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Dutasteride reduces alcohol’s sedative effects in men in a human laboratory setting and reduces drinking in the natural environment

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Abstract

Rationale

Preclinical studies support the hypothesis that endogenous neuroactive steroids mediate some effects of alcohol.

Objectives

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.

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Acknowledgments

Supported by NIH grants R01 AA015606 (to JC), K24 AA13736 (to HRK), P60 AA03510 (Alcohol Research Center), and M01 RR06192 (University of Connecticut General Clinical Research Center). The authors thank Linda Burian and Pamela Fall for their expert technical assistance in the conduct of this study.

Conflict of interest

JC, RF, AJA, and TP have no disclosures to make. HK has been a consultant or advisory board member for the following pharmaceutical companies: Alkermes, Lilly, Lundbeck, Pfizer, and Roche. He is also a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which is supported by Lilly, Lundbeck, AbbVie, and Pfizer. CO has received study supplies from Pfizer Pharmaceuticals for a smoking cessation study.

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Authors and Affiliations

  1. Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA

    Jonathan Covault

  2. Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA

    Cheryl Oncken

  3. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and Philadelphia VAMC, Philadelphia, PA, USA

    Timothy Pond & Henry R. Kranzler

  4. Department of Medical Sciences, Frank Netter School of Medicine, Quinnipiac University, North Haven, CT, USA

    Richard Feinn

  5. Department of Psychiatry, Yale University and VA CT Healthcare, West Haven, CT, USA

    Albert J. Arias

  6. Department of Psychiatry, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030-1410, USA

    Jonathan Covault

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  1. Jonathan Covault
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  4. Albert J. Arias
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  6. Henry R. Kranzler
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Correspondence to Jonathan Covault.

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Covault, J., Pond, T., Feinn, R. et al. Dutasteride reduces alcohol’s sedative effects in men in a human laboratory setting and reduces drinking in the natural environment. Psychopharmacology 231, 3609–3618 (2014). https://doi.org/10.1007/s00213-014-3487-4

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  • DOI: https://doi.org/10.1007/s00213-014-3487-4

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