Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine’s putative anti-addictive activity

Introduction

Indolealkylamines include centrally active compounds that can produce stimulant and anxiogenic effects. One such derivative, ibogaine, has been reported to reduce behaviours related to opiate, stimulant and alcohol dependence in animal and some human observations. Previous animal studies found that ibogaine decreased morphine self-administration, attenuated morphine- and cocaine-induced dopamine turnover, reduced morphine-induced motor activity, and antagonised cocaine-induced locomotion. These findings pointed to several neurotransmitter systems — bioaminergic (dopamine/serotonin), peptidergic (opioid), and amino acidergic (GABA) — as candidate molecular targets, but no single, clearly defined mechanism has been established that would explain ibogaine’s putative anti-addictive effects. This study set out to characterise ibogaine’s in vitro pharmacological profile across a broad panel of targets. Using over 50 radioligand binding assays, the investigators aimed to identify receptor, transporter, and ion‑channel interactions and to assess potency where activity was detected. The goal was to determine whether ibogaine acts selectively at one target or interacts with multiple sites at concentrations plausibly achieved in brain, thereby informing hypotheses about its mechanisms in addiction models and guiding subsequent medicinal chemistry efforts.