Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo

Solar ultraviolet radiation (UVR) exposure of human skin has beneficial and harmful effects on health, including impact on immune function, inflammation and reportedly mood, but these are not fully elucidated. Since the endocannabinoid system is implicated in many activities including mood alteration, our objective was to (i) determine and quantify circulating levels of a wide range of endocannabinoid and N-acyl ethanolamine (NAE) species (ii) evaluate whether these are modulated by cutaneous UVR exposures, as attained through repeated low level summer sunlight exposure. Wearing goggles to prevent eye exposure, 16 healthy volunteers (23-59 y; 10 light skin, phototype II, and 6 dark skin, phototype V) received the same UVR exposures (1.3 SED, 95% UVA/5% UVB) thrice weekly for 6 weeks, whilst casually dressed to expose similar to 35% skin surface area. Blood samples were taken at baseline, days 1, 3 and 5 of week one, then at weekly intervals, and analysed by LC-MS/MS. Eleven endocannabinoids and NAEs were detected and quantified at baseline, with N-palmitoyl ethanolamine the most abundant (30% of total). Levels did not vary according to phototype (p > 0.05), except for the NAE docosapentaenoyl ethanolamide, which was higher in phototype II than V (p = 0.0002). Level of the endocannabinoid, 2-AG, was elevated during the UVR exposure course (p < 0.05 vs. baseline for all subjects; p < 0.01 for each phototype group), with maximum levels reached by week 2-3, while NAE species did not significantly alter. These findings suggest differential involvement of the cutaneous endocannabinoid system in low dose solar UVR responses in humans.