Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
Attila Oláh, … , Ralf Paus, Tamás Bíró
Attila Oláh, … , Ralf Paus, Tamás Bíró
Published July 25, 2014
Citation Information: J Clin Invest. 2014;124(9):3713-3724. https://doi.org/10.1172/JCI64628.
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Research Article Dermatology

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Abstract

The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.

Authors

Attila Oláh, Balázs I. Tóth, István Borbíró, Koji Sugawara, Attila G. Szöllõsi, Gabriella Czifra, Balázs Pál, Lídia Ambrus, Jennifer Kloepper, Emanuela Camera, Matteo Ludovici, Mauro Picardo, Thomas Voets, Christos C. Zouboulis, Ralf Paus, Tamás Bíró

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Figure 6

Anti-acne actions of CBD are mediated by parallel, partly independent signaling mechanisms.

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Anti-acne actions of CBD are mediated by parallel, partly independent si...
(A) CyQUANT proliferation assay after 72-hour treatments. *P < 0.05 compared with the vehicle control. #P < 0.05. The solid line indicates the level of the 24-hour vehicle control. Dashed line indicates the level of the 72-hour vehicle control. Results are expressed as the percentage of the 24-hour vehicle control (mean ± SEM of 4 independent determinations). (B) TNFA mRNA expression following 24-hour LPS treatments with or without CBD and HC. *P < 0.05 compared with the vehicle control; #P < 0.05 compared with the CBD-free LPS-treated group. Data are presented using the ΔΔCT method; peptidyl-prolyl isomerase A–normalized (PPIA-normalized) TNFA mRNA expression of the vehicle control was set as 1. Data are expressed as mean ± SD of 3 independent determinations. Two additional experiments yielded similar results. (C) Validation of the key microarray results. mRNA expression of various target genes following 24-hour CBD treatments with or without HC. **P < 0.01, ***P < 0.001 compared with the vehicle control. ###P < 0.001. Data are presented using the ΔΔCT method; PPIA-normalized mRNA expression of the vehicle control was set as 1 (solid line). Data are expressed as mean ± SD of 3 to 6 independent determinations. Two additional experiments yielded similar results.