The unique pharmacology of fentanyl contributes to its exceptional overdose risk: fentanyl has high affinity and intrinsic activity at mu-opioid receptors (MOR) (>50-fold more potent than heroin) and is very lipophilic, resulting in rapid activation of central MORs to produce euphoria, respiratory depression, and other classical MOR-mediated effects2–4. This evidence concerns the gene OPRM1 and respiratory depression.