UC Davis

Approximately 6% of the United States adult population (20 million people) battle a substance use disorder (SUD). The number of people dealing with a SUD has increased exponentially over the last 20 years. Drug-involved overdose deaths parallel the increase in users as the U.S. recorded 92,000 deaths in 2020 alone. Furthermore, the cost related to alcohol and drug use in the United States exceeds $700 billion dollars per year. Less than 10% of people battling a SUD seek help, which is indicative of the ineffectiveness in current SUD treatments. Ibogaine, the main component in the root of Tabernanthe iboga, has been reported to display anti-addictive properties in animal models and human studies. However, ibogaine’s mechanism of action remains unknown because of its promiscuous binding to multiple receptors and transporters. While ibogaine’s use as treatment for SUDs is tempting, safety concerns related to heart conditions and hallucinations led the DEA to classify it as a schedule I controlled substance. This schedule I classification has made ibogaine increasingly difficult to thoroughly investigate because of special licenses that are required. Research labs that hold DEA licenses to study ibogaine face another issue which is its scarcity. Currently, the main source in which ibogaine is obtained is through isolation from plants in Africa which is leading to deforestation. To prevent damage to the ecosystem and facilitate its availability for further biological investigation, we developed a short and truly scalable total synthesis of ibogaine. Furthermore, we developed a series of analogs that contain the similar ibogaine scaffold because we believe they might retain the anti-addictive properties but lack the off-target effects.