Pulido-Saavedra Alejandra, Oliva Henrique Nunes Pereira, Prudente Tiago Paiva, Kitaneh Razi, Nunes Eric J, Fogg Colleen, Funaro Melissa C, Weleff Jeremy, Nia Anahita Bassir, Angarita Gustavo A
Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT, 06511, USA.
Clinical Neuroscience Research Unit, Connecticut Mental Health Center, Room 359, 34 Park Street, New Haven, CT, 06519, USA.
Cell Mol Life Sci. 2025 Jan 21;82(1):49. doi: 10.1007/s00018-024-05519-2.
The current opioid crisis has had an unprecedented public health impact. Approved medications for opioid use disorder (OUD) exist, yet their limitations indicate a need for innovative treatments. Limited preliminary clinical studies suggest specific psychedelics might aid OUD treatment, though most clinical evidence remains observational, with few controlled trials. This review aims to bridge the gap between preclinical findings and potential clinical applications, following PRISMA-ScR guidelines. Searches included MEDLINE, Embase, Scopus, and Web of Science, focusing on preclinical in vivo studies involving opioids and psychedelics in animals, excluding pain studies and those lacking control groups. Forty studies met criteria, covering both classic and non-classic psychedelics. Most studies showed that 18-methoxycoronaridine (18-MC), ibogaine, noribogaine, and ketamine could reduce opioid self-administration, alleviate withdrawal symptoms, and change conditioned place preference. However, seven studies (two on 2,5-dimethoxy-4-methylamphetamine (DOM), three on ibogaine, one on 18-MC, and one on ketamine) showed no improvement over controls. A methodological quality assessment rated most of the studies as having unclear quality. Interestingly, most preclinical studies are limited to iboga derivatives, which were effective, but these agents may have higher cardiovascular risk than other psychedelics under-explored to date. This review strengthens support for translational studies testing psychedelics as potential innovative targets for OUD. It also suggests clinical studies need to include a broader range of agents beyond iboga derivatives but can also explore several ongoing questions in the field, such as the mechanism of action behind the potential therapeutic effect, safety profiles, doses, and frequency of administrations needed.
当前的阿片类药物危机已产生了前所未有的公共卫生影响。虽然存在已获批用于治疗阿片类药物使用障碍（OUD）的药物，但其局限性表明需要创新疗法。有限的初步临床研究表明特定的致幻剂可能有助于OUD治疗，不过大多数临床证据仍为观察性的，对照试验很少。本综述旨在遵循PRISMA-ScR指南弥合临床前研究结果与潜在临床应用之间的差距。检索范围包括MEDLINE、Embase、Scopus和Web of Science，重点关注涉及动物体内阿片类药物和致幻剂的临床前体内研究，不包括疼痛研究和缺乏对照组的研究。40项研究符合标准，涵盖经典和非经典致幻剂。大多数研究表明，18-甲氧基冠狗牙花定碱（18-MC）、伊博格碱、去甲伊博格碱和氯胺酮可减少阿片类药物的自我给药、减轻戒断症状并改变条件性位置偏爱。然而，7项研究（2项关于2,5-二甲氧基-4-甲基苯丙胺（DOM）、3项关于伊博格碱、1项关于18-MC和1项关于氯胺酮）显示与对照组相比无改善。方法学质量评估将大多数研究评定为质量不明确。有趣的是，大多数临床前研究仅限于伊博格衍生物，这些衍生物是有效的，但这些药物可能比迄今研究较少的其他致幻剂具有更高的心血管风险。本综述加强了对将致幻剂作为OUD潜在创新靶点进行转化研究的支持。它还表明临床研究需要纳入除伊博格衍生物之外更广泛的药物，同时也可探索该领域一些悬而未决的问题，如潜在治疗效果背后的作用机制、安全性概况、所需剂量和给药频率等。
