Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA, 70112, USA.
Neuropharmacology. 2023 Jun 15;231:109504. doi: 10.1016/j.neuropharm.2023.109504. Epub 2023 Mar 13.
Psychedelic compounds have shown extraordinary potential in treating a wide range of neuropsychiatric disorders. Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3-12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. Here we review the preclinical models and experimental approaches that have been used to study the neurobiological actions of psychedelic drugs. We further summarize the insights these studies have provided into the possible mechanisms underlying the induction of their therapeutic actions, including the receptors to which psychedelics bind and the second messenger signaling cascades that they activate. We also discuss potential biological processes that psychedelics may alter to produce the lasting amelioration of symptoms, including improvements in synaptic structure and function and suppression of inflammation. Improved mechanistic understanding of psychedelic drug actions will aid in the advancement of these promising new medicines. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".
迷幻化合物在治疗广泛的神经精神疾病方面显示出了非凡的潜力。例如，在几项临床试验中，裸盖菇素已被证明能在数天内迅速（within days）并持续（3-12 个月）改善人类治疗抵抗性抑郁症和其他神经精神疾病。在这里，我们回顾了用于研究迷幻药物神经生物学作用的临床前模型和实验方法。我们进一步总结了这些研究为了解诱导其治疗作用的可能机制提供的见解，包括迷幻剂结合的受体和它们激活的第二信使信号级联。我们还讨论了迷幻剂可能改变以产生持久症状改善的潜在生物学过程，包括改善突触结构和功能以及抑制炎症。对迷幻药物作用的机制理解的提高将有助于推进这些有前途的新药。本文是“美国国立卫生研究院裸盖菇素研究演讲系列”特刊的一部分。
