Researchers Make Progress Toward a Pain-Relieving Medication with Minimal Risk of Addiction
Developing effective pain-relieving medication with a low risk of addiction has long been a significant challenge in medical research. This year, a team of researchers at the National Institutes of Health (NIH) identified a novel, highly potent synthetic opioid compound that demonstrates substantial pain reduction without the classic hallmarks of addiction.
The research team, led by scientists at the National Institute on Drug Abuse (NIDA), revisited an understudied class of synthetic opioids known as nitazenes. Originally developed in the 1950s but abandoned due to overdose risks, these compounds were re-engineered to possess a safe pharmacological profile. The resulting novel compound selectively engages mu-opioid receptors in the brain. Unlike traditional opioids that cause rapid dopamine spikes—leading to intense cravings and potential opioid use disorder (OUD)— this compound acts as a unique mu-opioid receptor agonist. It triggers a slow, sustained release of dopamine while simultaneously increasing brain oxygen levels, offering a dual potential to safely alleviate pain and as a maintenance therapy for OUD.
In animal models, this exciting study revealed a unique therapeutic window: the compound entered the brain for only 5 to 10 minutes, yet the resulting pain relief persisted for at least 2 hours. Crucially, the compound did not decrease respiration (respiratory depression), and repeated doses failed to produce tolerance, drug dependence, or meaningful withdrawal symptoms.
Future initiatives include additional preclinical studies in animal models to satisfy the FDA requirements necessary to initiate human clinical trials. The research team anticipates this compound could safely address acute surgical, cancer-related, and chronic pain, and be a maintenance therapy for OUD.
This study was supported in part by the NIH Intramural Research Program and NIDA grant DA056354. The full publication can be reviewed directly at:
The Article
Gomez, J. L., Ventriglia, E. N., Frangos, Z. J., Sulima, A., Robertson, M. J., Sacco, M. D., Budinich, R. C., Giosan, I. M., Xie, T., Solis, O., Tischer, A. E., Bossert, J. M., Caldwell, K. E., Bonbrest, H., Essmann, A., Garçon-Poca, Z. M., Choi, S., Noya, M. R., Limiac, F., Arce, A., … Michaelides, M. (2026). A µ-opioid receptor superagonist analgesic with minimal adverse effects. Nature, 652(8112), 1393–1404. https://doi.org/10.1038/s41586-026-10299-9
