Topical nanoencapsulated cannabidiol cream as an innovative strategy combating UV-A–induced nuclear and mitochondrial DNA injury: A pilot randomized clinical study

BackgroundUV-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.Objective/MethodsThis 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.ResultsAt 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 (P = .01). Immunohistochemistry detected reduced cytoplasmic/nuclear 8-oxoguanine glycosylase 1 staining in nCBD-treated skin compared with VC (P < .01). Quantitative mtDNA polymerase chain reaction demonstrated that UV-A–induced deletion of ND4 (proxy:4977 bp deletion; P = .003) and ND1 (proxy:3895 bp deletion; P = .002) was significantly reduced by in vivo nCBD treatment compared with VC.LimitationsSmall sample size is this study's limitation.ConclusionTopically 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. 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 (P = .01). Immunohistochemistry detected reduced cytoplasmic/nuclear 8-oxoguanine glycosylase 1 staining in nCBD-treated skin compared with VC (P < .01). Quantitative mtDNA polymerase chain reaction demonstrated that UV-A–induced deletion of ND4 (proxy:4977 bp deletion; P = .003) and ND1 (proxy:3895 bp deletion; P = .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.