Palmitoylethanolamide (PEA)

Fatty Acidoral · inferred

Endogenous fatty acid amide that acts on PPAR-α receptors and indirectly modulates the endocannabinoid system (entourage effect with anandamide via FAAH inhibition). Potent anti-inflammatory and analgesic without CNS side effects. Produced naturally by the body in response to tissue damage. Micronized and ultra-micronized formulations dramatically improve oral bioavailability. Studied in neuropathic pain, sciatica, carpal tunnel, endometriosis, and chronic pelvic pain.

Projected serum levels — 600 mg, once daily

Palmitoylethanolamide (PEA)
Palmitoylethanolamide (PEA) modeled serum levels, 600 mg once daily over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 1 days. 0 50 100 150 200 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 1

Maintenance schedule: 600 mg once daily (oral).

Modeled steady state after ~1 days: peak ≈ 112 mg, trough ≈ 7.2 mg body load. Population-based estimate over 15 days for a 600 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Fatty Acid
Route modeled
Oral
Model confidence
inferred
Half-life
4.6 h
Common dose
600 mg
Suggested maximum
1.2k mg/day
Reference dose range
300–1.2k mg (single dose)
Suggested cadence
once daily

Documented interactions

  • danger
    Levothyroxine (Synthroid) + Palmitoylethanolamide (PEA) Protein binding

    Palmitoylethanolamide (PEA) may displace Levothyroxine (Synthroid) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic index; free…

  • danger
    Tacrolimus (Prograf) + Palmitoylethanolamide (PEA) Protein binding

    Palmitoylethanolamide (PEA) may displace Tacrolimus (Prograf) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic index; free…

  • danger
    Warfarin (Coumadin) + Palmitoylethanolamide (PEA) Protein binding

    Palmitoylethanolamide (PEA) may displace Warfarin (Coumadin) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic index; free…

  • warning
    Apigenin + Palmitoylethanolamide (PEA) Protein binding

    Apigenin may displace Palmitoylethanolamide (PEA) from plasma protein binding sites, transiently raising free drug concentration.

  • warning
    Aripiprazole (Abilify) + Palmitoylethanolamide (PEA) Protein binding

    Palmitoylethanolamide (PEA) may displace Aripiprazole (Abilify) from plasma protein binding sites, transiently raising free drug concentration.

  • warning
    Armour Thyroid (Desiccated Thyroid Extract) + Palmitoylethanolamide (PEA) Protein binding

    Palmitoylethanolamide (PEA) may displace Armour Thyroid (Desiccated Thyroid Extract) from plasma protein binding sites, transiently raising free drug concentration.

Serum checks 141 modeled interaction pairings for palmitoylethanolamide (pea) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy Petrosino S, Di Marzo V · British Journal of Clinical Pharmacology, 2017 DOI

    Comprehensive review of 21 clinical trials finding PEA 300-1200 mg/day significantly reduces pain across multiple conditions (sciatic, neuropathic, pelvic, dental) with an excellent safety profile and no drug…

  2. Palmitoylethanolamide in the treatment of chronic pain: a systematic review and meta-analysis Gabrielsson L et al. · CNS & Neurological Disorders Drug Targets, 2016 DOI

    Meta-analysis of 12 trials confirming PEA significantly reduces pain intensity versus placebo/controls across neuropathic, inflammatory, and idiopathic pain conditions, with NNT of approximately 3.

  3. Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations Bortoletto R et al. · Brain, Behavior, & Immunity - Health, 2025 DOI

    PRISMA-compliant systematic review of 48 publications from 47 randomized trials across neurological, neuropsychiatric, somatic, and visceral conditions. The strongest evidence concerned pain and general wellbeing,…

  4. Palmitoylethanolamide (Levagen+) for acute menstrual pain: a randomized, crossover, double-blind, placebo-controlled trial. Rao A, Erickson J, Briskey D · Women & health, 2025 DOI

    This citation reports a human clinical study involving Palmitoylethanolamide (PEA). It does not by itself establish a qualified dose, safety profile, efficacy claim, or pharmacokinetic route for this record.

4 published studies referenced in the app, each with a plain-language summary.