Beyond Oxycodone: A New Drug Aims to Fight Pain Without Addiction

MONMOUTH JUNCTION, NJ – January 08, 2026 – In a development that could mark a turning point in the fight against both severe pain and the opioid crisis, Tris Pharma has announced the acceptance of a peer-reviewed article validating a new class of painkillers designed to provide potent relief without the high risks of addiction and overdose associated with traditional opioids.

The publication in the journal Pain and Therapy details the science behind dual NOP-MOP (dual-NMR) agonists, a novel approach that underpins Tris Pharma's investigational drug, cebranopadol. This new class of medication aims to solve a decades-old medical dilemma: how to effectively treat moderate-to-severe pain without exposing patients to the dangers of dependency, respiratory failure, and abuse that have fueled a public health catastrophe. For millions suffering from conditions ranging from post-surgical pain to chronic ailments, this research signals a potential future where relief doesn't come with life-altering risks.

A New Blueprint for Pain Relief

The foundation of this new approach lies in the complex interplay of two key receptors in the body's pain modulation system: the μ-opioid (MOP) receptor and the nociception/orphanin FQ (NOP) receptor. For decades, powerful painkillers like oxycodone and morphine have worked by activating the MOP receptor, which provides strong analgesia but also triggers a cascade of dangerous side effects, including euphoria, physical dependence, and potentially fatal respiratory depression.

The new research, co-authored by leading pharmacologists, highlights how dual-NMR agonists like cebranopadol activate both MOP and NOP receptors simultaneously. This dual-action mechanism is the key to its unique profile. While MOP activation delivers the necessary pain relief, the concurrent activation of the NOP receptor acts as a built-in safety brake. Scientific evidence shows that NOP activation not only produces its own analgesic effects but also actively counteracts many of the MOP receptor's most dangerous consequences. It has been shown to reduce the euphoric high that drives addiction and, crucially, mitigate the risk of respiratory depression.

“Since its discovery 30 years ago, our understanding of the nociceptin system has grown,” said Dr. Roberto Ciccocioppo, PhD, a Professor of Pharmacology at the University of Camerino and an author of the paper. “NOP receptor stimulation was first seen to provide analgesia, then discovered to counter many of the effects of MOP receptor stimulation, and now many studies across multiple compounds have shown that coactivation of NOP and MOP can provide strong analgesia with lower risks of serious side effects than MOP receptor stimulation alone. As a result, I believe dual-NMR agonists represent an important new breakthrough in pain management.”

From Lab to Clinic: Cebranopadol's Promising Trial Results

The theoretical promise of dual-NMR agonism is being borne out by extensive clinical data. Cebranopadol, a first-in-class drug candidate, has been studied in over 33 clinical trials involving more than 2,200 participants, building a robust profile for its efficacy and safety.

Recently, Tris Pharma announced positive top-line results from two pivotal Phase 3 trials, known as ALLEVIATE-1 and ALLEVIATE-2, which evaluated the drug's performance in treating acute pain following common surgical procedures. The studies found that cebranopadol delivered a statistically significant and high level of pain reduction compared to a placebo.

More importantly, the data points toward the significantly improved safety profile that researchers have been seeking. Studies have demonstrated that cebranopadol produces substantially less respiratory depression—the primary cause of death in opioid overdoses—compared to oxycodone. Furthermore, human abuse potential (HAP) studies, designed to assess a drug's likelihood for misuse, have indicated a low potential for abuse. Patients treated with cebranopadol also required fewer doses of rescue medication, suggesting sustained and effective pain control.

"For too long, we have been stuck with pain medications that either don't work well enough or carry an unacceptable burden of risk," commented one professor of medicine at a leading university medical school who is familiar with the challenges in pain management. "An agent that could deliver strong analgesia with a demonstrably lower risk of addiction and respiratory events would be a transformative solution for clinicians and patients alike."

Beyond Pain: A Dual-Pronged Attack on the Opioid Crisis

The potential impact of cebranopadol extends beyond the operating room and chronic pain clinics. Its unique mechanism of action has also positioned it as a promising candidate for treating Opioid Use Disorder (OUD), the clinical diagnosis for addiction to opioids.

This potential has attracted significant federal attention. The National Institute on Drug Abuse (NIDA), a part of the National Institutes of Health (NIH), has awarded Tris Pharma a five-year grant of up to $16.6 million to study cebranopadol's role in helping patients break the cycle of addiction. The grant, part of the NIH's broader HEAL (Helping to End Addiction Long-term) Initiative, will fund studies to determine if the drug can deter self-administration of other opioids, block withdrawal symptoms, and assess its own addictive potential.

This dual-use capability—treating severe pain while also potentially treating addiction—could make cebranopadol a uniquely powerful tool. The global market for OUD treatments is already valued in the billions and is projected to exceed $9 billion by 2034, reflecting the desperate need for more effective therapies. If proven successful, cebranopadol could not only prevent new cases of addiction by providing a safer alternative for pain but also help treat those already suffering from the disorder.

Navigating the Market and Regulatory Hurdles

With a mountain of promising data, Tris Pharma is charting a course toward commercialization. The U.S. Food and Drug Administration (FDA) has already granted cebranopadol Fast Track Designation for the treatment of chronic low back pain. This status is designed to expedite the review of drugs that address serious conditions and fill an unmet medical need, potentially shortening the timeline to market approval. The company has announced plans to submit a New Drug Application (NDA) to the FDA based on its positive Phase 3 results.

If approved, cebranopadol would enter the market as the first-in-class dual-NMR therapy, giving it a significant advantage in a landscape dominated by generic opioids and less-effective non-opioid alternatives. The challenge for clinicians has always been balancing efficacy with safety. One pain research specialist who has been involved in clinical trials noted the urgent need for such an agent, stating that physicians struggle to find safe and effective options for patients with severe pain that currently necessitates opioid use.

By offering a therapy that promises the analgesic power of traditional opioids with a substantially lower risk profile, cebranopadol could redefine the standard of care. It represents a significant step toward the long-sought goal of effective pain management without the devastating personal and societal costs of addiction, offering a glimmer of hope for a safer future.