How Neuropeptides Shape Anxiety — and Could Lead to Better Treatments

Multiple neuropeptide systems contribute to anxiety regulation through distinct mechanisms. Neuropeptide Y is anxiolytic (reduces anxiety), while CRH, substance P, vasopressin, and cholecystokinin are generally anxiogenic (increase anxiety). PACAP modulates stress responses. Each represents a potential drug target for anxiety disorders.

Narrative review of preclinical and clinical literature on neuropeptide involvement in anxiety. Examines evidence from animal behavioral studies, human genetic association studies, and early-phase clinical trials targeting neuropeptide receptors.

Current anxiety medications have significant limitations — SSRIs take weeks to work, benzodiazepines are addictive, and many patients don't respond adequately. Neuropeptide-targeted therapies could offer faster-acting, more precise treatments with potentially fewer side effects.

This review highlights a paradigm shift in understanding anxiety: from a simple serotonin/GABA imbalance to a complex interplay of peptide signaling systems. As peptide drug delivery improves, these targets become increasingly practical for clinical development.

Review article with no original data. Much of the neuropeptide anxiety evidence comes from animal models with uncertain human translation. Several neuropeptide-targeted drugs have failed in clinical trials despite strong preclinical data.