LETTERATURA SCIENTIFICA DI RIFERIMENTO

Giovanni Sarnelli, Marcella Pesce, Luisa Seguella, Jie Lu, Eleonora Efficie, Jan Tack, Fatima Domenica, Elisa De Palma, Alessandra D’Alessandro, Giuseppe Esposito. Impaired Duodenal Palmitoylethanolamide Release Underlies Acid-Induced Mast Cell Activation in Functional Dyspepsia. Cellular and Molecular Gastroenterology and Hepatology. Volume 11, Issue 3, 2021, Pages 841-855.

Esposito, G.; Pesce, M.; Seguella, L.; Lu, J.; Corpetti, C.;Del Re, A.; De Palma, F.D.E.; Esposito, G.; Sanseverino, W.; Sarnelli, G. Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice. Int. J. Mol. Sci. 2021.

Esposito G, Corpetti C, Pesce M, Seguella L, Annunziata G, Del Re A, Vincenzi M, Lattanzi R, Lu J, Sanseverino W, Sarnelli G. A Palmitoylethanolamide Producing Lactobacillus paracasei Improves Clostridium difficile Toxin A-Induced Colitis. Front Pharmacol. 2021 Apr 27;12:639728. doi: 10.3389/fphar.2021.639728.

Sadee W, Wang D, Hartmann K, et al. Pharmacogenomics: driving personalized medicine. Pharmacol Rev. 2023;75(4):789–814. doi:10.1124/ pharmrev.122.000810.

Stamatopoulos K. Precision medicine in cancer: a paradigm shift. Semin Cancer Biol. 2022;84:1–2. doi:10.1016/j. semcancer. 2022.05.008.

Zhang L, Tang W, Ouyang Y, et al. N-palmitoylethanolamine modulates hippocampal neuroplasticity in rats with stress-induced depressive behavior phenotype. Eur J Pharmacol. 2023;957:176041. doi:10.1016/j.ejphar.2023.176041.

Zhou G, Fu X, Wang L, et al. Palmitoylethanolamide ameliorates neuroinflammation via modulating PPAR-α to promote the functional outcome after intracerebral hemorrhage. Neurosci Lett. 2022;781:136648. doi:10.1016/j.neulet.2022.136648.

Zeraatkar D, Cooper A, Agarwal A, et al. Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies. BMJ open. 2022;12(8):e054282. doi:10.1136/bmjopen-2021-054282.

Di Stefano V, Steardo L, D’Angelo M, et al. Palmitoylethanolamide: a multifunctional molecule for neuroprotection, chronic pain, and immune modulation. Biomedicines. 2025;13(6):1271. doi:10.3390/biomedicines13061271.

Wang Y, Duan X, Li Z, et al. Palmitoylethanolamide in the treatment of pain and its clinical application prospects. Drug Des Devel Ther.2025;19:6897–6923. doi:10.2147/DDDT.S540327.

Scuteri, D.; Guida, F.; Boccella, S.; Palazzo, E.; Maione, S.; Rodríguez-Landa, J.F.; Martínez-Mota, L.; Tonin, P.; Bagetta, G.; Corasaniti, M.T. Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence. Pharmaceutics 2022, 14, https://doi.org/10.3390/pharmaceutics14081672.

Schweiger V, Martini A, Bellamoli P, Donadello K, Schievano C, Balzo GD, Sarzi-Puttini P, Parolini M, Polati E. Ultramicronized Palmitoylethanolamide (um-PEA) as Add-on Treatment in Fibromyalgia Syndrome (FMS): Retrospective Observational Study on 407 Patients. CNS Neurol Disord Drug Targets. 2019;18(4):326-333.
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Paladini A, Varrassi G, Bentivegna G, Carletti S, Piroli A, Coaccioli S. Palmitoylethanolamide in the Treatment of Failed Back Surgery Syndrome. Pain Res Treat. 2017;2017:1486010. doi:
10.1155/2017/1486010. Epub 2017 Aug 10. PMID: 28875041; PMCID: PMC5569747.

Clayton, P.; Hill, M.; Bogoda, N.; Subah, S.; Venkatesh, R. Palmitoylethanolamide: A Natural Compound for Health Management. Int. J. Mol. Sci. 2021, 22, 5305. [CrossRef].

Lo Monte, G.; Soave, I.; Marci, R. Administration of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis: Preliminary results. Minerva Ginecol. 2013, 65, 453–463.

Stochino Loi, E.; Pontis, A.; Cofelice, V.; Pirarba, S.; Fais, M.F.; Daniilidis, A.; Melis, I.; Paoletti, A.M.; Angioni, S. 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. Int. J. Women’s Health 2019, 11, 443–449.

Piccolino I, Iannuzzi F, Lionetti L, Mazzonello B, Barreca V, Banaj N, Arezzini V, Piras F, Bossù P. The immunomodulating effect of palmitoylethanolamide on human myeloid dendritic cells and its possible impact on Alzheimer’s diseas.Front Immunol. 2026 Jan 2;16:1664164. doi: 10.3389/fimmu.2025.1664164. PMID: 41550956; PMCID: PMC12807896.

Beggiato S, Tomasini MC, Ferraro L. Palmitoylethanolamide (PEA) as a potential therapeutic agent in Alzheimer’s disease.Front Pharmacol. (2019) 10:821. doi: 10.3389/ fphar.2019.00821.

Esposito E, Impellizzeri D, Mazzon E, Paterniti I, Cuzzocrea S. Neuroprotective activities of palmitoylethanolamide in an animal model of Parkinson’s disease.PloS One. (2012) 7:e41880. doi: 10.1371/journal.pone.0041880.

Brotini S, Schievano C, Guidi L. Ultra-micronized palmitoylethanolamide: an efficacious adjuvant therapy for Parkinson’s disease.CNSNDDT. (2017) 16:705–713. doi: 10.2174/1871527316666170 321124949.

Colizzi M, Bortoletto R, Colli C, Bonomo E, Pagliaro D, Maso E, et al. Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence.Front Psychiatry. (2022) 13:1038122. doi:10.3389/fpsyt.2022.103812.

Assogna M, Di Lorenzo F, Bonnì S, Borghi I, Cerulli Irelli E, Mencarelli L, et al.Phase 2 study of palmitoylethanolamide combined with luteoline in frontotemporal dementia patients. Brain Commun. (2025) 7:fcaf080. doi: 10.1093/braincomms/fcaf080.

Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. A&D Transl Res Clin Interv. (2018) 4:575–90. doi: 10.1016/j. trci.2018.06.014.

Gabrielsson L, Gouveia-Figueira S, Häggström J, Alhouayek M, Fowler CJ. The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line.Pharmacol Res Perspect. (2017) 5:e00300. doi: 10.1002/prp2.300.

Assogna M, Di Lorenzo F, Martorana A, Koch G. Synaptic effects of palmitoylethanolamide in neurodegenerative disorders.Biomolecules. (2022) 12:1161. doi:10.3390/biom12081161.

Scuderi C, Stecca C, Valenza M, Ratano P, Bronzuoli MR, Bartoli S, et al. Palmitoylethanolamide controls reactive gliosis and exerts neuroprotective functions in a rat model of Alzheimer’s disease.Cell Death Dis. (2014) 5:e1419–9. doi: 10.1038/cddis.2014.376.

Bronzuoli MR, Facchinetti R, Steardo L, Romano A, Stecca C, Passarella S, et al. Palmitoylethanolamide dampens reactive astrogliosis and improves neuronal trophic support in a triple transgenic model of Alzheimer’s disease: in vitroandIn vivo-Evidence.Oxid Med Cell Longevity. (2018) 2018:4720532. doi: 10.1155/2018/4720532.

Ozaki T, Kamiyama N, Saechue B, Soga Y, Gotoh R, Nakayama T, et al. Comprehensive lipidomics of lupus-prone mice using LC–MS/MS identifies the reduction of palmitoylethanolamide that suppresses TLR9-mediated inflammation.Genes to Cells. (2022) 27:493–504. doi: 10.1111/gtc.12944.

Rankin L, Fowler CJ. The Basal Pharmacology of Palmitoylethanolamide.Int J Mol Sci. 2020 Oct 26;21(21):7942. doi: 10.3390/ijms21217942.

Palenca, I.; Basili Franzin, S.; Sarnelli, G.; Esposito, G. Palmitoylethanolamide for Nickel Allergy: Plausible, Untested, and Worth Considering.Biomedicines 2026, 14, 177. https://doi.org/10.3390/biomedicines14010177.

Couch, D.G.; Cook, H.; Ortori, C.; Barrett, D.; Lund, J.N.; O’Sullivan, S.E. Palmitoylethanolamide and Cannabidiol Prevent Inflammation-Induced Hyperpermeability of the Human Gut In Vitro and In Vivo-A Randomized, Placebo-Controlled, Double- Blind Controlled Trial.Inflamm. Bowel Dis. 2019, 25, 1006–1018.

Petrosino, S.; Di Marzo, V. The Pharmacology of Palmitoylethanolamide and First Data on the Therapeutic Efficacy of Some of Its New Formulations.Br. J. Pharmacol. 2017, 174, 1349–1365.

Petrosino, S.; Cristino, L.; Karsak, M.; Gaffal, E.; Ueda, N.; Tüting, T.; Bisogno, T.; De Filippis, D.; D’Amico, A.; Saturnino, C.; et al. Protective Role of Palmitoylethanolamide in Contact Allergic Dermatitis.Allergy 2010, 65, 698–711.

Rao, A.; Moussa, A.A.; Erickson, J.; Briskey, D. Efficacy of Topical Palmitoylethanolamide (Levagen+) for the Management of Eczema Symptoms: A Double-Blind, Comparator-Controlled, Randomized Clinical Trial.Skin. Pharmacol. Physiol. 2023, 36, 288–295.

Szepietowski, J.C.; Szepietowski, T.; Reich, A. Efficacy and Tolerance of the Cream Containing Structured Physiological Lipids with Endocannabinoids in the Treatment of Uremic Pruritus: A Preliminary Study.Acta Dermatovenerol. Croat. 2005, 13, 97–103.

Orefice, N.S.; Alhouayek, M.; Carotenuto, A.; Montella, S.; Barbato, F.; Comelli, A.; Calignano, A.; Muccioli, G.G.; Orefice, G. Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-B1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis. Neurotherapeutics 2016, 13, 428–438.

Lang-Illievich, K.; Klivinyi, C.; Lasser, C.; Brenna, C.T.A.; Szilagyi, I.S.; Bornemann-Cimenti, H. Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.Nutrients 2023, 15, 1350.

Isola, G. Impact of Palmitoylethanolamide (PEA) in the Management of Oro-Facial Pain.ClinicalTrials.gov Identifier: NCT05877170. University of Catania. Double-Blind, Placebo-Controlled Interventional Study of PEA for Management of Orofacial Pain. Available online: https://clinicaltrials.gov/ (accessed on 16 November 2025).

Sarnelli, G.; D’Alessandro, A.; Iuvone, T.; Capoccia, E.; Gigli, S.; Pesce, M.; Seguella, L.; Nobile, N.; Aprea, G.; Maione, F.; et al. Palmitoylethanolamide Modulates Inflammation-Associated Vascular Endothelial Growth Factor (VEGF) Signaling via the Akt/mTOR Pathway in a Selective Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α)-Dependent Manner.PLoS ONE 2016, 11, e0156198

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Luo F, Sandhu AF, Rungratanawanich W, Williams GE, Akbar M, Zhou S, Song BJ, Wang X. Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases.Int J Mol Sci. 2020 Sep.

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Compare D, Rocco A, Sgamato C, Coccoli P, Campo SM, Nazionale I, Larussa T, Luzza F, Chiodini P, Nardone G. Lactobacillus paracasei F19 versus placebo for the prevention of proton pump inhibitor-induced bowel symptoms: a randomized clinical trial.Dig Liver Dis. 2015 Apr;47(4):273-9. doi: 10.1016/j.dld.2015.01.004. Epub 2015 Jan 19. PMID: 25660822.

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Annibale B., Maconi G., Lahner E., De Giorgi F., Cuomo R. Efficacy of Lactobacillus paracasei sub. paracasei F19 on abdominal symptoms in patients with symptomatic uncomplicated diverticular disease: a pilot study.Minerva Gastroenterol Dietol 2011;57:1-10.

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Di Stefano, V.; Steardo, L., Jr.; D’Angelo, M.; Monaco, F.; Steardo, L. Palmitoylethanolamide: A Multifunctional Molecule for Neuroprotection, Chronic Pain, and Immune Modulation. Biomedicines 2025, 13, 1271. https://doi.org/10.3390/biomedicines1306127

Branković M, Gmizić T, Dukić M, Zdravković M, Daskalović B, Mrda D, Nikolić N, Brajković M, Gojgić M, Lalatović J, Kralj Đ, Pantić I, Vojnović M, Milovanović T, Đurašević S, Todorović Z. Therapeutic Potential of Palmitoylethanolamide in Gastrointestinal Disorders. Antioxidants (Basel). 2024 May 14;13(5):600. doi: 10.3390/antiox13050600. PMID: 38790705; PMCID: PMC11117950.

Couch, D.G.; Tasker, C.; Theophilidou, E.; Lund, J.N.; O’Sullivan, S.E. Cannabidiol and Palmitoylethanolamide Are Anti-Inflammatory in the Acutely Inflamed Human Colon. Clin. Sci. 2017, 131, 2611–2626.

Di Nardo, G.; Bernardo, L.; Cremon, C.; Barbara, G.; Felici, E.; Evangelisti, M.; Ferretti, A.; Furio, S.; Piccirillo, M.; Coluzzi, F.; et al. Palmitoylethanolamide and Polydatin in Pediatric Irritable Bowel Syndrome: A Multicentric Randomized Controlled Trial. Nutrition 2024, 122, 112397.

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Pan Y, Wei P, Li Z, Wang J, Wang X. The Prospects of Palmitylethanolamide in Tumor Prevention and Treatment. J Inflamm Res. 2026;19:1-24 – ttps://doi.org/10.2147/JIR.S549752