This study highlights the benefits of using iPS and iN cell technology for in-depth analysis of gene variants that have been associated with a particular human disease. To date, we have not yet tested the synaptic effect of acute or chronic ethanol application on other cell types such as excitatory or dopaminergic neurons. Therefore, it remains unknown whether the differential sensitivities we observe in response to ethanol, between MOR N40 and D40, is characteristic to inhibitory iNs or observed across other neuronal cell types. This can only be determined experimentally. In addition, a combination of neuronal cell types can be combined with the use of microfluidic devices Fantuzzo, De Filippis et al., 2017) to mimic reward neurocircuitry. However, our focus in this study was to understand how ethanol sensitivity impacts synaptic function in inhibitory iNs that mimic those in reward circuitry. Therefore, characterization of MOR N40D in other neuronal cell types will be addressed in future studies. This work identifies neurophysiological differences in the human neuronal response to alcohol that is influenced by common variation in human OPRM1. Our findings