In Vivo Neurobiological Effects of Ibogaine and Its O-Desmethyl Metabolite, 12-Hydroxyibogamine (Noribogaine), in Rats
Michael H. Baumann, Richard B Rothman, John Pablo, Deborah C. Mash
Journal of Pharmacology and Experimental Therapeutics May 1, 2001 DOI: 10.1016/s0022-3565(24)29567-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male rats |
| Interventions | Ibogaine Noribogaine |
| Dose | 1 and 10 mg/kg |
| Topics | Serotonin Ibogaine |
| Keywords | Pharmacology Nucleus accumbens Microdialysis Metabolite In vivo Extracellular Dopamine Endocrinology Biochemistry Receptor |
| Citations | 69 |
| Key findings | Noribogaine is biologically active, approximately 10 times more potent than ibogaine as an indirect serotonin agonist, and less apt to produce tremors, suggesting it may be a safer alternative. |
Abstract
Ibogaine is a naturally occurring compound with purported antiaddictive properties. When administered to primates, ibogaine is rapidly o-demethylated to form the metabolite 12-hydroxyibogamine (noribogaine). Peak blood levels of noribogaine exceed those of ibogaine, and noribogaine persists in the bloodstream for at least 1 day. Very few studies have systematically evaluated the neurobiological effects of noribogaine in vivo. In the present series of experiments, we compared the effects of i.v. administration of ibogaine and noribogaine (1 and 10 mg/kg) on motor behaviors, stress hormones, and extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of male rats. Ibogaine caused dose-related increases in tremors, whereas noribogaine did not. Both ibogaine and noribogaine produced significant elevations in plasma corticosterone and prolactin, but ibogaine was a more potent stimulator of corticosterone secretion. Neither drug altered extracellular DA levels in the nucleus accumbens. However, both drugs increased extracellular 5-HT levels, and noribogaine was more potent in this respect. Results from in vitro experiments indicated that ibogaine and noribogaine interact with 5-HT transporters to inhibit 5-HT uptake. The present findings demonstrate that noribogaine is biologically active and undoubtedly contributes to the in vivo pharmacological profile of ibogaine in rats. Noribogaine is approximately 10 times more potent than ibogaine as an indirect 5-HT agonist. More importantly, noribogaine appears less apt to produce the adverse effects associated with ibogaine, indicating the metabolite may be a safer alternative for medication development.
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 49
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse 2018
- The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. Journal of Biological Chemistry May 25, 2012
- The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation Molecules January 29, 2015
- Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology 2018
and 44 more in the library
Cites 26
- Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience July 1, 1993
- Treatment of acute opioid withdrawal with ibogaine. American Journal on Addictions 1999
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- 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. Brain Research September 19, 1994
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
and 21 more in the library