Advertisement

Brain Mu-Opioid Receptor Binding Predicts Treatment Outcome in Cocaine-Abusing Outpatients

  • Udi E. Ghitza
    Correspondence
    Address correspondence to Udi E. Ghitza, Ph.D., National Institute on Drug Abuse, Center for the Clinical Trials Network, 6001 Executive Boulevard, Room 3109, MSC 9557, Bethesda, MD 20892-9557
    Affiliations
    Intramural Research Program, Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
    Search for articles by this author
  • Kenzie L. Preston
    Affiliations
    Intramural Research Program, Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
    Search for articles by this author
  • David H. Epstein
    Affiliations
    Intramural Research Program, Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
    Search for articles by this author
  • Hiroto Kuwabara
    Affiliations
    Departments of Radiology and Radiological Sciences and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland
    Search for articles by this author
  • Christopher J. Endres
    Affiliations
    Departments of Radiology and Radiological Sciences and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland
    Search for articles by this author
  • Badreddine Bencherif
    Affiliations
    Departments of Radiology and Radiological Sciences and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland
    Search for articles by this author
  • Susan J. Boyd
    Affiliations
    Intramural Research Program, Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
    Search for articles by this author
  • Marc L. Copersino
    Affiliations
    Intramural Research Program, Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
    Search for articles by this author
  • J. James Frost
    Affiliations
    Departments of Radiology and Radiological Sciences and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland
    Search for articles by this author
  • David A. Gorelick
    Affiliations
    Office of the Scientific Director, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland
    Search for articles by this author

      Background

      Cocaine users not seeking treatment have increased regional brain mu-opioid receptor (mOR) binding that correlates with cocaine craving and tendency to relapse. In cocaine-abusing outpatients in treatment, the relationship of mOR binding and treatment outcome is unknown.

      Methods

      We determined whether regional brain mOR binding before treatment correlates with outcome and compared it with standard clinical predictors of outcome. Twenty-five individuals seeking outpatient treatment for cocaine abuse or dependence (DSM-IV) received up to 12 weeks of cognitive-behavioral therapy and cocaine abstinence reinforcement, whereby each cocaine-free urine was reinforced with vouchers redeemable for goods. Regional brain mOR binding was measured before treatment using positron emission tomography with [11C]-carfentanil (a selective mOR agonist). Main outcome measures were: 1) overall percentage of urines positive for cocaine during first month of treatment; and 2) longest duration (weeks) of abstinence from cocaine during treatment, all verified by urine toxicology.

      Results

      Elevated mOR binding in the medial frontal and middle frontal gyri before treatment correlated with greater cocaine use during treatment. Elevated mOR binding in the anterior cingulate, medial frontal, middle frontal, middle temporal, and sublobar insular gyri correlated with shorter duration of cocaine abstinence during treatment. Regional mOR binding contributed significant predictive power for treatment outcome beyond that of standard clinical variables such as baseline drug and alcohol use.

      Conclusions

      Elevated mOR binding in brain regions associated with reward sensitivity is a significant independent predictor of treatment outcome in cocaine-abusing outpatients, suggesting a key role for the brain endogenous opioid system in cocaine addiction.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Knapp W.P.
        • Soares B.G.
        • Farrel M.
        • Lima M.S.
        Psychosocial interventions for cocaine and psychostimulant amphetamines related disorders.
        Cochrane Database Syst Rev. 2007; 3 (CD003023)
        • Poling J.
        • Kosten T.R.
        • Sofuoglu M.
        Treatment outcome predictors for cocaine dependence.
        Am J Drug Alcohol Abus. 2007; 33: 191-206
        • Unterwald E.M.
        Regulation of opioid receptors by cocaine.
        Ann NY Acad Sci. 2001; 937: 74-92
        • Tang X.C.
        • McFarland K.
        • Cagle S.
        • Kalivas P.W.
        Cocaine-induced reinstatement requires endogenous stimulation of mu-opioid receptors in the ventral pallidum.
        J Neurosci. 2005; 25: 4512-4520
        • Simmons D.
        • Self D.W.
        Role of mu- and delta-opioid receptors in the nucleus accumbens in cocaine-seeking behavior.
        Neuropsychopharmacology. 2009; 34: 1946-1957
        • Zubieta J.K.
        • Gorelick D.A.
        • Stauffer R.
        • Ravert H.T.
        • Dannals R.F.
        • Frost J.J.
        Increased mu-opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving.
        Nat Med. 1996; 2: 1225-1229
        • Gorelick D.A.
        • Kim Y.K.
        • Bencherif B.
        • Boyd S.J.
        • Nelson R.
        • Copersino M.
        • et al.
        Imaging brain mu-opioid receptors in abstinent cocaine users: Time course and relation to cocaine craving.
        Biol Psychiatry. 2005; 57: 1573-1582
        • Gorelick D.A.
        • Kim Y.K.
        • Bencherif B.
        • Boyd S.J.
        • Nelson R.
        • Copersino M.L.
        • et al.
        Brain mu-opioid receptor binding: Relationship to relapse to cocaine use after monitored abstinence.
        Psychopharmacology (Berl). 2008; 200: 475-486
        • McLellan A.T.
        • Luborsky L.
        • Cacciola J.
        • Griffith J.
        • Evans F.
        • Barr H.L.
        • O'Brien C.P.
        New data from the Addiction Severity Index.
        J Nerv Ment Dis. 1985; 173: 412-423
        • Zachary R.A.
        Shipley Institute of Living Scale: Revised Manual.
        Western Psychological Services, Los Angeles1986
        • Robins L.N.
        • Cottler L.B.
        • Bucholz K.K.
        • Compton W.M.I.
        The Diagnostic Interview Schedule, Version IV.
        Washington University, St. Louis1995
        • Frost J.J.
        • Wagner Jr, H.N.
        • Dannals R.F.
        • Ravert H.T.
        • Links J.M.
        • Wilson A.A.
        • et al.
        Imaging opiate receptors in the human brain by positron tomography.
        J Comput Assist Tomogr. 1985; 9: 231-236
        • Logan J.
        • Fowler J.S.
        • Volkow N.D.
        • Wang G.J.
        • Ding Y.S.
        • Alexoff D.L.
        Distribution volume ratios without blood sampling from graphical analysis of PET data.
        J Cereb Blood Flow Metab. 1996; 16: 834-840
        • Guardia J.
        • Catafau A.M.
        • Batlle F.
        • Martin J.C.
        • Segura L.
        • Gonzalvo B.
        • et al.
        Striatal dopaminergic D(2) receptor density measured by [(123)I] iodobenzamide SPECT in the prediction of treatment outcome of alcohol-dependent patients.
        Am J Psychiatry. 2000; 157: 127-129
        • Endres C.J.
        • Bencherif B.
        • Hilton J.
        • Madar I.
        • Frost J.J.
        Quantification of brain mu-opioid receptors with [11C] carfentanil: Reference-tissue methods.
        Nucl Med Biol. 2003; 30: 177-186
        • Maes F.
        • Collignon A.
        • Vandermeulen D.
        • Marchal G.
        • Suetens P.
        Multimodality image registration by maximization of mutual information.
        IEEE Trans Med Imaging. 1997; 16: 187-198
        • Ashburner J.
        • Friston K.
        Spatial normalization using basis functions.
        in: Frackowiak R.S. Friston K.J. Frith C. Dolan R.J. Price C. Zeki S. Human Brain Function. 2nd ed. Academic Press, Oxford, UK2003: 655-672
        • Ashburner J.
        • Friston K.
        Rigid body registration.
        in: Frackowiak R.S. Friston K.J. Frith C. Dolan R.J. Price C. Zeki S. Human Brain Function. 2nd ed. Academic Press, Oxford, UK2003: 635-654
        • Brown R.A.
        • Lewinsohn P.M.
        A psychoeducational approach to the treatment of depression: Comparison of group, individual, and minimal contact procedures.
        J Consult Clin Psychol. 1984; 52: 774-783
        • Folkman S.
        • Lazarus R.S.
        • Gruen R.J.
        • DeLongis A.
        Appraisal, coping, health status, and psychological symptoms.
        J Pers Soc Psychol. 1986; 50: 571-579
        • Marlatt G.A.
        • Curry S.
        • Gordon J.R.
        A longitudinal analysis of unaided smoking cessation.
        J Consult Clin Psychol. 1988; 56: 715-720
        • Epstein D.H.
        • Hawkins W.E.
        • Covi L.
        • Umbricht A.
        • Preston K.L.
        Cognitive-behavioral therapy plus contingency management for cocaine use: Findings during treatment and across 12-month follow-up.
        Psychol Addict Behav. 2003; 17: 73-82
        • Poline J.B.
        • Worsley K.J.
        • Holmes A.P.
        • Frackowiak R.S.
        • Friston K.J.
        Estimating smoothness in statistical parametric maps: Variability of p values.
        J Comput Assist Tomogr. 1995; 19: 788-796
        • Yasuno F.
        • Ota M.
        • Ando K.
        • Ando T.
        • Maeda J.
        • Ichimiya T.
        • et al.
        Role of ventral striatal dopamine D1 receptor in cigarette craving.
        Biol Psychiatry. 2007; 61: 1252-1259
        • Schmahl C.G.
        • Vermetten E.
        • Elzinga B.M.
        • Bremner J.D.
        A positron emission tomography study of memories of childhood abuse in borderline personality disorder.
        Biol Psychiatry. 2004; 55: 759-765
        • Wong D.F.
        • Kuwabara H.
        • Schretlen D.J.
        • Bonson K.R.
        • Zhou Y.
        • Nandi A.
        • et al.
        Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving.
        Neuropsychopharmacology. 2006; 31: 2716-2727
        • Zubieta J.K.
        • Dannals R.F.
        • Frost J.J.
        Gender and age influences on human brain mu-opioid receptor binding measured by PET.
        Am J Psychiatry. 1999; 156: 842-848
        • Gabilondo A.
        • Meana J.
        • Garcia-Sevilla J.
        Increased density of μ-opioid receptors in the postmortem brain of suicide victims.
        Brain Res. 1995; 682: 245-250
        • Zubieta J.K.
        • Smith Y.R.
        • Bueller J.A.
        • Xu Y.
        • Kilbourn M.R.
        • Jewett D.M.
        • et al.
        Mu-opioid receptor-mediated antinociceptive responses differ in men and women.
        J Neurosci. 2002; 22: 5100-5107
        • Berrendero F.
        • Robledo P.
        • Trigo J.M.
        • Martín-García E.
        • Maldonado R.
        Neurobiological mechanisms involved in nicotine dependence and reward: Participation of the endogenous opioid system [published online ahead of print February 16].
        Neurosci Biobehav Rev. 2010;
        • Rousseeuw R.J.
        • Leroy A.M.
        Robust Regression and Outlier Detection.
        Wiley, New York1987
        • Ahmadi J.
        • Kampman K.
        • Dackis C.
        Outcome predictors in cocaine dependence treatment trials.
        Am J Addict. 2006; 15: 434-439
        • Reiber C.
        • Ramirez A.
        • Parent D.
        • Rawson R.A.
        Predicting treatment success at multiple timepoints in diverse patient populations of cocaine-dependent individuals.
        Drug Alcohol Depend. 2002; 68: 35-48
        • Montoya I.D.
        • Gorelick D.A.
        • Preston K.L.
        • Schroeder J.R.
        • Umbricht A.
        • Cheskin L.J.
        • et al.
        Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence.
        Clin Pharmacol Ther. 2004; 75: 34-48
        • Jayaram-Lindstrom N.
        • Hammarberg A.
        • Beck O.
        • Franck J.
        Naltrexone for the treatment of amphetamine dependence: A randomized, placebo-controlled trial.
        Am J Psychiatry. 2008; 165: 1442-1448
        • Bossert J.M.
        • Ghitza U.E.
        • Lu L.
        • Epstein D.H.
        • Shaham Y.
        Neurobiology of relapse to heroin and cocaine seeking: An update and clinical implications.
        Eur J Pharmacol. 2005; 526: 36-50
        • Gerrits M.A.
        • Kuzmin A.V.
        • van Ree J.M.
        Reinstatement of cocaine-seeking behavior in rats is attenuated following repeated treatment with the opioid receptor antagonist naltrexone.
        Eur Neuropsychopharmacol. 2005; 15: 297-303
        • Garavan H.
        • Pankiewicz J.
        • Bloom A.
        • Cho J.K.
        • Sperry L.
        • Ross T.J.
        • et al.
        Cue-induced cocaine craving: Neuroanatomical specificity for drug users and drug stimuli.
        Am J Psychiatry. 2000; 157: 1789-1798
        • Goldstein R.Z.
        • Volkow N.D.
        Drug addiction and its underlying neurobiological basis: Neuroimaging evidence for the involvement of the frontal cortex.
        Am J Psychiatry. 2002; 159: 1642-1652
        • Naqvi N.H.
        • Bechara A.
        The hidden island of addiction: The insula.
        Trends Neurosci. 2009; 32: 56-67
        • Naqvi N.H.
        • Rudrauf D.
        • Damasio H.
        • Bechara A.
        Damage to the insula disrupts addiction to cigarette smoking.
        Science. 2007; 315: 531-534
        • Paulus M.P.
        • Tapert S.F.
        • Schuckit M.A.
        Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse.
        Arch Gen Psychiatry. 2005; 62: 761-768

      Linked Article

      • Opioid–Dopamine Interactions: Implications for Substance Use Disorders and Their Treatment
        Biological PsychiatryVol. 68Issue 8
        • Preview
          Two imaging reports in this volume highlight the importance of the interaction between the brain's opioid and dopamine (DA) systems in the reinforcing and addictive effects of substances of abuse. These studies use positron emission tomography (PET) to measure, in one instance (1), changes in DA induced by acute alcohol administration in healthy subjects (with [11C] raclopride, a radioligand that binds to D2 and D3 receptors (D2R and D3R) and that is sensitive to competition with endogenous DA) and, in the other (2), μ opioid receptor (mOR) availability in cocaine abusers (with [11C] carfentanil, an mOR specific radioligand).
        • Full-Text
        • PDF