Palmitoylethanolamide is a supplement that is commonly called PEA. This amazing supplement has been linked to pain relief, and helping to regulate inflammation. PEA has also been linked to other impressive benefits, such as better sleep and lower blood pressure. It also appears to be neuroprotective, meaning it helps protect brain function, and it also has anticonvulsant or anti-seizure properties.

What is Palmitoylethanolamide?

Palmitoylethanolamide is a fatty acid amide that is classified as endogenous, which means that it is made by the body. It can also be found in foods, where it has been isolated from soy lecithin, egg yolks, and peanut meal. It is considered a type of phospholipid, and it is a non-endocannabinoid lipid mediator.

PEA tends to be a pretty safe product, with no serious drug interactions or side effects noted, since its discovery in 1957. It has been used for many years in Europe, with increasing interest developing in the United States. PEA has been the subject of numerous studies, in both animal and human models.

Palmitoylethanolamide has its effects on different inflammatory mechanisms, allowing it to help control neurogenic and neuropathic pain, which are different types of pain that may arise through dysfunction, of or damage to the nervous system. PEA largely acts on cells through modulating both mast cells, and spinal glial cells that affect neurons, which are the basic cells of the nervous system.

PEA works by activating PPAR alpha, which is a protein that boosts energy and burns fat, as well as stopping the activities of pro-inflammatory genes. It may also be related to activating cannabinoid receptors.

One of the ways that palmitoylethanolamide works is by affecting anandamide, whose name comes from the Sanskrit word “ananda,” referring to “bliss.” Anandamide is a fatty acid and neurotransmitter, and it comes from the metabolism of arachidonic acid, which is an essential omega-6 fatty acid. Inhibitors of the degradation pathway, such as PEA, have been linked to elevated anandamide levels, which in turn leads to benefits, such as decreases in feelings of depression.

What is a Phospholipid?

Phospholipids are essential to normal cell functioning. They are the primary component of cell membranes, which separate cells from the rest of their internal, and external environments. Most cells are made up of a phospholipid bilayer, where the phospholipids orient themselves into two layers that are parallel to each other. The phospholipids have a head that is hydrophilic and bonds with water, while they have hydrophobic tails, which do not bond with water. To allow different components through the cell membrane, there are channels located randomly around the cell to allow cellular messengers to pass through, or be transported.

Phospholipids have a variety of different functions, and do more than just function as a bilayer around cells, although this is a very important function. Phospholipids can also function as a type of signal messenger, relaying messages between cells, such as identifying an infection. Phospholipids can also block signal pathways that trigger inflammation, such as in the case of PEA. Other phospholipids form insulation around neuronal cells, such as sphingomyelin.

Palmitoylethanolamide Benefits and Uses

Palmitoylethanolamide or PEA has numerous potential benefits. The main thing that is seems to do is help control pain and inflammation, although it has also been linked to other benefits, such as improving sleep and feelings of depression and anxiety.

Palmitoylethanolamide and Inflammation

There is a fair amount of research that supports that PEA has the ability to reduce pain, with over 30 different clinical trials around the world. By controlling inflammation, PEA appears to reduce pain in numerous forms, including visceral or abdominal pain, as well as neuropathic pain from conditions such as sciatica.

During studies, PEA generally needed at least 2 weeks to achieve pain relief, and taking it over a longer period seemed to strengthen its effects. So far, no research has shown that tolerance develops. In one trial that included over 600 people, PEA was given at a dosage of 300 or 600 mg per day. At these dosages, it reduced sciatic pain by over 50% in just three weeks. PEA significantly reduced lower back pain in people taking 600 mg per day. It was noted that roughly half of the participants in the lower back pain study even stopped taking additional pain killing medications while they were on the PEA.

PEA has been used, and shown to be effective, with various other types of pain and inflammation. One study of women, with pain triggered by endometriosis, found that PEA relieved pain, as well as improved sexual function, over a period of 6 months. In people with fibromyalgia, one study showed that PEA helped to reduce pain and tenderness, when it was combined with a standard treatment medication called pregabalin. It has also been used to treat cancer and arthritis pain.

In animal models, there is even more evidence for benefits of using PEA. It reduced nerve pain associated with certain chemotherapeutic medications in one study. In other studies, it reduced inflammation and lung damage, as well as decreased inflammation related to spinal cord injuries.

Palmitoylethanolamide and Brain Health

Palmitoylethanolamide has also shown promise with treating neurodegenerative diseases and even strokes. PEA appears to help brain cells survive, and decreases inflammation. One study was performed on people suffering from a stroke, where a medication made from PEA and luteolin, called Glialia, improved recovery outcomes, with positive effects on cognitive skills, brain health, and even daily functioning.

In Parkinson’s disease, dopamine receptors are affected. In a study on mice, PEA helped prevent the development of Parkinson’s disease, with reduced damage to the brain, and helping to protect dopamine neurons. Also in mice, spinal cord injuries were treated in one study with PEA and luteolin. The combination helped increase proteins, that create new cells that are needed to regenerate tissues, after traumatic damage to the brain or spinal cord.

PEA has more than just direct effects on brain cells. By affecting the endocannabinoid system, it can help improve mood and cognition. For some people, PEA may even reduce the risk, or occurrence of seizures, as impaired natural cannabinoid function has been linked to epilepsy in some people. In a study with rats, it showed effects on CB1 and CB2 receptors.

Palmitoylethanolamide and Sleep

Palmitoylethanolamide may improve sleep by decreasing pain and inflammation. In one study of subjects awaiting carpal tunnel surgery, who had sleep disturbances, supplementation with PEA greatly improved their quality of sleep. Participants had an increase in continuous sleep time, as well as a decrease in sleep disturbances. While more studies need to be done in this arena, it appears that PEA is very effective in helping to improve sleep quality scores.

Palmitoylethanolamide and Blood Pressure

PEA has been linked to lowered blood pressure in a study of spontaneously hypertensive rats, so it may hold potential benefits for humans suffering from high blood pressure. In the study, rats were treated with PEA for five weeks, and numerous values were evaluated. The supplementation with PEA was linked to effects on the renin angiotensin system, where it led to lower blood pressure.

Palmitoylethanolamide – Anxiety and Depression

PEA was studied in animals, and showed a positive improvement over symptoms of depression. In a study on people, PEA was given with antidepressant therapy, at a rate of 1,200 mg per day. Over a period of 6 weeks, it improved people’s mood and depression-related symptoms. This study was very important in showing the benefits of PEA, because it was a double-blind study that was also placebo controlled. The improvement was statistically significant.

PEA has also shown promise when cognitive disorders, such as anxiety and depression, result from traumatic brain injuries. In a mouse model that was studied, behaviors such as anxiety were decreased, with supplementation of PEA.

Palmitoylethanolamide and Eye Health

PEA has been linked to protecting retinal nerve cells. Inflammatory damages to the eyes can be caused by disease processes such as diabetes and glaucoma. In multiple studies, PEA reduced eye nerve damage when it was used in dosages up to 1,800 mg per day. In one study, PEA was used on people with elevated eye pressure, or glaucoma. In this study, PEA reduced the participant’s elevated eye pressure, and also improved their vision over the course of 6 months. At the same time, it did not appear to cause any side effects. In a small study of people undergoing laser eye surgery, which runs the risk of temporarily increasing eye pressure, PEA prevented increases in intra-ocular eye pressure, when given shortly after the laser eye surgery was performed.

In animals, PEA works by reducing key inflammatory substances within the eye, that break down the retinal barrier with the blood. This eye barrier helps to protect the eye from harmful substances, while nourishing the eye.

Palmitoylethanolamide and Dogs

PEA has been successfully used in animal models to combat the effects of osteoarthritis, which is a progressive joint disease that occurs commonly in dogs and cats. Osteoarthritis is commonly treated with non-steroidal anti-inflammatory medications, such as carprofen and meloxicam, in dogs and cats, but the side effects of the medications tend to be undesirable. In one study, PEA was used in rats and compared to the treatment with meloxicam. PEA decreased inflammatory markers and had improved analgesia, as compared to meloxicam. Other studies with different formulations of PEA have shown similar results.

Palmitoylethanolamide Dosage

PEA has been used at a range of dosages, with studied amounts ranging between 300-1,800mg taken per day. When taking PEA for nerve pain, at least 600 mg per day is suggested, while doses of 1,200 mg per day were used in studies of diabetic nerve pain. In people with diabetes or glaucoma, PEA was administered in amounts of up to 1,800 mg per day. In addition, the standard dosage for fighting the effects of the common cold is 1,200 mg per day.

PEA comes in several different forms, and most manufacturers recommend that the dosage of PEA be split into two doses during the day, so if you are taking 1,200 mg per day, it is recommended that you take 600 mg twice daily. Micronized forms of PEA are commonly used in studies for human and animal models, with many scientists considering them to be the more superior, as they tend to be better absorbed.

Forms of Palmitoylethanolamide

Palmitoylethanolamide comes in several different formulations, the most common being palmitoylethanolamide capsules and powder forms. The powder form is generally micronized, which is considered to be the best formulation of PEA on the market, although this may vary by different manufacturers.

A palmitoylethanolamide cream is also available, but its use has been limited. It has been used to treat topical pain in countries such as the Netherlands, but it is now available in the United States as well. More research needs to be done into its effectiveness.

Negative Effects of Palmitoylethanolamide

PEA is classified as a supplement, and it has not been approved by the FDA for medical use. The current data available about PEA, including numerous clinical studies, supports that it is safe. Within the small scale studies that it has been used in, it does not appear to have any long-term side effects. In addition, it has not been linked to a build up in tolerance, which is the case with many chronic medications.

Things to Keep in Mind When Using Palmitoylethanolamide

Because PEA has not been extensively studied, scientists do not know the potential effects of PEA on pregnancy. While it appears to be safe in pregnant animals, it should be used with caution in pregnant and breastfeeding women.

In Summary

Palmitoylethanolamide is a potentially very beneficial supplement that has a variety of positive effects, from reducing pain and inflammation to controlling symptoms of depression. The product has been on the market in various forms for decades and appears to be very safe, with no reported adverse effects. As always, consult with your doctor before taking this, or any other supplement.


These statements have not been evaluated by the Food and Drug Administration. Products discussed are not intended to diagnose, treat, cure, or prevent any disease.