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.

Cannabidiol and Cannabigerol Inhibit Cholangiocarcinoma Growth In Vitro via Divergent Cell Death Pathways

“…CBG has shown to be more effective than CBD in reducing ultraviolet-light-induced inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6 [ 25 ]. CBG is more effective in reducing the Cutibacterium acne- induced interleukin 1-beta production in primary normal human epidermal keratinocytes [ 33 ]. Immunofluorescent staining of BAX revealed heavy expression of the pro-apoptotic mitochondrial pore protein from CBD treatment but not CBG; again, the DAPI staining show similar nuclear condensation patterns to the Ki-67 staining performed.…”

Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes

“…At any rate, it seems noteworthy that CBG markedly, yet not significantly, increased the DAGLα/β to MAGL activity ratio ( Table 4 ) and doubled CB 1/2 binding ( Table 3 ), thus suggesting the selective enhancement of 2-AG signaling in human keratinocytes by this pCB. Moreover, the increase in the anti-inflammatory PEA following CBG treatment seems to be of note because a recent study showed that CBG, when applied topically, promotes skin health by reducing the appearance of redness and improving barrier function via anti-inflammatory activity [ 59 ].…”

Medical Cannabis Activity Against Inflammation: Active Compounds and Modes of Action

“…Furthermore, the researchers performed a single-blind clinical study on 20 healthy volunteers with sodium lauryl sulfate (SLS)-induced contact dermatitis and found that topical application of 0.1% CBG serum showed significantly lower trans-epidermal water loss (TEWL) values compared to placebo and untreated sites. Moreover, the CBG serum reduced redness and inflammation following 48 h treatment, and after 2 weeks of application, the skin condition almost returned to baseline levels of visual grade ( Perez et al, 2022 ).…”

“…In a study that characterized the anti-inflammatory properties of CBG on human skin cells in vitro , it was demonstrated that CBG treatment reduced ROS levels in human dermal fibroblasts, better than vitamin C. CBG also protected human epidermal keratinocytes by inhibiting pro-inflammatory cytokines that were released following induction using UVA, UVB or Cutibacterium acnes exposure, including TNF-α, IL-1β, IL-6 and IL-8 ( Figure 1 ; Perez et al, 2022 ). Furthermore, the researchers performed a single-blind clinical study on 20 healthy volunteers with sodium lauryl sulfate (SLS)-induced contact dermatitis and found that topical application of 0.1% CBG serum showed significantly lower trans-epidermal water loss (TEWL) values compared to placebo and untreated sites.…”