Conditions: Alcohol Related Disorders Alcoholism Alcohol Abuse
Keywords: steroid 5Alpha Reductase dutasteride neuroactive steroid
Allocation: RANDOMIZED | Intervention model: FACTORIAL
Enrollment: 94
Healthy volunteers: yes

Brief summary:
This study will explore the hypothesis that effects of alcohol are in part mediated by increased production of neuroactive steroids, which interact with GABAA-receptors. We propose to study non-dependent drinkers using a 4-session within-subjects design in which alcohol / placebo is paired with dutasteride / placebo pretreatment. Dutasteride is a 5-alpha steroid reductase (5AR) inhibitor that limits the production of dihydrotestosterone and the 5a-reduced neuroactive steroids allopregnanolone, pregnanolone and 3a,5a-androstanediol.

Detailed description:
Alcohol has multiple pharmacological effects, though which of these effects relate to the risk of alcohol dependence is not clear. Animal studies indicate that the neuroactive steroid allopregnanolone is an alcohol-modulated endogenous agonist at GABAA receptors and that genetic variation in steroid 5a-reductase type I gene which generates neuroactive steroids, may moderate alcohol effects. To better define the role of neuroactive steroids we will conduct a laboratory study of non-alcohol dependent drinkers using a 4-session design in which alcohol/placebo beverage is paired with dutasteride/placebo pretreatment. Dutasteride, an inhibitor of both type I and type II 5a-reductase enzymes, blocks the production of 5a-reduced neuroactive steroids. This study will extend our preliminary findings with finasteride by including a) a placebo control for alcohol, b) a more specific inhibitor of both 5a-reductase isoenzymes, c) a larger group of subjects (including both light and heavy drinkers).

Arms:
arm 1: None arm 2: None arm 3: None arm 4: None

Interventions: intervention 1: dutasteride + ethanol intervention 2: placebo medication + ethanol intervention 3: dutasteride + placebo alcohol intervention 4: placebo medication + placebo alcohol
Intervention descriptions: intervention 1: 4 mg dutasteride administered 2-4 days prior to ingestion of 0.8 mg/kg ethanol divided between three drinks consumed over 36 minutes intervention 2: placebo medication administered 2-4 days prior to ingestion of 0.8 gr/kg ethanol divided between three drinks consumed over 36 minutes intervention 3: 4 mg dutasteride administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes intervention 4: placebo medication administered 2-4 days prior to ingestion of three drinks each containing 1 cc ethanol consumed over 36 minutes

Protocol document: