Assessment of neurotoxicity from potential medications for drug abuse: ibogaine testing and brain imaging.

New brain-monitoring technologies can detect pharmacological effects more sensitively than clinical exams, but each detected change must be assessed for clinical significance. Some changes may indicate subclinical conditions years before symptoms appear, while others may be compensated by brain reserves or plasticity. Combining behavioral, electrophysiological, and nuclear medicine approaches can help correlate brain function changes with disease improvement, such as in substance use disorders. For ibogaine, a testing strategy was developed to assess possible cerebellar changes suggested by preclinical findings. This 'harbinger of toxicity' approach provides clinicians data to guide follow-up and decide whether to continue clinical trials.

Study at a glance

Abstract

New technologies utilized for monitoring brain function can be more sensitive in the assessment of desired or undesired pharmacological effects than can clinical examination. Nonetheless, careful case-by-case analysis is required to determine to what extent a change detected with a sensitive imaging modality will have clinical significance. Whereas in some instances the technology may suggest a subclinical condition years before clinical signs develop, in other instances changes seen may be compensated for through system reserves, redundancy, or plasticity. Furthermore, simultaneous application of several assay instruments, including behavioral, electrophysiological, and nuclear medicine approaches, may be appropriate and useful for establishing correlations between changes in specific aspects of brain function and amelioration of a disease (drug abuse disorder) or its sequelae. In the example of ibogaine, a testing strategy was developed to assess human subjects for possible changes in cerebellar function (that were suggested by preclinical findings indicating subtle damage). Thus, subjects may be tested for subclinical alterations during and immediately following a clinical trial. This "harbinger of toxicity" approach would provide clinicians the critical data necessary for appropriate follow-up of subjects as well as the propriety of continuance of the clinical trials within the ibogaine project.