What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders.

Ibogaine, the main psychoactive alkaloid in Tabernanthe iboga, has been studied for decades as a possible treatment for substance use disorders because it may interrupt addiction to multiple drugs. Its inhibition of α3β4 nicotinic acetylcholine receptors in the brain is a likely mechanism for this anti-addictive effect. This perspective examines several classes of compounds developed to target α3β4 nAChRs, focusing on those effective in pre-clinical models of drug abuse and evaluated clinically. It highlights the promising potential of α3β4 nAChRs as viable targets for treating a wide array of substance use disorders and discusses challenges that must be overcome to develop these ligands into therapeutic treatments.

Study at a glance

Abstract

For decades, ibogaine─the main psychoactive alkaloid found in Tabernanthe iboga─has been investigated as a possible treatment for substance use disorders (SUDs) due to its purported ability to interrupt the addictive properties of multiple drugs of abuse. Of the numerous pharmacological actions of ibogaine and its derivatives, the inhibition of α3β4 nicotinic acetylcholine receptors (nAChRs), represents a probable mechanism of action for their apparent anti-addictive activity. In this Perspective, we examine several classes of compounds that have been discovered and developed to target α3β4 nAChRs. Specifically, by focusing on compounds that have proven efficacious in pre-clinical models of drug abuse and have been evaluated clinically, we highlight the promising potential of the α3β4 nAChRs as viable targets to treat a wide array of SUDs. Additionally, we discuss the challenges faced by the existing classes of α3β4 nAChR ligands that must be overcome to develop them into therapeutic treatments.