How toxic is ibogaine?
Ruud P. W. Litjens, Tibor M Brunt
Clinical Toxicology 2016 DOI: 10.3109/15563650.2016.1138226 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ibogaine |
| Keywords | Cardiotoxicity Crucial Risks Medical supervision Pre-existing conditions Drug interactions Ibogaine toxicity neurotoxicity Adverse effects Disrupting heart rhythms Arrhythmias Ibogaine mortality fatalities Sudden deaths Linked |
| Citations | 74 |
| Key findings | Ibogaine and its metabolite noribogaine can cause neurotoxicity in rats and cardiotoxicity in humans, including fatal arrhythmias, even in individuals without pre-existing heart conditions. |
Abstract
Ibogaine is a psychoactive indole alkaloid found in the African rainforest shrub Tabernanthe Iboga. It is unlicensed but used in the treatment of drug and alcohol addiction. However, reports of ibogaine's toxicity are cause for concern. To review ibogaine's pharmacokinetics and pharmacodynamics, mechanisms of action and reported toxicity. A search of the literature available on PubMed was done, using the keywords "ibogaine" and "noribogaine". 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 toxicological case reports. PHARMACOKINETICS AND PHARMACODYNAMICS: Ibogaine is metabolized mainly by CYP2D6 to the primary metabolite noribogaine (10-hydroxyibogamine). Noribogaine is present in clinically relevant concentrations for days, long after ibogaine has been cleared. Ibogaine and noribogaine interact with multiple neurotransmitter systems. They show micromolar affinity for N-methyl-D-aspartate (NMDA), κ- and μ-opioid receptors and sigma-2 receptor sites. Furthermore, ibogaine has been shown to interact with the acetylcholine, serotonin and dopamine systems; it alters the expression of several proteins including substance P, brain-derived neurotrophic factor (BDNF), c-fos and egr-1. NEUROTOXICITY: Neurodegeneration was shown in rats, probably mediated by stimulation of the inferior olive, which has excitotoxic effects on Purkinje cells in the cerebellum. Neurotoxic effects of ibogaine may not be directly relevant to its anti-addictive properties, as no signs of neurotoxicity were found following doses lower than 25 mg/kg intra-peritoneal in rats. Noribogaine might be less neurotoxic than ibogaine. CARDIOTOXICITY: Ether-a-go-go-related gene (hERG) potassium channels in the heart might play a crucial role in ibogaine's cardiotoxicity, as hERG channels are vital in the repolarization phase of cardiac action potentials and blockade by ibogaine delays this repolarization, resulting in QT (time interval between the start of the Q wave and the end of the T wave in the electrical cycle of the heart) interval prolongation and, subsequently, in arrhythmias and sudden cardiac arrest. Twenty-seven fatalities have been reported following the ingestion of ibogaine, and pre-existing cardiovascular conditions have been implicated in the death of individuals for which post-mortem data were available. However, in this review, 8 case reports are presented which suggest that ibogaine caused ventricular tachyarrhythmias and prolongation of the QT interval in individuals without any pre-existing cardiovascular condition or family history. Noribogaine appears at least as harmful to cardiac functioning as ibogaine. TOXICITY FROM DRUG-DRUG INTERACTION: Polymorphism in the CYP2D6 enzyme can influence blood concentrations of both ibogaine and its primary metabolite, which may have implications when a patient is taking other medication that is subject to significant CYP2D6 metabolism. Alternative therapists and drug users are still using iboga extract, root scrapings, and ibogaine hydrochloride to treat drug addiction. With limited medical supervision, these are risky experiments and more ibogaine-related deaths are likely to occur, particularly in those with pre-existing cardiac conditions and those taking concurrent medications.
Comparable studies
Other narrative reviews on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca. | 2014 | Review | |
| The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation Humans, animals | 2015 | Review | |
| Ibogaine in the treatment of substance dependence. | 2013 | Review | |
| Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. | 2008 | Review | |
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
Citations in the library
Cited by 54
- A systematic literature review of clinical trials and therapeutic applications of ibogaine. Journal of Substance Abuse Treatment July 1, 2022
- Magnesium-ibogaine therapy in veterans with traumatic brain injuries. Nature Medicine February 1, 2024
- Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine. Journal of Psychoactive Drugs 2018
- Ibogaine as a treatment for substance misuse: Potential benefits and practical dangers. Progress in Brain Research 2018
- Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study. Addiction 2022
and 49 more in the library
Cites 31
- Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience July 1, 1993
- Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Brain Research September 19, 1994
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Journal of Neuroscience January 19, 2005
- The Olivocerebellar Projection Mediates Ibogaine-Induced Degeneration of Purkinje Cells: A Model of Indirect, Trans-Synaptic Excitotoxicity Journal of Neuroscience November 15, 1997
and 26 more in the library