, Volume 212, Issue 4, pp 603–612 | Cite as

Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study

  • Jon E. Grant
  • Samuel R. Chamberlain
  • Brian L. Odlaug
  • Marc N. Potenza
  • Suck Won Kim
original investigation



Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl d-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG.


This study sought to examine the safety and efficacy of Memantine in PG.


Twenty-nine subjects (18 females) with DSM-IV PG were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra-dimensional (ID/ED) set shift task (assessing cognitive flexibility).


Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8 ± 4.3 at baseline to 8.9 ± 7.1 at study endpoint (p < 0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p < 0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p = 0.037) at study endpoint. The mean effective dose of memantine was 23.4 ± 8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility.


These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.


Cognition Glutamate Impulsivity Treatment Pharmacology Addiction 



Cambridge Neuropsychological Test Automated Battery


Clinical Global Impressions


Gambling Symptom Assessment Scale


Hamilton Anxiety Scale Rating


Hamilton Depression Scale Rating


Intra-dimensional/Extra-dimensional Set Shift task


N-methyl d-aspartate


Pathological Gambling


Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling


Quality of Life Inventory


Structured Clinical Interview for DSM-IV


Sheehan Disability Scale


Stop Signal Test


Funding/disclosures/conflicts of interest

This study was funded by a research grant from Forest Pharmaceuticals.

Dr. Grant has received research grants from NIMH, NIDA, and National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, Forest Pharmaceuticals and GlaxoSmithKline. Dr. Grant receives yearly compensation from Springer Publishing for acting as Editor-in-Chief of the Journal of Gambling Studies. Dr. Grant has performed grant reviews for NIH and the Ontario Gambling Association. Dr. Grant has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, and McGraw Hill. Dr. Grant has received honorarium from Indiana University Medical School, University of South Florida, the Mayo Medical School, the California Society of Addiction Medicine, the State of Arizona, the State of Massachusetts, the State of Oregon, the Province of Nova Scotia, and the Province of Alberta. Dr. Grant has received compensation as a consultant for law offices on issues related to impulse control disorders.

Dr. Chamberlain has consulted for Cambridge Cognition, P1Vital, and Shire Pharmaceuticals.

Dr. Potenza has consulted for and advised Boehringer Ingelheim; has received research support from the National Institutes of Health, Veteran’s Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories pharmaceuticals; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law offices on issues related to addictions or impulse control disorders; has provided clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; has performed grant reviews for the National Institutes of Health and other agencies; has guest-edited journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts.

Dr. Kim and Mr. Odlaug have no financial disclosures to report.


  1. Aron AR, Robbins TW, Poldrack RA (2004) Inhibition and the right inferior frontal cortex. Trends Cogn Sci 8:170–177CrossRefPubMedGoogle Scholar
  2. Baker DA, McFarland K, Lake RW, Shen H, Toda S, Kalivas PW (2003) N-acetyl cysteine-induced blockade of cocaine-induced reinstatement. Ann NY Acad Sci 1003:349–351CrossRefPubMedGoogle Scholar
  3. Bisaga A, Evans SM (2004) Acute effects of memantine in combination with alcohol in moderate drinkers. Psychopharmacol 172:16–24CrossRefGoogle Scholar
  4. Black DW (2004) An open-label trial of bupropion in the treatment of pathologic gambling. J Clin Psychopharmacol 24:108–110CrossRefPubMedGoogle Scholar
  5. Black DW, Shaw MC, Allen J (2008) Extended release carbamazepine in the treatment of pathological gambling: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry 32:1191–1194CrossRefPubMedGoogle Scholar
  6. Blanco C, Petkova E, Ibáñez A, Sáiz-Ruiz J (2002) A pilot placebo-controlled study of fluvoxamine for pathological gambling. Ann Clin Psychiatry 14:9–15PubMedGoogle Scholar
  7. Cambridge Cognition Limited (2006) CANTABeclipse, version 3. Cambridge Cognition Limited, CambridgeGoogle Scholar
  8. Cunningham-Williams RM, Cottler LB, Compton WM III, Spitznagel EL (1998) Taking chances: problem gamblers and mental health disorders—results from the St. Louis Epidemiologic Catchment Area study. Am J Publ Health 88:1093–1096CrossRefGoogle Scholar
  9. Evans SM, Levin FR, Brooks DJ, Garawi F (2007) A pilot double-blind treatment trial of memantine for alcohol dependence. Alcohol Clin Exp Res 31:775–782CrossRefPubMedGoogle Scholar
  10. Farlow MR, Graham SM, Alva G (2008) Memantine for the treatment of Alzheimer’s disease: tolerability and safety data from clinical trials. Drug Saf 31(7):577–585CrossRefPubMedGoogle Scholar
  11. First MB, Spitzer RL, Gibbon M, Williams JBW (1995) Structured clinical interview for DSM-IV-patient edition (SCID-I/P, Version 2.0). Biometrics Research Department, New York State Psychiatric Institute, New YorkGoogle Scholar
  12. Frisch MB, Cornell J, Villaneuva M (1993) Clinical validation of the quality of life inventory: a measure of life satisfaction for use in treatment planning and outcome assessment. Psychol Assess 4:92–101CrossRefGoogle Scholar
  13. Grant JE, Kim SW (2005) Quality of life in kleptomania and pathological gambling. Compr Psychiatry 46:34–37CrossRefPubMedGoogle Scholar
  14. Grant JE, Potenza MN (2006) Compulsive aspects of impulse control disorders. Psychiatr Clin North Am 29:539–551CrossRefPubMedGoogle Scholar
  15. Grant JE, Steinberg MA, Kim SW, Rounsaville BJ, Potenza MN (2004) Preliminary validity and reliability testing of a structured clinical interview for pathological gambling (SCI-PG). Psychiatry Res 128:79–88CrossRefPubMedGoogle Scholar
  16. Grant JE, Levine L, Kim D, Potenza MN (2005) Impulse control disorders in adult psychiatric inpatients. Am J Psychiatry 162:2184–2188CrossRefPubMedGoogle Scholar
  17. Grant JE, Potenza MN, Hollander E, Cunningham-Williams R, Nurminen T, Smits G, Kallio A (2006) A multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry 163:303–312CrossRefPubMedGoogle Scholar
  18. Grant JE, Kim SW, Odlaug BL (2007) N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry 62:652–657CrossRefPubMedGoogle Scholar
  19. Grant JE, Kim SW, Hartman BK (2008) A double-blind, placebo-controlled study of the opiate antagonist, naltrexone, for the treatment of pathological gambling urges. J Clin Psychiatry 69:783–789CrossRefPubMedGoogle Scholar
  20. Grant JE, Donahue CJ, Odlaug BL, Kim SW, Miller MJ, Petry NM (2009) Imaginal desensitization plus motivational interviewing in the treatment of pathological gambling: a randomized controlled trial. Br J Psychiatry 195:266–267CrossRefPubMedGoogle Scholar
  21. Grant JE, Schreiber L, Odlaug BL, Kim SW (2010) Pathologic gambling and bankruptcy. Compr Psychiatry 51:115–120CrossRefPubMedGoogle Scholar
  22. Guy W (1976) ECDEU assessment manual for psychopharmacology. US Dept Health, Education and Welfare publication (ADM) 76–338. National Institute of Mental Health, Rockville, pp 218–222Google Scholar
  23. Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55PubMedGoogle Scholar
  24. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62CrossRefPubMedGoogle Scholar
  25. Hampshire A, Owen AM (2006) Fractionating attentional control using event-related fMRI. Cereb Cortex 16(12):1679–1689CrossRefPubMedGoogle Scholar
  26. Hampshire A, Chamberlain SR, Monti MM, Duncan J, Owen AM (2010) The role of the right inferior frontal gyrus: inhibition and attentional control. Neuroimage 50(3):1313–1319CrossRefPubMedGoogle Scholar
  27. Hollander E, Pallanti S, Allen A, Sood E, Baldini Rossi N (2005) Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders? Am J Psychiatry 162:137–145CrossRefPubMedGoogle Scholar
  28. Kim SW, Grant JE, Adson DE, Shin YC (2001) Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling. Biol Psychiatry 49:914–921CrossRefPubMedGoogle Scholar
  29. Kim SW, Grant JE, Potenza MN, Blanco C, Hollander E (2009) The Gambling Symptom Assessment Scale (G-SAS): a reliability and validity study. Psychiatry Res 166:76–84CrossRefPubMedGoogle Scholar
  30. Krystal JH, Petrakis IL, Krupitsky E, Schutz C, Trevisan L, D'Souza DC (2003) NMDA receptor antagonism and the ethanol intoxication signal: from alcoholism risk to pharmacotherapy. Ann NY Acad Sci 1003:176–184CrossRefPubMedGoogle Scholar
  31. Lezak MD, Howieson DB, Loring DW, Hannay HJ, Fischer JS (2004) Neuropsychological assessment. Oxford University Press, New YorkGoogle Scholar
  32. Logan GD, Cowan WB, Davis KA (1984) On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform 10:276–291CrossRefPubMedGoogle Scholar
  33. Ma YY, Cepeda C, Cui CL (2009) The role of NMDA receptors in drug addiction. Int Rev Neurobiol 89:131–146CrossRefPubMedGoogle Scholar
  34. Meisner F, Scheller C, Kneitz S, Sopper S, Neuen-Jacob E, Riederer P, Meulen V, Koutsilieri E (2008) Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: a novel pharmacological action of memantine. Neuropsychopharmacol 33:2228–2236CrossRefGoogle Scholar
  35. Minkeviciene R, Banerjee P, Tanila H (2008) Cognition-enhancing and anxiolytic effects of memantine. Neuropharmacol 54:1079–1085CrossRefGoogle Scholar
  36. Owen AM, Roberts AC, Polkey CE, Sahakian BJ, Robbins TW (1991) Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia 29(10):993–1006CrossRefPubMedGoogle Scholar
  37. Pallanti S, DeCaria CM, Grant JE, Urpe M, Hollander E (2005) Reliability and validity of the pathological gambling adaptation of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS). J Gambl Stud 21:431–443CrossRefPubMedGoogle Scholar
  38. Petry NM (2005) Pathological gambling: etiology, comorbidity, and treatment. American Psychological Association, WashingtonCrossRefGoogle Scholar
  39. Petry NM, Ammerman Y, Bohl J, Doersch A, Gay H, Kadden R, Molina C, Steinberg K (2006) Cognitive–behavioral therapy for pathological gamblers. J Consult Clin Psychol 74:555–567CrossRefPubMedGoogle Scholar
  40. Potenza MN, Fiellin DA, Heninger GR, Rounsaville BJ, Mazure CM (2002) Gambling: an addictive behavior with health and primary care implications. J Gen Intern Med 17:721–732CrossRefPubMedGoogle Scholar
  41. Repantis D, Laisney O, Heuser I (2010) Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res 61(6):473–481CrossRefPubMedGoogle Scholar
  42. Shaffer HJ, Hall MN, Vander Bilt J (1999) Estimating the prevalence of disordered gambling behavior in the United States and Canada: a research synthesis. Am J Publ Health 89:1369–1376CrossRefGoogle Scholar
  43. Sheehan DV (1983) The anxiety disease. Scribner's, New YorkGoogle Scholar
  44. Tait DS, Marston HM, Shahid M, Brown VJ (2009) Asenapine restores cognitive flexibility in rats with medial prefrontal cortex lesions. Psychopharmacol (Berl) 202:295–306CrossRefGoogle Scholar
  45. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I (2004) Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 291:317–324CrossRefPubMedGoogle Scholar
  46. Van Wageningen H, Jorgensen HA, Specht K, Hugdahl K (2010) A 1H-MR spectroscopy study of changes in glutamate and glutamine (Glx) concentrations in frontal spectra after administration of memantine. Cereb Cortex 20:798–803CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jon E. Grant
    • 1
  • Samuel R. Chamberlain
    • 2
  • Brian L. Odlaug
    • 1
  • Marc N. Potenza
    • 3
  • Suck Won Kim
    • 1
  1. 1.Department of PsychiatryUniversity of Minnesota School of MedicineMinneapolisUSA
  2. 2.Department of Psychiatry, University of CambridgeAddenbrooke’s HospitalCambridgeUK
  3. 3.Department of PsychiatryYale UniversityNew HavenUSA

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