - Effects of a new compound containing Palmitoylethanolamide and Baicalein in myocardial ischaemia/reperfusion injury in vivo
PEA-baicalein treatment reduced myocardial tissue injury, neutrophil infiltration, chymase and tryptase expression, and TNF-alpha and IL-1beta production.
Laboratory studyOther animalsWith baicalein - The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review
A significant number of trials show pain relief, with weaker evidence for non-pain symptoms, no reported drug interactions and few adverse effects; the authors note little is known about pharmacokinetics.
ReviewHumans - Role of palmitoylethanolamide (PEA) in depression: Translational evidence
Antidepressant-like activity appears in animal models.
ReviewHumansOther animals - Food database of N-acyl-phosphatidylethanolamines, N-acylethanolamines and endocannabinoids and daily intake from a Western, a Mediterranean and a vegetarian diet
This laboratory study found:
Laboratory studyOther animals - Formation of HETE-EAs and dihydroxy derivatives in mouse kidney tissue and analysis by high-performance liquid chromatography tandem mass spectrometry
The authors synthesised reference DiHETE-EA metabolites using mouse liver cytosol and present a solid phase extraction and HPLC-MS/MS method that quantifies anandamide, 2-AG, their metabolites, oleoylethanolamide and palmitoylethanolamide, and detects DiHETE-EAs formed in kidney after anandamide injection.
Laboratory studyOther animals - Altered Metabolism of Phospholipases, Diacylglycerols, Endocannabinoids, and N-Acylethanolamines in Patients with Mastocytosis
The study found:
Observational studyHumans - Efficacy of a Combination of N-Palmitoylethanolamide, Beta-Caryophyllene, Carnosic Acid, and Myrrh Extract on Chronic Neuropathic Pain: A Preclinical Study
This laboratory study found:
Laboratory studyOther animalsWith beta-caryophyllene, carnosic acid and myrrh extract (a commercial combination product, Noxiall) - N-Palmitoylethanolamide-Oxazoline Protects against Middle Cerebral Artery Occlusion Injury in Diabetic Rats by Regulating the SIRT1 Pathway
PEA-OXA treatment improved tissue histology, reducing lesion size and apoptosis, and reduced mast cell degranulation and NF-kappa-B pathway, cytokine and neurotrophic factor changes caused by MCAo.
Laboratory studyOther animalsWith PEA-OXA (2-pentadecyl-2-oxazoline, a PEA analogue, tested alone) - First evidence on the role of palmitoylethanolamide in energy homeostasis in fish
Acute PEA reduced food intake at 6 and 8 hours after injection, linked with increased hepatic leptin and reduced hypothalamic NPY expression.
Laboratory studyOther animals - Diurnal Profiles of N-Acylethanolamines in Goldfish Brain and Gastrointestinal Tract: Possible Role of Feeding
This laboratory study found:
Laboratory studyOther animals - Determination of endocannabinoids and endocannabinoid-like substances in human K3EDTA plasma - LC-MS/MS method validation and pre-analytical characteristics
This laboratory study found:
Laboratory studyHumans - Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity
This case report found:
Case seriesHumans - Opposite Effects of Neuroprotective Cannabinoids, Palmitoylethanolamide, and 2-Arachidonoylglycerol on Function and Morphology of Microglia
PEA or 2-AG alone reduced neuronal damage after excitotoxic lesion, but combining them removed this protective effect, independent of microglial cells.
Laboratory studyOther animalsWith 2-arachidonoylglycerol (2-AG, tested alongside PEA, not as a fixed combination product) - The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice
This laboratory study found:
Laboratory studyOther animals - Molecular Targets of Fatty Acid Ethanolamides in Asthma
Nerve growth factor, which regulates mast cell differentiation and is linked to allergic airway inflammation, is one target of palmitoylethanolamide in asthma, the authors propose.
ReviewHumansOther animals - Broad Lipidomic and Transcriptional Changes of Prophylactic PEA Administration in Adult Mice
Prophylactic PEA produced broad transcriptional changes in inflammatory pathways in both tissues and, in hippocampus, regulation of genes for neuronal activity and excitability.
Laboratory studyOther animals - N-Palmitoylethanolamide Exerts Antidepressant-Like Effects in Rats: Involvement of PPAR α Pathway in the Hippocampus
PEA normalised weight gain, sucrose preference, locomotor activity and hippocampal PPAR-alpha levels, and lowered serum ACTH and corticosterone in stressed rats.
Laboratory studyOther animals - Stimulation of Peroxisome Proliferator-Activated Receptor-α by N-Palmitoylethanolamine Engages Allopregnanolone Biosynthesis to Modulate Emotional Behavior
The study found:
Laboratory studyOther animals - Co-ultraPEALut: Role in Preclinical and Clinical Delirium Manifestations
Glialia prevented the onset of postoperative delirium and reduced symptom intensity and duration.
Controlled trialHumansOther animalsWith luteolin - Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder
The study found:
Controlled trialHumans - Intracellular Ca2+-dependent formation of N-acyl-phosphatidylethanolamines by human cytosolic phospholipase A2ε
Induced cells given a calcium ionophore produced large amounts of diacyl and alkenylacyl NAPEs and of NAEs, while diacyl and alkenylacyl PEs and diacyl PCs fell and lysoPEs and lysoPCs rose.
Laboratory studyHumans - Effect of dietary supplementation with ultramicronized palmitoylethanolamide in maintaining remission in cats with nonflea hypersensitivity dermatitis: a double-blind, multicentre, randomized, placebo-controlled study
Mean time to relapse was 40.5 days in the supplement group against 22.2 days with placebo (P = 0.04).
Randomised controlled trialCats - Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment
The clinical score improved (p = 0.034) and the decremental response on masseter nerve stimulation lessened (p = 0.018) during treatment, while antibody titres did not change.
Open-label, no control groupHumans - Efficacy of ultramicronized palmitoylethanolamide in burning mouth syndrome-affected patients: a preliminary randomized double-blind controlled trial
Burning sensation fell significantly more in the treatment group than with placebo at 60 days (p < 0.0132), with no treatment-related side effects observed.
Randomised controlled trialHumans - Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy with Different Antioxidant Molecules Present in Diets
The authors describe palmitoylethanolamide as an ALIAmide present in foods and made by the body, used in acute and chronic inflammatory conditions alone or with antioxidants or analgesics.
ReviewHumansOther animals - Oleoyl glycine: interference with the aversive effects of acute naloxone-precipitated MWD, but not morphine reward, in male Sprague-Dawley rats
Oleoyl glycine at 1 and 5 mg/kg blocked the aversive effect of morphine withdrawal; AM251 (a CB1 antagonist) reversed this but MK886 (a PPAR-alpha antagonist) did not, and morphine reward was unchanged.
Laboratory studyOther animals - Palmitoylethanolamide counteracts substance P-induced mast cell activation in vitro by stimulating diacylglycerol lipase activity
Substance P increased mast cell degranulation and histamine release.
Laboratory studyOther animals - Biomarkers of response to alpha-lipoic acid ± palmitoiletanolamide treatment in patients with diabetes and symptoms of peripheral neuropathy
This observational study found:
Observational studyHumansWith alpha-lipoic acid (all treated patients received it; PEA was added in some) - The ventral pallidum as a critical region for fatty acid amide hydrolase inhibition of nausea-induced conditioned gaping in male Sprague-Dawley rats
PF-3845 into the ventral pallidum reduced conditioned gaping in a dose-dependent way through PPAR-alpha, not CB1.
Laboratory studyOther animals - Combination of Rehabilitative Therapy with Ultramicronized Palmitoylethanolamide for Chronic Low Back Pain: An Observational Study
Average pain intensity progressively decreased over the study, ending at a level the authors describe as not clinically relevant.
Observational studyHumans - Ultramicronized Palmitoylethanolamide (um-PEA) as Add-on Treatment in Fibromyalgia Syndrome (FMS): Retrospective Observational Study on 407 Patients
This retrospective study found:
Observational studyHumans - Oligodendrocyte precursor cells as a therapeutic target for demyelinating diseases
This discusses why remyelination fails with age and in multiple sclerosis, and possible drug targets for promoting precursor cell differentiation.
ReviewHumansOther animals - A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis
Lower WOMAC total scores than placebo in both dose groups (300 mg: p = 0.0372; 600 mg: p = 0.0012), with lower pain and stiffness sub-scores in both groups and a lower function sub-score in the 600 mg group.
Randomised controlled trialHumans - Altered relationship between anandamide and glutamate in circulation after 30 min of arm cycling: A comparison of chronic pain subject with healthy controls
This controlled trial found:
Controlled trialHumans - 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
This open-label pilot study found:
Open-label, no control groupHumansWith polydatin - Endocannabinoid and N-acylethanolamide levels in rat brain and spinal cord following systemic dipyrone and paracetamol administration
This laboratory study found:
Laboratory studyOther animals - Manganese affects the growth and metabolism of Ganoderma lucidum based on LC-MS analysis
The study found:
Laboratory studyOther animals - N-Acylethanolamine acid amidase (NAAA) inhibitor F215 as a novel therapeutic agent for osteoarthritis
Osteoarthritic rats had higher NAAA and lower palmitoylethanolamide in synovium and spinal cord.
Laboratory studyOther animals - Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses
FAAH overexpression raised its enzymatic activity and lowered hippocampal anandamide and PEA (2-AG and OEA unchanged).
Laboratory studyOther animals - Micronized palmitoylethanolamide reduces joint pain and glial cell activation
CFA-injected animals showed TMJ edema and mechanical allodynia along with increased GFAP-positive satellite glial cells and macrophage activation in the trigeminal ganglion.
Laboratory studyOther animals - Palmitoylethanolamide Blunts Amyloid-β42-Induced Astrocyte Activation and Improves Neuronal Survival in Primary Mouse Cortical Astrocyte-Neuron Co-Cultures
Astrocytes pre-exposed to amyloid-beta42 lowered neuronal viability, raised apoptotic nuclei counts, reduced MAP-2 positive neuron numbers, and increased neurite aggregation.
Laboratory studyOther animals - Effects of Add-On Ultramicronized N-Palmitol Ethanol Amide in Patients Suffering of Migraine With Aura: A Pilot Study
The trial found:
Controlled trialHumans - Nonsurgical lumbar radiculopathies treated with ultramicronized palmitoylethanolamide (umPEA): A series of 100 cases
The case series found:
Case seriesHumans - Palmitoylethanolamide counteracts autistic-like behaviours in BTBR T+tf/J mice: Contribution of central and peripheral mechanisms
PEA reversed the altered behavioural phenotype of BTBR mice, an effect tied to PPARalpha activation.
Laboratory studyOther animals - N-palmitoylethanolamide Prevents Parkinsonian Phenotypes in Aged Mice
PEAm pretreatment lessened MPTP-induced behavioural deficits and preserved tyrosine hydroxylase and dopamine transporter expression, while blunting the rise in alpha-synuclein and beta3-tubulin in the substantia nigra.
Laboratory studyOther animals - Ultra-micronized Palmitoylethanolamide Effects on Sleep-wake Rhythm and Neuropathic Pain Phenotypes in Patients with Carpal Tunnel Syndrome: An Open-label, Randomized Controlled Study
Sleep quality and pain both improved significantly in the treated group by the end of the pre-surgery period (p < 0.0001 for each), results the authors describe as preliminary.
Controlled trialHumans - Localization of cannabinoid receptors CB1, CB2, GPR55, and PPAR-alpha in the canine gastrointestinal tract
This laboratory study found:
Laboratory studyDogs - Palmitoylethanolamide as adjunctive therapy in major depressive disorder: A double-blind, randomized and placebo-controlled trial
Depression scores fell more in the palmitoylethanolamide group at week 2 (8.30 against 5.81 points, P = .004) and across the trial, the authors reported.
Randomised controlled trialHumans - Prophylactic Palmitoylethanolamide Prolongs Survival and Decreases Detrimental Inflammation in Aged Mice With Bacterial Meningitis
This laboratory study found:
Laboratory studyOther animals - Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction After Perinatal Asphyxia in the Immature Rat Brain
Perinatal asphyxia caused CA1 neuronal degeneration and changes in neurofilament and GFAP markers, with vertical exploration impairment and anxiety-related behaviour.
Laboratory studyOther animals - Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia
Neonatal AI reduced locomotion and impaired recognition and spatial memory, with more neuroinflammation and astrogliosis and less PPARalpha expression.
Laboratory studyOther animals - Palmitoylethanolamide as adjunctive therapy for autism: Efficacy and safety results from a randomized controlled trial
Irritability and hyperactivity improved more with palmitoylethanolamide added to risperidone than with risperidone alone (p = 0.001).
Randomised controlled trialHumans - Palmitoylethanolamide Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats
PEA reduced TGF-beta1-induced alpha-SMA expression and SMAD2 phosphorylation in hepatic stellate cells and upregulated SMAD7.
Laboratory studyOther animals - Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Levels and Spinal Anti-hyperalgesic Effect
This laboratory study found:
Laboratory studyOther animals - Oleoylethanolamide and Palmitoylethanolamide Protect Cultured Cortical Neurons Against Hypoxia
OEA and PEA protected cultured cortical neurons from hypoxia.
Laboratory studyOther animalsWith RN1734 (a TRPV4 antagonist), co-treated with PEA in some experiments; oleoylethanolamide (OEA) tested alongside PEA - Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy
Subchronic PEA significantly lessened seizure intensity, promoted neuroprotection, and changed plasma and hippocampal endocannabinoid and eicosanoid levels after kainic acid-induced seizures in mice.
Laboratory studyOther animals - Innovative Nanoparticles Enhance N-Palmitoylethanolamide Intraocular Delivery
PEA-NLC significantly raised PEA levels in ocular tissues compared with a plain PEA suspension, with vitreous Cmax of 5919±541 pmol/g and retinal Cmax of 315±70 pmol/g.
Laboratory studyOther animalsTopical - HIV-1 Tat-induced diarrhea is improved by the PPARalpha agonist, palmitoylethanolamide, by suppressing the activation of enteric glia
HIV-1 Tat protein caused rapid-onset diarrhoea and enteric glial activation, raising TLR4, NF-kB, S100B and iNOS.
Laboratory studyOther animals - Ultramicronized palmitoylethanolamide rescues learning and memory impairments in a triple transgenic mouse model of Alzheimer's disease by exerting anti-inflammatory and neuroprotective effects
Um-PEA improved learning, memory and depressive/anhedonia-like behaviour, reduced amyloid-beta formation and tau phosphorylation, and supported neuronal survival in hippocampal CA1.
Laboratory studyOther animals - Palmitoylethanolamide attenuates cocaine-induced behavioral sensitization and conditioned place preference in mice
Repeated PEA at both doses blocked acquisition of cocaine-induced behavioural sensitization.
Laboratory studyOther animals - Synthesis, biological evaluation, and structure activity relationship (SAR) study of pyrrolidine amide derivatives as N-acylethanolamine acid amidase (NAAA) inhibitors
The study found:
Laboratory studyOther animals - Ultramicronized palmitoylethanolamide counteracts the effects of compound 48/80 in a canine skin organ culture model
This lab study found:
Laboratory studyDogs - Identification of a Widespread Palmitoylethanolamide Contamination in Standard Laboratory Glassware
New 5.75-inch glass Pasteur pipettes, commonly used for lipid extraction, contained high levels of a contaminant indistinguishable from PEA.
Laboratory studyOther animals - Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis
This meta-analysis found:
Meta-analysisHumans - A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models
The combination reduced paw swelling by 30 to 45% in the first model.
Laboratory studyOther animalsWith quercetin - Ultra-micronized Palmitoylethanolamide: An Efficacious Adjuvant Therapy for Parkinson's Disease
A significant and progressive fall in the total rating scale score over the year, with a reduction in most motor and non-motor symptoms.
Observational studyHumans - Effects of a co-micronized composite containing palmitoylethanolamide and polydatin in an experimental model of benign prostatic hyperplasia
Testosterone caused prostate enlargement with raised prostaglandin E2, dihydrotestosterone and 5alpha-reductase expression, plus inflammation and apoptosis pathway changes.
Laboratory studyOther animalsWith polydatin - Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
Palmitoylethanolamide reduced inflammatory signalling in cells and explants and prevented the rise in cytokine release in explant colon, an effect blocked by a PPAR-alpha antagonist.
Laboratory studyHumans - Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome
The treatment did not significantly change the biological profile of the gut, including the mast cell count, which was the target it was chosen for.
Randomised controlled trialHumansWith polydatin - Use of Topical Cannabinomimetic Palmitoylethanolamide in Ocular Surface Disease Associated with Antiglaucoma Medications
In the PEA group, Schirmer test (p < 0.05), tear break-up time (p < 0.0001) and conjunctival redness (p < 0.0001) improved from baseline by day 30.
Controlled trialHumansTopical - Use of palmitoylethanolamide in carpal tunnel syndrome: a prospective randomized study
The trial found:
Randomised controlled trialHumans - The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line
PEA did not change COX-2 mRNA levels but reduced prostaglandin D2 and E2 and 11- and 15-HETE, an effect that held even when PEA breakdown to palmitic acid was blocked.
Laboratory studyOther animals - N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients with Chronic Pain
A small, statistically significant effect on pain favoured palmitoylethanolamide in 2 of the 7 patients, about 8% of baseline pain, with an effect on function in 1 patient, the authors reported.
Randomised controlled trialHumans - The efficacy of an association of palmitoylethanolamide and alpha-lipoic acid in patients with chronic prostatitis/chronic pelvic pain syndrome: A randomized clinical trial
The combination improved the urinary symptom score and reduced the prostatitis symptom score more than saw palmetto, the authors reported, though erectile function scores did not change significantly.
Randomised controlled trialHumansWith alpha-lipoic acid - Palmitoylethanolamide and Polydatin combination reduces inflammation and oxidative stress in vascular injury
PEA/polydatin 30 mg/kg reduced the vascular structural damage caused by carotid ligation, along with adhesion molecule expression (ICAM-1, VCAM-1), the proinflammatory cytokines TNF-alpha and IL-1beta, iNOS, PAR formation, NF-kB activation and apoptosis markers, all of which ligation had raised.
Laboratory studyOther animalsWith polydatin - Palmitoylethanolamide Reduces Neuropsychiatric Behaviors by Restoring Cortical Electrophysiological Activity in a Mouse Model of Mild Traumatic Brain Injury
PEA reduced the behavioural changes seen in mice with mild traumatic brain injury and partly normalised the biochemical and functional changes.
Laboratory studyOther animals - Micronized palmitoylethanolamide/trans-polydatin treatment of endometriosis-related pain: a meta-analysis
Across a mixed sample, the combination gave a clinically relevant improvement in pelvic pain and dysmenorrhoea, a limited improvement in deep dyspareunia and none in dyschezia.
Meta-analysisHumansWith transpolydatin - Palmitoylethanolamide Modulates GPR55 Receptor Signaling in the Ventral Hippocampus to Regulate Mesolimbic Dopamine Activity, Social Interaction, and Memory Processing
Intra-hippocampal PEA produced a hyper-dopaminergic mesolimbic state, with increased firing and bursting of dopamine neurons, and disrupted social interaction, recognition memory, spatial location memory and context-dependent fear memory, but not opiate-related reward memory.
Laboratory studyOther animals - Relationship Between Circulating Fatty Acids and Fatty Acid Ethanolamide Levels After a Single 2-h Dietary Fat Feeding in Male Sprague-Dawley Rats : Elevated levels of oleoylethanolamide, palmitoylethanolamide, linoleoylethanolamide, arachidonoylethanolamide and docosahexanoylethanolamide after a single 2 h dietary fat feeding in male Sprague Dawley rats
Levels of each ethanolamide changed over time in patterns specific to the compound and fat type.
Laboratory studyOther animals - Palmitoylethanolamide in the Treatment of Failed Back Surgery Syndrome
Tapentadol and pregabalin alone reduced VAS pain from 5.7±0.12 to 4.3±0.11 after 1 month (p<0.0001) but gave little subjective relief.
Observational studyHumansWith tapentadol and pregabalin - 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
The add-on group had larger reductions in pain, neuropathic component, disability and tapentadol dose than the tapentadol-only group, with no serious side effects.
Observational studyHumans - The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations
Palmitoylethanolamide is described as a compound made in many plant and animal foods and in mammalian tissues, with protective, anti-inflammatory and pain-related actions in laboratory work.
ReviewHumansOther animals - Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse
OVA sensitisation lowered bronchial PEA levels and raised CB2 and GPR55 receptor expression.
Laboratory studyOther animals - Effect of palmitoylethanolamide on inflammatory and neuropathic pain in rats
Spinal nerve transection lowered the mechanical threshold and raised acetone-response frequency, but not cold-withdrawal frequency.
Laboratory studyOther animals - Efficacy of Body Lotion Containing N-palmitoylethanolamine in Subjects with Chronic Pruritus due to Dry Skin: A Dermatocosmetic Study
The study found:
Randomised controlled trialHumansTopical - Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: A randomized, double-blind, placebo-controlled trial
Pain intensity did not differ between palmitoylethanolamide and placebo (P = 0.46): scores fell by 0.4 points on palmitoylethanolamide and 0.7 points on placebo.
Randomised controlled trialHumans - Palmitoylethanolamide protects mice against 6-OHDA-induced neurotoxicity and endoplasmic reticulum stress: In vivo and in vitro evidence
This lab study found:
Laboratory studyHumansOther animals - Co-ultramicronized Palmitoylethanolamide/Luteolin in the Treatment of Cerebral Ischemia: from Rodent to Man
In rats the combination reduced oedema and infarct size and improved behaviour.
Observational studyHumansOther animalsWith luteolin - Administration of palmitoylethanolamide in combination with topiramate in the preventive treatment of nummular headache
Combined oral PEA and topiramate improved the patient's pain symptoms and pain scale scores.
Case seriesHumansWith topiramate - A novel protective formulation of Palmitoylethanolamide in experimental model of contrast agent induced nephropathy
PEA-um reduced contrast-induced kidney dysfunction, normalised plasma sodium and potassium, and lowered urine and plasma NGAL and alpha-GST in diabetic rats.
Laboratory studyOther animals - Adelmidrol, a Palmitoylethanolamide Analogue, as a New Pharmacological Treatment for the Management of Inflammatory Bowel Disease
Colitis raised NF-kB translocation, COX-2, ERK phosphorylation, cytokines and markers of oxidative/nitrosative stress.
Laboratory studyOther animalsWith adelmidrol (a PEA analogue, tested alone) - Co-Ultramicronized Palmitoylethanolamide/Luteolin Promotes Neuronal Regeneration after Spinal Cord Injury
Co-ultraPEALut increased the numbers of bromodeoxyuridine-positive and doublecortin-positive cells in the injured spinal cord and raised expression of BDNF, GDNF, nerve growth factor and neurotrophin-3.
Laboratory studyOther animalsWith luteolin - Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO
PEA-um reduced heart tissue injury, neutrophil infiltration, adhesion molecule and cytokine levels, nitrotyrosine and PAR formation, NF-kB expression and apoptosis markers in normal mice.
Laboratory studyOther animals - Co-micronized Palmitoylethanolamide/Polydatin Treatment Causes Endometriotic Lesion Regression in a Rodent Model of Surgically Induced Endometriosis
Treated rats had smaller endometriotic cyst diameter, better fibrosis scores and fewer mast cells.
Laboratory studyOther animalsWith polydatin - Ultramicronized palmitoylethanolamide (PEA-um(®)) in the treatment of idiopathic pulmonary fibrosis
Compared with bleomycin alone, PEA-um at 3 and 10 mg/kg reduced weight loss, mortality, inflammation, lung histological damage and fibrosis at both 7 and 21 days.
Laboratory studyOther animals - Palmitoylethanolamide Reverses Paclitaxel-Induced Allodynia in Mice
This laboratory study found:
Laboratory studyOther animalsWith gabapentin - A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation
This laboratory study found:
Laboratory studyOther animalsWith polydatin - Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy
This review concluded:
ReviewHumans - Adelmidrol, a palmitoylethanolamide analogue, as a new pharmacological treatment for the management of acute and chronic inflammation
Adelmidrol markedly reduced carrageenan-induced paw edema, hyperalgesia and NF-kB activation; a PPAR-gamma antagonist blocked this, while lack of PPAR-alpha did not change it.
Laboratory studyOther animalsWith adelmidrol (a PEA analogue, tested alone) - Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis: role of mast cells
PEA-treated rats had fewer, shorter and less complex ureteral pain episodes, shorter uterine pain, smaller cysts, and a higher rate of stone expulsion than placebo-treated rats.
Laboratory studyOther animals - Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential
MicroPEA caused no mutations in five Salmonella strains and no genotoxic effects in human lymphocytes, with or without metabolic activation.
Laboratory studyHumansOther animals - N-palmitoylethanolamide in the anterior cingulate cortex attenuates inflammatory pain behaviour indirectly via a CB1 receptor-mediated mechanism
Intra-ACC PEA reduced early formalin-evoked pain behaviour, an effect blocked by a CB1 antagonist but not by PPAR-alpha, PPAR-gamma or TRPV1 antagonists, and PEA raised anandamide levels in the ACC.
Laboratory studyOther animals - Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing–Remitting Multiple Sclerosis
Pain at the injection site was lower at 6 and 12 months than with placebo, quality of life scores were better and inflammatory cytokine levels were lower.
Randomised controlled trialHumans - Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis
Pain fell by about 1.04 points every 2 weeks on PEA against 0.20 on control.
Meta-analysisHumans - Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy
Palmitoylethanolamide reduced the rundown of acetylcholine currents in muscle membranes from ALS and denervated patients, acting on the adult epsilon-type receptor, and treated ALS patients had a slower decline in forced vital capacity than untreated patients.
Observational studyHumans - The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2-arachidonoyl-glycerol and potentiates its actions at TRPV1 cation channels
Oral PEA raised plasma 2-AG about 2-fold in people and about 20-fold in dogs, and 3-fold in keratinocytes.
Laboratory studyHumansDogsOther animals - Adelmidrol increases the endogenous concentrations of palmitoylethanolamide in canine keratinocytes and down-regulates an inflammatory reaction in an in vitro model of contact allergic dermatitis
Adelmidrol raised PEA concentrations in dog keratinocytes and other cells, without inhibiting the PEA-degrading enzymes, and reduced MCP-2 release.
Laboratory studyDogsOther animals - Palmitoylethanolamide reduces inflammation and itch in a mouse model of contact allergic dermatitis
PEA reduced the ear thickness increase, mast cell numbers, and VEGF/Flk-1 expression in the late stage of contact allergic dermatitis, and reduced scratching 48 hours after the final challenge.
Laboratory studyOther animals - Palmitoylethanolamide attenuates PTZ-induced seizures through CB1 and CB2 receptors
PEA increased the time to seizure onset and shortened seizure duration after PTZ injection.
Laboratory studyOther animals - Beneficial Effects of Palmitoylethanolamide on Expressive Language, Cognition, and Behaviors in Autism: A Report of Two Cases
Both boys showed significant improvement in expressive language and overall autism severity scores, plus a reduction in atopic symptoms in the first child.
Case seriesHumans - Co-ultramicronized Palmitoylethanolamide/Luteolin Promotes the Maturation of Oligodendrocyte Precursor Cells
Co-ultramicronised PEA/luteolin produced a time-dependent rise in MBP mRNA and protein and in lipid-production genes, and promoted morphological maturation of the precursor cells without affecting their proliferation.
Laboratory studyOther animalsWith luteolin - Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent
This lab study found:
Laboratory studyOther animals - Chronic pelvic pain, quality of life and sexual health of women treated with palmitoylethanolamide and alpha-lipoic acid
No change in any measure at 3 months.
Open-label, no control groupHumansWith alpha-lipoic acid - Enhancement of Antihyperalgesia by the Coadministration of N-palmitoylethanolamide and Acetaminophen in Diabetic Rats
PEA and acetaminophen each reduced pain in a dose-dependent way.
Laboratory studyOther animalsWith paracetamol (acetaminophen) - Synergistic antinociceptive interaction between palmitoylethanolamide and tramadol in the mouse formalin test
PEA and tramadol combined produced a synergistic reduction in pain response: the effective combined dose (9.5 micrograms per paw) was lower than the dose calculated by adding the two drugs' individual effects (24.8 micrograms per paw).
Laboratory studyOther animalsWith tramadol - Palmitoylethanolamide in Fibromyalgia: Results from Prospective and Retrospective Observational Studies
The study found:
Observational studyHumans - Delay of morphine tolerance by palmitoylethanolamide
PEA roughly doubled the number of days morphine remained effective compared with morphine alone.
Laboratory studyOther animals - Palmitoylethanolamide relieves pain and preserves pancreatic islet cells in a murine model of diabetes
PEA reduced mechanical allodynia, countered a deficit in nerve growth factor, raised insulin levels, and preserved Langerhans islet structure while reducing insulitis in diabetic mice.
Laboratory studyOther animals - Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice
PEA treatment reduced pain-related behaviours and depression-like signs in nerve-injured mice and restored glutamate synapse proteins and amino acid release toward normal.
Laboratory studyOther animals - Effects of palmitoylethanolamide and silymarin combination treatment in an animal model of kidney ischemia and reperfusion
Silymarin alone reduced kidney dysfunction, tissue damage, neutrophil infiltration and oxidative stress in a dose-dependent way.
Laboratory studyOther animalsWith silymarin - The anti-inflammatory effects of palmitoylethanolamide (PEA) on endotoxin-induced uveitis in rats
PEA reduced inflammatory cell infiltration and histological eye damage, lowered TNF-alpha, protein leakage and lipid peroxidation, and reduced ICAM-1 and nitrotyrosine staining.
Laboratory studyOther animals - Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome
PEA reduced pain in each trial reviewed, including the 636-patient Guida trial (VAS 7.1 to 2.1 on 600 mg versus 6.6 to 4.6 on placebo), a 111-patient replication by Canteri, and several open-label carpal tunnel and sciatica studies.
ReviewHumans - Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy
Palmitoylethanolamide has been tested in at least nine double-blind placebo-controlled studies, two in glaucoma, and found safe and effective up to 1.8 g a day, the authors state.
ReviewHumans - Palmitoylethanolamide inhibits glutamate release in rat cerebrocortical nerve terminals
PEA reduced calcium-dependent glutamate release from cortical nerve terminals in a concentration-dependent way, alongside a fall in cytosolic calcium.
Laboratory studyOther animals - Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system
PEA increased blood-vessel dilation in response to acetylcholine in hypertensive rats, lowered the raised CYP2C23 and CYP2J2 enzyme levels seen in these rats, reduced soluble epoxide hydrolase and its breakdown product, and lowered angiotensin receptor 1 and angiotensin-converting enzyme expression.
Laboratory studyOther animals - Sex differences in N-palmitoylethanolamide effectiveness in neuropathic pain associated with lumbosciatalgia
Men improved on all measures with palmitoylethanolamide added; women improved on pain only.
Controlled trialHumans - Efficacy of ultra-micronized palmitoylethanolamide in canine atopic dermatitis: an open-label multi-centre study
This open-label study found:
Open-label, no control groupDogs - Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats
Diabetic rats showed raised VEGF, ICAM-1 and nitrotyrosine in the retina.
Laboratory studyOther animals - Protective effect of palmitoylethanolamide in a rat model of cystitis
Cyclophosphamide raised bladder PEA levels, increased CB1 receptor expression and lowered PPAR-alpha expression.
Laboratory studyOther animals - Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice
Cannabidiol or PEA given alone each reduced disease severity scores, inflammation, demyelination, axon damage and cytokine expression.
Laboratory studyOther animalsWith cannabidiol - Differential Effects of Palmitoylethanolamide against Amyloid-β Induced Toxicity in Cortical Neuronal and Astrocytic Primary Cultures from Wild-Type and 3xTg-AD Mice
Amyloid-beta reduced cell viability and altered glutamate levels in cultured neurons and astrocytes from wild-type mice, but not in cells from 3xTg-AD mice.
Laboratory studyOther animals - Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs
The pegylated prodrugs delayed and extended PEA's activity by changing how it accumulated in skin, particularly when the prodrug had a flexible structure and lower molecular weight.
Laboratory studyOther animalsTopicalWith polyethylene glycol (PEG) prodrugs of PEA, tested alone as modified forms of PEA - Amino Acid Derivatives as Palmitoylethanolamide Prodrugs: Synthesis, In Vitro Metabolism and In Vivo Plasma Profile in Rats
The study of amino acid ester prodrugs found:
Laboratory studyOther animalsWith L-Val-PEA and D-Val-PEA (amino-acid ester prodrugs of PEA, tested alone) - Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis
PEA and related lipids were higher in atopic skin than in healthy skin, PEA most of all.
Laboratory studyDogs - Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain
VAS pain score fell from 8.20 to 6.40 within 10 days (P<0.002) and to 5.80 by 40 days (P<0.001).
Open-label, no control groupHumans - Effect of Palmitoylethanolamide on Visual Field Damage Progression in Normal Tension Glaucoma Patients: Results of an Open-Label Six-Month Follow-Up
The trial found:
Controlled trialHumans - Effects of two different specific neck exercise interventions on palmitoylethanolamide and stearoylethanolamide concentrations in the interstitium of the trapezius muscle in women with chronic neck shoulder pain
Muscle PEA was higher in the pain patients than in controls, before and after either exercise program.
Randomised controlled trialHumans - Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain
Oral micronised and ultramicronised PEA reduced inflammatory cell infiltration, myeloperoxidase activity, paw swelling and thermal hyperalgesia, but oral nonmicronised PEA (PeaPure) did not.
Laboratory studyOther animals - Marketing messages in pharmacological papers and scientific chapters: the case of palmitoylethanolamide and its formulations
Some scientific papers on palmitoylethanolamide carry marketing messages for particular formulations, the author argues.
ReviewHumans - Palmitoylethanolamide: problems regarding micronization, ultra-micronization and additives
No study had compared micronised or ultramicronised palmitoylethanolamide against the pure compound in patients, the author points out, the minimum needed to support the claim of superiority.
ReviewHumans - Quantification of anandamide, oleoylethanolamide and palmitoylethanolamide in rodent brain tissue using high performance liquid chromatography-electrospray mass spectroscopy
The method gave recovery rates of 85.4 to 89.5 percent for PEA, with a lower limit of quantification of 0.5 ng/mL, and intraday and interday accuracy and precision under 15 percent.
Laboratory studyOther animals - Retrospective observational study to investigate Sinerga, a multifactorial nutritional product, and bacterial extracts in the prevention of recurrent respiratory infections in children
49 percent of children on the supplement had no antibiotic-treated infection, against 5 percent of those on bacterial extracts, and all supplement children had two or fewer episodes, against 51 percent of the comparison group.
Observational studyHumansWith bovine colostrum, phenylethylamine and a probiotic yeast - Micronized Palmitoylethanolamide Reduces the Symptoms of Neuropathic Pain in Diabetic Patients
This open-label study found:
Open-label, no control groupHumans - N-palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic eczema: results of a randomized, double-blind, controlled study in 60 patients
The trial found:
Randomised controlled trialHumansTopicalWith acetylethanolamine - Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold
The results support effectiveness and safety, the authors say, drawing on six earlier trials in respiratory infection.
ReviewHumans - Administration of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis: preliminary results
Pelvic pain, dysmenorrhoea and dyspareunia fell from baseline, though dysuria and dyschezia did not change significantly.
Open-label, no control groupHumansWith transpolydatin - Vestibulodynia: Synergy Between Palmitoylethanolamide + Transpolydatin and Transcutaneous Electrical Nerve Stimulation
Both groups improved significantly with TENS, and the improvement was similar between groups (VAS p = 0.57; dyspareunia p = 0.38).
Randomised controlled trialHumansWith transpolydatin - Effectiveness of Palmitoylethanolamide on Endothelial Dysfunction in Ocular Hypertensive Patients: A Randomized, Placebo-Controlled Cross-Over Study
This crossover trial found:
Randomised controlled trialHumans - Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs
The study found:
Laboratory studyDogs - Inhibitory effect of topical adelmidrol on antigen-induced skin wheal and mast cell behavior in a canine model of allergic dermatitis
Wheal areas were smaller on the adelmidrol-treated side on days 4 and 7, and mast cell numbers in biopsies were lower after 8 days of treatment.
Controlled trialDogsTopicalWith adelmidrol (a PEA analogue, tested alone) - Palmitoylethanolamide in the Treatment of Chronic Pain Caused by Different Etiopathogenesis
Mean pain intensity fell in patients who completed the study, regardless of the underlying condition and also in those taking no other analgesic.
Observational studyHumans - Palmitoylethanolamide Versus a Nonsteroidal Anti-Inflammatory Drug in the Treatment of Temporomandibular Joint Inflammatory Pain
A larger fall in pain in the palmitoylethanolamide group than in the ibuprofen group (P = .0001), and a larger gain in mouth opening (P = .022).
Randomised controlled trialHumans - Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study
The trial found:
Randomised controlled trialHumansWith transpolydatin - Use of palmitoylethanolamide in the entrapment neuropathy of the median in the wrist
PEA shortened the prolonged median nerve latency (p < 0.0004), with a larger effect at the higher dose.
Controlled trialHumans - Palmitoylethanolamide reduces granuloma-induced hyperalgesia by modulation of mast cell activation in rats
Palmitoylethanolamide reduced mast cell degranulation in a dose-dependent way (p < 0.01 at the highest dose), lowered nerve growth factor, prevented nerve sprouting into the granuloma and reduced touch sensitivity.
Laboratory studyOther animals - Ocular hypotensive effect of oral palmitoyl-ethanolamide: a clinical trial
This trial found:
Randomised controlled trialHumans - Palmitoylethanolamide Effects on Intraocular Pressure After Nd:YAG Laser Iridotomy: An Experimental Clinical Study
Pressure rose significantly after iridotomy in placebo-pretreated eyes (p ≤ 0.05) but not in PEA-pretreated eyes, and the slopes of the two pressure trends differed (p = 0.022).
Controlled trialHumans - Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy
Pain and all neurophysiological measures of myelinated A-alpha, A-beta and A-delta fibres improved (p < 0.05), though none returned to normal.
Open-label, no control groupHumans - Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNF-alpha release from canine skin mast cells
PEA inhibited release of all three mediators.
Laboratory studyDogs - Palmitoylethanolamide (Normast) in chronic neuropathic pain by compressive type lumbosciatalgia: multicentric clinical study
This trial found:
Randomised controlled trialHumans - Effect of palmitoylethanolamide–polydatin combination on chronic pelvic pain associated with endometriosis: Preliminary observations
All four patients had less pain within a month.
Case seriesHumansWith polydatin - Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study)
The study found:
Observational studyHumansTopical - Effect of PEA on LPS inflammatory action in human adipocytes
PEA did not block the lipopolysaccharide-driven rise in IL-6, but it did strengthen the lipopolysaccharide-driven fall in leptin release.
Laboratory studyHumans - Clinical and histological evaluation of an analogue of palmitoylethanolamide, PLR 120 (comicronized Palmidrol INN) in cats with eosinophilic granuloma and eosinophilic plaque: a pilot study
10 of 15 cats (67 percent) improved clinically.
Open-label, no control groupCats
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