Topical nanoencapsulated cannabidiol cream as an innovative strategy combating UV-A-induced nuclear and mitochondrial DNA injury: A pilot randomized clinical study
Erika McCormick 1, Haowei Han 2, Sara Abdel Azim 1, Cleo Whiting 1, Nitish Bhamidipati 3, Alexi Kiss 3, Tatiana Efimova 4, Brian Berman 5, Adam Friedman 6
- 1Department of Dermatology, George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia.
- 2Center for Clinical and Cosmetic Research, Aventura, Florida.
- 3George Washington Cancer Center, Washington, District of Columbia.
- 4Department of Biomedical Engineering, Northwestern University, Chicago, Illinois.
- 5Center for Clinical and Cosmetic Research, Aventura, Florida; Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida. Electronic address: bbmdphd@gmail.com.
- 6Department of Dermatology, George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia. Electronic address: ajfriedman@mfa.gwu.edu.
Affiliationer
Background: 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.
Objective/methods: 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.
Results: 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.
Limitations: Small sample size is this study’s limitation.
Conclusion: 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.