Cannabidiol Mitigates Pollution-Induced Inflammatory, Oxidative, and Barrier Damage in Ex Vivo Human Skin

Biomolecules. 2025 Dec 20;16(1):10. doi: 10.3390/biom16010010.

Abstract

Airborne particulate matter (PM) is a major environmental pollutant that accelerates skin aging, inflammation, and barrier impairment. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has shown anti-inflammatory and cytoprotective effects, yet its role in protecting full-thickness human skin from pollution-induced damage remains unclear. In this study, human full-thickness ex vivo skin explants were topically exposed to PM (0.54 mg/cm2) and treated with CBD (6.4 mM) administered via the culture medium for 48 h. Proinflammatory mediators (interleukin-6, IL-6; matrix metalloproteinase-1, MMP-1; cyclooxygenase-2, COX-2), oxidative stress markers (reactive oxygen species, ROS; 8-hydroxy-2'-deoxyguanosine, 8-OHdG), the xenobiotic sensor aryl hydrocarbon receptor (AhR), extracellular matrix proteins (procollagen type I C-peptide, PIP; fibrillin), and the barrier protein filaggrin were quantified using ELISA and immunofluorescence. PM exposure triggered significant inflammation, oxidative stress, AhR induction, extracellular matrix degradation, and barrier disruption. CBD selectively counteracted these effects by reducing IL-6, MMP-1, COX-2, ROS, and 8-OHdG levels, downregulating AhR expression, and restoring PIP, fibrillin, and filaggrin expression. No measurable effects were observed in unstressed control tissues. These results demonstrate that CBD protects human skin from PM-induced molecular damage and supports its potential as a functional bioactive ingredient for anti-pollution applications.

Keywords: cannabidiol (CBD); ex vivo skin model; oxidative stress; particulate matter (PM); skin inflammation; skin structural integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cannabidiol* / pharmacology
  • Cyclooxygenase 2 / metabolism
  • Filaggrin Proteins
  • Humans
  • Inflammation* / chemically induced
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Interleukin-6 / metabolism
  • Oxidative Stress* / drug effects
  • Particulate Matter* / adverse effects
  • Particulate Matter* / toxicity
  • Reactive Oxygen Species / metabolism
  • Receptors, Aryl Hydrocarbon / metabolism
  • Skin* / drug effects
  • Skin* / metabolism
  • Skin* / pathology

Substances

  • Cannabidiol
  • Particulate Matter
  • Filaggrin Proteins
  • FLG protein, human
  • Cyclooxygenase 2
  • Receptors, Aryl Hydrocarbon
  • Reactive Oxygen Species
  • Interleukin-6