Blocking CRF activity via CRF1R antagonism remains an attractive principle for addiction pharmacotherapy, and initial clinical development targeting this mechanism is now underway (see e.g. www.clinicaltrials.gov: NCT01227980). The complex actions of urocortins hold the promise of offering additional opportunities for developing addiction treatments. Because their relative preference for CRF2 relative to CRF1 receptors differs, understanding the role of individual urocortins will provide important clues to the optimal properties of therapeutics that could be developed to target this system. The lack of selective non-peptide ligands for the CRF2R is a limitation in this regard, and developing selective molecules to target this receptor is an important research priority.
