title: Moderators of naltrexone's effects on drinking, urge, and alcohol effects in non-treatment-seeking heavy drinkers in the natural environment.
abstract: BACKGROUND
  Naltrexone (NTX) has proven to be effective with alcoholics in treatment, with most controlled clinical trials showing beneficial effects on heavy drinking rates. However, little is known about the behavioral mechanisms underlying the effects of NTX on drinking, or about patient characteristics that may moderate NTX's effects on drinking. In this study, ecological momentary assessment (EMA) techniques were used to investigate some of the putative mechanisms of naltrexone's effects on drinking in heavy drinkers who were not seeking treatment for alcohol problems. Polymorphisms in the D4 dopamine receptor (DRD4) gene and the mu-opiate receptor (OPRM1) gene, family history of alcohol problems, age of onset of alcoholism and gender were explored as potential moderators of NTX's effects.
  
  
  METHODS
  After a 1-week placebo lead-in period, heavy drinkers (n = 180), 63% of whom were alcohol-dependent, were randomized to 3 weeks of daily naltrexone (50 mg) or placebo. Throughout the study, participants used EMA on palm-pilot computers to enter, in real time, drink data, urge levels, and subjective effects of alcohol consumption.
  
  
  RESULTS
  Naltrexone reduced percentage drinking days in all participants and reduced percent heavy drinking days in DRD4-L individuals; NTX decreased urge levels in participants with younger age of alcoholism onset; NTX increased time between drinks in participants who had more relatives with alcohol problems; and NTX reduced the stimulating effects of alcohol in women. OPRM1 status did not moderate any of NTX's effects.
  
  
  CONCLUSIONS
  These results confirm earlier findings of NTX's effects on drinking and related subjective effects, and extend them by describing individual difference variables that moderate these effects in the natural environment, using data collected in real time.
authors.affiliation: Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island 02912, USA. jennifer_tidey@brown.edu
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Tidey
authors.forename: Peter M
authors.initials: PM
authors.lastname: Monti
authors.forename: Damaris J
authors.initials: DJ
authors.lastname: Rohsenow
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Gwaltney
authors.forename: Robert
authors.initials: R
authors.lastname: Miranda
authors.forename: John E
authors.initials: JE
authors.lastname: McGeary
authors.forename: James
authors.initials: J
authors.lastname: MacKillop
authors.forename: Robert M
authors.initials: RM
authors.lastname: Swift
authors.forename: David B
authors.initials: DB
authors.lastname: Abrams
authors.forename: Saul
authors.initials: S
authors.lastname: Shiffman
authors.forename: Jean A
authors.initials: JA
authors.lastname: Paty
mesh_terms: D000328:Adult; D017668:Age of Onset; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000437:Alcoholism / Q000235:genetics; D004777:Environment; D005260:Female; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010349:Patient Compliance; D020641:Polymorphism, Single Nucleotide; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D015203:Reproducibility of Results; D012737:Sex Factors; D013997:Time Factors
chemical_list: C493599:DRD4 protein, human; D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D050638:Receptors, Dopamine D4; D009271:Naltrexone