Has the time come for predictive computer modeling in CNS drug discovery and development?

We discuss whether a new paradigm, quantitative systems pharmacology (QSP), based on computational neuroscience modeling combined with proper drug target engagement and pharmacology, human pathology, imaging studies, and calibration and validation using clinical studies in human subjects might improve the success rate of central nervous systems research and development (CNS R&D) projects. We suggest that an improved understanding of neuronal circuit interactions using a humanized computer-based integration of physiology and pharmacology knowledge can substantially de-risk new CNS projects.