Hilal Fahd, Jeanblanc Jérôme, Naassila Mickaël
Groupe de recherche sur l'alcool et les pharmacodépendances, INSERM U1247, CURS, Amiens, France.
Biol Aujourdhui. 2023;217(3-4):161-182. doi: 10.1051/jbio/2023028. Epub 2023 Nov 29.
Alcohol Use Disorder (AUD) is a psychiatric condition characterized by chronic and excessive drinking despite negative consequences on overall health and social or occupational functioning. There are currently limited treatment options available for AUD, and the effects size and the response rates to these treatments are often low to moderate. The World Health Organization has identified the development of medications to treat AUD as one of its 24 priorities. This past decade was marked by a renewed interest in psychedelic use in psychiatry. At the centre of this renaissance, ketamine, an atypical psychedelic already used in the treatment of major depression, is an NMDA receptor antagonist that exists as a racemic compound made of two enantiomers, S-ketamine, and R-ketamine. Each form can be metabolized into different metabolites, some of which having antidepressant properties. In this article, we review both clinical and preclinical studies on ketamine and its metabolites in the treatment of AUD. Preclinical as well as clinical studies have revealed that ketamine is effective in reducing withdrawal symptoms and alcohol craving. Convergent data showed that antidepressant properties of ketamine largely contribute to the decreased likelihood of alcohol relapse, especially in patients undergoing ketamine-assisted psychotherapies. Its effectiveness is believed to be linked with its ability to regulate the glutamatergic pathway, enhance neuroplasticity, rewire brain resting state network functional connectivity and decrease depressive-like states. However, it remains to further investigate (i) why strong differences exist between male and female responses in preclinical studies and (ii) the respective roles of each of the metabolites in the ketamine effects in both genders. Interestingly, current studies are also focusing on ketamine addiction and the comorbidity between alcohol addiction and depression occurring more frequently in females.
酒精使用障碍（AUD）是一种精神疾病，其特征是尽管对整体健康以及社会或职业功能产生负面影响，但仍长期过度饮酒。目前针对AUD的治疗选择有限，而且这些治疗的效应大小和反应率通常较低。世界卫生组织已将开发治疗AUD的药物确定为其24项重点工作之一。在过去十年中，精神医学领域对迷幻药的使用重新产生了兴趣。在这场复兴的核心，氯胺酮是一种已用于治疗重度抑郁症的非典型迷幻药，它是一种NMDA受体拮抗剂，以由两种对映体S-氯胺酮和R-氯胺酮组成的外消旋化合物形式存在。每种形式都可以代谢为不同的代谢物，其中一些具有抗抑郁特性。在本文中，我们综述了关于氯胺酮及其代谢物在治疗AUD方面的临床和临床前研究。临床前以及临床研究均表明，氯胺酮在减轻戒断症状和酒精渴望方面有效。趋同的数据表明，氯胺酮的抗抑郁特性在很大程度上有助于降低酒精复发的可能性，尤其是在接受氯胺酮辅助心理治疗的患者中。其有效性被认为与其调节谷氨酸能通路、增强神经可塑性、重塑大脑静息态网络功能连接以及减轻抑郁样状态的能力有关。然而，仍有待进一步研究：（i）为什么在临床前研究中雄性和雌性反应之间存在强烈差异；（ii）每种代谢物在氯胺酮对两性的作用中各自所起的作用。有趣的是，目前的研究也聚焦于氯胺酮成瘾以及酒精成瘾与抑郁症之间的共病情况，这种共病在女性中更为常见。
