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国际药理学联合会(IUPHAR)特邀综述——伊博格碱——当前迷幻疗法复兴中的一个遗产。

IUPHAR - invited review - Ibogaine - A legacy within the current renaissance of psychedelic therapy.

作者信息

Mash Deborah C

机构信息

Professor Emerita University of Miami Miller School of Medicine, Depts. Neurology and Molecular and Cellular Pharmacology.

出版信息

Pharmacol Res. 2023 Apr;190:106620. doi: 10.1016/j.phrs.2022.106620. Epub 2023 Mar 11.

Abstract

Ibogaine is a powerful psychoactive substance that not only alters perception, mood and affect, but also stops addictive behaviors. Ibogaine has a very long history of ethnobotanical use in low doses to combat fatigue, hunger and thirst and, in high doses as a sacrament in African ritual contexts. In the 1960's, American and European self-help groups provided public testimonials that a single dose of ibogaine alleviated drug craving, opioid withdrawal symptoms, and prevented relapse for weeks, months and sometimes years. Ibogaine is rapidly demethylated by first-pass metabolism to a long-acting metabolite noribogaine. Ibogaine and its metabolite interact with two or more CNS targets simultaneously and both drugs have demonstrated predictive validity in animal models of addiction. Online forums endorse the benefits of ibogaine as an "addiction interrupter" and present-day estimates suggest that more than ten thousand people have sought treatment in countries where the drug is unregulated. Open label pilot studies of ibogaine-assisted drug detoxification have shown positive benefit in treating addiction. Ibogaine, granted regulatory approval for human testing in a Phase 1/2a clinical trial, joins the current landscape of psychedelic medicines in clinical development.

摘要

伊博格碱是一种强效精神活性物质,它不仅会改变感知、情绪和情感,还能阻止成瘾行为。伊博格碱在民族植物学中的使用历史悠久,低剂量时用于对抗疲劳、饥饿和口渴,高剂量时在非洲仪式场合用作圣礼。在20世纪60年代,美国和欧洲的自助团体提供公开证词称,单剂量的伊博格碱能缓解药物渴望、阿片类药物戒断症状,并在数周、数月甚至有时数年的时间里预防复吸。伊博格碱通过首过代谢迅速去甲基化,生成一种长效代谢物去甲伊博格碱。伊博格碱及其代谢物同时与两个或更多中枢神经系统靶点相互作用,这两种药物在成瘾动物模型中均已证明具有预测有效性。在线论坛认可伊博格碱作为“成瘾阻断剂”的益处,目前的估计表明,在该药物不受监管的国家,超过一万人寻求过治疗。伊博格碱辅助药物排毒的开放标签试点研究已显示出在治疗成瘾方面的积极效果。伊博格碱在1/2a期临床试验中获得了人体试验的监管批准,加入了目前正在临床开发的迷幻药物行列。

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