Marquez-Meneses Juan David, Olaya-Bonilla Santiago Arturo, Barrera-Carreño Samuel, Tibaduiza-Arévalo Lucía Catalina, Forero-Cárdenas Sara, Carrillo-Vaca Liliana, Rojas-Rodríguez Luis Carlos, Calderon-Ospina Carlos Alberto, Rodríguez-Quintana Jesús
Pharmacology Unit, Department of Biomedical Sciences, School of Medicine and Health Sciences, Universidad del Rosario, Bogota 111221, Colombia.
Research Group in Applied Biomedical Sciences (UR Biomed), School of Medicine and Health Sciences, Universidad del Rosario, Bogota 111221, Colombia.
Int J Mol Sci. 2025 Jun 1;26(11):5338. doi: 10.3390/ijms26115338.
Glucagon-like peptide-1 receptor agonists, originally developed for the treatment of metabolic disorders, have recently emerged as promising candidates for the management of substance use disorders. This review synthesizes preclinical, clinical, and translational evidence on the effects of glucagon-like peptide-1 receptor agonists across addiction models involving alcohol, nicotine, psychostimulants, and opioids. In animal studies, glucagon-like peptide-1 receptor agonists consistently reduce drug intake, attenuate dopamine release in reward circuits, and decrease relapse-like behavior. Clinical and observational studies provide preliminary support for these findings, particularly among individuals with comorbid obesity or insulin resistance. However, several translational barriers remain, including limited blood-brain barrier penetration, species differences in pharmacokinetics, and variability in treatment response due to genetic and metabolic factors. Ethical considerations and methodological heterogeneity further complicate clinical translation. Future directions include the development of central nervous system penetrant analogues, personalized medicine approaches incorporating pharmacogenomics, and rigorously designed trials in diverse populations. Glucagon-like peptide-1 receptor agonists may offer a novel therapeutic strategy that addresses both metabolic and neuropsychiatric dimensions of addiction, warranting further investigation to define their role in the evolving landscape of substance use disorder treatment.
胰高血糖素样肽-1受体激动剂最初是为治疗代谢紊乱而开发的，最近已成为治疗物质使用障碍的有前景的候选药物。这篇综述综合了关于胰高血糖素样肽-1受体激动剂在涉及酒精、尼古丁、精神兴奋剂和阿片类药物的成瘾模型中的作用的临床前、临床和转化证据。在动物研究中，胰高血糖素样肽-1受体激动剂持续减少药物摄入，减弱奖赏回路中的多巴胺释放，并减少复发样行为。临床和观察性研究为这些发现提供了初步支持，特别是在患有合并肥胖或胰岛素抵抗的个体中。然而，仍然存在一些转化障碍，包括血脑屏障穿透有限、药代动力学的物种差异以及由于遗传和代谢因素导致的治疗反应变异性。伦理考量和方法学异质性进一步使临床转化复杂化。未来的方向包括开发可穿透中枢神经系统的类似物、纳入药物基因组学的个性化医疗方法，以及在不同人群中进行严格设计的试验。胰高血糖素样肽-1受体激动剂可能提供一种新颖的治疗策略，可解决成瘾的代谢和神经精神层面问题，值得进一步研究以确定它们在不断发展的物质使用障碍治疗格局中的作用。
