Wayne State University School of Medicine Professor Mark Greenwald, Ph.D., is on the roster of researchers chosen to provide expertise in a multi-million-dollar international research project funded by the National Institutes of Health that will accelerate the development of the drug cebranopadol for treatment of opioid use disorder.

Cebranopadol is a relatively new and promising medication in the benzenoid class already used to treat pain. 

“It’s a significant and innovative project with high potential impact,” said Dr. Greenwald, a professor of Psychiatry and Behavioral Neurosciences and the department’s director of the Substance Abuse Research Division.

Under a grant expected to provide up to $16.6 million over five years from the National Institute on Drug Abuse, New Jersey-based Tris Pharma will conduct preclinical studies to assess cebranopadol’s ability to deter the self-administration of Schedule II opioids, as well as to assess the respiratory function during co-administration of cebranopadol and Schedule II opioids. Additionally, the company will conduct clinical studies to assess the addictive potential of cebranopadol, as well as the dosage of cebranopadol needed to block withdrawal and subjective effects of opioid dependence.

“I will be involved in overall decision making; reviewing and monitoring the data, safety and progress of the studies; and interpreting, presenting and publishing the findings,” said Dr. Greenwald, the WSU Gertrude Levin Endowed Chair in Addiction and Pain Biology.

The initiative is designed to harness the power of collaboration, using complementary expertise and effort to fight substance use disorders, including by developing new safe and effective medications for treatment, he added.

According to the NIH website, approximately 107,000 people died from overdose in 2022, and 80% of those deaths were from opioids (including highly potent synthetic opioids like fentanyl and drug combinations with stimulants).  Nearly 10 million Americans ages 12 and older misused opioids in the past year, and more than 2 million live with opioid addiction.

Through the Helping to End Addiction Long-term Initiative launched in April 2018, the NIH has awarded grants to fund the optimization of new therapies to prevent and treat opioid use disorder. The initiative aims to improve treatments for chronic pain, curb the rates of opioid use disorder and overdose, and achieve long-term recovery from opioid addiction.

“The process for conducting our studies will follow a similar pathway to what I’ve previously done with another company for developing long-acting buprenorphine for treating opioid use disorder, which received FDA approval a few years ago,” Dr. Greenwald said. “Tris Pharma has already developed cebranopadol in multiple animal studies and clinical trials for treating chronic pain – they plan to submit to FDA for approval this year for that indication for use – and it appears to be quite safe. Given the importance and need for expanding access to treatments for opioid use disorder during the ongoing epidemic of overdoses and deaths, this is extremely important.”

In addition to Dr. Greenwald, Tris will collaborate with experts at multiple global institutions, including Professor Roberto Ciccocioppo of Unicam: Università degli Studi di Camerino, in Italy, to complete preclinical through Phase 2 studies evaluating cebranopadol.

Current treatments for opioid use disorder have well-known limitations, including high risks for overdose, withdrawal symptoms and physical dependence. Activation of the NOP receptor has been shown in preclinical studies to block addictive drugs from producing drug-seeking behaviors. Cebranopadol has demonstrated reduced cocaine and heroin self-administration and drug-seeking behaviors.

“This NIDA award will help accelerate exploration of cebranopadol as a potential tool to address the opioid crisis, moving Tris closer to our goal of offering a novel and effective solution that could help change the trajectory of the countless lives afflicted by this disease,” said Joseph Grieco, M.S., Ph.D., Tris vice president of Clinical Development. “We understand the urgency for new OUD treatment options, and I am optimistic about the potential of our upcoming NIDA-supported trials. We look forward to sharing updates on our progress.”

The grant number for this National Institute on Drug Abuse award is UG3 DA059285.