Ibogaine

Ibogaine is a psychoactive indole alkaloid derived from plants such as Tabernanthe iboga, characterized by hallucinogenic and oneirogenic effects. Traditionally used by Central African foragers, it has undergone controversial research for the treatment of substance use disorders. Ibogaine exhibits complex pharmacology by interacting with multiple neurotransmitter systems, notably affecting opioid, serotonin, sigma, and NMDA receptors, while its metabolite noribogaine primarily acts as a serotonin reuptake inhibitor and κ-opioid receptor agonist.

The psychoactivity of the root bark of the iboga tree, T. iboga, one of the plants from which ibogaine is extracted, was first discovered by forager tribes in Central Africa, who passed the knowledge to the Bwiti tribe of Gabon. It was first documented in the 19th century for its spiritual use, later isolated and synthesized for its psychoactive properties, briefly marketed in Europe as a stimulant, and ultimately researched—and often controversial—for its potential in treating addiction despite being classified as a controlled substance. Ibogaine can be semisynthetically produced from voacangine, with its total synthesis achieved in 1956 and its structure confirmed by X-ray crystallography in 1960. Ibogaine has been studied for treating substance use disorders, especially opioid addiction, by alleviating withdrawal symptoms and cravings, but its clinical use and development has been limited due to regulatory barriers and serious safety risks like cardiotoxicity. A 2022 systematic review suggested that ibogaine and noribogaine show promise in treating substance use disorders and comorbid depressive symptoms and psychological trauma but carry serious safety risks, necessitating rigorous clinical oversight.

Ibogaine produces a two-phase experience—initially visionary and dream-like with vivid imagery and altered perception, followed by an introspective period marked by lingering side effects like nausea and mood disturbances, which may persist for days. Long-term risks include mania and heart issues such as long QT syndrome, and potential fatal interactions with other drugs.

Ibogaine is federally illegal in the United States, but is used in treatment clinics abroad under legal gray areas, with growing media attention highlighting both its potential and risks in addiction therapy. It has inspired the development of non-hallucinogenic, non-cardiotoxic analogues like 18-MC and tabernanthalog for therapeutic use. In 2025, Texas allocated $50 million for clinical research on ibogaine to develop FDA-approved treatments for opioid use disorder, co-occurring substance use disorders, and other ibogaine-responsive conditions.