Sharp Trevor, Ippolito Aurelija
University Department of Pharmacology, Oxford, UK.
Br J Pharmacol. 2025 May 23. doi: 10.1111/bph.70050.
Psychedelic drugs such as LSD and psilocin were once relegated to the fringes of medical research because of their association with counterculture movements and a perceived concern about harm through recreational use, and their consequent legal prohibition in the early 1970s. However, these drugs are now experiencing a renaissance in the field of psychiatry based on increasing evidence that they can produce long-lasting improvements in health across a wide variety of mental illnesses, including major depression, addictions and anxiety disorders. These drugs interact with many different 5-HT receptor subtypes but the powerful psychedelic experience, which (depending on set and setting) includes profound alterations in perception, mood and cognition, accompanied by vivid hallucinations, is now widely considered mediated by an agonist action at 5-HT receptors. However, the link between the psychedelic experience, 5-HT receptor agonism and therapeutic effects is currently uncertain. Indeed, recent research has revealed a new class of 5-HT receptor agonists which appear to retain the therapeutic potential of psychedelics drugs without inducing disorienting hallucinatory experiences. Biased signalling, partial agonism and non-selectivity at the 5-HT receptor are amongst the possible explanations for the differential properties of these drugs, whereas increased neuroplasticity offers a likely account of their common therapeutic effects. This article explores the neuropsychopharmacological properties of hallucinogenic and non-hallucinogenic 5-HT receptor agonists in the context of their promise as novel drug treatments in psychiatry.
诸如麦角酸二乙酰胺（LSD）和裸盖菇素等致幻药物曾一度被排除在医学研究边缘，原因是它们与反主流文化运动相关联，且人们认为存在因娱乐性使用而造成伤害的担忧，以及随后在20世纪70年代初被法律禁止。然而，基于越来越多的证据表明这些药物能在包括重度抑郁症、成瘾症和焦虑症在内的多种精神疾病中产生持久的健康改善，它们如今正在精神病学领域经历复兴。这些药物与许多不同的5-羟色胺（5-HT）受体亚型相互作用，但强大的致幻体验（取决于心境和环境）包括感知觉、情绪和认知的深刻改变，并伴有生动的幻觉，现在普遍认为是由对5-HT受体的激动剂作用介导的。然而，致幻体验、5-HT受体激动作用和治疗效果之间的联系目前尚不确定。事实上，最近的研究揭示了一类新的5-HT受体激动剂，它们似乎保留了致幻药物的治疗潜力，却不会引发使人迷失方向的幻觉体验。5-HT受体处的偏向性信号传导、部分激动作用和非选择性是这些药物具有不同特性的可能解释，而神经可塑性增加则可能解释了它们共同的治疗效果。本文在致幻和非致幻5-HT受体激动剂有望成为精神病学新型药物治疗手段的背景下，探讨了它们的神经精神药理学特性。
