A Complete Guide to Palmitoylethanolamide

What is Palmitoylethanolamide?

Palmitoylethanolamide (PEA) is a protective and regenerative fatty molecule produced in humans as well as other animals and plants. It can be extracted from sources such as peanuts, almonds, soybeans, eggs, etc to supplement the body with the quantities needed for normal cellular and functions.

The history of PEA goes as far back as 1943, with several decades of studies confirming its various medicinal properties. Nobel Prize winner Levi-Montalcini is credited for formally proving the potentials of the substance for the treatment of chronic infections and pains. Her studies showed that PEA is a naturally-produced, biologically active lipid which interacts with receptor systems, especially the cannabinoid receptor (CR2) and inflammatory cells in the nervous system.

Her conclusions have also been reaffirmed by hundreds of subsequent studies which have proved that the substance is one of the most powerful natural painkillers. These studies have also gone on to prove that the substance can influence a host of cellular functions related to pain and chronic diseases.

Health Benefits and Side Effects

PEA plays a critical role in the body’s healing and regenerative mechanisms. src

PEA plays a central role in the treatment of a wide range of chronic illnesses due to its capacity to regulate a slew of cellular functions. It’s even been shown to boost the efficacy of other medications, thereby making it an ideal supplement that can make a difference in just about any treatment. Studies have also shown that the drug can rise to the occasion in certain cases that are unyielding to traditional medicine, such as sciatica and carpal tunnel syndrome.

People who can benefit the most from the anti-inflammatory, anti-nociception (pain relieving) and neuroprotective properties of PEA include those suffering from:

Fibromyalgia (FM)

In a 2015 study of FM patients, the addition of PEA to the treatment regimen involving duloxetine (Cymbalta) and pregabalin (Lyrica) led to a dramatic decrease in the intensity of the patient’s symptoms within 2 months.

Muscular Cramps

It’s been shown that PEA might be capable of inhibiting excessive activities in muscles that result in cramps. In a 2016 study, patients with acute, persistent muscle cramps reported the total elimination of cramps within 2-4 weeks of being place on PEA.


Recent studies show that patients with osteoarthritis or rheumatoid arthritis have significantly lower levels of PEA in their synovial (joint) fluid, indicating a protective role the substance might play in these conditions. PEA interacts indirectly with CB2 receptors, which play a protective role in the skeletal system. PEA also interacts with PRARc receptors which prevent the degradation of cartilages.

Traumatic Brain Injury/Chronic Traumatic Encephalopathy (CTE)

PEA’s anti-inflammatory and neuroprotective properties help maintain cellular homeostasis when the body is faced with neuroinflammation – a common denominator of CTE cases. Studies involving mice show that PEA inhibits amyloid β-peptide-induced learning and memory impairment, which are also factors commonly associated with CTE.

Post-Operative Pain

Since it inhibits the activation of mast cells and glial cells – two major components of chronic pain systems, PEA can prove effective in mitigating post-surgery pain.

Other Health Ails

In addition to the conditions above, PEA can also prove effective in the treatment of:

  • Shingles
  • Depression
  • Autism
  • peripheral neuropathy
  • dental pains
  • neuropathic pain in stroke and multiple sclerosis
  • chronic regional pain syndrome
  • chronic pelvic pain
  • post herpetic neuralgia
  • vaginal pains

There are currently no known major side effects of PEA, as its presence is naturally essential to the functions of every cell in the body. So far, the side effects that have been recorded in clinical trials are abdominal discomfort and diarrhea, which have been linked to the sorbitol sweetener used in the supplement. Studies also show that the substance doesn’t interact negatively with but rather promotes the effectiveness of other drugs.

Is It Safe To Use Palmitoylethanolamide?

Unlike most over-the-counter counter painkillers and opioids, PEA isn’t harmful nor addictive. Clinical trials show the substance remains innocuous even at doses as high as 1200 mg per day. No serious side effects have been reported in the hundreds of studies involving both humans and animals. Even in cases of dysfunctional livers and kidneys which tend to trigger serious side effects of some drugs, PEA has proven to be safe for the patients, shoring up the failing organs and promoting metabolism.

Palmitoylethanolamide and Cannabidiol

PEA and CBD are both products of healing and homeostatic mechanisms of the body capable of regulating cell functions. Both substances have highly-potent anti-inflammatory and neuroprotective properties. But although they interact with similar receptor systems, they do so in slightly variant ways, so one isn’t a worthy replacement for the other in certain treatments. However, several studies have shown that the combination of CBD and PEA is the most effective for the treatment of a wide range of health ails, especially those related to inflamed colonic tissues, active inflammatory bowel disorders, and acute appendicitis.

Availability of Palmitoylethanolamide in AU

PEA is currently classified as a nutraceutical, that is, a natural medicinal substance that is innocuous and doesn’t require a doctor’s prescription or supervision to ensure the safety of its intake. PEA is mostly available in Australia in capsule and topical cream forms.

Published by Neil

Neil believes Cannabis has medical benefits and should be prescribed by a Doctor. This site aims to provide accurate information on the science and legality of Cannabis so you can make informed decisions.

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