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References - Palmitoylethanolamide (PEA) and pain relief

  1. Petrosino S, Schiano Moriello A, Verde R, Allarà M, Imperatore R, Ligresti A, et al. Palmitoylethanolamide counteracts substance P-induced mast cell activation in vitro by stimulating diacylglycerol lipase activity. J Neuroinflammation. 2019 Dec;16(1):274. DOI:10.1186/s12974-019-1671-5
  2. Petrosino S, Di Marzo V. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. British J Pharmacology. 2017 Jun;174(11):1349-65. DOI:10.1111/bph.13580
  3. Guida F, Luongo L, Boccella S, Giordano ME, Romano R, Bellini G, et al. Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor. Sci Rep. 2017 Mar 23;7(1): 375.  DOI:10.1038/s41598-017-00342-1
  4. Skaper SD, Facci L. Mast cell–glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide. Phil Trans R Soc B. 2012 Dec 5;367(1607):3312-25. DOI:10.1098/rstb.2011.0391
  5. Alshelh Z, Mills E, Kosanovic D, Di Pietro F, Macey P, Vickers ER, et al. Effects of the glial modulator palmitoylethanolamide on chronic pain intensity and brain function. JPR. 2019 Aug;12:2427-39. DOI:10.2147/jpr.s209657
  6. Skaper SD, Facci L, Fusco M, della Valle MF, Zusso M, Costa B, et al. Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacol. 2014 Apr;22(2):79-94. DOI:10.1007/s10787-013-0191-7
  7. Keppel Hesselink JM. Chronic Pain and the Use of Palmitoylethanolamide. Austin J Neurol Disord Epilepsy. 2018; 5(2):1042.
  8. Skaper SD, Facci L, Giusti P. Mast cells, glia and neuroinflammation: partners in crime?. Immunology. 2014 Mar;141(3):314-27. DOI:10.1111/imm.12170
  9. Kytikova O, Novgorodtseva T, Antonyuk M, Denisenko Y, Gvozdenko T. Molecular Targets of Fatty Acid Ethanolamides in Asthma. Medicina. 2019 Apr 1;55(4):87. DOI:10.3390/medicina55040087
  10. Steels E, Venkatesh R, Steels E, Vitetta G, Vitetta L. A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacol. 2019 Jun;27(3):475-85. DOI:10.1007/s10787-019-00582-9
  11. Lang-Illievich K, Klivinyi C, Lasser C, Brenna CTA, Szilagyi IS, Bornemann-Cimenti H. Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Nutrients. 2023 Mar 10;15(6):1350. DOI:10.3390/nu15061350
  12. Artukoglu BB, Beyer C, Zuloff-Shani A, Brener E, Bloch MH. Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis. Pain Physician. 2017 Jul;20(5):353-62.
  13. Passavanti MB, Fiore M, Sansone P, Aurilio C, Pota V, Barbarisi M, et al. 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. BMC Anesthesiol. 2017 Dec;17(1):171. DOI:10.1186/s12871-017-0461-9
  14. Marini I, Bartolucci ML, Bortolotti F, Gatto MR, Bonetti GA. Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain. J Orofac Pain. 2012;26(2):99-104.
  15. Conigliaro R, Drago V, Foster PS, Schievano C, Di Marzo V. Use of palmitoylethanolamide in the entrapment neuropathy of the median in the wrist. Minerva Med. 2011 Apr;102(2):141-7.
  16. Evangelista M, Cilli V, De Vitis R, Militerno A, Fanfani F. Ultra-micronized Palmitoylethanolamide Effects on Sleep-wake Rhythm and Neuropathic Pain Phenotypes in Patients with Carpal Tunnel Syndrome: An Open-label, Randomized Controlled Study. CNS & Neurol Disord Drug Targets. 2018;17(4):291-298. DOI: 10.2174/1871527317666180420143830
  17. Cocito D, Peci E, Ciaramitaro P, Merola A, Lopiano L. Short-Term Efficacy of Ultramicronized Palmitoylethanolamide in Peripheral Neuropathic Pain. Pain Research and Treatment. 2014 May 20;2014:1-4. DOI:10.1155/2014/854560
  18. Gatti A, Lazzari M, Gianfelice V, Di Paolo A, Sabato E, Sabato AF. Palmitoylethanolamide in the Treatment of Chronic Pain Caused by Different Etiopathogenesis. Pain Med. 2012 Sep;13(9):1121-30. DOI:10.1111/j.1526-4637.2012.01432.x
  19. Ghazizadeh-Hashemi M, Ghajar A, Shalbafan M, Ghazizadeh-Hashemi F, Afarideh M, Malekpour F, et al. Palmitoylethanolamide as adjunctive therapy in major depressive disorder: A double-blind, randomized and placebo-controlled trial. Journal of Affective Disorders. 2018 May;232:127-33. DOI:10.1016/j.jad.2018.02.057
  20. Brotini S, Schievano C, Guidi L. Ultra-micronized Palmitoylethanolamide: An Efficacious Adjuvant Therapy for Parkinson’s Disease. CNSNDDT. 2017 Aug 23;16(6):705-13. DOI:10.2174/1871527316666170321124949
  21. Khalaj M, Saghazadeh A, Shirazi E, Shalbafan M, Alavi K, Shooshtari MH, et al. Palmitoylethanolamide as adjunctive therapy for autism: Efficacy and safety results from a randomized controlled trial. Journal of Psychiatric Research. 2018 Aug;103:104-11. DOI:10.1016/j.jpsychires.2018.04.022
  22. Bortoletto R, Piscitelli F, Candolo A, Bhattacharyya S, Balestrieri M, Colizzi M. Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence. Front Psychiatry. 2023 Jul 18;14:1231710. DOI:10.3389/fpsyt.2023.1231710
  23. 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 Oct 28;13:1038122. DOI:10.3389/fpsyt.2022.1038122
  24. Keppel Hesselink JM, de Boer T, Witkamp RF. Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold. International Journal of Inflammation. 2013;2013:1-8. DOI:10.1155/2013/151028
  25. Dalla Volta G. Ultramicronized palmitoylethanolamide reduces frequency and pain intensity in migraine. A pilot study. IJNBD. 2016;3(2):1-5. DOI:10.15436/2377-1348.16.019
  26. Chirchiglia D, Della Torre A, Signorelli F, Volpentesta G, Guzzi G, Stroscio C, et al. Administration of palmitoylethanolamide in combination with topiramate in the preventive treatment of nummular headache. IMCRJ. 2016 Jul;Volume 9:193-5. DOI:10.2147/imcrj.s106323
  27. Davis MP, Behm B, Mehta Z, Fernandez C. The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review. Am J Hosp Palliat Care. 2019 Dec;36(12):1134-54. DOI:10.1177/1049909119850807
  28. Keppel Hesselink J, Kopsky DJ. The Role of Palmitoylethanolamide, an Autacoid, in the Symptomatic Treatment of Muscle Cramps: Three Case Reports and Review of Literature. J Clin Case Rep. 2016;06(03):1-2. DOI:10.4172/2165-7920.1000744
  29. Varrassi G, Fusco M, Skaper SD, Battelli D, Zis P, Coaccioli S, et al. A Pharmacological Rationale to Reduce the Incidence of Opioid Induced Tolerance and Hyperalgesia: A Review. Pain Ther. 2018 Jun;7(1):59-75. DOI:10.1007/s40122-018-0094-9
  30. Di Cesare Mannelli L, Corti F, Micheli L, Zanardelli M, Ghelardini C. Delay of Morphine Tolerance by Palmitoylethanolamide. BioMed Research International. 2015;2015:1-12. DOI:10.1155/2015/894732
  31. Passavanti MB, Alfieri A, Pace MC, Pota V, Sansone P, Piccinno G, et al. Clinical applications of palmitoylethanolamide in pain management: protocol for a scoping review. Syst Rev. 2019 Dec;8(1):9. DOI:10.1186/s13643-018-0934-z
  32. Nestmann ER. Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential. Food Science & Nutrition. 2017 Mar;5(2):292-309. DOI:10.1002/fsn3.392
  33. Iannotti FA, Di Marzo V, Petrosino S. Endocannabinoids and endocannabinoid-related mediators: Targets, metabolism and role in neurological disorders. Prog in Lip Res. 2016 Apr;62:107-28. DOI:10.1016/j.plipres.2016.02.002
  34. Fusco M, Skaper SD, Coaccioli S, Varrassi G, Paladini A. Degenerative Joint Diseases and Neuroinflammation. Pain Practice. 2017 Apr;17(4):522-32. DOI:10.1111/papr.12551
  35. Kumar D, Jacob D, PS S, Maliakkal A, NM J, Kuttan R, et al. Enhanced bioavailability and relative distribution of free (unconjugated) curcuminoids following the oral administration of a food-grade formulation with fenugreek dietary fibre: A randomised double-blind crossover study. Journal of Functional Foods. 2016 Apr;22:578-87. DOI:10.1016/j.jff.2016.01.039
  36. Akay Natural Ingredients. Human pharmacokinetic study report of FenuMAT-palmitoylethanolamide (PEA 40%). [Unpublished data].
  37. Hill MN, McLaughlin RJ, Morrish AC, Viau V, Floresco SB, Hillard CJ, et al. Suppression of Amygdalar Endocannabinoid Signaling by Stress Contributes to Activation of the Hypothalamic–Pituitary–Adrenal Axis. Neuropsychopharmacol. 2009 Dec;34(13):2733-45. DOI:10.1038/npp.2009.114
  38. Hill MN, Kumar SA, Filipski SB, Iverson M, Stuhr KL, Keith JM, et al. Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure. Mol Psychiatry. 2013 Oct;18(10):1125-35. DOI:10.1038/mp.2012.90
  39. Zimmermann T, Bartsch JC, Beer A, Lomazzo E, Guggenhuber S, Lange MD, et al. Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses. Neuropsychopharmacol. 2019 Jul;44(8):1377-88. DOI:10.1038/s41386-018-0274-7
  40. Gertsch J. Immunomodulatory Lipids in Plants: Plant Fatty Acid Amides and the Human Endocannabinoid System. Planta Med. 2008 May;74(6):638-50. DOI:10.1055/s-2008-1034302
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  43. Fiasella A, Nuzzi A, Summa M, Armirotti A, Tarozzo G, Tarzia G, et al. 3‐Aminoazetidin‐2‐one Derivatives as N‐Acylethanolamine Acid Amidase (NAAA) Inhibitors Suitable for Systemic Administration. Chem Med Chem. 2014 Jul;9(7):1602-14. DOI:10.1002/cmdc.201300546
  44. Gabrielsson L, Mattsson S, Fowler CJ. Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Brit J Clinical Pharma. 2016 Oct;82(4):932-42. DOI:10.1111/bcp.13020
  45. Petrosino S, Schiano Moriello A, Cerrato S, Fusco M, Puigdemont A, De Petrocellis L, et al. The anti‐inflammatory mediator palmitoylethanolamide enhances the levels of 2‐arachidonoyl‐glycerol and potentiates its actions at TRPV1 cation channels. British J Pharmacology. 2016 Apr;173(7):1154-62. trosino, S., et al., The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2-arachidonyl-glycerol and potentiates its actions at TRPV1 cation channels. Br J Pharmacol, 2015. 173(7): p. 1154-1162. DOI:10.1111/bph.13084
  46. Paladini A, Varrassi G, Bentivegna G, Carletti S, Piroli A, Coaccioli S. Palmitoylethanolamide in the Treatment of Failed Back Surgery Syndrome. Pain Research and Treatment. 2017 Aug 10;2017:1-6. DOI:10.1155/2017/1486010
  47. Keppel Hesselink J, Kopsky D. Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome. JPR. 2015 Oct;8:729. DOI:10.2147/jpr.s93106
  48. Schweiger V, Martini A, Bellamoli P, Donadello K, Schievano C, Balzo GD, et al. Ultramicronized Palmitoylethanolamide (um-PEA) as add-on treatment in fibromyalgia syndrome (fms): retrospective observational study on 407 patients. CNS Neurol Disord Drug Targets. 2019 Jul 17;18(4):326-33. DOI:10.2174/1871527318666190227205359
  49. Del Giorno R, Skaper S, Paladini A, Varrassi G, Coaccioli S. Palmitoylethanolamide in Fibromyalgia: Results from Prospective and Retrospective Observational Studies. Pain Ther. 2015 Dec;4(2):169-78. DOI:10.1007/s40122-015-0038-6
  50. Schifilliti C, Cucinotta L, Fedele V, Ingegnosi C, Luca S, Leotta C. Micronized Palmitoylethanolamide Reduces the Symptoms of Neuropathic Pain in Diabetic Patients. Pain Research and Treatment. 2014 Apr 2;2014:1-5. DOI:10.1155/2014/849623
  51. Antonucci N, Cirillo A, Siniscalco D. Beneficial Effects of Palmitoylethanolamide on Expressive Language, Cognition, and Behaviors in Autism: A Report of Two Cases. Case Reports in Psychiatry. 2015;2015:1-6. DOI:10.1155/2015/325061
  52. Bacci C, Cassetta G, Emanuele B, Berengo M. Randomized Split-Mouth Study on Postoperative Effects of Palmitoylethanolamide for Impacted Lower Third Molar Surgery. ISRN Surgery. 2011 Apr 17;2011:1-6. DOI:10.5402/2011/917350



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