Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • NEWS AND VIEWS

Super-potent opioids could be safer-than-expected alternatives to conventional painkillers

Modified nitazenes, opioids 1,000 times stronger than morphine, show remarkably few adverse effects in rodents, renewing the potential of these drugs for pain relief.
By
  1. Victor Mathis

    1. Victor Mathis is in the National Institute of Health and Medical Research (INSERM) unit UMR-S1329, Strasbourg Translational Neuroscience & Psychiatry, University of Strasbourg (UNISTRA), Strasbourg 67084, France.

  2. Emmanuel Darcq

    1. Emmanuel Darcq is in the National Institute of Health and Medical Research (INSERM) unit UMR-S1329, Strasbourg Translational Neuroscience & Psychiatry, University of Strasbourg (UNISTRA), Strasbourg 67084, France.

Opioids, including morphine, are the gold standard for pain management. Yet they are accompanied by a considerable number of side effects and a high risk of misuse1,2. The side effects include phenomena such as tolerance and dependence, and symptoms such as nausea, constipation, and, crucially, respiratory depression, which is the main cause of death after an overdose. Opioids exert their pain-relieving (analgesic) and euphoric effects mainly through the µ-opioid receptor (MOR), the activation of which strongly influences brain circuits that mediate reward and reinforcement1,2. Chronic exposure to opioids can progressively rewire these circuits, contributing to the development of opioid-use disorder. These mechanisms help to explain the opioid crisis observed in the United States and other countries, and they underscore the pressing need for alternative analgesics with reduced adverse effects. Writing in Nature, Gomez et al.3 report a step along the way to this long-sought4 goal.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

doi: https://doi.org/10.1038/d41586-026-00806-3

References

  1. Darcq, E. & Kieffer, B. L. Nature Rev. Neurosci. 19, 499–514 (2018).

    Article  PubMed  Google Scholar 

  2. Mathis, V. P., Ehrlich, A. T. & Darcq, E. Nature Rev. Neurosci. 26, 778–797 (2025).

    Article  PubMed  Google Scholar 

  3. Gomez, J. L. et al. Nature https://doi.org/10.1038/s41586-026-10299-9 (2026).

    Article  Google Scholar 

  4. Kieffer, B. L. & Evans, C. J. Cell 108, 587–590 (2002).

    Article  PubMed  Google Scholar 

  5. Manglik, A. et al. Nature 537, 185–190 (2016).

    Article  PubMed  Google Scholar 

  6. Stahl, E. L. et al. Nature 650, 500–508 (2026).

    Article  PubMed  Google Scholar 

  7. Ehrlich, A. T., Kieffer, B. L. & Darcq, E. Expert Opin. Ther. Targets 23, 315–326 (2019).

    Article  PubMed  Google Scholar 

  8. United Nations Office on Drugs and Crime. World Drug Report 2025 (UNODC, 2025).

    Google Scholar 

  9. Ujváry, I. et al. ACS Chem. Neurosci. 12, 1072–1092 (2021).

    Article  PubMed  Google Scholar 

  10. Koch, T. & Höllt, V. Pharmacol. Ther. 117, 199–206 (2008).

    Article  PubMed  Google Scholar 

  11. Volkow, N. D. & Blanco, C. Mol. Psychiatry 26, 218–233 (2021).

    Article  PubMed  Google Scholar 

Download references

Competing Interests

The authors declare no competing interests.

Subjects

Latest on:

Nature Careers

Jobs

  • Postdoctoral Researcher

    R&D targeting rechargeable batteries focusing on degradation analysis and automated experimentation technologies

    Tsukuba, Ibaraki (JP)

    National Institute for Materials Science (NIMS)

  • Postdoctoral Researcher in Ultrafast Magnetization Dynamics

    Postdoctoral position in ultrafast spin dynamics and magnetization processes in magnetic thin films using advanced time-resolved measurements at NIMS.

    Tsukuba, Ibaraki (JP)

    National Institute for Materials Science (NIMS)

  • Solution Specialist

    Job Title: Solution Specialist Location: Beijing, China - hybrid working model   About the Springer Nature Springer Nature is one of the leading pu...

    Beijing (CN)

    Springer Nature Ltd

  • Faculty Positions in the Center for Interdisciplinary Studies (CIS), Westlake University

    Positions are open at all ranks, including tenured Associate, Full, and Chair Professors, as well as tenure-track Assistant and Associate Professors.

    Hangzhou, Zhejiang (CN)

    Westlake University

  • Chemistry Faculty Positions at Westlake University

    Chemistry at the School of Science is committed to fostering inclusive excellence in a variety of research and teaching activities.

    Hangzhou, Zhejiang (CN)

    Westlake University

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing

Search

Advanced search

Quick links