OKLAHOMA CITY – A researcher at the University of Oklahoma College of Pharmacy at OU Health Sciences is playing a key role in a preclinical trial that is testing a non-addictive drug to treat post-traumatic stress disorder and alcohol use disorder. Recent findings from the trial are promising: The drug reduces symptoms of post-traumatic stress disorder like anxiety and increased pain sensitivity, while also decreasing alcohol consumption.
Kelly Standifer, Ph.D., professor and chair of the Department of Pharmaceutical Sciences in the OU College of Pharmacy, and her lab study focus on finding treatments for PTSD and traumatic brain injuries. Standifer led OU’s participation in the trial, collaborating with Yong Zhang, Ph.D., research associate in the OU College of Pharmacy, and Panini Patankar, MBBS, M.D., graduate research assistant in the OU College of Pharmacy. Together they used the lab’s PTSD research model to test the drug’s ability to reduce pain and alleviate anxiety. The drug is provided by Phoenix PharmaLabs Inc., a private company developing non-addictive treatments for pain and substance use disorders. The preclinical trial is an important first step before a drug is tested in humans.
The work is funded by the U.S. Department of Defense, through the Pharmacotherapies for Alcohol and Substance Use Disorders Alliance, which supports research about conditions like PTSD that affect veterans and service members at a higher rate than the general population. Because people with PTSD are more likely to develop alcohol use disorder, the research community is seeking a drug that can treat both conditions. Importantly, the search is for a drug that is effective without having addictive qualities itself.
“In my research, I have always been interested in conditions that often occur with PTSD, such as increased sensitivity to pain and increased anxiety,” Standifer said. “Our research model produces a wide range of comorbidities experienced by those diagnosed with PTSD. In this preclinical trial, it appears that the drug is especially effective in those that are prone to drink more alcohol because of their anxiety. It’s exciting that something non-addictive appears to reduce pain, anxiety behaviors and alcohol consumption so effectively.”
The drug being tested, called PPL-138, is similar to buprenorphine, which is used to treat pain and opioid dependence, but not alcohol use disorder. PPL-138 is unique because of the way it interacts in the brain with the nociceptin receptor, a molecule that helps to regulate reward and aversion. PPL-138 activates the nociceptin receptor more strongly than buprenorphine does, meaning PPL-138 has the ability to relieve pain and stress-induced anxiety and block the rewarding effects of alcohol, without activating the part of the brain that craves more of the drug.
Thus far, the drug has been tested in a male research model for PTSD; next, the drug will be tested in a female research model for PTSD. Historically, females have been underrepresented in such trials, Standifer said, but most funding agencies now require testing in both sexes because their symptoms can vary.
“Across society, a higher percentage of females experience PTSD than males, but their primary symptoms can differ,” she said. “For instance, men often experience hypervigilance and increased anxiety. Women may be anxious as well, but they also might become more withdrawn and socially isolated or depressed. Of course, some people are unaffected and never develop these symptoms, but some are very susceptible.”
One of the aims of a research institution like OU is to collaborate with companies like Phoenix PharmaLabs Inc. to develop therapies that may one day be widely used. The drug PPL-138 is one of Phoenix’s leading candidates for the non-addictive treatment of pain. Through collaborative research between Phoenix, OU, and another partner, Florida Atlantic University, it became clear that the drug also holds the potential to treat PTSD and alcohol use disorder. That’s when Standifer began working with the OU Office of Technology Commercialization for protection of her intellectual property. A patent application has been jointly filed by OU and Florida Atlantic University for this new use of PPL-138. Standifer is named as an inventor.
“Recognizing the significance of the work, Dr. Standifer reached out to the Office of Technology Commercialization. We are proud to be a resource for OU faculty, staff and graduate students interested in commercialization of intellectual property resulting from their novel research findings,” said Gina McMillen, DVM, Ph.D., director of the Office of Technology Commercialization for OU Health Sciences.
The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Alcohol and Substance Abuse Research Program under Award No. W81XWH-18-2-0044. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.
The University of Oklahoma Health Sciences Center
The University of Oklahoma Health Sciences is one of the nation’s few academic health centers with all health professions colleges — Allied Health, Dentistry, Medicine, Nursing, Pharmacy, Public Health, Graduate Studies and School of Community Medicine. OU Health Sciences serves approximately 4,000 students in more than 70 undergraduate and graduate degree programs on campuses in Oklahoma City and Tulsa and is the academic and research partner of OU Health, the state’s only comprehensive academic healthcare system. OU Health Sciences is ranked 129 out of over 2,849 institutions in funding received from the National Institutes of Health, according to the Blue Ridge Institute for Medical Research. For more information, visit ouhsc.edu.
About the University of Oklahoma
Founded in 1890, the University of Oklahoma is a public research university located in Norman, Oklahoma. As the state’s flagship university, OU serves the educational, cultural, economic and health care needs of the state, region and nation. OU was named the state’s highest-ranking university in U.S. News & World Report’s most recent Best Colleges list. For more information about the university, visit www.ou.edu.