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

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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 (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.

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Acknowledgments

This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Drug Abuse and NIH grant RO1 DA-09479 to JJF.

Financial Disclosures

The authors have no competing financial interests to declare.

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Author notes

  1. Yu Kyeong Kim

    Present address: Department of Nuclear Medicine, Seoul National University, Seoul, South Korea

  2. Badreddine Bencherif

    Present address: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

  3. Susan J. Boyd

    Present address: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA

  4. Marc L. Copersino

    Present address: McLean Hospital, Harvard University, Belmont, MA, USA

Authors and Affiliations

  1. Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA

    David A. Gorelick, Susan J. Boyd, Richard Nelson & Marc L. Copersino

  2. Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Yu Kyeong Kim, Badreddine Bencherif, Robert F. Dannals & J. James Frost

  3. NIDA IRP, 251 Bayview Boulevard, suite 200, Baltimore, 21224, MD, USA

    David A. Gorelick

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  1. David A. Gorelick
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Correspondence to David A. Gorelick.

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Gorelick, D.A., Kim, Y.K., Bencherif, B. et al. Brain mu-opioid receptor binding: relationship to relapse to cocaine use after monitored abstinence. Psychopharmacology 200, 475–486 (2008). https://doi.org/10.1007/s00213-008-1225-5

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  • DOI: https://doi.org/10.1007/s00213-008-1225-5

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