This rodent study investigates behavioral effects of acute ibogaine and noribogaine administration in rats. It found that both produced a dose-and time-dependent antidepressant effect without substantial changes in animal locomotor activity.
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.“
Authors: Paola Rodrı́guez, Jessika Urbanavicius, José P. Prieto, Sara Fabius, Ana L. Reyes, Vaclav Havel, Dalibor Sames & Cecilia S. I. Carrera
Summary of A Single Administration of the Atypical Psychedelic Ibogaine or Its Metabolite Noribogaine Induces an Antidepressant-Like Effect in Rats
Introduction
Ibogaine is an atypical psychedelic drug that induces waking dream-like states and vivid memory recall and replay. It has been shown to relieve drug withdrawal symptoms and cravings and improve quality of life in subjects diagnosed with opioid dependence. Preclinical work has shown that ibogaine reduces self-administration of opioids, cocaine, nicotine, and alcohol, and reduces opioid withdrawal symptoms in opioid-dependent animals. Ibogaine induces a dose-dependent upregulation of glial cell-derived neurotrophic factor (GDNF) in the mesocorticolimbic and nigral dopaminergic circuits in rats, and a large upregulation of brain-derived neurotrophic factor (BDNF) expression in the prefrontal cortex, suggesting that ibogaine may exert an antidepressant-like effect. We hypothesized that ibogaine administration in rats would exhibit antidepressant-like effects because ibogaine inhibits the plasma membrane serotonin transporter (SERT). However, ibogaine can also block N-methyl-D-aspartate receptors (NMDA-R) and promote neuritogenesis in rat cortical primary cultures. We examined the effects of ibogaine and noribogaine in the forced swim test in rats, using a widely used preclinical assay, to determine the behavioral effect of ibogaine and noribogaine on the coping strategy to an acute inescapable stress.
Results and discussion
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https://doi.org/10.1021/acschemneuro.0c00152
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Study details
Compounds studied
Ibogaine
Topics studied
Depression
Study characteristics
Animal Study