The neurobiology of opioid use

The endogenous opioid system consists of opioid receptors and endogenous opioid peptide ligands, and it is the body's internal system that contributes to survival by regulating pain and mood states, and by promoting reward by natural stimuli (like food, sex, and social interaction). Mu-opioid receptors are the primary targets of harmfully used opioids, making them one of the best characterized opioid receptors. More than 20 endogenous peptides have been identified for opioid receptors, all derived from 3 precursors: proopiomelanocortin (POMC), proenkephalin, and prodynorphin. Overall, it is thought that opioid use disorder (OUD) induces a dysregulation of brain pathways involved in reward and cognition in which reward-stress pathways are strengthened, and connectivity associated with cognitive control is weakened. This chapter outlines detailed information about the neurobiology of these systems and the neural circuitry of opioid use disorder, including a discussion of the neural circuit, opioid-induced alterations in neurotransmitter systems due to opioids, and specific neurotransmitter contributions to opioid effects. The impact of sex on these systems is also discussed. Finally, a neurobiological understanding of medications and treatments for opioid use disorder is presented.