Prof. Dr. Lajos Kemeny

Endocannabionid containing topical product ameliorates p53 activation and thymine dimers formation in human skin in vivo

Department of Dermatology, University of Szeged (Hungary)

Endocannabinoids are endogenous ligands of cannabinoid receptors and are ubiquitously present in nearly all aerobic cells. Research in the last decade revealed the involvement of endocannabinoids in cognitive functions, pain perception, appetite and food intake, drug and alcohol dependence, hormone release, reproduction, immune response, and in gastrointestinal and cardiovascular function. N-palmitoylethanolamine is the most abundant and the most studied endocannabinoid, with potent antioxidant and anti-inflammatory activity. In the present study we investigated the effect of N-palmitoylethanolamine (formulated as a commercially available creme) on the ultraviolet-B (UVB) induced thymidine dimer formation and p53 activation in normal human skin. Furthermore, we compared the anti-inflammatory effects of N-palmitoylethanolamine containing creme and 1% hydrocortisone actetate containing cream in patients with atopic dermatitis.

The effects of N-palmitoylethanolamine containing creme on UVB-induced thymidine dimer formation and p53 expression were studied in 5 healthy volunteers. The buttocks of the individuals were treated with N-palmitoylethanolamine containing creme or with the ointment base for one months, than irradiated with 2xMED of UVB light. Twenty four hours thereafter, the same skin areas were than irradiated again, and just after irradiation biopsies were taken from both the nonirradiated, and each irradiated areas. The paraffin embadded tissue specimens were than stained with anti-human p53-antibodies and anti-thymidine dimer antibodies. We found that pretreatment of the human skin with N-palmitoylethanolamine containing creme inhibited the UVB-induced thymidine dimer formation and p53 expression in the human skin .

Eighteen patients with atopic dermatitis have been enrolled into the comparative study, where the patients's left side was treated with N-palmitoylethanolamine containing creme and the right side with hydrocortisone 1% creme. Three patients were dropped out because of lack of complience. We found that N-palmitoylethanolamine containing creme and hydrocortisone 1% creme were equally effective in reducing the itch, skin infiltration, excoriation and lichenification of the atopic dermatitis lesions. Hydrocortisone 1% creme was significantly better than N-palmitoyletanolamine containing cream in reducing the erythema of the lesions throughout the 3-week investigational period (Wilcoxon signed ranks test, p<0.05). On the other hand, N-palmitoylethanolamine containing creme proved to be significantly better than hydrocortisone 1% in reducing skin dryness in the first week of the treatment (Wilcoxon signed ranks test, p<0.05). Patients with mild to moderate atopic dermatitis responded to N-palmitoylethanolamine containing creme at least as well as to hydrocortisone 1%, with the exemption in reducing erythema, but the improvement of skin dryness was significantly better in N-palmitoylethanolamine containing creme treated side as compared to that of hydrocortisone 1% treated side.

These results suggest that the N-palmitoylethanolamine containing creme is highly effective in reducing UVB-induced oxidative damage in human skin, and is also suppressing the clinical symptoms of patients with atopic dermatitis.

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