FAU study examines how a new drug could help treat PTSD and its common side effects.

FAU study examines how a new drug could help treat PTSD and its common side effects.

Post-traumatic stress disorder (PTSD) and its effects

PTSD affects approximately 12 million adults in the United States, accounting for between 4% and 8% of the adult population – and even up to 30% of military personnel and veterans. Strikingly, 63% of veterans with post-traumatic stress disorder also suffer from alcohol use disorder (AUD) and/or chronic pain. These conditions often occur together, with individuals with AUD or chronic pain often also experiencing PTSD.

What is PTSD?

PTSD is a psychological disorder that occurs after traumatic experiences, such as war, a serious accident or a serious illness. Those affected often experience flashbacks, nightmares and severe anxiety.

When these disorders occur together, they reinforce each other, making effective treatment much more difficult. There are currently no approved medications that effectively treat PTSD and AUD together, and many available medications have serious side effects or provide limited results.

New research into a possible drug

Researchers at Florida Atlantic University's Charles E. Schmidt Medical School, in collaboration with the University of Oklahoma College of Pharmacy, have conducted two complementary studies in rats to examine how a new drug, PPL-138, might help treat PTSD and its common companions - anxiety, chronic pain and AUD – to treat. PPL-138 is a partial agonist of opioids that works by targeting specific opioid receptors in the brain.

The intellectual property associated with PPL-138 belongs to Phoenix PharmaLabs, Inc. The company is currently in the process of developing PPL-138 through clinical trials.

The studies carried out

The first study, conducted at the University of Oklahoma, examined whether long-term treatment with PPL-138 could reduce symptoms of PTSD associated with chronic stress. The second study, conducted at FAU, focused on the relationship between trauma, anxiety and alcohol use, with researchers dividing the rats into different groups.

The results, published inBritish Journal of Pharmacology, provide promising evidence that PPL-138 could become a valuable treatment for PTSD and alcohol abuse—particularly when the symptoms are rooted in anxiety. By targeting a brain system linked to both stress and addiction, researchers believe PPL-138 could one day provide a much-needed breakthrough for people struggling with these life-altering conditions.

Results of the studies

• PPL-138 reduzierte signifikant angstähnliches Verhalten, Schmerzempfindungen und den Alkoholverbrauch – jedoch nur bei Ratten, die PTBS-ähnliche Symptome entwickelten.
• Bei sowohl männlichen als auch weiblichen Ratten reduzierte das Medikament selektiv den Alkoholgebrauch bei denjenigen, die auch Anzeichen von traumaassoziierter Angst zeigten, ohne die scheinbar stressresistenten Ratten zu beeinträchtigen.

"Our results demonstrate that PPL-138 not only reduces trauma-associated anxiety and pain, but also selectively attenuates alcohol use in rats most susceptible to stress-related drinking. Such a targeted treatment could revolutionize our management of PTSD and its comorbidities - particularly for the large number of patients currently failing existing therapies."

Andrea Cippitelli, Ph.D., lead author and assistant professor, Department of Biomedical Science in the Schmidt College of Medicine and member of the FAU Stiles-Nicholson Brain Institute

The study results also emphasize the need to consider gender differences in both the causes and treatment of these overlapping conditions. In female rats, PPL-138 reduced alcohol consumption in those who exhibited anxiety, even when their drinking behavior did not increase. This suggests that anxiety alone may be a primary factor driving alcohol use in women.

Differences between the sexes

“Anxious male rats were twice as likely as female rats to increase their alcohol intake after trauma, while almost all female rats with higher alcohol consumption also showed clear signs of anxiety,” Cippitelli said. "This reflects well-documented patterns in people where women are more susceptible to anxiety-related disorders such as PTSD and often use alcohol to cope with emotional distress, while men generally engage in more severe, widespread drinking habits."

Importantly, the effects of PPL-138 were not due to sedation or reduced activity. The compound did not alter exercise or alcohol consumption in rats experiencing anxiety-related behavior or traumatic stress. In fact, exercise levels remained unchanged in male rats and increased slightly in female rats - supporting the idea that the drug targets stress- and anxiety-related behaviors and does not cause general suppression or sedation.

“This research represents a much-needed step to help both civilians and veterans living with the invisible wounds of trauma,” Cippitelli said. “In our preclinical studies, PPL-138 demonstrates strong potential as a single therapy for the overlapping symptoms of PTSD, chronic pain and alcohol abuse – and may provide a safer and more effective alternative to current multiple medication approaches.”

Study co-authors are Yong Zhang, Ph.D., University of Oklahoma College of Pharmacy; Kyle Kealoha, a graduate student in the FAU Department of Biomedical Science; Ali Idriss, former research laboratory technician, FAU Department of Biomedical Science; Panini S. Patankar, M.D., University of Oklahoma College of Pharmacy; Benjamin Carper, RTI International, Research Triangle Park; Lawrence Toll, Ph.D., professor of biomedical science, Schmidt College of Medicine and member of the FAU Stiles-Nicolson Brain Institute; and Kelly M. Standifer, Ph.D., University of Oklahoma College of Pharmacy.

This work was supported by the U.S. Office of the Assistant Secretary of Defense for Health Affairs supported by the Alcohol and Substance Use Research Program.

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