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

Erika McCormick, Haowei Han, Sara Abdel Azim, Cleo Whiting, Nitish Bhamidipati, Alexi Kiss, Tatiana Efimova, Brian Berman*, Adam Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)855-862
Number of pages8
JournalJournal of the American Academy of Dermatology
Volume91
Issue number5
DOIs
StatePublished - Nov 2024
Externally publishedYes

Keywords

  • 8-oxoguanine
  • UV-A
  • cannabidiol
  • cannabinoid
  • common deletion
  • mitochondrial DNA
  • mitochondrial mutation
  • photoaging
  • photodamage
  • photoprotection
  • reactive oxygen species

ASJC Scopus subject areas

  • Dermatology

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