Palmitoylethanolamide for Neuro Inflammation and Mast Cell Activation

By Bryant Rubright


Palmitoylethanolamide (PEA) is a substance that is naturally produced in the body, and it can be taken as a supplement to help with certain conditions or symptoms (Not to be confused with the supplement phenylethlamine, which is also abbreviated as PEA). It is little talked about, yet plays an important role in brain health and regulating pain and inflammation. PEA was discovered in the 1950’s, but once it was also discovered to be an effective treatment for colds and flus, it was phased out of the market in the United States. For a while PEA was only available for purchase in Europe and had to shipped to the US, but due to rising popularity from new research in its use for treating autism, it is now easier to purchase.

PEA is a fatty acid that is similar to the endocannabinoids anandamide and 2-arachidonoglycerol, though is not considered an endocannabinoid since it does not bind to the CB1 and CB2 receptors. PEA indirectly has an effect is on the endocannabinoid system by upregulating anandamide activity. Anandamide and THC from cannabis both act on the CB1 receptors, which is why PEA and THC have similar effects such as reducing brain inflammation and pain, although PEA is non-psychoactive. In a sense, PEA can be considered an anti-stress molecule. During times of stress, PEA stores can be used up quickly, which is why supplementing PEA can be helpful for many different conditions.

PEA has mostly been researched for treating pain disorders of all kinds and has found to be effective for almost any kind of pain. On study even showed that it outperformed ibuprofen in treating temporomandibular joint disorders (1). PEA is popularly used for fibromyalgia. PEA is also one of the breakdown products of Procaine, which may partially contribute to the effectiveness of neural therapy.

One of the most profound benefits of PEA is its effect on glial cells. When glial cells become too active, they can cause brain inflammation. PEA modulates and reduces glial cell activity (3). This is the main reason why PEA has been found to be an effective treatment for autism (4). Many people notice that supplementing with PEA can reduce brain fog and improve cognitive function.

Mast cells have receptors that are sensitive to PEA, and research has shown that supplementing with PEA can reduce mast cell activation (2). Mast Cell Activation Syndrome (MCAS) is a very common symptom in chronic illnesses, and PEA supplementation can be of great benefit for reducing symptoms. PEA supplements are often combined with the plant pigment luteolin in a 10:1 ratio. Luteolin on its own is also used to calm mast cells, but the combination of PEA and luteolin has been shown to be more effective than either substance by itself (5).

The most researched PEA supplement is Glialia, a micronized combination of PEA and luteolin. Another PEA/luteolin combination product available is Mirica. PEA can also be purchased as a stand-alone supplement. PEA supplements are generally very well tolerated and side effects or sensitivities are almost unheard of. Effects noticed from starting PEA may or may not be noticed immediately. It may take weeks or months to notice the positive benefits of PEA as it can be cumulative.