Researchers from Florida Atlantic University’s Charles E. Schmidt College of Medicine, working with the University of Oklahoma College of Pharmacy, have reported that a new drug, PPL-138, may help treat post-traumatic stress disorder (PTSD), chronic pain, and alcohol use disorder (AUD) simultaneously. PTSD affects about 12 million adults in the United States each year, with military personnel and veterans particularly impacted. According to recent data, up to 30% of military personnel and veterans experience PTSD, and more than half also struggle with AUD or chronic pain.
The overlapping nature of these conditions complicates treatment options. Currently, there are no approved medications that effectively address both PTSD and AUD at the same time. Existing drugs often have significant side effects or provide limited relief.
In two studies using rats, researchers examined whether PPL-138 could reduce symptoms associated with PTSD as well as related anxiety, pain responses, and alcohol consumption. The first study focused on the impact of long-term treatment with PPL-138 on trauma-induced behaviors. The second study explored how trauma exposure influenced anxiety and alcohol use in different groups.
Results published in the British Journal of Pharmacology indicate that PPL-138 reduced anxiety-like behavior, pain sensitivity, and alcohol intake—but only among rats displaying PTSD-like symptoms. In both male and female rats, those exhibiting trauma-related anxiety responded to the drug with lower alcohol consumption; unaffected rats did not show changes.
“Our results show that PPL-138 not only reduces trauma-related anxiety and pain, but also selectively curbs alcohol use in rats most vulnerable to stress-induced drinking,” said Andrea Cippitelli, Ph.D., lead author and assistant professor at FAU’s Schmidt College of Medicine. “This kind of targeted treatment could transform how we manage PTSD and its comorbidities – especially for the large number of patients who currently fall through the cracks of existing therapies.”
The findings suggest important differences between males and females in response to trauma and substance use. Among female rats with anxiety traits—even if their overall drinking had not increased—PPL-138 lowered alcohol intake. This points to anxiety as a key factor behind alcohol use in females.
“Anxious male rats were twice as likely as females to increase their alcohol intake following trauma, while nearly all female rats with more alcohol intake also displayed clear signs of anxiety,” said Cippitelli. “This mirrors well-documented patterns in humans, where women are more prone to anxiety-related disorders like PTSD and often use alcohol to cope with emotional distress, whereas men typically engage in heavier, more generalized drinking.”
The research team found that PPL-138’s effects were not due to sedation or reduced activity; movement levels stayed steady for male rats and slightly increased for females receiving the drug.
“This research represents a much-needed step toward helping both civilians and veterans living with the invisible wounds of trauma,” said Cippitelli. “In our preclinical studies, PPL-138 shows strong potential as a single therapy for the overlapping symptoms of PTSD, chronic pain, and alcohol misuse – offering a potentially safer and more effective alternative to current multi-drug approaches.”
Phoenix PharmaLabs owns intellectual property rights for PPL-138 and is advancing it through clinical trials. Funding for this research came from the U.S. Office of the Assistant Secretary of Defense for Health Affairs under its Alcohol and Substance Use Research Program.
Study co-authors include Yong Zhang (University of Oklahoma College of Pharmacy), Kyle Kealoha (FAU Department of Biomedical Science), Ali Idriss (former FAU lab technician), Panini S. Patankar (University of Oklahoma College of Pharmacy), Benjamin Carper (RTI International), Lawrence Toll (FAU Schmidt College of Medicine/Stiles-Nicholson Brain Institute), Kelly M. Standifer (University of Oklahoma College of Pharmacy).
