title: Dutasteride reduces alcohol's sedative effects in men in a human laboratory setting and reduces drinking in the natural environment.
abstract: BACKGROUND
  Preclinical studies support the hypothesis that endogenous neuroactive steroids mediate some effects of alcohol.
  
  
  OBJECTIVE
  The aim of this study was to examine the effect of dutasteride inhibition of 5α-reduced neuroactive steroid production on subjective responses to alcohol in adult men.
  
  
  METHODS
  Using a within-subject factorial design, 70 men completed four randomly ordered monthly sessions in which pretreatment with 4 mg dutasteride or placebo was paired with a moderate dose of alcohol (0.8 g/kg) or placebo beverage. The pharmacologic effect of dutasteride was measured by an assay of serum androstanediol glucuronide. Self-reports of alcohol effects were obtained at 40-min intervals following alcohol administration using the Biphasic Alcohol Effects Scale (BAES) and the Alcohol Sensation Scale (SS). We used linear mixed models to examine the effects of dutasteride and alcohol on BAES and SS responses and the interaction of dutasteride with the GABRA2 alcohol dependence-associated polymorphism rs279858. We also examined whether exposure to dutasteride influenced drinking in the weeks following each laboratory session.
  
  
  RESULTS
  A single 4-mg dose of dutasteride produced a 70 % reduction in androstanediol glucuronide. Dutasteride pretreatment reduced alcohol effects on the BAES sedation and SS anesthesia scales. There was no interaction of dutasteride with rs279858. Heavy drinkers had fewer heavy drinking days during the 2 weeks following the dutasteride sessions and fewer total drinks in the first week after dutasteride.
  
  
  CONCLUSIONS
  These results provide evidence that neuroactive steroids mediate some of the sedative effects of alcohol in adult men and that dutasteride may reduce drinking, presumably through its effects on neuroactive steroid concentrations.
authors.affiliation: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA, jocovault@uchc.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Covault
authors.forename: Timothy
authors.initials: T
authors.lastname: Pond
authors.forename: Richard
authors.initials: R
authors.lastname: Feinn
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Arias
authors.forename: Cheryl
authors.initials: C
authors.lastname: Oncken
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D015113:Androstane-3,17-diol / Q000097:blood; D001378:Azasteroids / Q000627:therapeutic use*; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000068538:Dutasteride; D004777:Environment; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000235:genetics; D055815:Young Adult
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D002492:Central Nervous System Depressants; C484841:GABRA2 protein, human; D011963:Receptors, GABA-A; D015113:Androstane-3,17-diol; D000431:Ethanol; D000068538:Dutasteride