Herb & supplement monograph

Palmitoylethanolamide (pea) Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by ·Updated July 2026
What is this page for?

First and foremost: how Palmitoylethanolamide (pea) interacts with medications. The heart of this page is the interaction list — every drug Palmitoylethanolamide (pea) is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what Palmitoylethanolamide (pea) is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

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Interaction report

Drugs that interact with Palmitoylethanolamide (pea)

0 medications have a known interaction with Palmitoylethanolamide (pea), graded by severity. Select any drug for the full evidence-based detail.

We don’t currently list any known drug interactions for Palmitoylethanolamide (pea). This doesn’t guarantee none exist — always confirm with your pharmacist before combining supplements with your medications.

Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

  • Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
  • Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
  • Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
  • No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

  • Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
  • Probable. Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • Possible. Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
  • Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

  • Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
  • Each drug listed above links to the full report for that exact Palmitoylethanolamide (pea) combination — clinical detail, likelihood, evidence level, and citations.
  • Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.
Monograph

Palmitoylethanolamide (pea): Uses, Safety & Side Effects

Medically reviewed by · Reviewed July 2026 ·
The bottom line

Palmitoylethanolamide (PEA) is a fat-like molecule made naturally in the body and studied mainly for pain and inflammation. Some research suggests it may help certain types of chronic and nerve pain, but the overall evidence is still limited and more high-quality studies are needed. It appears generally well tolerated, but talk with your pharmacist or doctor before starting it.

Part used
Not a plant; a fatty acid compound made in the body and found in some foods
Common forms
Capsules, tablets, sublingual tablets, powders, and 'micronized' or 'ultramicronized' formulations
People commonly use it for
  • Chronic pain
  • Nerve (neuropathic) pain
  • Inflammation
  • Low back and sciatica pain
  • General immune and recovery support

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance
OverallUse caution

Generally well tolerated in studies, but long-term safety data are limited.

PregnancyInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full pregnancy detail
BreastfeedingInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Jump to a section

Overview

Palmitoylethanolamide, usually shortened to PEA, is a fatty acid compound that your own body makes. It belongs to a group of natural molecules called fatty acid amides. Your cells tend to make more of it in response to stress, injury, or inflammation, which is why scientists became interested in it.

PEA is also found in small amounts in some foods, such as egg yolk, soybeans, peanuts, and certain meats. Supplement versions are usually made in a lab and sold as capsules, tablets, or powders. You may see special forms labeled micronized or ultramicronized, which are processed into smaller particles in an effort to help the body absorb them better.

People most often take PEA to help with chronic pain, nerve pain, and inflammation. It has become popular as a supplement option for people looking for alternatives or add-ons to standard pain relievers.

How it works

PEA is thought to work mainly by calming overactive inflammation and pain signaling. One leading idea is that it acts on a cell receptor called PPAR-alpha, which helps control genes involved in inflammation.

Researchers also believe PEA may quiet down mast cells and glial cells—immune-type cells that can release substances driving pain and swelling. Some scientists describe PEA as supporting the body's own endocannabinoid-like system, helping it manage pain and inflammation, though it does not directly act like THC or CBD.

It's worth noting that many of these mechanisms come from laboratory and animal research. They help explain why PEA might work, but they don't prove it will work in any given person.

Effectiveness

Does Palmitoylethanolamide (pea) work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by .

Evidence overview · 49 uses evaluated
1 Possibly effective 1 Leans ineffective 47 Insufficient evidence
How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.
2Likely EffectiveGood evidence, though not yet conclusive.
3Possibly EffectiveSome evidence suggests a benefit.
4Possibly IneffectiveSome evidence it may not help.
5Likely IneffectiveFairly strong evidence it doesn’t help.
6IneffectiveStrong evidence it doesn’t work.
7Insufficient Reliable Evidence to RateToo little research to say either way.
Possibly Effective Osteoarthritis
Rating & evidence shown verbatim from Natural Medicines

Oral PEA seems to reduce pain and stiffness and improve function in patients with osteoarthritis.

Possibly Ineffective Spinal cord injury
Rating & evidence shown verbatim from Natural Medicines

Oral PEA does not seem to reduce pain or spasticity associated with spinal cord injury.

Also studied for 47 conditions — evidence insufficient to rate
Insufficient Reliable Evidence To Rate Allergic rhinitis (hay fever)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for allergic rhinitis (hay fever).

Insufficient Reliable Evidence To Rate Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for ALS.

Insufficient Reliable Evidence To Rate Atopic dermatitis (eczema)
Rating & evidence shown verbatim from Natural Medicines

Topical PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Autism spectrum disorder
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for autism.

Insufficient Reliable Evidence To Rate Back pain
Rating & evidence shown verbatim from Natural Medicines

Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Bipolar disorder
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for bipolar disorder.

Insufficient Reliable Evidence To Rate Cannabis use disorder
Rating & evidence shown verbatim from Natural Medicines

Although there is interest in using oral PEA for cannabis withdrawal, there is insufficient reliable information about the clinical effects of PEA for this condition.

Insufficient Reliable Evidence To Rate Carpal tunnel syndrome
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for carpal tunnel syndrome.

Insufficient Reliable Evidence To Rate Chemotherapy-induced peripheral neuropathy
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for chemotherapy-induced peripheral neuropathy.

Insufficient Reliable Evidence To Rate Chronic kidney disease (CKD)
Rating & evidence shown verbatim from Natural Medicines

Although there is interest in using oral PEA for CKD, there is insufficient reliable information about the clinical effects of PEA for this condition.

Insufficient Reliable Evidence To Rate Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS)
Rating & evidence shown verbatim from Natural Medicines

Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Circadian rhythm sleep disorders
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial in patients with disturbed sleep patterns.

Insufficient Reliable Evidence To Rate Cognitive function
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for improving cognitive function in healthy individuals.

Insufficient Reliable Evidence To Rate Cognitive impairment
Rating & evidence shown verbatim from Natural Medicines

Although there is interest in using oral PEA for cognitive impairment, there is insufficient reliable information about the clinical effects of PEA for this condition.

Insufficient Reliable Evidence To Rate Complex regional pain syndrome
Rating & evidence shown verbatim from Natural Medicines

Although there is interest in using topical PEA for complex regional pain syndrome, there is insufficient reliable information about the clinical effects of PEA for this condition.

Insufficient Reliable Evidence To Rate Coronavirus disease 2019 (COVID-19)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for improving persistent symptoms following COVID-19 infection, including impaired sense of smell or cognitive complaints.

Insufficient Reliable Evidence To Rate Depression
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for depression when used in combination with citalopram.

Insufficient Reliable Evidence To Rate Diabetic neuropathy
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for diabetic neuropathy.

Insufficient Reliable Evidence To Rate Dry eye
Rating & evidence shown verbatim from Natural Medicines

It is unclear if eye drops containing PEA are beneficial for dry eye.

Insufficient Reliable Evidence To Rate Dry skin
Rating & evidence shown verbatim from Natural Medicines

It is unclear if topical PEA is beneficial for dry skin.

Insufficient Reliable Evidence To Rate Dysmenorrhea
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for dysmenorrhea.

Insufficient Reliable Evidence To Rate Endometriosis
Rating & evidence shown verbatim from Natural Medicines

Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Exercise-induced muscle damage
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for the prevention or treatment of exercise-induced muscle damage.

Insufficient Reliable Evidence To Rate Exercise-induced muscle soreness
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for the prevention or treatment of exercise-induced muscle soreness.

Insufficient Reliable Evidence To Rate Fibromyalgia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for fibromyalgia.

Insufficient Reliable Evidence To Rate Glaucoma
Rating & evidence shown verbatim from Natural Medicines

Taking oral PEA seems to have a small beneficial effect on intraocular pressure. However, it is unclear if oral PEA is beneficial for glaucoma.

Insufficient Reliable Evidence To Rate Herniated disc
Rating & evidence shown verbatim from Natural Medicines

Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Inflammatory bowel disease (IBD)
Rating & evidence shown verbatim from Natural Medicines

Although there is interest in using oral PEA for IBD, including Crohn disease and ulcerative colitis, there is insufficient reliable information about the clinical effects of PEA for these conditions.

Insufficient Reliable Evidence To Rate Interstitial cystitis
Rating & evidence shown verbatim from Natural Medicines

Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Irritable bowel syndrome (IBS)
Rating & evidence shown verbatim from Natural Medicines

Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Migraine headache
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for reducing the frequency and severity of migraines in children and adults.

Insufficient Reliable Evidence To Rate Multiple sclerosis (MS)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for MS.

Insufficient Reliable Evidence To Rate Muscle strength
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for improving muscle strength, power, or mass during resistance training.

Insufficient Reliable Evidence To Rate Neuropathic pain
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for improving neuropathic pain.

Insufficient Reliable Evidence To Rate Obesity
Rating & evidence shown verbatim from Natural Medicines

Although there is interest in using oral PEA for weight loss, there is insufficient reliable information about the clinical effects of PEA for this use.

Insufficient Reliable Evidence To Rate Parkinson disease
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for patients with Parkinson disease using levodopa.

Insufficient Reliable Evidence To Rate Postoperative pain
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for reducing postoperative pain.

Insufficient Reliable Evidence To Rate Prurigo nodularis
Rating & evidence shown verbatim from Natural Medicines

Topical PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Respiratory tract infections
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for preventing respiratory tract infections.

Insufficient Reliable Evidence To Rate Schizophrenia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for schizophrenia.

Insufficient Reliable Evidence To Rate Sciatica
Rating & evidence shown verbatim from Natural Medicines

Small clinical studies suggest that oral PEA may be beneficial for reducing pain associated with sciatica.

Insufficient Reliable Evidence To Rate Shigellosis
Rating & evidence shown verbatim from Natural Medicines

Although there is interest in using oral PEA for shigellosis, there is insufficient reliable information about the clinical effects of PEA for this use.

Insufficient Reliable Evidence To Rate Stroke
Rating & evidence shown verbatim from Natural Medicines

Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Insufficient Reliable Evidence To Rate Temporomandibular disorders (TMD)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for TMD.

Insufficient Reliable Evidence To Rate Tourette syndrome
Rating & evidence shown verbatim from Natural Medicines

Although there is interest in using oral PEA for Tourette syndrome, there is insufficient reliable information about the clinical effects of PEA for this use.

Insufficient Reliable Evidence To Rate Upper respiratory tract infection (URTI)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral PEA is beneficial for preventing URTI in generally healthy individuals.

Insufficient Reliable Evidence To Rate Vulvar pain
Rating & evidence shown verbatim from Natural Medicines

Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

Source & disclaimer. Effectiveness ratings and evidence summaries are provided by Natural Medicines (Therapeutic Research Center) and shown as licensed. Where Natural Medicines hasn’t rated a use, HelloPharmacist’s pharmacists may add their own reviewed rating and evidence (each such entry is labeled). This is educational information, not medical advice — talk with your pharmacist or doctor before starting, stopping, or changing a supplement.

Safety & precautions

In the studies done so far, PEA has generally appeared well tolerated, with few reported side effects. Still, most studies were relatively short, so we don't have strong information about long-term safety or about use in people with serious medical conditions.

If you have a chronic illness, take prescription medicines, or are managing ongoing pain, talk with your pharmacist or doctor before adding PEA. It should not replace treatments your healthcare provider has recommended without their input.

Because there is not enough reliable safety data, PEA should be avoided during pregnancy and breastfeeding. It is also not well studied in children, so it should only be used in young people under medical guidance. As with any supplement, choose products from reputable companies, since supplements are not tightly regulated and quality can vary.

Side effects

PEA is usually described as having a low risk of side effects in studies. When side effects do occur, they tend to be mild, such as stomach upset, nausea, or a feeling of fullness or discomfort.

Serious side effects have not been commonly reported, but because long-term and large-scale safety data are limited, rare or delayed effects cannot be ruled out. If you notice an allergic reaction—such as rash, swelling, or trouble breathing—stop taking it and seek medical care right away.

Palmitoylethanolamide (pea): Reported Adverse Effects

Documented safety reports on Palmitoylethanolamide (pea) from the evidence-graded Natural Medicines (TRC Healthcare) database, shown word-for-word from the licensed record.

Orally and topically, PEA seems to be generally well tolerated.

Most Common Adverse Effects:

Orally: Nausea.

Reports by condition
Dry skin Dermatologic

Topically, applying a lotion containing PEA twice daily worsened pruritus and caused stinging, scaling, or reddening in 13% of patients with dry skin. However, these adverse effects did not occur more frequently than in patients applying the vehicle alone.

  1. Visse K, Blome C, Phan NQ, Augustin M, Ständer S. Efficacy of body lotion containing N-palmitoylethanolamine in subjects with chronic pruritus due to dry skin: A dermatocosmetic study. Acta Derm Venereol. 2017;97(5):639-641.
Nausea and vomiting Gastrointestinal

Orally, PEA has been rarely reported to cause mild and transient gastrointestinal symptoms, such as nausea.

  1. 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.
  2. 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.
  3. Papetti L, Sforza G, Tullo G, et al. Tolerability of palmitoylethanolamide in a pediatric population suffering from migraine: A pilot study. Pain Res Manag 2020;2020:3938640.
DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

Adverse-effects data: Natural Medicines, Therapeutic Research Center

Dosing

There is no official, standardized dose of PEA. Studies have used a range of amounts and different formulations, including micronized and ultramicronized versions, which can affect how the body absorbs it.

Because of this, the best approach is to follow the directions on the product label and start with the lowest suggested amount. PEA is often taken once or twice a day, sometimes split into doses, and it may take several weeks before any effect is noticed.

Before starting, check with your pharmacist or doctor to make sure PEA is appropriate for you and to confirm a reasonable amount based on the product you choose.

Pregnancy & Breastfeeding

Palmitoylethanolamide (pea) & Pregnancy

Insufficient reliable information

Insufficient reliable information available; avoid using.

Palmitoylethanolamide (pea) & Breastfeeding

Insufficient reliable information

Insufficient reliable information available; avoid using.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

© 2026 Therapeutic Research Center

Pregnancy & lactation ratings: Natural Medicines, Therapeutic Research Center

References & further reading

The 4 references that drive our Palmitoylethanolamide (pea) monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. 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. PubMed
  2. 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.
  3. Papetti L, Sforza G, Tullo G, et al. Tolerability of palmitoylethanolamide in a pediatric population suffering from migraine: A pilot study. Pain Res Manag 2020;2020:3938640. PubMed
  4. Visse K, Blome C, Phan NQ, Augustin M, Ständer S. Efficacy of body lotion containing N-palmitoylethanolamine in subjects with chronic pruritus due to dry skin: A dermatocosmetic study. Acta Derm Venereol. 2017;97(5):639-641. PubMed
Keep reading

This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Brand directory

Brands that make products with Palmitoylethanolamide (pea)

47 brands in our database make a supplement containing Palmitoylethanolamide (pea).

Product directory

Supplement products with Palmitoylethanolamide (pea)

97 products in our database contain Palmitoylethanolamide (pea). Open any to see its full ingredient list and every drug interaction we check.

Pharmacist Counseling Corner

Palmitoylethanolamide (pea): Common Questions

What is Palmitoylethanolamide (pea) used for, and does it work?
People use Palmitoylethanolamide (pea) for many reasons, but the evidence varies by use. According to the Natural Medicines database, there is at least some clinical evidence supporting Palmitoylethanolamide (pea) for Osteoarthritis. For most other uses it has been studied for, the evidence is currently insufficient to rate. See the graded list on this page, and always confirm with your pharmacist or doctor.
Does Palmitoylethanolamide (pea) interact with prescription medications?
We do not currently list any known drug interactions for Palmitoylethanolamide (pea). This does not guarantee that none exist, so always confirm with your pharmacist before combining it with your medications.
How are Palmitoylethanolamide (pea) interactions rated?
Each interaction is graded major, moderate, or minor based on how clinically significant it is and the strength of the evidence behind it. Major interactions are the most serious and are best avoided, or used only under close professional supervision.
Is it safe to take Palmitoylethanolamide (pea) with my medications?
It depends on the specific medication. Some combinations are fine, while others call for monitoring, timing changes, or should be avoided. Check your exact drug above and confirm with your pharmacist or doctor before starting, stopping, or changing anything.
Where does this Palmitoylethanolamide (pea) interaction information come from?
Our interaction data is built on the Natural Medicines database — an evidence-graded reference for vitamins, herbs, and supplements — and is reviewed by licensed HelloPharmacist pharmacists, who may add clinical context.
What is PEA used for?
People most commonly use PEA for chronic pain, nerve pain, and inflammation. Some research suggests it may help certain types of pain, but the evidence is still limited and not fully conclusive.
Is PEA safe to take?
PEA has generally been well tolerated in studies, with mostly mild side effects like stomach upset. However, long-term safety data are limited, so it's best to check with your pharmacist or doctor before using it regularly.
Can I take PEA while pregnant or breastfeeding?
There isn't enough reliable safety information for use during pregnancy or breastfeeding, so it's best to avoid PEA during these times unless your doctor advises otherwise.
How long does PEA take to work?
PEA is not a fast-acting pain reliever. In studies it often takes several weeks of regular use before any benefit is noticed, and not everyone responds to it.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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