Abstract

Prenatal cannabis use is on the rise, and observational studies suggest that such use results in neurodevelopmental deficits in the offspring. Because observational studies can be confounded by unaccounted factors, we studied the neurodevelopmental consequences, at the molecular level, of prenatal cannabis use. We applied an integrated multi-omics approach, combining transcriptomics and global proteomics, tofirst trimester(T1) andsecond trimester(T2) humanfetal brains from pregnancies with and without documented maternal cannabis exposureand nouse of drugsof abuse.Prenatal cannabis exposure produced minimal molecular effects in female T1 fetal brains but induced pronounced system-level disruption in male T2 fetal brains. These disrupted pathways have molecular signatures linked to neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder, schizophrenia-related pathology, and disorders of cortical connectivity, raising significant concerns of prenatal cannabis use.