Main targets of ibogaine and noribogaine associated with its putative anti-addictive effects: A mechanistic overview

Abstract

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: IBO displays complex effects through multiple targets. The information detailed here should guide future research on both mechanistic and therapeutic studies.

Predicting the Hallucinogenic Potential of Molecules Using Artificial Intelligence

“…2,3 Psychedelics can display polypharmacology such as ibogaine which is known to interact with numerous targets (opioid receptors, dopamine transporter, serotonin transporter, glutamate receptors, nicotinic receptors and neurotrophic factors). 4 Activation of the 5-HT 2A receptor is known to facilitate the downstream release of brain-derived neurotrophic factor (BDNF) as well as cause profound changes in the default-model network (DMN), and it is through these two downstream effects that psychedelics are proposed to offer their therapeutic value. 5 Changes in restingstate functional connectivity (RSFC) in the DMN have been found in patients with depression taking psilocybin, and these changes have been shown to be predictive of treatment response.…”

“…Common psychedelics include lysergic acid diethylamine (LSD), the prodrug psilocybin and the active metabolite psilocin, as well as N,N -dimethyltryptamine (DMT). Many psychedelics are thought to act as agonists of serotonin 5-HT 2A , as well as other 5-HT receptors along with dopaminergic and glutamatergic systems, where they can induce long-term changes in neuronal structures. , Psychedelics can display polypharmacology such as ibogaine which is known to interact with numerous targets (opioid receptors, dopamine transporter, serotonin transporter, glutamate receptors, nicotinic receptors and neurotrophic factors) . Activation of the 5-HT 2A receptor is known to facilitate the downstream release of brain-derived neurotrophic factor (BDNF) as well as cause profound changes in the default-model network (DMN), and it is through these two downstream effects that psychedelics are proposed to offer their therapeutic value .…”