Reviews and meta-analyses
A meta-analysis pools the numbers from several trials. A narrative review summarises the literature in the authors' own words. Both depend on the quality of the trials they include, and this page states those limits for each one.
Two things to check on any review page here: who wrote it and how the studies were chosen. Several reviews of palmitoylethanolamide were written by authors linked to the companies that make it, and several meta-analyses pooled open-label studies with no comparison group. Each entry says so where it applies.
Meta-analyses
16 listed, newest first.
- Efficacy, safety, and tolerability of palmitoylethanolamide in the management of diabetic neuropathic pain: a systematic review and meta-analysis
PEA, alone or in combination, was associated with significant reductions in neuropathic pain scores versus control, with a pooled effect of SMD -5.44 (95% CI -8.47 to -0.41, p=0.0004, I2=96%).
Meta-analysisHumans - 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 - Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding
Pooled standardised mean difference in pain favoured palmitoylethanolamide at every timepoint: -0.36 at 4 weeks (95% CI -0.65 to -0.07), -0.9 at 6 weeks (-1.60 to -0.31), -0.98 at 8 weeks (-1.61 to -0.36) and -1.16 at 24 to 26 weeks (-2.15 to -0.17).
Meta-analysisHumans - Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis
Pain fell a further 1.36 points between day 30 and day 60 (95% CI 0.98 to 1.74).
Meta-analysisHumans - Efficacy of Palmitoylethanolamide and Luteolin Association on Post-Covid Olfactory Dysfunction: A Systematic Review and Meta-Analysis of Clinical Studies
PEA plus luteolin, given with olfactory training, favoured recovery of smell over conventional therapy.
Meta-analysisHumansWith luteolin - 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 - 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 - 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 - Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis
Plasma OEA and stearoylethanolamide were higher in fibromyalgia than controls (P = 0.005 and P < 0.0001).
Meta-analysisHumans - Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence
The six non-randomised studies favoured palmitoylethanolamide over control (p < 0.00001).
Meta-analysisHumans - Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies
Very low certainty evidence that adverse events are common (26.0%, 95% CI 13.2% to 41.2%), including psychiatric events (13.5%).
Meta-analysisHumans - 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
PPAR-alpha agonists, predominantly palmitoylethanolamide, along with CB1, CB2 and non-selective cannabinoid agonists, significantly reduced pain behaviours across inflammatory and neuropathic models.
Meta-analysisOther animals - Dietary interventions for multiple sclerosis-related outcomes
All 30 trials had at least one issue giving unknown or high risk of bias.
Meta-analysisHumans - Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis
PEA reduced pain more than inactive control: weighted mean difference 2.03 points (95 percent CI 1.19 to 2.87, p < 0.001).
Meta-analysisHumans - 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, 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
Reviews in people
45 listed.
- 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 - 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 - 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 - 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 - 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 - 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 - 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 - Efficacy of mast cell directed therapies in irritable bowel syndrome: a systematic review
From 1,384 citations, 11 trials were included: ten randomised controlled trials and one cohort study, only three at low risk of bias.
ReviewHumansWith polydatin (palmitoylethanolamide-polydatin was one of the therapies reviewed) - Cannabinoids and Sleep: Exploring Biological Mechanisms and Therapeutic Potentials
THC can promote sleep at first but alters sleep architecture with long-term use, the authors write, while CBD is reported to improve sleep quality without psychoactive effects.
ReviewHumans - 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 - 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) - Emerging drugs for the treatment of irritability associated with autism spectrum disorder
After risperidone and aripiprazole, memantine monotherapy may be beneficial, and palmitoylethanolamide and 15 other agents given as adjuncts to risperidone, plus clonidine and methylphenidate, outperformed placebo in trials.
ReviewHumans - 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
Six observational studies found raised plasma levels of palmitoylethanolamide in people with psychosis, described as a possible early compensatory response.
ReviewHumans - 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 - 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 - 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 - 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) - 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 - 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 - 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 - Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review
Cannabis use prevalence was 13% to 27%, and 61% to 95.5% of users reported pain relief.
ReviewHumansWith Reviewed studies included PEA-combination medicines (partners not named in the abstract) alongside cannabis products - 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) - 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 - 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 - 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) - Effectiveness of Nonpharmacologic Treatments of Burning Mouth Syndrome: A Systematic Review
Seven placebo-controlled alpha-lipoic acid trials showed significant pain relief.
ReviewHumans - Endocannabinoid markers in autism spectrum disorder: A scoping review of human studies
Three studies reported significantly lower anandamide in autism than in controls.
ReviewHumans - 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 - 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 - Phytotherapics in COVID19: Why palmitoylethanolamide?
No PEA-specific data on COVID-19 are reported.
ReviewHumans - 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 - 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 - 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 - 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) - 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 - 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 - 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 - Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy
For treatment of up to 49 days, the data argue against serious adverse reactions at a rate of 1 in 200 or more, the authors concluded.
ReviewHumans - 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 - 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 - 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
Reviews in animals
53 listed.
- 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Review of Alzheimer's disease drugs and their relationship with neuron-glia interaction
The abstract gives no specific findings on palmitoylethanolamide.
ReviewHumansOther 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 - 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 - 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 - 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
PEA levels are reduced in osteoarthritic joints, and adelmidrol, a PEA enhancer, reduced mast cell infiltration, cytokine release and cartilage degeneration in preclinical and clinical studies, the authors state.
ReviewHumansOther animalsWith adelmidrol (a PEA analogue) with high molecular weight hyaluronic acid, by intra-articular injection - 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 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 - 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 - 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 - 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 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma
The abstract reports no palmitoylethanolamide-specific findings or numbers.
ReviewHumansOther 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 - 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 - 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 - 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 - 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 - 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 - 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 - The Basal Pharmacology of Palmitoylethanolamide
PPAR-alpha is described as the best supported target, with further evidence for TRPV1 and GPR55 and for effects on mast cells.
ReviewHumansOther animals - 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) - Role of palmitoylethanolamide (PEA) in depression: Translational evidence
Antidepressant-like activity appears in animal models.
ReviewHumansOther 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 - 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 - 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 - 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