Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Nat Neurosci. 2022 Nov;25(11):1407-1419. doi: 10.1038/s41593-022-01177-4. Epub 2022 Oct 24.
Psychedelics are serotonin 2A receptor agonists that can lead to profound changes in perception, cognition and mood. In this review, we focus on the basic neurobiology underlying the action of psychedelic drugs. We first discuss chemistry, highlighting the diversity of psychoactive molecules and the principles that govern their potency and pharmacokinetics. We describe the roles of serotonin receptors and their downstream molecular signaling pathways, emphasizing key elements for drug discovery. We consider the impact of psychedelics on neuronal spiking dynamics in several cortical and subcortical regions, along with transcriptional changes and sustained effects on structural plasticity. Finally, we summarize neuroimaging results that pinpoint effects on association cortices and thalamocortical functional connectivity, which inform current theories of psychedelic action. By synthesizing knowledge across the chemical, molecular, neuronal, and network levels, we hope to provide an integrative perspective on the neural mechanisms responsible for the acute and enduring effects of psychedelics on behavior.
迷幻剂是血清素 2A 受体激动剂，可导致感知、认知和情绪发生深刻变化。在这篇综述中，我们专注于迷幻药物作用的基础神经生物学。我们首先讨论化学，突出显示精神活性分子的多样性以及控制其效力和药代动力学的原则。我们描述了血清素受体及其下游分子信号通路的作用，强调了药物发现的关键要素。我们考虑了迷幻剂对几个皮质和皮质下区域神经元尖峰动力学的影响，以及转录变化和对结构可塑性的持续影响。最后，我们总结了神经影像学结果，这些结果指出了迷幻剂对联合皮质和丘脑皮质功能连接的影响，为迷幻剂作用的当前理论提供了信息。通过综合化学、分子、神经元和网络水平的知识，我们希望对迷幻剂对行为的急性和持久影响的神经机制提供综合观点。
