Preclinical models for evaluating psychedelics in the treatment of major depressive disorder.

IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY British Journal of Pharmacology Pub Date : 2024-10-28 DOI:10.1111/bph.17370
Laith Alexander, Dasha Anderson, Luke Baxter, Matthew Claydon, James Rucker, Emma S J Robinson
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Abstract

Psychedelic drugs have seen a resurgence in interest as a next generation of psychiatric medicines with potential as rapid-acting antidepressants (RAADs). Despite promising early clinical trials, the mechanisms which underlie the effects of psychedelics are poorly understood. For example, key questions such as whether antidepressant and psychedelic effects involve related or independent mechanisms are unresolved. Preclinical studies in relevant animal models are key to understanding the pharmacology of psychedelics and translating these findings to explain efficacy and safety in patients. Understanding the mechanisms of action associated with the behavioural effects of psychedelic drugs can also support the identification of novel drug targets and more effective treatments. Here we review the behavioural approaches currently used to quantify the psychedelic and antidepressant effects of psychedelic drugs. We discuss conceptual and methodological issues, the importance of using clinically relevant doses and the need to consider possible sex differences in preclinical psychedelic studies.

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评估治疗重度抑郁症的迷幻剂的临床前模型。
迷幻药作为新一代精神科药物,具有作为速效抗抑郁药(RAAD)的潜力,再次引起了人们的兴趣。尽管早期的临床试验前景看好,但人们对迷幻药的作用机制仍知之甚少。例如,抗抑郁和迷幻药的作用是涉及相关机制还是独立机制等关键问题尚未解决。相关动物模型的临床前研究是了解迷幻药药理学并将这些发现转化为解释对患者的疗效和安全性的关键。了解与迷幻药行为效应相关的作用机制也有助于确定新的药物靶点和更有效的治疗方法。在此,我们回顾了目前用于量化迷幻药的迷幻和抗抑郁作用的行为学方法。我们讨论了概念和方法问题、使用临床相关剂量的重要性以及在临床前迷幻药研究中考虑可能的性别差异的必要性。
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来源期刊
CiteScore
15.40
自引率
12.30%
发文量
270
审稿时长
2.0 months
期刊介绍: The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries. Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues. In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.
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