Volume 21, Issue 1, January 2018

Significance StatementAnxiety and trauma-related disorders are among the most prevalent medical conditions in the United States. Posttraumatic stress disorder (PTSD) in particular is a debilitating disorder that develops in a subset of individuals exposed to extreme stress. Drug discovery for PTSD and anxiety disorders has been largely stagnant, contributing to a substantial disease burden and continued patient suffering. A large body of evidence implicates neuropeptide Y (NPY) in the regulation of stress-related behaviors, and preclinical data suggest that enhancing NPY signaling may reduce anxiety and symptoms of PTSD. Herein, we conducted phase Ib double-blind, randomized, placebo-controlled, dose-ranging study of intranasal administration of NPY in subjects with PTSD. We found that NPY was well tolerated at all tested doses and that high, but not low, doses of NPY were associated with reduced anxiety on some measures. The NPY system may represent a promising target for treatment development for anxiety and trauma-related disorders.