The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use d
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ORIGINAL INVESTIGATION
The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder Allison R. Coker 1 & Dawn N. Weinstein 1 & Taylor A. Vega 1,2 & Catriona S. Miller 1 & Andrew S. Kayser 1,2 & Jennifer M. Mitchell 1,3 Received: 14 April 2020 / Accepted: 23 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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: NCT 02740582 Keywords Alcohol use disorder . AUD . Tolcapone . COMT . Impulsivity . Decision-making
Introduction The medical, social, and emotional costs of drug and alcohol abuse are extensive. The CDC estimates the economic burden of alcohol use disorder (AUD) to be in excess of 250 billion dollars per year in the USA alone (CDC 2019). Despite this widespread burden, the Food and Drug Administration has
* Allison R. Coker [email protected] 1
Department of Neurology, University of California, San Francisco, CA, USA
2
Department of Neurology, VA Northern California Health Care System, Mather, CA, USA
3
Department of Psychiatry, University of California, San Francisco, CA, USA
only approved three drugs to treat AUD: disulfiram, acamprosate, and naltrexone. Disulfiram, an irreversible inhibitor of alcohol dehydrogenase, primarily works by inducing unpleasant physiological effects if combined with alcohol and is therefore only effective in highly compliant patients. Acamprosate, a positive allosteric modulator, and naltrexon
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