In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties

Abstract

Cannabigerol (CBG) is a minor non-psychoactive cannabinoid present in Cannabis sativa L. (C. sativa) at low levels (<1% per dry weight) that serves as the direct precursor to both cannabidiol (CBD) and tetrahydrocannabinol (THC). Consequently, efforts to extract and purify CBG from C. sativa is both challenging and expensive. However, utilizing a novel yeast fermentation technology platform, minor cannabinoids such as CBG can be produced in a more sustainable, cost-effective, and timely process as compared to plant-based production. While CBD has been studied extensively, demonstrating several beneficial skin properties, there are a paucity of studies characterizing the activity of CBG in human skin. Therefore, our aim was to characterize and compare the in vitro activity profile of non-psychoactive CBG and CBD in skin and be the first group to test CBG clinically on human skin. Gene microarray analysis conducted using 3D human skin equivalents demonstrates that CBG regulates more genes than CBD, including several key skin targets. Human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (NHEKs) were exposed in culture to pro-inflammatory inducers to trigger cytokine production and oxidative stress. Results demonstrate that CBG and CBD reduce reactive oxygen species levels in HDFs better than vitamin C. Moreover, CBG inhibits pro-inflammatory cytokine (Interleukin-1β, -6, -8, tumor necrosis factor α) release from several inflammatory inducers, such as ultraviolet A (UVA), ultraviolet B (UVB), chemical, C. acnes, and in several instances does so more potently than CBD. A 20-subject vehicle-controlled clinical study was performed with 0.1% CBG serum and placebo applied topically for 2 weeks after sodium lauryl sulfate (SLS)-induced irritation. CBG serum showed statistically significant improvement above placebo for transepidermal water loss (TEWL) and reduction in the appearance of redness. Altogether, CBG's broad range of in vitro and clinical skin health-promoting activities demonstrates its strong potential as a safe, effective ingredient for topical use and suggests there are areas where it may be more effective than CBD.

Keywords: anti-aging; antioxidant; cannabidiol; cannabigerol; cannabis; fermentation.

Figure 1

Gene microarray analysis of CBG and CBD. (a) Gene differential expression was quantified using Clariom™ S assay microarray system method after 24 h incubation in 3D skin model EpiDerm-FT™. (b) Data subset of gene expression related to skin. Data represent mean from n = 3 tissues. All genes shown were significantly different (p value < 0.05) relative to vehicle-only treated tissues.

Figure 2

CBG and CBD protect against chemical and bacteria-induced inflammation. Primary NHEKs were cultured in the presence of CBD or CBG for 1 h. Later, cells were co-treated with compounds and 5 ng/mL TPA or 1 × 10⁷ CFU C. acnes (ATCC^® 6919™) for 24 h. Media supernatants were collected after 24 h and analyzed by ELISA for (a) Interleukin-8 (IL-8) or (b) Interleukin-1β (IL-1β). Data represent mean ± SE from three independent experiments. * p < 0.05; ** p ≤ 0.01 relative to inducer + vehicle group.

Figure 3

Clinical study utilizing 0.1% CBG in serum formulation shows improvement in hydration levels over untreated and vehicle-treated skin. Transepidermal water loss (TEWL) was measured with a Tewameter^® TM300 instrument with lower readings demonstrating an increase in hydration and skin barrier function. Data (n = 20) represent mean ± SEM. * p < 0.05; ** p ≤ 0.01 indicates a statistically significant difference compared to baseline reading.

Figure 4

Skin irritancy was improved by 0.1% CBG in serum formulation as measured by visual grading. (a) Visual grade data represent mean ± SEM from 20 participants from each group. * p < 0.05; ** p ≤ 0.01 indicates a statistically significant difference compared to untreated group. (b) Photographs of a representative subject on day 1, 7, and 14 of the study where patch 1 = Untreated; 2 = 0.1% CBG; and 3 = Vehicle (placebo).