A Non-Narcotic Synergic Drug Combination for the Treatment of Severe Chronic Pain

Summary of the technology

Novel synergic drug-combination for improved activation of the human opioid receptor (MOR), with expected avoidance of drug-addiction, using lower effective clinical doses
Avoiding Drug Addiction Using a Novel Drug Combination for Improved Activation of the Opioid Receptor
Project ID : 6-2018-5679

Details of the Technology Offer


LifeSciences and BioTechnology


Pain, Opioid receptor, Addiction, Opioid addiction, Narcotics, Analgesia


Severe, high-impact chronic pain affects 20 million people in the US annually, and presents a common, difficult-to-treat clinical challenge. All the drugs currently approved for chronic treatment of severe pain are narcotics, and their main mechanism of action is activation of the mu-opioid receptor (MOR) in the CNS. Long-term narcotic use is associated with dependence and addiction, with the risk of death by overdose, and with other severe adverse effects. In the US, an estimated 2 million individuals suffer from opioid addiction associated with prescription opioids, accounting for an estimated $78.5 billion in economic costs annually. The estimated overall annual cost of chronic pain in the US is $560 billion in direct medical costs, lost productivity, and disability programs. Thus, there is an urgent and widespread need for safer, non-narcotic drugs that will provide strong and chronic pain relief without the adverse effects associated with narcotic use.

Our Innovation

We have identified a combination of two approved, non-narcotic drugs (Drug A and Drug B) that together are capable of activating MOR synergistically, at very low doses of either drug: Drug A at < 10% of its usually-prescribed dose, and Drug B at < 5% of its usually-prescribed dose.


To test the synergy between Drugs A & B, we utilized a cell-based assay system in which the human mu-opioid receptor (h-MOR) is expressed exclusively. In addition, the system includes h MOR’s downstream cAMP signaling pathway, and a sensitive means to measure Gi’s inhibitory effect on adenylyl cyclase activity following Gi’s activation by h-MOR.

A dose-response test was performed for each drug separately, and for various combinations of Drug A and Drug B. We found that at concentrations in which Drug A and Drug B by themselves only produced negligible responses, their combination yielded robust adenylyl cyclase inhibition of more than 5 times that of the individual drugs.

Moreover, this synergic effect extended through a range close to two orders of magnitude of drug concentrations for either drug, at pharmacologically-relevant concentrations.


This is a novel combination of two non-opioid, clinically-approved drugs that together achieve a synergistic activation of MOR in very low doses of either drug. This combination, with a possible 505b2 route of approval, offers narcotic-strength analgesia without the dangerous adverse effects associated with chronic narcotic use.

Project manager

Keren-Or Amar
VP, Business Development, Healthcare

Project researchers

Shmuel Ben-Sasson
HUJI, School of Medicine - IMRIC
Developmental Biology and Cancer Research

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About Yissum - Research Development Company of the Hebrew University

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.

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