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Article: Disulfiram Treatment of Alcoholism.

Anton, Raymond F

2019 Volume 19, Issue 1, Page(s) 56–57

Language	English
Publishing date	2019-12-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	427760-0
ISSN	0090-838X
ISSN	0090-838X
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Article: Medications for Treating Alcoholism.

Anton, Raymond F

Alcohol health and research world

2019 Volume 18, Issue 4, Page(s) 265–271

Abstract: Researchers are evaluating medications to assist in treating alcoholism. Such medications may be used to treat withdrawal or co-occurring psychiatric disorders or as an adjunct to psychosocial treatment. ...

Abstract	Researchers are evaluating medications to assist in treating alcoholism. Such medications may be used to treat withdrawal or co-occurring psychiatric disorders or as an adjunct to psychosocial treatment.
Language	English
Publishing date	2019-12-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	427760-0
ISSN	0090-838X
ISSN	0090-838X
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Article ; Online: A randomized trial of the effects of COMT inhibition on subjective response to alcohol: Moderation by baseline COMT activity and mediation of alcohol self-administration.

Schacht, Joseph P / Kubicki, Matthew / Anton, Raymond F

Alcohol, clinical & experimental research

2023 Volume 48, Issue 1, Page(s) 178–187

Abstract: Background: Poor inhibitory control and enhanced subjective response to alcohol are interrelated risk factors for alcohol use disorder (AUD) that share underlying neural substrates, including dopamine signaling in the right prefrontal cortex, a ... ...

Abstract	Background: Poor inhibitory control and enhanced subjective response to alcohol are interrelated risk factors for alcohol use disorder (AUD) that share underlying neural substrates, including dopamine signaling in the right prefrontal cortex, a potential target for pharmacological intervention. Cortical dopamine inactivation is primarily regulated by catechol-O-methyltransferase (COMT), an enzyme with large variation in activity as a function of the COMT rs4680 (val158met) single nucleotide polymorphism. In a previous randomized, placebo-controlled trial of the COMT inhibitor tolcapone (200 mg TID) in non-treatment-seeking participants with AUD, we found that tolcapone, relative to placebo, reduced alcohol self-administration only among rs4680 val-allele homozygotes, whose COMT activity is higher than in met-allele carriers. Methods: We conducted secondary analyses of the effects of tolcapone and baseline COMT activity, as indexed by both rs4680 genotype and an enzymatic activity assay, on the subjective response to alcohol in a bar-laboratory paradigm among 60 participants in the previous trial. Results: Tolcapone did not affect alcohol-induced stimulation or sedation more than placebo. However, baseline COMT activity moderated the effects of the drug on both outcomes, such that tolcapone-treated participants with higher baseline COMT activity had less stimulation (p = 0.008) and sedation (p = 0.053) than participants with lower baseline COMT activity and those treated with placebo. Additionally, alcohol-induced stimulation significantly mediated the interacting effects of baseline COMT activity and tolcapone on bar-laboratory self-administration. Conclusions: Tolcapone may reduce subjective response to alcohol more effectively among individuals with preexisting high COMT activity an effect that could account for the drug's reduction of alcohol consumption among these individuals.
Language	English
Publishing date	2023-11-21
Publishing country	United States
Document type	Journal Article
ISSN	2993-7175
ISSN (online)	2993-7175
DOI	10.1111/acer.15227
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Article ; Online: Changed Primary Outcome Between Trial Registration and Publication-Reply.

Anton, Raymond F / Hoffman, Michaela

JAMA internal medicine

2020 Volume 180, Issue 11, Page(s) 1551–1552

MeSH term(s)	Humans ; Publishing ; Registries
Language	English
Publishing date	2020-07-17
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2699338-7
ISSN	2168-6114 ; 2168-6106
ISSN (online)	2168-6114
ISSN	2168-6106
DOI	10.1001/jamainternmed.2020.2173
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Article ; Online: Alcohol Cue Processing in Co-Occurring Bipolar Disorder and Alcohol Use Disorder.

Mellick, William H / Tolliver, Bryan K / Brenner, Helena M / Anton, Raymond F / Prisciandaro, James J

JAMA psychiatry

2023 Volume 80, Issue 11, Page(s) 1150–1159

Abstract: ... revealed a BD × AUD interaction (F = 10.64; P = .001; η2 = 0.09) within a cluster spanning portions ... F = 8.02; P = .006; η2 = 0.07) within the dorsal striatum. In each instance, individuals with BD ...

Abstract	Importance: Reward circuitry dysfunction is a candidate mechanism of co-occurring bipolar disorder and alcohol use disorder (BD + AUD) that remains understudied. This functional magnetic resonance imaging (fMRI) research represents the first evaluation of alcohol cue reward processing in BD + AUD. Objective: To determine how alcohol cue processing in individuals with BD + AUD may be distinct from that of individuals with AUD or BD alone. Design, setting, and participants: This cross-sectional case-control study (April 2013-June 2018) followed a 2 × 2 factorial design and included individuals with BD + AUD, AUD alone, BD alone, and healthy controls. A well-validated visual alcohol cue reactivity fMRI paradigm was administered to eligible participants following their demonstration of 1 week or more of abstinence from alcohol and drugs assessed via serial biomarker testing. Study procedures were completed at the Medical University of South Carolina. Analysis took place between June and August 2022. Main outcomes and measures: Past-week mood symptoms were rated by clinicians using the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. The Alcohol Dependence Scale, Obsessive-Compulsive Drinking Scale, and Barratt Impulsiveness Scale were included questionnaires. Functional MRI whole-brain data were analyzed along with percent signal change within a priori regions of interest located in the ventral striatum, dorsal striatum, and ventromedial prefrontal cortex. Exploratory analyses of associations between cue reactivity and select behavioral correlates (alcohol craving, impulsivity, maximum number of alcohol drinks on a single occasion, and days since last alcohol drink) were also performed. Results: Of 112 participants, 28 (25.0%) had BD + AUD, 26 (23.2%) had AUD alone, 31 (27.7%) had BD alone, and 27 (24.1%) were healthy controls. The mean (SD) age was 38.7 (11.6) years, 50 (45.5%) were female, 33 (30%) were smokers, and 37 (34.9%) reported recent alcohol consumption. Whole-brain analyses revealed a BD × AUD interaction (F = 10.64; P = .001; η2 = 0.09) within a cluster spanning portions of the right inferior frontal gyrus and insula. Region of interest analyses revealed a main association of BD (F = 8.02; P = .006; η2 = 0.07) within the dorsal striatum. In each instance, individuals with BD + AUD exhibited reduced activation compared with all other groups who did not significantly differ from one another. These hypoactivations were associated with increased impulsivity and obsessive-compulsive alcohol craving exclusively among individuals with BD + AUD. Conclusion and relevance: The findings of this study suggest conceptualizing reward dysfunction in BD + AUD by the potential interaction between blunted reward responsivity and deficient inhibitory control may help guide treatment development strategies. To this end, reduced right inferior frontal gyrus and insula alcohol cue reactivity represents a novel candidate biomarker of BD + AUD that may respond to pharmacological interventions targeting impulsivity-related neural mechanisms for improved executive control.
MeSH term(s)	Humans ; Female ; Adult ; Male ; Alcoholism/drug therapy ; Bipolar Disorder/diagnostic imaging ; Cross-Sectional Studies ; Case-Control Studies ; Cues ; Alcohol Drinking/drug therapy ; Ethanol ; Biomarkers ; Magnetic Resonance Imaging/methods
Chemical Substances	Ethanol (3K9958V90M) ; Biomarkers
Language	English
Publishing date	2023-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2701203-7
ISSN	2168-6238 ; 2168-622X
ISSN (online)	2168-6238
ISSN	2168-622X
DOI	10.1001/jamapsychiatry.2023.2726
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Article ; Online: Commentary on: ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials.

Anton, Raymond F

Alcoholism, clinical and experimental research

2014 Volume 38, Issue 7, Page(s) 1826–1828

MeSH term(s)	Controlled Clinical Trials as Topic ; Ethanol/administration & dosage ; Ethanol/pharmacokinetics ; Female ; Glucuronates/urine ; Humans ; Male ; Substance Abuse Detection/methods ; Sulfuric Acid Esters/urine
Chemical Substances	Glucuronates ; Sulfuric Acid Esters ; ethyl glucuronide (17685-04-0) ; Ethanol (3K9958V90M) ; diethyl sulfate (K0FO4VFA7I)
Language	English
Publishing date	2014-06-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/acer.12495
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Article ; Online: Epigenetic moderators of naltrexone efficacy in reducing heavy drinking in Alcohol Use Disorder: a randomized trial.

Schacht, Joseph P / Hoffman, Michaela / Chen, Brian H / Anton, Raymond F

The pharmacogenomics journal

2021 Volume 22, Issue 1, Page(s) 1–8

Abstract: Polymorphisms in genes associated with opioid signaling and dopamine reuptake and inactivation may moderate naltrexone efficacy in Alcohol Use Disorder (AUD), but the effects of epigenetic modification of these genes on naltrexone response are largely ... ...

Abstract	Polymorphisms in genes associated with opioid signaling and dopamine reuptake and inactivation may moderate naltrexone efficacy in Alcohol Use Disorder (AUD), but the effects of epigenetic modification of these genes on naltrexone response are largely unexplored. This study tested interactions between methylation in the μ-opioid receptor (OPRM1), dopamine transporter (SLC6A3), and catechol-O-methyltransferase (COMT) genes as predictors of naltrexone effects on heavy drinking in a 16-week randomized, placebo-controlled trial among 145 treatment-seeking AUD patients. OPRM1 methylation interacted with both SLC6A3 and COMT methylation to moderate naltrexone efficacy, such that naltrexone-treated individuals with lower methylation of the OPRM1 promoter and the SLC6A3 promoter (p = 0.006), COMT promoter (p = 0.005), or SLC6A3 3' untranslated region (p = 0.004), relative to placebo and to those with higher OPRM1 and SLC6A3 or COMT methylation, had significantly fewer heavy drinking days. Epigenetic modification of opioid- and dopamine-related genes may represent a novel pharmacoepigenetic predictor of naltrexone efficacy in AUD.
MeSH term(s)	Adult ; Alcoholism/drug therapy ; Alcoholism/genetics ; Cartilage Oligomeric Matrix Protein/genetics ; DNA Methylation ; Dopamine Plasma Membrane Transport Proteins/genetics ; Epigenesis, Genetic/genetics ; Female ; Humans ; Male ; Middle Aged ; Naltrexone/therapeutic use ; Narcotic Antagonists/therapeutic use ; Predictive Value of Tests ; Receptors, Opioid, mu/genetics ; Treatment Outcome
Chemical Substances	COMP protein, human ; Cartilage Oligomeric Matrix Protein ; Dopamine Plasma Membrane Transport Proteins ; Narcotic Antagonists ; OPRM1 protein, human ; Receptors, Opioid, mu ; SLC6A3 protein, human ; Naltrexone (5S6W795CQM)
Language	English
Publishing date	2021-08-11
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2106831-8
ISSN	1473-1150 ; 1470-269X
ISSN (online)	1473-1150
ISSN	1470-269X
DOI	10.1038/s41397-021-00250-8
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Article ; Online: Commentary on Subbaraman et al. (2013) [corrected]: cravings as a mediator and moderator of drinking outcomes in the COMBINE Study.

Anton, Raymond F

Addiction (Abingdon, England)

2013 Volume 108, Issue 10, Page(s) 1745–1746

MeSH term(s)	Alcohol Deterrents/administration & dosage ; Alcohol Drinking/therapy ; Alcoholism/therapy ; Behavior Therapy/methods ; Humans ; Naltrexone/administration & dosage ; Narcotic Antagonists/administration & dosage
Chemical Substances	Alcohol Deterrents ; Narcotic Antagonists ; Naltrexone (5S6W795CQM)
Language	English
Publishing date	2013-09-05
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1141051-6
ISSN	1360-0443 ; 0965-2140
ISSN (online)	1360-0443
ISSN	0965-2140
DOI	10.1111/add.12328
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Article ; Online: Reductions in WHO risk drinking levels correlate with alcohol craving among individuals with alcohol use disorder.

Tuchman, Felicia R / Hallgren, Kevin A / Richards, Dylan K / Aldridge, Arnie / Anton, Raymond F / Aubin, Henri-Jean / Kranzler, Henry R / Mann, Karl / O'Malley, Stephanie S / Witkiewitz, Katie

Alcohol, clinical & experimental research

2024 Volume 48, Issue 2, Page(s) 420–429

Abstract: Background: Abstinence has historically been considered the preferred goal of alcohol use disorder (AUD) treatment. However, most individuals with AUD do not want to abstain and many are able to reduce their drinking successfully. Craving is often a ... ...

Abstract	Background: Abstinence has historically been considered the preferred goal of alcohol use disorder (AUD) treatment. However, most individuals with AUD do not want to abstain and many are able to reduce their drinking successfully. Craving is often a target of pharmacological and behavioral interventions for AUD, and reductions in craving may signal recovery. Whether reductions in drinking during AUD treatment are associated with reductions in craving has not been well examined. Methods: We conducted secondary analyses of data from three AUD clinical trials (N's= 1327, 346, and 200). Drinking reductions from baseline to the end of treatment were measured as changes in World Health Organization (WHO) risk drinking levels; alcohol craving was measured using validated self-report measures. Regression analyses tested whether drinking reductions were associated with end-of-treatment craving reductions; moderation analyses tested whether associations between drinking reduction and end-of-treatment craving differed across AUD severity. Results: Reductions of at least 1 or at least 2 WHO risk drinking levels were associated with lower craving (all p's < 0.05). Results were substantively similar after removing abstainers at the end-of-treatment. Associations between drinking reductions and craving were generally not moderated by AUD severity. Conclusions: Individuals with WHO risk drinking level reductions reported significantly lower craving, as compared to those who did not achieve meaningful reductions in drinking. The results demonstrate the utility of WHO risk drinking levels as AUD clinical trial endpoints and provide evidence that drinking reductions mitigate craving.
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ISSN	2993-7175
ISSN (online)	2993-7175
DOI	10.1111/acer.15257
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Article ; Online: Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone.

Schacht, Joseph P / Yeongbin Im / Hoffman, Michaela / Voronin, Konstantin E / Book, Sarah W / Anton, Raymond F

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2022 Volume 47, Issue 11, Page(s) 1953–1960

Abstract: Alcohol Use Disorder (AUD) is characterized by loss of control over drinking. Behavioral control is mediated, in part, by cortical dopamine signaling. Inhibition of catechol-O-methyltransferase (COMT), the enzyme primarily responsible for cortical ... ...

Abstract	Alcohol Use Disorder (AUD) is characterized by loss of control over drinking. Behavioral control is mediated, in part, by cortical dopamine signaling. Inhibition of catechol-O-methyltransferase (COMT), the enzyme primarily responsible for cortical dopamine inactivation, may increase cortical dopamine, especially among individuals with genetically mediated lower dopaminergic tone, such as COMT rs4680 (val158met) val-allele homozygotes. This study was a randomized, placebo-controlled, pharmacogenetic trial of the COMT inhibitor tolcapone. Ninety non-treatment-seeking AUD individuals were prospectively genotyped for rs4680 and randomized to tolcapone (200 mg t.i.d.) or placebo for 8 days. At baseline and on day 7, peripheral COMT activity was assayed, and participants completed an fMRI alcohol cue-reactivity task; on day 8, they completed a bar-lab paradigm. Primary outcomes were: (1) natural drinking during the medication period; (2) alcohol self-administration in the bar lab; and (3) alcohol cue-elicited cortical (right inferior frontal gyrus [rIFG]) and ventral striatal activation. At baseline, the rs4680 val-allele had an additive effect on COMT activity. Tolcapone, relative to placebo, reduced COMT activity in all genotype groups. COMT genotype moderated tolcapone's effect on drinking during the medication period and in the bar lab, such that tolcapone, relative to placebo, reduced drinking only among val-allele homozygotes. Tolcapone did not affect cue-elicited ventral striatal activation but reduced rIFG activation; less rIFG activation on day 7 was associated with less drinking during the medication period. Taken together, these data suggest that COMT inhibition may reduce drinking specifically among individuals genetically predisposed to excessive COMT activity and potentially low cortical dopamine tone.ClinicalTrials.gov identifier: NCT02949934 https://clinicaltrials.gov/ct2/show/NCT02949934.
MeSH term(s)	Alcoholism/diagnostic imaging ; Alcoholism/drug therapy ; Alcoholism/genetics ; Catechol O-Methyltransferase/genetics ; Catechol O-Methyltransferase Inhibitors/pharmacology ; Catechol O-Methyltransferase Inhibitors/therapeutic use ; Dopamine ; Ethanol ; Humans ; Tolcapone/pharmacology
Chemical Substances	Catechol O-Methyltransferase Inhibitors ; Ethanol (3K9958V90M) ; Tolcapone (CIF6334OLY) ; COMT protein, human (EC 2.1.1.6) ; Catechol O-Methyltransferase (EC 2.1.1.6) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-05-06
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-022-01335-z
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