南方医科大学学报

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (1): 1-5.doi: 10.12122/j.issn.1673-4254.2026.01.01

• •    下一篇

致幻剂抗抑郁治疗的研究进展

夏可1,2(), 高天明1,2()   

  1. 1.南方医科大学基础医学院神经生物学教研室，广东 广州 510515
    2.粤港澳大湾区脑科学与类脑研究中心，广东 广州 510515
  • 收稿日期:2025-11-01 出版日期:2026-01-20 发布日期:2026-01-16
  • 通讯作者: 高天明 E-mail:xiake1604@163.com;tgao@smu.edu.cn
  • 作者简介:夏 可，在读博士研究生，E-mail: xiake1604@163.com
    中国工程院院士，南方医科大学基础医学院教授，国家高端人才、中国医学科学院学术咨询委员会学部委员、中国中医科学院学部委员、国务院学位委员会学科评议组成员。粤港澳大湾区脑科学与类脑研究中心主任、精神健康研究教育部重点实验室主任。兼任Pharmacol Res及Neurosci Bull副主编。长期从事抗抑郁/焦虑的基础和转化研究。先后主持了国家自然科学基金重大和重点项目、教育部创新团队项目及滚动项目、973课题等基金课题，以第一完成人获国家自然科学奖二等奖2项，省部级科技一等奖3项。代表性论文发表在Nat Med、Nat Neurosci、Neuron、Nat Cancer等国际著名学术刊物上。培养的博士中，获国家高端人才4人、国家“万人计划”3人、广东省高端人才3人、全国优博论文奖1人、全军/广东省优博论文奖5人，博士，教授，E-mail: tgao@smu.edu.cn。
  • 基金资助:
    国家科技创新2030重大项目课题(K122283288)

Clinical application and mechanistic studies of psychedelics for treatment of depression: progress and future challenges

Ke XIA1,2(), Tianming GAO1,2()   

  1. 1.Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
    2.The Great Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou 510515, China
  • Received:2025-11-01 Online:2026-01-20 Published:2026-01-16
  • Contact: Tianming GAO E-mail:xiake1604@163.com;tgao@smu.edu.cn

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摘要：

抑郁症是一种复杂的全球性精神疾病，传统抗抑郁药物存在起效慢、疗效不足等局限。近年来，以裸盖菇素为代表的经典致幻剂在临床研究中展现出快速、强效且持久的抗抑郁潜力，其独特作用机制与临床应用前景已成为精神医学与神经科学领域的研究热点。本文综述了该领域近5年的最新进展。临床上多项随机对照试验表明，单次或少量次数的致幻剂辅助心理治疗，可对难治性抑郁症产生快速且持久的抗抑郁效果。在机制层面，致幻剂能够快速促进神经营养因子释放，增强神经可塑性，促进脑功能重组，为心理干预创造关键的“神经窗口期”。然而，其具体分子与环路机制尚未完全阐明，目前围绕5-羟色胺2A受体依赖与TrkB神经营养通路依赖这两种观点仍存在争议。尽管前景广阔，但其转化应用仍面临致幻风险、机制尚未完全明确、治疗方案缺乏标准化以及长期安全性证据不足等多重挑战。未来研究需进一步揭示其神经生物学机制，研发非致幻型药物，建立标准化治疗体系，并探索精准生物标志物，以推动该疗法向更安全、规范、个体化的方向发展。

关键词: 致幻剂, 裸盖菇素, 抗抑郁, 5-HT2A受体, 神经可塑性

Abstract:

Depression is a complex and globally prevalent mental disorder, for which conventional antidepressant medications face limitations such as delayed onset and insufficient efficacy. Classic psychedelics, most notably psilocybin, have recently emerged as promising candidates for treatment of depression and demonstrated rapid, robust, and sustained antidepressant effects in controlled clinical settings. Their unique mechanisms of action and clinical prospects have become a key research focus in psychiatry and neuroscience. This review synthesizes the latest advances in the field over the past 5 years. Results from multiple randomized controlled trials indicate that a single or limited number of sessions of psychedelic-assisted psychotherapy can induce rapid and durable antidepressant effects in patients with treatment-resistant depression. At the mechanistic level, psychedelics rapidly promote the release of neurotrophic factors, enhance neuroplasticity, and facilitate brain network reorganization, thereby creating a critical "neuroplastic window" for psychotherapeutic intervention. However, the specific molecular and circuit-level mechanisms have not been fully understood with ongoing debate primarily over the 5-HT2A receptor-dependent hypothesis versus the TrkB neurotrophic pathway-dependent hypothesis. Despite the promising outlook, translational applications of these substances faces several key challenges, including psychedelic-related risks, incomplete mechanistic understanding, lack of standardized treatment protocols, and insufficient long-term safety data. Future research should focus on elucidating the underlying neurobiological mechanisms, developing non-hallucinogenic derivatives, establishing standardized treatment frameworks, and identifying precise biomarkers to advance this therapeutic approach toward safer, more standardized, and personalized clinical implementation.

Key words: psychedelic, psilocybin, antidepressant, 5-hydroxytryptamine receptor 2A, neuroplasticity