Goenka Shilpi
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, USA.
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5281, USA.
J Xenobiot. 2022 Jun 10;12(2):131-144. doi: 10.3390/jox12020012.
Δ9-tetrahydrocannabinol (THC) is one of the primary ingredients of cannabis plants and is responsible for the psychoactive properties of cannabis. While cannabidiol (CBD), the non-psychoactive compound from cannabis, has been shown to stimulate human epidermal melanogenesis, the effects of THC have not been addressed in human epidermal melanocytes. Moreover, to date, no study has tested the effects of these compounds on melanocytes differing in pigmentation, representative of different skin phototypes, which would be significant as different ethnicities are known to differentially metabolize these xenobiotics. Herein, the effects of THC were studied and compared alongside CBD in human epidermal melanocytes derived from lightly-pigmented (HEMn-LP; Caucasian) and darkly-pigmented (HEMn-DP; African-American) cells over a chronic exposure of 6 d. Results demonstrated that both compounds displayed cytotoxicity at 4 µM but stimulated melanin synthesis and tyrosinase activity in a similar manner in LP and DP cells at nontoxic concentrations of 1-2 µM. However, THC and CBD showed a differential effect on dendricity in both cells; THC and CBD reversibly increased dendricity in LP cells while there was no significant change in DP cells. THC and CBD induced higher levels of reactive oxygen species (ROS) in LP cells while there was no change in the ROS levels in DP cells. In summary, although THC was relatively less cytotoxic as compared to CBD to both LP and DP cells, it exhibited a similar capacity as CBD to stimulate melanin synthesis and export in LP cells which was accompanied by a significant oxidative stress. DP cells were relatively resistant to the effects of both THC and CBD which might implicate the protective effects conferred by melanin in dark-skinned individuals.
Δ9-四氢大麻酚（THC）是大麻植物的主要成分之一，负责大麻的精神活性特性。虽然来自大麻的非精神活性化合物大麻二酚（CBD）已被证明能刺激人类表皮黑色素生成，但THC对人类表皮黑素细胞的影响尚未得到研究。此外，迄今为止，尚无研究测试这些化合物对不同色素沉着的黑素细胞（代表不同的皮肤光类型）的影响，鉴于已知不同种族对这些外源性物质的代谢存在差异，这一点具有重要意义。在此，我们研究了THC的影响，并在6天的长期暴露过程中，将其与CBD对来自浅色（HEMn-LP；白种人）和深色（HEMn-DP；非裔美国人）细胞的人类表皮黑素细胞的影响进行了比较。结果表明，两种化合物在4μM时均表现出细胞毒性，但在1-2μM的无毒浓度下，它们以相似的方式刺激LP和DP细胞中的黑色素合成和酪氨酸酶活性。然而，THC和CBD对两种细胞的树突状形态有不同影响；THC和CBD使LP细胞中的树突状形态可逆增加，而DP细胞中则无显著变化。THC和CBD在LP细胞中诱导了更高水平的活性氧（ROS），而DP细胞中的ROS水平没有变化。总之，尽管与CBD相比，THC对LP和DP细胞的细胞毒性相对较小，但它在LP细胞中表现出与CBD相似的刺激黑色素合成和输出的能力，同时伴随着显著的氧化应激。DP细胞对THC和CBD的影响相对具有抗性，这可能意味着黑色素对深色皮肤个体具有保护作用。
