Ibogaine is the main alkaloid of the African shrub Tabernanthe iboga. It produces hallucinogenic and psychostimulant effects, but it is currently known for the anti-addictive properties. Despite the potential therapeutic effects, several cases of fatalities and serious adverse events related to ibogaine/noribogaine use can be found in the literature. Most studies consist in case reports or were conducted under non-controlled settings, so causation cannot be clearly established.
To update (2015–2020) the literature on the adverse events and fatalities associated with ibogaine/noribogaine administration.
Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
Eighteen studies were included in the final selection. Highly heterogeneous results were found in terms of kind of product used or the known dosages. The adverse events were classified in acute effects (< 24 h), mainly cardiac (the most common was QTc prolongation), gastrointestinal, neurological, and clinical alterations, and long-lasting effects (> 24 h), mainly persistent cardiac alterations, psychiatric, and neurological signs.
There is a high need of phase I clinical trials that can describe the safety of different dosages of ibogaine with standardized products. Further research should perform clinical profiling of vulnerable populations, and design effective screening methods and clinical procedures.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Aceto M, Bowman E, Harris L (1990) Dependence studies of new compounds in the rhesus monkey, rat, and mouse. Natl Instit Drug Addict Res Monogr 95:578–631
Alper KR (2001) Ibogaine: a review. Alkaloids Chem Biol 56:1–38. https://doi.org/10.1016/s0099-9598(01)56005-8
Alper KR, Lotsof HS. (2007) Psychedelic medicine: new evidence for hallucinogenic substances as treatments. Westport (CT): Praeger Perspectives. The use of ibogaine in the treatment of addictions; p. 43–66.
Alper KR, Lotsof HS, Kaplan CD (2008) The ibogaine medical subculture. J Ethnopharmacol 115:9–24. https://doi.org/10.1016/j.jep.2007.08.034
Alper KR, Stajić M, Gill JR (2012) Fatalities temporally associated with the ingestion of ibogaine. J Forensic Sci 57(2):398–412. https://doi.org/10.1111/j.1556-4029.2011.02008.x
Alper K, Bai R, Liu N et al (2016) hERG blockade by iboga alkaloids. Cardiovasc Toxicol 16(1):14–22. https://doi.org/10.1007/s12012-015-9311-5
Barsuglia JP, Polanco M, Palmer R et al (2018) A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder. Prog Brain Res 242:121–158. https://doi.org/10.1016/bs.pbr.2018.08.002
Baumann MH, Rothman RB, Pablo J et al (2001) In vivo neurobiological effects of ibogaine and its odesmethyl metabolite, 12-hydroxyibogaine (noribogaine) in rats. J Pharmacol Exp Ther 297:531–539. https://doi.org/10.1177/0960327107087802
Belgers M, Leenaars M, Homberg JR et al (2016) Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Transl Psychiatry 6(5):e826. https://doi.org/10.1038/tp.2016.71
Bouso JC, Fornís I, Vilamala MV et al (2020) An analytical study of iboga alkaloids contained in Tabernanthe iboga-derived products offered by ibogaine treatment providers. Arch Clin Psychiatry 47(2):51–54. https://doi.org/10.1590/0101-60830000000231
Breuer L, Kasper BS, Schwarze B et al (2015) “Herbal seizures”-atypical symptoms after ibogaine intoxication: a case report. J Med Case Rep 9:243. https://doi.org/10.1186/s13256-015-0731-4
Brown TK (2013) Ibogaine in the treatment of substance dependence. Curr Drug Abuse Rev 6(1):3–16. https://doi.org/10.2174/15672050113109990001
Brown TK, Alper K (2018) Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. Am J Drug Alcohol Abuse 44(1):24–36. https://doi.org/10.1080/00952990.2017.1320802
Celeste RK (2008) Erros metodológicos mais comuns encontrados em artigos dos tipos relatos e série de casos. Federação Brasileira das Sociedades de Ginecologia e Obstetrícia
Cloutier-Gill L, Wood E, Millar T et al (2016) Remission of severe opioid use disorder with ibogaine: a case report. J Psychoactive Drugs 48(3):214–217. https://doi.org/10.1080/02791072.2016.1180467
Dos Santos RG, Bouso JC, Hallak JEC (2016) The antiaddictive effects of ibogaine: a systematic literature review of human studies. J Psychedelic Studies 1(1):20–28. https://doi.org/10.1556/2054.01.2016.001
Dos Santos RG, Hallak JEC (2020) Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neurosci Biobehav Rev 108:423–434. https://doi.org/10.1016/j.neubiorev.2019.12.001
Dworkin SI, Gleeson S, Meloni D et al (1995) Effects of ibogaine on responding maintained by food, cocaine and heroin reinforcement in rats. Psychopharmacol (berl) 117(3):257–261. https://doi.org/10.1007/BF02246099
Dzoljic ED, Kaplan CD, Dzoljic MR (1988) Effect of ibogaine on naloxone-precipitated withdrawal syndrome in chronic morphine dependent rats. Arch Int Pharmacodyn Ther 294:64–70
Ernst E, Bartu A, Popescu A (2002) Methadone-related deaths in Western Australia 1993–99. Aust N Z J Public Health 26:364–370. https://doi.org/10.1111/j.1467-842X.2002.tb00188.x
Fernandez JW (1982) Bwiti: an Ethnography of the religious imagination in Africa. Princeton University Press, Princeton
Frances B, Gout R, Cros J et al (1992) Effects of ibogaine on naloxone-precipitated withdrawal in morphine-dependent mice. Fundam Clin Pharmacol 6(8–9):327–332. https://doi.org/10.1111/j.1472-8206.1992.tb00127.x
Glick SD, Kuehne ME, Raucci J et al (1994) Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tumorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Brain Res 657(1–2):14–22. https://doi.org/10.1016/0006-8993(94)90948-2
Glick SD, Rossman K, Rao NC et al (1992) Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Neuropharmacol 31:497–500. https://doi.org/10.1016/0028-3908(92)90089-8
Glue P, Cape G, Tunnicliff D et al (2016) Ascending single-dose, double-blind, placebo controlled safety study of noribogaine in opioid-dependent patients. Clin Pharmacol Drug Dev 5(6):460–468. https://doi.org/10.1002/cpdd.254
Glue P, Winter H, Garbe K et al (2015) Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers. J Clin Pharmacol 55(6):680–687. https://doi.org/10.1002/jcph.471
Goutarel R, Gollnhofer O, Sillans R (1993) Pharmacodynamics and therapeutic applications of iboga and ibogaine. Psych Monogr Essays 6:70–111
Grogan J, Gerona R, Snow JW et al (2019) Ibogaine consumption with seizure-like episodes, QTc-prolongation, and captured cardiac dysrhythmias. J Emerg Med 57(4):e99–e104. https://doi.org/10.1016/j.jemermed.2019.06.052
Helsley S, Fiorella D, Rabin RA et al (1997) Effects of ibogaine on performance in the 8-arm radial maze. Pharmacol Biochem Behav 58(1):37–41. https://doi.org/10.1016/s0091-3057(96)00476-5
Henstra M, Wong L, Chahbouni A et al (2017) Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine. Clin Toxicol (phila) 55(6):600–602. https://doi.org/10.1080/15563650.2017.1287372
Hildyard C, Macklin P, Prendergast B et al (2016) A case of QT prolongation and torsades de pointes caused by ibogaine toxicity. J Emerg Med 50(2):e83-87. https://doi.org/10.1016/j.jemermed.2015.06.051
Jebberi Z, Marazzato J, De Ponti R et al (2019) Polymorphic wide QRS complex tachycardia: differential diagnosis. Card Electrophysiol Clin 11(2):333–344. https://doi.org/10.1016/j.ccep.2019.02.004
Kapur J (2018) Role of NMDA receptors in the pathophysiology and treatment of status epilepticus. Epilepsia Open 3(2):165–168. https://doi.org/10.1002/epi4.12270
Knuijver T, Belgers M, Markus W et al (2018) Hallucinogen persisting perception disorder after ibogaine treatment for opioid dependence. J Clin Psychopharmacol 38(6):646–648. https://doi.org/10.1097/JCP.0000000000000966
Koenig X, Hilber K (2015) The anti-addiction drug ibogaine and the heart: a delicate relation. Molecules 20(2):2208–2228. https://doi.org/10.3390/molecules20022208
Kuryshev YA, Bruening-Wright A, Brown AM et al (2010) Increased cardiac risk in concomitant methadone and diazepam treatment: pharmacodynamic interactions in cardiac ion channels. J Cardiovasc Pharmacol 56:420–430. https://doi.org/10.1097/FJC.0b013e3181f1d21b
Larsen P (2019) The opioid epidemic: a public health emergency. Rehabil Nurs 44(2):67–68
Luz M, Mash DC (2021) Evaluating the toxicity and therapeutic potential of ibogaine in the treatment of chronic opioid abuse. Expert Opin Drug Metab Toxicol. https://doi.org/10.1080/17425255.2021.1944099
Marta CJ, Ryan WC, Kopelowicz A et al (2015) Mania following use of ibogaine: a case series. Am J Addict 24(3):203–205. https://doi.org/10.1111/ajad.12209
Mash DC, Duque L, Page B et al (2018) Ibogaine detoxification transitions opioid and cocaine abusers between dependence and abstinence: clinical observations and treatment outcomes. Front Pharmacol 9:529. https://doi.org/10.3389/fphar.2018.00529
Matamoros-Castillo JM, Jávega-Manjó C, Sierra-San PM et al (2019) The paradox of iboga: intoxication by a natural detoxification remedy. Actas Esp Psiquiatr 47(2):70–78
Mazoyer C, Carlier J, Boucher A (2013) Fatal case of a 27-year-old male after taking iboga in withdrawal treatment: GC-MS/MS determination of ibogaine and ibogamine in iboga roots and postmortem biological material. J Forensic Sci 58:1666–1672. https://doi.org/10.1111/1556-4029.12250
Meisner JA, Wilcox SR, Richards JB (2016) Ibogaine-associated cardiac arrest and death: case report and review of the literature. Ther Adv Psychopharmacol 6(2):95–98. https://doi.org/10.1177/2045125315626073
Moher D, Liberati A, Tetzlaff J et al (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med 6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097
O’Connell CW, Gerona RR, Friesen MW et al (2015) Internet-purchased ibogaine toxicity confirmed with serum, urine, and product content levels. Am J Emerg Med 33(7):985–986. https://doi.org/10.1016/j.ajem.2014.12.023
Pleskovic A, Gorjup V, Brvar M (2012) Ibogaine-Associated Ventricular Tachyarrhythmias Clin Toxicol (phila) 50(2):157. https://doi.org/10.3109/15563650.2011.647031
Popik P, Layer RT, Fossom LH et al (1995) NMDA antagonist properties of the putative antiaddictive drug, ibogaine. J Pharmacol Exp Ther 275(2):753–760
Ruan Y, Bai R, Liu N, et al (2014) Herg blockade by iboga alkaloids. In Proceedings of the European Society of Cardiology Congress, Barcelona, Spain.
Sharpe LG, Jaffe JH (1990) Ibogaine fails to reduce naloxone-precipitated withdrawal in the morphine-dependent rat. NeuroReport 1(1):17–19
Sowunmi A, Salako LA, Laoye OJ et al (1990) Combination of quinine, quinidine and cinchonine for the treatment of acute falciparum malaria: correlation with the susceptibility of Plasmodium falciparum to the cinchona alkaloids in vitro. Trans R Soc Trop Med Hyg 84:626–629. https://doi.org/10.1016/0035-9203(90)90127-z
Steinberg C, Deyell MW (2018) Cardiac arrest after ibogaine intoxication. J Arrhythm 34(4):455–457. https://doi.org/10.1002/joa3.12061
Tournier N, Chevillard L, Megarbane B et al (2010) Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Int J Neuropsychopharmacol 13(7):905–915. https://doi.org/10.1017/S1461145709990848
Vlaanderen L, Martial LC, Franssen EJ (2014) Cardiac arrest after ibogaine ingestion. Clin Toxicol (phila) 52:642–643. https://doi.org/10.3109/15563650.2014.927477
Wilkins C, dos Santos RG, Solá J et al (2017) Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report. J Psychedelic Studies 1(1):29–34. https://doi.org/10.1556/2054.01.2017.005
Wilson C, Millar T, Matieschyn Z (2021) Novel treatment of opioid use disorder using ibogaine and iboga in two adults. J Psychedelic Studies 4(3):149–155. https://doi.org/10.1556/2054.2020.00133
JMR received funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil). JECH is recipient of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) 1A productivity fellowship. Research was supported in part by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). RGS is Fellow of the Programa Nacional de Pós-Doutorado, Brazil (PNPD/CAPES).
Conflict of interest
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article belongs to a Special Issue on Psychopharmacology on Psychedelic Drugs
Below is the link to the electronic supplementary material.
About this article
Cite this article
Ona, G., Rocha, J.M., Bouso, J.C. et al. The adverse events of ibogaine in humans: an updated systematic review of the literature (2015–2020). Psychopharmacology (2021). https://doi.org/10.1007/s00213-021-05964-y
- Adverse events
- Drug interactions