Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

• Published in: The Journal of clinical investigation 2014-09, Vol.124 (9), p.3713-3724
• Main Authors: Oláh, Attila, Tóth, Balázs I, Borbíró, István, Sugawara, Koji, Szöllõsi, Attila G, Czifra, Gabriella, Pál, Balázs, Ambrus, Lídia, Kloepper, Jennifer, Camera, Emanuela, Ludovici, Matteo, Picardo, Mauro, Voets, Thomas, Zouboulis, Christos C, Paus, Ralf, Bíró, Tamás
• Format: Article
• Language: English
• Subjects: Acne; Acne Vulgaris - drug therapy; Acne Vulgaris - etiology; Anti-Inflammatory Agents - pharmacology; Anti-inflammatory drugs; Apoptosis; Biomedical research; Cannabidiol - pharmacology; Cannabinoids; Cannabis sativa; Care and treatment; Dosage and administration; Extracellular Signal-Regulated MAP Kinases - physiology; Gene expression; Humans; Lipids; Lipogenesis - drug effects; Patient outcomes; Rodents; Sebaceous Glands - cytology; Sebaceous Glands - drug effects; Sebaceous Glands - pathology; Sebum - physiology; Signal transduction; Skin; TRPV Cation Channels - physiology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci64628

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.