The skin is one of the largest organs in the body and has a variety of cells including: keratinocytes, sebaceous glands, fibroblasts, melanocytes, adipocytes (fat cells) and so on. These cells in turn have a large range of receptors among others, endocannabinoid and related receptors like CB1, CB2, TRPV1, PPAR, COX, opioid, TLR, GRP55, GPR119 etc.

Observational reports from the 1990s showed that when cannabis, hashish and other variants of cannabis were abused, there was accompanied skin disorders like hair loss, acne, ageing, dermatitis, dry skin etc. These observations indicated that cannabinoids may modulate these receptors and that using the correct cannabinoid is important to get the desired health benefit.

PEA is an endocannabinoid like fat molecule that is produced by the body whenever these is demand e.g., in situations of stress. In fact, nature has designed PEA as a “go to” molecule for the body in times of distress, danger and disease.

Orally, PEA has been widely studied for a range of conditions including as an analgesic, anti-inflammatory, anti aging, immune enhancer, various gut health conditions like Chron’s and inflammatory bowel disease, cognitive health and many other conditions. One of the key functions of PEA is to downgrade the activity of mast cells which are one of the first responders at the site of stress, disease and infection. Mast cells can be compared to mercenaries who are loaded to the hilt with all sorts of arms at the scene of battle and may be highly effective as long as their activities are kept in check. If, however they are left to their own devices they can easily get out of control and wreak havoc and be a major obstacle to deal with. Mast cells carry a large and varied payload of “armaments” which they release including histamine, range of enzymes, and other molecules like adenosine which unless carefully managed can cause the body more harm than good. One good example is allergies and various auto-immune disorders like rheumatoid arthritis where there is excess and unchecked release of such molecules.

Interestingly, PEA has also been found to be effective topically for a range of skin conditions including acne, pain, inflammation, dermatitis, psoriasis, photo-damage etc. The reason PEA is effective topically is because the skin large number of these receptors.

Let us review some of the studies when PEA has been used topically.

1. Protection against UVA and UVB irradiation.
   When a topical PEA cream was applied in healthy volunteers who were later exposed to UVA and UVB radiation, the PEA group were protected as judged by reduced levels of inflammatory markers and redness of the skin. This is an interesting finding and suggests that PEA may be used to alleviate UV- photodamage. Of course, more studies are needed to confirm this finding.
2. Atopic Dermatitis (AD)
   A milder skin condition than psoriasis, in AD cells multiply excessively due to increase in inflammation with the resulting breach of the skin barrier which exacerbates allergic reaction and infections. Several studies have shown that dogs and cats suffering from atopic dermatitis have increased immunoreactivity or a loss of immune intolerance. PEA levels are raised indicating the body is trying to alert this go to molecule to increase its concentration so that the body can halt and overcome the offending stressor. Topical use of PEA has been shown to alleviate this in animals.
   
   TRPV1 receptor is an anti-inflammatory receptor, its activity is greatly increased as per evidence from the biopsies of the skin taken from the affected patients. One of the primary receptors PEA acts on is TRPV1. Along with its histamine dampening nature, PEA packs a one-two punch to curb both inflammation and allergic reaction both of which are heightened in AD.
   
   One study in dogs found topical PEA to be effective, safe in reducing pruritis and skin lesions as well as improving quality of life (QoL) in dogs with moderate atopic dermatitis and pruritis a related skin condition of redness and itching. A 2008 human study found topical PEA to be effective in atopic dermatitis as well as improving QoL like improvement of sleep, less irritability and reduction in the need for corticosteroid use as a rescue medication. Another study in 60 patients found PEA along with N-acetyl cysteine (NAC) topical cream was also effective in reducing AD symptoms.
   
   Because of PEA’s action on multitude of receptors for inflammation, pain, allergies, and wound healing, another human study showed that application of PEA caused reduction in redness, scaling (shedding of excessive skin cells), lichenification and dryness. Finally, a 2010 study showed that PEA cream applied to scars following herpes infection was effective in healing and reducing neuralgic pain which is often very difficult to treat.
3. Anti redness
   A recent large 2019 human study with 382 subjects, used PEA as a stand alone as well as with combination with another B vitamin during winter months, showed that not only was there significant reduction of skin proliferation, facial redness, but also less photo sensitization and improvement and health of the skin overall. The texture and firmness of the skin was more akin to health skin. The researchers suggested that PEA formulations were well tolerated and suited for sensitive skin especially during winter xerosis.
4. Psoriasis
   Psoriasis is a chronic inflammatory skin condition which is often accompanied by other auto immune condition like arthritis. There is unchecked increase in multiplication and proliferation of skin cells accompanied by irritation and shedding of skin cells. As in most conditions there is an immune component whereby cells have lost the ability to communicate effectively. Animal studies show that PEA may be beneficial in psoriasis however, no human studies have been conducted so far.

Conclusion
PEA is an endocannabinoid like molecule produced by the body and therefore safe, effective in a host of dermatological conditions like winter xerosis, dryness, pruritis, atopic dermatitis, wound healing and in postherpetic neuralgia. In animals PEA is found to be highly effective in a range of conditions.

References:
Nisbet S J et-al, ‘Clinical and in-vitro evaluation of new anti-redness cosmetic products in subject with winter xerosis and sensitive skin” In J Cosmetic Science, 2019, 41: 534-547
Wang Y et-al, “Assessment of a new complex anti-sensitive skin cream”, J Cosmet Dermatol, 2018, 17: 1101-1107
Visse K et-l, “Efficacy of body lotion containing N-palmitoylethanolamine in subjects with chronic pruritis due to dry skin: A derma-cosmetic study”, Acta Derm Venerol 2017, 97: 639-641
Yuan C et-al, “N-Palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic eczema: results of a randomized, double-blind, controlled study in 60 patients”, Clin Interv Aging 2014, 9: 1163-1169
Eberlin B et-al, “Adjuvant treatment of atopic eczema: Assessment of an emmolient containing N-palmitoylethanolamine (atopa study)”, J Eur Acad Dermatol Venerol, 2008, 22: 73-82
Phan NQ et-l, “Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia”, 2010, J Dtsch Dermatol Ges, 8: 88-91
Toth KF et-al, “Cannabinoid signaling in the skin: Therapeutic potential of the “C(ut)annabinoid” system”, Molecules, 2019, 24: 918-974