UV-A radiation contributes to photoaging/photocarcinogenesis by generating inflammation and oxidative damage. Current photoprotective strategies are limited by the availability/utilization of UV-A filters, highlighting an unmet need. Cannabidiol (CBD), having anti-inflammatory/antioxidant properties via regulation of nuclear erythroid 2–related factor, heme oxygenase 1, and peroxisome proliferator-activated receptor gamma, could potentially mitigate damage from UV-A exposure. This is a prospective, single-center, pilot clinical trial (NCT05279495). Nineteen participants applied nano-CBD (nCBD) or vehicle (VC) cream to randomized, blinded buttock sites twice daily for 14 days; then, the treated sites were irradiated with ≤3× UV-A minimal erythema dose. After 24 hours, punch biopsies were obtained for histology, immunohistochemistry, and real-time polymerase chain reaction. At 24 hours, 21% of participants had less observed erythema on CBD-treated skin than on VC skin. Histologically, nCBD-treated skin had reduced UV-A–induced epidermal hyperplasia than VC ( = .01). Immunohistochemistry detected reduced cytoplasmic/nuclear 8-oxoguanine glycosylase 1 staining in nCBD-treated skin compared with VC ( < .01). Quantitative mtDNA polymerase chain reaction demonstrated that UV-A–induced deletion of ND4 (proxy:4977 bp deletion; = .003) and ND1 (proxy:3895 bp deletion; = .002) was significantly reduced by in vivo nCBD treatment compared with VC. Small sample size is this study’s limitation. Topically applied nCBD cream reduced UV-A–induced formation of a frequent mutagenic nuclear DNA base lesion and protected against mtDNA mutations associated with UV-A–induced skin aging. To our knowledge, this trial is the first to identify UV-protective capacity of CBD-containing topicals in humans.

中文翻译：

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局部纳米胶囊大麻二酚乳膏作为对抗 UV-A 诱导的核和线粒体 DNA 损伤的创新策略：一项试点随机临床研究


UV-A 辐射通过产生炎症和氧化损伤来促进光老化/光致癌。目前的光保护策略受到 UV-A 过滤器的可用性/利用率的限制，凸显了未满足的需求。大麻二酚 （CBD） 通过调节核红细胞 2 相关因子、血红素加氧酶 1 和过氧化物酶体增殖物激活受体 γ 具有抗炎/抗氧化特性，可能会减轻 UV-A 暴露造成的损害。这是一项前瞻性、单中心、试点临床试验 （NCT05279495）。19 名参与者将纳米 CBD （nCBD） 或载体 （VC） 乳膏涂抹在随机、盲法的臀部部位，每天两次，持续 14 天;然后，用 ≤3× UV-A 最小红斑剂量照射治疗部位。24 小时后，进行穿刺活检，用于组织学、免疫组化和实时聚合酶链反应。在 24 小时时，21% 的参与者在 CBD 治疗的皮肤上观察到的红斑比在 VC 皮肤上少。从组织学上讲，nCBD 处理的皮肤比 VC 减少了 UV-A 诱导的表皮增生 （ = .01）。免疫组织化学检测到与 VC 相比，nCBD 处理的皮肤细胞质/核 8-氧鸟嘌呤糖基化酶 1 染色减少 （ < .01）。定量 mtDNA 聚合酶链反应表明，与 VC 相比，体内 nCBD 处理显着降低了 UV-A 诱导的 ND4 （代理：4977 bp 缺失;= .003） 和 ND1 （代理：3895 bp 缺失;= .002） 的缺失。小样本量是本研究的限制。局部应用的 nCBD 乳膏减少了 UV-A 诱导的频繁诱变核 DNA 碱基病变的形成，并防止与 UV-A 诱导的皮肤老化相关的 mtDNA 突变。 据我们所知，这项试验是首次确定含CBD的外用药在人体中的紫外线防护能力。