Thomas Alexander, Chambers R Andrew
Indiana University School of Medicine Addiction Psychiatry Fellowship Program, Goodman Hall, Department of Psychiatry, Indianapolis, IN 46202, USA.
NeuroSci. 2025 Aug 27;6(3):83. doi: 10.3390/neurosci6030083.
Interest in ketamine as a novel treatment for substance use disorders (SUDs) has been increasing due to its N-methyl-D-aspartate (NMDA) glutamate receptor antagonism and mounting evidence that glutamate neurotransmission is involved in the pathogenesis of both depression and addictions. This narrative review provides an outline of clinical evidence reported in the literature from the 1970s to 2025 that examines the efficacy of ketamine for the treatment of SUDs, focusing primarily on randomized blinded controlled trials (RBCTs). Key cohort studies, retrospective studies, secondary analyses, case reports, and relevant basic neuroscience studies are reviewed to complement the more rigorous human controlled trial data. Thus far, ketamine has been tested in nine RBCTs targeting cocaine (three studies), alcohol (three studies), opioid use disorder (two studies), and nicotine (one study), suggesting efficacy for addiction in combination with psychotherapies, and often when doses produce subjectively reported mystical or psychedelic experiences. This review highlights promising preliminary evidence, and the need for more rigorous studies to elucidate the scope of drug addictions ketamine may target, its optimal dosing or route of administration, the importance of concurrent psychotherapies, professional supervision and safety monitoring, and which psychiatric comorbidities or contexts may contraindicate its use for SUDs.
由于氯胺酮对N-甲基-D-天冬氨酸（NMDA）谷氨酸受体具有拮抗作用，且越来越多的证据表明谷氨酸神经传递参与了抑郁症和成瘾的发病机制，因此人们对氯胺酮作为物质使用障碍（SUDs）的一种新型治疗方法的兴趣与日俱增。这篇叙述性综述概述了20世纪70年代至2025年文献中报道的临床证据，这些证据考察了氯胺酮治疗SUDs的疗效，主要侧重于随机双盲对照试验（RBCTs）。对关键队列研究、回顾性研究、二次分析、病例报告及相关基础神经科学研究进行了综述，以补充更为严格的人体对照试验数据。到目前为止，氯胺酮已在9项RBCTs中进行了测试，这些试验针对可卡因（3项研究）、酒精（3项研究）、阿片类物质使用障碍（2项研究）和尼古丁（1项研究），表明其与心理治疗联合使用时对成瘾有效，且通常在剂量产生主观报告的神秘或迷幻体验时有效。本综述强调了有前景的初步证据，以及需要进行更严格的研究，以阐明氯胺酮可能针对的药物成瘾范围、其最佳剂量或给药途径、同时进行心理治疗的重要性、专业监督和安全监测，以及哪些精神科合并症或情况可能禁忌其用于SUDs的治疗。
