Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: A Systematic Review of the Current Literature

About this resource

This page closely follows the systematic review published by Mosca and colleagues in 2023. The review covered human studies of ibogaine or its principal metabolite, noribogaine, in relation to substance use disorders, craving, abstinence, withdrawal, and detoxification. The authors aimed to organize the existing clinical evidence on addiction-related outcomes and quantitatively examine adverse effects.

What is presented here consists of observations reported in research papers and the authors’ interpretations of them. “Improvement was reported” is not the same as “a treatment effect was established in a controlled trial.” Most included studies were case reports, case series, or observational studies; only two were comparable double-blind, placebo-controlled studies. This review does not provide guidance on self-administration, dose selection, or withdrawal management.

Study design

Following PRISMA 2020, the authors searched PubMed, Scopus, and Web of Science on November 29, 2021. The search combined terms for ibogaine/noribogaine with terms related to substance use disorders, craving, abstinence, withdrawal, dependence, and detoxification, while excluding animal studies, reviews, and in vitro research. The protocol was registered in PROSPERO as CRD42021287034.

The search yielded 310 records (56 from PubMed, 102 from Scopus, 149 from Web of Science, and 3 from other sources). After removing 98 duplicates, 212 records underwent title and abstract screening. The authors excluded 119 records as off-topic, 6 because they were not in English, and 45 because they were not original research, leaving 42 full-text articles for assessment. Six did not meet the criteria and five full texts could not be obtained; 31 studies were ultimately included. Two reviewers extracted data independently, with questions discussed among several senior investigators.

The six exclusion criteria were: not original research, not a full-length article, not in English, an animal or in vitro study, not involving ibogaine/noribogaine, or not addressing treatment of substance use disorders. The Cochrane risk-of-bias tool was used only for double-blind randomized controlled trials.

The adverse-effect meta-analysis used Review Manager 5.4. Because double-blind trials were scarce and zero-event outcomes occurred, the authors used risk difference rather than risk ratio. They applied a fixed-effect model, 95% confidence intervals, and I² to assess heterogeneity, with statistical significance set at p < 0.05. The quantitative analysis therefore did not pool all 31 studies; it was based only on the two studies that were sufficiently comparable.

Content

Background and framing of mechanisms

The original article begins with the history of iboga use in the religious traditions of West and Central Africa. Pharmaceutical research generally examines orally administered ibogaine hydrochloride, which is converted in the liver to the active metabolite noribogaine. The authors explain that activity at numerous targets—including dopamine and serotonin transporters, opioid, NMDA, sigma, and nicotinic acetylcholine receptors—has been proposed, while the mechanisms underlying addiction-related effects remain uncertain. Preclinical discussions of GDNF, BDNF, and changes in gene expression do not directly demonstrate therapeutic efficacy in humans.

Case reports and case series

Seventeen of the 31 studies were case reports or case series. Together they described 33 men and 10 women, aged 25–61 years. Most concerned opioid/heroin use disorder, although cocaine, alcohol, and polysubstance use also appeared. Every administration was described as oral, but reported amounts varied widely—from 50–525 mg up to a maximum of 4 g—and some reports did not identify the amount or formulation. Eleven reports involved home or informal settings, five involved medical or clinical settings, and one included both.

Observed addiction-related outcomes included reduced craving, reduced self-administration, cessation of use, and relief of withdrawal symptoms. The same body of reports also included deaths, QTc prolongation, arrhythmias, polymorphic ventricular tachycardia, bradycardia, and cardiac arrest. Individual psychiatric and neurologic events included hallucinations, psychosis-like experiences, insomnia, ataxia, muscle spasms, manic symptoms, persistent perceptual disturbance, and suicidal ideation. Because these were selected, published cases rather than controlled incidence data, they cannot be used to estimate frequency.

Comparative trials, open-label research, and surveys

There were two double-blind, placebo-controlled studies. The first involved 27 adults with opioid use disorder (21 men and 6 women; mean age 41.2 years) who received noribogaine 60, 120, or 180 mg, or placebo, in a medical setting. A trend toward lower withdrawal ratings was reported, but the difference from placebo was not statistically significant. Headache, nausea, changes in light perception, and a concentration-dependent increase in QTc were described.

The second study included 20 men with cocaine use disorder and compared capsules containing 1,800 mg of a 75%-pure dried extract with placebo. The authors reported differences in acute symptoms and return to use, but each group contained only 10 participants. Visual experiences within 72 hours were reported as adverse events; no cardiovascular events were reported.

An open-label study of 27 participants described reductions in self-reported depressive symptoms and craving after 500–800 mg of oral ibogaine hydrochloride. A survey study based on retrospective responses from 27 people reported reductions in withdrawal and craving while also recording dizziness, nausea, diarrhea, hallucinations, and other effects. Neither was a blinded confirmation of efficacy.

Observational studies

The review included 10 observational studies; two publications used the same data and were therefore interpreted together. Participants were predominantly men, with mean ages of approximately 27–38 years. The studies mainly addressed opioid use disorder. Doses ranged from 1 mg/kg to a mean of 31.4 ± 7.6 mg/kg, administration was almost always oral, and most studies took place in medical or clinical settings.

Individual studies reported improvements in craving, self-administration, continued use, or withdrawal, but many lacked control groups or relied on self-report surveys. Adverse events included one death, changes in QTc and bradycardia, ataxia, nausea and vomiting, hallucinations, and elevated mood. Four studies, by contrast, reported no adverse events. Differences in dose, formulation, population, concomitant substances, follow-up duration, and outcome definitions prevent these studies from being reduced to a single simple effect estimate.

Results

Only two trials entered the quantitative analysis, with 28 participants receiving ibogaine/noribogaine and 19 receiving placebo. There was no significant difference for nausea (p = 0.5, I² = 0%). Visual disturbances were borderline at the conventional significance threshold (risk difference 0.21, 95% confidence interval 0.00–0.42, p = 0.05), with I² = 85%. A statistical difference was reported for headache, which the original article interpreted as increased risk after ibogaine/noribogaine (reported risk difference −0.33, 95% confidence interval −0.51 to −0.15, p < 0.001). However, heterogeneity was very high at I² = 94%, and the result came from only two studies.

As an observed fact, multiple studies described improvements in craving, withdrawal, amount of use, or abstinence. At the same time, the review included reports of serious cardiovascular events and deaths. The authors discussed possible contributions from receptor activity, neurotrophic factors, and acute subjective experience to addiction-related outcomes, but these are mechanistic hypotheses rather than findings directly tested by this review.

The authors concluded that, although findings suggest possible efficacy for substance use disorders, concerns about cardiotoxicity and death are substantial and there are too few adequately controlled trials to provide a definitive answer about efficacy or safety. They called for studies incorporating randomization, double blinding, placebo control, and assessment of metabolic characteristics.

Limitations

The greatest limitation is the heterogeneity of the evidence. Most of the 31 studies were case reports, case series, or observational studies; only two were double-blind studies. Reports from homes and informal settings often provided insufficient information about formulation purity, actual dose, concomitant substances, medical history, monitoring, and outcome confirmation. Administration procedures and outcome definitions were not standardized.

The meta-analysis had a small sample, and heterogeneity was extremely high in the analyses of headache and visual disturbances. Estimates from a fixed-effect model alone cannot be generalized. Although case reports included many deaths, the absence of a denominator means that mortality cannot be calculated. Conversely, small studies reporting “no adverse events” cannot establish the absence of rare fatal arrhythmias.

This review did not establish an optimal dose, a standard protocol, long-term maintenance of abstinence, superiority over existing treatments, or the balance of benefit and risk for a particular patient. Discussion of pharmacologic mechanisms and related compounds also does not directly demonstrate clinical efficacy.

Safety

The central safety concern is an effect on cardiac repolarization. The review included QTc prolongation, bradycardia, polymorphic ventricular tachycardia, torsades de pointes, ventricular fibrillation, cardiac arrest, and death. The authors discussed possible contributions from effects on cardiac ion channels including hERG, electrolyte abnormalities, heart disease, co-use of QT-prolonging medications or other substances, formulation purity, and dose variation. The review alone did not, however, establish causation in each death.

Reported non-cardiac effects included nausea and vomiting, headache, ataxia, muscle spasms, dizziness, diarrhea, insomnia, hallucinations or psychosis-like experiences, and manic symptoms. Safety information was uneven across studies, and some studies did not actively measure it. An absence of reporting therefore does not mean an event did not occur.

This resource does not recommend treatment selection or self-administration. Because the evidence includes serious cardiovascular risk, reports of improvement from observational studies alone cannot establish that ibogaine is safe or effective.

Source and rights

Original source: Mosca A, et al. Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: A Systematic Review of the Current Literature. Current Neuropharmacology. 2023;21(11):2178–2194. DOI: 10.2174/1570159X21666221017085612. PMID 36263479; PMCID PMC10556383.

The original article is published under Creative Commons Attribution 4.0 (CC BY 4.0). This page follows the original source but does not reproduce every table cell, reference, figure, or supplement verbatim. It renders the principal design, results, safety findings, and limitations while preserving the distinctions made in the original and avoiding extended quotations.