Provided herein is an in vitro model of the blood brain barrier. In some embodiments, the model includes: an endothelial cell layer, and brain tissue layer comprising neuronal cells, and optionally one or more of astrocytes, pericytes, oligodendrocytes, and microglia. In some embodiments, the model further comprises a porous membrane between said endothelial cell layer and the neuronal cell layer. A microfluidic device comprising the same and methods of use thereof are also provided.