UCIBIO REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal.
Addict Biol. 2020 Mar;25(2):e12824. doi: 10.1111/adb.12824. Epub 2019 Aug 23.
Cannabinoids comprise a broad group of psychoactive substances that activate endogenous cannabinoid (EC) receptors (ie, CB R and CB R), altering neurotransmitter release in the brain. The importance of their regulatory role in different biological processes has prompted the development of synthetic cannabinoids (SCs), substantially more potent than tetrahydrocannabinol (THC, the main psychoactive substance of cannabis). Although SCs were primarily designed given their therapeutic applications, their recreational use has become a major public health concern due to several reports of severe intoxications and deaths. SCs have favored increased popularity over recent years due to their intensified psychoactive effects, compared with THC, turning regular cannabis users into SCs. Among cannabinoid users (mainly young people), pregnant women and women of child-bearing potential (WoCBP) comprise particular risk groups, due to the potential onset of neurodevelopment disorders in the offspring (eg, schizophrenia and autism spectrum disorders). Understanding the role played by cannabinoids, and the potential action of emerging SCs in the regulation of the neuronal function, especially during neuronal development, thus assumes critical relevance. Here, we review the mechanistic regulation of neuronal processes, namely during neuronal development, by the endocannabinoid system. Most important, we further develop on the potential of SCs to modulate such mechanisms and subsequently disrupt proper neurodevelopment.
大麻素是一组广泛的具有精神活性的物质，可激活内源性大麻素（EC）受体（即 CB1R 和 CB2R），改变大脑中的神经递质释放。由于它们在不同生物过程中的调节作用非常重要，因此开发了合成大麻素（SCs），其效力远远超过四氢大麻酚（THC，大麻的主要精神活性物质）。尽管 SC 最初是基于其治疗应用而设计的，但由于有几起因严重中毒和死亡的报告，它们的娱乐用途已成为一个主要的公共卫生问题。近年来，由于与 THC 相比，它们的精神活性作用更强，因此 SC 受到了更多的欢迎，这使得经常使用大麻的人转而使用 SC。在大麻素使用者（主要是年轻人）、孕妇和生育能力妇女（WoCBP）中，由于后代可能出现神经发育障碍（例如精神分裂症和自闭症谱系障碍），因此他们构成了特定的风险群体。了解大麻素所起的作用，以及新兴的 SC 在调节神经元功能方面的潜在作用，特别是在神经元发育过程中，因此具有至关重要的意义。在这里，我们综述了内源性大麻素系统对神经元过程的机制调节，尤其是在神经元发育过程中的调节。最重要的是，我们进一步研究了 SC 调节这些机制并随后破坏正常神经发育的潜力。
