Evigrade
DrugsCosmetic ingredientsCalculatorsInteractionsEvigrade SkinEvigrade Meds ↗
ConditionsJournalMethodologyPro for practitioners
ESRU

Palmitoylethanolamide

Endogenous fatty-acid amide (aliamide); in Italy and Spain registered as a complemento alimenticio and «specialty food for medical purposes» for chronic neuropathic pain

ATC code: N02BG-PEA

Brand names – supplements: NOW Foods PEA 300 mg, Normast, PeaPure, Jarrow Formulas PEASupplements are not tested in clinical trials and are not registered as medications.

Updated · Methodology

Indications

C

Neuropathic pain

Adjunct

PEA is an endogenous fatty-acid amide widely used in Italy and Spain for chronic neuropathic pain (sciatica, diabetic polyneuropathy, post-herpetic neuralgia, carpal tunnel, pelvic pain). The Paladini meta-analysis (Pain Physician 2016) pooled 12 RCTs and observational studies with 1484 participants: at 600–1200 mg/day for 30–60 days, PEA reduced VAS pain by a mean 1.8 points versus placebo or standard care. Effect size is small, confidence intervals wide and most studies are funded by the manufacturer Epitech. Cochrane opened a 2017 review protocol on PEA for chronic pain but withdrew it in 2018 without a full review – the Cochrane Library has no quality meta-analytic base. CG173 for neuropathic pain recommends amitriptyline, duloxetine, gabapentin and pregabalin as first line; PEA is not in international guidelines. In Italy and Spain, neurologists and pain clinicians prescribe PEA off-label as adjunct therapy when first-line drugs are contraindicated. If PEA is being considered instead of pregabalin or duloxetine, discuss with a doctor – the first-line drugs have stronger evidence.

Sources

  1. Pain Physician (Paladini et al.): Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis (2016)
  2. CNS Neurol Disord Drug Targets (Guida et al.): Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice (2017)
  3. Cochrane (Derry et al.): Palmitoylethanolamide for chronic pain in adults (2017)
  4. NICE: Neuropathic pain in adults: pharmacological management in non-specialist settings (2020)
  5. EMA / AEMPS: Palmitoiletanolamida: revision regulatoria como complemento alimenticio en Espana (2019)

ICD-10: M79.2 · ICD-11: MG30.5Z

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

D

Superfoods and adaptogens (marketing category)

Not recommended

PEA is marketed as a «magic pill for chronic pain of any kind» – from migraine and fibromyalgia to back pain, endometriosis, post-COVID syndrome and even anxiety and depression. The real evidence base is limited to neuropathic pain with a small effect size and high study bias risk. Systematic reviews outside neuropathic pain (migraine, fibromyalgia, post-COVID) either do not exist or state insufficient data. There is no Cochrane review – the protocol was withdrawn in 2018. has not approved PEA health claims. There is no HMPC monograph. The «universal analgesic» idea is marketing: different chronic-pain types (nociceptive, neuropathic, nociplastic, central sensitisation) run through different mechanisms and need different targeted therapy. The product sells at 40–80 euro per month – a meaningful cost for a small effect. If PEA was bought instead of seeing a pain specialist for persistent pain, discuss with a doctor – chronic pain needs cause diagnosis (disc herniation, neuropathy, central sensitisation) and targeted treatment.

Sources

  1. Pain Physician (Paladini et al.): Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis (2016)
  2. Cochrane (Derry et al.): Palmitoylethanolamide for chronic pain in adults (2017)
  3. NICE: Neuropathic pain in adults: pharmacological management in non-specialist settings (2020)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

PEA (palmitoylethanolamide) is an endogenous N-acylethanolamide related to anandamide, produced by neurons, glia, immune cells and peripheral tissues in response to inflammation and tissue injury. PEA does not bind directly to CB1 or CB2 cannabinoid receptors; its main target is the nuclear receptor PPAR-alpha, with indirect cannabinoid-system effects via FAAH inhibition and TRPV1 and GPR55 receptor activation. The net effect is reduced mast-cell and microglia activation and lower release of TNF-alpha, NGF and other pro-inflammatory mediators in neuropathic and chronic pain pathways. No HMPC monograph exists; PEA is not registered as a drug in the EU. In Italy, Normast and PeaPure (Epitech Group) are «alimento a fini medici speciali» under Italian decree 169/2004 for chronic neuropathic pain. In Spain AEMPS and AESAN classify PEA as a complemento alimenticio without a formal therapeutic indication, but neurologists and pain clinicians often prescribe it off-label. The has not registered PEA as a drug; it is sold as a dietary supplement.

Safety

Contraindications

  • Known hypersensitivity to palmitoylethanolamide or excipients
  • Severe hepatic impairment without physician supervision
  • Pregnancy or lactation without a clinical indication

Serious adverse effects

  • Severe allergic reactions in sensitised users (rare)

Common adverse effects

  • Gastrointestinal discomfort, nausea
  • Drowsiness in the first days of use
  • Headache

Pregnancy: can you take Palmitoylethanolamide?

PEA safety in human pregnancy has not been studied in RCTs. PEA is an endogenous amide present at physiologic concentrations in plasma, placenta and breast milk, but the safety of pharmacologic doses in pregnant women is not established. AEMPS and AESAN advise against complementos alimenticios without therapeutic indication during pregnancy.

Breastfeeding: can you take Palmitoylethanolamide?

PEA is present in human milk at physiologic concentrations. Lactation safety of supplemental dosing has not been studied in RCTs. PEA is not justified during lactation without clear clinical indications and physician supervision.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Check interaction with another drug

Opens the checker prefilled with this drug. Pick the second one from your regimen.

Open checker

Summary of a multi-drug list →

Medicine list: everything you take in one place →

Frequently asked

What is Palmitoylethanolamide used for?

Palmitoylethanolamide is evaluated for the following indications with varying evidence strength: Neuropathic pain (evidence tier C), Superfoods and adaptogens (marketing category) (evidence tier D). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Palmitoylethanolamide?

Common side effects of Palmitoylethanolamide (≥ 1 in 100): Gastrointestinal discomfort, nausea, Drowsiness in the first days of use, Headache. See the Safety section for uncommon and serious reactions.

Is Palmitoylethanolamide safe during pregnancy?

PEA safety in human pregnancy has not been studied in RCTs. PEA is an endogenous amide present at physiologic concentrations in plasma, placenta and breast milk, but the safety of pharmacologic doses in pregnant women is not established. AEMPS and AESAN advise against complementos alimenticios without therapeutic indication during pregnancy.

Is Palmitoylethanolamide compatible with breastfeeding?

PEA is present in human milk at physiologic concentrations. Lactation safety of supplemental dosing has not been studied in RCTs. PEA is not justified during lactation without clear clinical indications and physician supervision.

Who should not take Palmitoylethanolamide?

Palmitoylethanolamide is contraindicated in: Known hypersensitivity to palmitoylethanolamide or excipients; Severe hepatic impairment without physician supervision; Pregnancy or lactation without a clinical indication. Full list in the Safety section.

Other drugs in this group

Rizatriptan, Sumatriptan, Tapentadol, Tramadol, Buprenorphine (transdermal), Fentanyl, Morphine, Tramadol + Paracetamol