A dose-response study of ibogaine-induced neuropathology in the rat cerebellum.
Z Xu, L W Chang, William Slikker, S F Ali, Robert Rountree, Andrew C. Scallet
Toxicological sciences : an official journal of the Society of Toxicology September 1, 2000 DOI: 10.1093/toxsci/57.1.95 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Dose-response study Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Rats |
| Intervention | Ibogaine |
| Dose | 25 mg/kg, 50 mg/kg, 75 mg/kg, 100 mg/kg |
| Duration | Single injection |
| Topics | Addiction Ibogaine |
| Keywords | Addiction therapy Substance abuse treatment Dependency management Recovery intervention Drug addiction treatment Neurotoxicity Brain cell damage Neuronal damage Neurodegenerative effects Brain toxicity Neurological harm Cells Compound Dose-response study Pharmacodynamics Dosage effects Concentration-effect relationship Dose dependency Dose-effect relationship Safety assessment Toxicity evaluation Safe threshold Adverse effects Therapeutic range Safety level Risk assessment |
| Citations | 37 |
| Key points | Ibogaine caused dose-dependent neurodegeneration in rat cerebellum, with 25 mg/kg identified as a no-observable-adverse-effect level. |
Abstract
Ibogaine (IBO) is an indole alkaloid from the West African shrub, Tabernanthe iboga. It is structurally related to harmaline, and both these compounds are rigid analogs of melatonin. IBO has both psychoactive and stimulant properties. In single-blind trials with humans, it ameliorated withdrawal symptoms and interrupted the addiction process. However, IBO also produced neurodegeneration of Purkinje cells and gliosis of Bergmann astrocytes in the cerebella of rats given even a single dose (100 mg/kg, ip). Here, we treated rats (n = 6 per group) with either a single ip injection of saline or with 25 mg/kg, 50 mg/kg, 75 mg/kg, or 100 mg/kg of IBO. As biomarkers of cerebellar neurotoxicity, we specifically labeled degenerating neurons and axons with silver, astrocytes with antisera to glial fibrillary acidic protein (GFAP), and Purkinje neurons with antisera to calbindin. All rats of the 100-mg/kg group showed the same pattern of cerebellar damage previously described: multiple bands of degenerating Purkinje neurons. All rats of the 75-mg/ kg group had neurodegeneration similar to the 100-mg/kg group, but the bands appeared to be narrower. Only 2 of 6 rats that received 50 mg/kg were affected; despite few degenerating neuronal perikarya, cerebella from these rats did contain patches of astrocytosis similar to those observed with 75 or 100 mg/kg IBO. These observations affirm the usefulness of GFAP immunohistochemistry as a sensitive biomarker of neurotoxicity. None of the sections from the 25-mg/kg rats, however stained, were distinguishable from saline controls, indicating that this dose level may be considered as a no-observable-adverse-effect level (NOAEL).
Comparable studies
Other preclinical and animal studies on ibogaine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study | |
| Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Morphine-dependent rats | 1992 | Randomized controlled trial | |
| Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions of the anti-addiction drug, Ibogaine. Dopaminergic-like SHSY5Y cell line | 2006 | In vitro cell culture study | |
| Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents. Mice and rats | 2016 | Experimental study with three experiments | |
| Noribogaine reduces nicotine self-administration in rats. Adult male Sprague-Dawley rats | 2015 | Within-subject design with a Latin square test schedule |
Citations in the library
Cited by 8
- The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation Molecules January 29, 2015
- Treating drug dependence with the aid of ibogaine: a retrospective study. Journal of psychopharmacology (Oxford, England) November 1, 2014
- Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Human & Experimental Toxicology March 1, 2008
- How toxic is ibogaine? Clinical toxicology (Philadelphia, Pa.) 2016
- Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Translational Psychiatry May 31, 2016
and 3 more in the library
Cites 6
- Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience July 1, 1993
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Neuropharmacology May 1, 1992
- Ibogaine induces glial activation in parasagittal zones of the cerebellum. Neuroreport March 1, 1993
- Ibogaine neurotoxicity: a re-evaluation. Brain Research October 21, 1996
and 1 more in the library