Serotonin approaches to reverse fentanyl-caused breathing failure

Serotonin mechanisms in fentanyl-induced respiratory depression

['FUNDING_R01'] · UNIVERSITY OF MICHIGAN AT ANN ARBOR · NIH-11324556

Seeing if drugs that turn on serotonin (5HT2A) receptors can help restore breathing during fentanyl overdoses.

Quick facts

Phase['FUNDING_R01']
Study typeNih_funding
SexAll
SponsorUNIVERSITY OF MICHIGAN AT ANN ARBOR (nih funded)
Locations1 site (ANN ARBOR, UNITED STATES)
Trial IDNIH-11324556 on ClinicalTrials.gov

What this research studies

Researchers will study how fentanyl disrupts serotonin-driven mechanisms that normally support breathing, focusing on 5HT2A receptors in brainstem breathing centers. The team will use laboratory models and targeted neural manipulations to pinpoint which serotonin pathways are affected by fentanyl and how activating 5HT2A receptors influences respiration. The work aims to reveal whether serotonin activation can restore breathing independently of opioid receptors, which could complement naloxone. Findings will guide development of non-opioid respiratory stimulants to counter ultrapotent synthetic opioid poisoning.

Who could benefit from this research

Good fit: People at risk of fentanyl overdose or those with opioid use disorder who might need faster or additional ways to reverse life-threatening breathing suppression could ultimately benefit.

Not a fit: Patients whose breathing problems are caused by non-opioid medical conditions or chronic respiratory diseases may not benefit from serotonin-based reversal of opioid-induced respiratory depression.

Why it matters

Potential benefit: If successful, this work could lead to new non-opioid drugs that restore breathing during fentanyl overdoses, supplementing current antidotes like naloxone.

How similar studies have performed: Prior animal studies suggest serotonergic (including 5HT2A) activation can counter opioid respiratory depression, but fentanyl-specific mechanisms and translational potential remain under investigation.

Where this research is happening

ANN ARBOR, UNITED STATES

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.

View on NIH RePORTER →

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.