A Single Administration of the Atypical Psychedelic Ibogaine or its Metabolite Noribogaine Induces an Antidepressant-like Effect in Rats
Paola Rodrı́guez, Jessika Urbanavicius, José Pedro Prieto, Sara Fabius, Ana Laura Jaimes Reyes, Václav Havel, Dalibor Sameš, Cecilia Scorza, Ignacio Carrera
ChemRxiv March 19, 2020 Peer reviewed DOI: 10.26434/chemrxiv.12001407 via OpenAlex
Summary
Ibogaine and its metabolite noribogaine demonstrated a dose- and time-dependent antidepressant-like effect in rats, as measured by the forced swim test. Noribogaine's effect lasted for 30 minutes and correlated with high brain concentrations, while ibogaine's effect was significant at 3 hours. At that time, both substances were present in the brain at levels insufficient to produce their effects independently. These findings suggest a complex mechanism behind their antidepressant-like properties.
Study at a glance
| Population | rats |
|---|---|
| Key finding | Ibogaine and noribogaine induced a dose- and time-dependent antidepressant-like effect in rats without significant changes in locomotor activity. |
Abstract
Anecdotal reports and open label case studies in humans indicated that the psychedelic alkaloid ibogaine exert profound anti-addictive effects. Ample preclinical evidence demonstrated the efficacy of ibogaine, and its main metabolite noribogaine, in substance use disorder rodent models. In contrast to addiction research, depression-relevant effects of ibogaine or noribogaine in rodents have not been previously examined. We have recently reported that the acute ibogaine administration induced a long-term increase of brain-derived neurotrophic factor mRNA levels in the rat prefrontal cortex, which led us to hypothesize that ibogaine may elicit antidepressant-like effects in rats. Accordingly, we characterized behavioral effects (dose and time-dependence) induced by the acute ibogaine and noribogaine (20 and 40 mg/kg, i.p.) administration in rats using the forced swim test (FST). We also examined the correlation between plasma and brain concentrations of ibogaine and noribogaine and the elicited behavioral response. We found that ibogaine and noribogaine induced a dose- and time-dependent antidepressant-like effect without significant changes of animal locomotor activity. Noribogaine’s FST effect was short lived (30 minutes) and correlated with high brain concentrations (estimated > 8 mM of free drug), while the ibogaine’s antidepressant-like effect was significant at 3 hours. At this time point, both ibogaine and noribogaine were present in rat brain, at concentrations which cannot produce the same behavioral outcome on their own (ibogaine ~ 0.5 mM, noribogaine ~ 2.4 mM). Our data suggest a polypharmacological mechanism underpinning the antidepressant-like effects of ibogaine and noribogaine.