2024
Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo‐controlled crossover laboratory study
Petrakis I, Nolen T, Vandergrift N, Hirsch S, Krystal J, De Vivo M, Sabados J, Pisani E, Newcomb J, Kosten T. Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo‐controlled crossover laboratory study. American Journal On Addictions 2024 PMID: 39152094, DOI: 10.1111/ajad.13637.Peer-Reviewed Original ResearchPathophysiology of posttraumatic stress disorderAlcohol use disorderSubjective effects of alcoholEffects of alcoholUse disorderComorbid alcohol use disorderAlcohol cue reactivityPosttraumatic stress disorderCrossover laboratory studyCue reactivityAlcohol cravingNoradrenergic dysregulationStress disorderBlood pressureSubjective effectsEthanol administrationClinically significant adverse effectsPharmacotherapeutic approachesTest daysReceptor agonistsPotential treatmentDouble-blind fashionCravingDrinking alcoholDisordersProblem Opioid Use Among US Military Veterans: Prevalence, Correlates, and Psychiatric Characteristics
Na P, Petrakis I, Krystal J, Pietrzak R. Problem Opioid Use Among US Military Veterans: Prevalence, Correlates, and Psychiatric Characteristics. Journal Of Addiction Medicine 2024, 18: 313-318. PMID: 38498625, PMCID: PMC11150085, DOI: 10.1097/adm.0000000000001286.Peer-Reviewed Original ResearchInstrumental activities of daily livingInstrumental activities of daily living disabilityLifetime suicide attemptsProblem opioid useUS military veteransUS veteransPsychiatric characteristicsSuicide attemptsMilitary veteransAssociated with black race/ethnicityActivities of daily livingNational Health and ResilienceLifetime alcohol use disorderMental health morbidityPosttraumatic stress disorderMental health disordersAlcohol use disorderNon-Hispanic race/ethnicityMultivariate logistic regression modelNationally representative sampleOpioid useLogistic regression modelsInstrumental activitiesHealth morbidityDaily living
2023
Trajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study
Na P, Montalvo-Ortiz J, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Trajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study. Drug And Alcohol Dependence 2023, 246: 109833. PMID: 36963160, PMCID: PMC10811960, DOI: 10.1016/j.drugalcdep.2023.109833.Peer-Reviewed Original ResearchConceptsAlcohol consumption groupCurrent mental health treatmentDysphoric arousal symptomsMental health treatmentUS veteransAlcohol consumptionHealth treatmentConsumption groupArousal symptomsYounger agePopulation-based longitudinal studyPublic health problemLongitudinal studyExcessive alcohol consumptionAlcohol use disorderPosttraumatic stress disorderU.S. military veteransMedical comorbiditiesChronic courseNational HealthClose monitoringUse disordersHealth problemsVeterans StudyStress disorder
2022
Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder
Smart K, Worhunsky PD, Scheinost D, Angarita GA, Esterlis I, Carson RE, Krystal JH, O'Malley SS, Cosgrove KP, Hillmer AT. Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder. Alcohol Clinical And Experimental Research 2022, 46: 770-782. PMID: 35342968, PMCID: PMC9117461, DOI: 10.1111/acer.14816.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsDefault mode networkFunctional magnetic resonance imagingReceptor availabilityPositron emission tomographyAUD groupFunctional connectivityReceptor positron emission tomographyResting-state functional magnetic resonance imagingNetwork-level functional connectivityBrain connectivityWeeks of abstinenceGlobal functional connectivityAlcohol use disorderMagnetic resonance imagingFMRI outcomesHealthy controlsSupervised abstinencePET resultsUse disordersSynaptic plasticityResonance imagingBrain regionsEmission tomographyOrbitofrontal cortex
2021
Mapping data‐driven individualized neurobehavioral phenotypes in heavy alcohol drinkers
DeMartini KS, Gueorguieva R, Pearlson G, Krishnan‐Sarin S, Anticevic A, Ji LJ, Krystal JH, O’Malley S. Mapping data‐driven individualized neurobehavioral phenotypes in heavy alcohol drinkers. Alcohol Clinical And Experimental Research 2021, 45: 841-853. PMID: 33605439, DOI: 10.1111/acer.14580.Peer-Reviewed Original ResearchConceptsConfirmatory factor analysisIncentive salienceNeurofunctional domainsAlcohol use disorderExecutive functionLatent factorsPhysical neglectSelf-report measuresChildhood emotional abuseUse disordersChildhood physical neglectEarly life stressSignificant predictorsMultiple significant predictorsMultiple causes modelCurrent AUDNegative emotionalityAddiction developmentEmotional abuseChildhood neglectFactor structureDrinking frequencySalienceCause modelFactor analysis
2020
The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk
Spiegelman D, Lovato LC, Khudyakov P, Wilkens TL, Adebamowo CA, Adebamowo SN, Appel LJ, Beulens JW, Coughlin JW, Dragsted LO, Edenberg HJ, Eriksen JN, Estruch R, Grobbee DE, Gulayin PE, Irazola V, Krystal JH, Lazo M, Murray MM, Rimm EB, Schrieks IC, Williamson JD, Mukamal KJ. The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk. European Journal Of Preventive Cardiology 2020, 27: 1967-1982. PMID: 32250171, PMCID: PMC7541556, DOI: 10.1177/2047487320912376.Peer-Reviewed Original ResearchConceptsModerate alcohol consumptionCardiovascular Health TrialAlcohol consumptionHealth trialsCardiovascular diseaseModerate alcoholNon-fatal ischemic strokeNon-fatal myocardial infarctionPrimary composite endpointCongestive heart failureCoronary heart diseaseModerate alcohol consumersAdults 50 yearsPublic health guidelinesAlcohol use disorderPreferred alcoholic beverageCardiometabolic effectsCardiometabolic riskCarotid revascularizationIschemic strokeSecondary outcomesComposite endpointHeart failurePrimary outcomeMyocardial infarctionCharacteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov
Wallach JD, Krystal JH, Ross JS, O’Malley S. Characteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov. JAMA Psychiatry 2020, 77: 1081-1084. PMID: 32459295, PMCID: PMC7254444, DOI: 10.1001/jamapsychiatry.2020.1167.Peer-Reviewed Original ResearchLongitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence
Hillmer AT, Angarita GA, Esterlis I, Anderson JM, Nabulsi N, Lim K, Ropchan J, Carson RE, Krystal JH, Malley S, Cosgrove KP. Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence. Neuropsychopharmacology 2020, 46: 380-385. PMID: 32919411, PMCID: PMC7852514, DOI: 10.1038/s41386-020-00856-9.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsSmoking statusAlcohol abstinenceEarly abstinenceMGlu5 receptor negative allosteric modulatorReceptor negative allosteric modulatorChronic alcohol useCortical brain regionsAlcohol use disorderEmission Tomography ImagingPositron emission tomography (PET) imagingNegative allosteric modulatorsDSM-5 criteriaCue-induced reinstatementHealthy controlsPreclinical literatureGlutamate systemPreclinical modelsHuman evidenceReceptor drugsPET scansUse disordersHuman studiesReceptor availabilityStudy durationExamining the Relationship Between Self‐Reported Drinking and In‐Laboratory Drinking and Craving: Is There Concordance?
DeMartini KS, Pittman B, Krystal JH, O’Malley S, Krishnan‐Sarin S. Examining the Relationship Between Self‐Reported Drinking and In‐Laboratory Drinking and Craving: Is There Concordance? Alcohol Clinical And Experimental Research 2020, 44: 1151-1157. PMID: 32352581, PMCID: PMC10158572, DOI: 10.1111/acer.14329.Peer-Reviewed Original ResearchConceptsSelf-reported drinkingAlcohol cravingDrinking daysAlcohol consumptionDrinking paradigmHeavy drinking daysAlcohol use disorderSummary drinking measuresMaximum drinksPharmacotherapy studiesAdult heavy drinkersMedication administrationAverage drinksUse disordersHeavy drinkersAlcohol assessmentSignificant associationTotal drinksDrinking sessionDrinking indicesAdditional outcomesBehavioral interventionsLimited evidenceRisk classificationCravingSystematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder
Hartwell EE, Feinn R, Morris PE, Gelernter J, Krystal J, Arias AJ, Hoffman M, Petrakis I, Gueorguieva R, Schacht JP, Oslin D, Anton RF, Kranzler HR. Systematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder. Addiction 2020, 115: 1426-1437. PMID: 31961981, PMCID: PMC7340566, DOI: 10.1111/add.14975.Peer-Reviewed Original ResearchConceptsAsn40Asp single-nucleotide polymorphismRandomized clinical trialsAlcohol use disorderNaltrexone treatmentMu-opioid receptor geneUse disordersSingle nucleotide polymorphismsPlacebo-controlled randomized clinical trialsSystematic reviewPublication biasOpioid receptor antagonist naltrexoneWide inter-individual variabilityHeavy drinkingRisk of biasNaltrexone treatment responseReceptor geneRandom-effects modelAlcohol consumption outcomesAntagonist naltrexoneInter-individual variabilityStudy criteriaClinical trialsNucleotide polymorphismsTreatment responseMinor alleleDNA methylation signature on phosphatidylethanol, not on self-reported alcohol consumption, predicts hazardous alcohol consumption in two distinct populations
Liang X, Justice AC, So-Armah K, Krystal JH, Sinha R, Xu K. DNA methylation signature on phosphatidylethanol, not on self-reported alcohol consumption, predicts hazardous alcohol consumption in two distinct populations. Molecular Psychiatry 2020, 26: 2238-2253. PMID: 32034291, PMCID: PMC8440221, DOI: 10.1038/s41380-020-0668-x.Peer-Reviewed Original ResearchConceptsHazardous alcohol drinkingSelf-reported alcohol consumptionAlcohol consumptionCohort 2Cohort 1Epigenome-wide association studiesSelf-reported dataHazardous alcohol consumptionAlcohol use disorderDNAm signaturesObjective measuresAlcohol drinkingClinical assessmentUse disordersRobust biomarkersDNA methylation signaturesValidation setDistinct populationsCharacteristic curvePEthEpigenetic biomarkersMethylation signatures
2019
Regulation of Craving and Negative Emotion in Alcohol Use Disorder
Suzuki S, Mell MM, O'Malley SS, Krystal JH, Anticevic A, Kober H. Regulation of Craving and Negative Emotion in Alcohol Use Disorder. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2019, 5: 239-250. PMID: 31892465, PMCID: PMC7010564, DOI: 10.1016/j.bpsc.2019.10.005.Peer-Reviewed Original ResearchConceptsAlcohol use disorderNegative emotionsNegative affectPrefrontal cortexIndividual differencesRegulation conditionsCognitive behavioral therapy treatmentEmotion regulation taskFunctional magnetic resonance imagingNegative affect conditionRegulation of cravingNegative alcohol expectanciesNotable individual differencesSelf-reported cravingBehavioral therapy treatmentUse disordersRegulation successCognitive strategiesAffect conditionRegulation strategiesAlcohol expectanciesPFC regionsNeural mechanismsRegulation taskAUD treatmentThe Association of Impulsivity and Family History of Alcohol Use Disorder on Alcohol Use and Consequences
Haeny AM, Gueorguieva R, Morean ME, Krishnan‐Sarin S, DeMartini KS, Pearlson GD, Anticevic A, Krystal JH, O'Malley SS. The Association of Impulsivity and Family History of Alcohol Use Disorder on Alcohol Use and Consequences. Alcohol Clinical And Experimental Research 2019, 44: 159-167. PMID: 31693193, PMCID: PMC6981005, DOI: 10.1111/acer.14230.Peer-Reviewed Original ResearchConceptsFacets of impulsivityBarratt Impulsiveness ScaleAlcohol-related problemsAlcohol use disorderProblem drinkingAssociation of impulsivityImpulsivity-related traitsAlcohol-related consequencesUse disordersFHP individualsAlcohol outcomesImpulsiveness ScaleImpulsivityProblematic drinkingFHN individualsDrinking quantityAlcohol quantityTranslational neuroscienceAlcohol misuseAlcohol useTransdisciplinary Tobacco Use Research CenterMain effectAnalysis of covariancePhenotypic riskStrong positive associationAssociation of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder
Yoon G, Petrakis IL, Krystal JH. Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder. JAMA Psychiatry 2019, 76: 337-338. PMID: 30624551, PMCID: PMC6439824, DOI: 10.1001/jamapsychiatry.2018.3990.Peer-Reviewed Original Research
2018
Trajectories of alcohol consumption in U.S. military veterans: Results from the National Health and Resilience in Veterans Study
Fuehrlein BS, Kachadourian LK, DeVylder EK, Trevisan LA, Potenza MN, Krystal JH, Southwick SM, Pietrzak RH. Trajectories of alcohol consumption in U.S. military veterans: Results from the National Health and Resilience in Veterans Study. American Journal On Addictions 2018, 27: 383-390. PMID: 29667712, DOI: 10.1111/ajad.12731.Peer-Reviewed Original ResearchMajor depressive disorderLifetime major depressive disorderAlcohol consumptionPredominant trajectoriesNational HealthVeterans StudyAlcohol Use Disorders Identification Test-ConsumptionBrief alcohol screensExcessive drinkingPopulation-based preventionSocial supportExcessive alcohol consumptionAlcohol use disorderLow social supportU.S. military veteransAlcohol screenBaseline determinantsDepressive disorderLatent growth mixture modelingMedical conditionsModerate drinkersRare drinkersModerate drinkingUse disordersGreater social support
2017
Mecamylamine treatment for alcohol dependence: a randomized controlled trial
Petrakis IL, Ralevski E, Gueorguieva R, O'Malley SS, Arias A, Sevarino KA, Jane JS, O'Brien E, Krystal JH. Mecamylamine treatment for alcohol dependence: a randomized controlled trial. Addiction 2017, 113: 6-14. PMID: 28710873, PMCID: PMC5725262, DOI: 10.1111/add.13943.Peer-Reviewed Original ResearchConceptsHeavy drinking daysDrinking daysAlcohol use disorderUse disordersAlcohol consumptionAlcohol dependenceDouble-blind clinical trialNicotinic acetylcholine receptor antagonistWeeks of treatmentAcetylcholine receptor antagonistCurrent alcohol dependenceSignificant differencesTreatment-seeking smokersMecamylamine treatmentPlacebo groupMonth 3Primary outcomeSmoking statusNicotine withdrawalReceptor antagonistNovel pharmacotherapiesClinical trialsManagement therapyMecamylamineTreatment groups
2016
The burden of alcohol use disorders in US military veterans: results from the National Health and Resilience in Veterans Study
Fuehrlein BS, Mota N, Arias AJ, Trevisan LA, Kachadourian LK, Krystal JH, Southwick SM, Pietrzak RH. The burden of alcohol use disorders in US military veterans: results from the National Health and Resilience in Veterans Study. Addiction 2016, 111: 1786-1794. PMID: 27061707, DOI: 10.1111/add.13423.Peer-Reviewed Original ResearchConceptsProbable alcohol use disorderAlcohol use disorderUS military veteransAlcohol Use Disorders Identification Test-ConsumptionUse disordersLife-time historyMale sexPsychiatric comorbidityUS veteransNational HealthMilitary veteransSuicidal ideationVeterans StudyYounger ageMini International Neuropsychiatric InterviewPast-year alcohol use disorderCommon psychiatric comorbiditiesLower annual household incomeDSM-IV diagnostic criteriaLife-time diagnosisDrug use disordersInternational Neuropsychiatric InterviewMajor depressive disorderRisk of AUDLife-time suicide attempts
2015
N‐Methyl‐d‐Aspartate Receptor Antagonism has Differential Effects on Alcohol Craving and Drinking in Heavy Drinkers
Krishnan‐Sarin S, O'Malley SS, Franco N, Cavallo DA, Morean M, Shi J, Pittman B, Krystal JH. N‐Methyl‐d‐Aspartate Receptor Antagonism has Differential Effects on Alcohol Craving and Drinking in Heavy Drinkers. Alcohol Clinical And Experimental Research 2015, 39: 300-307. PMID: 25664775, PMCID: PMC4331214, DOI: 10.1111/acer.12619.Peer-Reviewed Original ResearchConceptsAlcohol drinkingFamily historyHeavy drinkersAlcohol cravingN-methyl-D-aspartate receptor antagonistN-methyl-D-aspartate receptor antagonismAlcohol cue-induced cravingEffects of FHHigher baseline levelsPresence of impulsivityAlcohol use disorderCue-induced cravingAlcohol-induced stimulationReceptor antagonismReceptor antagonistPriming doseNMDA receptorsUse disordersMemantineBaseline levelsModulatory influencePotential efficacyAlcohol accessDrinkersEighth day
2013
Glutamatergic targets for new alcohol medications
Holmes A, Spanagel R, Krystal JH. Glutamatergic targets for new alcohol medications. Psychopharmacology 2013, 229: 539-554. PMID: 23995381, PMCID: PMC3811052, DOI: 10.1007/s00213-013-3226-2.Peer-Reviewed Original ResearchConceptsGlutamate systemGlycineB siteAlcohol-related behaviorsNMDA receptorsAlcohol abuseAlcohol consumptionN-methyl-D-aspartate receptorsChronic alcohol exposureElevated extracellular glutamatePathophysiology of alcoholismAMPA receptor subunitsAlcohol use disorderNovel pharmacotherapeutic approachesEffects of alcoholAlcohol medicationsBlocking NMDAHyperglutamatergic stateMetabotropic receptorsPharmacotherapeutic approachesAlcohol exposureExcess glutamateExtracellular glutamateGlutamate receptorsPreclinical studiesKainate receptors
2011
Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence
Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, Krystal JH. Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence. Neuropsychopharmacology 2011, 37: 996-1004. PMID: 22089316, PMCID: PMC3280636, DOI: 10.1038/npp.2011.283.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderSerotonin uptake inhibitorNorepinephrine uptake inhibitorUptake inhibitorAlcohol dependenceMale veteransTreatment of PTSDUse outcomesSymptoms of PTSDDouble-blind conditionsMain outcome measuresEvidence of efficacyComorbid alcohol dependenceCurrent diagnostic criteriaAlcohol use disorderAlcohol use outcomesComorbid conditionsAdjunctive efficacyOutcome measuresOnly FDADiagnostic criteriaUse disordersClinical advantagesAlcohol consumptionDrug Administration