Ingredient Reference
Palmitoylethanolamide (PEA): Chemistry, Forms, Studied Amounts and Safety
Structure, history, particle size forms, label checks, human studies and their amounts, safety data, interactions and US status.
Shop Anandamide SupplementPEA on the Label
Exactly how much palmitoylethanolamide is in each of our products, straight from the label.
How to use it (label directions): Anandamide Supplement: take 2 capsules each morning, with food or without. OEA Supplement: take 2 capsules a day, 15 to 30 minutes ahead of your biggest meal. How this compares with research amounts: the trials below gave 300 to 1,200 mg a day of PEA, mostly on its own. Our formulas pair 150 or 200 mg with related compounds, so the amounts are not directly comparable. Use each product as directed on its label.
PEA at a Glance
| Item | Details |
|---|---|
| Names | Palmitoylethanolamide; palmidrol; N-(2-hydroxyethyl)hexadecanamide; PubChem CID 4671. |
| Formula | C18H37NO2, about 299.5 g/mol. Waxy and poorly soluble in water. |
| Family | Fatty acid ethanolamides, with anandamide and oleoylethanolamide (OEA). |
| First sources | Egg yolk and soybean lecithin (1957); peanut oil (1959). |
| In the body | Made in tissues on demand; broken down by FAAH and NAAA. |
| Amounts in human studies | 300 to 1,200 mg a day; case series up to 2,000 mg. |
| Main cautions | Upset stomach, allergic reactions, pregnancy and breastfeeding, prescription medicines. |
| US status | Dietary supplement ingredient. FDA does not approve supplements before sale. |
Looking for what PEA is used for? Benefits, the pain, sleep and memory findings in plain language, and the PEA versus phenylethylamine versus pea protein mix-up are covered in Palmitoylethanolamide (PEA): Benefits, Dosage and Side Effects. This page sticks to reference facts.
Structure, History and Biology
Palmitoylethanolamide joins palmitic acid, the 16-carbon saturated fatty acid common in plant and animal fats, to ethanolamine through an amide bond (Lo Verme 2005). The long fatty tail makes it waxy and poorly soluble in water, so dissolving is often the slow step in absorbing it by mouth (Gabrielsson 2016). Palmidrol is its international nonproprietary drug name.
A short history
In 1957 Kuehl and colleagues isolated a crystalline compound from egg yolk and soybean lecithin and identified it as N-(2-hydroxyethyl)palmitamide. A 1959 paper listed egg yolk, peanut oil and soybean lecithin as sources. Czechoslovakia approved manufacture of a PEA drug, Impulsin, in 1970, and it was sold in Spain as Palmidrol. Italian microPEA products followed (Nestmann 2017).
Made and used in the body
Animal and human tissues make PEA locally, and production rises on demand after tissue injury or stress. Two enzymes break it down: fatty acid amide hydrolase (FAAH) and N-acylethanolamine acid amidase (NAAA) (Petrosino 2018). In mouse studies its main target was the PPAR-alpha receptor (Lo Verme 2005); the guide covers that mechanism and the entourage effect with anandamide.
Particle Size, Forms and How to Read a Label
| Form | Particle size | What to know |
|---|---|---|
| Unprocessed PEA | About 100 to 2,000 µm | Large particles of a poorly soluble compound. |
| Micronized PEA | About 2 to 10 µm | Milled for more surface area (Nestmann 2017 tested 0.5 to 10 µm material). |
| Ultramicronized PEA | About 0.8 to 6 µm | Finer milling; one batch had a median size of 2.52 µm. |
| Dispersible PEA (Levagen+) | Not a size grade | Uses the LipiSperse dispersion system; the form in the 2021 sleep and 2024 memory trials. |
Particle sizes from Petrosino 2018.
Label checks
- The full name: palmitoylethanolamide. "PEA" alone can also mean phenylethylamine or pea protein.
- Milligrams of PEA per serving, and how many capsules make a serving.
- The form: micronized, ultramicronized or a dispersible branded ingredient.
- Other ingredients: PEA is often paired with anandamide, OEA or other compounds, each with its own amount.
PEA in Human Studies
These studies measured blood levels, pain and joint scores, sleep, memory and safety. Groups are named as the authors describe them.
| Study | Who | Amount a day | Length | Measured | Result |
|---|---|---|---|---|---|
| Petrosino data, reported in Gabrielsson 2016 | 10 healthy volunteers | 300 mg micronized PEA, once | 6 hours | Plasma PEA | Rose from about 10 to about 23 pmol/ml at 2 hours, then back to baseline |
| Steels 2019, Inflammopharmacology | 111 adults with mild to moderate knee osteoarthritis | 300 or 600 mg in two doses, or placebo | 8 weeks | WOMAC joint index, pain ratings, mood and sleep scales, safety | WOMAC total and pain scores improved at both amounts versus placebo, function at 600 mg; clinical markers unchanged |
| Rao 2021, Sleep Sci Pract | 103 adults | 350 mg Levagen+, or placebo | 8 weeks | Wrist actigraphy, sleep diary, questionnaires | Shorter time to fall asleep and to feel fully awake, better thinking on waking; quality scores rose in both groups |
| Kim 2024, Nutrients | 39 healthy students, mean age 22 | 700 mg Levagen+ (600 mg PEA per the methods), or placebo | 6 weeks per arm, crossover | Serum BDNF, memory, attention and working memory tests | BDNF up 2.76 ng/mL; fewer paired associates learning errors; attention and working memory unchanged |
| Terribili 2024, Nutrients | 50 adults with fibromyalgia | 1,200 mg PEA plus 0.2 mg melatonin at bedtime | 3 months, open label, no control group | Pain scale, Insomnia Severity Index, disability index | Pain score 7.12 to 4.78 and sleep index 17.36 to 9.58 at 3 months; no adverse events |
| Viña 2025, Nutr Rev | 18 randomized trials pooled, 1,196 people with long-lasting pain | Varied | Up to 24 to 26 weeks | Pain scores, quality of life | Lower pain scores than comparison groups at 6, 8 and 24 to 26 weeks |
Studied Amounts by Setting
Amounts from research, not directions. Follow your product's label.
| Setting | Amount |
|---|---|
| Single dose blood level study | 300 mg once |
| Joint study | 300 or 600 mg a day, split morning and evening |
| Sleep and memory trials | 350 mg and 700 mg (formulated) a day |
| Open-label combination | 1,200 mg a day at bedtime |
| Trials reviewed in 2016 | 300 to 1,200 mg a day for 14 to 120 days; case series 1,200 to 2,000 mg |
| Our labels | 150 mg (Anandamide Supplement) and 200 mg (OEA Supplement) per 2 capsules |
Safety, Side Effects and Interactions
A 2016 review of the clinical trials found one adverse event clearly reported: palpitations lasting 2 to 3 hours in one person taking 300 mg, plus one case of drowsiness. Over courses of up to 49 days, the pooled data make serious reactions affecting 1 person in 200 or more unlikely; for courses of 60 days or longer, too few people had been studied to rule out reactions rarer than 1 in 100 (Gabrielsson 2016).
In laboratory testing, micronized PEA did not cause mutations in bacterial tests or chromosome damage in human cells. The single-dose LD50 in rats was above 2,000 mg per kg, and in a 90-day rat study the highest dose, 1,000 mg per kg a day, caused no effects (Nestmann 2017).
| Topic | What is reported |
|---|---|
| Common side effect | Upset stomach is the most common (WebMD). |
| Allergic reactions | Possible and can be serious; stop and get help right away (WebMD). |
| Prescription medicines | No known interactions, but they are not fully understood (WebMD). |
| Alcohol | Unknown whether alcohol affects PEA (WebMD). |
| Pregnancy and breastfeeding | Unknown effect on pregnancy; unknown whether it passes into breast milk (WebMD). |
Who should ask a clinician first
Check with a clinician before use during pregnancy or breastfeeding, alongside prescription medicine, while under care for a health condition, or under age 18. Our formulas also contain L-theanine and other ingredients, so check each ingredient's own page.
Regulatory Status in the US
In the US, PEA is sold in dietary supplements, which fall under the Dietary Supplement Health and Education Act of 1994 (DSHEA). FDA does not approve supplements before they are marketed; the company is responsible for making sure its products are not adulterated, and FDA can act once a product is sold. WebMD notes that FDA has not reviewed PEA for safety and effectiveness. Outside the US, PEA has a history as a medicine, under the drug name palmidrol (Nestmann 2017).
PEA FAQ
What is PEA made of chemically?
It is the amide formed from palmitic acid, a 16-carbon saturated fatty acid, and ethanolamine. Its formula is C18H37NO2 and its systematic name is N-(2-hydroxyethyl)hexadecanamide. The drug name palmidrol refers to the same molecule.
Where was PEA first found?
In 1957, researchers isolated it as a crystalline compound from egg yolk and soybean lecithin. A 1959 report added peanut oil as a source. It was later shown to be made in animal and human tissues.
What do micronized and ultramicronized PEA mean?
Both describe PEA milled to smaller particles. Unprocessed PEA particles run about 100 to 2,000 micrometers, micronized PEA about 2 to 10 micrometers and ultramicronized PEA about 0.8 to 6 micrometers.
What is Levagen+?
A branded PEA ingredient that uses the LipiSperse dispersion system. It was the form used in a 2021 trial at 350 mg a day and a 2024 trial at 700 mg a day.
How does the body break down PEA?
Two enzymes split it: fatty acid amide hydrolase (FAAH) and N-acylethanolamine acid amidase (NAAA). In 10 healthy volunteers given 300 mg, blood PEA roughly doubled at 2 hours, then returned to baseline.
Has PEA been sold as a medicine?
Yes, outside the US. Czechoslovakia approved manufacture of a PEA drug, Impulsin, in 1970, and PEA was marketed in Spain as Palmidrol. In the US it is sold as a dietary supplement ingredient.
How much PEA is in Synchronicity Health products?
Anandamide Supplement has 150 mg and OEA Supplement has 200 mg of palmitoylethanolamide per serving of 2 capsules, as listed on the labels.
More on PEA
Shop and learn
Ingredient pages
Sources
- Lo Verme J, et al. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Molecular Pharmacology, 2005. PubMed 15465922
- Nestmann ER. Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential. Food Science and Nutrition, 2017. PubMed 28265364
- Petrosino S, et al. Oral ultramicronized palmitoylethanolamide: plasma and tissue levels and spinal anti-hyperalgesic effect. Frontiers in Pharmacology, 2018. DOI 10.3389/fphar.2018.00249
- Gabrielsson L, Mattsson S, Fowler CJ. Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. British Journal of Clinical Pharmacology, 2016. PubMed 27220803
- Steels E, et al. A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology, 2019. DOI 10.1007/s10787-019-00582-9
- Rao A, et al. Palmitoylethanolamide for sleep disturbance. A double-blind, randomised, placebo-controlled interventional study. Sleep Science and Practice, 2021. PubMed 34522787
- Kim N, et al. Formulated palmitoylethanolamide supplementation improves parameters of cognitive function and BDNF levels in young, healthy adults: a randomised cross-over trial. Nutrients, 2024. mdpi.com
- Terribili R, et al. A fixed combination of palmitoylethanolamide and melatonin (PEATONIDE) for the management of pain, sleep, and disability in patients with fibromyalgia: a pilot study. Nutrients, 2024. mdpi.com
- Viña I, López-Moreno M. Meta-analysis of palmitoylethanolamide in pain management: addressing literature gaps and enhancing understanding. Nutrition Reviews, 2025. PubMed 39798151
- WebMD. Palmitoylethanolamide (PEA). Vitamins and Supplements. webmd.com
- US Food and Drug Administration. Questions and Answers on Dietary Supplements. fda.gov
- National Library of Medicine. PubChem Compound Summary: Palmitoylethanolamide, CID 4671. PubChem
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. If you are pregnant, nursing, taking prescription medication or managing a health condition, talk with a qualified healthcare professional before use.