PEA is believed to work through a variety of mechanisms that have synergistic effects. Its main target is believed to be peroxisome proliferator-activated receptor alpha (PPAR-α), which regulates gene networks that control pain and inflammation.³ PEA binds to PPAR-α receptors on immune cells, reducing the production of inflammatory signals and reducing pain signals.⁴ It also modulates mast cell activation.⁵ Mast cells are important immune cells involved in the maintenance of many physiological functions, but they are also involved in the inflammatory process and are implicated in environmental allergies, asthma, and food allergies.⁶ PEA also indirectly supports the endocannabinoid system, which regulates numerous functions of the body including learning, memory, sleep, mood, and pain. PEA appears to decrease the breakdown of anandamide (a brain chemical that helps maintain homeostasis), enhancing the effects of naturally produced endocannabinoids, and by increasing the expression of endocannabinoid receptors.⁷

PEA’s Effect on Pain

Even though PEA is produced in response to injury and inflammation, chronic inflammation or pain is believed to exhaust its levels.⁸ Through the above-mentioned mechanisms, PEA helps modulate pain in ways that differ from most conventional analgesics and with impressive results. In human clinical trials, PEA has been shown to reduce pain associated with mild to moderate knee osteoarthritis, temporomandibular joint (TMJ) arthritis, pelvic pain, carpal tunnel syndrome, sciatic pain, and more.^{9 10 11 12 13} Some studies have even used PEA as an adjunct to conventional pain medications with good effect, although if you are currently taking any pain medication, you should check with your doctor before adding PEA.^{14 15}

PEA’s Neuroprotective Effects

PEA is abundantly produced in and works on the central nervous system, where its anti-inflammatory and analgesic effects appear to have wide-reaching benefits. By modulating inflammation of non-neuronal cells in the central nervous system, PEA helps to maintain homeostasis.¹⁶ Animal models, small human clinical trials, and/or case studies suggest PEA may offer benefit to those with Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), traumatic brain injury, and stroke.^{17 18 19}

Safety and Dosing

The use of PEA appears to be generally well-tolerated with no serious adverse events reported. Standard doses used in studies have ranged from 600 to 1,200 mg per day, with many tapering to a lower dose after initial loading.^{20 21} Micronized versions of PEA appear to be more bioavailable.^{22 23}

References

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