Ibogaine for the treatment of opioid dependence: From mechanisms of action to clinical efficacy

Identifier:  TDX:4540

Handle: https://hdl.handle.net/20.500.11797/TDX4540

Authors:  Oña Esteve, Genís

Abstract:
Substance use disorders remain one of the most challenging health problems to address. In particular, opioid dependence has caused serious public health issues in countries such as the United States and Canada, underscoring the need for innovative treatments. Recently, there has been renewed interest in psychedelic drugs. Among these, ibogaine, a natural alkaloid from the African plant Tabernanthe iboga, seems particularly effective in treating substance use disorders. However, controlled trials on ibogaine's safety and efficacy are lacking, and its mechanisms of action are not well understood. In this thesis, we conducted clinical and preclinical studies on ibogaine. A systematic review of adverse effects associated with ibogaine was performed. We also designed a Phase II, double-blind clinical trial with low doses of ibogaine (100 mg) in methadone detoxification. Plasma samples were analyzed using a metabolomic approach. The narrative review identified potential targets of ibogaine and its mechanisms of action. Preclinically, we designed a study with mice to investigate these mechanisms. Following ibogaine administration, brain tissue was analyzed using transcriptomic analysis. The systematic review highlighted the need for medical supervision during ibogaine treatments. In the clinical trial with 20 patients, we observed a significant decrease in methadone tolerance and opioid withdrawal syndrome, without serious adverse effects. Metabolomic analysis results suggest that ibogaine may reverse the effects of chronic opioid use on energy metabolism. The preclinical study revealed new potential pathways associated with ibogaine's anti-addictive effects. This thesis provides data on the safety and efficacy of ibogaine in a Phase II study and delves into its mechanisms of action. We conclude that ibogaine is a promising molecule for treating substance use disorders, warranting further research.