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

Abstract

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 (-)-Δ(9) -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.

Neuroendocrinology and neurobiology of sebaceous glands

“…In cutaneous nerves of humans and rodents, the ECS modulates both nociception and temperature sensation (Cravatt et al ., ; Potenzieri, Brink & Simone, ; Guindon et al ., , ; Caterina, ). Only recently has a non‐neuronal ECS been described in human skin, which also appears to regulate several key aspects of sebocyte biology (Maccarrone et al ., ; Oláh et al ., ; Zákány et al ., ).…”

“…In contrast to ECs, several phytocannabinoids have been shown to negatively regulate lipid and interleukin production in SZ95 sebocytes (Oláh et al ., , ). For example, cannabidiol (CBD) dose‐dependently reverses AEA‐induced lipogenesis in SZ95 cells and in organ‐cultured human SGs.…”

Echinacea purpurea -derived alkylamides exhibit potent anti-inflammatory effects and alleviate clinical symptoms of atopic eczema

“…Collectively, these results strongly argue for that the homeostatic endocannabinoid signaling may be a crucial gate-keeper in controlling cutaneous immune processes. Moreover, several non-psychotropic phytocannabinoids (namely (À)-cannabidiol, (-)-cannabichromene, (-)-cannabidivarin, (-)-cannabigerol, (-)-cannabigerovarin and (-)-D 9 -tetrahydrocannabivarin) were recently shown to exert promising anti-inflammatory effects in human sebocytes, further arguing for that plant-derived agents influencing certain branches of the complex cannabinoid signaling may have potential in the management of cutaneous inflammation [15,16].…”

Prolactin as a candidate sebotrop(h)ic hormone?

“…Moreover, although the SG and HF are intimately related, there is also variable/compartment‐specific expression of both hormone receptors and the key enzymes in steroid hormone biosynthesis within the PSU . In addition, the SG intensively engages in hormone metabolism, not only (but particularly prominently) in steroid hormone metabolism, but also metabolises, for example important, multi‐functional lipid mediators that form part of the skin's endocannabinoid, endovanilloid or eicosanoid systems …”