The use of cannabinoids to treat fibrotic skin diseases is an emergent issue. Therefore, we aimed to evaluate systemic and skin endocannabinoid responses in the wound-healing process in humans. A prospective study was performed in 50 patients who underwent body-contouring surgery. Anandamide (N-arachidonoylethanolamine, AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were quantified using LC–MS/MS. Ten (20%) patients developed hypertrophic (HT) scars. No significant changes were observed between the normal (N) scar and HT scar groups in terms of plasma and skin endocannabinoids. Nevertheless, a positive correlation between plasma and skin AEA concentrations was found in the N group (r = 0.38, p = 0.015), which was absent in the HT group. Moreover, the AEA concentration was significantly lower in HT scar tissue than in normal scar tissue (0.77 ± 0.12 ng/g vs 1.15 ± 0.15 ng/g, p < 0.001). Interestingly, in all patients, the surgical intervention produced a time-dependent effect with a U shape for AEA, PEA and OEA plasma concentrations. In contrast, 2-AG plasma concentrations increased 5 days after surgery and were reduced and stabilized 3 months later. These results suggest crosstalk between systemic and local skin endocannabinoid systems during human wound healing. AEA appears to be the most likely candidate for this link, which is deficient in patients with HT scars.

使用大麻素治疗纤维化皮肤疾病是一个紧急的问题。因此，我们旨在评估人体伤口愈合过程中的全身和皮肤内大麻素反应。前瞻性研究在50例接受了身体轮廓手术的患者中进行。使用LC-MS / MS定量分析了花生四烯酸酰胺（N-花生四烯酸乙醇胺，AEA），2-花生四烯酸甘油酯（2-AG），棕榈酰乙醇酰胺（PEA）和油酰乙醇酰胺（OEA）。十名（20％）患者出现了肥厚性（HT）疤痕。在正常（N）瘢痕和HT瘢痕组之间，血浆和皮肤内大麻素未见明显变化。然而，在N组中，血浆和皮肤AEA浓度之间存在正相关（r = 0.38，p = 0.015），而HT组则不存在。此外，HT疤痕组织中的AEA浓度明显低于正常疤痕组织（0.77±0.12 ng / g对1.15±0.15 ng / g，p  <0.001）。有趣的是，在所有患者中，外科手术对AEA，PEA和OEA血浆浓度呈U形呈时间依赖性。相反，手术后5天2-AG血浆浓度升高，而3个月后降低并稳定。这些结果表明，在人类伤口愈合期间，全身和局部皮肤内源性大麻素系统之间存在串扰。AEA似乎是这种联系的最可能的候选者，这在HT疤痕患者中是不足的。