The US continues to suffer from a crisis of opioid abuse and mis-use as overdose deaths reached a record high in 2021 with over 100,000 deaths. Activation of certain chemokine receptors promotes drug-seeking and substance abuse disorders – giving them a central role at the crossroads of chronic pain and the opioid crisis. Current decades-old addiction treatments like methadone, buprenorphine or naloxone are not up to the magnitude of this problem, and themselves have abuse liability concerns. Blocking chemokines (rather than opioid receptors) provides an exciting and untested treatment opportunity to block drug-seeking or withdrawal, and could be new treatments for opioid use disorders (OUD). We have been funded through the NIH HEAL initiative to determine if our lead peptide RAP-103 can block self-administration of opioids in animals.