Ibogaine and Noribogaine: Mechanisms and Therapeutic Potential as Addiction Medicines

As part of the ongoing Student/Postdoc-Run Speaker Series (SPRSS), and on behalf of the Neural Mechanisms of Psychedelic Drug Action Group, Dr. Deborah Mash from the University of Miami will give a talk titled "Ibogaine and Noribogaine: Mechanisms and Therapeutic Potential as Addiction Medicines."  The talk can also be accessed via Zoom here.

Abstract: Ibogaine is a powerful psychoactive substance that not only alters perception, mood and affect, but also stops addictive behaviors.
Ibogaine has a very long history of ethnobotanical use in low doses to combat fatigue, hunger and thirst and, in high doses as a sacrament in African ritual contexts. In the 1960’s, American and European self-help groups provided public testimonials that a single dose of ibogaine alleviated drug craving, opioid withdrawal symptoms, and prevented relapse for weeks, months and sometimes years. Noribogaine was identified in 1995 as an active metabolite of ibogaine.  Pharmacokinetic studies demonstrate that ibogaine undergoes extensive first pass metabolism to noribogaine.
We hypothesized that the potential therapeutic utility of ibogaine for substance use disorders and persistence of beneficial effects was mediated by noribogaine.  Other researchers have demonstrated that noribogaine is capable of promoting structural neural plasticity, a mechanism that is shared by serotonergic psychedelics and ketamine.  Noribogaine is a potent “psychoplastogen” that increases glial cell line-derived neurotrophic factor (GDNF)expression in the midbrain, the formation of new synapses, and cortical neuron dendritic arbor complexity. The mechanism underlying ibogaine’s long-term effect and treatment durability remains unknown.
Ibogaine is a dissociative psychedelic with oneiric properties that interrupts multiple aspects of addiction, including the withdrawal/negative affect and the preoccupation/anticipation of the rewarding effects of psychoactive substances. Noribogaine may promote neuroplastic changes at the synapse which drive functional change at the circuit level to affect cognition and behavior.  Opening a window of neuroplasticity with noribogaine highlights a potential opportunity to target the underlying mechanisms of substance use disorders. Treatment with noribogaine avoid the subjective effects which may not be therapeutic.  A multiple ascending dose study of noribogaine is underway to optimize dose selection for a Phase 2 study in alcohol use disorder.

For information on other talks organized by the 'Neural Mechanisms of Psychedelic Drug Action' Student/Postdoc-Run Group, view the program overview here.