What is PEA

N-Palmitoylethanolamide (PEA) is a natural substance produced by the body; it is an endogenous fatty acid amide, belonging to the class of nuclear factor agonists, and can be used as a supplement for pain and inflammation treatment (1).  PEA is a natural, protective, fatty molecule produced in our body, helping support the myelin nerve sheaths for good nerve function.  PEA can be found in the tissues of most mammals and food such as meat, eggs, soy beans and peanuts (1).

PEA is involved in a variety of cellular functions, and has been shown to have neuroprotective, anti-inflammatory, anti-nociceptive (anti-pain) and anti-convulsant properties (1). It also reduces gastrointestinal motility and cancer cell proliferation, as well as protecting the vascular endothelium in the ischemic heart (2). Often in people with chronic disorders, the body does not produce enough PEA, thus by taking PEA to supplement the body’s shortage is may be beneficial in helping to treat these conditions (1).

How Does PEA work

PEA has been demonstrated to bind to a receptor in the cell-nucleus (a nuclear receptor) and exert a large variety of biological functions. The main target of PEA is thought to be the peroxisome proliferator-activated receptor alpha (PPAR-?). PEA also has affinity to cannabinoid-like G-coupled receptors GPR55 and GPR119. However, PEA cannot be strictly considered a classic endocannabinoid because it lacks affinity for the cannabinoid receptors CB1 and CB2 receptors (4). PEA harnesses the endogenous regulatory mechanisms suppressing chronic neurogenic inflammation, and can be well combined with all other analgesics and medications (3).

PEA Dosing

General PEA pain relief dosing guidelines are as follows:

Initially with or without food, for the first 6 weeks, given in 3 divided doses. If response is successful, the patient may taper down to the lowest successful dose for maintenance treatment.

Doses may be taken or without food.

Response mostly occurs in the first 1-2 months of treatment (5).

If after some weeks in the case of insufficient effects, patient could increase the PEA pain relief medication dose to two 400mg capsules three times daily (3).

For a more individualized approach, a minimum dose of 20 mg per kg of body weight and maximum dose of 100 mg per kg of body weight can be used (5).

For children PEA doses of up to 50 mg per kg Bodyweight was tolerated without side effects (3).

The use of PEA in pregnancy and lactation is still insufficiently investigated (5).

A successful response to PEA would include the patient first noticing a general feeling of increased comfort, and a decrease of the intense peaks of pain. In the following weeks responders note a less intense inflammation (less swelling, less temperature differences, less redness or bluishness) (3).

PEA is available in capsule form and as a topical cream. Best results are achieved if taken by mouth for 2-3 months, and used in conjunction with the cream. PEA capsules support the nerves from within, while the PEA used topically can help patients with poor oral absorption to still receive benefit, thanks to this alternative route of administration.

PEA Adverse Effects

Since 1972, dozens of clinical trials reported in the medical literature involving thousands of patients have documented the benefits of PEA, with results showing PEA is an effective and safe natural compound to use. In these studies, many of which included elderly and child subjects, no negative side effects have been identified (5). There are yet to be any reported drug-drug interactions involving PEA and other medications (5).


  1. http://www.whria.com.au/wp-content/uploads/2016/10/PEA-for-nerve-pain-and-inflammation.pdf
  2. https://pubchem.ncbi.nlm.nih.gov/compound/Palmitoylethanolamide#section=Top
  3. http://www.neuropathie.nu/crps-dystrofie-/how-to-use-pea-in-crps.html
  4. https://www.linkedin.com/pulse/palmitoylethanolamidepea-victoria-xu/
  5. https://www.optipea.com/about-pea/safety/