Loften Anna, Farokhnia Mehdi, Vendruscolo Leandro F, Leggio Lorenzo
Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program, and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, Maryland, USA.
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
J Intern Med. 2025 Nov;298(5):392-423. doi: 10.1111/joim.70021. Epub 2025 Sep 23.
Alcohol and other substance use disorders (ASUDs) are prevalent and major contributors to global morbidity and mortality. Their impact extends beyond the individual, imposing significant burdens on families, communities, healthcare systems, and society at large. Treatments include psychosocial, behavioral, and pharmacological interventions. However, available pharmacological treatments remain limited, primarily targeting alcohol, tobacco, and opioid use disorders, with a lack of approved pharmacotherapies for other substance use disorders. This gap highlights a critical need to develop novel treatment options. Emerging evidence suggests that bidirectional brain-periphery communications play important roles in the pathophysiology and progression of ASUDs. Gut-brain hormones that are involved in the regulation of feeding and metabolism have been shown to influence reinforcing properties of food, alcohol, and other addictive substances. Additionally, stress-related pathways, especially the hypothalamic-pituitary-adrenal axis, play a significant role in regulating behaviors that are related to ASUDs. Accordingly, feeding- and stress-related neuroendocrine pathways represent novel pharmacotherapeutic targets for ASUDs. This narrative review discusses preclinical and clinical evidence for emerging pharmacotherapies that target ASUD-related neuroendocrine systems. Special emphasis is placed on recent work with glucagon-like peptide-1, ghrelin, fibroblast growth factor-21, amylin, glucocorticoids, and mineralocorticoids.
酒精及其他物质使用障碍（ASUDs）普遍存在，是全球发病和死亡的主要原因。其影响不仅限于个人，还会给家庭、社区、医疗系统及整个社会带来沉重负担。治疗方法包括心理社会、行为和药物干预。然而，现有的药物治疗仍然有限，主要针对酒精、烟草和阿片类物质使用障碍，缺乏针对其他物质使用障碍的获批药物疗法。这一差距凸显了开发新治疗方案的迫切需求。新出现的证据表明，脑-外周双向通讯在ASUDs的病理生理学和进展中起重要作用。参与调节进食和代谢的肠-脑激素已被证明会影响食物、酒精和其他成瘾物质的强化特性。此外，与应激相关的途径，尤其是下丘脑-垂体-肾上腺轴，在调节与ASUDs相关的行为中起重要作用。因此，与进食和应激相关的神经内分泌途径是ASUDs新的药物治疗靶点。这篇叙述性综述讨论了针对ASUDs相关神经内分泌系统的新兴药物疗法的临床前和临床证据。特别强调了最近关于胰高血糖素样肽-1、胃饥饿素、成纤维细胞生长因子-21、胰淀素、糖皮质激素和盐皮质激素的研究。
