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 Sames, Cecilia Scorza, Ignacio Carrera
ChemRxiv March 19, 2020 preprint DOI: 10.26434/chemrxiv.12001407 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Open-label |
|---|---|
| Population | Rats |
| Interventions | Ibogaine Noribogaine |
| Dose | 20 and 40 mg/kg, i.p. |
| Topics | Ibogaine |
| Keywords | Pharmacology Antidepressant Behavioural despair test Metabolite Hippocampus |
| Citations | 1 |
| Key points | 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 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.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |