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).