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

Abstract

Rationale: Cocaine users have increased regional brain mu-opioid 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 [11C]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 (R2= 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.

Fig. 1

Correlation of decreases in regional brain mu-opioid receptor (mOR) binding between one week and 12 weeks of enforced abstinence with time to relapse to cocaine use in 15 cocaine-dependent subjects (see Table 1). (A) Brain regions (in red) showing a significant positive correlation between ΔmOR binding (week 1 – week 12) and time to relapse. Color bar presents the T-scores. The axial plane is cut from 40 mm below the bicommissural plane at 4-mm intervals. Panels B and C show relationship between ΔmOR binding (Y axis) and log (time to relapse) (X axis) in the right inferior frontal cortex (Brodman area 11, yellow arrow (B)) and in the right ventrolateral frontal cortex (Brodman area 47, red arrow (C)). Each data point represents an individual subject.

Fig. 2

Correlation of regional brain mu-opioid receptor (mOR) binding after one week or 12 weeks of enforced abstinence with time to relapse to cocaine use in 15 cocaine-dependent subjects (see Table 2). Brain regions (in red) showing a significant negative correlation after one week 1 (A) or 12 weeks (B) of abstinence. Color bar presents the T-scores. The axial plane is cut from 24 mm below the bicommissural plane at 4 mm intervals. Panels C and D show the relationship between mOR binding (Y axis) in the left orbitofrontal cortex (yellow arrow in A and B) after one week (C) or 12 weeks (D) of abstinence and log (time to relapse) (X axis). Each data point represents an individual subject.

Fig. 3

Correlation of regional brain mu-opioid receptor (mOR) binding after 12 weeks of enforced abstinence with percent days of cocaine use during the month following relapse in 15 cocaine-dependent subjects (see Table 3). (A) Brain regions (in red) showing a significant positive correlation. Color bar presents the T-scores. The axial plane is cut from 24 mm below the bicommissural plane at 4 mm intervals. Panels B and C show the relationship between mOR binding (Y axis) in the left inferior frontal cortex (yellow arrow in A) (B) and right anterior cingulate cortex (red arrow in A) (C) after 12 weeks of abstinence and percent days of cocaine use (X axis) during the month after relapse. Each data point represents an individual subject.