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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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164 studies
- Levagen+ (palmitoylethanolamide) alleviates joint pain and reduces the impact of joint pain in canines and felines: a double-blind, placebo-controlled, randomized clinical trial
For dogs, the authors reported that 76% of the supplement group and 40% of the placebo group met the questionnaire's definition of treatment success (P < 0.05).
Randomised controlled trialDogsCats - 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 authors reported that 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 - Temporal effects of Palmitoylethanolamide (PEA) in modulating knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled trial
The authors reported that placebo showed the greater improvement at week 4, and that the palmitoylethanolamide groups showed larger falls over the following 8 weeks.
Randomised controlled trialHumans - Targeting PTSD with ultramicronized palmitoylethanolamide: Results from a randomized trial integrating pharmacotherapy and cognitive behavioral therapy
The authors reported the largest improvement 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
A clear pain reduction on the time-series graph for one of four participants.
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
Baseline symptom scores did not differ between treated and untreated men.
Observational studyHumansWith Epilobium and Calendula (with or without a saw palmetto, lycopene and selenium product) - Phase 2 study of palmitoylethanolamide combined with luteoline in frontotemporal dementia patients
The authors reported that the main score worsened by 0.53 points in the treatment group and by 1.39 points in the placebo group (difference 0.86, 95% CI 0.28 to 1.45, P = 0.005).
Randomised controlled trialHumansWith luteolin - Retrospective Evaluation of L-Acetyl Carnitine and Palmitoylethanolamide as Add-On Therapy in Patients with Fibromyalgia and Small Fiber Neuropathy
The authors reported a median fall of 19 points on the questionnaire in the add-on group (p < 0.001) and of 1 point in the standard care group (p = 0.12).
Observational studyHumansWith acetyl-L-carnitine, Boswellia serrata and vitamins B6 and E - Effects of palmitoylethanolamide in clinical high-risk for psychosis: A nonrandomized open-label trial
The authors reported that the total symptom score fell by 30% and the unusual thought content score by 52.5% at 12 weeks.
Open-label, no control groupHumans - Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations
The authors rated most of the included trials as good quality on the Joanna Briggs Institute tool, and two as fair.
ReviewHumans - Unlocking Relief: Investigating the Impact of a Fixed Combination of Acetyl-L-Carnitine and Palmitoylethanolamide on Traumatic Acute Low Back Pain
Both pain scores fell over 8 weeks, physical SF-36 domains improved and NSAID use fell.
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 authors reported small falls in body weight (86.4 to 85.3 kg), BMI and fat mass, and falls in CRP and ESR, during the supplement phase.
Randomised controlled trialHumansWith rutin and hydroxytyrosol - The effects of formulated palmitoylethanolamide supplementation on indicators of stress and heart rate variability in female university students: a randomised cross-over trial
The authors reported a rise in one heart rate variability measure (SDNN) on palmitoylethanolamide compared with placebo (p = 0.024).
Randomised controlled trialHumans - 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 - Evaluation of the Clinical Efficacy of a Novel Palmitoylethanolamide–Equisetum arvense Supplement for the Management of Chronic Pain: Findings from a Prospective Clinical Trial
The authors reported a fall of 3.8 points on the numeric pain rating scale (p < 0.0001) and a 35% rise in the quality of life score.
Open-label, no control groupHumansWith Equisetum arvense (horsetail) - Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial
The authors reported a fall in migraine days from 3.4 to 2.2 a month in the combination group, with no change in the placebo group.
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 - Chronic palmitoylethanolamide administration via slow-release subcutaneous pellets promotes neuroprotection and mitigates neuroinflammation in the Tg2576 mouse model of Alzheimer's disease
The authors reported 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 authors reported a pooled standardised mean difference in pain of -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), all in favour of palmitoylethanolamide.
Meta-analysisHumans - Palmitoylethanolamide in the Treatment of Pain and Its Clinical Application Prospects
The authors describe multi-target effects through PPAR-alpha and the endocannabinoid system and a low rate of adverse reactions, mainly mild gastrointestinal discomfort and dizziness.
ReviewHumans - Palmitoylethanolamide causes dose-dependent changes in brain function and the lipidome
The authors reported an inverse dose response in one imaging measure, with the lowest dose producing the largest effect, and a dose-dependent rise in functional connectivity.
Laboratory studyOther 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
The authors reported lower triglycerides and lower IL-2 on palmitoylethanolamide.
Randomised controlled trialHumans - Assessing the biobehavioral effects of ultramicronized-palmitoylethanolamide monotherapy in autistic adults with different severity levels: a report of two cases
The authors reported that one patient had improved depressive symptoms and social engagement, with lower inflammatory markers.
Case seriesHumans - 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
The authors reported that more migraine events resolved at 2 hours and at 8 hours in the Levagen+ group than in the placebo group, that pain scores were lower at 1.5 and 4 hours, and that rescue medication was used less often.
Randomised controlled trialHumans - Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics
TDI rose from 21.8 to 29.7 in the PEA-luteolin group and from 19.6 to 27.5 in the combination group (both p < 0.01).
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
The authors reported improvements in pain intensity (p = 0.0015), neuropathic pain symptoms (p = 0.0007) and quality of life (p = 0.0036) during treatment.
Open-label, no control groupHumans - Treatment of Established Chemotherapy-Induced Neuropathy with N-Palmitoylethanolamide: A Randomized, Double-Blind Phase II Pilot Study
The authors reported no suggestion that either palmitoylethanolamide group did better than placebo.
Randomised controlled trialHumans - Palmitoylethanolamide and polydatin in pediatric irritable bowel syndrome: A multicentric randomized controlled trial
The authors reported complete remission in 50% of the treatment group and 22% of the placebo group (P = 0.015).
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 authors reported that pain scores fell from 20.9 to 13.9 in the combination group (p < 0.001) and did not change on placebo.
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 authors reported that the supplement group improved in odour discrimination and overall smell scores, and the training-only group did not.
Randomised controlled trialHumansWith luteolin - 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
The authors reported similar gains in lean mass in both groups (2.0% on palmitoylethanolamide, 2.4% on placebo) and identical gains in thigh muscle size.
Randomised controlled trialHumans - Formulated Palmitoylethanolamide Supplementation Improves Parameters of Cognitive Function and BDNF Levels in Young, Healthy Adults: A Randomised Cross-Over Trial
The authors reported a rise in serum BDNF on palmitoylethanolamide compared with placebo (p = 0.0057) and better scores on two measures of one memory task.
Randomised controlled trialHumans - Palmitoylethanolamide in Postmenopausal Metabolic Syndrome: Current Evidence and Clinical Perspectives
The authors describe laboratory and preliminary clinical data suggesting effects on blood lipids, insulin sensitivity and inflammation through PPAR-alpha.
ReviewHumansOther animals - Micronized/ultramicronized palmitoylethanolamide improves depression and fatigue in coronavirus disease 2019 (COVID-19) survivors
The treated group improved more in depression and fatigue (both p < 0.05) but not in chronic pain or wellbeing.
Observational studyHumans - 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 - Efficacy of Topical Palmitoylethanolamide (Levagen+) for the Management of Eczema Symptoms: A Double-Blind, Comparator-Controlled, Randomized Clinical Trial
The authors reported lower scores for redness, dryness and the total eczema measure in the palmitoylethanolamide group at week 4 (p < 0.05), with less weeping and less roughness than the comparator.
Randomised controlled trialHumansTopical - 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 - Neuropathic pain in cats: Mechanisms and multimodal management
The author presents a structured approach to recognising and managing neuropathic pain in cats, drawing on the literature and her own experience.
ReviewCats - Palmitoylethanolamide Does Not Affect Recovery from Exercise-Induced Muscle Damage in Healthy Males
The authors reported that strength fell by up to about 40% and jump height by about 17% after the exercise in both conditions, with the same rise in soreness and creatine kinase.
Randomised controlled trialHumans - Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis
The authors reported a further fall in pain of 1.36 points between day 30 and day 60 (95% CI 0.98 to 1.74).
Meta-analysisHumans - A Fixed Combination of Palmitoylethanolamide and Melatonin (PEATONIDE) for the Management of Pain, Sleep, and Disability in Patients with Fibromyalgia: A Pilot Study
The authors reported that at 1 month pain fell by 1.16 points and the insomnia score improved by 6.24 points (both p < 0.01).
Open-label, no control groupHumansWith melatonin - Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence
The authors reported that six observational studies found raised plasma levels of palmitoylethanolamide in people with psychosis, which they describe as a possible early compensatory response.
ReviewHumans - The Effect of Levagen+ (Palmitoylethanolamide) Supplementation on Symptoms of Allergic Rhinitis—A Double-Blind Placebo-Controlled Trial
The authors reported no significant difference between the groups in nasal symptom scores over the 14 days.
Randomised controlled trialHumans - Efficacy of Palmitoylethanolamide and Luteolin Association on Post-Covid Olfactory Dysfunction: A Systematic Review and Meta-Analysis of Clinical Studies
The authors reported that the combination, given with olfactory training, favoured recovery of smell compared with conventional therapy.
Meta-analysisHumansWith luteolin - Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial
The authors reported that 89.2% of the group given the combination plus olfactory training improved by 3 points or more.
Randomised controlled trialHumansWith luteolin - Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials
The authors reported a pooled standardised mean difference in pain scores of 1.68 in favour of palmitoylethanolamide (95% CI 1.05 to 2.31).
Meta-analysisHumans - Alpha-Lipoic Acid, Palmitoylethanolamide, Myrrh, and Oxygen-Ozone Therapy Improve Pharmacological Therapy in Acute Painful Lumbosacral Radiculopathy due to Herniated Disc
All four groups improved.
Controlled trialHumansWith alpha-lipoic acid and myrrh - A randomized interventional clinical trial assessing the safety and effectiveness of PeaNoc XL tablets in managing joint pain and inflammation in arthritis patients
In the add-on group, all four inflammatory markers fell from baseline (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 improved from baseline.
Open-label, no control groupHumansWith astaxanthin - Palmitoylethanolamide counteracts high-fat diet-induced gut dysfunction by reprogramming microbiota composition and affecting tryptophan metabolism
The authors reported lower inflammatory markers in the colon, higher serotonin and lower kynurenine, and 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
The authors report that all patient-reported symptoms improved with supplementation, especially pain, mood, fatigue, brain fog and smell and taste.
Observational studyHumansWith luteolin - The Efficacy of Palmitoylethanolamide (Levagen+) on the Incidence and Symptoms of Upper Respiratory Tract Infection—A Double Blind, Randomised, Placebo-Controlled Trial
The authors reported 39 infection episodes in the Levagen+ group and 64 in the placebo group (p = 0.0056), and 32 participants with an infection in the Levagen+ group against 55 on placebo (p = 0.0116).
Randomised controlled trialHumans - Palmitoylethanolamide and acetyl-L-carnitine act synergistically with duloxetine and pregabalin in fibromyalgia: results of a randomised controlled study
The authors reported that 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 - Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome
LICI increased in the PEA-luteolin group (conditioned response fell from 67 to 32 percent of test amplitude) but not with placebo (67 to 71 percent); interaction p = 0.034.
Randomised controlled trialHumansWith luteolin - Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania: A randomized, double-blind, placebo-controlled trial
The authors reported a larger fall in mania scores in the palmitoylethanolamide group from baseline to week 4 (P = 0.018) and week 6 (P = 0.002).
Randomised controlled trialHumans - Effects of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Stages: A Case–Control Study
The authors reported lower CRP, IL-6 and neutrophil-to-lymphocyte ratio in the treated group at 28 days, lower D-dimer and higher antibody levels.
Controlled trialHumans - Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders
The authors describe actions through PPAR-alpha, GPR55 and TRPV1, and early clinical signs of effect on cortical plasticity in frontotemporal dementia.
ReviewHumansOther animalsWith luteolin - 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 - Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study
The authors reported an average improvement of 10.7 points in odour identification at 3 months (p < 0.0001), with improvements in parosmia and in mental clouding.
Open-label, no control groupHumansWith luteolin - Palmitoylethanolamide and Related ALIAmides for Small Animal Health: State of the Art
The authors summarise studies in dogs and cats, including an open multi-centre study of 160 dogs given 10 mg/kg a day for 56 days, and the cat trial by Noli and colleagues.
ReviewDogsCats - 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
At day 90, 92 percent of the PEA-luteolin group had improved TDI compared with 42 percent of the placebo group.
Randomised controlled trialHumansWith luteolin - Palmitoylethanolamide Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial
The authors reported that 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-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 - Circulating Endocannabinoids in Canine Multicentric Lymphoma Patients
PEA, oleoylethanolamide and anandamide were higher in dogs with lymphoma than in healthy dogs.
Observational studyDogs - Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice
The authors reported that 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 less activation of brain immune cells.
Laboratory studyOther animals - Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans
The authors describe laboratory evidence of protective and anti-inflammatory effects in models of the major neurodegenerative diseases.
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
The authors reported that 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 - A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain
The authors reported lower total pain, pain interference and NPSI scores than placebo from week 2 onward (P ≤ 0.001).
Randomised controlled trialHumans - The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study
The authors reported a significant improvement in functional status scores.
Observational studyHumans - Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial
The authors reported a greater improvement in negative symptoms in the palmitoylethanolamide group (p = 0.012).
Randomised controlled trialHumans - Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence
The authors reported that the six non-randomised studies favoured palmitoylethanolamide over the control (p < 0.00001).
Meta-analysisHumans - Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Model of Inflammatory Pain
The authors reported that the combined product at 5 mg/kg reduced swelling, heat sensitivity, mast cell infiltration and inflammatory markers, and did so more than either compound alone at higher doses, and more than a 200 mg/kg plain mixture.
Laboratory studyOther animalsWith acetyl-L-carnitine - A Phase-2 Pilot Study of a Therapeutic Combination of Delta-9-Tetrahydracannabinol and Palmitoylethanolamide for Adults With Tourette's Syndrome
Tic scores fell by about 7 points, over 20 percent, with a significant change within the first week.
Open-label, no control groupHumansWith delta-9-tetrahydrocannabinol (THC) - Palmitoylethanolamide Modulation of Microglia Activation: Characterization of Mechanisms of Action and Implication for Its Neuroprotective Effects
The authors reported that 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 - Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer's Disease
The authors reported that 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 supplement group improved more on the Sniffin' Sticks score than controls (p = 0.01).
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 - Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?
The authors conclude that the available evidence suggests a place for micronised palmitoylethanolamide in the dietary management of chronic pain.
ReviewDogsCats - Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?
The authors conclude that the evidence supports a place for micronised palmitoylethanolamide in the dietary management of chronic pain in dogs and cats.
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 - Effectiveness of a nutraceutical agent in the non-surgical periodontal therapy: a randomized, controlled clinical trial
The authors reported greater reductions in pocket depth (p = 0.003) and bleeding (p < 0.001) at 6 months in the supplement group, 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 - Tolerability profile of topical cannabidiol and palmitoylethanolamide: a compilation of single-centre randomized evaluator-blinded clinical and in vitro studies in normal skin
No irritation or sensitisation from any product.
Controlled trialHumansTopicalWith cannabidiol - Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients
The authors propose, from earlier laboratory and clinical work, that its effects on immune response and inflammation could limit organ damage in COVID-19.
ReviewHumansOther 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 in 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) - Palmitoylethanolamide for sleep disturbance. A double-blind, randomised, placebo-controlled interventional study
The authors reported no difference between groups in Pittsburgh Sleep Quality Index scores, sleep quantity or sleep quality at week 8.
Randomised controlled trialHumans - Impaired Duodenal Palmitoylethanolamide Release Underlies Acid-Induced Mast Cell Activation in Functional Dyspepsia
Acid raised mast cell density and mediator release in all biopsies, more so in dyspepsia.
Laboratory studyHumansOther animals - Increased Absorption of Palmitoylethanolamide Using a Novel Dispersion Technology System (LipiSperse)
The authors reported that 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 - An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events
The authors describe palmitoylethanolamide as protective and anti-inflammatory in laboratory models, and note that it has no antioxidant activity of its own.
ReviewHumansOther animalsWith luteolin - ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain
The authors describe clinical trials of several formulations in diabetic neuropathy, chemotherapy-related neuropathy, carpal tunnel syndrome, sciatica-type pain and jaw joint pain, and describe safety and tolerability as high.
ReviewHumansOther animals - Oral Supplementation with Ultramicronized Palmitoylethanolamide for Joint Disease and Lameness Management in Four Jumping Horses: A Case Report
The authors reported that lameness resolved in all four horses and that the horses returned to showjumping competition without recurrence during the report period.
Case seriesHorses - The Effect of Orally Dosed Levagen+™ (palmitoylethanolamide) on Exercise Recovery in Healthy Males—A Double-Blind, Randomized, Placebo-Controlled Study
The authors reported lower myoglobin at 1, 2 and 3 hours after exercise and lower blood lactate at 1 and 3 hours in the Levagen+ group.
Randomised controlled trialHumans - 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 - The Basal Pharmacology of Palmitoylethanolamide
The authors describe PPAR-alpha as the best supported target, with further evidence for TRPV1 and GPR55 and for effects on mast cells.
ReviewHumansOther animals - Effect of palmitoylethanolamide on inner retinal function in glaucoma: a randomized, single blind, crossover, clinical trial by pattern-electroretinogram
The authors reported a higher retinal response amplitude during the palmitoylethanolamide period (0.56 microvolts, p < 0.001), eye pressure lower by 1.58 mmHg (p < 0.001) and a better quality of life score.
Randomised controlled trialHumans - Effects of the glial modulator palmitoylethanolamide on chronic pain intensity and brain function
The authors reported that pain fell in 16 of the 22 participants, and by more than 20% in 11.
Open-label, no control groupHumans - 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 - Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo: A Randomized, Placebo-controlled, Double-blind Controlled Trial
Aspirin raised absorption of lactulose and mannitol, and PEA or cannabidiol reduced that rise (p < 0.001).
Randomised controlled trialHumans - Micronized Palmitoylethanolamide: A Post Hoc Analysis of a Controlled Study in Patients with Low Back Pain – Sciatica
The authors reported a number needed to treat of 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 - Co-ultraPEALut: Role in Preclinical and Clinical Delirium Manifestations
The abstract reports that Glialia prevented the onset of postoperative delirium and reduced symptom intensity and duration.
Controlled trialHumansOther animalsWith luteolin - Effect of dietary supplementation with ultramicronized palmitoylethanolamide in maintaining remission in cats with nonflea hypersensitivity dermatitis: a double-blind, multicentre, randomized, placebo-controlled study
The authors reported a mean time to relapse of 40.5 days in the supplement group and 22.2 days in the placebo group (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.
Open-label, no control groupHumans - Efficacy of ultramicronized palmitoylethanolamide in burning mouth syndrome-affected patients: a preliminary randomized double-blind controlled trial
The authors reported a statistically significant reduction in burning sensation in the treatment group compared with placebo at 60 days (p < 0.0132).
Randomised controlled trialHumans - Ultramicronized Palmitoylethanolamide (um-PEA) as Add-on Treatment in Fibromyalgia Syndrome (FMS): Retrospective Observational Study on 407 Patients
Among those analysed, VAS fell from 75.8 to 52.5 and the impact score from 68.4 to 49.1 (both p < 0.001).
Observational studyHumans - A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis
The authors reported 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 - 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
The authors reported that chronic pelvic pain scores fell from 7.2 to 2.6 (p < 0.0001), with smaller falls in period pain and other symptoms.
Open-label, no control groupHumansWith polydatin - Effects of Add-On Ultramicronized N-Palmitol Ethanol Amide in Patients Suffering of Migraine With Aura: A Pilot Study
The authors reported lower pain scores at 60 and 90 days in the supplement group, a fall in attacks from 3.1 to 2.0 a month, and a 50% reduction in anti-inflammatory use.
Controlled trialHumans - Nonsurgical lumbar radiculopathies treated with ultramicronized palmitoylethanolamide (umPEA): A series of 100 cases
After one month, mean VAS fell by 1.9, 2.7 and 2.3 points in the mild, moderate and severe baseline groups (p < 0.0001), with further improvement after the second cycle.
Case seriesHumans - Ultra-micronized Palmitoylethanolamide Effects on Sleep-wake Rhythm and Neuropathic Pain Phenotypes in Patients with Carpal Tunnel Syndrome: An Open-label, Randomized Controlled Study
The authors reported a highly significant improvement in sleep quality (p < 0.0001) and in pain (p < 0.0001) in the treated group at the end of the pre-surgery period.
Controlled trialHumans - Localization of cannabinoid receptors CB1, CB2, GPR55, and PPAR-alpha in the canine gastrointestinal tract
All four receptors were found in the dog gut.
Laboratory studyDogs - Palmitoylethanolamide as adjunctive therapy in major depressive disorder: A double-blind, randomized and placebo-controlled trial
The authors reported a larger fall in depression scores in the palmitoylethanolamide group at week 2 (8.30 against 5.81 points, P = .004) and across the trial.
Randomised controlled trialHumans - Palmitoylethanolamide as adjunctive therapy for autism: Efficacy and safety results from a randomized controlled trial
The authors reported a larger improvement in irritability and in hyperactivity in the palmitoylethanolamide group than with risperidone alone (p = 0.001).
Randomised controlled trialHumans - Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Levels and Spinal Anti-hyperalgesic Effect
The authors reported that the ultramicronised form gave a peak plasma level 5 times that of plain powder, reached at 5 minutes.
Laboratory studyOther animals - Ultramicronized palmitoylethanolamide counteracts the effects of compound 48/80 in a canine skin organ culture model
Compound 48/80 caused mast cell degranulation and capillary dilation.
Laboratory studyDogs - 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 - A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models
The authors reported that 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
The authors reported 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 - 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 authors reported that 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 authors reported that pain scores fell by 0.5 points on palmitoylethanolamide and 0.8 points on placebo.
Randomised controlled trialHumans - N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients with Chronic Pain
The authors reported a small, statistically significant effect on pain in favour of palmitoylethanolamide in 2 of the 7 patients, of about 8% of baseline pain, and an effect on function in 1 patient.
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 authors reported that the combination improved the urinary symptom score and reduced the prostatitis symptom score more than saw palmetto.
Randomised controlled trialHumansWith alpha-lipoic acid - 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.
Observational studyHumans - The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations
The authors describe palmitoylethanolamide 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 - Efficacy of Body Lotion Containing N-palmitoylethanolamine in Subjects with Chronic Pruritus due to Dry Skin: A Dermatocosmetic Study
The authors reported that itch fell significantly in both groups, and that the difference between the groups was not significant (a fall of 1.1 points with palmitoylethanolamide and 0.6 points without).
Randomised controlled trialHumansTopical - Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: A randomized, double-blind, placebo-controlled trial
The authors reported no difference in pain intensity between palmitoylethanolamide and placebo (P = 0.46).
Randomised controlled trialHumans - 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 - Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy
The authors concluded that for treatment of up to 49 days, the data argue against serious adverse reactions at a rate of 1 in 200 or more.
ReviewHumans - Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing–Remitting Multiple Sclerosis
The authors reported less pain at the injection site at 6 and 12 months than with placebo, a better quality of life score and lower levels of inflammatory cytokines.
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 - 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 the other cells, without inhibiting the PEA-degrading enzymes, and reduced MCP-2 release.
Laboratory studyDogsOther 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 - Palmitoylethanolamide in Fibromyalgia: Results from Prospective and Retrospective Observational Studies
The authors reported that on duloxetine and pregabalin alone, pain scores fell from 6.9 to 3.0 over 6 months.
Observational studyHumans - Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome
The authors conclude 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 - 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
The authors reported that mean itch scores fell from 5.7 cm to 3.63 cm (P < 0.0001).
Open-label, no control groupDogs - 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 - Effect of Palmitoylethanolamide on Visual Field Damage Progression in Normal Tension Glaucoma Patients: Results of an Open-Label Six-Month Follow-Up
The authors reported that eye pressure fell from 14.4 to 11.1 mmHg in the treated group (p < 0.01), and that two visual field indices improved compared with baseline.
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 - Marketing messages in pharmacological papers and scientific chapters: the case of palmitoylethanolamide and its formulations
The author argues that some scientific papers on palmitoylethanolamide carry marketing messages for particular formulations.
ReviewHumans - Micronized Palmitoylethanolamide Reduces the Symptoms of Neuropathic Pain in Diabetic Patients
All three scores fell by day 30 and further by day 60 (p < 0.0001), across pain, burning, paraesthesia and numbness.
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 authors reported that both emollients improved the skin measures.
Randomised controlled trialHumansTopicalWith acetylethanolamine - Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold
The authors note that palmitoylethanolamide has been known as a food component since 1957, and that most research since the work of Levi-Montalcini in 1993 has concerned nerve pain and mast cell disorders.
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.
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
Baseline FMD was lower in ocular hypertension than in controls (6.1 versus 10.9 percent).
Randomised controlled trialHumans - Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs
The authors reported smaller wheals after allergen challenge following a dose.
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
The authors reported 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
All three groups improved after surgery.
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
The authors reported that 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
On PEA, pressure fell by 3.2 mmHg at 1 month and 3.5 mmHg (15.9 percent) at 2 months from a baseline of 21.6.
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.
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
Pain and disability changes differed across the three groups (p < 0.001).
Randomised controlled trialHumans - Effect of palmitoylethanolamide–polydatin combination on chronic pelvic pain associated with endometriosis: Preliminary observations
The authors reported that 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 authors reported a 58.6% fall in the combined symptom score by the end of the study.
Observational studyHumansTopical - 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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