How toxic is ibogaine?

References

• Alper KR. Ibogaine: a review. Alkaloids Chem Biol. 2001;56:1–38.
   PubMedGoogle Scholar
• Mash DC, Kovera CA, Buck BE, et al. Medication development of ibogaine as a pharmacotherapy for drug dependence. N Y Acad Sci. 1998;844:274–292.
   PubMed Web of Science ®Google Scholar
• Lotsof HS, Alexander NE. Case studies of ibogaine treatment: implications for patient management strategies. Alkaloids Chem Biol. 2001;56:293–313.
   PubMedGoogle Scholar
• Popik P, Layer RT, Skolnick P. 100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug. Pharmacol Rev. 1995;47:235–253.
   PubMed Web of Science ®Google Scholar
• Maciulaitis R, Kontrimaviciute V, Bressolle FM, et al. Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Hum Exp Toxicol. 2008;27:181–194.
   PubMed Web of Science ®Google Scholar
• Alper KR, Lotsof HS, Kaplan CD. The ibogaine medical subculture. J Ethnopharmacol. 2008;115:9–24.
   PubMed Web of Science ®Google Scholar
• Hough LB, Pearl SM, Glick SD. Tissue distribution of ibogaine after intraperitoneal and subcutaneous administration. Life Sci. 1996;58:119–122.
   Google Scholar
• Mash DC, Kovera CA, Pablo J, et al. Ibogaine in the treatment of heroin withdrawal. Alkaloids Chem Biol. 2001;56:155–171.
   PubMedGoogle Scholar
• Glue P, Lockhart M, Lam F, et al. Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. J Clin Pharmacol. 2015;55:189–194.
   PubMed Web of Science ®Google Scholar
• Kontrimaviciūte V, Mathieu O, Mathieu-Daudé JC, et al. Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the Tabernanthe iboga shrub. J Anal Toxicol. 2006;30:434–440.
   PubMed Web of Science ®Google Scholar
• Bowen WD. Sigma receptors: recent advances and new clinical potentials. Pharm Acta Helv. 2000;74:211–218.
   PubMedGoogle Scholar
• He DY, Ron D. Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions of the anti-addiction drug, Ibogaine. FASEB J. 2006;20:2420–2422.
   PubMed Web of Science ®Google Scholar
• Glick SD, Maisonneuve IS. Mechanisms of antiaddictive actions of ibogaine. Ann N Y Acad Sci. 1998;844:214–226.
   PubMed Web of Science ®Google Scholar
• Trujillo KA, Akil H. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science. 1991;251:85–87.
   PubMed Web of Science ®Google Scholar
• Sershen H, Hashim A, Lajtha A. The effect of ibogaine on kappa-opioid- and 5-HT3-induced changes in stimulation-evoked dopamine release in vitro from striatum of C57BL/6By mice. Brain Res Bull. 1995;36:587–591.
   PubMed Web of Science ®Google Scholar
• Alburges ME, Hanson GR. Ibogaine pretreatment dramatically enhances the dynorphin response to cocaine. Brain Res. 1999;847:139–142.
   PubMed Web of Science ®Google Scholar
• Broderick PA, Phelan FT, Eng F, et al. Ibogaine modulates cocaine responses which are altered due to environmental habituation: in vivo microvoltammetric and behavioral studies. Pharmacol Biochem Behav. 1994;49:711–728.
   PubMed Web of Science ®Google Scholar
• He DY, McGough NN, Ravindranathan A, et al. Glial cell line-derived neurotrophic factor mediates the desirable actions of the anti-addiction drug ibogaine against alcohol consumption. J Neurosci. 2005;25:619–628.
   PubMed Web of Science ®Google Scholar
• Carnicella S, Ron D. GDNF–a potential target to treat addiction. Pharmacol Ther. 2009;122:9–18.
   PubMed Web of Science ®Google Scholar
• O’Hearn E, Molliver ME. Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience. 1993;55:303–310.
   PubMed Web of Science ®Google Scholar
• O’Hearn E, Molliver ME. The olivocerebellar projection mediates ibogaine-induced degeneration of Purkinje cells: a model of indirect, trans-synaptic excitotoxicity. J Neurosci. 1997;17:8828–8841.
   PubMed Web of Science ®Google Scholar
• Molinari HH, Maisonneuve IM, Glick SD. Ibogaine neurotoxicity: a re-evaluation. Brain Res. 1996;737:255–262.
   PubMed Web of Science ®Google Scholar
• Xu Z, Chang LW, Slikker Jr. W, et al. A dose-response study of ibogaine-induced neuropathology in the rat cerebellum. Toxicol Sci. 2000;57:95–101.
   PubMed Web of Science ®Google Scholar
• Helsley S, Dlugos CA, Pentney RJ, et al. Effects of chronic ibogaine treatment on cerebellar Purkinje cells in the rat. Brain Res. 1997;759:306–308.
   PubMed Web of Science ®Google Scholar
• Glick SD, Kuehne ME, Raucci J, et al. 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 Res. 1994;657:14–22.
   PubMed Web of Science ®Google Scholar
• Miwa H. Rodent models of tremor. Cerebellum. 2007;6:66–72.
   PubMed Web of Science ®Google Scholar
• Scallet AC, Ye X, Rountree R, et al. Ibogaine produces neurodegeneration in rat, but not mouse, cerebellum. Neurohistological biomarkers of Purkinje cell loss. Ann N Y Acad Sci. 1996;801:217–222.
   PubMed Web of Science ®Google Scholar
• Kubiliene A, Marksiene R, Kazlauskas S, et al. Acute toxicity of ibogaine and noribogaine. Medicina (Kaunas). 2008;44:984–988.
   PubMed Web of Science ®Google Scholar
• Jalal S, Daher E, Hilu R. A case of death due to ibogaine use for heroin addiction: case report. Am J Addict. 2013;22:302
   PubMed Web of Science ®Google Scholar
• Asua I. Growing menace of ibogaine toxicity. Br J Anaesth. 2013;111:1029–1030.
   PubMed Web of Science ®Google Scholar
• Hoelen DW, Spiering W, Valk GD. Long-QT syndrome induced by the antiaddiction drug ibogaine. N Engl J Med. 2009;360:308–309.
   PubMed Web of Science ®Google Scholar
• O’Connell CW, Gerona RR, Friesen MW, et al. Internet-purchased ibogaine toxicity confirmed with serum, urine, and product content levels. Am J Emerg Med. 2015;33:e5–e6.
   PubMed Web of Science ®Google Scholar
• Paling FP, Andrews LM, Valk GD, et al. Life-threatening complications of ibogaine: three case reports. Neth J Med. 2012;70:422–424.
   PubMed Web of Science ®Google Scholar
• Vlaanderen L, Martial LC, Franssen EJ, et al. Cardiac arrest after ibogaine ingestion. Clin Toxicol (Phila). 2014;52:642–643.
   PubMed Web of Science ®Google Scholar
• Marta CJ, Ryan WC, Kopelowicz A, et al. Mania following use of ibogaine: a case series. Am J Addict. 2015;24:203–205.
   PubMed Web of Science ®Google Scholar
• Alper KR, Stajić M, Gill JR. Fatalities temporally associated with the ingestion of ibogaine. J Forensic Sci. 2012;57:398–412.
   PubMed Web of Science ®Google Scholar
• Maas U, Strubelt S. Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction. Med Hypotheses. 2006;76:960–964.
   Web of Science ®Google Scholar
• Mazoyer C, Carlier J, Boucher A, et al. 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. 2013;58:1666–1672.
   PubMed Web of Science ®Google Scholar
• Papadodima SA, Dona A, Evaggelakos CI, et al. Ibogaine related sudden death: a case report. J Forensic Leg Med. 2013;20:809–811.
   PubMed Web of Science ®Google Scholar
• Chèze M, Lenoan A, Deveaux M, et al. Determination of ibogaine and noribogaine in biological fluids and hair by LC-MS/MS after Tabernanthe iboga abuse Iboga alkaloids distribution in a drowning death case. Forensic Sci Int. 2008;176:58–66.
   PubMed Web of Science ®Google Scholar
• Pleskovic A, Gorjup V, Brvar M, et al. Ibogaine-associated ventricular tachyarrhythmias. Clin Toxicol (Phila). 2012;50:157
   PubMed Web of Science ®Google Scholar
• Hildyard C, Macklin P, Prendergast B, et al. A case of QT prolongation and Torsades de Pointes caused by Ibogaine toxicity. J Emerg Med. 2015; doi: 10.1016/j.jemermed.2015.06.051.
   PubMedGoogle Scholar
• Glue P, Winter H, Garbe K, et al. Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers. J Clin Pharmacol. 2015;55:680–687.
   PubMed Web of Science ®Google Scholar
• Mash DC, Kovera CA, Pablo J, et al. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Ann N Y Acad Sci. 2000;914:394–401.
   PubMed Web of Science ®Google Scholar
• Baumann MH, Pablo J, Ali SF, et al. Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine. Alkaloids Chem Biol. 2001;56:79–113.
   PubMedGoogle Scholar
• Koenig X, Kovar M, Rubi L, et al. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug’s cardiac ion channel profile. Toxicol Appl Pharmacol. 2013;273:259–268.
   PubMed Web of Science ®Google Scholar
• Koenig X, Kovar M, Boehm S, et al. Anti-addiction drug ibogaine inhibits hERG channels: a cardiac arrhythmia risk. Addict Biol. 2014;19:237–239.
   PubMed Web of Science ®Google Scholar
• Bhargava HN, Cao YJ. Effects of noribogaine on the development of tolerance to antinociceptive action of morphine in mice. Brain Res. 1997;771:343–346.
   PubMed Web of Science ®Google Scholar
• Sunder Sharma S, Bhargava HN. Enhancement of morphine antinociception by ibogaine and noribogaine in morphine-tolerant mice. Pharmacology. 1998;57:229–232.
   PubMed Web of Science ®Google Scholar
• Kobayashi K, Yamamoto T, Chiba K, Tani M, Shimada N, Ishizaki T, Kuroiwa Y. Human buprenorphine N-dealkylation is catalyzed by cytochrome P450 3A4. Drug Metab Dispos. 1998;26:818–821.
   PubMed Web of Science ®Google Scholar