title: Variation in Mu-Opioid Receptor Gene(OPRM1)as a Moderator of Naltrexone Treatment to Reduce Heavy Drinking in a High Functioning Cohort.
abstract: BACKGROUND
  It is well known that naltrexone, an FDA-approved medication for treatment of alcohol dependence, is effective for only a subset of individuals. Recent studies have examined the utility of a functional A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene(OPRM1)as a predictor of naltrexone treatment response. Although the findings to date have generally been consistent with a moderating effect of the SNP, further evaluation of this hypothesis is warranted.
  
  
  OBJECTIVE
  To evaluate whether problem drinkers with one or two copies of the 118G allele respond better to naltrexone treatment. The treatment goal in this cohort of high functioning men who have sex with men (MSM) was to reduce heavy drinking, rather than to promote abstinence.
  
  
  METHODS
  112 subjects of European ancestry from a randomized clinical trial of naltrexone and behavioral therapy for problem drinking MSM were included in the analysis. Subjects were treated for 12 weeks with 100 mg/day of oral naltrexone hydrochloride. All participants received medical management with a modified version of the Brief Behavioral Compliance Enhancement Treatment (BBCET), alone or in combination with Modified Behavioral Self-control Therapy (MBSCT).
  
  
  RESULTS
  Naltrexone-treated subjects with one or two 118G alleles had a significantly greater percentage of non-hazardous drinking (NoH) (p < 0.01) than those treated with placebo or A118 homozygotes in either medication group.
  
  
  CONCLUSIONS
  These results are consistent with a modest moderating effect of theOPRM1118G allele on the reduction of heavy drinking by naltrexone treatment.
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, USA.
authors.forename: Andrew Ch
authors.initials: AC
authors.lastname: Chen
authors.affiliation: Research Foundation for Mental Hygiene, Inc., New York State Psychiatric Institute, New York, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Morgenstern
authors.affiliation: Department of Psychiatry, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Davis
authors.affiliation: Treatment Research Center, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania and VISN4 MIRECC, Philadelphia VAMC Philadelphia, USA.
authors.forename: Alexis N
authors.initials: AN
authors.lastname: Kuerbis
authors.forename: Jonathan
authors.initials: J
authors.lastname: Covault
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
keywords: Alcohol; Hazardous drinking; Moderation; Pharmacogenetics
references.citation: Biometrics. 1986 Mar;42(1):121-30
references.pmid: 3719049
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Br J Addict. 1989 Jul;84(7):801-14
references.pmid: 2758153
references.citation: Cochrane Database Syst Rev. 2010 Dec 08;(12):CD001867
references.pmid: 21154349
references.citation: PCR Methods Appl. 1995 Jun;4(6):357-62
references.pmid: 7580930
references.citation: JAMA. 2006 May 3;295(17):2003-17
references.pmid: 16670409
references.citation: Arch Gen Psychiatry. 2007 Sep;64(9):1069-77
references.pmid: 17768272
references.citation: Alcohol Alcohol. 2000 Nov-Dec;35(6):587-93
references.pmid: 11093966
references.citation: Arch Gen Psychiatry. 2008 Feb;65(2):135-44
references.pmid: 18250251
references.citation: Psychopharmacology (Berl). 2009 Jan;201(4):611-8
references.pmid: 18795264
references.citation: Neuropsychopharmacology. 2003 Aug;28(8):1546-52
references.pmid: 12813472
references.citation: Drug Alcohol Depend. 2009 Dec 1;105(3):256-8
references.pmid: 19717248
references.citation: Alcohol Clin Exp Res. 2004 Dec;28(12):1789-95
references.pmid: 15608594
references.citation: Curr Pharm Des. 2010;16(19):2141-8
references.pmid: 20482509
references.citation: Alcohol Clin Exp Res. 2010 Dec;34(12):2022-34
references.pmid: 20659066
references.citation: Alcohol Clin Exp Res. 2007 Apr;31(4):555-63
references.pmid: 17374034
references.citation: Recent Dev Alcohol. 2003;16:217-45
references.pmid: 12638640
references.citation: Addict Biol. 2012 May;17(3):505-12
references.pmid: 22515274
references.citation: Addiction. 2001 Nov;96(11):1565-73
references.pmid: 11784454
references.citation: J Consult Clin Psychol. 2012 Oct;80(5):863-75
references.pmid: 22612306
references.citation: J Clin Psychopharmacol. 2006 Dec;26(6):610-25
references.pmid: 17110818