Substance Use Disorders (SUD)Safety & Risk ManagementMedicinal Chemistry & Drug DevelopmentIbogaine

Ibogaine: a review

This book chapter (2001) reviews the topics of the First International Conference on Ibogaine, and reviews the chemical structure of ibogaine, its biological mechanisms of action, effects in humans and animal models, pharmacokinetics, and safety profile, etc. Case reports in humans and effects in preclinical models of drug dependence suggest the iboga alkaloids may have efficacy in addiction on the basis of mechanisms that are not yet known and which can possibly be dissociated from toxic effects and may present significant promise as a paradigm for the study and development of pharmacotherapy for addiction.

Authors

  • Alper, K.

Published

The Alkaloids Chemistry and Biology
meta Study

Abstract

The chapter discusses ibogaine, which is a naturally occurring plant alkaloid with a history of use as a medicinal and ceremonial agent in West Central Africa and has been alleged to be effective in the treatment of drug abuse. The National Institute on Drug Abuse (NIDA) has given significant support to animal research, and the U.S. Food and Drug Administration (FDA) has approved Phase I studies in humans. The chapter discusses the first International Conference on Ibogaine. A major focus of the Conference was the possible mechanism(s) of action of ibogaine. Another important focus of the Conference was to discuss human experience with ibogaine and preclinical and clinical evidence of efficacy and safety. The Conference also featured presentations related to the sociological and anthropological aspects of the sacramental context of the use of iboga in Africa and the distinctive ibogaine subculture of the U.S and Europe. Ibogaine is the most abundant alkaloid in the root bark of the Apocynaceous shrub Tabernanthe iboga, which grows in West Central Africa. The chapter presents a timeline that outlines the historical events relating to the development of ibogaine as a treatment for drug dependence. Ibogaine and serotonin both contain an indole ring in their structure, and ibogaine has been shown to bind to the serotonin transporter and to increase serotonin levels in the nucleus accumbens (NAc). Stereotypy is a methodologic issue that might explain some of the disparate results regarding ibogaine's interaction with the locomotor response to cocaine.

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Research Summary of 'Ibogaine: a review'

Introduction

Ibogaine is a naturally occurring indole alkaloid derived from the root bark of Tabernanthe iboga with a long ethnomedical and ceremonial history in West Central Africa and a contemporary reputation for reducing opioid and stimulant dependence. Earlier animal studies suggested reductions in drug self-administration and attenuation of withdrawal, and a small but persistent body of human case reports described rapid relief of opioid withdrawal and, in some patients, reduced craving or extended abstinence. Interest has been limited by regulatory restrictions, the inability to patent the natural product, safety concerns (notably reported cerebellar toxicity in rodents), and mixed or preliminary clinical data. This review sets out to summarise the chemistry, pharmacology, preclinical efficacy and safety data, and the available human experience with ibogaine and related iboga alkaloids, with attention to mechanisms of action (including noribogaine, the principal O‑desmethyl metabolite), neurotoxicology, and socio-political issues that have shaped research and access. The authors frame ibogaine as a pharmacological prototype that may uncover novel targets or inspire congeners (for example 18‑methoxycoronaridine, 18‑MC) that retain putative antiaddictive properties with less toxicity, and they call for rigorous controlled clinical trials to resolve efficacy and safety uncertainties.

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