Full-spectrum cannabidiol-rich extract prevents UVB-induced skin carcinogenesis by suppressing CB1/CB2/GPR55 signalling and COX-2/IL-6 inflammatory pathways

This study aimed to evaluate whether full-spectrum cannabidiol-rich extract (FS-CBD) prevents UVB-induced skin carcinogenesis through the modulation of endocannabinoid receptors and inflammatory pathways in HaCaT keratinocytes and CD-1 et/et mice. In vitro, UVB exposure increased cannabinoid receptor type 1 (CB 1 ) and cannabinoid receptor type 2 (CB 2 ) expression by approximately 83% and decreased G protein-coupled receptor 55 (GPR55) expression. FS-CBD attenuated the upregulation and restored GPR55 expression to approximately four times the value measured after UVB exposure alone. In vivo, compared with the control treatment, UVB treatment resulted in an 80% increase in tumour incidence, while FS-CBD pretreatment for 2 h reduced the incidence to 20%, corresponding to a 75% reduction. Tumour multiplicity and size decreased by approximately 50%, accompanied by significant reductions in the immunodetection of CB 1 , CB 2 , GPR55, COX-2, and IL-6, as assessed by confocal microscopy. Notably, prolonged FS-CBD pre-treatment was associated with a marked increase in epidermal apoptosis, displaying a moderate-intensity, multifocal-to-diffuse pattern, which coincided with a lower frequency of malignant transformation. Overall, these findings suggest that FS-CBD pre-treatment may have chemopreventive potential against UVB-induced skin carcinogenesis.