Gestational THC exposure in rodents activated the same placental gene expression signature associated with schizophrenia risk in humans, including altered expression of Furin, Rccd1, and Atp5mk genes. The exposed offspring showed reduced fetal weights and sex-specific changes in additional genes like Eif5 and Rps10, with some markers persisting into adulthood alongside schizophrenia-like behaviors. This mechanistic discovery bridges a critical gap in understanding how cannabis use during pregnancy might influence neurodevelopmental outcomes. Previous epidemiological studies have suggested links between maternal cannabis use and psychiatric disorders in offspring, but the biological pathways remained unclear. The placental gene signature represents a potentially measurable biomarker that could identify at-risk pregnancies before behavioral symptoms emerge. However, the translation from rodent models to human outcomes requires caution, as placental biology and cannabis metabolism differ between species. The sex-specific gene expression changes also suggest that male and female fetuses may respond differently to THC exposure, potentially explaining variable risk patterns observed in human populations. While confirmatory of suspected mechanisms, this single preclinical study needs replication in human cohorts before informing clinical recommendations about cannabis use during pregnancy.