Substance abuse disorder continues to have devastating consequences for individuals and society and current therapies are not sufficient to provide the magnitude of medical impact required. Although some evidence suggests the use of ketamine in treating various substance use related- symptoms, its adverse event profile including dissociation, dysphoria, and abuse liability limit its potential as a therapy. Here, we outline experiments to test our hypothesis that (R)-ketamine can both alleviate withdrawal symptoms and produce effects that help sustain abstinence. In morphine-dependent rats, (R)-ketamine alleviated naloxone-precipitated withdrawal signs. (R)-ketamine also blocked morphine-induced place preference in mice without inducing place preference on its own. We also evaluated whether (R)-ketamine would induce anhedonia, a counter-indicated effect for a drug abuse treatment agent. S-(+)- but not R-(−)-ketamine produced anhedonia-like responses in rats that electrically self-stimulated the medial forebrain bundle (ICSS). However, time-course studies of ICSS are needed to fully appreciate these differences. These data begin to support the claim that (R)-ketamine will dampen withdrawal symptoms and drug liking, factors known to contribute to the cycle of drug addiction. In addition, these data suggest that (R)-ketamine would not produce negative mood or anhedonia that could interfere with treatment. It is suggested that continued investigation of (R)-ketamine as a novel therapeutic for substance abuse disorder be given consideration by the preclinical and clinical research communities. This suggestion is further encouraged by a recent report on the efficacy of (R)-ketamine in treatment-resistant depressed patients at a dose with little measurable dissociative side-effects.

药物滥用症继续对个人和社会造成毁灭性后果，目前的疗法不足以提供所需的医疗影响。尽管一些证据表明氯胺酮可用于治疗各种与物质使用相关的症状，但其不良事件包括解离，烦躁不安和滥用倾向限制了其作为治疗手段的潜力。在这里，我们概述了实验以检验我们的假设，即（R）-氯胺酮既可以缓解戒断症状，​​又可以产生有助于维持戒断的效果。在吗啡依赖性大鼠中，（R）-氯胺酮减轻了纳洛酮沉淀的戒断症状。（R）-氯胺酮还可以阻止小鼠吗啡诱导的位置偏爱，而不会自行诱导位置偏爱。我们还评估了（R）-氯胺酮是否会引起快感不足，这是药物滥用治疗剂的反作用。S-（+）-而不是R-（-）-氯胺酮在电刺激内前脑束（ICSS）的大鼠中产生类似于快感的反应。但是，需要对ICSS进行时程研究以充分理解这些差异。这些数据开始支持这样的说法，即（R）-氯胺酮将缓解戒断症状和吸毒现象，这是已知导致吸毒成瘾周期的因素。此外，这些数据表明，（ř氯胺酮不会产生会干扰治疗的不良情绪或快感不足。建议临床前和临床研究界考虑继续研究（R）-氯胺酮作为一种新的药物滥用障碍疗法。关于（R）-氯胺酮在治疗难治性抑郁症患者中的剂量几乎没有可测量的解离性副作用的近期报道进一步鼓励了这一建议。