The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder.

Autor: Coker AR; Department of Neurology, University of California, San Francisco, CA, USA. allison.coker@ucsf.edu., Weinstein DN; Department of Neurology, University of California, San Francisco, CA, USA., Vega TA; Department of Neurology, University of California, San Francisco, CA, USA.; Department of Neurology, VA Northern California Health Care System, Mather, CA, USA., Miller CS; Department of Neurology, University of California, San Francisco, CA, USA., Kayser AS; Department of Neurology, University of California, San Francisco, CA, USA.; Department of Neurology, VA Northern California Health Care System, Mather, CA, USA., Mitchell JM; Department of Neurology, University of California, San Francisco, CA, USA.; Department of Psychiatry, University of California, San Francisco, CA, USA.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2020 Oct; Vol. 237 (10), pp. 3139-3148. Date of Electronic Publication: 2020 Jul 02.
DOI: 10.1007/s00213-020-05599-5
Abstrakt: Rationale: Individuals suffering from alcohol use disorder (AUD) demonstrate difficulty with decision-making and impulsivity that may be associated with impaired frontal cortical function. Therapeutics that enhance frontal dopamine tone could decrease impulsivity and in turn reduce alcohol consumption in individuals with AUD.
Objectives: To determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory-based decision-making tasks.
Methods: We used daily self-report and a novel group laboratory bar task to assess the effects of randomized double-blind crossover administration of tolcapone (100 mg TID for 5 days) on alcohol consumption and laboratory tasks assessing impulsivity in 55 non-treatment-seeking subjects with AUD.
Results: Tolcapone significantly reduced self-reported alcohol consumption (t (54) = 2.05, p = 0.045). The effects of tolcapone on drinking significantly correlated with changes in impulsive decision-making, such that subjects with the greatest decrease in impulsive choice on tolcapone also reported the greatest decrease in alcohol consumption (r (45) = 0.40, p = 0.0053). We did not see effects of tolcapone on laboratory bar consumption. Adverse event (AE) reporting was low, with no significant difference in frequency or severity of AEs on tolcapone versus placebo.
Conclusions: These data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD.
Trial Registration: ClinicalTrials.gov Identifier: NCT02740582.
Databáze: MEDLINE
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