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

Autor: Taylor Vega, Catriona S. Miller, Allison R. Coker, Jennifer M. Mitchell, Dawn Weinstein, Andrew S. Kayser
Rok vydání: 2020
Předmět:
Male
AUD
Alcohol use disorder
Pharmacology
Medical and Health Sciences
Choice Behavior
Alcohol Use and Health
Substance Misuse
0302 clinical medicine
Psychiatry
Cross-Over Studies
Alcoholism
6.1 Pharmaceuticals
Mental health
Female
medicine.symptom
Alcohol consumption
medicine.drug
Adult
Impulsivity
Alcohol Drinking
Clinical Trials and Supportive Activities
Placebo
Article
03 medical and health sciences
Young Adult
Double-Blind Method
Dopamine
Clinical Research
mental disorders
medicine
Humans
Adverse effect
Catechol-O-methyl transferase
Tolcapone
business.industry
Psychology and Cognitive Sciences
Evaluation of treatments and therapeutic interventions
Catechol O-Methyltransferase Inhibitors
medicine.disease
COMT
030227 psychiatry
Brain Disorders
Good Health and Well Being
Impulsive Behavior
business
030217 neurology & neurosurgery
Decision-making
Zdroj: Psychopharmacology (Berl)
Psychopharmacology, vol 237, iss 10
ISSN: 1432-2072
Popis: RationaleIndividuals 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.ObjectivesTo 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.MethodsWe used daily self-report and a novel group laboratory bar task to assess the effects of randomized double-blind crossover administration of tolcapone (100mg TID for 5days) on alcohol consumption and laboratory tasks assessing impulsivity in 55 non-treatment-seeking subjects with AUD.ResultsTolcapone 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.ConclusionsThese data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD.Trial registrationClinicalTrials.gov Identifier: NCT02740582.
Databáze: OpenAIRE
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