Jensen Kathrine Louise, Jensen Søren Brøgger, Madsen Kenneth Lindegaard
Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Front Pharmacol. 2022 Sep 8;13:854176. doi: 10.3389/fphar.2022.854176. eCollection 2022.
Psychostimulant use disorder is a major health issue around the world with enormous individual, family-related and societal consequences, yet there are no effective pharmacological treatments available. In this review, a target-based overview of pharmacological treatments toward psychostimulant addiction will be presented. We will go through therapeutic approaches targeting different aspects of psychostimulant addiction with focus on three major areas; 1) drugs targeting signalling, and metabolism of the dopamine system, 2) drugs targeting either AMPA receptors or metabotropic glutamate receptors of the glutamate system and 3) drugs targeting the severe side-effects of quitting long-term psychostimulant use. For each of these major modes of intervention, findings from pre-clinical studies in rodents to clinical trials in humans will be listed, and future perspectives of the different treatment strategies as well as their potential side-effects will be discussed. Pharmaceuticals modulating the dopamine system, such as antipsychotics, DAT-inhibitors, and disulfiram, have shown some promising results. Cognitive enhancers have been found to increase aspects of behavioural control, and drugs targeting the glutamate system such as modulators of metabotropic glutamate receptors and AMPA receptors have provided interesting changes in relapse behaviour. Furthermore, CRF-antagonists directed toward alleviating the symptoms of the withdrawal stage have been examined with interesting resulting changes in behaviour. There are promising results investigating therapeutics for psychostimulant addiction, but further preclinical work and additional human studies with a more stratified patient selection are needed to prove sufficient evidence of efficacy and tolerability.
精神兴奋剂使用障碍是一个全球性的重大健康问题，会给个人、家庭和社会带来巨大后果，但目前尚无有效的药物治疗方法。在本综述中，将对针对精神兴奋剂成瘾的药物治疗进行基于靶点的概述。我们将探讨针对精神兴奋剂成瘾不同方面的治疗方法，重点关注三个主要领域：1）针对多巴胺系统信号传导和代谢的药物；2）针对谷氨酸系统的AMPA受体或代谢型谷氨酸受体的药物；3）针对长期停用精神兴奋剂的严重副作用的药物。对于这些主要干预模式中的每一种，将列出从啮齿动物的临床前研究到人类临床试验的结果，并讨论不同治疗策略的未来前景及其潜在副作用。调节多巴胺系统的药物，如抗精神病药物、多巴胺转运体抑制剂和双硫仑，已显示出一些有前景的结果。认知增强剂已被发现可增强行为控制能力，而针对谷氨酸系统的药物，如代谢型谷氨酸受体和AMPA受体调节剂，已在复发行为方面产生了有趣的变化。此外，针对缓解戒断期症状的促肾上腺皮质激素释放因子拮抗剂也已进行了研究，并在行为方面产生了有趣的变化。在研究精神兴奋剂成瘾的治疗方法方面有一些有前景的结果，但需要进一步的临床前工作以及更多采用分层患者选择的人体研究，以证明疗效和耐受性的充分证据。
