Opioid Antagonists in the Treatment of Pathological Gambling and Kleptomania

  • Jon E. Grant
Part of the Contemporary Neuroscience book series (CNEURO)


This chapter reviews the current knowledge of the clinical characteristics, associated psychopathology, family history, and neurobiology of pathological gambling and kleptomania. This chapter also presents study results of the pharmacological use of opioid antagonists in treating these disorders.


Impulse control disorders Pathological gambling Behavioral addiction Kleptomania 


  1. 1.
    Cunningham-Williams RM, Cottler LB, Compton III WM, Spitznagel EL. Taking chances: problem gamblers and mental health disorders — results from the St. Louis Epidemiologic Catchment Area study. Am J Pub Health 1998; 88:1093–1096.CrossRefGoogle Scholar
  2. 2.
    Grant JE, Potenza MN, Levine L, Kim D. Prevalence of impulse control disorders in adult psychiatric inpatients. Am J Psychiatry (in press).Google Scholar
  3. 3.
    Hollander E. Obsessive-compulsive spectrum disorders: an overview. Psychiatr Ann 1993; 23:355–358.Google Scholar
  4. 4.
    Grant JE, Potenza MN. Pathological gambling and other “behavioral addictions.” In: Frances RJ, Miller SI, Mack AH, eds. Clinical Handbook of Addictive Disorders (3rd edn.); New York: Guilford Press, 2005, pp. 303–320.Google Scholar
  5. 5.
    Argo TR, Black DW. Clinical characteristics. In: Grant JE, Potenza MN, eds. Pathological Gambling: A Clinical Guide to Treatment; Washington, DC: American Psychiatric Publishing, 2004, pp. 39–53.Google Scholar
  6. 6.
    Ibanez A, Blanco C, Moreyra P, Saiz-Ruiz J. Gender differences in pathological gambling. J Clin Psychiatry 2003; 64:295–301.CrossRefPubMedGoogle Scholar
  7. 7.
    Volberg RA. The prevalence and demographics of pathological gamblers: implications for public health. Am J Public Health 1994; 84:237–240.CrossRefPubMedGoogle Scholar
  8. 8.
    Potenza MN, Steinberg MA, McLaughlin SD, Wu R, Rounsaville B, O'Malley SS. Gender-related differences in the characteristics of problem gamblers using a gambling helpline. Am J Psychiatry 2001; 158:1500–1505.CrossRefPubMedGoogle Scholar
  9. 9.
    Ladd GT, Petry NM. Gender differences among pathological gamblers seeking treatment. Exp Clin Psychopharmacol 2002; 10:302–309.CrossRefPubMedGoogle Scholar
  10. 10.
    Grant JE, Kim SW. Demographic and clinical features of 131 adult pathological gamblers. J Clin Psychiatry 2001; 62:957–962.CrossRefPubMedGoogle Scholar
  11. 11.
    Goldman MJ. Kleptomania: making sense of the nonsensical. Am J Psychiatry 1991; 148:986–996.PubMedGoogle Scholar
  12. 12.
    McElroy SL, Pope HG, Hudson JI, Keck PE, White KL. Kleptomania: a report of 20 cases. Am J Psychiatry 1991; 148:652–657.PubMedGoogle Scholar
  13. 13.
    Presta S, Marazziti D, Dell'Osso L, Pfanner C, Pallanti S, Cassano GB. Kleptomania: clinical features and comorbidity in an Italian sample. Compr Psychiatry 2002; 43:7–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Grant JE, Kim SW. Clinical characteristics and associated psychopathology of 22 patients with kleptomania. Compr Psychiatry 2002; 43:378–384.CrossRefPubMedGoogle Scholar
  15. 15.
    Blanco C, Moreyra P, Nunes E V, Saiz-Ruiz J, Ibanez A. Pathological gambling: addiction or compulsion? Semin Clin Neuropsychiatry 2001; 6:167–176.CrossRefPubMedGoogle Scholar
  16. 16.
    Crockford DN, el-Guebaly N. Psychiatric comorbidity in pathological gambling: a critical review. Can J Psychiatry 1998; 43:43–50.PubMedGoogle Scholar
  17. 17.
    Petry NM, Oncken C. Cigarette smoking is associated with increased severity of gambling problems in treatment-seeking gamblers. Addiction 2002; 97:745–753.CrossRefPubMedGoogle Scholar
  18. 18.
    Petry NM. Pathological Gambling: Etiology, Comorbidity, and Treatment. Washington, DC: American Psychological Association, 2005.CrossRefGoogle Scholar
  19. 19.
    Spunt B, Lesieur H, Hunt D, Cahill L. Gambling among methadone patients. Int J Addict 1995; 30:929–962.PubMedGoogle Scholar
  20. 20.
    Grant JE. Family history and psychiatric comorbidity in persons with kleptomania. ComprPsychiatry 2003; 44:437–441.Google Scholar
  21. 21.
    Slutske WS, Eisen S, True WR, Lyons MJ, Goldberg J, Tsuang M. Common genetic vulnerability for pathological gambling and alcohol dependence in men. Arch Gen Psychiatry 2000; 57:666–673.CrossRefPubMedGoogle Scholar
  22. 22.
    Comings DE, Rosenthal RJ, Lesieur HR, Rugle LJ, Muhleman D, Chiu C, Dietz G, Gade R. A study of the dopamine D2 receptor gene in pathological gambling. Pharmacogenetics 1996; 6:223–234.CrossRefPubMedGoogle Scholar
  23. 23.
    Kelley AE. Memory and addiction: shared neural circuitry and molecular mechanisms. Neuron 2004; 44:161–179.CrossRefPubMedGoogle Scholar
  24. 24.
    Tobler, PN, Fiorillo CD, Schultz W. Adaptive coding of reward by dopamine neurons. Science 2005; 307:1642–1645.CrossRefPubMedGoogle Scholar
  25. 25.
    Fiorillo CD, Tobler PN, Schultz W. Discrete coding of reward probability and uncertainty by dopamine neurons. Science 2003; 299:1898–1902.CrossRefPubMedGoogle Scholar
  26. 26.
    Kosten TR, Scanley, BE, Tucker KA, Oliveto A, Prince C, Sinha R, Potenza MN, Skudlarski P, Wexler BE. Cue-induced brain activity changes and relapse in cocaine-dependent patients. Neuropsychopharmacology 2006; 31:644–650.CrossRefPubMedGoogle Scholar
  27. 27.
    Wexler BE, Gottschalk CH, Fulbright RK, Prohovnik I, Lacadie CM, Rounsaville BJ, Gore JC. Functional magnetic resonance imaging of cocaine craving. Am J Psychiatry 2001; 158:86–95.CrossRefPubMedGoogle Scholar
  28. 28.
    Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Hitzemann R, Chen AD, Dewey SL, Pappas N. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 1997; 386:830–833.CrossRefPubMedGoogle Scholar
  29. 29.
    Bergh C, Eklund T, Sodersten P, Nordin C. Altered dopamine function in pathological gambling. Psychol Med 1997; 27:473–475.CrossRefPubMedGoogle Scholar
  30. 30.
    Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 2005; 162:1403–1413.CrossRefPubMedGoogle Scholar
  31. 31.
    Loba P, Stewart SH, Klein RM, Blackburn JR. Manipulations of the features of standard video lottery terminal (VLT) games: effects in pathological and non-pathological gamblers. J Gambl Stud 2001; 17:297–320.CrossRefPubMedGoogle Scholar
  32. 32.
    Shalev U, Grimm JW, Shaham Y. Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 2002; 54:1–42.CrossRefPubMedGoogle Scholar
  33. 33.
    Zack M, Poulos CX. Amphetamine primes motivation to gamble and gambling-related semantic networks in problem gamblers. Neuropsychopharmacology 2004; 29:195–207.CrossRefPubMedGoogle Scholar
  34. 34.
    Johnson SW, North RA. Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 1992; 12:483–488.PubMedGoogle Scholar
  35. 35.
    Shinohara K, Yanagisawa A, Kagota Y, Gomi A, Nemoto K, Moriya E, Furusawa E, Furuya K, Terasawa K. Physiological changes in Pachinko players; beta-endorphin, catecholamines, immune system substances and heart rate. Appl Human Sci 1999;18:37–42.CrossRefPubMedGoogle Scholar
  36. 36.
    Tamminga CA, Nestler EJ. Pathological gambling: focusing on the addiction, not the activity. Am J Psychiatry 2006; 163:180–181.CrossRefPubMedGoogle Scholar
  37. 37.
    Dreher JC, Kohn P, Berman KF. Neural coding of distinct statistical properties of reward information in humans. Cereb Cortex 2006; 16:561–573.CrossRefPubMedGoogle Scholar
  38. 38.
    Crockford DN, Goodyear B, Edwards J, Edwards J, Quickfall J, el-Guebaly N. Cue-induced brain activity in pathological gamblers. Biol Psychiatry 2005; 58:787–795.CrossRefPubMedGoogle Scholar
  39. 39.
    Reuter J, Raedler T, Rose M, Hand I, Glascher J, Buchel C. Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nature Neurosci 2005; 8:147–148.CrossRefPubMedGoogle Scholar
  40. 40.
    Potenza MN, Leung HC, Blumberg HP, Peterson BS, Fulbright RK, Lacadie CM, Skudlarski P, Gore JC. An FMRI Stroop task study of ventromedial prefrontal cortical function in pathological gamblers. Am J Psychiatry 2003; 160:1990–1994.CrossRefPubMedGoogle Scholar
  41. 41.
    Jentsch JD, Taylor JR. Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology (Berl) 1999; 146:373–390.CrossRefPubMedGoogle Scholar
  42. 42.
    Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for involvement of the frontal cortex. Am J Psychiatry 2002; 159:523–528.CrossRefGoogle Scholar
  43. 43.
    Sood ED, Pallanti S, Hollander E. Diagnosis and treatment of pathologic gambling. Curr Psychiatry Rep 2003; 5:9–15.CrossRefPubMedGoogle Scholar
  44. 44.
    Brahen LS, Capone T, Wiechert V, Desiderio D. Naltrexone and cyclazocine. A controlled treatment study. Arch Gen Psychiatry 1977; 34:1181–1184.PubMedGoogle Scholar
  45. 45.
    Berridge KC, Robinson TE What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev 1998; 28:309–369.CrossRefPubMedGoogle Scholar
  46. 46.
    Kim SW. Opioid antagonists in the treatment of impulse control disorders. J Clin Psychiatry 1998; 59:159–162.CrossRefPubMedGoogle Scholar
  47. 47.
    Broekkamp CL, Phillips AG. Facilitation of self-stimulation behavior following intracerebral microinjections of opioids into the ventral tegmental area. Pharmacol Biochem Behav 1979; 11:289–295.CrossRefPubMedGoogle Scholar
  48. 48.
    Stewart J. Reinstatement of heroin and cocaine self-administration behavior in the rat by intracerebral application of morphine in the ventral tegmental area. Pharmacol Biochem Behav 1984; 20:917–923.CrossRefPubMedGoogle Scholar
  49. 49.
    van Wolfswinkel L, van Ree JM. Effects of morphine and naloxone on thresholds of ventral tegmental electrical self-stimulation. Naunyn-Schmiedebergs Arch Pharmacol 1985; 330:84–92.CrossRefPubMedGoogle Scholar
  50. 50.
    Koob GF. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 1992; 13:177–184.CrossRefPubMedGoogle Scholar
  51. 51.
    Crockford DN, el-Guebaly N. Naltrexone in the treatment of pathological gambling and alcohol dependence. Can J Psychiatry 1998; 43:86 [letter].PubMedGoogle Scholar
  52. 52.
    Kim SW, Grant JE. An open naltrexone treatment study in pathological gambling disorder. Int Clin Psychopharmacol 2001; 16:285–289.CrossRefPubMedGoogle Scholar
  53. 53.
    Kim SW, Grant JE, Adson DE, Shin YC. Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling. Biol Psychiatry 2001; 49:914–921.CrossRefPubMedGoogle Scholar
  54. 54.
    Kim SW, Grant JE, Adson DE, Remmel RP. A preliminary report on possible naltrexone and nonsteroidal analgesic interactions. J Clin Psychopharmacol 2001; 21:632–634 [letter].CrossRefPubMedGoogle Scholar
  55. 55.
    Grant JE, Potenza MN, Hollander E, Cunningham-Williams R, Nurminen T, Smits G, Kallio A. A multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry 2006; 163:303–312.CrossRefPubMedGoogle Scholar
  56. 56.
    Grant JE, Kim SW. An open-label study of naltrexone in the treatment of kleptomania. J Clin Psychiatry 2002; 63:349–356.PubMedGoogle Scholar
  57. 57.
    Grant JE. Outcome study of kleptomania patients treated with naltrexone: a chart review. Clin Neuropharmacol 2005; 28:11–14.CrossRefPubMedGoogle Scholar
  58. 58.
    Pfohl DN, Allen JI, Atkinson RL, Knopman DS, Malcolm RJ, Mitchell JE, Morley JE. Naltrexone hydrochloride (Trexan): a review of serum transaminase elevations at high dosage. NIDA Res Monogr 1986; 67:66–72.PubMedGoogle Scholar
  59. 59.
    Verebey KG, Mule SJ. Naltrexone (Trexan): a review of hepatotoxicity issues. NIDA Res Monogr 1986; 67:73–81.PubMedGoogle Scholar
  60. 60.
    Kim SW, Grant JE, Yoon G, Williams KA, Remmel RP. Safety of high-dose naltrexone treatment: hepatic transaminase profiles among outpatients. Clin Neuropharmacol 2006; 29:77–79.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jon E. Grant
    • 1
  1. 1.Department of PsychiatryUniversity of Minnesota Medical SchoolMinneapolisMN

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