OPRM1 and respiratory depression: Although the precise pathways are still debated, adverse side effects of tolerance and respiratory depression are also mediated through the MOR.7–9 The medicinal chemists who designed the first synthetic opioids reasoned that compounds with high analgesic potency would be safer than morphine.10 They touted the high binding affinity of sufentanil to the MOR.11 Unfortunately, the hypothesis that potent compounds would be safe was incorrect; due to their dangerous side effects, synthetic opioids have become the leading cause of drug overdose deaths in the United States!12