New medicine approach to reverse fentanyl overdose

Negative allosteric modulation of mu opioid receptors to reverse fentanyl overdose

NIH-funded research Trustees of Indiana University · NIH-11193285

This project will try compounds that change how fentanyl binds to opioid receptors so naloxone can restore breathing more quickly in people overdosing on fentanyl.

Quick facts

Grant typeR21 grant
Study typeNIH-funded research
Funding institutionTrustees of Indiana University NIH-funded
Lab location1 site (Bloomington, United States)
Project IDNIH-11193285 on NIH RePORTER

What this research studies

If I'm worried about fentanyl overdose, this research is working on drugs that tweak the mu opioid receptor to make fentanyl let go or signal less strongly. The team is screening chemical relatives of cannabidiol and other negative allosteric modulators to find molecules that weaken fentanyl’s effect on the receptor. They plan lab experiments to see if these compounds speed up or strengthen naloxone’s ability to restore breathing in preclinical models. The idea is to develop a fast-acting adjunct treatment that could be given alongside naloxone in overdoses.

Who could benefit from this research

Good fit: Ideal candidates for later trials would include adults at high risk of fentanyl overdose, such as people with opioid use disorder, and healthy volunteers for early safety testing.

Not a fit: People experiencing non-opioid overdoses or those with conditions unrelated to mu opioid receptor effects would not benefit from this approach.

Why it matters

Potential benefit: If successful, this could make naloxone work faster and more reliably against fentanyl, potentially saving lives during overdoses.

How similar studies have performed: Naloxone already reverses many opioid overdoses but can fail with fentanyl, and using mu opioid receptor negative allosteric modulators is a novel approach with only preliminary laboratory evidence (for example, low-potency effects seen with CBD) and no proven human results yet.

Where this research is happening

Bloomington, 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.
Last reviewed 2026-06-13 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.