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

Psychopharmacology (Berl). 2008 Nov;200(4):475-86. doi: 10.1007/s00213-008-1225-5. Epub 2008 Sep 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Behavior, Addictive / physiopathology*
  • Brain / metabolism*
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / rehabilitation
  • Female
  • Fentanyl / analogs & derivatives
  • Fentanyl / pharmacokinetics
  • Follow-Up Studies
  • Forecasting / methods
  • Frontal Lobe / metabolism
  • Humans
  • Linear Models
  • Male
  • Positron-Emission Tomography / methods
  • Protein Binding
  • Receptors, Opioid, mu / metabolism*
  • Recurrence
  • Temporal Lobe / metabolism
  • Time Factors

Substances

  • Receptors, Opioid, mu
  • carfentanil
  • Fentanyl