Introducing Palmitoylethanolamide (PEA) - An Extract from Safflower Lecithin that Modulates Pain and Mood Receptors to Support Physiological Stress

Affiliate Disclosure

Portrait young stressed woman thinking too hard steam coming out up of head isolated on grey wall background. Face expression emotion perceptionPEA has been clinically studied to support mood, pain, inflammation, neuropathy and more.

Palmitoylethanolamide (PEA) is a compound your body naturally produces in response to pain, inflammation, neuropathy, and cellular stress. It can also be derived from both plant and animal sources including safflower lecithin.

Most interestingly, PEA has been shown to modulate two of the primary cannabinoid receptors (CB1 and CB2) dispersed throughout the body.

These receptors are located throughout the body, but are richly concentrated in the brain, gastrointestinal tract, and peripheral nerves. PEA helps indirectly modulate CB1 and B1 receptor activity potentially by boosting the availability similar compounds.

Most notably - the key mediating molecule may be anandamide - known as the "bliss molecule' which does directly bind to cannabinoid receptors.

By indirect modulation of these receptors PEA can bring balance to immune, gut and nerve function - especially when it comes to inflammation.

PEA works directly on PPAR receptors - which are a group of cellular receptors involved in fatty acid & cholesterol metabolism but also pain and inflammatory pathways. Your body produces PEA from components of cell membranes to help your body, especially your brain and nervous system, in response to emotional swings, as well as chemical stress, pain, & inflammation.

Phosphatidylcholine (PC) and phosphatidylserine (PS) may also help modulate these systems as they serve as those phospholipid components in cell membranes, including those of the brain.

PC and PS are known to help with stress resilience, and detoxification - in part, perhaps due to "ethanolamide" end products like PEA, anandamide and the modulation of cannabinoid receptors.

I have used high-dose phosphatidylserine orally and topically to support recovery from chronic stress. I turn to phosphatidylcholine for support of nervous system recovery, detoxification, metabolism, and for those who have trouble focusing or with slow gut motility. Individuals carrying PEMT snps have trouble making their own choline - phosphatidylcholine can provide a source for these individuals.

Those with PEMT snps have trouble with lipid metabolism as well as detoxifying pesticides - but the implications may also extend to chronic neuro-inflammation like that seen in depression, neuropathy, Alzheimer's and Parkinson's.

After diving into some of this research, I will likely bring both in more assertively in my clients with adrenal fatigue, pain, or physical and emotional trauma.

I find that many of my clients that fit this profile are constipated, depressed, have difficulty focusing, and have lower than average thresholds for pain - it's all connected by the same systems!

Those with chronic pain, inflammation, and depression can see disruptions in the balance of the endocannabinoid system. CBD, THC, anandamide and PEA help modulate this system! 

Many are aware of CBD and THC, and the focus now includes these other molecules.

So while many jump to CBD products to modulate this same receptor system, PEA is a non-hemp derived molecule that can bring balance to this important endocannabinoid system at arguably less cost and considerably less social stigma & regulatory hurdles.

PEA is produced by the body and helps the body balance mood, inflammation, pain, & stress.

Clinical trials show a positive effect over placebo in doses of 300-600mg, once to twice daily. 

PEA has been clinically studied for: low back pain, sciatica, osteoarthritis, fibromyalgia, carpal tunnel, peripheral neuropathy, dental pain, post-herpetic neuralgia (Shingles), as well as chronic pelvic or vaginal pain.

More people experience a measurable benefit from PEA than those taking ibuprofen (as determined by number needed to treat [NNT] comparisons)

PEA and Depression

PEA has also been studied with depression, clients taking Celexa (citalopram), were split into two randomized groups and one had PEA added to their protocol (600mg twice a day) & the other received a placebo. Those receiving PEA had significantly higher drops in depression scores compared to placebo (p<.01).

I've written previously how our understanding of depression has adapted into a "cytokine model of depression" with inflammation at the core roots.

PEA+ may be a novel and affordable way to support mood balance by modulating the inflammatory roots of depression at a cellular level, while also modulating the endocannabinoid system.

PEA may also help down-regulate inflammation-promoting genes related to cognitive decline - like that see in in Alzheimer’s, Parkinson’s, or Multiple Sclerosis patients.

While you may not have heard about PEA until today, over a million people supplement with it. It is not associated with significant adverse events, yet the problem with most PEA supplements is that they use a synthetic solvent known as toluene to derive the substance.

Inevitably, toluene residues make it to the final product which is something I wasn’t comfortable supplementing with.

Luckily, a new derivation process has emerged.

Enzyme Science, a subsidiary of Enzymedica, naturally derives PEA without the use of synthetic solvents.

Enzyme Science naturally derives palmitoylethanolamide (PEA) from safflower lecithin found in safflower seeds. Enzyme Science naturally derives palmitoylethanolamide (PEA) from safflower lecithin found in safflower seeds

The new formulation is known as PEA+ (view product).

Comparing PEA and CBD - It's in the Numbers...

I’m knowledgeable about the benefits of cannabidiol (CBD) & understand the regulatory climate has been easing, yet I'm still uneasy about carrying it. 

The regulatory risk is too much for me to carry it in my practice or store when I have so many other tools to choose from in the natural health world. [Like PEA, curcumin, hops extract, phosphatidylcholine, phosphatidylserine, proteolytic & anti-inflammatory enzymes, and others...]

After speaking with CBD product reps across the country, the information I received about dosage was a bit murky at best. My take was that there was a lot of rationalizing going on in the dosing conversation.

And, while some of their discussions made sense, I intuitively knew I needed more dosage to get the much-touted benefits and it was going to be exceedingly expensive to get there.

Published research demonstrates clinical benefits at doses much higher than seen in CBD formulas. Dosing CBD at this level is impractically expensive for most people.

While "some CBD" is more modulatory than "no CBD", and some people may need less modulation than others, the research has given us some ballpark figures as to the doses needed to see statistically significant effects.

If expense was not a concern, due to regulatory hurdles, the next problem you might face is that product you use might be out of business the next time you go to reorder (due to the constant threat of pharmaceutical, commercial takedowns, or federal government control).

This can still be the case if regulation eases. With the boom in cannabis agriculture and related business, the price per pound of hemp is dropping. Soon, I foresee only a few big players left to survive  on the thinner margins that the industry will present. With only a few big players - we'll likely see them also lobby and write their own regulatory controls - a model repeated over and over again in history.

Right now, many mom and pops are racing to profit as much as they can in the short-term until the inevitable end materializes. And that profit surge is coming from consumer pockets like yours.

As a business owner, carrying CBD might also put all of my products and services at risk - which wasn't worth it for a single product category.

You might need 1000mg or more to see some of the touted benefits of CBD, and at least 100-150mg to support a sleep benefit, and possibly more than 300mg as mixed reports have been published.

Even a dose of 100-150mg of CBD is cost-prohibitive for many people, let alone 1000mg+ as seen necessary in other research supports. 

Most CBD products on the market come in at 5-25mg doses - not enough to move the needle for me, and too expensive to experiment with larger doses.

CBD has low bioavailability (as low as 6% absorption), and, while new soluble forms are being promoted - the cost is still counterintuitive for me when I know other anti-inflammatory approaches exist.

I found my perfect compromise of these issues with PEA+ by Enzyme Science.

The new formulation combines a well-known and well-absorbed curcumin extract known as Meriva along with 300mg of PEA+ in 60 capsule bottle. It comes in at a very fair price point compared to CBD products, and is a no-doubter more cost-effective option when you compare necessary dosages.

Curcumin (turmeric extract) on its own is one of the most researched herbal extracts known to man - with its emphasis on anti-inflammatory benefits and detoxification support. Meriva is the most popular form of curcumin and one of the best absorbed. Theracurmin HP has been proven by 3rd party research to be more bioavailable, Meriva is still a great form of curcumin. BCM-95 is another licensed curcumin supplement also worth a mention.

So while I'm not ready to marry into the CBD industry, I can confidently support the curcumin and PEA combination found in PEA+ by Enzyme Science.

While other PEA supplements exist, Enzyme Science's PEA+ is the ONLY formulation as of this writing that does not use the synthetic solvent toluene in its PEA extraction method - which makes me extra comfortable working with it.

How Much PEA Should I Take?

I generally recommend starting with 600mg twice a day for the first month, and dropping down to 300mg twice a day on-going. Each case is considered independently.

You can still see clinically significant benefit with 300mg twice daily, and can still see modulatory & wellness effects at 300mg once per day. The more pronounced the need, the more pronounced the support.

With higher intakes (2400-3000mg of PEA; 8-10 capsules of PEA+ in divided doses), it's the Meriva/curcumin content in PEA+ that can be less tolerated, and less so the palmitoylethanolamide itself.

At two capsules twice per day (600mg twice per day), this is an unlikely concern - making it the preferred dosage.

I'm excited to see what PEA+ can do not just for neuropathy, mood balance, and pain - but for my gut protocols where inflammation is a primary concern. 

In order to heal the mucosal lining, the gut cannot be inflamed and healing at the same time - it's one or the other.

Compounds like curcumin and PEA may help support this inflammation - especially when you consider the gut has it's own nervous system - directed by the vagus nerve.

I often need to retreat from my protocol and cool off inflammation before moving forward. I often use curcumin (my favorite is Theracurmin HP by Integrative Therapeutics) as well as Lion's Mane by Host Defense due to their unique nerve-protective qualities.

I will now be integrating PEA+ in the mix to expand on more anti-inflammatory and nerve-protective mechanisms of curcumin & Lion's mane mushroom. 

Shop Supplements

Dr Alex Rinehart

Most Popular