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

The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020)

This review (s=18) did a qualitative analysis of studies with ibogaine and describes the acute adverse events (cardiac, gastrointestinal, neurological) and long-lasting effects (persistent cardiac, psychiatric, neurological). The authors note that phase I studies with standardized products are necessary as the products quantity and mix was widely varied.

Authors

  • Jamie Hallak
  • Rafael dos Santos
  • Gonzalo Ona

Published

Psychopharmacology
meta Study

Abstract

Context

Ibogaine is the main alkaloid of the African shrub Tabernanthe iboga. It produces hallucinogenic and psychostimulant effects, but it is currently known for the anti-addictive properties. Despite the potential therapeutic effects, several cases of fatalities and serious adverse events related to ibogaine/noribogaine use can be found in the literature. Most studies consist in case reports or were conducted under non-controlled settings, so causation cannot be clearly established.

Objectives

To update (2015-2020) the literature on the adverse events and fatalities associated with ibogaine/noribogaine administration.

Methods

Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results

Eighteen studies were included in the final selection. Highly heterogeneous results were found in terms of kind of product used or the known dosages. The adverse events were classified in acute effects (< 24 h), mainly cardiac (the most common was QTc prolongation), gastrointestinal, neurological, and clinical alterations, and long-lasting effects (> 24 h), mainly persistent cardiac alterations, psychiatric, and neurological signs.

Conclusions

There is a high need of phase I clinical trials that can describe the safety of different dosages of ibogaine with standardized products. Further research should perform clinical profiling of vulnerable populations, and design effective screening methods and clinical procedures.

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Research Summary of 'The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020)'

Introduction

Ona and colleagues situate ibogaine as the principal alkaloid of Tabernanthe iboga, historically used in West Central African rituals and later explored for stimulant and anti-addictive properties. Preclinical studies have shown dose- and route-dependent reductions in opioid self-administration in animals, but human evidence remains limited and largely observational. Prior systematic reviews documented multiple fatalities and serious adverse events associated with ibogaine/noribogaine, frequently occurring in uncontrolled settings and often involving co‑existing medical conditions, electrolyte disturbances, or concomitant drugs. Cardiotoxicity, notably QTc prolongation with risk of arrhythmia, has been a central safety concern highlighted in earlier work, and pharmacokinetic factors such as CYP2D6 metabolism and the longer half-life of noribogaine have been proposed as contributors to delayed adverse events. This paper aims to update the literature on adverse events and fatalities associated with ibogaine and noribogaine between July 2015 and July 2020. The investigators set out to identify human studies reporting adverse events, serious adverse events (SAEs), deaths, and potential drug–drug interactions, with particular attention to cases combining ibogaine with other substances. The review emphasises the need to characterise safety profiles across dosages and contexts given renewed interest in ibogaine for substance use disorders.

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Study Details

References (15)

Papers cited by this study that are also in Blossom

Ibogaine: a review

Alper, K. · The Alkaloids Chemistry and Biology (2001)

146 cited
The ibogaine medical subculture

Alper, K. R., Lotsof, H. S., Kaplan, C. D. · Journal of Ethnopharmacology (2007)

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Brown, T. K. · Current Drug Abuse Reviews (2013)

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Brown, T. K., Alper, K. · The American Journal of Drug and Alcohol Abuse (2017)

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Dos Santos, R. G., Bouso, J. C., Hallak, J. E. · Journal of Psychedelic Studies (2016)

Ascending single-dose, double-blind, placebo-controlled safety study of noribogaine in opioid-dependent patients

Glue, P., Cape, G., Tunnicliff, D. et al. · Clinical Pharmacology in Drug Development (2016)

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Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers

Glue, P., Lenagh-Glue, Z., Winter, H. et al. · Journal of Clinical Pharmacology (2015)

Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid Dependence

Knuijver, T., Belgers, M., Markus, W. et al. · Journal of Clinical Psychopharmacology (2018)

8 cited
Show all 15 references
The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation

Koenig, X., Hilber, K. · Journal of Humanistic Psychology (2015)

Mania following use of ibogaine: A case series

Marta, C. J., Ryan, W. C., Kopelowicz, A. et al. · The American Journal on Addictions (2015)

Cardiac arrest after ibogaine intoxication

Steinberg, C., Deyell, M. W. · Journal of Arrhythmia (2018)

10 cited
Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report

Wilkins, C., Dos Santos, R. G., Solá, J. et al. · Journal of Psychedelic Studies (2017)

12 cited

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