Skip to main content
Supplement ScienceSupplementScience

Palmitoylethanolamide (PEA) Side Effects & Safety

Evidence:Moderate
·

This content is for informational purposes only and does not constitute medical advice. Statements about dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary — consult your healthcare provider before starting any supplement. Full disclaimer

Safety Profile

Overall safety rating: Generally Safe

Potential Side Effects

  • Very well tolerated — no significant side effects reported in clinical trials at doses up to 1,200mg/day
  • Rare mild GI discomfort
  • No psychoactive effects despite endocannabinoid system modulation
  • No withdrawal effects or tolerance development reported

Drug & Supplement Interactions

  • No known drug interactions — PEA is an endogenous compound with a very clean safety profile
  • May complement analgesics (NSAIDs, acetaminophen, pregabalin) — additive pain relief without adverse interactions
  • Theoretically safe to combine with most medications, but inform your healthcare provider

Maximum Dose

Do not exceed: Up to 1,200mg/day has been used in clinical trials; no dose-limiting toxicity has been identified

Full Palmitoylethanolamide (PEA) Guide

References

  1. Meta-analysisPaladini A, Fusco M, Cenacchi T, et al. (2016). Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis. Pain Physician. PubMed
  2. ObservationalHesselink JM, Hekker TA (2012). Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. Journal of Pain Research. DOI PubMed
  3. ReviewPetrosino S, Di Marzo V (2017). The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. British Journal of Pharmacology. DOI PubMed
  4. Meta-analysisSchweiger V, Schievano C, Martini A, Polati L, et al. (2024). Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis.. Nutrients. DOI PubMed
  5. Rao A, Erickson J, Briskey D (2025). Palmitoylethanolamide (Levagen+) for acute menstrual pain: a randomized, crossover, double-blind, placebo-controlled trial.. Women & health. DOI PubMed
  6. Meta-analysisBortoletto R, Comacchio C, Garzitto M, Piscitelli F, et al. (2025). Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations.. Brain, behavior, & immunity - health. DOI PubMed
  7. Cornali K, Di Lauro M, Marrone G, Masci C, et al. (2025). The Effects of a Food Supplement, Based on Co-Micronized Palmitoylethanolamide (PEA)-Rutin and Hydroxytyrosol, in Metabolic Syndrome Patients: Preliminary Results.. Nutrients. DOI PubMed
Show 5 more references
  1. Invernizzi M, Mulè S, Lippi L, Galla R, et al. (2025). Evaluation of the Clinical Efficacy of a Novel Palmitoylethanolamide-Equisetum arvense Supplement for the Management of Chronic Pain: Findings from a Prospective Clinical Trial.. Medical sciences (Basel, Switzerland). DOI PubMed
  2. Cominacini M, Valenti MT, Braggio M, Caramori A, et al. (2025). Unlocking Relief: Investigating the Impact of a Fixed Combination of Acetyl-L-Carnitine and Palmitoylethanolamide on Traumatic Acute Low Back Pain.. European journal of neurology. DOI PubMed
  3. Piccolo V, Marzocchi A, Maisto M, Summa V, et al. (2025). Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial.. Frontiers in nutrition. DOI PubMed
  4. Didangelos T, Karlafti E, Kotzakioulafi E, Giannoulaki P, et al. (2024). Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy.. Nutrients. DOI PubMed
  5. Rhodes CH, Hong BV, Tang X, Weng CY, et al. (2024). Absorption, anti-inflammatory, antioxidant, and cardioprotective impacts of a novel fasting mimetic containing spermidine, nicotinamide, palmitoylethanolamide, and oleoylethanolamide: A pilot dose-escalation study in healthy young adult men.. Nutrition research (New York, N.Y.). DOI PubMed