Quick-acting targeted therapies with minimal side effects are an urgent need for the treatment of anxiety-related disorders. While delta opioid receptor (DOP) agonists have shown ‘anxiolytic’ or anxiety-reducing effects, their mechanism of action is not well-understood. A new study highlights the role of specific neuronal circuits in the brain involved in the development of anxiety, and distinct mechanisms of action of the therapeutic DOP agonist — KNT-127.