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
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Acknowledgments
The authors thank Valeant Pharmaceuticals for the generous donation of study drug.
Funding
This study was supported by the Department of Defense funds for Alcohol and Substance Abuse Disorders Research Program (W81XWH-12-2-0048 & W81XWH-13-2-0075) awarded to JMM. ASK and JMM were supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R01 AA026587).
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Coker, A.R., Weinstein, D.N., Vega, T.A. et al. The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder. Psychopharmacology 237, 3139–3148 (2020). https://doi.org/10.1007/s00213-020-05599-5
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DOI: https://doi.org/10.1007/s00213-020-05599-5