Department of Biobehavioral Health, Pennsylvania State University, United States.
Neurosci Biobehav Rev. 2021 Jul;126:573-589. doi: 10.1016/j.neubiorev.2021.05.006. Epub 2021 May 11.
Excessive alcohol consumption is involved in 1/10 of deaths of U.S. working-age adults and costs the country around $250,000,000 yearly. While Alcohol Use Disorder (AUD) pathology is complex and involves multiple neurotransmitter systems, changes in synaptic plasticity, hippocampal neurogenesis, and neural connectivity have been implicated in the behavioral characteristics of AUD. Depressed mood and stress are major determinants of relapse in AUD, and there is significant comorbidity between AUD, depression, and stress disorders, suggesting potential for overlap in their treatments. Disulfiram, naltrexone, and acamprosate are current pharmacotherapies for AUD, but these treatments have limitations, highlighting the need for novel therapeutics. Ketamine is a N-methyl-D-Aspartate receptor antagonist, historically used in anesthesia, but also affects other neurotransmitters systems, synaptic plasticity, neurogenesis, and neural connectivity. Currently under investigation for treating AUDs and other Substance Use Disorders (SUDs), ketamine has strong support for efficacy in treating clinical depression, recently receiving FDA approval. Ketamine's effect in treating depression and stress disorders, such as PTSD, and preliminary evidence for treating SUDs further suggests a role for treating AUDs. This review explores the behavioral and neural evidence for treating AUDs with ketamine and clinical data on ketamine therapy for AUDs and SUDs.
过量饮酒是导致美国成年劳动力 1/10 的人死亡的原因之一，每年给美国造成约 25 亿美元的损失。虽然酒精使用障碍（AUD）的发病机制很复杂，涉及多种神经递质系统，但突触可塑性、海马神经发生和神经连接的变化与 AUD 的行为特征有关。情绪低落和压力是 AUD 复发的主要决定因素，AUD、抑郁和压力障碍之间存在显著的共病，表明它们的治疗可能存在重叠。双硫仑、纳曲酮和阿坎酸是 AUD 的当前药物治疗方法，但这些治疗方法存在局限性，突出了对新型治疗方法的需求。氯胺酮是一种 N-甲基-D-天冬氨酸受体拮抗剂，历史上用于麻醉，但也影响其他神经递质系统、突触可塑性、神经发生和神经连接。目前正在研究氯胺酮治疗 AUD 和其他物质使用障碍（SUD）的方法，氯胺酮在治疗临床抑郁症方面有很强的疗效支持，最近获得了 FDA 的批准。氯胺酮在治疗抑郁症和应激障碍（如 PTSD）方面的作用，以及初步证据表明氯胺酮可用于治疗 SUD，进一步表明氯胺酮可用于治疗 AUD。这篇综述探讨了用氯胺酮治疗 AUD 的行为和神经证据，以及氯胺酮治疗 AUD 和 SUD 的临床数据。
