Neuronal mechanisms underlying opioid-induced respiratory depression: our current understanding

J Neurophysiol. 2021 May 1;125(5):1899-1919. doi: 10.1152/jn.00017.2021. Epub 2021 Apr 7.


Opioid-induced respiratory depression (OIRD) represents the primary cause of death associated with therapeutic and recreational opioid use. Within the United States, the rate of death from opioid abuse since the early 1990s has grown disproportionally, prompting the classification as a nationwide "epidemic." Since this time, we have begun to unravel many fundamental cellular and systems-level mechanisms associated with opioid-related death. However, factors such as individual vulnerability, neuromodulatory compensation, and redundancy of opioid effects across central and peripheral nervous systems have created a barrier to a concise, integrative view of OIRD. Within this review, we bring together multiple perspectives in the field of OIRD to create an overarching viewpoint of what we know, and where we view this essential topic of research going forward into the future.

Keywords: OIRD; breathing; neuromodulation; opioid; respiration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Central Pattern Generators / drug effects*
  • Humans
  • Medulla Oblongata / drug effects*
  • Opioid-Related Disorders / complications*
  • Respiratory Insufficiency / chemically induced*


  • Analgesics, Opioid