| Reference | [1]. Pain Physician. 2017 Jul;20(5):353-362.<br />
Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis.<br />
Artukoglu BB(1), Beyer C(1), Zuloff-Shani A(2), Brener E(2), Bloch MH(1).<br />
Author information: (1)Yale Child Study Center, New Haven, CT. (2)Therapix Biosciences, Tel Aviv, Israel.<br />
BACKGROUND: Palmitoylethanolamide (PEA) is a cannabimimetic compound that has been investigated as an analgesic agent in animal models and clinical trials. OBJECTIVES: We conducted a meta-analysis to examine the efficacy of PEA for treating pain in randomized, controlled trials. STUDY DESIGN: Systematic review and meta-analysis. SETTING: This meta-analysis examined all randomized, controlled trials involving the effect of PEA on pain score. METHODS: We searched PubMed and Embase for randomized, active or placebo-controlled trials of PEA for the treatment of acute or chronic pain. Our primary outcome was the weighted mean difference in visual analog pain scales of PEA treatment compared to inactive controls. RESULTS: We identified 10 studies including data from 786 patients who received PEA and 512 controls for inclusion in our systematic review. Eight trials included an inactive control group and were included in the meta-analysis. PEA was associated with significantly greater pain reduction compared to inactive control conditions (WMD = 2.03, 95% CI: 1.19 – 2.87, z = 4.75, P < 0.001). Use of placebo control, presence of blinding, allowance for concomitant treatments, and duration or dose of PEA treatment did not affect the measured efficacy of PEA. All-cause dropout was non-significantly reduced in the PEA group compared to inactive control conditions (RR = 0.36, 95% CI: 0.10 – 1.26, z = -1.60, P = 0.11). LIMITATIONS: This meta-analysis relied on a relatively small number of trials across a variety of conditions causing pain with differing trial designs. Overall quality of the underlying studies and assessment of side effects were often poor. CONCLUSIONS: PEA may be a useful treatment for pain and is generally well tolerated in research populations. Further, well-designed, randomized, placebo-controlled trials are needed to provide reliable estimates of its efficacy and to identify less serious adverse events associated with this compound. KEY WORDS: PEA, palmidrol, palmitoylethanolamide, efficacy, pain, pain management, meta-analysis.<br />
PMID: 28727699<br />
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[2]. Int J Mol Sci. 2020 Oct 26;21(21):7942. doi: 10.3390/ijms21217942.<br />
The Basal Pharmacology of Palmitoylethanolamide.<br />
Rankin L(1), Fowler CJ(1).<br />
Author information: (1)Department of Integrative Medical Biology, Umeå University, SE-901 87 Umeå, Sweden.<br />
Palmitoylethanolamide (PEA, N-hexadecanoylethanolamide) is an endogenous compound belonging to the family of N-acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α), but PPAR-α-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.<br />
DOI: 10.3390/ijms21217942 PMCID: PMC7662788 PMID: 33114698<br />
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[3]. Br J Clin Pharmacol. 2016 Oct;82(4):932-42. doi: 10.1111/bcp.13020. Epub 2016 Jun 29.<br />
Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy.<br />
Gabrielsson L(1), Mattsson S(1), Fowler CJ(2).<br />
Author information: (1)Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87, Umeå, Sweden. (2)Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87, Umeå, Sweden. [email protected].<br />
Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta-analysis of PEA as an analgesic have been published in the literature. For treatment times up to 49 days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater. For treatment lasting more than 60 days, the number of patients is insufficient to rule out a frequency of ADRs of less than 1/100. The six published randomized clinical trials are of variable quality. Presentation of data without information on data spread and nonreporting of data at times other than the final measurement were among issues that were identified. Further, there are no head-to-head clinical comparisons of unmicronized vs. micronized formulations of PEA, and so evidence for superiority of one formulation over the other is currently lacking. Nevertheless, the available clinical data support the contention that PEA has analgesic actions and motivate further study of this compound, particularly with respect to head-to-head comparisons of unmicronized vs. micronized formulations of PEA and comparisons with currently recommended treatments.<br />
DOI: 10.1111/bcp.13020 PMCID: PMC5094513 PMID: 27220803<br />
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[4]. Br J Pharmacol. 2017 Jun;174(11):1349-1365. doi: 10.1111/bph.13580. Epub 2016 Sep 29.<br />
The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations.<br />
Petrosino S(1)(2), Di Marzo V(1).<br />
Author information: (1)Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy. (2)Epitech Group S.p.A., Saccolongo (PD), Italy.<br />
Palmitoylethanolamide (PEA) has emerged as a potential nutraceutical, because this compound is naturally produced in many plant and animal food sources, as well as in cells and tissues of mammals, and endowed with important neuroprotective, anti-inflammatory and analgesic actions. Several efforts have been made to identify the molecular mechanism of action of PEA and explain its multiple effects both in the central and the peripheral nervous system. Here, we provide an overview of the pharmacology, efficacy and safety of PEA in neurodegenerative disorders, pain perception and inflammatory diseases. The current knowledge of new formulations of PEA with smaller particle size (i.e. micronized and ultra-micronized) when given alone or in combination with antioxidant flavonoids (i.e. luteolin) and stilbenes (i.e. polydatin) is also reviewed. LINKED ARTICLES: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.<br />
DOI: 10.1111/bph.13580 PMCID: PMC5429331 PMID: 27539936<br />
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[5]. Int J Mol Sci. 2020 Jul 27;21(15):5330. doi: 10.3390/ijms21155330.<br />
ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain.<br />
D'Amico R(1), Impellizzeri D(1), Cuzzocrea S(1)(2), Di Paola R(1).<br />
Author information: (1)Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy. (2)Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd, St Louis, MO 63104, USA.<br />
Neuropathic pain results from lesions or diseases of the somatosensory nervous system and it remains largely difficult to treat. Peripheral neuropathic pain originates from injury to the peripheral nervous system (PNS) and manifests as a series of symptoms and complications, including allodynia and hyperalgesia. The aim of this review is to discuss a novel approach on neuropathic pain management, which is based on the knowledge of processes that underlie the development of peripheral neuropathic pain; in particular highlights the role of glia and mast cells in pain and neuroinflammation. ALIAmides (autacoid local injury antagonist amides) represent a group of endogenous bioactive lipids, including palmitoylethanolamide (PEA), which play a central role in numerous biological processes, including pain, inflammation, and lipid metabolism. These compounds are emerging thanks to their anti-inflammatory and anti-hyperalgesic effects, due to the down-regulation of activation of mast cells. Collectively, preclinical and clinical studies support the idea that ALIAmides merit further consideration as therapeutic approach for controlling inflammatory responses, pain, and related peripheral neuropathic pain.<br />
DOI: 10.3390/ijms21155330 PMCID: PMC7432736 PMID: 32727084
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