Cannabidiol and Minor Phytocannabinoids: A Preliminary Study to Assess Their Anti-Melanoma, Anti-Melanogenic, and Anti-Tyrosinase Properties

Abstract

Currently, there is an increased interest from both scientists and consumers in the application of cannabis/hemp/phytocannabinoids in skin-related disorders. However, most previous investigations assessed the pharmacological properties of hemp extracts, cannabidiol (CBD), or tetrahydrocannabinol (THC), with very few studies focusing on minor phytocannabinoids from hemp. In this context, the current work explored the in vitro anti-melanoma, anti-melanogenic, and anti-tyrosinase effects of cannabidiol (CBD) and three minor phytocannabinoids, namely cannabigerol (CBG), cannabinol (CBN), and cannabichromene (CBC). Among the tested human malignant melanoma cells (A375, SH4, and G361), only A375 cells were highly susceptible to the 48 h treatment with the four phytocannabinoids (IC50 values between 12.02 and 25.13 μg/mL). When melanogenesis was induced in murine melanoma B16F10 cells by α-melanocyte stimulating hormone (αMSH), CBD, CBG, and CBN significantly decreased the extracellular (29.76–45.14% of αMSH+ cells) and intracellular (60.59–67.87% of αMSH+ cells) melanin content at 5 μg/mL. Lastly, CBN (50–200 μg/mL) inhibited both mushroom and murine tyrosinase, whereas CBG (50–200 μg/mL) and CBC (100–200 μg/mL) down-regulated only the mushroom tyrosinase activity; in contrast, CBD was practically inactive. The current data show that tyrosinase inhibition might not be responsible for reducing the melanin biosynthesis in α-MSH-treated B16F10 cells. By evaluating for the first time the preliminary anti-melanoma, anti-melanogenic, and anti-tyrosinase properties of CBN and CBC and confirming similar effects for CBD and CBG, this study can expand the utilization of CBD and, in particular, of minor phytocannabinoids to novel cosmeceutical products for skin care.

Comprehensive Insight into Cutaneous Application of Hemp

“…Methanol and hemp flower extracts inhibit tyrosinase activity and melanin synthesis [22]. The same was observed for minor cannabinoids-CBN, CBC, and CBG [21]. On the other hand, CBD and THC stimulate in vitro tyrosinase activity and melanin synthesis in human epidermal melanocytes [23,24].…”

Phytochemical Profiling, Antioxidant and Tyrosinase Regulatory Activities of Extracts from Herb, Leaf and In Vitro Culture of Achillea millefolium (Yarrow)

“…The amino acid structure of murine tyrosinase is ca. 85% similar to the human enzyme [ 38 ]. Differences in inhibitory activity toward tyrosinases obtained from different sources were previously detected by our [ 37 ] and other research groups [ 39 , 40 ] and are considered as a significant factor influencing the in vivo activity of newly identified skin-lightening cosmetic ingredients.…”

Bipiperidinyl Derivatives of Cannabidiol Enhance Its Antiproliferative Effects in Melanoma Cells

“…Although several cannabis extracts have been reported to exert inhibitory effects on the growth of melanoma cells [15,16], only limited studies explored the antiproliferative activity of the individual cannabinoids. A study reported that CBD and CBG showed the most promising antiproliferative effect (IC 50 = 12.0 and 12.1 µM, respectively) compared to other minor cannabinoids, such as CBN and CBC, in human melanoma A375 cells [17]. It was also reported that CBD had the highest inhibitory effect on the growth of murine melanoma cells (B16F10) with an IC 50 of 80 µM compared to other minor cannabinoids [17].…”

“…A study reported that CBD and CBG showed the most promising antiproliferative effect (IC 50 = 12.0 and 12.1 µM, respectively) compared to other minor cannabinoids, such as CBN and CBC, in human melanoma A375 cells [17]. It was also reported that CBD had the highest inhibitory effect on the growth of murine melanoma cells (B16F10) with an IC 50 of 80 µM compared to other minor cannabinoids [17]. This trend was in agreement with data from our current study showing that the cytotoxicity of CBD was higher than other minor cannabinoids in murine melanoma cells.…”