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Ibogaine

A psychoactive alkaloid researched chiefly for its potential to interrupt opioid and stimulant dependence.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Ibogaine, iboga, noribogaine, then ranked by relevance.

Ibogaine shows preliminary evidence for reducing opioid withdrawal symptoms and drug craving, with several observational studies and case series reporting rapid detoxification and sustained abstinence in some individuals. However, the evidence is limited by small sample sizes, lack of randomized controlled trials, and significant safety concerns including neurotoxicity in animal models and risk of cardiac arrhythmia and death, particularly during opioid detoxification. The overall evidence is insufficient to support clinical use without rigorous safety monitoring.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.

Ibogaine noncompetitively inhibits serotonin transport by stabilizing the cytoplasm-facing state of SERT, providing a structural mechanism for its psychoactive and anti-addictive properties.

preclinical

Ibogaine and harmaline cause degeneration of Purkinje cells in parasagittal stripes of the cerebellar vermis in rats, indicating selective neurotoxicity.

preclinical

Resolution of opioid withdrawal signs within 24 hours in 25 of 33 patients, sustained over 72 hours, with one fatality possibly due to surreptitious heroin use.

observational Sample size: 33

Ibogaine dose-dependently decreased morphine self-administration acutely and produced persistent decreases for days to weeks in some rats, with no aftereffect on water-reinforced responding.

preclinical

Ibogaine and several iboga alkaloids dose-dependently decreased morphine and cocaine self-administration acutely, with some producing aftereffects the next day; tremorigenic activity was noted.

preclinical

68% of individuals took ibogaine for substance-related disorders, 53% specifically for opioid withdrawal, indicating widespread use for detoxification despite lack of clinical standards.

observational Sample size: 3414

Ibogaine decreased ethanol self-administration in rats and increased GDNF expression in the VTA; intra-VTA GDNF mimicked and anti-GDNF antibodies reduced the effect, identifying a molecular mechanism.

preclinical

A single injection of ibogaine (40 mg/kg) significantly decreased cocaine intake for over 48 hours, with repeated weekly injections producing more prominent inhibition.

preclinical

Single doses of 700-1800 mg ibogaine eliminated opiate withdrawal symptoms; three of seven remained drug-free for 14 weeks or more, while others relapsed after days to weeks.

observational Sample size: 7

Ibogaine-induced Purkinje cell degeneration is indirect and dependent on integrity of the olivocerebellar projection, consistent with excitotoxic mechanism via climbing fiber activation.

preclinical

Ibogaine significantly reduced opioid withdrawal scores acutely; at 1-month follow-up, 50% reported no opioid use in prior 30 days, with sustained improvement in drug use scores over 12 months.

observational Sample size: 30

Significant reductions in addiction severity and depression scores from baseline to 12-month follow-up after a single ibogaine treatment; acute withdrawal symptoms also reduced.

observational Sample size: 14

Ibogaine noncompetitively inhibits serotonin transport by stabilizing the cytoplasm-facing state of SERT, contrasting with cocaine's mechanism.

preclinical

Ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification and reduced depressive symptoms at 30 days post-discharge; complex pharmacokinetics noted.

observational

Ibogaine has relatively high affinity for sigma-2 receptors (Ki=90.4 nM) and much lower affinity for sigma-1 receptors (Ki=9310 nM), suggesting a novel mechanism.

preclinical

Ibogaine shows therapeutic potential across substance use disorders, trauma, mood disorders, and suicidality, but clinical translation is hindered by safety concerns, regulatory barriers, and complex pharmacology.

review

The Michigan Society of Addiction Medicine opposed a bill allocating $50 million in opioid settlement funds to ibogaine research, indicating professional skepticism.

other

A validated UPLC-MS/MS method was developed to quantify ibogaine, noribogaine, ibogamine, and oxa-noribogaine in rat brain microdialysate, enabling real-time neuropharmacokinetic monitoring.

preclinical

Six deaths occurred within 72 hours among 10,382 opioid use disorder patients, with none among 8,689 non-SUD patients; mortality risk is concentrated in opioid detoxification.

observational Sample size: 19071

A bio-hybrid framework using Physarum-mediated biofeedback for ibogaine-assisted neural recovery is proposed as a defensive publication, with no empirical data.

theoretical

Ibogaine shows multimodal action and potential for reducing withdrawal and craving, but safety remains the main limitation due to QTc prolongation, arrhythmias, and cardiac events.

review

An integrative iboga microdosing protocol (estimated 3.8-38.5 mg/day ibogaine) paired with psychotherapy was associated with clinical improvement in three cases of brain injury.

observational Sample size: 3

Participants associated ibogaine treatment with rapid detoxification, improved mood, reduced anxiety, and periods of sustained abstinence, though relapse occurred in some cases.

qualitative Sample size: 10

A single dose of ibogaine (40 mg/kg) reinstated juvenile-like experience-dependent plasticity in the adult mouse visual cortex, reducing perineuronal nets and inhibitory synaptic markers.

preclinical

Only three RCTs were identified: one showed reduced cocaine craving, one found noribogaine safe in healthy volunteers, and one showed QTc prolongation with non-significant withdrawal reduction in opioid-dependent patients.

review

Points of agreement

  • Multiple observational studies and case series report that ibogaine reduces opioid withdrawal symptoms acutely.
  • Preclinical studies consistently show that ibogaine decreases self-administration of morphine, cocaine, and ethanol in rats.
  • Ibogaine has complex pharmacology, including inhibition of serotonin transport, sigma-2 receptor affinity, and GDNF upregulation.
  • Safety concerns are consistently noted: neurotoxicity in animal models (Purkinje cell degeneration) and cardiac risk (QTc prolongation, arrhythmias) in humans.

Conflicts

  • Durability of effect varies widely: some studies report sustained abstinence for months, while others show relapse within days to weeks.
  • The large retrospective study (27250) found mortality only in opioid detoxification, but other studies report no deaths or attribute fatalities to surreptitious drug use.
  • Professional organizations (e.g., MiSAM) oppose funding ibogaine research, while other researchers advocate for its development with safety protocols.

Gaps

  • No large, double-blind, placebo-controlled RCTs of ibogaine for opioid use disorder exist.
  • Long-term safety data, especially regarding cardiac and neurological effects, are lacking.
  • Optimal dosing, route of administration, and patient selection criteria are not established.
  • The role of active metabolites (e.g., noribogaine) and their contribution to efficacy and toxicity is unclear.
  • Most studies are small, open-label, or observational, with high risk of bias and lack of standardized outcome measures.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Ibogaine, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Ibogaine or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

Latest monthly recap: June 2026 →

591 articles · 117 from the last two years · 47,120 participants across 112 studies reporting sample size

Common study designs

review 111 preclinical study 17 systematic review 23 experimental study 113 theoretical or philosophical paper 23

Sustained abstinence in severe ketamine use disorder following ibogaine treatment case report

Frontiers in Psychiatry July 20, 2026 Sergio Pérez Rosal, Sonya C. Faber, Markus Backmund

A 30-year-old man with severe polysubstance dependence on ketamine, cocaine, and alcohol, along with recurrent depression, underwent ibogaine-assisted treatment in a 13-day residential program in Mexico. He received an initial 800 mg ibogaine HCl dose (10.1 mg/kg) and two 300 mg booster doses (3.8 mg/kg) under medical monitoring. He reported immediate cessation of cravings for all substances. Over 17 months of follow-up, including a later medically supervised ibogaine intervention, toxicology and psychometric assessments showed continued abstinence from all substances and significant improvements in depression, anxiety, and quality of life. This is the first documented case of sustained abstinence in severe ketamine use disorder following ibogaine treatment.

Toward a nuanced framework for the medical development of ibogaine and its analogues and derivatives: implications for psychopharmacology

Expert Opinion on Drug Discovery July 4, 2026 Christopher D. Verrico, Lynnette A. Averill, Cameron J Moore et al.

Ibogaine, a natural alkaloid, shows potential for treating substance use disorders, trauma, mood disorders, and suicidality, but clinical use is limited by safety concerns and regulatory barriers. Researchers are pursuing two main strategies: developing ibogaine-like compounds that keep broad effects while reducing risks, and creating selective 'bespoke' analogs targeting specific conditions like opioid use disorder, traumatic brain injury, or PTSD. The authors emphasize that the field should avoid oversimplified views that derivatives are uniformly better or interchangeable, and call for greater conceptual clarity and mechanistic humility as ibogaine-based therapies move toward regulated medical use.

MiSAM opposes bill giving $50 million in opioid settlement funds to ibogaine research

Alcoholism & Drug Abuse Weekly June 29, 2026 Alison Knopf

The Michigan Society of Addiction Medicine opposes a bill that would redirect opioid settlement funds toward research on ibogaine, a psychedelic drug, arguing that such funds should instead be used for evidence-based treatments for opioid use disorder.

Development and validation of a UPLC-MS/MS method for real-time neuropharmacokinetic monitoring of iboga alkaloids in rat brain.

Journal of Pharmaceutical and Biomedical Analysis June 24, 2026 Scot Mcintosh, Isabella Maldonado, Nickalus C Smith et al.

A sensitive UPLC-MS/MS method was developed and validated to quantify ibogaine, noribogaine, ibogamine, and oxa-noribogaine in rat brain microdialysate, measuring pharmacologically active, unbound drug in brain extracellular fluid rather than total tissue content. The method achieved lower limits of quantification of 0.78-1.56 ng/mL with a 6-minute run time, and calibration curves were linear over 0.78-75 ng/mL for ibogamine and 1.56-75 ng/mL for the other analytes. Accuracy and precision met acceptance criteria. Applied to rats (n=4), noribogaine in nucleus accumbens after 10 mg/kg intraperitoneal administration reached a peak unbound concentration of 292 ± 68 ng/mL at 50 minutes, demonstrating suitability for real-time neuropharmacokinetic profiling of iboga alkaloids.

Indication-stratified mortality risk of ibogaine treatment under contemporary safety protocols: a multisite analysis of 19,071 patients and updated systematic review of fatalities

Research Square June 17, 2026 Martijn Arns, Kenneth Shinozuka, Joseph P Barsuglia

Ibogaine, a substance showing early promise for treating substance use disorders and PTSD in veterans, carries a risk of cardiac arrhythmia and death. A retrospective multisite study of 19,071 patients treated under safety guidelines at 11 international clinics found that all six deaths occurring within 72 hours were among patients treated for opioid use disorder (6 out of 10,382), with no deaths among 8,689 non-SUD patients. A systematic review of ibogaine-associated fatalities mirrored this pattern: 41 of 44 fatalities with known indication involved substance use disorder, predominantly opioid detoxification. The findings indicate that ibogaine-associated mortality is largely confined to opioid detoxification and rare in non-SUD indications.

Physarum-Mediated Biofeedback Rehabilitation: A Bio-Hybrid Framework for Ibogaine-Assisted Neural Recovery

Zenodo (CERN European Organization for Nuclear Research) June 12, 2026 Saeid Ghiasi

A system is described that maps human brain activity (EEG frequency, amplitude, and phase) to the behavior of a living slime mold (Physarum polycephalum) to create a biohybrid interface for addiction recovery. The slime mold's network growth and retraction are controlled by nutrient gradients that correspond to neural signals: higher activation in addiction-related brain regions reduces food at corresponding Physarum nodes, causing network retraction. The system is presented as a structural isomorphism—not a metaphor—between neural plasticity, Physarum tube reinforcement, and ibogaine's neurorestorative mechanisms (NMDA receptor blockade, BDNF/GDNF upregulation). The document is a defensive publication establishing prior art under patent treaties, released under CC-BY 4.0.

Clinical improvement following an integrative iboga microdosing protocol in post-concussive and hypoxic brain injury syndromes: a case series

Frontiers in Pharmacology June 3, 2026 Burton J. Tabaac, Robin Carhart-Harris, Teresa Yung

Three individuals with persistent symptoms after traumatic brain injury or hypoxic-ischemic brain injury completed a six-week protocol combining a participant-directed iboga-containing microdosing regimen (using whole root bark biomass with about 3.845% ibogaine content, yielding an estimated 3.8–38.5 mg/day ibogaine equivalent) with weekly Accelerated Experiential Dynamic Psychotherapy and supportive nutraceuticals. All three showed progressive neurological recovery; two reported complete symptom remission at long-term follow-up. Participants discontinued all prescription medications and reported resolution of headaches, brain fog, fatigue, irritability, and mood swings, with a return to regular activities and renewed enthusiasm. The authors note that the findings do not establish causality or iboga-specific efficacy due to the multimodal intervention and methodological limitations.

Uso da ibogaína no tratamento da dependência química: uma revisão de literatura

DELOS Desarrollo Local Sostenible June 3, 2026 Ana Lara Mendonça, Déborah Rezende, Gabriela Alves et al.

Ibogaine, an indole alkaloid from Tabernanthe iboga, may reduce withdrawal symptoms, craving, and relapse in substance use disorders. A literature review of publications from PubMed, Scopus, Medline, Google Scholar, and SciELO shows ibogaine acts via multiple systems: glutamatergic, opioid, serotonergic, and nicotinic, with possible effects on neuroplasticity and reward circuits. Observational clinical studies indicate reductions in withdrawal and craving, and recent research describes improved psychiatric and cognitive outcomes in controlled settings. However, safety remains a major limitation, particularly the risk of corrected QT interval prolongation, ventricular arrhythmias, and serious cardiac events. The therapeutic potential is relevant but depends on randomized controlled trials, rigorous monitoring, clear regulatory criteria, and hospital protocols to reduce patient risks.

Exploring the Use of Ibogaine in Opioid Recovery: Insights from Lived Experience

Journal of Psychoactive Drugs May 22, 2026 Jamie Walker, Daryle Deering, Bruno Hamish Unger

Ten opioid-dependent people in New Zealand who used ibogaine for detoxification described rapid withdrawal relief, improved mood, reduced anxiety, and periods of sustained abstinence, though some later relapsed. Participants were motivated by desperation to be opioid-free and sought ibogaine because of limited treatment options beyond opioid substitution therapy. They emphasized the importance of safety practices, medical screening, and post-treatment psychosocial support for positive outcomes. The study identified seven themes including motivations, treatment effects on depression and anxiety, and spiritual effects. Ibogaine is legally available by prescription in New Zealand, providing a unique context for understanding user experiences.

Ibogaine induces juvenile-like plasticity and modulates functional and structural regulators of plasticity in the adult mouse visual cortex.

BMC Neuroscience May 13, 2026 Alejo Acuña, Federico Billeri, Valentino Totaro et al.

A single dose of ibogaine (40 mg/kg) reinstates juvenile-like experience-dependent plasticity in the adult mouse visual cortex. Adult mice given ibogaine and then four days of monocular deprivation showed reduced visual acuity in the deprived eye and decreased dendritic spine density in the binocular visual cortex, effects not seen in vehicle-treated mice. Ibogaine alone did not alter these measures. The plasticity-enhancing effect was accompanied by reductions in perineuronal nets, parvalbumin-positive interneuron staining, and vesicular GABA transporter-labeled inhibitory puncta. These findings suggest ibogaine can reopen windows of heightened cortical adaptability by reducing structural and inhibitory brakes on plasticity.

Clinical trials

All Ibogaine trials →