Palmitoylethanolamide (PEA)

Paper effect bottom

Palmitoylethanolamide is a substance which is naturally produced in the cells and tissues of the body, as well as in plant and animal sources. It can be found in soybean lecithin, egg yolk, peanut meal and other foods. There is no established Recommended Daily Amount (RDA) for PEA.

How does it work in the body?

PEA is thought to help regulate networks which are associated with pain and inflammation and therefore it is considered to have anti-inflammatory and analgesic properties. It is believed to have beneficial effects on diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, failed back surgery syndrome, dental pains, neuropathic pain in stroke and multiple sclerosis, chronic pelvic pain, postherpetic neuralgia, and vaginal pain.


Pain relief– A meta-analysis of 10 studies including data from 786 patients who received PEA and 512 controls showed that PEA was associated with significantly greater pain reduction compared to inactive control conditions (1). A separate study of rats subjected to induced inflammatory and neuropathic pain showed that PEA significantly reduced hypersensitivity to pain resulting from chronic inflammation. PEA has also been shown to be safe and effective in treating nerve compression syndromes such as sciatic pain and pain due to carpal tunnel syndrome (2).

Seven different cases have also been cited in a separate research paper supporting the efficacy of PEA in the management of pain in treatment-resistant patients. The first case described a 61-year-old Caucasian male suffering from prostate cancer who had been treated, unsuccessfully with a number of pain management therapies. Prior to starting treatment with PEA in 2009, the patient had a pain score of 7/10 and at peak times a score of 9. Following administration of 600mg twice daily with PEA the patient was in a stable condition, medication free with virtually no pain by 2010 (3). Another case involving a 66-year-old Caucasian male suffering from chronic idiopathic axonal polyneuropathy (a condition which involves damage to both sensory and motor nerves), showing a mean pain score of 8 on the numeric rating scale (NRS) experienced a significant reduction in pain and improvement in walking ability following treatment with PEA over a period of 3 months, reporting an NRS of 1-2 (3). A third case involved a 64-year-old Caucasian male who had been suffering from type II diabetes for 8 years and had been treated with metformin. He was being treated with pregabalin (225 mg/day) however he still scored NRS 6. Treatment with 600mg twice daily combined with 2000 IE of vitamin D3 and three times 100 mg R-alpha-lipoic acid together with a topical cream twice daily consisting of adelmidrol and capsaicin (Algonerv) was implemented. After 3 weeks, the pain was reduced from 6 to 4, and after 3 months of treatment, the pain was reduced to 1.5 (3). For the majority of all seven cases PEA – alone or added to standard analgesics – was able to reduce pain by 40%–80% compared to baseline scores on the NRS (3).

Depression- Preclinical studies have shown the antidepressant activity of PEA in animal paradigms of depression and of depression associated with neuropathic pain and traumatic brain injury. In a translational perspective, PEA is increased in stress conditions, and a randomized, double-blind study in depressed patients indicated a fast-antidepressant action of PEA when associated with citalopram (an anti-depressant medication) which shows that PEA is effective alone or in combination with other anti-depressant medications in the treatment of depression (4).

Our take on how PEA may help you;

Pain relief- due to the reported analgesic and anti-inflammatory properties of palmitoylethanolamide, a supplement may provide benefit for those suffering from painful conditions such as carpal tunnel syndrome and sciatic pain.

Depression-Due to the action of palmitoylethanolamide on receptor cells in the brain, a supplement may be of benefit when used alone or in combination with other medications for the treatment of depression.

Safety and side effects

PEA is generally well tolerated in research populations and has not been associated with any serious side effects or drug-drug interactions. There is no established Tolerable Upper Intake Level for PEA.


  1. 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):353-362. Review. PMID: 28727699
  2. 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. doi: 10.2147/JPR.S93106. eCollection 2015. Review. PMID: 26604814
  3. 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. doi: 10.2147/JPR.S32143. Epub 2012 Oct 26. PMID: 23166447
  4. De Gregorio D, Manchia M, Carpiniello B, Valtorta F, Nobile M, Gobbi G, Comai S: Role of palmitoylethanolamide (PEA) in depression: Translational evidence.J Affect Disord. 2018 Oct 25. pii: S0165-0327(18)31599-4. doi: 10.1016/j.jad.2018.10.117