A Single Administration of the Atypical Psychedelic Ibogaine or Its Metabolite Noribogaine Induces an Antidepressant-Like Effect in Rats.
Paola Rodrı Guez, Jessika Urbanavicius, José Pedro Prieto, Sara Fabius, Ana Laura Reyes, Václav Havel, Dalibor Sames, Cecilia Scorza, Ignacio Carrera
ACS Chemical Neuroscience June 3, 2020 DOI: 10.1021/acschemneuro.0c00152 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Open-label Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ibogaine Noribogaine |
| Dose | 20 and 40 mg/kg i.p., single injection for each dose |
| Topics | Depression Serotonin Ibogaine |
| Keywords | Sert Preclinical test Psychedelic drugs Psychedelic antidepressants Preclinical drug research Ibogaine pharmacology |
| Citations | 44 |
| Key findings | Ibogaine and noribogaine induce dose- and time-dependent antidepressant-like effects in rats, likely through a polypharmacological mechanism. |
Abstract
Anecdotal reports and open-label case studies in humans indicated that the psychedelic alkaloid ibogaine exerts profound antiaddictive 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 administration in rats using the forced swim test (FST, 20 and 40 mg/kg i.p., single injection for each dose). 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 min) and correlated with high brain concentrations (estimated >8 μM of free drug), while the ibogaine's antidepressant-like effect was significant at 3 h. At this time point, both ibogaine and noribogaine were present in rat brain at concentrations that cannot produce the same behavioral outcome on their own (ibogaine ∼0.5 μM, noribogaine ∼2.5 μM). Our data suggests a polypharmacological mechanism underpinning the antidepressant-like effects of ibogaine and noribogaine.