The Endocannabinoid System in Prefrontal Synaptopathies

Endocannabinoid (eCB) function in the prefrontal cortex (PFC) presents as a highly connected, widespread hub for the modulation of a vast array of synaptic functions. Given the known role of the PFC in a range of disorders from mental retardation, neurodegenerative diseases, and schizophrenia to drug addiction, stress, and anxiety, all of which are characterized by aberrant function at the synaptic compartment (here termed “synaptopathies”), it follows that eCB dysfunction is implicated as a significant causal factor in a plethora of disease states. Genetic and environmental manipulation of the eCB system in the PFC has thus been extensively studied with regard to many of these diseases and highlighted significant causal factors in their development and expression. Here, we examine the current body of literature as well as extensions of theoretical implications regarding the role of eCBs in the generation and presenting characteristics of a range of disorders. Elucidating the functions of eCBs in disease states will participate to the understanding of their etiology and the development of innovative pharmacotherapies.