Safety of ibogaine administration in detoxification of opioid dependent individuals: a descriptive open-label observational study
This open‑label study (n=14) of opioid‑dependent patients given a single 700 mg per 70kg dose of ibogaine‑HCl, treatment produced clinically relevant but reversible cardiac and cerebellar toxicity. The mean maximal QTc(F) prolongation was 95 ms, with 50% of participants exceeding 500 ms, accompanied by bradycardia and severe transient ataxia. Psychomimetic and withdrawal effects were generally manageable, and no torsades de pointes were observed.
Authors
- Robbert-Jan Verkes
- Arnt Schellekens
Published
Abstract
Background and aims
Ibogaine is an indole alkaloid used in rituals of the African Bwiti tribe. It is also used in non‐medical settings to treat addiction. However, ibogaine has been linked to several deaths, mainly due to cardiac events called torsades de pointes preceded by QTc prolongation, as well as other safety concerns. This study aimed to evaluate the cardiac, cerebellar, and psychomimetic safety of ibogaine in patients with opioid use disorder.
Design
A descriptive open‐label observational study.
Setting
Department of psychiatry in a university medical center, the Netherlands.
Participants
Patients with opioid use disorder (n = 14) on opioid maintenance treatment with a lasting wish for abstinence, who failed to reach abstinence with standard care.
Intervention and measurements
After conversion to morphine‐sulphate, a single dose of ibogaine‐HCl 10 mg/kg was administered, and patients were monitored at regular intervals for at least 24 hours, assessing QTc, blood pressure, and heart rate, scale for the assessment and rating of ataxia (SARA) to assess cerebellar side effects, and the delirium observation scale (DOS) to assess psychomimetic effects.
Findings
The maximum QTc (Fridericia) prolongation was on average 95ms (range 29‐146ms). Fifty percent of subjects reached a QTc of over 500ms during the observation period. In six out of 14 subjects, prolongation above 450ms lasted beyond 24 hours after ingestion of ibogaine. No torsades de pointes were observed. Severe transient ataxia with inability to walk without support was seen in all patients. Withdrawal and psychomimetic effects were mostly well‐tolerated and manageable (11/14 did not return to morphine within 24 hours, DOS scores remained below threshold).
Conclusions
This open‐label observational study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia.
Research Summary of 'Safety of ibogaine administration in detoxification of opioid dependent individuals: a descriptive open-label observational study'
Blossom's Take
This Dutch study of ibogaine shows generally manageable risks for those undergoing acute opioid withdrawal (eight days of substitution treatment). In eight of the 14 participants, magnesium was used to help combat heart rate interval (QTc) lengthening (prolongation). The study focused on safety and made limited claims about efficacy (also because it included only 14 participants).
Introduction
Knuijver and colleagues situate ibogaine as the principal indole alkaloid of Tabernanthe iboga rootbark, traditionally used as an entheogen and increasingly used outside medical settings to treat substance use disorders. Earlier clinical case series and small observational studies suggest ibogaine can reduce withdrawal, craving and drug self-administration in humans and animals, but safety concerns have been repeatedly raised. In vitro and clinical reports implicate inhibition of hERG potassium channels, QT interval prolongation on the electrocardiogram and risk of torsades de pointes (TdP). Additional concerns include transient cerebellar ataxia observed in animals and limited human reports, as well as anecdotal accounts of seizures, mania and persistent perceptual disturbances. The study aimed to evaluate the clinical safety of a single administration of ibogaine-HCl in patients with opioid use disorder (OUD) who were receiving opioid substitution therapy (OST) and seeking detoxification. Specifically, the investigators tested the hypotheses that ibogaine produces reversible QTc prolongation, induces cerebellar ataxia, and causes psychomimetic behavioural effects. The team also collected limited observations of opioid withdrawal to assess potential short-term benefit and durability.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
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- APA Citation
Knuijver, T., Schellekens, A., Belgers, M., Donders, R., van Oosteren, T., Kramers, K., & Verkes, R. (2022). Safety of ibogaine administration in detoxification of opioid‐dependent individuals: a descriptive open‐label observational study. Addiction, 117(1), 118-128.
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References (12)
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Marta, C. J., Ryan, W. C., Kopelowicz, A. et al. · The American Journal on Addictions (2015)
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Brown, T. K., Alper, K. · The American Journal of Drug and Alcohol Abuse (2017)
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Frampton, C. M., Yazar-Klosinski, B., Nollar, G. E. · The American Journal of Drug and Alcohol Abuse (2017)
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Mash, D. C. · Pharmacological Research (2023)
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