Correct!
3. Ibogaine

Ibogaine is an indole alkaloid with psychoactive and dissociative properties, widely regarded by tribes in West Africa as a cure for hunger, thirst, and even fatigue at low doses (1). Higher doses play a central role in tribal rites of passage and ritualistic attempts to communicate with ancestors. Today, ibogaine is best known for its purported anti-addiction properties and potential role in polysubstance detoxification as well as its toxicity (2).

A former heroin addict turned ibogaine researcher inadvertently stumbled upon this agent in the 1960’s when after ingestion, five of six users completely lost the urge for further opioid use. After years of in vitro and in vivo studies characterizing the anti-addictive properties of ibogaine, the FDA approved a clinical trial exploring the compound (3). However, owing to conflicting in vivo data suggesting cerebellar neurotoxicity and institutional financial constraints, the National Institute on Drug Abuse abandoned plans for ongoing investigational trials in 1995.

Due to its psychedelic/dissociative properties, ibogaine remains as a Schedule I drug in the USA. Nevertheless, ibogaine continues to be explored by individuals seeking detoxification from a variety of substances, opioids being the most common. It can be obtained through non-legal means and self-administered, or can be administered by medical personnel in countries without current bans.

Ibogaine use can lead to death (2). In a multinational forensic case series, 19 deaths were temporally associated with ibogaine ingestion (4). Cardiac disease, specifically cardiac arrhythmias are considered of greatest concern. QT prolongation is common with ibogaine toxicity (5). With blockage of the potassium voltage-gated ion channels encoded by the human ether-a-go-go-related gene there is a heightened risk of polymorphic ventricular tachycardia, torsades de pointes. Also, those presenting with toxicity are often at elevated risk for electrolyte and nutritional disturbances which themselves predispose to cardiac irritability and arrhythmia.

In rats given ibogaine, neurotoxicity was seen with high doses particularly in the olivocerebellar neural projections. This parallels the human side effects seen after acute ingestion, that of tremor and ataxia (6), demonstrated in the current case.

References

  1. Mash DC, Kovera CA, Pablo J, Tyndale RF, Ervin FD, Williams IC, Singleton EG, Mayor M. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Ann N Y Acad Sci. 2000;914:394-401. [CrossRef] [PubMed]
  2. Jalal S, Daher E, Hilu R. A case of death due to ibogaine use for heroin addiction. Am J Addict. 2013;22(3):302. [CrossRef] [PubMed]
  3. Maciulaitis R, Kontrimaviciute V, Bressolle FM, Briedis V. Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Hum Exp Toxicol. 2008;27(3):181-94. [CrossRef] [PubMed]
  4. Alper KR, Stajic M, Gill JR. Fatalities temporally associated with the ingestion of ibogaine. J Forensic Sci. 2012;57(2):398-412. [CrossRef] [PubMed]
  5. Hoelen DW, Spiering W, Valk GD. Long-QT syndrome induced by antiaddiction drug ibogaine. N Engl J Med. 2009;360(3):308-9. [CrossRef] [PubMed]
  6. 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(22):8828-41. [PubMed]

Home/Critical Care