Differential effectiveness of selected non‐psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment

Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands. We have previously shown that a non‐psychotropic phytocannabinoid ((–)‐cannabidiol [CBD]) exerted complex anti‐acne effects by normalizing ‘pro‐acne agents’‐induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes. Therefore, in this study we aimed to explore the putative anti‐acne effects of further non‐psychotropic phytocannabinoids ((–)‐cannabichromene [CBC], (–)‐cannabidivarin [CBDV], (–)‐cannabigerol [CBG], (–)‐cannabigerovarin [CBGV] and (–)‐Δ9‐tetrahydrocannabivarin [THCV]). Viability and proliferation of human SZ95 sebocytes were investigated by MTT and CyQUANT assays; cell death and lipid synthesis were monitored by DilC1(5)‐SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT‐qPCR, ELISA). Up to 10 μm, the phytocannabinoids only negligibly altered the viability of the sebocytes, whereas high doses (≥50 μm) induced apoptosis. Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, and CBDV had only minor effects, whereas CBG and CBGV increased it. Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)‐induced ‘acne‐like’ lipogenesis. Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti‐inflammatory actions. Our data suggest that CBG and CBGV may have potential in the treatment of dry‐skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti‐acne agents. Moreover, based on their remarkable anti‐inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations.