Exploring the efficacy of cholinergic agents for the treatment of psychostimulant use disorder: a systematic review.

IF 3.5 3区 医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-11-01 Epub Date: 2024-10-21 DOI:10.1007/s00213-024-06696-5
Nicolas Salloum, Margot Chouchana, Romain Icick, Vanessa Bloch, Stéphanie Daumas, Salah El Mestikawy, Florence Vorspan, Virgile Clergue-Duval
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Abstract

Rationale: No drugs are currently validated to treat psychostimulant use disorder (PUD). Pathophysiological studies consistently highlight the contribution of cholinergic mechanisms in psychostimulant use, including the vulnerability to PUD, paving the way for potential therapeutic strategies.

Objectives: The aim of this systematic review is to describe and discuss the efficacy of cholinergic agents in drug trials for patients with PUD.

Methods: A systematic review was conducted on April 4, 2024 in MedLine, Embase and Cochrane Library databases on controlled clinical drug trial of cholinergic agents in humans with PUD, psychostimulant abuse or dependence and psychostimulant use in recent year.

Results: Twenty-eight articles were included, twenty-one on cocaine and seven on amphetamines. Cholinergic agents used in these studies were biperiden (a muscarinic antagonist), mecamylamine (a nicotinic antagonist), nicotinic agonists, acetylcholinesterase inhibitors (AChEI), or citicoline. Two types of trials were identified. There were seventeen randomized controlled clinical trials evaluating cholinergic agents on psychostimulant use reduction in outpatients seeking treatment. Additionally, we retrieved eleven short-term «proof-of-concept» laboratory trials mainly with supervised psychostimulant administration and/or triggered craving challenges. Outpatient trials were heterogeneous and for most, inconclusive. Only two studies on galantamine (AChEI) and citicoline, reported a significant reduction of cocaine consumption. «Proof-of-concept» laboratory trials showed no evidence of efficacy on the selected outcomes, notably on craving.

Conclusions: This review does not support the current prescription of cholinergic agents to treat PUD. Replication clinical trials notably on galantamine or other AChEI, and proof-of-concept trials on comedown symptoms will be necessary to identify a potential therapeutic indication for cholinergic agents in PUD.

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探索胆碱能药物治疗精神兴奋剂使用障碍的疗效:系统综述。
理由:目前尚无有效药物可治疗精神兴奋剂使用障碍(PUD)。病理生理学研究一直强调胆碱能机制在精神兴奋剂使用中的作用,包括对 PUD 的易感性,为潜在的治疗策略铺平了道路:本系统综述旨在描述和讨论药物试验中胆碱能药物对 PUD 患者的疗效:方法:2024年4月4日,在MedLine、Embase和Cochrane图书馆数据库中对胆碱能药物在PUD患者、精神刺激剂滥用或依赖以及近年来精神刺激剂使用中的临床对照药物试验进行了系统综述:结果:共收录了 28 篇文章,其中 21 篇涉及可卡因,7 篇涉及苯丙胺。这些研究中使用的胆碱能药物包括比哌立登(一种毒蕈碱拮抗剂)、麦卡米拉明(一种烟碱拮抗剂)、烟碱激动剂、乙酰胆碱酯酶抑制剂(AChEI)或柠檬胆碱。共发现两类试验。有 17 项随机对照临床试验评估了胆碱能药物在减少门诊病人精神兴奋剂使用方面的效果。此外,我们还检索到 11 项短期 "概念验证 "实验室试验,这些试验主要是在监督下使用精神刺激剂和/或触发渴求挑战。门诊病人的试验各不相同,大多数都没有结论。只有两项关于加兰他敏(乙酰胆碱酯酶抑制剂)和柠檬胆碱的研究报告称可卡因的消耗量显著减少。"概念验证 "实验室试验显示,没有证据表明对所选结果具有疗效,尤其是对渴求的疗效:本综述不支持目前使用胆碱能药物治疗 PUD 的处方。为了确定胆碱能药物在 PUD 中的潜在治疗适应症,有必要对加兰他敏或其他 AChEI 进行重复临床试验,并对镇静症状进行概念验证试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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