Imaging brain mu-opioid receptors in abstinent cocaine users: Time course and relation to cocaine craving

Background: Cocaine treatment upregulates brain mu-opioid receptors (mOR) in animals. Human data regarding this phenomenon are limited. We previously used positron emission tomography (PET) with [¹¹C]-carfentanil to show increased mOR binding in brain regions of 10 cocaine-dependent men after 1 and 28 days of abstinence. Methods: Regional brain mOR binding potential (BP) was measured with [¹¹C]carfentanil PET scanning in 17 cocaine users over 12 weeks of abstinence on a research ward and in 16 healthy control subjects. Mu-opioid receptor BP was increased in the frontal, anterior cingulate, and lateral temporal cortex after 1 day of abstinence. Results: Mu-opioid receptor BP remained elevated in the first two regions after 1 week and in the anterior cingulate and anterior frontal cortex after 12 weeks. Increased binding in some regions at 1 day and 1 week was positively correlated with self-reported cocaine craving. Mu-opioid receptor BP was significantly correlated with percentage of days with cocaine use and amount of cocaine used per day of use during the 2 weeks before admission and with urine benzoylecgonine concentration at the first PET scan. Conclusions: These results suggest that chronic cocaine use influences endogenous opioid systems in the human brain and might explain mechanisms of cocaine craving and reinforcement.