The dynamic nature of neurodevelopmental processes creates critical windows for external factors such as drugs to impact brain epigenetic mechanisms that lead to protracted alterations on adult brain and behavior. The recent increases in the legalization of marijuana for medicinal and recreational use has highlighted the lack of neurobiological knowledge available regarding the long-term impact of cannabis on the developing brain. This talk will provide an overview of our research exploring the effects of prenatal and adolescent exposure to Δ9-tetrahydrocannabinol (THC; the psychoactive component of marijuana) on the mesocorticolimbic system and behavior in adulthood. The talk will provide insights regarding common molecular and epigenetic features in the neurogenesis of the prefrontal cortex and striatum that highlight discrete disturbances of cytoskeletal and dendritic regulation in adults with developmental THC exposure. The dysregulation of synaptic plasticity and motivated behavior extend even across generations highlighting the epigenetic legacy that overall has significant relevance to psychiatric vulnerability.