The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020)

This review (s=18) did a qualitative analysis of studies with ibogaine and describes the acute adverse events (cardiac, gastrointestinal, neurological) and long-lasting effects (persistent cardiac, psychiatric, neurological). The authors note that phase I studies with standardized products are necessary as the products quantity and mix was widely varied.

Abstract

Context: 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.

Objectives: To update (2015-2020) the literature on the adverse events and fatalities associated with ibogaine/noribogaine administration.

Methods: Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results: 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.

Conclusions: 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.

Authors: Genís Ona, Juliana M. Rocha, José C. Bouso, Jaime E. C. Hallak, Tre Borràs, Maria T. Colomina & Rafael G. dos Santos

Notes

Psychedelics don’t come without risks. Most are physiologically safe, with for instance virtually no risks of overdosing, for instance with magic mushrooms (psilocybin) unless one stomachs 20kg in one sitting. But, not every psychedelic is made equally and there are known differences within this class of compounds. Ibogaine is one notable exception with known cardiovascular risks. Reports of seizures, gastrointestinal issues, loss of balance (ataxia), and heart failure are not uncommon.

Before we dive into the most recent review of adverse events with ibogaine, let’s first ask why it is being used in the first place. Ibogaine is known to disrupt the opioid system and thus can reduce, and temporarily eliminate, withdrawal symptoms and drug cravings. Many clinics around the world are currently treating those with substance use disorders, such as addictions to cocaine or opioids (e.g. heroin). Although promising, there hasn’t been much study on the considerable risks of ibogaine ingestion. This study lays out what we know.

The top risks of ibogaine:

  • Acute effects (<24 hours): QTc prolongation, where the time between contraction and relaxation of the heart chambers (cardiac ventricals)
  • Prolonged adverse events (>24 hours): psychiatric alterations, with insomnia for up to two weeks, delusions, agressiveness, and hallucinations being some of the most often mentioned events
  • Interactions with other drugs: where one case of ‘standard practice’ medications led to a fatal interaction

Although the risks of ibogaine alone can be characterized as graver than other psychedelics, it should be known that many (if not most) of the participants in the studies had pre-existing medical conditions and most a dependence on a variety of drugs (sometimes still present in their bodies during treatment). Or in other words, the participants don’t reflect the average population and although they may be most helped by ibogaine treatment, they are also the ones with heightened health risks.

One factor that makes finding out the risk of ibogaine treatment difficult is the variability of the amount of ibogaine and the exact substance administered (sometimes noribogaine, the active metabolite of ibogaine, was used directly). An earlier study found that the amount of ibogaine in root bark (of the Tabernanthe iboga bush) ranged from 0.6% to 11.2% (a 19-fold difference). The study analyzed both case reports from private clinics and clinical trials in hospitals. The former reported the most severe adverse events, whilst the latter only reported mild to moderate adverse events.

Although promising, ibogaine treatment doesn’t come without significant risks. For some, the risks are worth it to potentially break free from addiction. Future clinical trials should be able to better differentiate the risk at which dose level. Or second generation psychedelics such as 18-MC and Tabernanthalog could provide anti-addictive properties with lower to no cardiovascular risks. We will find out in the coming years.

The data comes from studies conducted between 2015 and 2020 and most were case studies.

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