Substance use disorders (SUDs) are a major global health burden, and psychedelic-assisted therapies are now gaining scientific interest, with ibogaine being considered as a candidate for anti-addictive effects across multiple substance classes. Ibogaine is a multi-target indole alkaloid acting on opioid, glutamatergic, serotonergic, and sigma systems with potential to rapidly reduce withdrawal and cravings after a single administration. Ibogaine is metabolized into noribogaine, which has a longer half-life and contributes to sustained pharmacological effects. These compounds act on multiple neurotransmitter systems including NMDA receptors, serotonin receptors, and opioid receptors, which allow it to have a broad neurobiological effect. It also has anti-addictive properties linked to neuroplasticity, dopamine modulation, and opioid receptor activity. Additionally, iboga has use in African rituals, with modern interest increasing in the twentieth century. Ibogaine now is an unregulated or semi-regulated substance with increased interest in controlled clinical development as well. Clinical evidence for ibogaine comes from observational studies and case reports, e.g., particularly in opioid use disorder. Ibogaine carries significant risks, particularly cardiotoxicity, neurological adverse effects including hallucinations, and reported fatalities. Safer derivates such as noribogaine and tabernanthalog (TBG) are being developed to retain anti-addictive efficacy and reduce toxicity. Ibogaine induces prolonged oneirogenic states involved in autobiographical memory processing, and outcomes are influenced by setting, integration therapy, and psychotherapy. Current research is largely observational, and studies are small, which highlights the need for standardized protocols and clinical trials. Overall, ibogaine represents a therapeutic candidate for SUDs, with broad anti-addictive potential. In this review, we provide an overview of ibogaine's history and pharmacology, critically examine its therapeutic potential in multiple SUDs, and discuss current limitations, emerging alternatives, and future directions.
