Dear list,

I would like to draw your attention to a very important paper out of the
Division of Neurotoxicology, National Center for Toxicological Research. The
paper indicates a no effect dose for ibogaine neurotoxicity supporting the
Molinari et al., "Ibogaine neurotoxicity: A reevaluation", 1996.

Abstracts for many papers may be found on Medline <
http://www.ncbi.nlm.nih.gov/pubmed/>.

Howard
********
: Toxicol Sci 2000 Sep;57(1):95-101

A dose-response study of ibogaine-induced neuropathology in the rat
cerebellum.

Xu Z, Chang LW, Slikker W Jr, Ali SF, Rountree RL, Scallet AC

Department of Pathology and Department of Pharmacology & Toxicology,
University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
Division of Neurotoxicology, National Center for Toxicological Research,
Jefferson, Arkansas 72.

[Medline record in process]

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).


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