Narendran R, et al. - In chronic cocaine-abusing humans, researchers sought to report the in vivo status of nociceptive opioid peptide (NOP). They examined 24 individuals with cocaine use disorder and 26 healthy control subjects matched for age, sex, and smoking status for in vivo NOP binding using [¹¹C]NOP-1A and positron emission tomography (PET). The cocaine use disorder group showed significantly increased [¹¹C]NOP-1A distribution volume vs the healthy control group. This implies an adaptive response to decreased nociceptin/orphanin FQ (N/OFQ; an antistress neuropeptide transmitter in the brain), or increased corticotropin-releasing factor (CRF) transmission, or both. They recommend exploring NOP agonist medications to enhance N/OFQ as a means to treat cocaine use disorder.