The pathophysiology of opioid-induced respiratory depression

Handb Clin Neurol. 2022:188:339-355. doi: 10.1016/B978-0-323-91534-2.00003-5.


Opiates, such as morphine, and synthetic opioids, such as fentanyl, constitute a class of drugs acting on opioid receptors which have been used therapeutically and recreationally for centuries. Opioid drugs have strong analgesic properties and are used to treat moderate to severe pain, but also present side effects including opioid dependence, tolerance, addiction, and respiratory depression, which can lead to lethal overdose if not treated. This chapter explores the pathophysiology, the neural circuits, and the cellular mechanisms underlying opioid-induced respiratory depression and provides a translational perspective of the most recent research. The pathophysiology discussed includes the effects of opioid drugs on the respiratory system in patients, as well as the animal models used to identify underlying mechanisms. Using a combination of gene editing and pharmacology, the neural circuits and molecular pathways mediating neuronal inhibition by opioids are examined. By using pharmacology and neuroscience approaches, new therapies to prevent or reverse respiratory depression by opioid drugs have been identified and are currently being developed. Considering the health and economic burden associated with the current opioid epidemic, innovative research is needed to better understand the side effects of opioid drugs and to discover new therapeutic solutions to reduce the incidence of lethal overdoses.

Keywords: Brainstem; Control of breathing; Opioid; Overdose; Pathophysiology; Respiratory depression.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid* / adverse effects
  • Animals
  • Humans
  • Respiratory Insufficiency* / chemically induced
  • Respiratory Insufficiency* / drug therapy


  • Analgesics, Opioid