TY - JOUR
T1 - Topical nanoencapsulated cannabidiol cream as an innovative strategy combating UV-A–induced nuclear and mitochondrial DNA injury
T2 - A pilot randomized clinical study
AU - McCormick, Erika
AU - Han, Haowei
AU - Abdel Azim, Sara
AU - Whiting, Cleo
AU - Bhamidipati, Nitish
AU - Kiss, Alexi
AU - Efimova, Tatiana
AU - Berman, Brian
AU - Friedman, Adam
N1 - Publisher Copyright:
© 2024 American Academy of Dermatology, Inc.
PY - 2024/11
Y1 - 2024/11
N2 - 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.
AB - 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.
KW - 8-oxoguanine
KW - UV-A
KW - cannabidiol
KW - cannabinoid
KW - common deletion
KW - mitochondrial DNA
KW - mitochondrial mutation
KW - photoaging
KW - photodamage
KW - photoprotection
KW - reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85200809704&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85200809704&partnerID=8YFLogxK
U2 - 10.1016/j.jaad.2024.06.088
DO - 10.1016/j.jaad.2024.06.088
M3 - Article
C2 - 39025264
AN - SCOPUS:85200809704
SN - 0190-9622
VL - 91
SP - 855
EP - 862
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 5
ER -