A morphine molecule that only switches on under light eased bone-cancer pain in animals without the usual tolerance

A morphine-based molecule called AM-3 relieved bone-cancer pain and gut pain in animal tests only where ultraviolet light was shone on it, and it showed reduced or absent tolerance and constipation. Researchers at Weill Cornell Medicine, the University of Pennsylvania and USC Dornsife reported the work in the journal Cell on October 15, 2026. It is preclinical science, and no human has received the compound.

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An azobenzene hinge turns the drug up and down

The Cornell Chronicle account by Jim Schnabel describes AM-3 as morphine fitted with an azobenzene component that changes shape under light. Near-ultraviolet light produces a form that strongly activates the mu-opioid receptor, the target of morphine, codeine and fentanyl. Blue light produces a form that activates it much more weakly. The team calls the approach photopharmacology, and it designed several morphine-azobenzene compounds with electron microscopy and other structural biology tools. The switching stayed stable and reversible across many on-off cycles.

In the pain models, which included bone-cancer pain and visceral pain, the researchers injected AM-3 and then briefly lit the painful site with ultraviolet light to induce its high-potency shape. That produced morphine-like relief at that site. The release does not name the species used.

Why tolerance and constipation may stay away

Standard opioids act throughout the body, which is the root of constipation, tolerance, addiction and the breathing suppression that makes overdoses fatal. The Chronicle cites CDC data showing more than 40,000 Americans died of opioid-involved overdoses in the prior year. AM-3 offers a different design: the drug reaches the receptor with full force only in lit tissue, and it crosses into the brain poorly, which the authors suggest may limit addiction and respiratory effects. News-Medical’s summary of the work repeats the finding of reduced or no tolerance and constipation.

Joshua Levitz, a professor of biochemistry and biophysics at Weill Cornell Medicine and co-senior author, called the results a significant breakthrough that reaches beyond pain management. He said the idea of light-switched receptors has existed for about 15 years and that these data take it further than anyone else has. Dirk Trauner, the Penn Integrates Knowledge Professor whose lab collaborated, described the goal as making opioids safer by controlling them with light in the periphery, rather than reducing how many are used.

Wording matters in how these results travel. News-Medical headlined its summary as eliminating dangerous side effects, while Cornell’s own headline says only that the painkiller may work without them, and the body of the Cornell story reports reduced or no tolerance and constipation. The brain-penetration point is likewise framed by the authors as a suggestion about addiction and respiratory risk, not a measured outcome in people. Readers weighing the claim should hold it at the Cornell strength.

A December 2024 bioRxiv preprint on the same approach was published as “An opioid efficacy switch for reversible optical control of peripheral analgesia.” The peer-reviewed paper is in Cell. Co-first authors are Luca Posa and Giovanna Romano of Weill Cornell, Xiang Ji of Penn, and Saif Khan and Antonina Nazarova of USC Dornsife, and USC’s Vsevolod Katritch and Cornelius Gati were major contributors.

Trauner’s group had explored the idea before. An earlier release from his lab at LMU Munich described a fentanyl derivative that still binds mu-type opioid receptors but can be switched on and off with light of different colors, a reaction shown in cells rather than animals. First author Matthias Schönberger said at the time that the approach could offer a route to novel treatments of chronic pain syndromes. The new Cell work moves from cultured cells to living animals and from fentanyl to a morphine scaffold.

Ultraviolet light is the obvious obstacle

Ultraviolet light can damage eyes and skin, and AM-3 needs it, which is a serious constraint on any use in patients. The team is developing successor molecules that respond to visible light, with red light as the goal because it travels deeper through tissue. Trauner noted that the photochemistry still needs improvement and mentioned unpublished preliminary results.

Funding came from the National Institutes of Health, the Rohr Family Research Scholar Award, the Monique Weill-Caulier Award and the Charles H. Revson Fellowship. Levitz is an inventor on a patent application covering the technology, and Weill Cornell’s licensing portfolio lists the light-activated opioid compounds for locally restricted and reversible pain management.

Because the drug is injected and then lit locally, any clinical version would pair a medicine with a light-delivery step. The team hopes to advance the work to clinical trials, but none is described in the Cornell account. Whether a light source can be delivered to a tumor deep in bone, and whether visible-light successors match the potency of AM-3, are the questions the next papers will have to answer before human testing is plausible. Trauner has said the target is safer opioids rather than fewer of them, so the measure of success will be whether a lit, local dose can match morphine’s relief without the systemic costs that now define the drug class.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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