Cannabinoids and Their Receptors in Skin Diseases

Abstract

The therapeutic application of cannabinoids has gained traction in recent years. Cannabinoids interact with the human endocannabinoid system in the skin. A large body of research indicates that cannabinoids could hold promise for the treatment of eczema, psoriasis, acne, pruritus, hair disorders, and skin cancer. However, most of the available data are at the preclinical stage. Comprehensive, large-scale, randomized, controlled clinical trials have not yet been fully conducted. In this article, we describe new findings in cannabinoid research and point out promising future research areas.

Keywords: acne; atopic dermatitis; cannabidiol (CBD); cannabinoid receptor 1 (CB1R); cannabinoid receptor 2 (CB2R); cannabinoids; eczema; endocannabinoids; hair growth; psoriasis; skin aging.

Figure 1

Schematic presentation of the endocannabinoid system. The endocannabinoid system consists of endocannabinoids, receptors, and enzymes. Cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC) are phytocannabinoids, and palmitoylethanolamide (PEA) and 2-arachidonoyl-glycerol (2-AG) are endocannabinoids. CB1R, cannabinoid receptor 1; CB2R, cannabinoid receptor 2; TRP, transient receptor potential; CBD, cannabidiol; THC, Δ-9-tetrahydrocannabinol; PEA, palmitoylethanolamide; 2-AG, 2-arachidonoyl-glycerol. This figure was created with Biorender at www.biorender.com (accessed on 21 August 2023).

Figure 2

Mechanism of action of CBD and THC in atopic dermatitis and eczema. CBD inhibited pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α. CB1R-deficient mice showed increased levels of IL-4, TSLP, IFN-γ, and CCL-8, which induces Th2-type inflammation. The interaction between cannabinoids and CB1R/CB2R suppressed cytokines including MCP-1, MCP-2, which recruits mast cell. Mast cells are also known to express CB1R/CB2R, which inhibited mast cell growth. THC decreased keratinocyte-derived pro-inflammatory mediators such as CCL2, CCL8, and CXCL10, which are induced by IFN-γ, limiting myeloid immune cell infiltration. TSLP, thymic stromal lymphopoietin; MCP, monocyte chemoattractant protein; Th2, T-helper 2 cell; TNF-α, tumor necrosis factor; CBD, cannabidiol; THC, Δ-9-tetrahydrocannabinol; TRPV, transient receptor potential vanilloid. This figure was created with Biorender at www.biorender.com (accessed on 21 August 2023).

Figure 3

Mechanism of action for cannabinoids in pruritis. CB1R/CB2R agonist ameliorated chronic itching by suppressing Il-13 and IL-31. CB1R knockout in sensory neurons promoted the production of substance P, which induces the accumulation of mast cells in the dermis through ERK. CBD: cannabidiol; ERK: extracellular signal-regulated kinase. This figure was created with Biorender at www.biorender.com (accessed on 21 August 2023).

Figure 4

Mechanism of action of cannabinoids in psoriasis CBD inhibited TNF-α-induced NF-κB transcription, which plays important role in psoriasis, and keratinocyte proliferation through PPAR-γ. CB2R deficiency inhibited the differentiation of CD4 T cells through STAT5/ROR γ T. Human mesenchymal stem cells express all of the components of endocannabinoid system, including CB1R/CB2R. And CB2R stimulation reduced pro-inflammatory cytokines in mesenchymal stem cells. MMP: matrix metallopeptidase; Th17: T-helper 17 cell; TNF-α: tumor necrosis factor; CBD: cannabidiol; THC: Δ-9-tetrahydrocannabinol; TRPV: transient receptor potential vanilloid; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; PPAR-γ: peroxisome proliferator-activated receptor; ROR: AR-related orphan nuclear receptor. This figure was created with Biorender at www.biorender.com (accessed on 21 August 2023).

Figure 5

Mechanism of action of cannabinoids in acne and seborrhea Endocannabinoids enhance lipid synthesis and apoptosis of sebocytes through CB2R dependent manner. The lipostatic action of CBD is mediated by the TRPV4 ion channel through the inhibition of the MAPK/Erk pathway. A hemp seed hexane extract inhibited the NF- κB and MAPK pathway in keratinocytes and regulated lipid production via AMPK and AKT/FoxO1 signaling in sebocytes. CBD: cannabidiol; TRPV: transient receptor potential vanilloid; MAPK/Erk: mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; FoxO1: Forkhead box protein O1. This figure was created with Biorender at www.biorender.com (accessed on 21 August 2023).