The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

Davis, Mellar P.; Behm, Bertrand; Mehta, Zankhana; Fernandez, Carlos

doi:10.1177/1049909119850807

Cited by 17 publications

(24 citation statements)

References 215 publications

(261 reference statements)

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“…In addition, this survey found that nearly all respondents were unfamiliar with PEA, which is an endogenous cannabinoid classified as a nutraceutical, or a food that has potential health or medicinal benefits. 29 PEA has activity at both CB 1 and CB 2 receptors, although it is not itself a component of cannabis 29 and possesses anti-inflammatory effects. 30 - 32 Therefore, the endocannabinoid system could be positively manipulated via PEA without negotiating the legal restrictions surrounding cannabis.…”

Section: Discussionmentioning

confidence: 99%

Knowledge and Opinion on Cannabinoids Among Orthopaedic Traumatologists

Chin¹,

Etiz²,

Nelson³

et al. 2021

JAAOS Glob Res Rev

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Introduction: Cannabinoids are an increasingly popular therapy among orthopaedic patients for musculoskeletal conditions. A paucity of evidence to support their use in orthopaedics exists, likely because of the incongruence of federal and state legalization and the stigma surrounding cannabis. The purpose of this study is to elucidate sentiments and knowledge base of the orthopaedic trauma community with regard to cannabinoid-containing compounds. Methods: A 21-question online survey was distributed to the members of the Orthopaedic Trauma Association with a response window of 3 months. Results: We evaluated 251 responses. Most (88%) of the respondents did not believe that they were knowledgeable about the mechanism of action of cannabis/cannabidiol (CBD) but did feel that cannabis or CBD products play a role in managing postoperative pain (73%). Most respondents did not believe that they would be stigmatized if they suggested CBD (83%) or cannabis (67%) to patients. Despite this, fewer respondents have suggested CBD (38%) or cannabis (29%) to their patients. Conclusions: Sentiment toward cannabinoids among orthopaedic traumatologists is remarkably favorable; however, in-depth understanding is admittedly poor and routine use is uncommon. More clinical research for cannabinoids is needed to help orthopaedic traumatologists provide guidance for patients seeking advice for this recently popular therapeutic.

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Section: Discussionmentioning

confidence: 99%

Knowledge and Opinion on Cannabinoids Among Orthopaedic Traumatologists

Chin¹,

Etiz²,

Nelson³

et al. 2021

JAAOS Glob Res Rev

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“…This could be due to the fact that very little is known about the pharmacokinetics of PEA in humans ( please see Pharmacokinetic). In fact, the bioavailability and apparent volume of distribution have not been clearly evaluated; and blood PEA levels, at least in animals, do not accurately reflect levels in the CNS (Davis et al, 2019). The micronized or ultramicronized forms of PEA increased bioavailability in animals compared with naïve forms, but there are very few and very recent clinical data to confirm that this is true for humans.…”

Section: Clinical Evidencementioning

confidence: 99%

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Disease

2019

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N -Palmitoylethanolamide (PEA) is a non-endocannabinoid lipid mediator belonging to the class of the N -acylethanolamine phospolipids and was firstly isolated from soy lecithin, egg yolk, and peanut meal. Either preclinical or clinical studies indicate that PEA is potentially useful in a wide range of therapeutic areas, including eczema, pain, and neurodegeneration. PEA-containing products are already licensed for use in humans as a nutraceutical, a food supplement, or a food for medical purposes, depending on the country. PEA is especially used in humans for its analgesic and anti-inflammatory properties and has demonstrated high safety and tolerability. Several preclinical in vitro and in vivo studies have proven that PEA can induce its biological effects by acting on several molecular targets in both central and peripheral nervous systems. These multiple mechanisms of action clearly differentiate PEA from classic anti-inflammatory drugs and are attributed to the compound that has quite unique anti(neuro)inflammatory properties. According to this view, preclinical studies indicate that PEA, especially in micronized or ultramicronized forms (i.e., formulations that maximize PEA bioavailability and efficacy), could be a potential therapeutic agent for the effective treatment of different pathologies characterized by neurodegeneration, (neuro)inflammation, and pain. In particular, the potential neuroprotective effects of PEA have been demonstrated in several experimental models of Alzheimer’s disease. Interestingly, a single-photon emission computed tomography (SPECT) case study reported that a mild cognitive impairment (MCI) patient, treated for 9 months with ultramicronized-PEA/luteolin, presented an improvement of cognitive performances. In the present review, we summarized the current preclinical and clinical evidence of PEA as a possible therapeutic agent in Alzheimer’s disease. The possible PEA neuroprotective mechanism(s) of action is also described.

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“…Additionally, PEA is known for its "entourage effect" on the endocannabinoid system (ECS), being able to potentiate the effect of prototypical endocannabinoids, but not carrying their potential side effects (Davis et al, 2019). Interestingly, the non-psychotropic cannabinoid cannabidiol (CBD) was able to prevent the cytotoxic damage caused by TcdA in vitro cultured Caco-2 cells (Gigli et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

A Palmitoylethanolamide Producing Lactobacillus paracasei Improves Clostridium difficile Toxin A-Induced Colitis

et al. 2021

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Genetically engineered probiotics, able to in situ deliver therapeutically active compounds while restoring gut eubiosis, could represent an attractive therapeutic alternative in Clostridium difficile infection (CDI). Palmitoylethanolamide is an endogenous lipid able to exert immunomodulatory activities and restore epithelial barrier integrity in human models of colitis, by binding the peroxisome proliferator–activated receptor-α (PPARα). The aim of this study was to explore the efficacy of a newly designed PEA-producing probiotic (pNAPE-LP) in a mice model of C. difficile toxin A (TcdA)-induced colitis. The human N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), a key enzyme involved in the synthesis of PEA, was cloned and expressed in a Lactobacillus paracasei that was intragastrically administered to mice 7 days prior the induction of the colitis. Bacteria carrying the empty vector served as negative controls (pLP).In the presence of palmitate, pNAPE-LP was able to significantly increase PEA production by 27,900%, in a time- and concentration-dependent fashion. Mice treated with pNAPE-LP showed a significant improvement of colitis in terms of histological damage score, macrophage count, and myeloperoxidase levels (−53, −82, and −70.4%, respectively). This was paralleled by a significant decrease both in the expression of toll-like receptor-4 (−71%), phospho-p38 mitogen-activated protein kinase (−72%), hypoxia-inducible factor-1-alpha (−53%), p50 (−74%), and p65 (−60%) and in the plasmatic levels of interleukin-6 (−86%), nitric oxide (−59%), and vascular endothelial growth factor (−71%). Finally, tight junction protein expression was significantly improved by pNAPE-LP treatment as witnessed by the rescue of zonula occludens-1 (+304%), Ras homolog family member A-GTP (+649%), and occludin expression (+160%). These protective effects were mediated by the specific release of PEA by the engineered probiotic as they were abolished in PPARα knockout mice and in wild-type mice treated with pLP. Herein, we demonstrated that pNAPE-LP has therapeutic potential in CDI by inhibiting colonic inflammation and restoring tight junction protein expression in mice, paving the way to next generation probiotics as a promising strategy in CDI prevention.

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The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

Cited by 17 publications

References 215 publications

Knowledge and Opinion on Cannabinoids Among Orthopaedic Traumatologists

Knowledge and Opinion on Cannabinoids Among Orthopaedic Traumatologists

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Disease

A Palmitoylethanolamide Producing Lactobacillus paracasei Improves Clostridium difficile Toxin A-Induced Colitis

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