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.
Phencyclidine (PCP) at doses of 0.5 to 10 mg/kg intravenously altered glucose use in 41 of 87 brain regions of rats, with changes ranging from 25% to 270% of control levels. Glucose metabolism increased throughout the limbic system except the habenula, increased in most sensory structures but decreased in specific layers of the somatosensory and auditory cortices and the inferior colliculus, and increased throughout the motor system with a striking columnar pattern in the motor cortex while decreasing in the frontal cortical pole. Effects of 5 mg/kg diminished over time, though eight regions maintained altered metabolism at 180 minutes. The findings suggest PCP activates functional circuits, especially the limbic system, which may underlie its psychotomimetic properties.