Placenta and Neurodevelopmental Effects of in utero Cannabis Exposure

Sociopolitical shifts in the U.S. and around the world have dramatically led to the decriminalization, medicalization, and legalization of cannabis use over the past years. The reduced risk perception of cannabis in society along with the growing wide exposure to potent cannabis (with high levels of Δ9-tetrahydrocanabinol;(THC) has contributed to it being commonly used by vulnerable groups relevant to sensitive windows of brain development such as pregnant women. Cannabinoids such as THC readily cross the placental barrier with the potential to impact the fetus. Our research group and others has accumulated evidence demonstrating that prenatal THC exposure does have long-term effects on behaviors—relevant to reward, motivation, negative affect — and molecular disturbances linked to synaptic plasticity with profound epigenetic dysregulation, especially in mesocorticolimbic brain areas. Despite the growing number of pregnant women who use cannabis and knowledge we have accrued about the long-term consequences of developmental THC exposure, there remains a dearth of information regarding biological systems downstream of such early cannabinoid perturbation that could contribute to the protracted effects especially relevant to the human condition. That question is of particular interest since it aligns with the tenet that most psychiatric disorders have a developmental genesis. Our research will fill this significant gap of knowledge by investigating an organ that is often forgotten, but which plays a crucial role during development — the placenta. We will study a unique resource of human specimens (placental and fetal brain; focus on the nucleus accumbens) to interrogate the proteome in relation to in utero cannabis exposure and subsequent offspring behavior as well as proteomic study of our translational rat model in which placenta, brain and behavior will be investigated. This study will identify early indices of psychiatric vulnerability and their developmental trajectory into adulthood.