PEA (Palmitoylethanolamide)

What is Palmitoylethanolamide (PEA)?

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide that acts as an endogenous modulator of pain and inflammation. It is produced in the body in response to pain, inflammation, and tissue damage, and is found in various tissues, including the brain, spinal cord, and immune cells.

How does it work?

PEA is thought to work by inhibiting the activity of certain inflammatory cells, including mast cells and microglia, and by activating the cannabinoid receptor type-2 (CB2) and peroxisome proliferator-activated receptor alpha (PPAR-?). These actions help to reduce pain and inflammation, and protect against damage to the nervous system.

What are the active ingredients that are important for its medicinal properties?

Palmitoylethanolamide is the active ingredient in PEA.

What forms does it come in?

PEA is available in various forms, including capsules, tablets, creams, and powders.

When was it first used for medicinal purposes?

PEA was first discovered in the 1950s, and has been investigated for its potential therapeutic effects since the 1970s.

What does PEA (Palmitoylethanolamide) help with?

PEA is short for palmitoylethanolamide. It is a fat-like substance the body makes on its own. It is also sold as a supplement, mostly for pain that lasts.

Most PEA research looks at long-term pain. Nerve pain is the best studied use, and several human trials found lower pain scores. Many of those trials were small, so the picture is hopeful but not settled.

• Long-lasting nerve pain, such as pain from diabetes or chemo
  Good evidence — the largest body of human trials on PEA, though sizes and doses are not recorded in this file. Nerve pain is where PEA has been studied most. This includes pain from diabetes, from chemo drugs, and from nerve damage with no clear cause. In trials, people taking PEA reported pain that felt less intense over time. Lab work suggests PEA calms nerve and immune cells that keep firing pain signals.
  Evidence grade B · Traditional tier T0
• Lower back pain
  Good evidence — clinical trials in both new and long-lasting back pain. Trials have tested PEA in short-term and long-term back pain. People reported less pain, including some cases with a pinched nerve. In these studies PEA did not bring the stomach trouble or habit risk seen with some standard pain drugs.
  Evidence grade B · Traditional tier T0
• Sciatica (pain running down the leg)
  Good evidence — controlled human studies. Sciatica is leg pain from a squeezed sciatic nerve. In controlled studies, people taking PEA reported meaningful pain relief. Lab work links this to less swelling around the squeezed nerve, rather than simply blocking the pain signal.
  Evidence grade B · Traditional tier T0
• Fibromyalgia (wide-spread body pain)
  Early evidence — several clinical trials, small in size. Fibromyalgia pain comes from a nervous system that stays on high alert. Several clinical trials found real drops in pain scores in people who took PEA. The trials were small, so the true size of the effect is not clear.
  Evidence grade C · Traditional tier T0
• Knee osteoarthritis pain and stiffness
  Early evidence — clinical studies in knee osteoarthritis. Joint pain here comes from wear plus swelling in and around the joint. Clinical studies in knee osteoarthritis found better pain scores and easier movement with PEA. Lab work ties this to the swelling part, not to the wear itself.
  Evidence grade C · Traditional tier T0
• Carpal tunnel syndrome (wrist and hand pain)
  Early evidence — clinical studies in mild to moderate cases. Carpal tunnel comes from a squeezed nerve at the wrist. Clinical studies found less pain and better nerve test scores with PEA. It has been looked at as one option besides surgery in mild to moderate cases.
  Evidence grade C · Traditional tier T0
• Long-term pelvic pain, such as endometriosis pain
  Early evidence — studies in women with endometriosis-related pain. Studies in women with endometriosis pain found clear drops in pain while taking PEA. The human studies on file are in endometriosis, not in other pelvic pain causes. Lab work links pelvic pain to mast cells and nerve swelling, which is where PEA acts.
  Evidence grade C · Traditional tier T0
• Migraine attacks
  Early evidence — a small amount of clinical work on migraine prevention. Some clinical work has tested PEA to cut down how often migraines strike. Groups given PEA had fewer attacks. This work is limited, so the finding still needs larger testing. Lab work suggests PEA calms mast cells in the lining of the brain.
  Evidence grade C · Traditional tier T0
• Long COVID pain, fatigue and brain fog
  Not yet tested in people — trials still running; early results only. Researchers are now testing PEA for lasting COVID symptoms. Early results have been described as encouraging. No finished human trial is on file here, so nothing can be said yet about what it does.
  Evidence grade insufficient · Traditional tier T0

What PEA (Palmitoylethanolamide) has not been shown to do

• PEA has not been shown to rebuild worn joint cartilage or to repair damaged nerves.
• Broad claims that PEA helps 'any inflammatory condition' rest mostly on lab work, not on trials in people with each disease.
• It has not been shown to help gut inflammation; no human trial for that is on file here.
• It has not been shown to treat long COVID, because those trials are still running.
• It has not been shown to replace carpal tunnel surgery; it has only been tested as an option in mild to moderate cases.

How to read this:

Grades here rate the human evidence for each use, not how strong the remedy is. A means steady results across randomised trials in people. B means at least one good randomised trial. C means small, mixed or early human studies. D means weak or clashing human results. Insufficient means no human study, only lab, animal or custom. Where a trial size or dose is known we print it; this file does not record them, so none are given. This page lists options and what studies found. It is not medical advice, and it is not a promise of results for you.

What can it help prevent?

PEA has been shown to prevent the development of neuropathic pain in animal models.

Which foods are rich in it?

PEA is not found in significant amounts in food, and is primarily synthesized in the body.

What are possible side effects?

PEA is generally well-tolerated, and few side effects have been reported. The most commonly reported side effects include mild gastrointestinal symptoms, such as bloating and diarrhea.

What’s the recommended daily dose?

The recommended daily dose of PEA varies depending on the condition being treated, but typically ranges from 300 to 1200 mg per day.

For pain: 1,200 mg daily in divided doses

How many days does it take to work?

The onset of action for PEA varies depending on the condition being treated, but may take several weeks to achieve maximum effect.

What time of day is best to take it?

The optimal time of day to take PEA has not been established, and can be taken at any time.

Is it best to take it with or without food?

PEA can be taken with or without food, although taking it with food may improve absorption.