PALMITOYLETHANOLAMIDE (PEA)

OTHER NAME(S):

Hydroxyethylpalmitamide, Impulsin, N-(2-Hydroxyethyl) hexadecanamide, N-(2-Hydroxyethyl)palmitamide, Palmidrol, Palmitamide MEA, Palmitic Acid Monoethanolamide, Palmitoylethanolamine, PEA.

Overview

Overview Information

Palmitoylethanolamide is a chemical made from fat. It is found naturally in foods such as egg yolks and peanuts, and in the human body. It is also used as a medicine.

Palmitoylethanolamide is used for pain, neuropathic pain, fibromyalgia, multiple sclerosis (MS), carpal tunnel syndrome, infections of the airway, and many other conditions, but there is no good scientific evidence to support these uses.

How does it work?

Palmitoylethanolamide is a chemical that can bind to cells in the body and reduce pain and swelling.
Uses

Uses & Effectiveness?

Possibly Effective for

  • Pain. Some research shows that taking a specific type of palmitoylethanolamide (Normast, Epitech Group) can reduce pain in people with chronic pain due to various causes.

Possibly Ineffective for

  • A muscle control disorder marked by involuntary movements and muscle tightness (spasticity). Research shows that taking palmitoylethanolamide does not reduce spasticity of the spine or help with sleep problems in people with spinal cord injury.

Insufficient Evidence for

  • Lou Gehrig's disease (amyotrophic lateral sclerosis, ALS). In people with ALS, early research shows that taking palmitoylethanolamide with the medication riluzole might improve how well the lungs work.
  • Carpal tunnel syndrome. Early research suggests that taking palmitoylethanolamide might reduce some of the pain and discomfort of carpal tunnel syndrome.
  • Nerve pain in people with diabetes (diabetic neuropathy). Early research shows that taking palmitoylethanolamide might reduce nerve pain in people with diabetic neuropathy.
  • Fibromyalgia. Early research in patients with fibromyalgia suggests that adding palmitoylethanolamide to other standard medications for fibromyalgia might help to reduce pain.
  • A group of eye disorders that can lead to vision loss (glaucoma). Glaucoma is caused by high pressure in the eye. Palmitoylethanolamide seems to reduce intraocular pressure in people with glaucoma or at risk of glaucoma. It also seems to reduce intraocular pressure in people that had surgery to prevent glaucoma.
  • Multiple sclerosis (MS). Early research shows that taking palmitoylethanolamide might help improve symptoms in people with MS who are receiving treatment with the medication interferon-beta1a. However, there are now better medications available to treat MS. It is not known if taking palmitoylethanolamide along with using these newer medications would be helpful.
  • Nerve pain. There are some reports of people having less nerve pain when they take palmitoylethanolamide. However, high-quality research is mixed. Some research in large groups of people show that taking palmitoylethanolamide might reduce pain in people with sciatica. But it might be less effective in people with nerve pain due to injury to the spine. More research is needed to clarify if palmitoylethanolamide is helpful for people with different kinds of nerve pain.
  • Pain after surgery. Early research suggests that taking a specific type of palmitoylethanolamide might reduce pain after having a tooth removed.
  • Infection of the airways. Some early research shows that taking palmitoylethanolamide might reduce the risk of developing a lung infection in adults and children. But not all research agrees.
  • A group of painful conditions that affect the jaw joint and muscle (temporomandibular disorders or TMD). Early research shows that taking palmitoylethanolamide might reduce pain and allow the mouth to open better in people with arthritis of the jaw joint.
  • Headaches.
  • Illness from a Shigella bacteria infection (shigellosis).
  • Autism.
  • Memory.
  • Depression.
  • Eczema.
  • A painful uterine disorder (endometriosis).
  • Eye conditions.
  • Long-term swelling (inflammation) in the digestive tract (inflammatory bowel disease or IBD).
  • Kidney disease.
  • Stroke.
  • Vulvar pain.
  • Weight loss.
  • Withdrawal from marijuana.
  • Dry skin.
  • Others.
More evidence is needed to rate the effectiveness of palmitoylethanolamide for these uses.
Side Effects

Side Effects & Safety

When taken by mouth: Taking palmitoylethanolamide is POSSIBLY SAFE for most adults when used for up to 3 months. Possible side effects, such as upset stomach, are very rare. There isn't enough reliable information to know if palmitoylethanolamide is safe to use for longer than 3 months.

When applied to the skin: There isn't enough reliable information to know if palmitoylethanolamide is safe to use or what the side effects might be.

Special Precautions & Warnings:

Pregnancy and breast-feeding: There isn't enough reliable information to know if palmitoylethanolamide is safe to use when pregnant or breast feeding. Stay on the safe side and avoid use.

Interactions

Interactions?

We currently have no information for PALMITOYLETHANOLAMIDE (PEA) Interactions.

Dosing

Dosing

The following doses have been studied in scientific research:

ADULTS

BY MOUTH:

  • Pain: Palmitoylethanolamide 300-1,200 mg daily for up to 60 days.

View References

REFERENCES:

  • Andresen SR, Bing J, Hansen RM, Biering-Sørensen F, Johannesen IL, Hagen EM, Rice AS, Nielsen JF, Bach FW, Finnerup NB. Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: a randomized, double-blind, placebo-controlled trial. Pain. 2016 Sep;157(9):2097-103. View abstract.
  • Bacci C, Cassetta G, Emanuele B, Berengo M. Randomized split-mouth study on postoperative effects of palmitoylethanolamide for impacted lower third molar surgery. ISRN Surg. 2011;2011:917350. View abstract.
  • Bertolino B, Crupi R, Impellizzeri D, Bruschetta G, Cordaro M, Siracusa R, Esposito E, Cuzzocrea S. Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism. CNS Neurosci Ther. 2016 Oct 4. View abstract.
  • Borrelli F, Romano B, Petrosino S, Pagano E, Capasso R, Coppola D, Battista G, Orlando P, Di Marzo V, Izzo AA. Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent. Br J Pharmacol. 2015 Jan;172(1):142-58. View abstract.
  • Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P. Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. Pain Med. 2010 May;11(5):781-4. View abstract.
  • Caltagirone C, Cisari C, Schievano C, Di Paola R, Cordaro M, Bruschetta G, Esposito E, Cuzzocrea S; Stroke Study Group. Co-ultramicronized Palmitoylethanolamide/Luteolin in the Treatment of Cerebral Ischemia: from Rodent to Man. Transl Stroke Res. 2016 Feb;7(1):54-69. View abstract.
  • Caruso S, Iraci Sareri M, Casella E, Ventura B, Fava V, Cianci A. Chronic pelvic pain, quality of life and sexual health of women treated with palmitoylethanolamide and a-lipoic acid. Minerva Ginecol. 2015 Oct;67(5):413-9. View abstract.
  • Cobellis L, Castaldi MA, Giordano V, Trabucco E, De Franciscis P, Torella M, Colacurci N. Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study. Eur J Obstet Gynecol Reprod Biol. 2011 Sep;158(1):82-6. View abstract.
  • Cocito D, Peci E, Ciaramitaro P, Merola A, Lopiano L. Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain. Pain Res Treat. 2014;2014:854560. View abstract.
  • 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. View abstract.
  • Costagliola C, Romano MR, dell'Omo R, Russo A, Mastropasqua R, Semeraro F. Effect of palmitoylethanolamide on visual field damage progression in normal tension glaucoma patients: results of an open-label six-month follow-up. J Med Food. 2014 Sep;17(9):949-54. View abstract.
  • 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. View abstract.
  • Di Paola R, Fusco R, Gugliandolo E, Crupi R, Evangelista M, Granese R, Cuzzocrea S. Co-micronized Palmitoylethanolamide/Polydatin Treatment Causes Endometriotic Lesion Regression in a Rodent Model of Surgically Induced Endometriosis. Front Pharmacol. 2016 Oct 14;7:382. View abstract.
  • Domínguez CM, Martín AD, Ferrer FG, Puertas MI, Muro AL, González JM, Prieto JP, Taberna IR. N-palmitoylethanolamide in the treatment of neuropathic pain associated with lumbosciatica. Pain Manag. 2012 Mar;2(2):119-24. View abstract.
  • Gabrielsson L, Mattsson S, Fowler CJ. Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Br J Clin Pharmacol. 2016 Oct;82(4):932-42. View abstract.
  • 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. View abstract.
  • Hesselink JM, Hekker TA. Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. J Pain Res. 2012;5:437-42. View abstract.
  • Hesselink JM. Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection. Int Med Case Rep J. 2013 Sep 13;6:49-53. View abstract.
  • Impellizzeri D, Bruschetta G, Cordaro M, Crupi R, Siracusa R, Esposito E, Cuzzocrea S. Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain. J Neuroinflammation. 2014 Aug 28;11:136. View abstract.
  • Indraccolo U, Barbieri F. Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations. Eur J Obstet Gynecol Reprod Biol. 2010 May;150(1):76-9. View abstract.
  • Keppel Hesselink JM, Costagliola C, Fakhry J, Kopsky DJ. Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy. J Ophthalmol. 2015;2015:430596. View abstract.
  • Keppel Hesselink JM, de Boer T, Witkamp RF. Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold. Int J Inflam. 2013;2013:151028. View abstract.
  • Keppel Hesselink JM, Kopsky DJ, Sajben N. New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells. J Pain Res. 2016 Oct 3;9:757-762. View abstract.
  • Keppel Hesselink JM, Kopsky DJ. Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome. J Pain Res. 2015 Oct 23;8:729-34. View abstract.
  • Keppel Hesselink JM, Kopsky DJ. Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells. J Pain Res. 2013 Mar 21;6:239-45. View abstract.
  • Kopsky DJ, Hesselink JM. Multimodal stepped care approach with acupuncture and PPAR-a agonist palmitoylethanolamide in the treatment of a patient with multiple sclerosis and central neuropathic pain. Acupunct Med. 2012 Mar;30(1):53-5. View abstract.
  • Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep 2015;5:11601. View abstract.
  • Marcucci M, Germini F, Coerezza A, Andreinetti L, Bellintani L, Nobili A, Rossi PD, Mari D. Efficacy of ultra-micronized palmitoylethanolamide (um-PEA) in geriatric patients with chronic pain: study protocol for a series of N-of-1 randomized trials. Trials. 2016 Jul 29;17:369. View abstract.
  • 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 Spring;26(2):99-104. View abstract.
  • Morera C, Sabates S, Jaen A. Sex differences in N-palmitoylethanolamide effectiveness in neuropathic pain associated with lumbosciatalgia. Pain Manag. 2015;5(2):81-7. View abstract.
  • Murina F, Graziottin A, Felice R, Radici G, Tognocchi C. Vestibulodynia: synergy between palmitoylethanolamide + transpolydatin and transcutaneous electrical nerve stimulation. J Low Genit Tract Dis. 2013 Apr;17(2):111-6. View abstract.
  • Nigro A, Nicastro A, Trodella R. Retrospective observational study to investigate Sinerga, a multifactorial nutritional product, and bacterial extracts in the prevention of recurrent respiratory infections in children. Int J Immunopathol Pharmacol. 2014 Jul-Sep;27(3):455-60. View abstract.
  • Orefice NS, Alhouayek M, Carotenuto A, Montella S, Barbato F, Comelli A, Calignano A, Muccioli GG, Orefice G. Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-ß1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis. Neurotherapeutics. 2016 Apr;13(2):428-38. View abstract.
  • Paladini A, Fusco M, Cenacchi T, Schievano C, Piroli A, Varrassi G. Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis. Pain Physician. 2016 Feb;19(2):11-24. View abstract.
  • Palma E, Reyes-Ruiz JM, Lopergolo D, Roseti C, Bertollini C, Ruffolo G, Cifelli P, Onesti E, Limatola C, Miledi R, Inghilleri M. Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3060-5. View abstract.
  • Pescosolido N, Librando A, Puzzono M, Nebbioso M. Palmitoylethanolamide effects on intraocular pressure after Nd:YAG laser iridotomy: an experimental clinical study. J Ocul Pharmacol Ther. 2011 Dec;27(6):629-35. View abstract.
  • 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. 2016 Aug 19. View abstract.
  • Schifilliti C, Cucinotta L, Fedele V, Ingegnosi C, Luca S, Leotta C. Micronized palmitoylethanolamide reduces the symptoms of neuropathic pain in diabetic patients. Pain Res Treat. 2014;2014:849623. View abstract.
  • Skaper SD, Facci L, Fusco M, Della Valle MF, Zusso M, Costa B, Giusti P. Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacology. 2014 Apr;22(2):79-94. View abstract.
  • Strobbe E, Cellini M, Campos EC. Effectiveness of palmitoylethanolamide on endothelial dysfunction in ocular hypertensive patients: a randomized, placebo-controlled cross-over study. Invest Ophthalmol Vis Sci. 2013 Feb 1;54(2):968-73. View abstract.
  • Truini A, Biasiotta A, Di Stefano G, La Cesa S, Leone C, Cartoni C, Federico V, Petrucci MT, Cruccu G. Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy. CNS Neurol Disord Drug Targets. 2011 Dec;10(8):916-20. View abstract.

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