Oxa-noribogaine reduces alcohol drinking through aversion learning and by altering glutamatergic activity in the mPFC
Research Square March 31, 2026 Marcus W. Meinhardt, Ivan Skorodumov, Florian Walter et al.
A compound derived from ibogaine, oxa-noribogaine, reduces alcohol consumption in rats by strengthening learning from negative drinking outcomes. It produces sustained decreases in alcohol intake and relapse-like drinking, matching or exceeding ibogaine's efficacy without detectable motor or cardiac side effects. These effects involve transient changes in prefrontal brain activity, lasting alterations in glutamatergic signaling after aversion-related learning, and normalization of neurotrophic signaling in cortico-striatal circuits. The results generalize across multiple models, genetically diverse animals, and independent study sites, identifying oxa-noribogaine as a promising treatment candidate for alcohol use disorder.