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.
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 |
Citations in the library
Cited by 33
- Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Cell May 11, 2023
- Psychedelics therapeutics: What we know, what we think, and what we need to research. Neuropharmacology September 27, 2022
- Structural pharmacology and therapeutic potential of 5-methoxytryptamines. Nature June 1, 2024
- The role of neurotrophic factors in novel, rapid psychiatric treatments. Neuropsychopharmacology 2024
- The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology International Journal of Molecular Sciences January 10, 2023
and 28 more in the library
Cites 38
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Serotonin transporter-ibogaine complexes illuminate mechanisms of inhibition and transport. Nature May 1, 2019
- Treatment of acute opioid withdrawal with ibogaine. American Journal on Addictions 1999
- Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Journal of Neuroscience January 19, 2005
- Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse 2018
and 33 more in the library