Main targets of ibogaine and noribogaine associated with its putative anti-addictive effects: A mechanistic overview.
Journal of psychopharmacology (Oxford, England) – December 01, 2023
Source: PubMed
Summary
Unlocking the mystery of how a single substance can combat addiction, a review highlights that the psychedelic Iboga derivative, ibogaine, and its metabolite noribogaine, don't just hit one target. Instead, this hallucinogen exerts its anti-addictive effects by complexly modulating multiple brain systems, creating beneficial synergies. This comprehensive analysis suggests ibogaine's potential for substance use disorders lies in its multifaceted action, offering a promising path for therapy.
Abstract
There is a growing interest in studying ibogaine (IBO) as a potential treatment for substance use disorders (SUDs). However, its clinical use has been hindered for mainly two reasons: First, the lack of randomized, controlled studies informing about its safety and efficacy. And second, IBO's mechanisms of action remain obscure. It has been challenging to elucidate a predominant mechanism of action responsible for its anti-addictive effects. To describe the main targets of IBO and its main metabolite, noribogaine (NOR), in relation to their putative anti-addictive effects, reviewing the updated literature available. A comprehensive search involving MEDLINE and Google Scholar was undertaken, selecting papers published until July 2022. The inclusion criteria were both theoretical and experimental studies about the pharmacology of IBO. Additional publications were identified in the references of the initial papers. IBO and its main metabolite, NOR, can modulate several targets associated with SUDs. Instead of identifying key targets, the action of IBO should be understood as a complex modulation of multiple receptor systems, leading to potential synergies. The elucidation of IBO's pharmacology could be enhanced through the application of methodologies rooted in the polypharmacology paradigm. Such approaches possess the capability to describe multifaceted patterns within multi-target drugs. IBO displays complex effects through multiple targets. The information detailed here should guide future research on both mechanistic and therapeutic studies.