Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD’s influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5 µM and 10 µM) and affected the viability of NPCs than at lower concentrations (1 µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and β-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.

最近的研究表明，大麻素在治疗各种神经系统疾病方面具有潜在的功效，而大麻二酚（CBD）是研究最多的化合物之一，已被提议作为一种无毒的选择。然而，CBD 对神经发育过程的不利影响很少在细胞培养系统中进行研究。为了更好地了解 CBD 对神经发育的影响，我们将神经祖细胞 (NPC) 暴露于不同浓度的 CBD（1 µM、5 µM 和 10 µM）。我们评估了 2D 和 3D 生物打印模型的形态、迁移、分化、细胞死亡和基因表达，以更有效地刺激生理条件。我们的结果表明，在 2D 和 3D 模型中，CBD 在较高浓度（5 µM 和 10 µM）下毒性更大，并且比较低浓度（1 µM）更影响 NPC 的活力。此外，我们的研究表明，较高浓度的 CBD 大大减少了神经球的大小和神经球内 NPC 的数量，损害了神经元和星形胶质细胞分化后的形态和活动性，并减少了神经突的萌芽。有趣的是，我们还发现 CBD 通过影响代谢途径早期和晚期糖酵解和 β-氧化酶的表达来改变细胞代谢。因此，我们的研究表明，较高浓度的 CBD 会促进细胞功能的重要变化，这在中枢神经系统发育过程中至关重要。