Department of Psychiatry, Stanford University, Palo Alto 94305, California.
Department of Neurosciences, University of California-San Diego, La Jolla 92093, California.
J Neurosci. 2023 Nov 8;43(45):7472-7482. doi: 10.1523/JNEUROSCI.1384-23.2023.
Serotonergic psychedelics, such as psilocybin and LSD, have garnered significant attention in recent years for their potential therapeutic effects and unique mechanisms of action. These compounds exert their primary effects through activating serotonin 5-HT receptors, found predominantly in cortical regions. By interacting with these receptors, serotonergic psychedelics induce alterations in perception, cognition, and emotions, leading to the characteristic psychedelic experience. One of the most crucial aspects of serotonergic psychedelics is their ability to promote neuroplasticity, the formation of new neural connections, and rewire neuronal networks. This neuroplasticity is believed to underlie their therapeutic potential for various mental health conditions, including depression, anxiety, and substance use disorders. In this mini-review, we will discuss how the 5-HT receptor activation is just one facet of the complex mechanisms of action of serotonergic psychedelics. They also interact with other serotonin receptor subtypes, such as 5-HT and 5-HT receptors, and with neurotrophin receptors (e.g., tropomyosin receptor kinase B). These interactions contribute to the complexity of their effects on perception, mood, and cognition. Moreover, as psychedelic research advances, there is an increasing interest in developing nonhallucinogenic derivatives of these drugs to create safer and more targeted medications for psychiatric disorders by removing the hallucinogenic properties while retaining the potential therapeutic benefits. These nonhallucinogenic derivatives would offer patients therapeutic advantages without the intense psychedelic experience, potentially reducing the risks of adverse reactions. Finally, we discuss the potential of psychedelics as substrates for post-translational modification of proteins as part of their mechanism of action.
血清素能致幻剂，如裸盖菇素和 LSD，近年来因其潜在的治疗效果和独特的作用机制而受到广泛关注。这些化合物主要通过激活 5-羟色胺 5-HT 受体发挥其主要作用，这些受体主要存在于皮质区域。通过与这些受体相互作用，血清素能致幻剂会引起感知、认知和情绪的改变，从而产生典型的致幻体验。血清素能致幻剂最重要的一个方面是它们促进神经可塑性的能力，即形成新的神经连接和重塑神经网络。这种神经可塑性被认为是它们治疗各种心理健康状况（如抑郁症、焦虑症和物质使用障碍）的潜在机制。在这篇迷你综述中，我们将讨论 5-HT 受体的激活如何只是血清素能致幻剂复杂作用机制的一个方面。它们还与其他 5-HT 受体亚型（如 5-HT 和 5-HT 受体）以及神经营养因子受体（如原肌球蛋白受体激酶 B）相互作用。这些相互作用导致了它们对感知、情绪和认知的影响的复杂性。此外，随着迷幻研究的进展，人们越来越有兴趣开发这些药物的非致幻衍生物，通过去除致幻特性，同时保留潜在的治疗益处，为精神障碍创造更安全、更有针对性的药物。这些非致幻衍生物将为患者提供治疗优势，而不会产生强烈的致幻体验，从而可能降低不良反应的风险。最后，我们讨论了迷幻剂作为蛋白质翻译后修饰的底物的潜力，这是它们作用机制的一部分。
