How toxic is ibogaine?

@article{Litjens2016HowTI,
  title={How toxic is ibogaine?},
  author={Ruud P W Litjens and Tibor Markus Brunt},
  journal={Clinical Toxicology},
  year={2016},
  volume={54},
  pages={297 - 302}
}
CONTEXT Ibogaine is a psychoactive indole alkaloid found in the African rainforest shrub Tabernanthe Iboga. [...] Key Method The search criteria were "mechanism of action", "pharmacokinetics", "pharmacodynamics", "neurotransmitters", "toxicology", "toxicity", "cardiac", "neurotoxic", "human data", "animal data", "addiction", "anti-addictive", "withdrawal", "death" and "fatalities". The searches identified 382 unique references, of which 156 involved human data. Further research revealed 14 detailed…Expand

Paper Mentions

Ibogaine as a treatment for substance misuse: Potential benefits and practical dangers.
TLDR
There is a need to develop better opiate detoxification treatment against a background of increasing opioid-related fatalities, and a congener of ibogaine, 18-MC, appears to be safer and is to undergo clinical trials.
The antiaddictive effects of ibogaine: A systematic literature review of human studies
Background and aimsIbogaine is a naturally occurring hallucinogenic alkaloid with a therapeutic potential for reducing drug craving and withdrawal. To the best of our knowledge, no systematic review
On the toxicity of ibogaine
TLDR
The totality of animal and human data suggests neurodegeneration does not occur with ‘‘therapeutic’’ ibogaine dosing, and serious adverse events during therapeutic use may be mitigated by pretreatment screening to include a careful medical history, careful medication history, blood chemistries, and ECG prior to enrolment into a proper treatment protocol.
Safety of ibogaine administration in detoxification of opioid dependent individuals: a descriptive open-label observational study.
TLDR
An open-label observation study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia.
Morphing of Ibogaine: A Successful Attempt into the Search for Sigma-2 Receptor Ligands
TLDR
A deconstruction study on the ibogaine tricyclic moiety and a successive scaffold-hopping of the indole counterpart are reported to facilitate the investigation of iboga alkaloid derivatives which may serve as templates for the design of selective σ2 receptor ligands.
Phytochemical characterization of Tabernanthe iboga root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice.
TLDR
The potential alleviating effects of the water extract of iboga root bark on high-fat diet (HFD)-induced hyperglycemia as well as its effects on cognitive function in male C57BL/6J mice were determined.
In reply – on the toxicity of ibogaine
TLDR
It is agreed that neurotoxicity is most likely not to occur at doses reported in therapeutic treatments, but questions their suggestion that some of the doses used in therapy could be considered ‘‘safe’’, like in Mash et al.
Ibogaine Consumption With Seizure-Like Episodes, QTc-Prolongation, and Captured Cardiac Dysrhythmias.
TLDR
A 34-year-old white woman with medical history significant for heroin and cocaine use disorder presented with reported seizures 1 day after ingestion of 2 g ibogaine powder purchased from an Internet supplier, and qualitative analysis confirmed the presence of ibogane in the empty foil packages containing the ingested substance.
Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report
TLDR
It is not clear if ibogaine at low doses could be used therapeutically in people on methadone maintenance treatments (MMT), but a case report of a female on MMT for 17 years who performed a self-treatment with several low and cumulative doses of ibogance over a 6-week period successfully eliminated her withdrawal symptoms.
Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine
TLDR
After (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due to its metabolite, and demonstrate a linear relationship between the concentration of the metabolite and long duration of action.
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References

SHOWING 1-10 OF 54 REFERENCES
Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures
TLDR
It is reported here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification and for short‐term stabilization of drug‐dependent persons as they prepare to enter substance abuse treatment.
Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review
TLDR
The purpose of this article was to review data from the literature concerning physicochemical properties, bio-analytical methods, and pharmacology of ibogaine; this article will be focused on the use of this drug as anti-addictive agent.
Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine.
TLDR
Ibogaine and noribogaine are equipotent in their ability to evoke a transient stimulation of dopamine metabolism that is characterized by profound depletion of tissue DA in mesolimbic, mesocortical, and mesostriatal terminal projection areas.
Fatalities Temporally Associated with the Ingestion of Ibogaine
TLDR
Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical and nonmedical settings for opioid detoxification and other substance use indications and the clinical and postmortem evidence did not suggest a characteristic syndrome of neurotoxicity.
Mechanisms of Antiaddictive Actions of Ibogaine a
TLDR
The authors' ongoing studies in rats suggest that kappa agonist and NMDA antagonist actions contribute to ibogaine's effects on opioid and stimulant self‐administration, while the serotonergic actions may be more important for ibogane‐induced decreases in alcohol intake.
Life-threatening complications of ibogaine: three case reports.
TLDR
It is of great importance that clinicians are aware of these potentially serious side effects and realise that widespread online marketing practices will give many more people access to ibogaine.
Ibogaine related sudden death: a case report.
TLDR
The case of a man who died suddenly 12-24 h after ibogaine use for alcohol detoxification treatment is reported, and the potential risks of ibogane use, especially for persons with pathological medical background, are discussed.
Medication development of ibogaine as a pharmacotherapy for drug dependence.
TLDR
A rising tolerance study using single administration of ibogaine for treatment of cocaine dependency is initiated to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients.
Ibogaine: a review.
  • K. Alper
  • Sociology, Medicine
    The Alkaloids. Chemistry and biology
  • 2001
TLDR
A timeline is presented that outlines the historical events relating to the development of ibogaine as a treatment for drug dependence and has been shown to bind to the serotonin transporter and to increase serotonin levels in the nucleus accumbens (NAc).
Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the Tabernanthe iboga shrub.
TLDR
The tissue distribution of ibogaine and noribogaine, the main metabolite of ibogsaine, in a 48-year-old Caucasian male found dead at his home after a poisoning involving the ingestion of root bark from the shrub Tabernanthe iboga is reported.
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