Ibogaine and Noribogaine

Ibogaine, a compound from the Tabernanthe iboga plant, has been used anecdotally since the 1960s to block opioid withdrawal and promote drug-free abstinence after a single oral dose, though it has never been tested in human clinical trials. This chapter reviews open-label evidence suggesting ibogaine may help manage opioid withdrawal symptoms and facilitate abstinence, while also discussing its complex mechanism of action related to mu-opioid receptor adaptations. The unregulated use of ibogaine in for-profit clinics raises serious safety concerns. The drug's future as a treatment depends on controlled trials that clarify its benefits, risks, and safety.

Study at a glance

Abstract

Abstract Ibogaine is an indole alkaloid derived from the root bark of Tabernanthe iboga. The anti-addictive actions of ibogaine were first reported in the 1960s by persons using heroin. They offered personal testimonials that single oral doses of ibogaine abruptly blocked opioid withdrawal, and they remained drug-free after ibogaine exposure. Today, online forums describe ibogaine use for opioid withdrawal management by for-profit clinics and unskilled lay people, despite a lack of regulatory testing of ibogaine in human clinical trials. Discontinuation of opioid agonist therapy results in severely painful opioid withdrawal symptoms (OWS) that are followed by a persistent negative affect. For many patients seeking to discontinue opioids, the post-acute emotional disruption is a major obstacle for completion of full withdrawal. This chapter summarizes ibogaine’s clinical experience and open-label observational evidence that the drug is useful for treating the OWS and facilitating a transition to drug-free abstinence. The drug’s polypharmacy mode of action is considered in light of neuroadaptations in mu-opioid processes observed during acute withdrawal, which are mechanistically related to the protracted negative mood state that follows during opioid abstinence. Finally, the dark side of the unregulated use of ibogaine and concerns for patient safety are considered. The value proposition for development of ibogaine as a psychedelic drug product for addiction treatment will ultimately depend on the drug’s single dose regimen, benefits, risks, and safety measures demonstrated in controlled clinical trials.