Opioid use disorder (OUD) has reached epidemic proportions, with many countries facing high levels of opioid use and related fatalities. Although currently prescribed medications for OUD are considered lifesaving, they inadequately address negative affect and cognitive impairment, resulting in high relapse rates to nonmedical opioid use even years after drug cessation (protracted abstinence). Evidence supports the notion that ketamine, an anesthetic and rapid-acting antidepressant drug, holds promise as a candidate for OUD treatment, including the management of acute withdrawal somatic symptoms, negative affect during protracted opioid abstinence, and prevention of retaking nonmedical opioids. In this review, we comprehensively discuss preclinical and clinical research that has evaluated ketamine and its metabolites as potential novel therapeutic strategies for treating OUD. Furthermore, we examine evidence that supports the relevance of the molecular targets of ketamine and its metabolites in relation to their potential effects and therapeutic outcomes in OUD. Overall, existing evidence demonstrates that ketamine and its metabolites can effectively modulate pathophysiological processes affected in OUD, suggesting a promising therapeutic role in the treatment of OUD and the prevention of return to opioid use during abstinence.

中文翻译：

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氯胺酮和羟基去甲氯胺酮作为治疗阿片类药物使用障碍的新型药物疗法


阿片类药物使用障碍 （OUD） 已达到流行病的程度，许多国家面临高水平的阿片类药物使用和相关死亡。尽管目前为 OUD 开具的处方药被认为可以挽救生命，但它们不能充分解决负面影响和认知障碍，导致即使在停药数年（长期戒断）后，非医疗阿片类药物使用的复发率也很高。证据支持氯胺酮（一种麻醉和速效抗抑郁药）有望成为 OUD 治疗的候选药物，包括急性戒断性躯体症状的管理、长期阿片类药物戒断期间的负面影响以及预防重新服用非药物阿片类药物。在这篇综述中，我们全面讨论了临床前和临床研究，这些研究将氯胺酮及其代谢物评估为治疗 OUD 的潜在新型治疗策略。此外，我们检查了支持氯胺酮及其代谢物的分子靶标与其在 OUD 中的潜在作用和治疗结果相关的相关性的证据。总体而言，现有证据表明，氯胺酮及其代谢物可以有效调节 OUD 中受影响的病理生理过程，这表明在 OUD 的治疗和防止戒断期间重新使用阿片类药物方面具有有前途的治疗作用。