Creative Bio-Peptides, Inc has been funded as part of the NIH’s HEAL Initiative on building technologies to stop the opioid crisis for our program to develop our novel chemokine receptor antagonist R103 to block opioid reinforcement, relapse, and physical dependence (BioSpace, Oct 22, 2020). Creative Bio-Peptides, Inc. is committed to providing effective and safe non-opioid treatments for the 50 million Americans suffering daily pain and the 2 million who live with opioid dependency or addiction. Current decades-old addiction treatments like methadone or naloxone are not up to the magnitude of this problem, and themselves have abuse liability concerns. Chemokines (hormones of the immune system that mediate innate immune inflammation) enhance pain, reduce opioid analgesia, and promote drug-seeking behavior and addiction – giving them a central role at the crossroads of chronic pain and the opioid crisis. Blocking chemokines (rather than opioid receptors) provides an exciting and untested treatment opportunity for opioid-sparing treatment of chronic pain and opioid use disorders (OUD). Our lead chemokine CCR2/CCR5 antagonist (blocker) peptide R103 (aka RAP-103) stops neuropathic pain and enhances the potency of morphine to relieve acute pain. Recent studies conducted by scientists at Temple University suggests that R103 could also become an effective treatment for OUD as blocking CCR5 lowers the rewarding, locomotor and reinforcing effects of drugs of abuse, with a better safety profile compared to current approved chemokine antagonists that cause liver toxicity or must be injected. We have been funded to assess, in animal self-administration models that mimic human drug-taking, whether R103 reduces morphine intake. Physical dependence develops during chronic opioid exposure and upon discontinuation of opioid intake, presents as a withdrawal syndrome that triggers opioid relapse. We will further assess if R103 will prevent or blunt naloxone-precipitated withdrawal signs in morphine-dependent rats. We will also evaluate the safety of R103 by determining a maximum tolerated dose. Successful execution of this program will help establish a regulatory approval plan for subsequent human efficacy studies in OUD’s.