ArticleBritish journal of pharmacology2016
The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2-arachidonoyl-glycerol and potentiates its actions at TRPV1 cation channels.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 4 syntheses or guidelines pooled it, 143 citations in OpenAlex.
- Cannabinoids, the Blood-Brain Barrier, and Neurodegeneration: Mechanisms, Dysregulation, and Therapeutic Perspectives.Biomolecules · 2026Pooled it
- Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.Nutrients · 2023Pooled it
- Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence.Frontiers in psychiatry · 2023Pooled it
- Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries-A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Palmitoylethanolamide Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial.The Journal of nutrition · 2022Trial
- Trial
- Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering from Migraine: A Pilot Study.Pain research & management · 2020Trial
- Endocannabinoids and related lipids in host metabolism-gut microbiome signalling.Nature reviews. Endocrinology · 2026Review
- The Effects of Palmitoylethanolamide or Ibuprofen on the Abundance Profile and Synthesis Rate of Proteins in C2C12 Skeletal Myotubes.FASEB bioAdvances · 2026Article
- Management strategies for burning mouth syndrome: a comprehensive review.Journal of oral & facial pain and headache · 2026Review
- Deciphering the interaction between N-palmitoyl-D-glucosamine and the endocannabinoidome.Scientific reports · 2025Article
- Palmitoylethanolamide: A Multifunctional Molecule for Neuroprotection, Chronic Pain, and Immune Modulation.Biomedicines · 2025Article
- Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations.Brain, behavior, & immunity - health · 2025Review
- Two-Step Cell Death Induction by the New 2-Arachidonoyl Glycerol Analog and Its Modulation by Lysophosphatidylinositol in Human Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Article
- Treatment of Migraine With Phytocannabinoids, the Involvement of Endocannabinoids in Migraine, and Potential Mechanisms of Action.Pain research & management · 2025Review
- Article
- Palmitoylethanolamide as a Supplement: The Importance of Dose-Dependent Effects for Improving Nervous Tissue Health in an In Vitro Model.International journal of molecular sciences · 2024Article
- The Impact of the CBMolecules (Basel, Switzerland) · 2024Review
- UltramicronizedCurrent neuropharmacology · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposePalmitoylethanolamide (PEA) is an endogenous congener of anandamide and potentiates its actions at cannabinoid CB1 and CB2 receptors, and at transient receptor potential vanilloid type-1 (TRPV1) channels. The other endocannabinoid, 2-arachidonoylglycerol (2-AG), was recently suggested to act as a TRPV1 channel agonist. We investigated if PEA enhanced levels of 2-AG in vitro or in vivo and 2-AG activity at TRPV1 channels. EXPERIMENTAL APPROACH: Endogenous lipid levels were measured by LC-MS in (i) human keratinocytes incubated with PEA (10-20 μM, 40 min, 6 and 24 h, 37°C); (ii) the blood of spontaneously Ascaris suum hypersensitive beagle dogs given a single oral dose of ultramicronized PEA (30 mg·kg(-1), 1, 2, 4 and 8 h from administration); (iii) the blood of healthy volunteers given a single oral dose of micronized PEA (300 mg, 2, 4 and 6 h from administration). Effects of 2-AG at TRPV1 channels were assessed by measuring intracellular Ca(2+) in HEK-293 cells over-expressing human TRPV1 channels. KEY
resultsPEA elevated 2-AG levels in keratinocytes (∼3-fold) and in human and canine plasma (∼2 and ∼20-fold respectively). 2-AG dose-dependently raised intracellular Ca(2+) in HEK-293-TRPV1 cells in a TRPV1-dependent manner and desensitized the cells to capsaicin. PEA only slightly enhanced 2-AG activation of TRPV1 channels, but significantly increased 2-AG-induced TRPV1 desensitization to capsaicin (IC50 from 0.75 ± 0.04 to 0.45 ± 0.02 μM, with PEA 2 μM). CONCLUSIONS AND IMPLICATIONS: These observations may explain why several effects of PEA are attenuated by cannabinoid receptor or TRPV1 channel antagonists. LINKED ARTICLES: This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.