The brain undergoes important growth and plasticity during prenatal development, and environmental exposures like stress and pharmacology play an important role during this time, partly through transcriptional dysregulation. To investigate these processes in humans, we use human-derived 3-dimensional in-vitro and ex-vivo systems systems called brain organoids. We employ a very novel organoid system derived from human fetal tissue via donation by pregnant individuals following elective termination of pregnancy during the first trimester. To determine tissue- and cell-type specific responses to treatment with drugs such as antidepressants, cannabinoids and glucocorticoids, we profile the epigenome, transcriptome, and proteome in organoids using bulk or single-cell sequencing approaches. Subsequently, we use immunofluorescence to better understand protein, and cell morphology-level long-term effects on cell-type population dynamics. Previously, we found that prolonged glucocorticoids exposure in cerebral organoids derived from human induced pluripotent stem cells can activate a robust cell-type-specific differential response of key transcription factors involved in neuronal cell fate regulation. in-vitro findings were consistent across diverse genetic backgrounds, and were supported by in vivo human fetal brain data. Therefore, our previous results showed that the likely outcome of aberrant overexposure to stress neurobiology is a lasting shift in neuronal type distribution and developing brain architecture. This previous work shed light on the mechanisms by which environmental stimuli like maternal stress-mediated elevated glucocorticoids could lead to subtle changes in brain development and ultimately vulnerability to mental illness. Following these findings, our current studies investigate the effect of pharmacology commonly used to treat stress-related disorders. We investigate the current standard of care selective serotonin reuptake inhibitors drug class, as well as rapid-acting antidepressants like psilocybin, compare cannabinoids THC and CBD, and finally continue the investigation of glucocorticoids such as dexamethasone. Importantly, we also use novel and physiologically improved human brain organoid models derived from fetal tissue, whereby we can compare donor differences in primary human tissue. Our multi-modal molecular approach to personalized medicine will allow identification of donor-specific and drug-specific cellular responses in the developing brain, therefore informing understanding of pharmacology exposure risk and and resilience mechanisms and their potential lasting impact.