Pharmacological Interventions for Opioid-Induced Respiratory Depression

Dear Colleagues,

The World Health Organization reported that, in 2019, approximately 125,000 people died from opioid overdose and that opioids were involved in nearly 480,000 deaths (https://www.who.int/news-room/fact-sheets/detail/opioid-overdose). Opioids suppress respiratory drive via mu-opioid receptor (MOR) activation in the brainstem, leading to potentially fatal hypoxia. While naloxone has shown effectiveness as an opioid overdose antidote, the shift in the illicit drug marketplace from naturally derived (e.g., morphine, heroin) and semi-synthetic (e.g., oxycodone) opioids to more potent synthetic opioid classes (e.g., fentanyls, nitazenes) and increasing adulteration with other CNS-active drugs has prompted significant concerns about the effectiveness of naloxone to produce a sustained reversal of overdose symptomatology. Additional considerations for naloxone include the propensity to precipitate withdrawal in opioid-dependent individuals and inability to reverse chest wall rigidity (i.e., wooden chest syndrome) caused by fentanyl.

Accordingly, a diverse panel of treatment approaches is urgently needed to improve overdose outcomes. Some examples of strategies currently being investigated include monoclonal antibodies, long-lasting MOR antagonists, vaccines, sequestrants, and sustained release naloxone formulations, among others.

In this Special Issue, we solicit original and review articles on preclinical and clinical research related to the identification and advancement of novel pharmacological interventions to treat opioid-induced respiratory depression amidst the evolving nature of the opioid overdose crisis.

We eagerly anticipate your insightful contributions.

Respectfully,

Dr. David Matthew Walentiny
Guest Editor

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