Brain mu-opioid receptor binding: relationship to relapse to cocaine use after monitored abstinence

Rationale Cocaine users have increased regional brain muopioid receptor (mOR) binding which correlates with cocaine craving. The relationship of mOR binding to relapse is unknown. Objective To evaluate regional brain mOR binding as a predictor of relapse to cocaine use is the objective of the study. Materials and methods Fifteen nontreatment-seeking, adult cocaine users were housed on a closed research ward for 12 weeks of monitored abstinence and then followed for up to 1 year after discharge. Regional brain mOR binding was measured after 1 and 12 weeks using positron emission tomography (PET) with [C-11] carfentanil (a selective mOR agonist). Time to first cocaine use (lapse) and to first two consecutive days of cocaine use (relapse) after discharge was based on self-report and urine toxicology. Results A shorter interval before relapse was associated with increased mOR binding in frontal and temporal cortical regions at 1 and 12 weeks of abstinence (Ps < 0.001) and with a lesser decrease in binding between 1 and 12 weeks (Ps < 0.0008). There were significant positive correlations between mOR binding at 12 weeks and percent days of cocaine use during first month after relapse (Ps < 0.002). In multiple linear regression analysis, mOR binding contributed significantly to the prediction of time to relapse (R-2 = 0.79, P< 0.001), even after accounting for clinical variables. Conclusions Increased brain mOR binding in frontal and temporal cortical regions is a significant independent predictor of time to relapse to cocaine use, suggesting an important role for the brain endogenous opioid system in cocaine addiction.