Other MOR ligands with greater bias, such as SR17018 (Schmid et al., 2017), show diminished respiratory depression in rodents compared to fentanyl (Gillis et al., 2020a), while PZM21 (Manglik et al., 2016; Kudla et al., 2019) and mitragynine(s) (Váradi et al., 2016; Kruegel et al., 2016; Kruegel et al., 2019; Chakraborty and Majumdar, 2020) display reduced abuse liability (Yue et al., 2018; Hemby et al., 2019). This evidence concerns the gene OPRM1 and respiratory depression.